Novel nucleotide and amino acid sequences, and assays methods of use thereof for diagnosis of colon cancer

FIELD OF THE INVENTION

The present invention is related to novel nucleotide and protein sequences that are diagnostic markers for colon cancer, and assays and methods of use thereof.

BACKGROUND OF THE INVENTION

Colon and rectal cancers are malignant conditions which occur in the corresponding segments of the large intestine. These cancers are sometimes referred to jointly as “colorectal cancer”, and, in many respects, the diseases are considered identical. The major differences between them are the sites where the malignant growths occur and the fact that treatments may differ based on the location of the tumors.

More than 95 percent of cancers of the colon and rectum are adenocarcinomas, which develop in glandular cells lining the inside (lumen) of the colon and rectum. In addition to adenocarcinomas, there are other rarer types of cancers of the large intestine: these include carcinoid tumors usually found in the appendix and rectum; gastrointestinal stromal tumors found in connective tissue in the wall of the colon and rectum; and lymphomas, which are malignancies of immune cells in the colon, rectum and lymph nodes. As with other malignant conditions, a number of genetic abnormalities have been associated with colon tumors (Bos et al, (1987) Nature 327:293-297; Baker et al, (1989) 244:217-2221; Nishisho et al, (1991) 253:665-669).

Colorectal cancer is the second most common cause of cancer death in the United States and the third most prevalent cancer in both men and women. Approximately 100,000 patients every year suffer from colon cancer and approximately half that number die of the disease. In large part this death rate is due to the inability to diagnose the disease at an early stage (Wanebo (1993) Colorectal Cancer, Mosby, St. Louis Mo.). In fact, the prognosis for a case of colon cancer is vastly enhanced when malignant tissue is detected at the early stage known as polyps. Polyps are usually benign growths protruding from the mucous membrane. Nearly all cases of colorectal cancer arise from adenomatous polyps, some of which mature into large polyps, undergo abnormal growth and development, and ultimately progress into cancer. This progression would appear to take at least 10 years in most patients, rendering it a readily treatable form of cancer if diagnosed early, when the cancer is localized. Simple removal of malignant polyps (polypectomy) through colonoscopy is now routine, and curing the condition from this procedure is effectively guaranteed. However, early detection of polyps and tumors depends on diligent and ongoing examination of patients at risk. The most reliable detection procedures to date include fecal occult blood tests, sigmoidoscopy, barium enema X-ray, digital rectal exam, and colonoscopy. Normally a malignant colon cancer will not cause noticeable symptoms (e.g., bowel obstruction, abdominal pain, anemia) until it has reached an advanced and far more serious stage of malignancy. At these stages, only risky, traumatic and/or invasive procedures are available, including chemotherapy, radiation therapy, and colonectomy.

Although current understanding of the etiology of colon cancer is undergoing continual refinement, extensive research in this area points to a combination of factors, including age, hereditary and non-hereditary conditions, and environmental/dietary factors. Age is a key risk factor in the development of colorectal cancer, since men and women over 40 years of age become increasingly susceptible to that cancer. Incidence rates increase considerably in each subsequent decade of life. A number of hereditary and nonhereditary conditions have also been linked to a heightened risk of developing colorectal cancer, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (Lynch syndrome or HNPCC), a personal and/or family history of colorectal cancer or adenomatous polyps, inflammatory bowel disease, diabetes mellitus, and obesity.

In the case of FAP, the tumor suppressor gene APC (adenomatous polyposis coli), located at 5q21, has been either mutationally inactivated or deleted (Alberts et al., Molecular Biology of the Cell 1288 (3d ed. 1994)). The APC protein plays a role in a number of functions, including cell adhesion, apoptosis, and repression of the c-myc oncogene. Of those patients with colorectal cancer who have normal APC genes, over 65% have such mutations in the cancer cells but not in other tissues. In the case of HPNCC, patients manifest abnormalities in the tumor suppressor gene HNPCC, but only about 15% of tumors contain the mutated gene. A host of other genes have also been implicated in colorectal cancer, including the K-ras, c-Ki-ras, N-ras, H-ras and c-myc oncogenes, and the tumor suppressor genes DCC (deleted in colon carcinoma), Wg/Wnt signal transduction pathway components and p53.

Some tyrosine kinases have been shown up-regulated in colorectal tumor tissues or cell lines like HT29. Focal adhesion kinase (FAK) and its up-stream kinase c-src and c-yes in colonic epithelial cells may play an important role in the promotion of colorectal cancers through the extracellular 1 5 matrix (ECM) and integrin-mediated signaling pathways. The formation of c-src/FAK complexes may coordinately deregulate VEGF expression and apoptosis inhibition.

Recent evidences suggest that a specific signal-transduction pathway for cell survival that implicates integrin engagement leads to FAK activation and thus activates PI-3 kinase and akt. In turn, akt phosphorylates BAD and blocks apoptosis in epithelial cells. The activation of c-src in colon cancer may induce VEGF expression through the hypoxia pathway. Other genes that may be implicated in colorectal cancer include Cox enzymes (Ota, S. et al. Aliment Pharmacol. Ther. 16 (Suppl 2): 102-106 (2002)), estrogen (alAzzawi, F. and Wahab, M. Climacteric 5: 3-14 (2002)), peroxisome proliferator-activated receptor-y (PPAR-y) (Gelman, L. et al. Cell Mol. Life. Sci. 5 5: 932-943 (1999)), IGF-I (Giovannucci (2001)), thymine DNA glycosylase (TDG) (Hardeland, U. et al. Prog. Nucleic Acid Res. Mol. Biol. 68: 235-253 (2001)) and EGF (Mendelsohn, J. EndocrineRelated Cancer 8: 3-9 (2001)).

Procedures used for detecting, diagnosing, monitoring, staging, and prognosticating colon cancer are of critical importance to the outcome of the patient. For example, patients diagnosed with early colon cancer generally have a much greater five-year survival rate as compared to the survival rate for patients diagnosed with distant metastasized colon cancer. Because colon cancer is highly treatable when detected at an early, localized stage, screening should be a part of routine care for all adults starting at age 50, especially those with first-degree relatives with colorectal cancer. One major advantage of colorectal cancer screening over its counterparts in other types of cancer is its ability to not only detect precancerous lesions, but to remove them as well. The key colorectal cancer screening tests in use today are fecal occult blood test, sigmoidoscopy, colonoscopy, double-contrast barium enema, and the carcinoembryonic antigen (CEA) test. New diagnostic methods which are more sensitive and specific for detecting early colon cancer are clearly needed.

Visual examination of the colon for abnormalities can be performed through endoscopic or radiographic techniques such as rigid proctosigmoidoscopy, flexible sigmoidoscopy, colonoscopy, and barium-contrast enema. These methods enable one to detect, biopsy, and remove adenomatous polyps. Despite the advantages of these procedures, there are accompanying downsides: they are expensive, and uncomfortable, and also carry with them a risk of complications. Sigmoidoscopy, by definition, is limited to the sigmoid colon and below, colonoscopy is a relatively expensive procedure, and both share the risk of possible bowel perforation and hemorrhaging. Double-contrast barium enema (DCBE) enables detection of lesions better than FOBT, and almost as well a colonoscopy, but it may be limited in evaluating the winding rectosigmoid region.

Another method of colon cancer diagnosis is the detection of carcinoembryonic antigen (CEA) in a blood sample from a subject, which when present at high levels, may indicate the presence of advanced colon cancer. But CEA levels may also be abnormally high when no cancer is present. Thus, this test is not selective for colon cancer, which limits the test's value as an accurate and reliable diagnostic tool. In addition, elevated CEA levels are not detectable until late-stage colon cancer, when the cure rate is low, treatment options limited, and patient prognosis poor.

Several classification systems have been devised to stage the extent of colorectal cancer, including the Dukes' system and the more detailed International Union against Cancer-American Joint Committee on Cancer TNM staging system, which is considered by many in the field to be a more useful staging system. These most widely used staging systems generally use at least one of the following characteristics for staging: the extent of tumor penetration into the colon wall, with greater penetration generally correlating with a more dangerous tumor; the extent of invasion of the tumor through the colon wall and into other neighboring tissues, with greater invasion generally correlating with a more dangerous tumor; the extent of invasion of the tumor into the regional lymph nodes, with greater invasion generally correlating with a more dangerous tumor; and the extent of metastatic invasion into more distant tissues, such as the liver, with greater metastatic invasion generally correlating with a more dangerous disease state.

“Dukes A” and “Dukes B” colon cancers are neoplasia that have invaded into the wall of the colon but have not spread into other tissues. Dukes A colon cancers are cancers that have not invaded beyond the submucosa. Dukes B colon cancers are subdivided into two groups: Dukes B1 and Dukes B2. “Dukes B1” colon cancers are neoplasias that have invaded up to but not through the muscularis propria. Dukes B2 colon cancers are cancers that have breached completely through the muscularis propria. Over a five year period, patients with Dukes A cancer who receive surgical treatment (i.e. removal of the affected tissue) have a greater than 90% survival rate. Over the same period, patients with Dukes B1 and Dukes B2 cancer receiving surgical treatment have a survival rate of about 85% and 75% respectively. Dukes A, B1 and B2 cancers are also referred to as T1, T2 and T3-T4 cancers, respectively. “Dukes C” colon cancers are cancers that have spread to the regional lymph nodes, such as the lymph nodes of the gut. Patients with Dukes C cancer who receive surgical treatment alone have a 35% survival rate over a five year period, but this survival rate is increased to 60% in patients that receive chemotherapy. “Dukes D” colon cancers are cancers that have metastasized to other organs. The liver is the most common organ in which metastatic colon cancer is found. Patients with Dukes D colon cancer have a survival rate of less than 5% over a five year period, regardless of the treatment regimen.

The TNM system, which is used for either clinical or pathological staging, is divided into four stages, each of which evaluates the extent of cancer growth with respect to primary tumor (T), regional lymph nodes (N), and distant metastasis (M). The system focuses on the extent of tumor invasion into the intestinal wall, invasion of adjacent structures, the number of regional lymph nodes that have been affected, and whether distant metastasis has occurred. Stage 0 is characterized by in situ carcinoma (Tis), in which the cancer cells are located inside the glandular basement membrane (intraepithelial) or lamina propria, (intramucosal). In this stage, the cancer has not spread to the regional lymph nodes (NO), and there is no distant metastasis (N40). In stage 1, there is still no spread of the cancer to the regional lymph nodes and no distant metastasis, but the tumor has invaded the submucosa (T1) or has progressed further to invade the muscularis propria (T2). Stage R also involves no spread of the cancer to the regional lymph nodes and no distant metastasis, but the tumor has invaded the subserosa, or the nonperitonealized pericolic or perirectal tissues (T3), or has progressed to invade other organs or structures, and/or has perforated the visceral peritoneum (T4). Stage 3 is characterized by any of the T substages, no distant metastasis, and either metastasis in 1 to 3 regional lymph nodes (N1) or metastasis in four or more regional lymph nodes (N2). Lastly, stage 4 involves any of the T or N substages, as well as distant metastasis.

Currently, pathological staging of colon cancer is preferable over clinical staging as pathological staging provides a more accurate prognosis. Pathological staging typically involves examination of the resected colon section, along with surgical examination of the abdominal cavity.

SUMMARY OF THE INVENTION

The background art does not teach or suggest markers for colon cancer that are sufficiently sensitive and/or accurate, alone or in combination. From the foregoing, it is clear that procedures used for detecting, diagnosing, monitoring, staging, prognosticating, and preventing the recurrence of colorectal cancer are of critical importance to the outcome of the patient. Moreover, current procedures, while helpful in each of these analyses, are limited by their specificity, sensitivity, invasiveness, and/or their cost. It would therefore be desirable to provide more sensitive and accurate methods and reagents for the early diagnosis, staging, prognosis, monitoring, and treatment of diseases associated with colon cancer, or to indicate a predisposition to such for preventative measures, as well as to determine whether or not such cancer has metastasized and for monitoring the progress of colon cancer in a human which has not metastasized for the onset of metastasis.

The present invention overcomes the deficiencies of the background art by providing novel markers for colon cancer that are both sensitive and accurate. Furthermore, these markers are able to distinguish between different stages of colon cancer, such as adenocarcinoma (mucinous or signet ring cell originating); leiomyocarcomas; carcinoid. Furthermore, at least some of these markers are able to distinguish, alone or in combination, between colon cancer between non-cancerous polyps. These markers are overexpressed in colon cancer specifically, as opposed to normal colon tissue. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of colon cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between colon cancer and non-cancerous states.

According to preferred embodiments of the present invention, examples of suitable biological samples include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, colon tissue or mucous and any human organ or tissue. In a preferred embodiment, the biological sample comprises colon tissue and/or a serum sample and/or a urine sample and/or a stool sample and/or any other tissue or liquid sample. The sample can optionally be diluted with a suitable eluant before contacting the sample to an antibody and/or performing any other diagnostic assay.

Information given in the text with regard to cellular localization was determined according to four different software programs: (i) tmhmm (from Center for Biological Sequence Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/TMHMM/TMHMM2.0b.guide.php) or (ii) tmpred (from EMBnet, maintained by the ISREC Bionformatics group and the LICR Information Technology Office, Ludwig Institute for Cancer Research, Swiss Institute of Bioinformatics, http://www.ch.embnet.org/software/TMPRED_form.html) for transmembrane region prediction; (iii) signalp_hmm or (iv) signalp_nn (both from Center for Biological Sequence Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/SignalP/background/prediction.php) for signal peptide prediction. The terms “signalp_hmm” and “signalp_nn” refer to two modes of operation for the program SignalP: hmm refers to Hidden Markov Model, while nn refers to neural networks. Localization was also determined through manual inspection of known protein localization and/or gene structure, and the use of heuristics by the individual inventor. In some cases for the manual inspection of cellular localization prediction inventors used the ProLoc computational platform [Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004) “Evolution of multicellularity in metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis.” Cell Biology International 2004; 28(3):171-8.], which predicts protein localization based on various parameters including, protein domains (e.g., prediction of trans-membranous regions and localization thereof within the protein), pI, protein length, amino acid composition, homology to pre-annotated proteins, recognition of sequence patterns which direct the protein to a certain organelle (such as, nuclear localization signal, NLS, mitochondria localization signal), signal peptide and anchor modeling and using unique domains from Pfam that are specific to a single compartment.

Information is given in the text with regard to SNPs (single nucleotide polymorphisms). A description of the abbreviations is as follows. “T->C”, for example, means that the SNP results in a change at the position given in the table from T to C. Similarly, “M->Q”, for example, means that the SNP has caused a change in the corresponding amino acid sequence, from methionine (M) to glutamine (Q). If, in place of a letter at the right hand side for the nucleotide sequence SNP, there is a space, it indicates that a frameshift has occurred. A frameshift may also be indicated with a hyphen (-). A stop codon is indicated with an asterisk at the right hand side (*). As part of the description of an SNP, a comment may be found in parentheses after the above description of the SNP itself. This comment may include an FTId, which is an identifier to a SwissProt entry that was created with the indicated SNP. An FTId is a unique and stable feature identifier, which allows construction of links directly from position-specific annotation in the feature table to specialized protein-related databases. The FTId is always the last component of a feature in the description field, as follows: FTId=XXX_number, in which XXX is the 3-letter code for the specific feature key, separated by an underscore from a 6-digit number. In the table of the amino acid mutations of the wild type proteins of the selected splice variants of the invention, the header of the first column is “SNP position(s) on amino acid sequence”, representing a position of a known mutation on amino acid sequence. SNPs may optionally be used as diagnostic markers according to the present invention, alone or in combination with one or more other SNPs and/or any other diagnostic marker. Preferred embodiments of the present invention comprise such SNPs, including but not limited to novel SNPs on the known (WT or wild type) protein sequences given below, as well as novel nucleic acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a variant amino acid and/or nucleic acid sequence described herein.

Information given in the text with regard to the Homology to the known proteins was determined by Smith-Waterman version 5.1.2 using special (non default) parameters as follows:

model=sw.model

GAPEXT=0

GAPOP=100.0

MATRIX=blosum100

Information is given with regard to overexpression of a cluster in cancer based on ESTs. A key to the p values with regard to the analysis of such overexpression is as follows:

- library-based statistics: P-value without including the level of expression in cell-lines (P1)
- library based statistics: P-value including the level of expression in cell-lines (P2)
- EST clone statistics: P-value without including the level of expression in cell-lines (SP1)
- EST clone statistics: predicted overexpression ratio without including the level of expression in cell-lines (R3)
- EST clone statistics: P-value including the level of expression in cell-lines (SP2)
- EST clone statistics: predicted overexpression ratio including the level of expression in cell-lines (R4)

Library-based statistics refer to statistics over an entire library, while EST clone statistics refer to expression only for ESTs from a particular tissue or cancer.

Information is given with regard to overexpression of a cluster in cancer based on microarrays. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. There are two types of microarray results: those from microarrays prepared according to a design by the present inventors, for which the microarray fabrication procedure is described in detail in Materials and Experimental Procedures section herein; and those results from microarrays using Affymetrix technology. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. For microarrays prepared according to a design by the present inventors, the probe name begins with the name of the cluster (gene), followed by an identifying number. Oligonucleotide microarray results taken from Affymetrix data were from chips available from Affymetrix Inc, Santa Clara, Calif., USA (see for example data regarding the Human Genome U133 (HG-U133) Set at www.affymetrix.com/products/arrays/specific/hgu133.affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133av2.affx; and Human Genome U133 Plus 2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133plus.affx). The probe names follow the Affymetrix naming convention. The data is available from NCBI Gene Expression Omnibus (see www.ncbi.nlm.nih.gov/projects/geo/and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1 207-210). The dataset (including results) is available from www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1133 for the Series GSE1133 database (published on March 2004); a reference to these results is as follows: Su et al (Proc Natl Acad Sci USA. 2004 Apr. 20; 101(16):6062-7. Epub 2004 Apr. 9). A list of probes is given below.

>M85491_0_0_25999

(SEQ ID NO: 1398)

GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC

>M85491_0_14_0

(SEQ ID NO: 1399)

GTCATGAAAATCAACACCGAGGTGCGGAGGTTCGGACCTGTGTCCCGCAG

>H53626_0_16_0

(SEQ ID NO: 1400)

ATGCGGGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTTC

>H53626_0_0_8391

(SEQ ID NO: 1401)

GGGTCTGGGGTGCTCTCCTGGTCTTTGTGTCGGCGTTCCCCTCCCTACCT

>HSENA78_0_1_0

(SEQ ID NO: 1402)

TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC

>HUMGROG5_0_0_16626

(SEQ ID NO: 1403)

GCAGAAACTTTGCAGTAACACCTTCAGTGAGTTCAAGGCTAGGATCCCTG

>R00299_0_8_0

(SEQ ID NO: 1404)

CCAAGGCTCGTCTGCGCACCTTGTGTCTTGTAGGGTATGGTATGTGGGAC

>S67314_0_0_741

(SEQ ID NO: 1405)

CACAGAGCCAGGATGTTCTTCTGACCTCAGTATCTACTCCAGCTCCAGCT

>S67314_0_0_744

(SEQ ID NO: 1406)

TGGCATGCTGGAACATGGACTCTAGCTAGCAAGAAGGGCTCAAGGAGGTG

>Z44808_0_8_0

(SEQ ID NO: 1407)

AAAAGCATGAGTTTCTGACCAGCGTTCTGGACGCGCTGTCCACGGACATG

>Z44808_0_0_72347

(SEQ ID NO: 1408)

ATGTTCTTAGGAGGCAAGCCAGGAGAAGCCGGGTCTGACTTTTCAGCTCA

>Z44808_0_0_72349

(SEQ ID NO: 1409)

TCCTCCAGACCCAAAGCCACAACCCATCGCAAGTCAAGAACACTTTCCAG

>Z25299_0_3_0

(SEQ ID NO: 1410)

AACTCTGGCACCTTGGGCTGTGGAAGGCTCTGGAAAGTCCTTCAAAGCTG

>HUMCA1XIA_0_0_14909

(SEQ ID NO: 1411)

GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG

>HUMCA1XIA_0_18_0

(SEQ ID NO: 1412)

TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG

>HSS100PCB_0_0_12280

(SEQ ID NO: 1413)

CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGCTCTAAAA

>HUMPHOSLIP_0_0_18458

(SEQ ID NO: 1414)

AAGGAAGCAGGACCAGTGGATGTGAGGCGTGGTCGAAGAACAACAGAAAG

>HUMPHOSLIP_0_0_18487

(SEQ ID NO: 1415)

ACAGGGGCCAGATGGTGACCCATGACCCAGCCTAAAAGGCAGCCAGAGGG

>D11853_0_0_0

(SEQ ID NO: 1416)

GAGGCCCCTGGGTGGGAATGGGGACAGGAATTGACAGTGGAAGGGGTTCT

>D11853_0_0_3085

(SEQ ID NO: 1417)

TGACTCCCTACATACTCCAGGACTAGCTTAGGTCCCAACCCAATAGTTCC

>D11853_0_0_3082

(SEQ ID NO: 1418)

TGGTCCCCATGTGATTCTCCGAGGATCCTGAGGGTCGTGGTTTATGGAGA

>M77903_0_0_21402

(SEQ ID NO: 1419)

ACGTGATGGTTGGAACGCGTACCTTAGAGCTTCCAGTTCCGTCTTAGGAC

>AA583399_0_12_0

(SEQ ID NO: 1420)

ATCCCCACTGAACCCAGTGCTTTCACCAGCCATATTAGCTCCCACTCACC

>AA583399_0_0_1681

(SEQ ID NO: 1421)

CACCGCATGCTGCCAATCTGATGGTGGAGACAGAACAGCAGTCCCGGATG

>AA583399_0_1_1687

(SEQ ID NO: 1422)

TTTCCACACTCAGTGCCACGAAGTGCAGCTCTAAGCTGGGGATTTCTGTG

>HUMCACH1A_0_12_0

(SEQ ID NO: 1423)

ACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCCAGTGTACTGCCAAT

>HUMCACH1A_0_3_14917

(SEQ ID NO: 1331)

AGAGAATATCACTCCGATGGTCGGTTTCTGACTGTCACGCTAAGGGCAAC

>HUMGACH1A_0_0_14922

(SEQ ID NO: 1332)

GAACACAGAGAACGTCAGCGGTGAAGGCGAGAACCGAGGCTGCTGTGGAA

>HUMCACH1A_0_0_14913

(SEQ ID NO: 1334)

GACTCAGGAGATGAACAGCTCCCAACTATTTGCCGGGAAGACCCAGAGAT

>HUMCACH1A_0_0_14924

(SEQ ID NO: 1333)

GGCCCAGCATTGGGAACCTTGAGCATGTGTCTGAAAATGGGCATCATTCT

>HUMCEA_0_0_96

(SEQ ID NO: 1338)

CAAGAGGGGTTTGGCTGAGACTTTAGGATTGTGATTCAGCTTAGAGGGAC

>HUMCEA_0_0_15183

(SEQ ID NO: 1429)

CCTGGTGGGAGCCCATGAGAAGCGAGTTCTCTGTGCAACGGACTTAGTAA

>HUMCEA_0_0_15182

(SEQ ID NO: 1430)

GCTCCCTGGAGCATCAGCATCATATTCTGGGGTGGAGTCTATCTGGTTCT

>HUMCEA_0_0_15168

(SEQ ID NO: 1339)

TCCTGCCTGTCACCTGAAGTTCTAGATCATTCCCTGGACTCCACTCTATC

>HUMCEA_0_0_15180

(SEQ ID NO: 1432)

TTTAACACAGGATTGGGACAGGATTCAGAGGGACACTGTGGCCCTTCTAC

>M78035_0_0_21693

(SEQ ID NO: 1433)

CCATCCACATTTATGGAAACACTTGCTGTATATCTGGTGATTTACGTGTG

>M78035_0_0_21691

(SEQ ID NO: 1434)

CCTTTCACCACTGTGTGCAAGCGAATACACGCGGAACAATCCTAGTGAAT

>M78035_0_1_21707

(SEQ ID NO: 1435)

TTTGCTAGAAATCTGGTGTGGTGCAGGAGCGACTCCAGGATTCACTCTGT

>T23657_0_18_0

(SEQ ID NO: 1436)

TCCGTGACCCTCAGAGATCCTTTGCCCTGGGAATCCAGTGGATTGTAGTT

>T51958_0_0_50903

(SEQ ID NO: 1437)

CCCATGGTGGCCAGAGTGTCAGGTCTCATCGTGACGCTCTTGTCCTCCTC

>T51958_0_0_50916

(SEQ ID NO: 1438)

GGGGCTGTGCCCAGTCCCCCTGTCAGACCCTCAATGACTGAGGCCTGGGG

>Z17877_0_4_0

(SEQ ID NO: 1439)

ACTTTGCACTGGAACTTACAACACCCGAGCAAGGACGCGACTCTCCCGAC

>HSHCGI_0_0_10611

(SEQ ID NO: 1440)

GCCTACTGATTCATCCACATACAATTCTCAGCGTATATCCAAATGCAGTC

>HSHCGI_0_0_10620

(SEQ ID NO: 1441)

GGACCTCTAAGTCTACAGGTGGTCAAAATGCTGTATCCACCCAATTCCAC

The following list of abbreviations for tissues was used in the TAA histograms. The term “TAA” stands for “Tumor Associated Antigen”, and the TAA histograms, given in the text, represent the cancerous tissue expression pattern as predicted by the biomarkers selection engine, as described in detail in examples 1-5 below:

- “BONE” for “bone”;
- “COL” for “colon”;
- “EPI” for “epithelial”;
- “GEN” for “general”;
- “LIVER” for “liver”;
- “LUN” for “lung”;
- “LYMPH” for “lymph nodes”;
- “MARROW” for “bone marrow”;
- “OVA” for “ovary”;
- “PANCREAS” for “pancreas”;
- “PRO” for “prostate”;
- “STOMACH” for “stomach”;
- “TCELL” for “T cells”;
- “THYROID” for “Thyroid”;
- “MAM” for “breast”;
- “BRAIN” for “brain”;
- “UTERUS” for “uterus”;
- “SKIN” for “skin”;
- “KIDNEY” for “kidney”;
- “MUSCLE” for “muscle”;
- “ADREN” for “adrenal”;
- “HEAD” for “head and neck”;
- “BLADDER” for “bladder”;

It should be noted that the terms “segment”, “seg” and “node” are used interchangeably in reference to nucleic acid sequences of the present invention; they refer to portions of nucleic acid sequences that were shown to have one or more properties as described below. They are also the building blocks that were used to construct complete nucleic acid sequences as described in greater detail below. Optionally and preferably, they are examples of oligonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary oligonucleotides may optionally be derived, and/or for any other use.

As used herein the phrase “colon cancer” refers to cancers of the colon or colorectal cancers.

The term “marker” in the context of the present invention refers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from subjects (patients) having colon cancer as compared to a comparable sample taken from subjects who do not have colon cancer.

The phrase “differentially present” refers to differences in the quantity of a marker present in a sample taken from patients having colon cancer as compared to a comparable sample taken from patients who do not have colon cancer. For example, a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in the other sample, for example as measured by hybridization and/or NAT-based assays. A polypeptide is differentially present between the two samples if the amount of the polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present.

As used herein the phrase “diagnostic” means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity. The “sensitivity” of a diagnostic assay is the percentage of diseased individuals who test positive (percent of “true positives”). Diseased individuals not detected by the assay are “false negatives.” Subjects who are not diseased and who test negative in the assay are termed “true negatives.” The “specificity” of a diagnostic assay is 1 minus the false positive rate, where the “false positive” rate is defined as the proportion of those without the disease who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it suffices if the method provides a positive indication that aids in diagnosis.

As used herein the phrase “diagnosing” refers to classifying a disease or a symptom, determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery. The term “detecting” may also optionally encompass any of the above.

Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease. It should be noted that a “biological sample obtained from the subject” may also optionally comprise a sample that has not been physically removed from the subject, as described in greater detail below.

As used herein, the term “level” refers to expression levels of RNA and/or protein or to DNA copy number of a marker of the present invention.

Typically the level of the marker in a biological sample obtained from the subject is different (i.e., increased or decreased) from the level of the same variant in a similar sample obtained from a healthy individual (examples of biological samples are described herein).

Numerous well known tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and/or polypeptide of the variant of interest in the subject.

Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy/sample is obtained the level of the variant can be determined and a diagnosis can thus be made.

Determining the level of the same variant in normal tissues of the same origin is preferably effected along-side to detect an elevated expression and/or amplification and/or a decreased expression, of the variant as opposed to the normal tissues.

A “test amount” of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of colon cancer. A test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).

A “control amount” of a marker can be any amount or a range of amounts to be compared against a test amount of a marker. For example, a control amount of a marker can be the amount of a marker in a patient with colon cancer or a person without colon cancer. A control amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).

“Detect” refers to identifying the presence, absence or amount of the object to be detected.

A “label” includes any moiety or item detectable by spectroscopic, photo chemical, biochemical, immunochemical, or chemical means. For example, useful labels include ³²P, ³⁵S, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin-streptavadin, dioxigenin, haptens and proteins for which antisera or monoclonal antibodies are available, or nucleic acid molecules with a sequence complementary to a target. The label often generates a measurable signal, such as a radioactive, chromogenic, or fluorescent signal, that can be used to quantify the amount of bound label in a sample. The label can be incorporated in or attached to a primer or probe either covalently, or through ionic, van der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides, or biotinylated nucleotides that are recognized by streptavadin. The label may be directly or indirectly detectable. Indirect detection can involve the binding of a second label to the first label, directly or indirectly. For example, the label can be the ligand of a binding partner, such as biotin, which is a binding partner for streptavadin, or a nucleotide sequence, which is the binding partner for a complementary sequence, to which it can specifically hybridize. The binding partner may itself be directly detectable, for example, an antibody may be itself labeled with a fluorescent molecule. The binding partner also may be indirectly detectable, for example, a nucleic acid having a complementary nucleotide sequence can be a part of a branched DNA molecule that is in turn detectable through hybridization with other labeled nucleic acid molecules (see, e.g., P. D. Fahrlander and A. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is achieved by, e.g., scintillation counting, densitometry, or flow cytometry.

Exemplary detectable labels, optionally and preferably for use with immunoassays, include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.

“Immunoassay” is an assay that uses an antibody to specifically bind an antigen. The immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen.

The phrase “specifically (or selectively) binds” to an antibody or “specifically (or selectively) immunoreactive with,” when referring to a protein or peptide (or other epitope), refers to a binding reaction that is determinative of the presence of the protein in a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample. Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein. For example, polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic variants and alleles of seminal basic protein. This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity). Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NOs: 1 and 2.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 and 99. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 534 and 535.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NOs: 3, 4, 5 and 6.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 100, 101, 102, 103, 104, 105, 106 and 107.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 536, 537, 538 and 539.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 7.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121 and 122.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 540.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NO. 8 and 9.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141 and 142.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 541, 542.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 10.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 143, 144, 145, 146, 147, 148 and 149.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 543.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 11, 12, 13 and 14.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166 and 167.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 544, 545, 546 and 547.

According to preferred embodiments of the present invention, there is provided an isolated polynucleoide comprising a transcript SEQ ID NO. 15.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183 and 184.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO. 548.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 16.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195 and 196.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 549.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 17 and 18.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210 and 211.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 550 and 551.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 19, 20, 21 and 22.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 212, 213, 214, 215, 216, 217, 218 and 219.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 552, 553, 554 and 555.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 23, 24, 25, 26 and 27.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239 and 240.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 556, 557, 558 and 559.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 28, 29, 30, 31 and 32.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 241, 242, 243, 244, 245, 246, 247, 248, 249, 250 and 251.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 560, 561, 562 and 563.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 33, 34, and 35.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 267, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 564, 565, and 566.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 36, 37, 38, 39, 40, 41, 42 and 43.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305 and 306.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 567, 568, 569, 570, 571, 572, 573 and 574.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 44.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 307, 308, 309, 310, 311, 312, 313, 314, 315 and 316.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO. 575.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 45, 46, 47 and 48.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361 and 362.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 576, 577, 578 and 579.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 49.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 363, 364 and 365.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO. 580.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 50, 51, 52, 53, 54, 55 and 56.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417 and 418.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 581, 582, 583, 584, 585, 586 and 587.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72 , 73 and 74.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 43, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448 and 449.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601 and 602.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 75, 76, 77, 78, 79 and 80.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474 and 475.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 603, 604, 605, 606 and 607.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 81, 82, 83 and 84.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503 and 504.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 608, 609, 610 and 611.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 85, 86, 87 and 88.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 505-532 and 533.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 612, 613, 614 and 615.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encodings from clusters M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 608, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-207 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-207 of SEQ ID NO. 608, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 208-214 of SEQ ID NO. 608, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 608, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to in SEQ ID NO. 608.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 609, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-207 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-207 of SEQ ID NO. 609.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 610, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-181 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-181 of SEQ ID NO. 610, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 182-192 of SEQ ID NO. 610, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 610, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to in SEQ ID NO. 610.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 611, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-93 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-93 of SEQ ID NO. 611, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 94-104 of SEQ ID NO. 611, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 611, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 611.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 1-110 of SEQ ID NO. 604, and a second amino acid sequence being at least 90% homologous to amino acids 1-112 of Q8IXM0, which also corresponds to amino acids 111-222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 604, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-110 of SEQ ID NO. 604.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-83 of Q96AC2, which also corresponds to amino acids 1-83 of SEQ ID NO. 604, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 84-222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 604.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-83 of Q8N2G4, which also corresponds to amino acids 1-83 of SEQ ID NO. 604, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 84-222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 90% homologous to amino acids 24-106 of BAC85518 (SEQ ID NO:1396), which also corresponds to amino acids 1-83 of SEQ ID NO. 604, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 84-222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-64 of Q96AC2, which also corresponds to amino acids 1-64 of SEQ ID NO. 605, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 65-93 of SEQ ID NO. 605, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 65-93 in SEQ ID NO. 605.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-64 of Q8N2G4, which also corresponds to amino acids 1-64 of SEQ ID NO. 605, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 65-93 of SEQ ID NO. 605, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1-5 of SEQ ID NO. 605, second amino acid sequence being at least 90% homologous to amino acids 22-80 of BAC85273 (SEQ ID NO:1397), which also corresponds to amino acids 6-64 of SEQ ID NO. 605, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 65-93 of SEQ ID NO. 605, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 605, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-5 of SEQ ID NO. 605.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90% homologous to amino acids 24-87 of BAC85518 (SEQ ID NO:1396), which also corresponds to amino acids 1-64 of SEQ ID NO. 605, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 65-93 of SEQ ID NO. 605, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-63 of Q96AC2, which also corresponds to amino acids 1-63 of SEQ ID NO. 606, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64-84 of SEQ ID NO. 606, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 606, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 64-84 in SEQ ID NO. 606.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-63 of Q96AC2, which also corresponds to amino acids 1-63 of SEQ ID NO. 607, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64-90 of SEQ ID NO. 607, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 64-90 in SEQ ID NO. 607.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-63 of Q8N2G4, which also corresponds to amino acids 1-63 of SEQ ID NO. 607, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64-90 of SEQ ID NO. 607 wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-5 of SEQ ID NO. 607, second amino acid sequence being at least 90% homologous to amino acids 22-79 of BAC85273 (SEQ ID NO:1397), which also corresponds to amino acids 6-63 of SEQ ID NO. 607, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64-90 of SEQ ID NO. 607, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 607, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-5 of SEQ ID NO. 607.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 90% homologous to amino acids 24-86 of BAC85518 (SEQ ID NO:1396), which also corresponds to amino acids 1-63 of SEQ ID NO. 607, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64-90 of SEQ ID NO. 607, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 588, a second amino acid sequence being at least 90% homologous to amino acids 13-187 of SEQ ID NO. 639, which also corresponds to amino acids 27-201 of SEQ ID NO. 588, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 588, and a third amino acid sequence being at least 90% homologous to amino acids 189-342 of SEQ ID NO. 639, which also corresponds to amino acids 203-356 of SEQ ID NO. 588, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 588, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino acids 1-26 of SEQ ID NO. 588.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-109 of SEQ ID NO. 588, a second amino acid sequence being at least 90% homologous to amino acids 1-159 of SEQ ID NO. 640, which also corresponds to amino acids 110-268 of SEQ ID NO. 588, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-356 of SEQ ID NO. 588, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 588, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 588.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 588, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 588, and a second amino acid sequence being at least 90% homologous to amino acids 130-356 of SEQ ID NO. 638, which also corresponds to amino acids 130-356 of SEQ ID NO. 588, wherein said first amino acid sequence, bridging amino acid and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to amino acids 1-26 of SEQ ID NO. 589, a second amino acid sequence being at least 90% homologous to amino acids 13-187 of SEQ ID NO. 639, which also corresponds to amino acids 27-201 of SEQ ID NO. 589, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 589, a third amino acid sequence being at least 90% homologous to amino acids 189-297 of SEQ ID NO. 639, which also corresponds to amino acids 203-311 of SEQ ID NO. 589, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312-315 of SEQ ID NO. 589, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 589.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 589.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence to amino acids 1-109 of SEQ ID NO. 589, a second amino acid sequence being at least 90% homologous to amino acids 1-159 of SEQ ID NO. 640, which also corresponds to amino acids 110-268 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-315 of SEQ ID NO. 589, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 589, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 589, a second amino acid sequence being at least 90% homologous to amino acids 130-311 of SEQ ID NO. 638, which also corresponds to amino acids 130-311 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 130-311 of SEQ ID NO. 589, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-311 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-311 of SEQ ID NO. 589, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312-315 of SEQ ID NO. 589, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-109 of SEQ ID NO. 589, a second amino acid sequence being at least 90% homologous to amino acids 1-159 of SEQ ID NO. 640, which also corresponds to amino acids 110-268 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-315 of SEQ ID NO. 589, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 589, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 589, a second amino acid sequence being at least 90% homologous to amino acids 130-311 of SEQ ID NO. 638, which also corresponds to amino acids 130-311 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312-315 of SEQ ID NO. 589, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-311 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-311 of SEQ ID NO. 589, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312-315 of SEQ ID NO. 589, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 590, a second amino acid sequence being at least 90% homologous to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of SEQ ID NO. 590, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 590, a third amino acid sequence being at least 90% homologous to amino acids 189-254 of SEQ ID NO. 639, which also corresponds to amino acids 203-268 of SEQ ID NO. 590, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-290 of SEQ ID NO. 590, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 590, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 590.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 590, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 590.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 590, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 590, a second amino acid sequence being at least 90% homologous to amino acids 130-268 of SEQ ID NO. 638, which also corresponds to amino acids 130-268 of SEQ ID NO. 590, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-290 of SEQ ID NO. 590, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-268 of SEQ ID NO. 590, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-290 of SEQ ID NO. 590, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 591, a second amino acid sequence being at least 90% homologous to amino acids 13-187 of SEQ ID NO. 639, which also corresponds to amino acids 27-201 of SEQ ID NO. 591, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 591, a third amino acid sequence being at least 90% homologous to amino acids 189-226 of SEQ ID NO. 639, which also corresponds to amino acids 282-397 of SEQ ID NO. 591, a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241-281 of SEQ ID NO. 591, and a fifth amino acid sequence being at least 90% homologous to amino acids 227-342 of SEQ ID NO. 639, which also corresponds to amino acids 282-397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 591, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 591.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 591, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding amino corresponding to SEQ ID NO. 591.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-109 of SEQ ID NO. 591, a second amino acid sequence being at least 90% homologous to amino acids 1-131 of SEQ ID NO. 640, which also corresponds to amino acids 110-240 of SEQ ID NO. 591, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241-281 of SEQ ID NO. 591, a fourth amino acid sequence being at least 90% homologous to amino acids 132-159 of SEQ ID NO. 640, which also corresponds to amino acids 282-309 of SEQ ID NO. 591, and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310-397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 591, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 591.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of SEQ ID NO. 591, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 591, a second amino acid sequence being at least 90% homologous to amino acids 241-281 of SEQ ID NO. 638, which also corresponds to amino acids 130-240 of SEQ ID NO. 591, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241-281 of SEQ ID NO. 591, and a fourth amino acid sequence being at least 90% homologous to amino acids 241-356 of SEQ ID NO. 638, which also corresponds to amino acids 282-397 of SEQ ID NO. 591, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-240 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-240 of SEQ ID NO. 591, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241-281 of SEQ ID NO. 591, and a third amino acid sequence being at least 90% homologous to amino acids 241-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 282-397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 592, a second amino acid sequence being at least 90% homologous to amino acids 13-187 of SEQ ID NO. 639, which also corresponds to amino acids 27-201 of SEQ ID NO. 592, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 592, a third amino acid sequence being at least 90% homologous to amino acids 189-254 of SEQ ID NO. 639, which also corresponds to amino acids 203-268 of SEQ ID NO. 592, and a fourth amino acid sequence being at least 90% homologous to amino acids 298-342 of SEQ ID NO. 639, which also corresponds to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 592.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268−x to 268; and ending at any of amino acid numbers 269+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence amino acids 1-109 of SEQ ID NO. 592, a second amino acid sequence being at least 90% homologous to amino acids 1-159 of SEQ ID NO. 640, which also corresponds to amino acids 110-268 of SEQ ID NO. 592, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 592, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 592.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 592, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 592, a second amino acid sequence being at least 90% homologous to amino acids 130-268 of SEQ ID NO. 638, which also corresponds to amino acids 130-268 of SEQ ID NO. 592, and a third amino acid sequence being at least 90% homologous to amino acids 312-356 of SEQ ID NO. 638, which also corresponds to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-268 of SEQ ID NO. 592, and a second amino acid sequence being at least 90% homologous to amino acids 312-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence amino acids 1-109 of SEQ ID NO. 592, a second amino acid sequence being at least 90% homologous to amino acids 1-159 of SEQ ID NO. 640, which also corresponds to amino acids 110-268 of SEQ ID NO. 592, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 592, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 592, a second amino acid sequence being at least 90% homologous to amino acids 130-268 of SEQ ID NO. 638, which also corresponds to amino acids 130-268 of SEQ ID NO. 592, and a third amino acid sequence being at least 90% homologous to amino acids 312-356 of SEQ ID NO. 638, which also corresponds to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-268 of SEQ ID NO. 592, and a second amino acid sequence being at least 90% homologous to amino acids 312-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 269-313 of SEQ ID NO. 592, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 593, a second amino acid sequence being at least 90% homologous to amino acids 13-187 of SEQ ID NO. 639, which also corresponds to amino acids 27-201 of SEQ ID NO. 593, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 593, a third amino acid sequence being at least 90% homologous to amino acids 227-254 of SEQ ID NO. 639, which also corresponds to amino acids 282-309 of SEQ ID NO. 593, a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241-281 of SEQ ID NO. 593, a fifth amino acid sequence being at least 90% homologous to amino acids 227-254 of SEQ ID NO. 639, which also corresponds to amino acids 282-309 of SEQ ID NO. 593, and a sixth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310-331 of SEQ ID NO. 593, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence, fifth amino acid sequence and sixth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 593.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 593, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino corresponding to SEQ ID NO. 593.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 593.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 593, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 593, a second amino acid sequence being at least 90% homologous to amino acids 130-240 of SEQ ID NO. 638, which also corresponds to amino acids 130-240 of SEQ ID NO. 593, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241-281 of SEQ ID NO. 593, a fourth amino acid sequence being at least 90% homologous to amino acids 241-268 of SEQ ID NO. 638, which also corresponds to amino acids 282-309 of SEQ ID NO. 593, and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310-331 of SEQ ID NO. 593, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-240 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-240 of SEQ ID NO. 593, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310-331 of SEQ ID NO. 593, a third amino acid sequence being at least 90% homologous to amino acids 241-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 282-309 of SEQ ID NO. 593, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310-331 of SEQ ID NO. 593, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 594, a second amino acid sequence being at least 90% homologous to amino acids 13-134 of SEQ ID NO. 639, which also corresponds to amino acids 27-148 of SEQ ID NO. 594, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149-183 of SEQ ID NO. 594, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 594, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 594.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 594.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 594, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 594, a second amino acid sequence being at least 90% homologous to amino acids 130-148 of SEQ ID NO. 638, which also corresponds to amino acids 130-148 of SEQ ID NO. 594, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149-183 of SEQ ID NO. 594, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-148 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-148 of SEQ ID NO. 594, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149-183 of SEQ ID NO. 594, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 595, a second amino acid sequence being at least 90% homologous to amino acids 13-180 of SEQ ID NO. 639, which also corresponds to amino acids 27-194 of SEQ ID NO. 595, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 195-220 of SEQ ID NO. 595, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 595, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 595.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 595.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 595, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 595, a second amino acid sequence being at least 90% homologous to amino acids 130-194 of SEQ ID NO. 638, which also corresponds to amino acids 130-194 of SEQ ID NO. 595, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 195-220 of SEQ ID NO. 595, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-194 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-194 of SEQ ID NO. 595, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 195-220 of SEQ ID NO. 595, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 596, a second amino acid sequence being at least 90% homologous to amino acids 13-134 of SEQ ID NO. 639, which also corresponds to amino acids 27-148 of SEQ ID NO. 596, a third amino acid sequence being at least 90% homologous to amino acids 180-187 of SEQ ID NO. 639, which also corresponds to amino acids 149-156 of SEQ ID NO. 596, a bridging amino acid A corresponding to amino acid 157 of SEQ ID NO. 596, and a fourth amino acid sequence being at least 90% homologous to amino acids 189-342 of SEQ ID NO. 639, which also corresponds to amino acids 158-311 of SEQ ID NO. 596, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, bridging amino acid and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 596, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 596.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148−x to 148; and ending at any of amino acid numbers 149+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149-223 of SEQ ID NO. 596, a second amino acid sequence being at least 90% homologous to amino acids 1-39 of SEQ ID NO. 640, which also corresponds to amino acids 110-148 of SEQ ID NO. 596, a third amino acid sequence being at least 90% homologous to amino acids 85-159 of SEQ ID NO. 640, which also corresponds to amino acids 149-223 of SEQ ID NO. 596, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 224-311 of SEQ ID NO. 596, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 596, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 596.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of SEQ ID NO. 596, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 596, a second amino acid sequence being at least 90% homologous to amino acids 130-148 of SEQ ID NO. 638, which also corresponds to amino acids 130-148 of SEQ ID NO. 596, and a third amino acid sequence being at least 90% homologous to corresponding to amino acids 194-356 of SEQ ID NO. 638, which also corresponds to amino acids 149-311 of SEQ ID NO. 596, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-148 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-148 of SEQ ID NO. 596, and a second amino acid sequence being at least 90% homologous to amino acids 194-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 149-311 of SEQ ID NO. 596, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 597, a second amino acid sequence being at least 90% homologous to amino acids 13-143 of SEQ ID NO. 639, which also corresponds to amino acids 27-157 of SEQ ID NO. 597, and a third amino acid sequence being at least 90% homologous to amino acids 295-342 of SEQ ID NO. 639, which also corresponds to amino acids 158-205 of SEQ ID NO. 597, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 597, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 597.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157−x to 157; and ending at any of amino acid numbers 158+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of SEQ ID NO. 597, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 597, a second amino acid sequence being at least 90% homologous to amino acids 130-157 of SEQ ID NO. 639, which also corresponds to amino acids 130-157 of SEQ ID NO. 597, and a third amino acid sequence being at least 90% homologous to amino acids 309-356 of ID NO. 639, which also corresponds to amino acids 158-205 of SEQ ID NO. 597, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 598, a second amino acid sequence being at least 90% homologous to amino acids 13-128 of SEQ ID NO. 639, which also corresponds to amino acids 27-142 of SEQ ID NO. 598, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 143-161 of SEQ ID NO. 598, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 598, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 598.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 598.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-128 of SEQ ID NO. 638, which also corresponds to amino acids 1-128 of SEQ ID NO. 598, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 598, a second amino acid sequence being at least 90% homologous to amino acids 130-142 of SEQ ID NO. 638, which also corresponds to amino acids 130-142 of SEQ ID NO. 598, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 143-161 of SEQ ID NO. 598, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-142 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-142 of SEQ ID NO. 598, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 143-161 of SEQ ID NO. 598, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 600, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-61 of SEQ ID NO. 638, which also corresponds to amino acids 1-61 of SEQ ID NO. 600, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62-102 of SEQ ID NO. 600, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 600, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino in SEQ ID NO. 600.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 600, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-61 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-61 of SEQ ID NO. 600, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62-102 of SEQ ID NO. 600, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 601, a second amino acid sequence being at least 90% homologous to amino acids 13-47 of SEQ ID NO. 639, which also corresponds to amino acids 27-61 of SEQ ID NO. 601, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62-72 of SEQ ID NO. 601, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 601, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 601.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 601, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 62-72 in SEQ ID NO. 601.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-61 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-61 of SEQ ID NO. 601, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62-72 of SEQ ID NO. 601, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-61 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-61 of SEQ ID NO. 601, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62-72 of SEQ ID NO. 601, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-26 of SEQ ID NO. 602, a second amino acid sequence being at least 90% homologous to amino acids 13-80 of SEQ ID NO. 639, which also corresponds to amino acids 27-94 of SEQ ID NO. 602, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 95-111 of SEQ ID NO. 602, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 602, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 602.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 602.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-94 of SEQ ID NO. 638, which also corresponds to amino acids 1-94 of SEQ ID NO. 602, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 95-111 of SEQ ID NO. 602, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-94 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-94 of SEQ ID NO. 602, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 95-111 of SEQ ID NO. 602, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 581, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-67 of SEQ ID NO. 581, and a second amino acid sequence being at least 90% homologous to amino acids 163-493 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 68-398 of SEQ ID NO. 581, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 581, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EK, having a structure as follows: a sequence starting from any of amino acid numbers 67−x to 67; and ending at any of amino acid numbers 68+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 582, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-427 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-427 of SEQ ID NO. 582, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 428-432 of SEQ ID NO. 582, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 582, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 582.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 584, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-67 of SEQ ID NO. 584, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 68-98 of SEQ ID NO. 584, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 584, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 68-98 in SEQ ID NO. 584.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 585, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-183 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-183 of SEQ ID NO. 585, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 184-200 of SEQ ID NO. 585, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 585, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 585.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 586, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-205 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-205 of SEQ ID NO. 586, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 206-217 of SEQ ID NO. 586, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 586, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 586.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 587, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-109 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-109 of SEQ ID NO. 587, a second amino acid sequence bridging amino acid sequence comprising of L, a third amino acid sequence being at least 90% homologous to amino acids 163-183 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 111-131 of SEQ ID NO. 587, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 132-148 of SEQ ID NO. 587, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 587, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise FLK having a structure as follows (numbering according to SEQ ID NO. 587): a sequence starting from any of amino acid numbers 109−x to 109; and ending at any of amino acid numbers 111+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 587, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 587.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 576, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-1056 of SEQ ID NO. 634, which also corresponds to amino acids 1-1056 of SEQ ID NO. 576, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1057-1081 of SEQ ID NO. 576, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 576, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1057-1081 in SEQ ID NO. 576.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 577, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-714 of SEQ ID NO. 634, which also corresponds to amino acids 1-714 of SEQ ID NO. 577, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 715-729 of SEQ ID NO. 577, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 577, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 577.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 578, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-648 of SEQ ID NO. 634, which also corresponds to amino acids 1-648 of SEQ ID NO. 578, a second amino acid sequence being at least 90% homologous to amino acids 667-714 of SEQ ID NO. 634, which also corresponds to amino acids 649-696 of SEQ ID NO. 578, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 697-738 of SEQ ID NO. 578, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 578, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648−x to 648; and ending at any of amino acid numbers 649+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 578, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 578.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 579, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-260 of SEQ ID NO. 634, which also corresponds to amino acids 1-260 of SEQ ID NO. 579, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 261-273 of SEQ ID NO. 579, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 579, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 579.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 575, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-13 of GFR2_HUMAN (SEQ ID NO:632), which also corresponds to amino acids 1-13 of SEQ ID NO. 575, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 14-30 of SEQ ID NO. 575, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 575, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 14-30 in SEQ ID NO. 575.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-123 of SEQ ID NO. 631, which also corresponds to amino acids 1-123 of SEQ ID NO. 567, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124-156 of SEQ ID NO. 567, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 567, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 567.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-73 of SEQ ID NO. 567, and a second amino acid sequence being at least 90% homologous to amino acids 1799-1881 of SEQ ID NO. 629, which also corresponds to amino acids 74-156 of SEQ ID NO. 567, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 567, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino acids 1-73 of SEQ ID NO. 567.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 567, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 567, a second amino acid sequence being at least 90% homologous to amino acids 54-124 of SEQ ID NO. 630, which also corresponds to amino acids 54-124 of SEQ ID NO. 567, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 125-156 of SEQ ID NO. 567, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 568, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 568.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 568, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 568, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 568, a second amino acid sequence being at least 90% homologous to amino acids 54-122 of SEQ ID NO. 630, which also corresponds to amino acids 54-122 of SEQ ID NO. 568, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 123-136 of SEQ ID NO. 568, and a fourth amino acid sequence being at least 90% homologous to amino acids 123-155 of SEQ ID NO. 630, which also corresponds to amino acids 137-169 of SEQ ID NO. 568, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 568, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 123-136, corresponding to SEQ ID NO. 568.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 569, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino in SEQ ID NO. 569.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 569, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 569, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 569, a second amino acid sequence being at least 90% homologous to amino acids 54-123 of SEQ ID NO. 630, which also corresponds to amino acids 54-123 of SEQ ID NO. 569, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124-148 of SEQ ID NO. 569, and a fourth amino acid sequence being at least 90% homologous to amino acids 124-155 of SEQ ID NO. 630, which also corresponds to amino acids 149-180 of SEQ ID NO. 569, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 569, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 124-148, corresponding to SEQ ID NO. 569.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 570, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-123 of SEQ ID NO. 631, which also corresponds to amino acids 1-123 of SEQ ID NO. 570, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124-145 of SEQ ID NO. 570, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 570, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 570.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 570, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 570, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 570, a second amino acid sequence being at least 90% homologous to amino acids 54-124 of SEQ ID NO. 630, which also corresponds to amino acids 54-124 of SEQ ID NO. 570, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 125-145 of SEQ ID NO. 570, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 571, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-101 of SEQ ID NO. 631, which also corresponds to amino acids 1-101 of SEQ ID NO. 571, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102-122 of SEQ ID NO. 571, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 571, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 571.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 571, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 571, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 571, a second amino acid sequence being at least 90% homologous to amino acids 54-101 of SEQ ID NO. 630, which also corresponds to amino acids 54-101 of SEQ ID NO. 571, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102-122 of SEQ ID NO. 571, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 572, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-62 of SEQ ID NO. 631, which also corresponds to amino acids 1-62 of SEQ ID NO. 572, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 572, a second amino acid sequence being at least 90% homologous to amino acids 64-123 of SEQ ID NO. 631, which also corresponds to amino acids 64-123 of SEQ ID NO. 572, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124-155 of SEQ ID NO. 572, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 572, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 572.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 572, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 572, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 572, a second amino acid sequence being at least 90% homologous to LSDDEETIS corresponding to amino acids 54-62 of SEQ ID NO. 630, which also corresponds to amino acids 54-62 of SEQ ID NO. 572, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 572, and a third amino acid sequence being at least 90% homologous to amino acids 64-155 of SEQ ID NO. 630, which also corresponds to amino acids 64-155 of SEQ ID NO. 572, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 573 comprising a first amino acid sequence being at least 90% homologous to amino acids 1-62 of SEQ ID NO. 631 which also corresponds to amino acids 1-62 of SEQ ID NO. 573, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 573, a second amino acid sequence being at least 90% homologous to amino acids 64-101 of SEQ ID NO. 631, which also corresponds to amino acids 64-101 of SEQ ID NO. 573, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102-109 of SEQ ID NO. 573, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 573, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 573.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 573, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630 which also corresponds to amino acids 1-52 of SEQ ID NO. 573, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 573, a second amino acid sequence being at least 90% homologous to amino acids 54-62 of SEQ ID NO. 630, which also corresponds to amino acids 54-62 of SEQ ID NO. 573, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 573, a third amino acid sequence being at least 90% homologous to amino acids 64-101 of SEQ ID NO. 630, which also corresponds to amino acids 64-101 of SEQ ID NO. 573, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102-109 of SEQ ID NO. 573, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 574, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-62 of SEQ ID NO. 631, which also corresponds to amino acids 1-62 of SEQ ID NO. 574, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 574, a second amino acid sequence being at least 90% homologous to amino acids 64-101 of SEQ ID NO. 631, which also corresponds to amino acids 64-101 of SEQ ID NO. 574, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102-133 of SEQ ID NO. 574, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 574, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 574.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 574, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-52 of SEQ ID NO. 630, which also corresponds to amino acids 1-52 of SEQ ID NO. 574, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 574, a second amino acid sequence being at least 90% homologous to amino acids 54-62 of SEQ ID NO. 630, which also corresponds to amino acids 54-62 of SEQ ID NO. 574, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 574, a third amino acid sequence being at least 90% homologous to amino acids 64-101 of SEQ ID NO. 630, which also corresponds to amino acids 64-101 of SEQ ID NO. 574, and a fourth amino acid sequence being at least 90% homologous to amino acids 124-155 of SEQ ID NO. 630, which also corresponds to amino acids 102-133 of SEQ ID NO. 574, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 574, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KV, having a structure as follows: a sequence starting from any of amino acid numbers 101−x to 101; and ending at any of amino acid numbers 102+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 564, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-1617 of SEQ ID NO. 627, which also corresponds to amino acids 1-1617 of SEQ ID NO. 564, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1618-1645 of SEQ ID NO. 564, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 564, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1618-1645 in SEQ ID NO. 564.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 565, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-2062 of SEQ ID NO. 627, which also corresponds to amino acids 1-2062 of SEQ ID NO. 565, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 2063-2074 of SEQ ID NO. 565, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 565, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 2063-2074 in SEQ ID NO. 565.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 566, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-587 of SEQ ID NO. 627, which also corresponds to amino acids 1-587 of SEQ ID NO. 566, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 588-603 of SEQ ID NO. 566, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 566, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 566.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 560, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-131 of SEQ ID NO. 625, which also corresponds to amino acids 1-131 of SEQ ID NO. 560, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 132-139 of SEQ ID NO. 560, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 560, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 560.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 561, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-131 of SEQ ID NO. 625, which also corresponds to amino acids 1-131 of SEQ ID NO. 561, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 132-156 of SEQ ID NO. 561, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 561, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 561.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 562, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-81 of SEQ ID NO. 625, which also corresponds to amino acids 1-81 of SEQ ID NO. 562, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 82-89 of SEQ ID NO. 562, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 562, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 82-89 in SEQ ID NO. 562.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 563, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-82 of SEQ ID NO. 625 which also corresponds to amino acids 1-82 of SEQ ID NO. 563.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 552, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of SEQ ID NO. 552, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-215 of SEQ ID NO. 552, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 552, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 552.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 552, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of SEQ ID NO. 552, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-215 of SEQ ID NO. 552, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-178 of SEQ ID NO. 553, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 553.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-178 of SEQ ID NO. 553, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-178 of SEQ ID NO. 553, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-178 of SEQ ID NO. 553, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 554, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of SEQ ID NO. 554, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-126 of SEQ ID NO. 554, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 554, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 554.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 554, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of SEQ ID NO. 554, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117-126 of SEQ ID NO. 554, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 555, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-24 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-24 of SEQ ID NO. 555, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 25-35 of SEQ ID NO. 555, and a third amino acid sequence being at least 90% homologous to amino acids 25-133 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 36-144 of SEQ ID NO. 555, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 555, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 25-35 corresponding to SEQ ID NO. 555.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 555, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-24 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-24 of SEQ ID NO. 555, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 25-35 of SEQ ID NO. 555, and a third amino acid sequence being at least 90% homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQK WDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding to amino acids 25-133 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 36-144 of SEQ ID NO. 555, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 534, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-476 of EPB2_HUMAN (SEQ ID NO:616), which also corresponds to amino acids 1-476 of SEQ ID NO. 534, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 477-496 of SEQ ID NO. 534, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 534, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 534.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 535, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:616), which also corresponds to amino acids 1-270 of SEQ ID NO. 535, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 271-301 of SEQ ID NO. 535, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 535, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 535.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 536, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-319 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-319 of SEQ ID NO. 536, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 320-324 of SEQ ID NO. 536, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 536, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 536.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 537, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-234 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-234 of SEQ ID NO. 537, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 235-256 of SEQ ID NO. 537, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 537, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 537.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 537, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-234 of Q13774 (SEQ ID NO:1382), which also corresponds to amino acids 1-234 of SEQ ID NO. 537, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 235-256 of SEQ ID NO. 537, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 538, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-320 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-320 of SEQ ID NO. 538, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 321-390 of SEQ ID NO. 538, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 538, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 538.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 539, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-141 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-141 of SEQ ID NO. 539, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 142-183 of SEQ ID NO. 539, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 539, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 539.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 540, comprising a first amino acid sequence being at least 90% homologous to amino acids 168-180 of Q9HAP5 (SEQ ID NO:1384), which also corresponds to amino acids 1-167 of SEQ ID NO. 540, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 168-180 of SEQ ID NO. 540, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 540, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 540.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 541, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-357 of Q8N441 (SEQ ID NO:1385), which also corresponds to amino acids 1-357 of SEQ ID NO. 541, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 358-437 of SEQ ID NO. 541, and a third amino acid sequence being at least 90% homologous to amino acids 358-504 of Q8N441 (SEQ ID NO:1385), which also corresponds to amino acids 438-584 of SEQ ID NO. 541, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 541, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for corresponding to SEQ ID NO. 541.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 542, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-269 of Q9H4D7 (SEQ ID NO:1386), which also corresponds to amino acids 1-269 of SEQ ID NO. 542, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 270-490 of SEQ ID NO. 542, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 542, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 542.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 542, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-269 of Q8N441 (SEQ ID NO:1385), which also corresponds to amino acids 1-269 of SEQ ID NO. 542, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 270-490 of SEQ ID NO. 542, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 543, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-81 of SZ05_HUMAN (SEQ ID NO:618), which also corresponds to amino acids 1-81 of SEQ ID NO. 543.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 544, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-74 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 1-74 of SEQ ID NO. 544.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 545, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-103 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 1-103 of SEQ ID NO. 545.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 546, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-61 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 1-61 of SEQ ID NO. 546, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62-98 of SEQ ID NO. 546, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 546, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 62-98 in SEQ ID NO. 546.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 547, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-103 of SEQ ID NO. 547, and a second amino acid sequence being at least 90% homologous to amino acids 34-107 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 104-177 of SEQ ID NO. 547, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 547, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-103 of SEQ ID NO. 547.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-29 of SEQ ID NO. 548, and a second amino acid sequence being at least 90% homologous to amino acids 151-461 of DCOR_HUMAN (SEQ ID NO:620), which also corresponds to amino acids 30-340 of SEQ ID NO. 548, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-29 of SEQ ID NO. 548.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-29 of SEQ ID NO. 548, and a second amino acid sequence being at least 90% homologous to amino acids 40-350 of AAA59968 (SEQ ID NO:1387), which also corresponds to amino acids 30-340 of SEQ ID NO. 548, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-29 of SEQ ID NO. 548, and a second amino acid sequence being at least 90% homologous to amino acids 86-396 of AAH14562 (SEQ ID NO:1388), which also corresponds to amino acids 30-340 of SEQ ID NO. 548, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 549, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-44 of SEQ ID NO. 549, second amino acid sequence being at least 90% homologous to amino acids 74-191 of Q9NWT9 (SEQ ID NO:1389), which also corresponds to amino acids 45-162 of SEQ ID NO. 549, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 163-238 of SEQ ID NO. 549, wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 549, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-44 of SEQ ID NO. 549.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 549, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 549.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 549, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-44 of SEQ ID NO. 549, and a second amino acid sequence being at least 90% homologous to amino acids 21-214 of TESC_HUMAN (SEQ ID NO:621), which also corresponds to amino acids 45-238 of SEQ ID NO. 549, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 550, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-130 of SEQ ID NO. 550, and a second amino acid sequence being at least 90% homologous to amino acids 1-172 of Q96C98 (SEQ ID NO:1390), which also corresponds to amino acids 131-302 of SEQ ID NO. 550, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 550, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-130 of SEQ ID NO. 550.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 550, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-74 of SEQ ID NO. 550, and a second amino acid sequence being at least 90% homologous to amino acids 53-280 of Q9BVA2 (SEQ ID NO:1391), which also corresponds to amino acids 75-302 of SEQ ID NO. 550, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 551, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-34 of SEQ ID NO. 551, and a second amino acid sequence being at least 90% homologous to corresponding to amino acids 60-172 of Q96C98 (SEQ ID NO:1390), which also corresponds to amino acids 35-147 of SEQ ID NO. 551, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 551 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-34 of SEQ ID NO. 551.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 551, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1-34 of SEQ ID NO. 551, and a second amino acid sequence being at least 90% homologous to corresponding to amino acids 168-280 of Q9BVA2 (SEQ ID NO:1391), which also corresponds to amino acids 35-147 of SEQ ID NO. 551, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 551, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-34 of SEQ ID NO. 551.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 556, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-441 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-441 of SEQ ID NO. 556, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 442-464 of SEQ ID NO. 556, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an An isolated polypeptide encoding for a tail of SEQ ID NO. 556, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 556.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 557, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-428 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-428 of SEQ ID NO. 557, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 429-434 of SEQ ID NO. 557, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 557, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino in SEQ ID NO. 557.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 558, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-441 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-441 of SEQ ID NO. 558, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 442-454 of SEQ ID NO. 558, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 558, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous amino in SEQ ID NO. 558.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 559, comprising a first amino acid sequence being at least 90% homologous to amino acids 1-170 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-170 of SEQ ID NO. 559, and a second amino acid sequence being at least 90% homologous to amino acids 188-446 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 171-429 of SEQ ID NO. 559, wherein said first and second amino acid sequences are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 559, comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TD, having a structure as follows: a sequence starting from any of amino acid numbers 170−x to 170; and ending at any of amino acid numbers 171+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR. Optionally said amino acid sequence corresponds to a bridge, edge portion, tail, head or insertion.

Optionally the antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein.

According to preferred embodiments of the present invention, there is provided a kit for detecting colon cancer, comprising a kit detecting overexpression of a splice variant from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR.

Optionally the kit comprises a NAT-based technology.

Optionally the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence.

Optionally the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence.

Optionally the kit comprises an antibody.

Optionally the kit further comprises at least one reagent for performing an ELISA or a Western blot.

According to preferred embodiments of the present invention, there is provided an method for detecting colon cancer, comprising detecting overexpression of a splice variant from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR.

Optionally detecting overexpression is performed with a NAT-based technology.

Optionally said detecting overexpression is performed with an immunoassay.

Optionally the immunoassay comprises an antibody.

According to preferred embodiments of the present invention, there is provided a biomarker capable of detecting colon cancer, comprising nucleic acid sequences or a fragment thereof, or amino acid sequences or a fragment thereof from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR.

According to preferred embodiments of the present invention, there is provided a method for screening for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay.

According to preferred embodiments of the present invention, there is provided a method for diagnosing colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay.

According to preferred embodiments of the present invention, there is provided a method for monitoring disease progression of colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay.

According to preferred embodiments of the present invention, there is provided a method of selecting a therapy for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay and selecting a therapy according to said detection.

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

AA583399_PEA_1_T0 (SEQ ID NO: 643)

AA583399_PEA_1_T1 (SEQ ID NO: 644)

AA583399_PEA_1_T2 (SEQ ID NO: 645)

AA583399_PEA_1_T3 (SEQ ID NO: 646)

AA583399_PEA_1_T4 (SEQ ID NO: 647)

AA583399_PEA_1_T5 (SEQ ID NO: 648)

AA583399_PEA_1_T6 (SEQ ID NO: 649)

AA583399_PEA_1_T7 (SEQ ID NO: 650)

AA583399_PEA_1_T8 (SEQ ID NO: 651)

AA583399_PEA_1_T9 (SEQ ID NO: 652)

AA583399_PEA_1_T10 (SEQ ID NO: 653)

AA583399_PEA_1_T11 (SEQ ID NO: 654)

AA583399_PEA_1_T12 (SEQ ID NO: 655)

AA583399_PEA_1_T15 (SEQ ID NO: 656)

AA583399_PEA_1_T16 (SEQ ID NO: 657)

AA583399_PEA_1_T17 (SEQ ID NO: 658)

a nucleic acid sequence comprising a sequence selected from the table below:

Segment Name

AA583399_PEA_1_node_0 (SEQ ID NO: 659)

AA583399_PEA_1_node_3 (SEQ ID NO: 660)

AA583399_PEA_1_node_9 (SEQ ID NO: 661)

AA583399_PEA_1_node_10 (SEQ ID NO: 662)

AA583399_PEA_1_node_12 (SEQ ID NO: 663)

AA583399_PEA_1_node_14 (SEQ ID NO: 664)

AA583399_PEA_1_node_21 (SEQ ID NO: 665)

AA583399_PEA_1_node_24 (SEQ ID NO: 666)

AA583399_PEA_1_node_25 (SEQ ID NO: 667)

AA583399_PEA_1_node_29 (SEQ ID NO: 668)

AA583399_PEA_1_node_1 (SEQ ID NO: 669)

AA583399_PEA_1_node_2 (SEQ ID NO: 670)

AA583399_PEA_1_node_4 (SEQ ID NO: 671)

AA583399_PEA_1_node_5 (SEQ ID NO: 672)

AA583399_PEA_1_node_6 (SEQ ID NO: 673)

AA583399_PEA_1_node_7 (SEQ ID NO: 674)

AA583399_PEA_1_node_8 (SEQ ID NO: 675)

AA583399_PEA_1_node_11 (SEQ ID NO: 676)

AA583399_PEA_1_node_19 (SEQ ID NO: 677)

AA583399_PEA_1_node_27 (SEQ ID NO: 678)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

AA583399_PEA_1_P3 (SEQ ID NO: 683)

AA583399_PEA_1_P2 (SEQ ID NO: 684)

AA583399_PEA_1_P4 (SEQ ID NO: 685)

AA583399_PEA_1_P5 (SEQ ID NO: 686)

AA583399_PEA_1_P6 (SEQ ID NO: 687)

AA583399_PEA_1_P8 (SEQ ID NO: 688)

AA583399_PEA_1_P10 (SEQ ID NO: 689)

AA583399_PEA_1_P11 (SEQ ID NO: 690)

AA583399_PEA_1_P12 (SEQ ID NO: 691)

AA583399_PEA_1_P14 (SEQ ID NO: 692)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

AI684092_PEA_1_T2 (SEQ ID NO: 693)

AI684092_PEA_1_T3 (SEQ ID NO: 694)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

AI684092_PEA_1_node_0 (SEQ ID NO: 695)

AI684092_PEA_1_node_2 (SEQ ID NO: 696)

AI684092_PEA_1_node_4 (SEQ ID NO: 697)

AI684092_PEA_1_node_5 (SEQ ID NO: 698)

AI684092_PEA_1_node_6 (SEQ ID NO: 699)

AI684092_PEA_1_node_7 (SEQ ID NO: 700)

AI684092_PEA_1_node_8 (SEQ ID NO: 701)

AI684092_PEA_1_node_9 (SEQ ID NO: 702)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

AI684092_PEA_1_P1 (SEQ ID NO: 703)

AI684092_PEA_1_P3 (SEQ ID NO: 704)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)

HUMCACH1A_PEA_1_T20 (SEQ ID NO: 721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO: 722)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

HUMCACH1A_PEA_1_node_2 (SEQ ID NO: 723)

HUMCACH1A_PEA_1_node_5 (SEQ ID NO: 724)

HUMCACH1A_PEA_1_node_9 (SEQ ID NO: 725)

HUMCACH1A_PEA_1_node_11 (SEQ ID NO: 726)

HUMCACH1A_PEA_1_node_14 (SEQ ID NO: 727)

HUMCACH1A_PEA_1_node_16 (SEQ ID NO: 728)

HUMCACH1A_PEA_1_node_27 (SEQ ID NO: 729)

HUMCACH1A_PEA_1_node_30 (SEQ ID NO: 730)

HUMCACH1A_PEA_1_node_33 (SEQ ID NO: 731)

HUMCACH1A_PEA_1_node_41 (SEQ ID NO: 732)

HUMCACH1A_PEA_1_node_43 (SEQ ID NO: 733)

HUMCACH1A_PEA_1_node_45 (SEQ ID NO: 734)

HUMCACH1A_PEA_1_node_47 (SEQ ID NO: 735)

HUMCACH1A_PEA_1_node_55 (SEQ ID NO: 736)

HUMCACH1A_PEA_1_node_57 (SEQ ID NO: 737)

HUMCACH1A_PEA_1_node_70 (SEQ ID NO: 738)

HUMCACH1A_PEA_1_node_72 (SEQ ID NO: 739)

HUMCACH1A_PEA_1_node_74 (SEQ ID NO: 740)

HUMCACH1A_PEA_1_node_86 (SEQ ID NO: 741)

HUMCACH1A_PEA_1_node_92 (SEQ ID NO: 742)

HUMCACH1A_PEA_1_node_94 (SEQ ID NO: 743)

HUMCACH1A_PEA_1_node_103 (SEQ ID NO: 744)

HUMCACH1A_PEA_1_node_104 (SEQ ID NO: 745)

HUMCACH1A_PEA_1_node_106 (SEQ ID NO: 746)

HUMCACH1A_PEA_1_node_109 (SEQ ID NO: 747)

HUMCACH1A_PEA_1_node_113 (SEQ ID NO: 748)

HUMCACH1A_PEA_1_node_114 (SEQ ID NO: 749)

HUMCACH1A_PEA_1_node_116 (SEQ ID NO: 750)

HUMCACH1A_PEA_1_node_119 (SEQ ID NO: 751)

HUMCACH1A_PEA_1_node_121 (SEQ ID NO: 752)

HUMCACH1A_PEA_1_node_123 (SEQ ID NO: 753)

HUMCACH1A_PEA_1_node_125 (SEQ ID NO: 754)

HUMCACH1A_PEA_1_node_128 (SEQ ID NO: 755)

HUMCACH1A_PEA_1_node_0 (SEQ ID NO: 756)

HUMCACH1A_PEA_1_node_3 (SEQ ID NO: 757)

HUMCACH1A_PEA_1_node_7 (SEQ ID NO: 758)

HUMCACH1A_PEA_1_node_23 (SEQ ID NO: 759)

HUMCACH1A_PEA_1_node_26 (SEQ ID NO: 760)

HUMCACH1A_PEA_1_node_32 (SEQ ID NO: 761)

HUMCACH1A_PEA_1_node_35 (SEQ ID NO: 762)

HUMCACH1A_PEA_1_node_37 (SEQ ID NO: 763)

HUMCACH1A_PEA_1_node_39 (SEQ ID NO: 764)

HUMCACH1A_PEA_1_node_49 (SEQ ID NO: 765)

HUMCACH1A_PEA_1_node_51 (SEQ ID NO: 766)

HUMCACH1A_PEA_1_node_53 (SEQ ID NO: 767)

HUMCACH1A_PEA_1_node_58 (SEQ ID NO: 768)

HUMCACH1A_PEA_1_node_60 (SEQ ID NO: 769)

HUMCACH1A_PEA_1_node_62 (SEQ ID NO: 770)

HUMCACH1A_PEA_1_node_64 (SEQ ID NO: 771)

HUMCACH1A_PEA_1_node_66 (SEQ ID NO: 772)

HUMCACH1A_PEA_1_node_68 (SEQ ID NO: 773)

HUMCACH1A_PEA_1_node_76 (SEQ ID NO: 774)

HUMCACH1A_PEA_1_node_77 (SEQ ID NO: 775)

HUMCACH1A_PEA_1_node_79 (SEQ ID NO: 776)

HUMCACH1A_PEA_1_node_81 (SEQ ID NO: 777)

HUMCACH1A_PEA_1_node_84 (SEQ ID NO: 778)

HUMCACH1A_PEA_1_node_88 (SEQ ID NO: 779)

HUMCACH1A_PEA_1_node_90 (SEQ ID NO: 780)

HUMCACH1A_PEA_1_node_96 (SEQ ID NO: 781)

HUMCACH1A_PEA_1_node_98 (SEQ ID NO: 782)

HUMCACH1A_PEA_1_node_100 (SEQ ID NO: 783)

HUMCACH1A_PEA_1_node_101 (SEQ ID NO: 784)

HUMCACH1A_PEA_1_node_107 (SEQ ID NO: 785)

HUMCACH1A_PEA_1_node_111 (SEQ ID NO: 786)

HUMCACH1A_PEA_1_node_117 (SEQ ID NO: 787)

HUMCACH1A_PEA_1_node_124 (SEQ ID NO: 788)

HUMCACH1A_PEA_1_node_126 (SEQ ID NO: 789)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

HUMCACH1A_PEA_1_P2 (SEQ ID NO: 792)

HUMCACH1A_PEA_1_P3 (SEQ ID NO: 793)

HUMCACH1A_PEA_1_P4 (SEQ ID NO: 794)

HUMCACH1A_PEA_1_P5 (SEQ ID NO: 795)

HUMCACH1A_PEA_1_P7 (SEQ ID NO: 796)

HUMCACH1A_PEA_1_P8 (SEQ ID NO: 797)

HUMCACH1A_PEA_1_P9 (SEQ ID NO: 798)

HUMCACH1A_PEA_1_P10 (SEQ ID NO: 799)

HUMCACH1A_PEA_1_P11 (SEQ ID NO: 800)

HUMCACH1A_PEA_1_P12 (SEQ ID NO: 801)

HUMCACH1A_PEA_1_P13 (SEQ ID NO: 802)

HUMCACH1A_PEA_1_P14 (SEQ ID NO: 803)

HUMCACH1A_PEA_1_P15 (SEQ ID NO: 804)

HUMCACH1A_PEA_1_P17 (SEQ ID NO: 805)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

HUMCEA_PEA_1_node_0 (SEQ ID NO: 816)

HUMCEA_PEA_1_node_2 (SEQ ID NO: 817)

HUMCEA_PEA_1_node_6 (SEQ ID NO: 818)

HUMCEA_PEA_1_node_11 (SEQ ID NO: 819)

HUMCEA_PEA_1_node_12 (SEQ ID NO: 820)

HUMCEA_PEA_1_node_31 (SEQ ID NO: 821)

HUMCEA_PEA_1_node_36 (SEQ ID NO: 822)

HUMCEA_PEA_1_node_42 (SEQ ID NO: 823)

HUMCEA_PEA_1_node_43 (SEQ ID NO: 824)

HUMCEA_PEA_1_node_44 (SEQ ID NO: 825)

HUMCEA_PEA_1_node_46 (SEQ ID NO: 826)

HUMCEA_PEA_1_node_48 (SEQ ID NO: 827)

HUMCEA_PEA_1_node_63 (SEQ ID NO: 828)

HUMCEA_PEA_1_node_65 (SEQ ID NO: 829)

HUMCEA_PEA_1_node_67 (SEQ ID NO: 830)

HUMCEA_PEA_1_node_3 (SEQ ID NO: 831)

HUMCEA_PEA_1_node_7 (SEQ ID NO: 832)

HUMCEA_PEA_1_node_8 (SEQ ID NO: 833)

HUMCEA_PEA_1_node_9 (SEQ ID NO: 834)

HUMCEA_PEA_1_node_10 (SEQ ID NO: 835)

HUMCEA_PEA_1_node_15 (SEQ ID NO: 836)

HUMCEA_PEA_1_node_16 (SEQ ID NO: 837)

HUMCEA_PEA_1_node_17 (SEQ ID NO: 838)

HUMCEA_PEA_1_node_18 (SEQ ID NO: 839)

HUMCEA_PEA_1_node_19 (SEQ ID NO: 840)

HUMCEA_PEA_1_node_20 (SEQ ID NO: 841)

HUMCEA_PEA_1_node_21 (SEQ ID NO: 842)

HUMCEA_PEA_1_node_22 (SEQ ID NO: 843)

HUMCEA_PEA_1_node_23 (SEQ ID NO: 844)

HUMCEA_PEA_1_node_24 (SEQ ID NO: 845)

HUMCEA_PEA_1_node_27 (SEQ ID NO: 846)

HUMCEA_PEA_1_node_29 (SEQ ID NO: 847)

HUMCEA_PEA_1_node_30 (SEQ ID NO: 848)

HUMCEA_PEA_1_node_33 (SEQ ID NO: 849)

HUMCEA_PEA_1_node_34 (SEQ ID NO: 850)

HUMCEA_PEA_1_node_35 (SEQ ID NO: 851)

HUMCEA_PEA_1_node_45 (SEQ ID NO: 852)

HUMCEA_PEA_1_node_49 (SEQ ID NO: 853)

HUMCEA_PEA_1_node_50 (SEQ ID NO: 854)

HUMCEA_PEA_1_node_51 (SEQ ID NO: 855)

HUMCEA_PEA_1_node_56 (SEQ ID NO: 856)

HUMCEA_PEA_1_node_57 (SEQ ID NO: 857)

HUMCEA_PEA_1_node_58 (SEQ ID NO: 858)

HUMCEA_PEA_1_node_60 (SEQ ID NO: 859)

HUMCEA_PEA_1_node_61 (SEQ ID NO: 860)

HUMCEA_PEA_1_node_62 (SEQ ID NO: 861)

HUMCEA_PEA_1_node_64 (SEQ ID NO: 862)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

HUMCEA_PEA_1_P4 (SEQ ID NO: 864)

HUMCEA_PEA_1_P5 (SEQ ID NO: 865)

HUMCEA_PEA_1_P7 (SEQ ID NO: 866)

HUMCEA_PEA_1_P10 (SEQ ID NO: 867)

HUMCEA_PEA_1_P14 (SEQ ID NO: 868)

HUMCEA_PEA_1_P19 (SEQ ID NO: 869)

HUMCEA_PEA_1_P20 (SEQ ID NO: 870)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

M78035_T0 (SEQ ID NO: 871)

M78035_T3 (SEQ ID NO: 872)

M78035_T4 (SEQ ID NO: 873)

M78035_T7 (SEQ ID NO: 874)

M78035_T9 (SEQ ID NO: 875)

M78035_T11 (SEQ ID NO: 876)

M78035_T17 (SEQ ID NO: 877)

M78035_T18 (SEQ ID NO: 878)

M78035_T19 (SEQ ID NO: 879)

M78035_T20 (SEQ ID NO: 880)

M78035_T27 (SEQ ID NO: 881)

M78035_T28 (SEQ ID NO: 882)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

M78035_node_4 (SEQ ID NO: 883)

M78035_node_6 (SEQ ID NO: 884)

M78035_node_10 (SEQ ID NO: 885)

M78035_node_17 (SEQ ID NO: 886)

M78035_node_18 (SEQ ID NO: 887)

M78035_node_21 (SEQ ID NO: 888)

M78035_node_25 (SEQ ID NO: 889)

M78035_node_33 (SEQ ID NO: 890)

M78035_node_55 (SEQ ID NO: 891)

M78035_node_58 (SEQ ID NO: 892)

M78035_node_60 (SEQ ID NO: 893)

M78035_node_62 (SEQ ID NO: 894)

M78035_node_63 (SEQ ID NO: 895)

M78035_node_64 (SEQ ID NO: 896)

M78035_node_65 (SEQ ID NO: 897)

M78035_node_69 (SEQ ID NO: 898)

M78035_node_71 (SEQ ID NO: 899)

M78035_node_14 (SEQ ID NO: 900)

M78035_node_15 (SEQ ID NO: 901)

M78035_node_20 (SEQ ID NO: 902)

M78035_node_24 (SEQ ID NO: 903)

M78035_node_26 (SEQ ID NO: 904)

M78035_node_28 (SEQ ID NO: 905)

M78035_node_29 (SEQ ID NO: 906)

M78035_node_30 (SEQ ID NO: 907)

M78035_node_31 (SEQ ID NO: 908)

M78035_node_34 (SEQ ID NO: 909)

M78035_node_35 (SEQ ID NO: 910)

M78035_node_37 (SEQ ID NO: 911)

M78035_node_40 (SEQ ID NO: 912)

M78035_node_48 (SEQ ID NO: 913)

M78035_node_49 (SEQ ID NO: 914)

M78035_node_50 (SEQ ID NO: 915)

M78035_node_52 (SEQ ID NO: 916)

M78035_node_53 (SEQ ID NO: 917)

M78035_node_54 (SEQ ID NO: 918)

M78035_node_56 (SEQ ID NO: 919)

M78035_node_57 (SEQ ID NO: 920)

M78035_node_59 (SEQ ID NO: 921)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

M78035_P2 (SEQ ID NO: 923)

M78035_P4 (SEQ ID NO: 924)

M78035_P6 (SEQ ID NO: 925)

M78035_P8 (SEQ ID NO: 926)

M78035_P18 (SEQ ID NO: 927)

M78035_P19 (SEQ ID NO: 928)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

R30650_PEA_2_T2 (SEQ ID NO: 929)

R30650_PEA_2_T3 (SEQ ID NO: 930)

R30650_PEA_2_T6 (SEQ ID NO: 931)

R30650_PEA_2_T14 (SEQ ID NO: 932)

R30650_PEA_2_T15 (SEQ ID NO: 933)

R30650_PEA_2_T18 (SEQ ID NO: 934)

R30650_PEA_2_T21 (SEQ ID NO: 935)

R30650_PEA_2_T23 (SEQ ID NO: 936)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

R30650_PEA_2_node_0 (SEQ ID NO: 937)

R30650_PEA_2_node_1 (SEQ ID NO: 938)

R30650_PEA_2_node_3 (SEQ ID NO: 939)

R30650_PEA_2_node_5 (SEQ ID NO: 940)

R30650_PEA_2_node_9 (SEQ ID NO: 941)

R30650_PEA_2_node_11 (SEQ ID NO: 942)

R30650_PEA_2_node_14 (SEQ ID NO: 943)

R30650_PEA_2_node_20 (SEQ ID NO: 944)

R30650_PEA_2_node_22 (SEQ ID NO: 945)

R30650_PEA_2_node_24 (SEQ ID NO: 946)

R30650_PEA_2_node_26 (SEQ ID NO: 947)

R30650_PEA_2_node_32 (SEQ ID NO: 948)

R30650_PEA_2_node_34 (SEQ ID NO: 949)

R30650_PEA_2_node_36 (SEQ ID NO: 950)

R30650_PEA_2_node_37 (SEQ ID NO: 951)

R30650_PEA_2_node_39 (SEQ ID NO: 952)

R30650_PEA_2_node_41 (SEQ ID NO: 953)

R30650_PEA_2_node_42 (SEQ ID NO: 954)

R30650_PEA_2_node_44 (SEQ ID NO: 955)

R30650_PEA_2_node_46 (SEQ ID NO: 956)

R30650_PEA_2_node_50 (SEQ ID NO: 957)

R30650_PEA_2_node_56 (SEQ ID NO: 958)

R30650_PEA_2_node_60 (SEQ ID NO: 959)

R30650_PEA_2_node_63 (SEQ ID NO: 960)

R30650_PEA_2_node_67 (SEQ ID NO: 961)

R30650_PEA_2_node_70 (SEQ ID NO: 962)

R30650_PEA_2_node_72 (SEQ ID NO: 963)

R30650_PEA_2_node_73 (SEQ ID NO: 964)

R30650_PEA_2_node_75 (SEQ ID NO: 965)

R30650_PEA_2_node_79 (SEQ ID NO: 966)

R30650_PEA_2_node_86 (SEQ ID NO: 967)

R30650_PEA_2_node_87 (SEQ ID NO: 968)

R30650_PEA_2_node_89 (SEQ ID NO: 969)

R30650_PEA_2_node_93 (SEQ ID NO: 970)

R30650_PEA_2_node_8 (SEQ ID NO: 971)

R30650_PEA_2_node_17 (SEQ ID NO: 972)

R30650_PEA_2_node_28 (SEQ ID NO: 973)

R30650_PEA_2_node_31 (SEQ ID NO: 974)

R30650_PEA_2_node_48 (SEQ ID NO: 975)

R30650_PEA_2_node_53 (SEQ ID NO: 976)

R30650_PEA_2_node_58 (SEQ ID NO: 977)

R30650_PEA_2_node_68 (SEQ ID NO: 978)

R30650_PEA_2_node_77 (SEQ ID NO: 979)

R30650_PEA_2_node_82 (SEQ ID NO: 980)

R30650_PEA_2_node_85 (SEQ ID NO: 981)

R30650_PEA_2_node_88 (SEQ ID NO: 982)

R30650_PEA_2_node_90 (SEQ ID NO: 983)

R30650_PEA_2_node_91 (SEQ ID NO: 984)

R30650_PEA_2_node_92 (SEQ ID NO: 985)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

R30650_PEA_2_P4 (SEQ ID NO: 991)

R30650_PEA_2_P5 (SEQ ID NO: 992)

R30650_PEA_2_P8 (SEQ ID NO: 993)

R30650_PEA_2_P12 (SEQ ID NO: 994)

R30650_PEA_2_P13 (SEQ ID NO: 995)

R30650_PEA_2_P15 (SEQ ID NO: 996)

R30650_PEA_2_P17 (SEQ ID NO: 997)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

T23657_T0 (SEQ ID NO: 998)

T23657_T1 (SEQ ID NO: 999)

T23657_T2 (SEQ ID NO: 1000)

T23657_T3 (SEQ ID NO: 1001)

T23657_T4 (SEQ ID NO: 1002)

T23657_T5 (SEQ ID NO: 1003)

T23657_T6 (SEQ ID NO: 1004)

T23657_T7 (SEQ ID NO: 1005)

T23657_T8 (SEQ ID NO: 1006)

T23657_T9 (SEQ ID NO: 1007)

T23657_T10 (SEQ ID NO: 1008)

T23657_T11 (SEQ ID NO: 1009)

T23657_T12 (SEQ ID NO: 1010)

T23657_T13 (SEQ ID NO: 1011)

T23657_T14 (SEQ ID NO: 1012)

T23657_T15 (SEQ ID NO: 1013)

T23657_T16 (SEQ ID NO: 1014)

T23657_T17 (SEQ ID NO: 1015)

T23657_T19 (SEQ ID NO: 1016)

T23657_T20 (SEQ ID NO: 1017)

T23657_T21 (SEQ ID NO: 1018)

T23657_T22 (SEQ ID NO: 1019)

T23657_T23 (SEQ ID NO: 1020)

T23657_T24 (SEQ ID NO: 1021)

T23657_T28 (SEQ ID NO: 1022)

T23657_T30 (SEQ ID NO: 1023)

T23657_T31 (SEQ ID NO: 1024)

T23657_T32 (SEQ ID NO: 1025)

T23657_T35 (SEQ ID NO: 1026)

T23657_T37 (SEQ ID NO: 1027)

T23657_T38 (SEQ ID NO: 1028)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

T23657_node_2 (SEQ ID NO: 1029)

T23657_node_3 (SEQ ID NO: 1030)

T23657_node_8 (SEQ ID NO: 1031)

T23657_node_16 (SEQ ID NO: 1032)

T23657_node_18 (SEQ ID NO: 1033)

T23657_node_23 (SEQ ID NO: 1034)

T23657_node_24 (SEQ ID NO: 1035)

T23657_node_27 (SEQ ID NO: 1036)

T23657_node_29 (SEQ ID NO: 1037)

T23657_node_34 (SEQ ID NO: 1038)

T23657_node_37 (SEQ ID NO: 1039)

T23657_node_38 (SEQ ID NO: 1040)

T23657_node_39 (SEQ ID NO: 1041)

T23657_node_40 (SEQ ID NO: 1042)

T23657_node_45 (SEQ ID NO: 1043)

T23657_node_46 (SEQ ID NO: 1044)

T23657_node_49 (SEQ ID NO: 1045)

T23657_node_0 (SEQ ID NO: 1046)

T23657_node_4 (SEQ ID NO: 1047)

T23657_node_6 (SEQ ID NO: 1048)

T23657_node_11 (SEQ ID NO: 1049)

T23657_node_20 (SEQ ID NO: 1050)

T23657_node_22 (SEQ ID NO: 1051)

T23657_node_25 (SEQ ID NO: 1052)

T23657_node_26 (SEQ ID NO: 1053)

T23657_node_28 (SEQ ID NO: 1054)

T23657_node_30 (SEQ ID NO: 1055)

T23657_node_31 (SEQ ID NO: 1056)

T23657_node_32 (SEQ ID NO: 1057)

T23657_node_41 (SEQ ID NO: 1058)

T23657_node_42 (SEQ ID NO: 1059)

T23657_node_43 (SEQ ID NO: 1060)

T23657_node_44 (SEQ ID NO: 1061)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

T23657_P1 (SEQ ID NO: 1063)

T23657_P2 (SEQ ID NO: 1064)

T23657_P3 (SEQ ID NO: 1065)

T23657_P4 (SEQ ID NO: 1066)

T23657_P5 (SEQ ID NO: 1067)

T23657_P6 (SEQ ID NO: 1068)

T23657_P7 (SEQ ID NO: 1069)

T23657_P8 (SEQ ID NO: 1070)

T23657_P9 (SEQ ID NO: 1071)

T23657_P10 (SEQ ID NO: 1072)

T23657_P11 (SEQ ID NO: 1073)

T23657_P12 (SEQ ID NO: 1074)

T23657_P16 (SEQ ID NO: 1075)

T23657_P17 (SEQ ID NO: 1076)

T23657_P19 (SEQ ID NO: 1077)

T23657_P21 (SEQ ID NO: 1078)

T23657_P22 (SEQ ID NO: 1079)

T23657_P23 (SEQ ID NO: 1080)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

T51958_PEA_1_T4 (SEQ ID NO: 1081)

T51958_PEA_1_T5 (SEQ ID NO: 1082)

T51958_PEA_1_T6 (SEQ ID NO: 1083)

T51958_PEA_1_T8 (SEQ ID NO: 1084)

T51958_PEA_1_T12 (SEQ ID NO: 1085)

T51958_PEA_1_T16 (SEQ ID NO: 1086)

T51958_PEA_1_T33 (SEQ ID NO: 1087)

T51958_PEA_1_T35 (SEQ ID NO: 1088)

T51958_PEA_1_T37 (SEQ ID NO: 1089)

T51958_PEA_1_T39 (SEQ ID NO: 1090)

T51958_PEA_1_T40 (SEQ ID NO: 1091)

T51958_PEA_1_T41 (SEQ ID NO: 1092)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

T51958_PEA_1_node_0 (SEQ ID NO: 1093)

T51958_PEA_1_node_7 (SEQ ID NO: 1094)

T51958_PEA_1_node_8 (SEQ ID NO: 1095)

T51958_PEA_1_node_9 (SEQ ID NO: 1096)

T51958_PEA_1_node_14 (SEQ ID NO: 1097)

T51958_PEA_1_node_16 (SEQ ID NO: 1098)

T51958_PEA_1_node_18 (SEQ ID NO: 1099)

T51958_PEA_1_node_21 (SEQ ID NO: 1100)

T51958_PEA_1_node_22 (SEQ ID NO: 1101)

T51958_PEA_1_node_24 (SEQ ID NO: 1102)

T51958_PEA_1_node_27 (SEQ ID NO: 1103)

T51958_PEA_1_node_29 (SEQ ID NO: 1104)

T51958_PEA_1_node_33 (SEQ ID NO: 1105)

T51958_PEA_1_node_40 (SEQ ID NO: 1106)

T51958_PEA_1_node_41 (SEQ ID NO: 1107)

T51958_PEA_1_node_46 (SEQ ID NO: 1108)

T51958_PEA_1_node_51 (SEQ ID NO: 1109)

T51958_PEA_1_node_55 (SEQ ID NO: 1110)

T51958_PEA_1_node_67 (SEQ ID NO: 1111)

T51958_PEA_1_node_70 (SEQ ID NO: 1112)

T51958_PEA_1_node_74 (SEQ ID NO: 1113)

T51958_PEA_1_node_78 (SEQ ID NO: 1114)

T51958_PEA_1_node_11 (SEQ ID NO: 1115)

T51958_PEA_1_node_15 (SEQ ID NO: 1116)

T51958_PEA_1_node_20 (SEQ ID NO: 1117)

T51958_PEA_1_node_26 (SEQ ID NO: 1118)

T51958_PEA_1_node_35 (SEQ ID NO: 1119)

T51958_PEA_1_node_36 (SEQ ID NO: 1120)

T51958_PEA_1_node_38 (SEQ ID NO: 1121)

T51958_PEA_1_node_39 (SEQ ID NO: 1122)

T51958_PEA_1_node_42 (SEQ ID NO: 1123)

T51958_PEA_1_node_43 (SEQ ID NO: 1124)

T51958_PEA_1_node_44 (SEQ ID NO: 1125)

T51958_PEA_1_node_45 (SEQ ID NO: 1126)

T51958_PEA_1_node_47 (SEQ ID NO: 1127)

T51958_PEA_1_node_48 (SEQ ID NO: 1128)

T51958_PEA_1_node_49 (SEQ ID NO: 1129)

T51958_PEA_1_node_50 (SEQ ID NO: 1130)

T51958_PEA_1_node_54 (SEQ ID NO: 1131)

T51958_PEA_1_node_61 (SEQ ID NO: 1132)

T51958_PEA_1_node_71 (SEQ ID NO: 1133)

T51958_PEA_1_node_72 (SEQ ID NO: 1134)

T51958_PEA_1_node_75 (SEQ ID NO: 1135)

T51958_PEA_1_node_76 (SEQ ID NO: 1136)

T51958_PEA_1_node_77 (SEQ ID NO: 1137)

T51958_PEA_1_node_80 (SEQ ID NO: 1138)

T51958_PEA_1_node_82 (SEQ ID NO: 1139)

T51958_PEA_1_node_84 (SEQ ID NO: 1140)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

T51958_PEA_1_P5 (SEQ ID NO: 1151)

T51958_PEA_1_P6 (SEQ ID NO: 1152)

T51958_PEA_1_P28 (SEQ ID NO: 1153)

T51958_PEA_1_P30 (SEQ ID NO: 1154)

T51958_PEA_1_P34 (SEQ ID NO: 1155)

T51958_PEA_1_P35 (SEQ ID NO: 1156)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

Z17877_PEA_1_T0 (SEQ ID NO: 1157)

Z17877_PEA_1_T2 (SEQ ID NO: 1158)

Z17877_PEA_1_T3 (SEQ ID NO: 1159)

Z17877_PEA_1_T4 (SEQ ID NO: 1160)

Z17877_PEA_1_T6 (SEQ ID NO: 1161)

Z17877_PEA_1_T7 (SEQ ID NO: 1162)

Z17877_PEA_1_T8 (SEQ ID NO: 1163)

Z17877_PEA_1_T11 (SEQ ID NO: 1164)

Z17877_PEA_1_T12 (SEQ ID NO: 1165)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

Z17877_PEA_1_node_0 (SEQ ID NO: 1166)

Z17877_PEA_1_node_3 (SEQ ID NO: 1167)

Z17877_PEA_1_node_8 (SEQ ID NO: 1168)

Z17877_PEA_1_node_9 (SEQ ID NO: 1169)

Z17877_PEA_1_node_10 (SEQ ID NO: 1170)

Z17877_PEA_1_node_11 (SEQ ID NO: 1171)

Z17877_PEA_1_node_13 (SEQ ID NO: 1172)

Z17877_PEA_1_node_15 (SEQ ID NO: 1173)

Z17877_PEA_1_node_16 (SEQ ID NO: 1174)

Z17877_PEA_1_node_18 (SEQ ID NO: 1175)

Z17877_PEA_1_node_1 (SEQ ID NO: 1176)

Z17877_PEA_1_node_2 (SEQ ID NO: 1177)

Z17877_PEA_1_node_4 (SEQ ID NO: 1178)

Z17877_PEA_1_node_5 (SEQ ID NO: 1179)

Z17877_PEA_1_node_6 (SEQ ID NO: 1180)

Z17877_PEA_1_node_14 (SEQ ID NO: 1181)

Z17877_PEA_1_node_17 (SEQ ID NO: 1182)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below

Protein Name

Z17877_PEA_1_P1 (SEQ ID NO: 1183)

Z17877_PEA_1_P2 (SEQ ID NO: 1184)

Z17877_PEA_1_P3 (SEQ ID NO: 1185)

Z17877_PEA_1_P6 (SEQ ID NO: 1186)

According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or:

Transcript Name

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)

HSHCGI_PEA_3_T21 (SEQ ID NO: 1207)

HSHCGI_PEA_3_T22 (SEQ ID NO: 1208)

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)

HSHCGI_PEA_3_T24 (SEQ ID NO: 1210)

a nucleic acid sequence comprising a sequence in the table below:

Segment Name

HSHCGI_PEA_3_node_0 (SEQ ID NO: 1211)

HSHCGI_PEA_3_node_2 (SEQ ID NO: 1212)

HSHCGI_PEA_3_node_7 (SEQ ID NO: 1213)

HSHCGI_PEA_3_node_8 (SEQ ID NO: 1214)

HSHCGI_PEA_3_node_14 (SEQ ID NO: 1215)

HSHCGI_PEA_3_node_16 (SEQ ID NO: 1216)

HSHCGI_PEA_3_node_18 (SEQ ID NO: 1217)

HSHCGI_PEA_3_node_20 (SEQ ID NO: 1218)

HSHCGI_PEA_3_node_26 (SEQ ID NO: 1219)

HSHCGI_PEA_3_node_28 (SEQ ID NO: 1220)

HSHCGI_PEA_3_node_30 (SEQ ID NO: 1221)

HSHCGI_PEA_3_node_32 (SEQ ID NO: 1222)

HSHCGI_PEA_3_node_33 (SEQ ID NO: 1223)

HSHCGI_PEA_3_node_34 (SEQ ID NO: 1224)

HSHCGI_PEA_3_node_36 (SEQ ID NO: 1225)

HSHCGI_PEA_3_node_1 (SEQ ID NO: 1226)

HSHCGI_PEA_3_node_4 (SEQ ID NO: 1227)

HSHCGI_PEA_3_node_6 (SEQ ID NO: 1228)

HSHCGI_PEA_3_node_9 (SEQ ID NO: 1229)

HSHCGI_PEA_3_node_11 (SEQ ID NO: 1230)

HSHCGI_PEA_3_node_13 (SEQ ID NO: 1231)

HSHCGI_PEA_3_node_19 (SEQ ID NO: 1232)

HSHCGI_PEA_3_node_21 (SEQ ID NO: 1233)

HSHCGI_PEA_3_node_22 (SEQ ID NO: 1234)

HSHCGI_PEA_3_node_23 (SEQ ID NO: 1235)

HSHCGI_PEA_3_node_24 (SEQ ID NO: 1236)

HSHCGI_PEA_3_node_27 (SEQ ID NO: 1237)

HSHCGI_PEA_3_node_31 (SEQ ID NO: 1238)

HSHCGI_PEA_3_node_35 (SEQ ID NO: 1239)

According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below:

Protein Name

HSHCGI_PEA_3_P17 (SEQ ID NO: 1243)

HSHCGI_PEA_3_P18 (SEQ ID NO: 1244)

HSHCGI_PEA_3_P19 (SEQ ID NO: 1245)

HSHCGI_PEA_3_P1 (SEQ ID NO: 1246)

HSHCGI_PEA_3_P4 (SEQ ID NO: 1247)

HSHCGI_PEA_3_P6 (SEQ ID NO: 1248)

HSHCGI_PEA_3_P7 (SEQ ID NO: 1249)

HSHCGI_PEA_3_P8 (SEQ ID NO: 1250)

HSHCGI_PEA_3_P9 (SEQ ID NO: 1251)

HSHCGI_PEA_3_P12 (SEQ ID NO: 1252)

HSHCGI_PEA_3_P13 (SEQ ID NO: 1253)

HSHCGI_PEA_3_P14 (SEQ ID NO: 1254)

HSHCGI_PEA_3_P15 (SEQ ID NO: 1255)

HSHCGI_PEA_3_P16 (SEQ ID NO: 1256)

HSHCGI_PEA_3_P20 (SEQ ID NO: 1257)

HSHCGI_PEA_3_P21 (SEQ ID NO: 1258)

HSHCGI_PEA_3_P22 (SEQ ID NO: 1259)

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCPQCITQIGETSCGFFKCPLCKTSVRRDAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YV corresponding to amino acids 1-218 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 1-218 of HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EIPLMPTVERSQEARCYP (SEQ ID NO:1442) corresponding to amino acids 219-236 of HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EIPLMPTVERSQEARCYP (SEQ ID NO:1442) in HSHCGI_PEA_—3_P17 (SEQ ID NO:1243).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRRDAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLE corresponding to amino acids 1-248 of TM31_HUMAN (SEQ ID NO:1242)_V2 (SEQ ID NO:1241), which also corresponds to amino acids 1-248 of HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWRKNSVKQNQDTTPSQGA (SEQ ID NO:1443) corresponding to amino acids 249-267 of HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWRKNSVKQNQDTTPSQGA (SEQ ID NO:1443) in HSHCGI_PEA_—3_P19 (SEQ ID NO:1245).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1-256 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-256 of HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YDGPPQMYFAY (SEQ ID NO:1444) corresponding to amino acids 257-267 of HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YDGPPQMYFAY (SEQ ID NO:1444) in HSHCGI_PEA_—3_P4 (SEQ ID NO:1247).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1-256 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-256 of HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PTPG (SEQ ID NO:1445) corresponding to amino acids 257-260 of HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PTPG (SEQ ID NO:1445) in HSHCGI_PEA_—3_P6 (SEQ ID NO:1248).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCRS corresponding to amino acids 1-257 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-257 of HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA (SEQ ID NO:1446) corresponding to amino acids 258-310 of HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA (SEQ ID NO:1446) in HSHCGI_PEA_—3_P7 (SEQ ID NO:1249).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGS LKKFKDQLQADRKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAG corresponding to amino acids 1-342 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 343-349 of HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KSPVSEY (SEQ ID NO:1447) corresponding to amino acids 343-349 of HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KSPVSEY (SEQ ID NO:1447) in HSHCGI_PEA_—3_P8 (SEQ ID NO:1250).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1-256 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-256 of HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TGEKTQ (SEQ ID NO:1448) corresponding to amino acids 257-262 of HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TGEKTQ (SEQ ID NO:1448) in HSHCGI_PEA_—3_P9 (SEQ ID NO:1251).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P12 (SEQ ID NO:1252), comprising a first amino acid sequence being at least 90% homologous to MNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASYD EISGQGASSQDTKTFDVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 312-425 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 1-114 of HSHCGI_PEA_—3_P12 (SEQ ID NO:1252).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P14 (SEQ ID NO:1254), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKH YVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGS LKKFKDQLQADRKKDENRFFKSMNKNDMKS corresponding to amino acids 1-319 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-319 of HSHCGI_PEA_—3_P14 (SEQ ID NO:1254), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CK corresponding to amino acids 320-321 of HSHCGI_PEA_—3_P14 (SEQ ID NO:1254), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRNL VEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQ IQVLQQKEKETVQVKAQGVHRVDVFT corresponding to amino acids 1-171 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-171 of HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRKTPSHDLWKQKHLCQSSWNPLLH (SEQ ID NO:1449) corresponding to amino acids 172-196 of HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRKTPSHDLWKQKHLCQSSWNPLLH (SEQ ID NO:1449) in HSHCGI_PEA_—3_P16 (SEQ ID NO:1256).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ (SEQ ID NO:1450) corresponding to amino acids 1-28 of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), and a second amino acid sequence being at least 90% homologous to FLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRIL TEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKvv LCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQLQADRKKDENRFFKSMNKNDMKSWGLLQ KNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASYDEISGQGASSQDTKTF DVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 112-425 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 29-342 of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ (SEQ ID NO:1450) of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P22 (SEQ ID NO:1259), comprising a first amino acid sequence being at least 90% homologous to MPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQLQADRKKDENRFFKSM NKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASYDEI SGQGASSQDTKTFDVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 241-425 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 1-185 of HSHCGI_PEA_—3_P22 (SEQ ID NO:1259).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P5 (SEQ ID NO:1151), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVPSWLKKPQDSQLEEGKPGYL DCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLRINSVEVYDGTWYRCMSSTPAGSIEAQARVQVLEKL KFTPPPQPQQCMEFDKEATVPCSATGREKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIAS NGPQGQIRAHVQLTVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTKLGPRMHIFQ NGSLVIHDVAPEDSGRYTCIAGNSCNIKHTEAPLYVV corresponding to amino acids 1-682 of PTK7_HUMAN_V4 (SEQ ID NO:1143), which also corresponds to amino acids 1-682 of T51958_PEA_—1_P5 (SEQ ID NO:1151), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS (SEQ ID NO:1451) corresponding to amino acids 683-733 of T51958_PEA_—1_P5 (SEQ ID NO:1151), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_—1_P5 (SEQ ID NO:1151), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS (SEQ ID NO:1451) in T51958_PEA_—1_P5 (SEQ ID NO:1151).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P6 (SEQ ID NO:1152), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVPSWLKKPQDSQLEEGKPGYL DCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLRINSVEVYDGTWYRCMSSTPAGSIEAQARVQVLEKL KFTPPPQPQQCMEFDKEATVPCSATGREKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIAS NGPQGQIRAHVQLTVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTKLGPRM corresponding to amino acids 1-641 of PTK7_HUMAN_V4 (SEQ ID NO:1143), which also corresponds to amino acids 1-641 of T51958_PEA_—1_P6 (SEQ ID NO:1152), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence APW corresponding to amino acids 642-644 of T51958_PEA_—1_P6 (SEQ ID NO:1152), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of PTK7_HUMAN_V11 (SEQ ID NO:1144), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) in T51958_PEA_—1_P28 (SEQ ID NO:1153).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA5 (SEQ ID NO:1147), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA6 (SEQ ID NO:1149), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA7 (SEQ ID NO:1148), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA8 (SEQ ID NO:1146), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLL TQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWWEHAGV RLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of AAN04862 (SEQ ID NO:1150), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV (SEQ ID NO:1452) corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P30 (SEQ ID NO:1154), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIK corresponding to amino acids 1-122 of PTK7_HUMAN (SEQ ID NO:1141)_V13 (SEQ ID NO:1145), which also corresponds to amino acids 1-122 of T51958_PEA_—1_P30 (SEQ ID NO:1154), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CESQGGCAQSPCQTLND (SEQ ID NO:1453) corresponding to amino acids 123-139 of T51958_PEA_—1_P30 (SEQ ID NO:1154), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_—1_P30 (SEQ ID NO:1154), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CESQGGCAQSPCQTLND (SEQ ID NO:1453) in T51958_PEA_—1_P30 (SEQ ID NO:1154).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P34 (SEQ ID NO:1155), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPR corresponding to amino acids 1-157 of PTK7_HUMAN_V3 (SEQ ID NO:1142), which also corresponds to amino acids 1-157 of T51958_PEA_—1_P34 (SEQ ID NO:1155).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_—1_P35 (SEQ ID NO:1156), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQPQ TQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNF TLSIA corresponding to amino acids 1-220 of PTK7_HUMAN_V11 (SEQ ID NO:1144), which also corresponds to amino acids 1-220 of T51958_PEA_—1_P35 (SEQ ID NO:1156), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEPGVGAEGMR (SEQ ID NO:1454) corresponding to amino acids 221-231 of T51958_PEA_—1_P35 (SEQ ID NO:1156), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_—1_P35 (SEQ ID NO:1156), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEPGVGAEGMR (SEQ ID NO:1454) in T51958_PEA_—1_P35 (SEQ ID NO:1156).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P2 (SEQ ID NO:1064), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTC QRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQC GQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-675 of T23657_P2 (SEQ ID NO:1064), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FQLPEVHHSLNVLNRKFQKQTVHNL (SEQ ID NO:1455) corresponding to amino acids 676-700 of T23657_P2 (SEQ ID NO:1064), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P2 (SEQ ID NO:1064), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FQLPEVHHSLNVLNRKFQKQTVHNL (SEQ ID NO:1455) in T23657_P2 (SEQ ID NO:1064).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P3 (SEQ ID NO:1065), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTC QRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQC GQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-675 of T23657_P3 (SEQ ID NO:1065), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TIKHKAF (SEQ ID NO:1456) corresponding to amino acids 676-682 of T23657_P3 (SEQ ID NO:1065), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P3 (SEQ ID NO:1065), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TIKHKAF (SEQ ID NO:1456) in T23657_P3 (SEQ ID NO:1065).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P4 (SEQ ID NO:1066), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTC QRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1-625 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-625 of T23657_P4 (SEQ ID NO:1066), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTVQCEEAMVSCTVCSLHKGM corresponding to amino acids 626-646 of T23657_P4 (SEQ ID NO:1066), a third amino acid sequence being at least 90% homologous to GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 626-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 647-696 of T23657_P4 (SEQ ID NO:1066), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TIKHKAF (SEQ ID NO:1456) corresponding to amino acids 697-703 of T23657_P4 (SEQ ID NO:1066), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of T23657_P4 (SEQ ID NO:1066), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GTVQCEEAMVSCTVCSLHKGM, corresponding to T23657_P4 (SEQ ID NO:1066).

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P4 (SEQ ID NO:1066), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TIKHKAF (SEQ ID NO:1456) in T23657_P4 (SEQ ID NO:1066).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P5 (SEQ ID NO:1067), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTC QRKPLLLVFIFVVIFFTFLSSIPALTATLR corresponding to amino acids 1-604 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-604 of T23657_P5 (SEQ ID NO:1067).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P6 (SEQ ID NO:1068), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKV corresponding to amino acids 1-547 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-574 of T23657_P6 (SEQ ID NO:1068), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQLVRESPSFWFSYSL (SEQ ID NO:1458) corresponding to amino acids 548-620 of T23657_P6 (SEQ ID NO:1068), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P6 (SEQ ID NO:1068), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQLVRESPSFWFSYSL (SEQ ID NO:1458) in T23657_P6 (SEQ ID NO:1068).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P7 (SEQ ID NO:1069), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQK corresponding to amino acids 1-546 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-546 of T23657_P7 (SEQ ID NO:1069), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCP corresponding to amino acids 547-549 of T23657_P7 (SEQ ID NO:1069), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P8 (SEQ ID NO:1070), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQK corresponding to amino acids 1-546 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-546 of T23657_P8 (SEQ ID NO:1070), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QHSCTNGNSTMCP (SEQ ID NO:1459) corresponding to amino acids 547-559 of T23657_P8 (SEQ ID NO:1070), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P8 (SEQ ID NO:1070), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence QHSCTNGNSTMCP (SEQ ID NO:1459) in T23657_P8 (SEQ ID NO:1070).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P10 (SEQ ID NO:1072), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTC QRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1-625 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-625 of T23657_P10 (SEQ ID NO:1072), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTVQCEEAMVSCTVCSLHKGM corresponding to amino acids 626-646 of T23657_P10 (SEQ ID NO:1072), and a third amino acid sequence being at least 90% homologous to GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSD GLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 626-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 647-743 of T23657_P10 (SEQ ID NO:1072), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of T23657_P10 (SEQ ID NO:1072), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GTVQCEEAMVSCTVCSLHKGM, corresponding to T23657_P10 (SEQ ID NO:1072).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P11 (SEQ ID NO:1073), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLF corresponding to amino acids 1-425 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-425 of T23657_P11 (SEQ ID NO:1073), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ASCPKAT (SEQ ID NO:1460) corresponding to amino acids 426-432 of T23657_P11 (SEQ ID NO:1073), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P11 (SEQ ID NO:1073), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ASCPKAT (SEQ ID NO:1460) in T23657_P11 (SEQ ID NO:1073).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P12 (SEQ ID NO:1074), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTC QRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWUVRILGGIPGPIAFGWVIDKACLLWQDQC GQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-675 of T23657_P12 (SEQ ID NO:1074), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEENEFRRL (SEQ ID NO:1461) corresponding to amino acids 676-684 of T23657_P12 (SEQ ID NO:1074), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P12 (SEQ ID NO:1074), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEENEFRRL (SEQ ID NO:1461) in T23657_P12 (SEQ ID NO:1074).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P16 (SEQ ID NO:1075), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGTSPMADPVPAGRQHGSGLDPTTRLSPLC (SEQ ID NO:1462) corresponding to amino acids 1-30 of T23657_P16 (SEQ ID NO:1075), and a second amino acid sequence being at least 90% homologous to SLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSG FGHATAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGW VIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSS APDSATDSQLQSSV corresponding to amino acids 491-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 31-262 of T23657_P16 (SEQ ID NO:1075), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T23657_P16 (SEQ ID NO:1075), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGTSPMADPVPAGRQHGSGLDPTTRLSPLC (SEQ ID NO:1462) of T23657_P16 (SEQ ID NO:1075).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P17 (SEQ ID NO:1076), comprising a first amino acid sequence being at least 90% homologous to MYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIP ALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILI MGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 525-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-198 of T23657_P17 (SEQ ID NO:1076).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P21 (SEQ ID NO:1078), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWTAR (SEQ ID NO:1463) corresponding to amino acids 1-5 of T23657_P21 (SEQ ID NO:1078), and a second amino acid sequence being at least 90% homologous to RCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK VLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 604-722 of S21C HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 6-124 of T23657_P21 (SEQ ID NO:1078), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T23657_P21 (SEQ ID NO:1078), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWTAR (SEQ ID NO:1463) of T23657_P21 (SEQ ID NO:1078).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P23 (SEQ ID NO:1080), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARGT HEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQSG LIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGA VCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGAL LNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMHQLKDSS RGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATLFGYLVVP AGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPEGHLNLTAP CNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKV corresponding to amino acids 1-547 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-547 of T23657_P23 (SEQ ID NO:1080), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNLSEKAPPSGFHIRC NFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS (SEQ ID NO:1464) corresponding to amino acids 548-661 of T23657_P23 (SEQ ID NO:1080), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P23 (SEQ ID NO:1080), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNLSEKAPPSGFHIRC NFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS (SEQ ID NO:1464) in T23657_P23 (SEQ ID NO:1080).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 90% homologous to MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELK HMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTE DGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAA AGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSII SARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQ EIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTS ALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTK NDNWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPV VTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTER AVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRV VSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKG SFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 126-1013 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 1-888 of R30650_PEA_—2_P4 (SEQ ID NO:991).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 90% homologous to MYLHIGEEIDGVDMRAEVGLLSRNIWMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELK HMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTE DGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAA AGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSII SARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQ EIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTS ALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTK ND corresponding to amino acids 474-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-504 of R30650_PEA_—2_P4 (SEQ ID NO:991), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAV VDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVS HTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSF RPIWVTLDTEDHKAKIFQVVPIPVVKKKKL (SEQ ID NO:1465) corresponding to amino acids 505-888 of R30650_PEA_—2_P4 (SEQ ID NO:991), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAV VDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVS HTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSF RPIWVTLDTEDHKAKIFQVVPIPVVKKKKL (SEQ ID NO:1465) in R30650_PEA_—2_P4 (SEQ ID NO:991).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELK HMGQQLVGQYPIHFHLAGD (SEQ ID NO:1466) corresponding to amino acids 1-91 of R30650_PEA_—2_P4 (SEQ ID NO:991), and a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSG TLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV GMYSPGYSEHIPLGKFYNNPAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAII RHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMD NRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVT GIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRG AICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAEL AIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG LLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTK DHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNY VATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQV VPIPVVKKKKL corresponding to amino acids 8-804 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 92-888 of R30650_PEA_—2_P4 (SEQ ID NO:991), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELK HMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTE DGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAA AGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNPAHSNYRAGMIIDNGVKTTEASAKDKRPFLSII SARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQ EIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1-389 of R30650_PEA_—2_P4 (SEQ ID NO:991), and a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYI QAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDW IRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNER EKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVKMESSK QHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLM ASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 2-500 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 390-888 of R30650_PEA_—2_P4 (SEQ ID NO:991), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELK HMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTE DGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAA AGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSII SARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQ EIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_—2_P4 (SEQ ID NO:991).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 90% homologous to MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWKP GDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMED KCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYI RDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPL GKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGA WLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSG RTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFF GEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYIQ AYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWI RVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNERE KFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQ HFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMA SKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 18-1013 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 1-996 of R30650_PEA_—2_P5 (SEQ ID NO:992).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 90% homologous to MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWKP GDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMED KCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYI RDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPL GKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGA WLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSG RTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFF GEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 366-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-612 of R30650_PEA_—2_P5 (SEQ ID NO:992), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAV VDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVS HTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSF RPIWVTLDTEDHKAKIFQVVPIPVVKKKKL (SEQ ID NO:1465) corresponding to amino acids 613-996 of R30650_PEA_—2_P5 (SEQ ID NO:992), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAV VDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVS HTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSF RPIWVTLDTEDHKAKIFQVVPIPVVKKKKL (SEQ ID NO:1465) in R30650_PEA_—2_P5 (SEQ ID NO:992).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWKP GDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMED KCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD (SEQ ID NO:1468) corresponding to amino acids 1-199 of R30650_PEA_—2_P5 (SEQ ID NO:992), and a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSG TLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAII RHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMD NRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVT GIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRG AICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAEL AIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG LLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTK DHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNY VATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQV VPIPVVKKKKL corresponding to amino acids 8-804 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 200-996 of R30650_PEA_—2_P5 (SEQ ID NO:992), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDGVNLSTEVVYKKGQDYRFACYDRGPACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWKP GDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMED KCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYI RDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPL GKFYNNPAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGA WLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1-497 of R30650_PEA_—2_P5 (SEQ ID NO:992), and a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYI QAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDW IRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNER EKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVKMESSK QHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLM ASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 2-500 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 498-996 of R30650_PEA_—2_P5 (SEQ ID NO:992), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWKP GDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMED KCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYI RDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPL GKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGA WLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_—2_P5 (SEQ ID NO:992).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK (SEQ ID NO:1469) corresponding to amino acids 1-348 of R30650_PEA_—2_P8 (SEQ ID NO:993), a second amino acid sequence being at least 90% homologous to AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNV NSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAE VGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLV KSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPT GPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGT EMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVP DWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQT APAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYW DEDSG corresponding to amino acids 1-788 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 349-1136 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR (SEQ ID NO:1470) corresponding to amino acids 1137-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KQRTISWR (SEQ ID NO:1470) in R30650_PEA_—2_P8 (SEQ ID NO:993).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 90% homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVRHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRIIPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDER GGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYS PGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIA YKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIW GPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFE DVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 1-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-977 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGKQRTISWR corresponding to amino acids 978-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGKQRTISWR in R30650_PEA_—2_P8 (SEQ ID NO:993).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1-564 of R30650_PEA_—2_P8 (SEQ ID NO:993), a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSG TLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAI RHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMD NRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVT GIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRG AICSGCYAQMYIQAYKTSNLRMKIIKNDFPSIHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAEL AIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 8-579 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 565-1136 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR (SEQ ID NO:1470) corresponding to amino acids 1137-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD of R30650_PEA_—2_P8 (SEQ ID NO:993).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDER GGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYS PGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIA YKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIW GPGGLDH corresponding to amino acids 1-862 of R30650_PEA_—2_P8 (SEQ ID NO:993), a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYI QAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDW IRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 2-275 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 863-1136 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR (SEQ ID NO:1470) corresponding to amino acids 1137-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTS SAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK (SEQ ID NO:1469) corresponding to amino acids 1-348 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 90% homologous to AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNV NSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAE VGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLV KSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPT GPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGT EMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVP DWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQT APAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYW DEDSG corresponding to amino acids 1-788 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 349-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 90% homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGPACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDER GGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYS PGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIA YKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIW GPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFE DVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 1-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-977 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSG (SEQ ID NO:1472) corresponding to amino acids 978-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVT LQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSG (SEQ ID NO:1472) in R30650_PEA_—2_P15 (SEQ ID NO:996).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1-564 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSG TLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAII RHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMD NRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVT GIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRG AICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAEL AIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 8-579 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 565-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD of R30650_PEA_—2_P15 (SEQ ID NO:996).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTS SAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICN RPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLE DNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRN IIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDER GGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYS PGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIA YKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIW GPGGLDH corresponding to amino acids 1-862 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYI QAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDW IRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 2-275 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 863-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_—2_P17 (SEQ ID NO:997), comprising a first amino acid sequence being at least 90% homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSAT VYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIGV GKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKES ERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIE YHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQ corresponding to amino acids 1-321 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-321 of R30650_PEA_—2_P17 (SEQ ID NO:997), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEEFQTIW (SEQ ID NO:1473) corresponding to amino acids 322-329 of R30650_PEA_—2_P17 (SEQ ID NO:997), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_—2_P17 (SEQ ID NO:997), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEEFQTIW (SEQ ID NO:1473) in R30650_PEA_—2_P17 (SEQ ID NO:997).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78035_P4 (SEQ ID NO:924), comprising a first amino acid sequence being at least 90% homologous to MPGLMRMRERYSASKPLKGARIAGCLHMTVETAVLIETLVTLGAEVQWSSCNIFSTQDHAAAAIAKAGIPV YAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMAN GILKVPAINVNDSVTKSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVII TEIDPINALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNE NAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDKYPVGV HFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 29-432 of SAHH_HUMAN (SEQ ID NO:922), which also corresponds to amino acids 1-404 of M78035_P4 (SEQ ID NO:924).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78035_P6 (SEQ ID NO:925), comprising a first amino acid sequence being at least 90% homologous to MILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMANGILKVPAINVNDSVTKSKFDNLYGCRES LIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVIITEIDPINALQAAMEGYEVTTMDEACQE GNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNENAVEKVNIKPQVDRYRLKNGRRIILLAE GRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDKYPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLT EKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 127-432 of SAHH_HUMAN (SEQ ID NO:922), which also corresponds to amino acids 1-306 of M78035_P6 (SEQ ID NO:925).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78035_P8 (SEQ ID NO:926), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MSDKLPYKV (SEQ ID NO:1474) corresponding to amino acids 1-9 of M78035_P8 (SEQ ID NO:926), and a second amino acid sequence being at least 90% homologous to VYAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMA NGILKVPAINVNDSVTKSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVI ITEIDPINALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNE NAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDKYPVGV HFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 99-432 of SAHH_HUMAN (SEQ ID NO:922), which also corresponds to amino acids 10-343 of M78035_P8 (SEQ ID NO:926), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of M78035_P8 (SEQ ID NO:926), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MSDKLPYKV (SEQ ID NO:1474) of M78035_P8 (SEQ ID NO:926).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P4 (SEQ ID NO:864), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGER VDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPK PSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCET QNPVSARRSDSVILNVL corresponding to amino acids 1-234 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-234 of HUMCEA_PEA_—1_P4 (SEQ ID NO:864), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGGS GSTPYDGRNR (SEQ ID NO:1475) corresponding to amino acids 235-315 of HUMCEA_PEA_—1_P4 (SEQ ID NO:864), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCEA_PEA_—1_P4 (SEQ ID NO:864), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGGS GSTPYDGRNR (SEQ ID NO:1475) in HUMCEA_PEA_—1_P4 (SEQ ID NO:864).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P5 (SEQ ID NO:865), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGER VDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPK PSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCET QNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNIT VNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNNQS LPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRPGVNLSL SCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELPKPSISSNN SKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSA NRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTY ACFVSNLATGRNNSIVKSITVS corresponding to amino acids 1-675 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-675 of HUMCEA_PEA_—1_P5 (SEQ ID NO:865), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO:1476) corresponding to amino acids 676-719 of HUMCEA_PEA_—1_P5 (SEQ ID NO:865), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCEA_PEA_—1_P5 (SEQ ID NO:865), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO:1476) in HUMCEA_PEA_—1_P5 (SEQ ID NO:865).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P7 (SEQ ID NO:866), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGER VDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPK PSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCET QNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNIT VNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNNQS LPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRPGVNLSL SCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELPKPSISSNN SKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSA NRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTY ACFVSNLATGRNNSIVKSITV corresponding to amino acids 1-674 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-674 of HUMCEA_PEA_—1_P7 (SEQ ID NO:866), and a second amino acid sequence being at least 90% homologous to SAGATVGIMIGVLVGVALI corresponding to amino acids 684-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 675-693 of HUMCEA_PEA_—1_P7 (SEQ ID NO:866), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P7 (SEQ ID NO:866), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise VS, having a structure as follows: a sequence starting from any of amino acid numbers 674−x to 674; and ending at any of amino acid numbers 675+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P10 (SEQ ID NO:867), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGER VDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPK PSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCET QNPVSARRSDS corresponding to amino acids 1-228 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-228 of HUMCEA_PEA_—1_P10 (SEQ ID NO:867), and a second amino acid sequence being at least 90% homologous to VILNVLYGPDDPTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQA NNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSN GNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQ YSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLV GVALI corresponding to amino acids 1-228 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 229-524 of HUMCEA_PEA_—1_P10 (SEQ ID NO:867), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P10 (SEQ ID NO:867), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SV, having a structure as follows: a sequence starting from any of amino acid numbers 228−x to 228; and ending at any of amino acid numbers 229+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P19 (SEQ ID NO:869), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGER VDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPELPK PSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCET QNPVSARRSDSVILN corresponding to amino acids 1-232 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-232 of HUMCEA_PEA_—1_P19 (SEQ ID NO:869), and a second amino acid sequence being at least 90% homologous to VLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLAT GRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 589-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 233-346 of HUMCEA_PEA_—1_P19 (SEQ ID NO:869), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P19 (SEQ ID NO:869), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise NV, having a structure as follows: a sequence starting from any of amino acid numbers 232−x to 232; and ending at any of amino acid numbers 233+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P20 (SEQ ID NO:870), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGER VDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYP corresponding to amino acids 1-142 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-142 of HUMCEA_PEA_—1_P20 (SEQ ID NO:870), and a second amino acid sequence being at least 90% homologous to ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAY VCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIA KITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 499-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 143-346 of HUMCEA_PEA_—1_P20 (SEQ ID NO:870), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P20 (SEQ ID NO:870), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PE, having a structure as follows: a sequence starting from any of amino acid numbers 142−x to 142; and ending at any of amino acid numbers 143+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), comprising a first amino acid sequence being at least 90% homologous to MPTSETESVNTENVSGEGENRGCCGSL corresponding to amino acids 466-492 of CCAD_HUMAN_V3 (SEQ ID NO:791), which also corresponds to amino acids 1-27 of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WCWWRRRGAAKAGPSGCRRWG corresponding to amino acids 28-48 of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), and a third amino acid sequence being at least 90% homologous to QAISKSKLSRRWRRWNRFNRRRCRAAVKSVTFYWLVIVLVFLNTLTISSEHYNQPDWLTQIQDIANKVLLA LFTCEMLVKMYSLGLQAYFVSLFNRFDCFVVCGGITETILVELEIMSPLGISVFRCVRLLRIFKVTRHWTSLS NLVASLLNSMKSIASLLLLLFLFIIIFSLLGMQLFGGKFNFDETQTKRSTFDNFPQALLTVFQILTGEDWNAVM YDGIMAYGGPSSSGMIVCIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEAEEKERKKIARKESLEN KKNNKPEVNQIANSDNKVTIDDYREEDEDKDPYPPCDVPVGEEEEEEEEDEPEVPAGPRPRRISELNMKEKI APIPEGSAFFILSKTNPIRVGCHKLINHHIFTNLILVFIMLSSAALAAEDPIRSHSFRNTILGYFDYAFTAIFTVEI LLKMTTFGAFLHKGAFCRNYFNLLDMLVVGVSLVSFGIQSSAISVVKILRVLRVLRPLRAINRAKGLKHVVQ CVFVAIRTIGNIMIVTTLLQFMFACIGVQLFKGKFYRCTDEAKSNPEECRGLFILYKDGDVDSPVVRERIWQN SDFNFDNVLSAMMALFTVSTFEGWPALLYKAIDSNGENIGPIYNHRVEISIFFIIYIIIVAFFMMNIFVGFVIVTF QEQGEKEYKNCELDKNQRQCVEYALKARPLRRYIPKNPYQYKFWYVVNSSPFEYMMFVLIMLNTLCLAM QHYEQSKMFNDAMDILNMVFTGVFTVEMVLKVIAFKPKGYFSDAWNTFDSLIVIGSIIDVALSEADPTESEN VPVPTATPGNSEESNRISITFFRLFRVMRLVKLLSRGEGIRTLLWTFIKSFQALPYVALLIAMLFFIYAVIGMQ MFGKVAMRDNNQINRNNNFQTFPQAVLLLFRCATGEAWQEIMLACLPGKLCDPESDYNPGEEYTCGSNFAI VYFISFYMLCAFLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWSEYDPEAKGRIKHLDVVTLLRRIQPP LGFGKLCPHRVACKRLVAMNMPLNSDGTVMFNATLFALVRTALKIKTEGNLEQANEELRAVIKKIWKKTS MKLLDQVVPPAGDDEVTVGKFYATFLIQDYFRKFKKRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRR AISCDLQDDEPEETKREEEDDVFKRNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPL FPPAGNSVCHNHHNHNSIGKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRR SSVKRTRYYETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRY PGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPH RTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSL PSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHETA DACDLTIDEMESAASTLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 494-2161 of CCAD_HUMAN_V3 (SEQ ID NO:791), which also corresponds to amino acids 49-1716 of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for WCWWRRRGAAKAGPSGCRRWG, corresponding to HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796).

According to preferred embodiments of the present invention, there is provided a bridge portion of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise L, having a structure as follows (numbering according to HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796)): a sequence starting from any of amino acid numbers 492−x to 492; and ending at any of amino acid numbers 28+((n−2)−x), in which x varies from 0 to n−2.

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL (SEQ ID NO:1477) corresponding to amino acids 1-47 of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), and a second amino acid sequence being at least 90% homologous to DDEVTVGKFYATFLIQDYFRKFKKRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRRAISCDLQDDEPEE TKREEEDDVFKRNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPLFPPAGNSVCHNH HNHNSIGKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYI RSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERPRGY HHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQI MAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEP DISYRTFTPASLTVPSSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESA ASTLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1598-2161 of CCAD_HUMAN (SEQ ID NO:790), which also corresponds to amino acids 48-611 of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL (SEQ ID NO:1477) of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803), comprising a first amino acid sequence being at least 90% homologous to MSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLPTICREDPEIHGYF RDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSP RRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRS WATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSD KQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVGPLSH RQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1763-2161 of CCAD_HUMAN (SEQ ID NO:790), which also corresponds to amino acids 1-399 of HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), comprising a first amino acid sequence being at least 90% homologous to MMMMMMMKKMQHQRQQQADHANEANYARGTRLPLSGEGPTSQPNSSKQTVLSWQAAIDAARQAKAA QTMSTSAPPPVGSLSQRKRQQYAKSKKQGNSSNSRPARALFCLSLNNPIRRACISIVEWKPFDIFILLAIFANC VALAIYIPFPEDDSNSTNHNLEKVEYAFLIIFTVETFLKIIAYGLLLHPNAYVRNGWNLLDFVIVIVGLFSVILE QLTKETEGGNHSSGKSGGFDVKALRAFRVLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIG LELFIGKMHKTCFFADSDIVAEEDPAPCAFSGNGRQCTANGTECRSGWVGPNGGITNFDNFAFAMLTVFQCI TMEGWTDVLYWMNDAMGFELPWVYFVSLVIFGSFFVLNLVLGVLSG corresponding to amino acids 1-407 of CCAD_HUMAN (SEQ ID NO:790), which also corresponds to amino acids 1-407 of HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence HGGSRL (SEQ ID NO:1478) corresponding to amino acids 408-413 of HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence HGGSRL (SEQ ID NO:1478) in HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_—1_P2 (SEQ ID NO:684), comprising a first amino acid sequence being at least 90% homologous to MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKGAQTGAGLSQEAED VDVSRARRVTDAPQGTLCGTGNRNSGSQSARVVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIMWA RMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVE ALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59-313 of MYEO_HUMAN_V1 (SEQ ID NO:680), which also corresponds to amino acids 1-255 of AA583399_PEA_—1_P2 (SEQ ID NO:684).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_—1_P4 (SEQ ID NO:685), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG (SEQ ID NO:1479) corresponding to amino acids 1-27 of AA583399_PEA_—1_P4 (SEQ ID NO:685), and a second amino acid sequence being at least 90% homologous to RNSGSQSARVVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIMWARMDVALRSPGRGLLAGAGALC MTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVEALGGWRMGVRRTGQVGPTMH PPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 150-313 of MYEO_HUMAN_V1 (SEQ ID NO:680), which also corresponds to amino acids 28-191 of AA583399_PEA_—1_P4 (SEQ ID NO:685), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of AA583399_PEA_—1_P4 (SEQ ID NO:685), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG (SEQ ID NO:1479) of AA583399_PEA_—1_P4 (SEQ ID NO:685).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_—1_P5 (SEQ ID NO:686), comprising a first amino acid sequence being at least 90% homologous to MEIMWARMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSW LTVVTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 192-313 of MYEO_HUMAN_V2 (SEQ ID NO:681), which also corresponds to amino acids 1-122 of AA583399_PEA_—1_P5 (SEQ ID NO:686).

According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_—1_P10 (SEQ ID NO:689), comprising a first amino acid sequence being at least 90% homologous to MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKGAQTGAGLSQEAED VDVSRARRVTDAPQGTLCGTGNRNSGSQSARAVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIMWA QMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVE ALGRWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59-313 of MYEO_HUMAN_V3 (SEQ ID NO:682), which also corresponds to amino acids 1-255 of AA583399_PEA_—1_P10 (SEQ ID NO:689).

According to preferred embodiments of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence as described herein.

Optionally the amino acid sequence corresponds to a bridge, edge portion, tail, head or insertion as described herein.

Optionally the antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein.

According to preferred embodiments of the present invention, there is provided a kit for detecting colon cancer, comprising a kit detecting overexpression of a splice variant as described herein.

Optionally the kit comprises a NAT-based technology.

Optionally said the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence as described herein. Optionally the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence as described herein. The kit optionally comprises an antibody as described herein. The kit optionally further comprises at least one reagent for performing an ELISA or a Western blot.

There is optionally provided a method for detecting colon cancer, comprising detecting overexpression of a splice variant as described herein. Detecting overexpression is optionally performed with a NAT-based technology.

Optionally s detecting overexpression is performed with an immunoassay, optionally wherein said immunoassay comprises an antibody as described herein. A biomarker capable of detecting colon cancer, comprising any of the above nucleic acid sequences or a fragment thereof, or any of the above amino acid sequences or a fragment thereof. A method for screening for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein. A method for diagnosing colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein. A method for monitoring disease progression and/or treatment efficacy and/or relapse of colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein. A method of selecting a therapy for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein and selecting a therapy according to said detection.

According to preferred embodiments of the present invention, preferably any of the above nucleic acid and/or amino acid sequences further comprises any sequence having at least about 70%, preferably at least about 80%, more preferably at least about 90%, most preferably at least about 95% homology thereto.

Unless otherwise noted, all experimental data relates to variants of the present invention, named according to the segment being tested (as expression was tested through RT-PCR as described).

All nucleic acid sequences and/or amino acid sequences shown herein as embodiments of the present invention relate to their isolated form, as isolated polynucleotides (including for all transcripts), oligonucleotides (including for all segments, amplicons and primers), peptides (including for all tails, bridges, insertions or heads, optionally including other antibody epitopes as described herein) and/or polypeptides (including for all proteins). It should be noted that oligonucleotide and polynucleotide, or peptide and polypeptide, may optionally be used interchangeably.

Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). All of these are hereby incorporated by reference as if fully set forth herein. As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1. is schematic summary of cancer biomarkers selection engine and the wet validation stages.

FIG. 2. Schematic illustration, depicting grouping of transcripts of a given cluster based on presence or absence of unique sequence regions.

FIG. 3 is schematic summary of quantitative real-time PCR analysis.

FIG. 4 is schematic presentation of the oligonucleotide based microarray fabrication.

FIG. 5 is schematic summary of the oligonucleotide based microarray experimental flow.

FIG. 6 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster M85491.

FIG. 7 is a histogram showing expression of the Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 (SEQ ID NO:1276) in normal and cancerous colon tissues.

FIG. 8 is a histogram showing the expression of M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 (SEQ ID NO:1276) in different normal issues.

FIG. 9 is histogram, showing Cancer and cell-line vs. normal tissue expression for Cluster T10888, demonstrating overexpression in colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma.

FIG. 10 is a histogram showing expression of the CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 (T10888) transcripts which are detectable by amplicon as depicted in sequence name T10888 junc11-17 (SEQ ID NO: 1279), in normal and cancerous colon tissues.

FIG. 11 is a the histogram showing the expression of T10888 transcripts, which are detectable by amplicon as depicted in sequence name T10888junc11-17 (SEQ ID NO: 1282), in different normal tissues.

FIG. 12 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster H14624.

FIG. 13 is a histogram, showing Cancer and cell-line vs. normal tissue expression for Cluster H53626, demonstrating overexpression in the epithelial malignant tumors, a mixture of malignant tumors from different tissues and myosarcoma.

FIG. 14 is a histogram showing expression of the above-indicated Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in sequence name H53626 junc24-27F1R3 (SEQ ID NO: 1285), in normal and cancerous colon tissues.

FIG. 15 is the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in sequence name H53626seg25 (SEQ ID NO: 1288), in normal and cancerous colon tissues.

FIG. 16 is a a histogram, showing Cancer and cell-line vs. normal tissue expression for Cluster HSENA78, demonstrating overexpression in the epithelial malignant tumors and lung malignant tumors.

FIG. 17 is a histogram, showing Cancer and cell-line vs. normal tissue expression for the Cluster HUMODCA, demonstrating overexpression in the brain malignant tumors, colorectal cancer, epithelial malignant tumors and a mixture of malignant tumors from different tissues.

FIG. 18 is a histogram, showing Cancer and cell-line vs. normal tissue expression for the cluster R00299, demonstratin overexpression in the lung malignant tumors.

FIG. 19 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster Z44808, demonstrating overexpression in the colorectal cancer, lung cancer and pancreas carcinoma.

FIG. 20 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster Z25299, demonstrating overexpression in the brain malignant tumors, a mixture of malignant tumors from different tissues and ovarian carcinoma.

FIG. 21 is a histogram showing expression of Z25299 transcripts, which are detectable by amplicon as depicted in sequence name Z25299seg20 (SEQ ID NO: 1294), in normal and cancerous colon tissues.

FIG. 22 is a histogram showing the expression of Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues Z25299 transcripts which are detectable by amplicon as depicted in sequence name Z25299seg20 (SEQ ID NO: 1294) in different normal tissues.

FIG. 23 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster HUMANK, demonstrating overexpression in epithelial malignant tumors.

FIG. 24 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster HUMCA1XIA, demonstrating overexpression in the bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

FIG. 25 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster HSS100PCB, demonstrating overexpression in the mixture of malignant tumors from different tissues.

FIG. 26 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster D11853, demonstrating overexpression in the brain malignant tumors, colorectal cancer and a mixture of malignant tumors from different tissues.

FIG. 27 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster R11723, demonstrating overexpression in the epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors

FIG. 28 is the histogram showing expression of the R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723 seg13 (SEQ ID NO: 1297) in normal and cancerous colon tissues.

FIG. 29 is the histogram showing expression of the R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723 junc11-18 (SEQ ID NO: 1300) in normal and cancerous colon tissues.

FIG. 30 is the histogram showing the expression of R11723 transcripts, detectable by amplicon depicted in sequence name R11723seg13 (SEQ ID NO: 1297) in different normal tissues.

FIG. 31 is the histogram showing the expression of R11723 transcripts, detectable by amplicon in sequence name R11723 junc11-18 (SEQ ID NO: 1300) in different normal tissues.

FIG. 32 is a histogram showing over expression of the SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808junc8-11 (SEQ ID NO: 1291) in cancerous colon samples relative to the normal samples

FIG. 33 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster M77903, demonstrating overexpression in ovarian carcinoma and uterine malignancies.

FIG. 34 is the histogram showing expression of the SSR-alpha M77903 transcripts, which are detectable by amplicon, as depicted in sequence name M77903seg18 (SEQ ID NO: 1303) in normal and cancerous colon tissues.

FIG. 35 is the histogram showing low over expression for amplicon M77903 junc20-34-35 (SEQ ID NO: 1309) in the experiment carried out with colon.

FIG. 36 is the histogram showing low over expression for amplicon M77903 junc20-28 (SEQ ID NO: 1306) in the experiment carried out with colon

FIGS. 37-38 are histograms showing differential expression of 6 sequences: (M85491seg24 (SEQ ID NO: 1276), M77903 seg18 (SEQ ID NO: 1303), M77903junc20-28 (SEQ ID NO: 1306), Z44808 junc8-11 (SEQ ID NO: 1291), Z25299 seg 20 (SEQ ID NO: 1294) and HSKITCR seg3 (SEQ ID NO: 1309) in normal and cancerous colon tissues, in different combinations.

FIG. 39 is a histogram showing the expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808 junc8-11 (SEQ ID NO: 1291) in different normal tissues.

FIG. 40 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster AA583399, demonstrating overexpression in brain malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and gastric carcinoma.

FIG. 41 is the histogram showing expression of the AA583399 transcripts, which are detectable by amplicon as depicted in sequence name AA583399seg30-32 (SEQ ID NO: 1321), in normal and cancerous colon tissues.

FIG. 42 is the histogram showing expression of the AA583399 transcripts which are detectable by amplicon as depicted in sequence name AA583399seg17 (SEQ ID NO: 1324) in normal and cancerous colon tissues.

FIG. 43 is the histogram showing expression of the AA583399 transcripts which are detectable by amplicon as depicted in sequence name AA583399seg1 (SEQ ID NO: 1327) in normal and cancerous colon tissues.

FIG. 44 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster AI684092, demonstrating overexpression in brain malignant tumors, epithelial malignant tumors and a mixture of malignant tumors from different tissues.

FIG. 45 is the histogram showing expression of the AA5315457 transcripts which are detectable by amplicon as depicted in sequence name AA5315457seg8 (SEQ ID NO: 1330) in normal and cancerous colon tissues.

FIG. 46 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster HUMCACH1A, demonstrating overexpression in a mixture of malignant tumors from different tissues.

FIG. 47 is the histogram showing expression of the Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 Transcripts, which are detectable by seg 113, 35, 109, 125, in normal and cancerous colon tissues.

FIG. 48 is the histogram showing expression of the HUMCACH1A Transcripts, which are detectable by amplicon as depicted in sequence name HUMCACH1Aseg101 (SEQ ID NO: 1337), in normal and cancerous colon tissues.

FIG. 49 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster HUMCEA, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

FIG. 50 is the histogram showing expression of the HUMCEA transcripts which are detectable by seg12 and seg9, in normal and cancerous colon tissues.

FIG. 51 is the histogram showing expression of the Carcinoembryonic antigen-related cell adhesion molecule 5 CEACAM5 HUMCEA transcripts which are detectable by amplicon as depicted in sequence name HUMCEA seg31 (SEQ ID NO: 1342) in normal and cancerous colon tissues.

FIG. 52 is the histogram showing expression of the Carcinoembryonic antigen-related cell adhesion molecule 5 CEACAM5 HUMCEA transcripts which are detectable by amplicon as depicted in sequence name HUMCEA seg33 (SEQ ID NO: 1345) in normal and cancerous colon tissues.

FIG. 53 is the histogram showing expression of the Carcinoembryonic antigen-related cell adhesion molecule 5 CEACAM5 HUMCEA transcripts which are detectable by amplicon as depicted in sequence name HUMCEA seg35 (SEQ ID NO: 1348) in normal and cancerous colon tissues.

FIG. 54 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster M78035, demonstrating overexpression in brain malignant tumors, colorectal cancer, epithelial malignant tumors, a mixture of malignant tumors from different tissues, malignant tumors involving the lymph nodes and pancreas carcinoma.

FIG. 55 is the histogram showing expression of the S-adenosylhomocysteine hydrolase (AHCY) M78035 transcripts, which are detectable by amplicon as depicted in sequence name M78035seg42 (SEQ ID NO: 1351), in normal and cancerous colon tissues

FIG. 56 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster R30650, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues.

FIG. 57 is the histogram showing expression of the R30650 transcripts which are detectable by amplicon as depicted in sequence name R30650 seg76 (SEQ ID NO: 1354) in normal and cancerous colon tissues.

FIG. 58 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster T23657, demonstrating overexpression in epithelial malignant tumors.

FIG. 59 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 seg17-18 (SEQ ID NO: 1357), in normal and cancerous colon tissues.

FIG. 60 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 seg22 (SEQ ID NO: 1360), in normal and cancerous colon tissues.

FIG. 61 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 seg29-32 (SEQ ID NO: 1363), in normal and cancerous colon tissues.

FIG. 62 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 seg41 (SEQ ID NO: 1366), in normal and cancerous colon tissues.

FIG. 63 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster T51958, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues.

FIG. 64 is the histogram showing expression of PTK7 protein tyrosine kinase 7 (PTK7) T51958 transcripts which are detectable by amplicon as depicted in sequence name T51958seg38 (SEQ ID NO: 1369) in normal and cancerous colon tissues.

FIG. 65 is the histogram showing expression of PTK7 protein tyrosine kinase 7 (PTK7) T51958 transcripts which are detectable by amplicon as depicted in sequence name T51958seg7 (SEQ ID NO: 1372) in normal and cancerous colon tissues.

FIG. 66 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster Z17877, demonstrating overexpression in brain malignant tumors and malignant tumors involving the bone marrow.

FIG. 67 is the histogram showing expression of c-myc-P64 mRNA, initiating from promoter P0 Z17877 transcripts, which are detectable by amplicon as depicted in sequence name Z17877seg8 (SEQ ID NO: 1375), in normal and cancerous colon tissues.

FIG. 68 is the histogram showing combined expression of 19 sequences (T23657seg 29 (SEQ ID NO: 1363), T23657seg 22 (SEQ ID NO: 1360), T23657seg 41 (SEQ ID NO: 1366), T23657seg17-18 (SEQ ID NO: 1357), AA315457seg8, R30650seg76 (SEQ ID NO: 1354), HUM-CEASeg 33 (SEQ ID NO: 1345), CEA-Seg35 (SEQ ID NO: 1348), CEA-Seg31 (SEQ ID NO: 1342), AA583399seg1 (SEQ ID NO: 1327), AA583399seg17 (SEQ ID NO: 1324), AA58339-seg30-32 (SEQ ID NO: 1321), HUMCACH1Aseg101 (SEQ ID NO: 1337), HSHCGI seg20 (SEQ ID NO: 1378), HSHCGI seg35 (SEQ ID NO: 1381), M78035seg 42 (SEQ ID NO: 1351), T51958seg7 (SEQ ID NO: 1372), T51958 seg3 (SEQ ID NO: 1369) and, Z17877 seg8 (SEQ ID NO: 1375)) in normal and cancerous colon tissues.

FIG. 69 is the histogram showing expression of TRIM31 tripartite motif HSHCGI transcripts which are detectable by amplicon as depicted in sequence name HSHCGI seg20 (SEQ ID NO: 1378) in normal and cancerous colon tissues.

FIG. 70 is the histogram showing expression of TRIM31 tripartite motif HSHCGI transcripts which are detectable by amplicon as depicted in sequence name HSHCGI seg35 (SEQ ID NO: 1381) in normal and cancerous colon tissues.

FIG. 71 is a histogram showing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 (SEQ ID NO: 1288) amplicon(s) and H53626 seg25F (SEQ ID NO: 1286) and H53626 seg25R (SEQ ID NO: 1287) in different normal tissues.

FIG. 72 is a histogram showing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 (SEQ ID NO: 1285) amplicon(s) and H53626 seg25F (SEQ ID NO: 1283) and H53626 junc24-27F1R3 (SEQ ID NO: 1284) in different normal tissues.

FIG. 73 is a histogram showing over expression of the Matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 junc21-27 (SEQ ID NO: 1312), in cancerous colon samples relative to the normal samples.

FIG. 74 is a histogram showing over expression of the Matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg25 (SEQ ID NO: 1315), in cancerous colon samples relative to the normal samples.

FIG. 75 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster HSSTROL3, demonstrating overexpression in transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

FIG. 76 is a histogram showing the expression of Stromelysin-3 HSSTROL3 transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24, in different normal tissues.

FIG. 77 is a histogram showing over expression of the Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by seg55—HUMCA1XIA_seg55 amplicon in cancerous Colon samples relative to the normal samples.

FIG. 78 is a histogram showing expression of the Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by seg55—HUMCA1XIA_seg55 amplicon in various normal tissues.

FIG. 79 is a histogram showing over expression of the Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by HUMCA1XIA_seg54-55F2R2 in normal and cancerous Colon tissues.

FIG. 80 is a histogram showing expression of the Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by HUMCA1XIA_seg54-55F2R2 in various normal tissues.

DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention is of novel markers for colon cancer that are both sensitive and accurate. Biomolecular sequences (amino acid and/or nucleic acid sequences) uncovered using the methodology of the present invention and described herein can be efficiently utilized as tissue or pathological markers and/or as drugs or drug targets for treating or preventing a disease.

These markers are specifically released to the bloodstream under conditions of colon cancer and/or other colon pathology, and/or are otherwise expressed at a much higher level and/or specifically expressed in colon cancer tissue or cells. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of colon cancer and/or pathology.

The present invention therefore also relates to diagnostic assays for colon cancer and/or colon pathology, and methods of use of such markers for detection of colon cancer and/or colon pathology, optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample.

In another embodiment, the present invention relates to bridges, tails, heads and/or insertions, and/or analogs, homologs and derivatives of such peptides. Such bridges, tails, heads and/or insertions are described in greater detail below with regard to the Examples.

As used herein a “tail” refers to a peptide sequence at the end of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a tail may optionally be considered as a chimera, in that at least a first portion of the splice variant is typically highly homologous (often 100% identical) to a portion of the corresponding known protein, while at least a second portion of the variant comprises the tail.

As used herein a “head” refers to a peptide sequence at the beginning of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a head may optionally be considered as a chimera, in that at least a first portion of the splice variant comprises the head, while at least a second portion is typically highly homologous (often 100% identical) to a portion of the corresponding known protein.

As used herein “an edge portion” refers to a connection between two portions of a splice variant according to the present invention that were not joined in the wild type or known protein. An edge may optionally arise due to a join between the above “known protein” portion of a variant and the tail, for example, and/or may occur if an internal portion of the wild type sequence is no longer present, such that two portions of the sequence are now contiguous in the splice variant that were not contiguous in the known protein. A “bridge” may optionally be an edge portion as described above, but may also include a join between a bead and a “known protein” portion of a variant, or a join between a tail and a “known protein” portion of a variant, or a join between an insertion and a “known protein” portion of a variant.

Optionally and preferably, a bridge between a tail or a head or a unique insertion, and a “known protein” portion of a variant, comprises at least about 10 amino acids, more preferably at least about 20 amino acids, most preferably at least about 30 amino acids, and even more preferably at least about 40 amino acids, in which at least one amino acid is from the tail/head/insertion and at least one amino acid is from the “known protein” portion of a variant. Also optionally, the bridge may comprise any number of amino acids from about 10 to about 40 amino acids (for example, 10, 11, 12, 13 . . . 37, 38, 39, 40 amino acids in length, or any number in between).

It should be noted that a bridge cannot be extended beyond the length of the sequence in either direction, and it should be assumed that every bridge description is to be read in such manner that the bridge length does not extend beyond the sequence itself.

Furthermore, bridges are described with regard to a sliding window in certain contexts below. For example, certain descriptions of the bridges feature the following format: a bridge between two edges (in which a portion of the known protein is not present in the variant) may optionally be described as follows: a bridge portion of CONTIG-NAME_P1 (representing the name of the protein), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise XX (2 amino acids in the center of the bridge, one from each end of the edge), having a structure as follows (numbering according to the sequence of CONTIG-NAME_P1): a sequence starting from any of amino acid numbers 49−x to 49 (for example); and ending at any of amino acid numbers 50+((n−2)−x) (for example), in which x varies from 0 to n−2. In this example, it should also be read as including bridges in which n is any number of amino acids between 10-50 amino acids in length. Furthermore, the bridge polypeptide cannot extend beyond the sequence, so it should be read such that 49−x (for example) is not less than 1, nor 50+((n−2)−x) (for example) greater than the total sequence length.

In another embodiment, this invention provides antibodies specifically recognizing the splice variants and polypeptide fragments thereof of this invention. Preferably such antibodies differentially recognize splice variants of the present invention but do not recognize a corresponding known protein (such known proteins are discussed with regard to their splice variants in the Examples below).

In another embodiment, this invention provides an isolated nucleic acid molecule encoding for a splice variant according to the present invention, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an isolated nucleic acid molecule, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an oligonucleotide of at least about 12 nucleotides, specifically hybridizable with the nucleic acid molecules of this invention. In another embodiment, this invention provides vectors, cells, liposomes and compositions comprising the isolated nucleic acids of this invention.

In another embodiment, this invention provides a method for detecting a splice variant according to the present invention in a biological sample, comprising: contacting a biological sample with an antibody specifically recognizing a splice variant according to the present invention under conditions whereby the antibody specifically interacts with the splice variant in the biological sample but do not recognize known corresponding proteins (wherein the known protein is discussed with regard to its splice variant(s) in the Examples below), and detecting said interaction; wherein the presence of an interaction correlates with the presence of a splice variant in the biological sample.

In another embodiment, this invention provides a method for detecting a splice variant nucleic acid sequences in a biological sample, comprising: hybridizing the isolated nucleic acid molecules or oligonucleotide fragments of at least about a minimum length to a nucleic acid material of a biological sample and detecting a hybridization complex; wherein the presence of a hybridization complex correlates with the presence of a splice variant nucleic acid sequence in the biological sample.

According to the present invention, the splice variants described herein are non-limiting examples of markers for diagnosing colon cancer and/or colon pathology. Each splice variant marker of the present invention can be used alone or in combination, for various uses, including but not limited to, prognosis, prediction, screening, early diagnosis, determination of progression, therapy selection and treatment monitoring of colon cancer and/or colon pathology.

According to optional but preferred embodiments of the present invention, any marker according to the present invention may optionally be used alone or combination. Such a combination may optionally comprise a plurality of markers described herein, optionally including any subcombination of markers, and/or a combination featuring at least one other marker, for example a known marker. Furthermore, such a combination may optionally and preferably be used as described above with regard to determining a ratio between a quantitative or semi-quantitative measurement of any marker described herein to any other marker described herein, and/or any other known marker, and/or any other marker. With regard to such a ratio between any marker described herein (or a combination thereof) and a known marker, more preferably the known marker comprises the “known protein” as described in greater detail below with regard to each cluster or gene.

According to other preferred embodiments of the present invention, a splice variant protein or a fragment thereof, or a splice variant nucleic acid sequence or a fragment thereof, may be featured as a biomarker for detecting colon cancer and/or colon pathology, such that a biomarker may optionally comprise any of the above.

According to still other preferred embodiments, the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence corresponding to a splice variant protein as described herein. Any oligopeptide or peptide relating to such an amino acid sequence or fragment thereof may optionally also (additionally or alternatively) be used as a biomarker, including but not limited to the unique amino acid sequences of these proteins that are depicted as tails, heads, insertions, edges or bridges. The present invention also optionally encompasses antibodies capable of recognizing, and/or being elicited by, such oligopeptides or peptides.

The present invention also optionally and preferably encompasses any nucleic acid sequence or fragment thereof, or amino acid sequence or fragment thereof, corresponding to a splice variant of the present invention as described above, optionally for any application.

Non-limiting examples of methods or assays are described below.

The present invention also relates to kits based upon such diagnostic methods or assays.

Nucleic Acid Sequences and Oligonucleotides

Various embodiments of the present invention encompass nucleic acid sequences described hereinabove; fragments thereof, sequences hybridizable therewith, sequences homologous thereto, sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or artificially induced, either randomly or in a targeted fashion.

The present invention encompasses nucleic acid sequences described herein; fragments thereof, sequences hybridizable therewith, sequences homologous thereto [e.g., at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95% or more say 100% identical to the nucleic acid sequences set forth below], sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or man induced, either randomly or in a targeted fashion. The present invention also encompasses homologous nucleic acid sequences (i.e., which form a part of a polynucleotide sequence of the present invention) which include sequence regions unique to the polynucleotides of the present invention.

In cases where the polynucleotide sequences of the present invention encode previously unidentified polypeptides, the present invention also encompasses novel polypeptides or portions thereof, which are encoded by the isolated polynucleotide and respective nucleic acid fragments thereof described hereinabove.

A “nucleic acid fragment” or an “oligonucleotide” or a “polynucleotide” are used herein interchangeably to refer to a polymer of nucleic acids. A polynucleotide sequence of the present invention refers to a single or double stranded nucleic acid sequences which is isolated and provided in the form of an RNA sequence, a complementary polynucleotide sequence (cDNA), a genomic polynucleotide sequence and/or a composite polynucleotide sequences (e.g., a combination of the above).

As used herein the phrase “complementary polynucleotide sequence” refers to a sequence, which results from reverse transcription of messenger RNA using a reverse transcriptase or any other RNA dependent DNA polymerase. Such a sequence can be subsequently amplified in vivo or in vitro using a DNA dependent DNA polymerase.

As used herein the phrase “genomic polynucleotide sequence” refers to a sequence derived (isolated) from a chromosome and thus it represents a contiguous portion of a chromosome.

As used herein the phrase “composite polynucleotide sequence” refers to a sequence, which is composed of genomic and cDNA sequences. A composite sequence can include some exonal sequences required to encode the polypeptide of the present invention, as well as some intronic sequences interposing therebetween. The intronic sequences can be of any source, including of other genes, and typically will include conserved splicing signal sequences. Such intronic sequences may further include cis acting expression regulatory elements.

Preferred embodiments of the present invention encompass oligonucleotide probes.

An example of an oligonucleotide probe which can be utilized by the present invention is a single stranded polynucleotide which includes a sequence complementary to the unique sequence region of any variant according to the present invention, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein).

Alternatively, an oligonucleotide probe of the present invention can be designed to hybridize with a nucleic acid sequence encompassed by any of the above nucleic acid sequences, particularly the portions specified above, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein).

Oligonucleotides designed according to the teachings of the present invention can be generated according to any oligonucleotide synthesis method known in the art such as enzymatic synthesis or solid phase synthesis. Equipment and reagents for executing solid-phase synthesis are commercially available from, for example, Applied Biosystems. Any other means for such synthesis may also be employed; the actual synthesis of the oligonucleotides is well within the capabilities of one skilled in the art and can be accomplished via established methodologies as detailed in, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988) and “Oligonucleotide Synthesis” Gait, M. J., ed. (1984) utilizing solid phase chemistry, e.g. cyanoethyl phosphoramidite followed by deprotection, desalting and purification by for example, an automated trityl-on method or HPLC.

Oligonucleotides used according to this aspect of the present invention are those having a length selected from a range of about 10 to about 200 bases preferably about 15 to about 150 bases, more preferably about 20 to about 100 bases, most preferably about 20 to about 50 bases. Preferably, the oligonucleotide of the present invention features at least 17, at least 18, at least 19, at least 20, at least 22, at least 25, at least 30 or at least 40, bases specifically hybridizable with the biomarkers of the present invention.

The oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3′ to 5′ phosphodiester linkage.

Preferably used oligonucleotides are those modified at one or more of the backbone, internucleoside linkages or bases, as is broadly described hereinunder.

Specific examples of preferred oligonucleotides useful according to this aspect of the present invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. Oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone, as disclosed in U.S. Pat. Nos. 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050.

Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Various salts, mixed salts and free acid forms can also be used.

Alternatively, modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH₂component parts, as disclosed in U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439.

Other oligonucleotides which can be used according to the present invention, are those modified in both sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for complementation with the appropriate polynucleotide target. An example for such an oligonucleotide mimetic, includes peptide nucleic acid (PNA). United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Other backbone modifications, which can be used in the present invention are disclosed in U.S. Pat. No. 6,303,374.

Oligonucleotides of the present invention may also include base modifications or substitutions. As used herein, “unmodified” or “natural” bases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified bases include but are not limited to other synthetic and natural bases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further bases particularly useful for increasing the binding affinity of the oligomeric compounds of the invention include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. and are presently preferred base substitutions, even more particularly when combined with 2′-O-methoxyethyl sugar modifications.

Another modification of the oligonucleotides of the invention involves chemically linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., hexyl-5-tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues, a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety, as disclosed in U.S. Pat. No. 6,303,374.

It is not necessary for all positions in a given oligonucleotide molecule to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide.

It will be appreciated that oligonucleotides of the present invention may include further modifications for more efficient use as diagnostic agents and/or to increase bioavailability, therapeutic efficacy and reduce cytotoxicity.

To enable cellular expression of the polynucleotides of the present invention, a nucleic acid construct according to the present invention may be used, which includes at least a coding region of one of the above nucleic acid sequences, and further includes at least one cis acting regulatory element. As used herein, the phrase “cis acting regulatory element” refers to a polynucleotide sequence, preferably a promoter, which binds a trans acting regulator and regulates the transcription of a coding sequence located downstream thereto.

Any suitable promoter sequence can be used by the nucleic acid construct of the present invention.

Preferably, the promoter utilized by the nucleic acid construct of the present invention is active in the specific cell population transformed. Examples of cell type-specific and/or tissue-specific promoters include promoters such as albumin that is liver specific, lymphoid specific promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular promoters of T-cell receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins; [Banerji et al. (1983) Cell 33729-740], neuron-specific promoters such as the neurofilament promoter [Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477], pancreas-specific promoters (Edlunch et al. (1985) Science 230:912-916] or mammary gland-specific promoters such as the milk whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). The nucleic acid construct of the present invention can further include an enhancer, which can be adjacent or distant to the promoter sequence and can function in up regulating the transcription therefrom.

The nucleic acid construct of the present invention preferably further includes an appropriate selectable marker and/or an origin of replication. Preferably, the nucleic acid construct utilized is a shuttle vector, which can propagate both in E. coli (wherein the construct comprises an appropriate selectable marker and origin of replication) and be compatible for propagation in cells, or integration in a gene and a tissue of choice. The construct according to the present invention can be, for example, a plasmid, a bacmid, a phagemid, a cosmid, a phage, a virus or an artificial chromosome.

Examples of suitable constructs include, but are not limited to, pcDNA3, pcDNA3.1 (+/−), pGL3, PzeoSV2 (+/−), pDisplay, pEF/myc/cyto, pCMV/myc/cyto each of which is commercially available from Invitrogen Co. (www.invitrogen.com). Examples of retroviral vector and packaging systems are those sold by Clontech, San Diego, Calif., including Retro-X vectors pLNCX and pLXSN, which permit cloning into multiple cloning sites and the trasgene is transcribed from CMV promoter. Vectors derived from Mo-MuLV are also included such as pBabe, where the transgene will be transcribed from the 5′LTR promoter.

Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs, such as adenovirus, lentivirus, Herpes simplex I virus, or adeno-associated virus (AAV) and lipid-based systems. Useful lipids for lipid-mediated transfer of the gene are, for example, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy are viruses, most preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct such as a retroviral construct includes at least one transcriptional promoter/enhancer or locus-defining element(s), or other elements that control gene expression by other means such as alternate splicing, nuclear RNA export, or post-translational modification of messenger. Such vector constructs also include a packaging signal, long terminal repeats (LTRs) or portions thereof, and positive and negative strand primer binding sites appropriate to the virus used, unless it is already present in the viral construct. In addition, such a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed. Preferably the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the polypeptide variants of the present invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. By way of example, such constructs will typically include a 5′ LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3′ LTR or a portion thereof. Other vectors can be used that are non-viral, such as cationic lipids, polylysine, and dendrimers.

Hybridization Assays

Detection of a nucleic acid of interest in a biological sample may optionally be effected by hybridization-based assays using an oligonucleotide probe (non-limiting examples of probes according to the present invention were previously described).

Traditional hybridization assays include PCR, RT-PCR, Real-time PCR, RNase protection, in-situ hybridization, primer extension, Southern blots (DNA detection), dot or slot blots (DNA, RNA), and Northern blots (RNA detection) (NAT type assays are described in greater detail below). More recently, PNAs have been described (Nielsen et al. 1999, Current Opin. Biotechnol. 10:71-75). Other detection methods include kits containing probes on a dipstick setup and the like.

Hybridization based assays which allow the detection of a variant of interest (i.e., DNA or RNA) in a biological sample rely on the use of oligonucleotides which can be 10, 15, 20, or 30 to 100 nucleotides long preferably from 10 to 50, more preferably from 40 to 50 nucleotides long.

Thus, the isolated polynucleotides (oligonucleotides) of the present invention are preferably hybridizable with any of the herein described nucleic acid sequences under moderate to stringent hybridization conditions.

Moderate to stringent hybridization conditions are characterized by a hybridization solution such as containing 10% dextrane sulfate, 1 M NaCl, 1% SDS and 5×10⁶cpm ³²P labeled probe, at 65° C., with a final wash solution of 0.2×SSC and 0.1% SDS and final wash at 65° C. and whereas moderate hybridization is effected using a hybridization solution containing 10% dextrane sulfate, 1 M NaCl, 1% SDS and 5×10⁶cpm ³²P labeled probe, at 65° C., with a final wash solution of 1×SSC and 0.1% SDS and final wash at 50° C.

More generally, hybridization of short nucleic acids (below 200 bp in length, e.g. 17-40 bp in length) can be effected using the following exemplary hybridization protocols which can be modified according to the desired stringency; (i) hybridization solution of 6×SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 μg/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature of 1-1.5° C. below the T_m, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5° C. below the T_m; (ii) hybridization solution of 6×SSC and 0.1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 μg/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature of 2-2.5° C. below the T_m, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5° C. below the T_m, final wash solution of 6×SSC, and final wash at 22° C.; (iii) hybridization solution of 6×SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 μg/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature.

The detection of hybrid duplexes can be carried out by a number of methods. Typically, hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected. Such labels refer to radioactive, fluorescent, biological or enzymatic tags or labels of standard use in the art. A label can be conjugated to either the oligonucleotide probes or the nucleic acids derived from the biological sample.

Probes can be labeled according to numerous well known methods. Non-limiting examples of radioactive labels include 3H, 14C, 32P, and 35S, Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies. Other detectable markers for use with probes, which can enable an increase in sensitivity of the method of the invention, include biotin and radio-nucleotides. It will become evident to the person of ordinary skill that the choice of a particular label dictates the manner in which it is bound to the probe.

For example, oligonucleotides of the present invention can be labeled subsequent to synthesis, by incorporating biotinylated dNTPs or rNTP, or some similar means (e.g., photo-cross-linking a psoralen derivative of biotin to RNAs), followed by addition of labeled streptavidin (e.g., phycoerythrin-conjugated streptavidin) or the equivalent. Alternatively, when fluorescently-labeled oligonucleotide probes are used, fluorescein, lissamine, phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, FluorX (Amersham) and others [e.g., Kricka et al. (1992), Academic Press San Diego, Calif] can be attached to the oligonucleotides.

Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes.

It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. For instance, samples may be hybridized to an irrelevant probe and treated with RNAse A prior to hybridization, to assess false hybridization.

Although the present invention is not specifically dependent on the use of a label for the detection of a particular nucleic acid sequence, such a label might be beneficial, by increasing the sensitivity of the detection. Furthermore, it enables automation. Probes can be labeled according to numerous well known methods.

As commonly known, radioactive nucleotides can be incorporated into probes of the invention by several methods. Non-limiting examples of radioactive labels include ³H, ¹⁴C, 32P, and 35S.

It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays.

Probes of the invention can be utilized with naturally occurring sugar-phosphate backbones as well as modified backbones including phosphorothioates, dithionates, alkyl phosphonates and a-nucleotides and the like. Probes of the invention can be constructed of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA.

NAT Assays

Detection of a nucleic acid of interest in a biological sample may also optionally be effected by NAT-based assays, which involve nucleic acid amplification technology, such as PCR for example (or variations thereof such as real-time PCR for example).

As used herein, a “primer” defines an oligonucleotide which is capable of annealing to (hybridizing with) a target sequence, thereby creating a double stranded region which can serve as an initiation point for DNA synthesis under suitable conditions.

Amplification of a selected, or target, nucleic acid sequence may be carried out by a number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous amplification techniques have been described and can be readily adapted to suit particular needs of a person of ordinary skill. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-based amplification, the q3 replicase system and NASBA (Kwoh et al., 1989, Proc. Natl. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260; and Sambrook et al., 1989, supra).

The terminology “amplification pair” (or “primer pair”) refers herein to a pair of oligonucleotides (oligos) of the present invention, which are selected to be used together in amplifying a selected nucleic acid sequence by one of a number of types of amplification processes, preferably a polymerase chain reaction. Other types of amplification processes include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based amplification, as explained in greater detail below. As commonly known in the art, the oligos are designed to bind to a complementary sequence under selected conditions.

In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions which favor the amplification of the most abundant differentially expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA. In another preferred embodiment, the amplification of the differentially expressed nucleic acids is carried out simultaneously. It will be realized by a person skilled in the art that such methods could be adapted for the detection of differentially expressed proteins instead of differentially expressed nucleic acid sequences.

The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be obtained according to well known methods.

Oligonucleotide primers of the present invention may be of any suitable length, depending on the particular assay format and the particular needs and targeted genomes employed. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, and they may be adapted to be especially suited to a chosen nucleic acid amplification system. As commonly known in the art, the oligonucleotide primers can be designed by taking into consideration the melting point of hybridization thereof with its targeted sequence (Sambrook et al., 1989, Molecular Cloning—A Laboratory Manual, 2nd Edition, CSH Laboratories; Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N.Y.).

It will be appreciated that antisense oligonucleotides may be employed to quantify expression of a splice isoform of interest. Such detection is effected at the pre-mRNA level. Essentially the ability to quantitate transcription from a splice site of interest can be effected based on splice site accessibility. Oligonucleotides may compete with splicing factors for the splice site sequences. Thus, low activity of the antisense oligonucleotide is indicative of splicing activity.

The polymerase chain reaction and other nucleic acid amplification reactions are well known in the art (various non-limiting examples of these reactions are described in greater detail below). The pair of oligonucleotides according to this aspect of the present invention are preferably selected to have compatible melting temperatures (Tm), e.g., melting temperatures which differ by less than that 7° C., preferably less than 5° C., more preferably less than 4° C., most preferably less than 3° C., ideally between 3° C. and 0° C.

Polymerase Chain Reaction (PCR): The polymerase chain reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a method of increasing the concentration of a segment of target sequence in a mixture of genomic DNA without cloning or purification. This technology provides one approach to the problems of low target sequence concentration. PCR can be used to directly increase the concentration of the target to an easily detectable level. This process for amplifying the target sequence involves the introduction of a molar excess of two oligonucleotide primers which are complementary to their respective strands of the double-stranded target sequence to the DNA mixture containing the desired target sequence. The mixture is denatured and then allowed to hybridize. Following hybridization, the primers are extended with polymerase so as to form complementary strands. The steps of denaturation, hybridization (annealing), and polymerase extension (elongation) can be repeated as often as needed, in order to obtain relatively high concentrations of a segment of the desired target sequence.

The length of the segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and, therefore, this length is a controllable parameter. Because the desired segments of the target sequence become the dominant sequences (in terms of concentration) in the mixture, they are said to be “PCR-amplified.”

Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes referred to as “Ligase Amplification Reaction” (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids. In LCR, four oligonucleotides, two adjacent oligonucleotides which uniquely hybridize to one strand of target DNA, and a complementary set of adjacent oligonucleotides, which hybridize to the opposite strand are mixed and DNA ligase is added to the mixture. Provided that there is complete complementarity at the junction, ligase will covalently link each set of hybridized molecules. Importantly, in LCR, two probes are ligated together only when they base-pair with sequences in the target sample, without gaps or mismatches. Repeated cycles of denaturation, and ligation amplify a short segment of DNA. LCR has also been used in combination with PCR to achieve enhanced detection of single-base changes: see for example Segev, PCT Publication No. WO9001069 A1 (1990). However, because the four oligonucleotides used in this assay can pair to form two short ligatable fragments, there is the potential for the generation of target-independent background signal. The use of LCR for mutant screening is limited to the examination of specific nucleic acid positions.

Self-Sustained Synthetic Reaction (3SR/NASBA): The self-sustained sequence replication reaction (3SR) is a transcription-based in vitro amplification system that can exponentially amplify RNA sequences at a uniform temperature. The amplified RNA can then be utilized for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5′ end of the sequence of interest. In a cocktail of enzymes and substrates that includes a second primer, reverse transcriptase, RNase H, RNA polymerase and ribo- and deoxyribonucleoside triphosphates, the target sequence undergoes repeated rounds of transcription, cDNA synthesis and second-strand synthesis to amplify the area of interest. The use of 3SR to detect mutations is kinetically limited to screening small segments of DNA (e.g., 200-300 base pairs).

Q-Beta (Qβ) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for Qβ replicase. A previously identified major problem with false positives resulting from the replication of unhybridized probes has been addressed through use of a sequence-specific ligation step. However, available thermostable DNA ligases are not effective on this RNA substrate, so the ligation must be performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents the use of high temperature as a means of achieving specificity as in the LCR, the ligation event can be used to detect a mutation at the junction site, but not elsewhere.

A successful diagnostic method must be very specific. A straight-forward method of controlling the specificity of nucleic acid hybridization is by controlling the temperature of the reaction. While the 3SR/NASBA, and Qβ systems are all able to generate a large quantity of signal, one or more of the enzymes involved in each cannot be used at high temperature (i.e., >55 degrees C.). Therefore the reaction temperatures cannot be raised to prevent non-specific hybridization of the probes. If probes are shortened in order to make them melt more easily at low temperatures, the likelihood of having more than one perfect match in a complex genome increases. For these reasons, PCR and LCR currently dominate the research field in detection technologies.

The basis of the amplification procedure in the PCR and LCR is the fact that the products of one cycle become usable templates in all subsequent cycles, consequently doubling the population with each cycle. The final yield of any such doubling system can be expressed as: (I+X)ⁿ=y, where “X” is the mean efficiency (percent copied in each cycle), “n” is the number of cycles, and “y” is the overall efficiency, or yield of the reaction. If every copy of a target DNA is utilized as a template in every cycle of a polymerase chain reaction, then the mean efficiency is 100%. If 20 cycles of PCR are performed, then the yield will be 220, or 1,048,576 copies of the starting material. If the reaction conditions reduce the mean efficiency to 85%, then the yield in those 20 cycles will be only 1.85²⁰, or 220,513 copies of the starting material. In other words, a PCR running at 85% efficiency will yield only 21% as much final product, compared to a reaction running at 100% efficiency. A reaction that is reduced to 50% mean efficiency will yield less than 1% of the possible product.

In practice, routine polymerase chain reactions rarely achieve the theoretical maximum yield, and PCRs are usually run for more than 20 cycles to compensate for the lower yield. At 50% mean efficiency, it would take 34 cycles to achieve the million-fold amplification theoretically possible in 20, and at lower efficiencies, the number of cycles required becomes prohibitive. In addition, any background products that amplify with a better mean efficiency than the intended target will become the dominant products.

Also, many variables can influence the mean efficiency of PCR, including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, and buffer composition, to name but a few. Contamination of the reaction with exogenous DNA (e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major consideration. Reaction conditions must be carefully optimized for each different primer pair and target sequence, and the process can take days, even for an experienced investigator. The laboriousness of this process, including numerous technical considerations and other factors, presents a significant drawback to using PCR in the clinical setting. Indeed, PCR has yet to penetrate the clinical market in a significant way. The same concerns arise with LCR, as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. In addition, both methods require expensive equipment, capable of precise temperature cycling.

Many applications of nucleic acid detection technologies, such as in studies of allelic variation, involve not only detection of a specific sequence in a complex background, but also the discrimination between sequences with few, or single, nucleotide differences. One method of the detection of allele-specific variants by PCR is based upon the fact that it is difficult for Taq polymerase to synthesize a DNA strand when there is a mismatch between the template strand and the 3′ end of the primer. An allele-specific variant may be detected by the use of a primer that is perfectly matched with only one of the possible alleles; the mismatch to the other allele acts to prevent the extension of the primer, thereby preventing the amplification of that sequence. This method has a substantial limitation in that the base composition of the mismatch influences the ability to prevent extension across the mismatch, and certain mismatches do not prevent extension or have only a minimal effect.

A similar 3′-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the thermostable ligase, but LCR still has the drawback of target-independent background ligation products initiating the amplification. Moreover, the combination of PCR with subsequent LCR to identify the nucleotides at individual positions is also a clearly cumbersome proposition for the clinical laboratory.

The direct detection method according to various preferred embodiments of the present invention may be, for example a cycling probe reaction (CPR) or a branched DNA analysis.

When a sufficient amount of a nucleic acid to be detected is available, there are advantages to detecting that sequence directly, instead of making more copies of that target, (e.g., as in PCR and LCR). Most notably, a method that does not amplify the signal exponentially is more amenable to quantitative analysis. Even if the signal is enhanced by attaching multiple dyes to a single oligonucleotide, the correlation between the final signal intensity and amount of target is direct. Such a system has an additional advantage that the products of the reaction will not themselves promote further reaction, so contamination of lab surfaces by the products is not as much of a concern. Recently devised techniques have sought to eliminate the use of radioactivity and/or improve the sensitivity in automatable formats. Two examples are the “Cycling Probe Reaction” (CPR), and “Branched DNA” (bDNA).

Cycling probe reaction (CPR): The cycling probe reaction (CPR), uses a long chimeric oligonucleotide in which a central portion is made of RNA while the two termini are made of DNA. Hybridization of the probe to a target DNA and exposure to a thermostable RNase H causes the RNA portion to be digested. This destabilizes the remaining DNA portions of the duplex, releasing the remainder of the probe from the target DNA and allowing another probe molecule to repeat the process. The signal, in the form of cleaved probe molecules, accumulates at a linear rate. While the repeating process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNases that may carried through sample preparation.

Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched structures that allow each individual oligonucleotide to carry 35 to 40 labels (e.g., alkaline phosphatase enzymes). While this enhances the signal from a hybridization event, signal from non-specific binding is similarly increased.

The detection of at least one sequence change according to various preferred embodiments of the present invention may be accomplished by, for example restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF).

The demand for tests which allow the detection of specific nucleic acid sequences and sequence changes is growing rapidly in clinical diagnostics. As nucleic acid sequence data for genes from humans and pathogenic organisms accumulates, the demand for fast, cost-effective, and easy-to-use tests for as yet mutations within specific sequences is rapidly increasing.

A handful of methods have been devised to scan nucleic acid segments for mutations. One option is to determine the entire gene sequence of each test sample (e.g., a bacterial isolate). For sequences under approximately 600 nucleotides, this may be accomplished using amplified material (e.g., PCR reaction products). This avoids the time and expense associated with cloning the segment of interest. However, specialized equipment and highly trained personnel are required, and the method is too labor-intense and expensive to be practical and effective in the clinical setting.

In view of the difficulties associated with sequencing, a given segment of nucleic acid may be characterized on several other levels. At the lowest resolution, the size of the molecule can be determined by electrophoresis by comparison to a known standard run on the same gel. A more detailed picture of the molecule may be achieved by cleavage with combinations of restriction enzymes prior to electrophoresis, to allow construction of an ordered map. The presence of specific sequences within the fragment can be detected by hybridization of a labeled probe, or the precise nucleotide sequence can be determined by partial chemical degradation or by primer extension in the presence of chain-terminating nucleotide analogs.

Restriction fragment length polymorphism (RFLP): For detection of single-base differences between like sequences, the requirements of the analysis are often at the highest level of resolution. For cases in which the position of the nucleotide in question is known in advance, several methods have been developed for examining single base changes without direct sequencing. For example, if a mutation of interest happens to fall within a restriction recognition sequence, a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis).

Single point mutations have been also detected by the creation or destruction of RFLPs. Mutations are detected and localized by the presence and size of the RNA fragments generated by cleavage at the mismatches. Single nucleotide mismatches in DNA heteroduplexes are also recognized and cleaved by some chemicals, providing an alternative strategy to detect single base substitutions, generically named the “Mismatch Chemical Cleavage” (MCC). However, this method requires the use of osmium tetroxide and piperidine, two highly noxious chemicals which are not suited for use in a clinical laboratory.

RFLP analysis suffers from low sensitivity and requires a large amount of sample. When RFLP analysis is used for the detection of point mutations, it is, by its nature, limited to the detection of only those single base changes which fall within a restriction sequence of a known restriction endonuclease. Moreover, the majority of the available enzymes have 4 to 6 base-pair recognition sequences, and cleave too frequently for many large-scale DNA manipulations. Thus, it is applicable only in a small fraction of cases, as most mutations do not fall within such sites.

A handful of rare-cutting restriction enzymes with 8 base-pair specificities have been isolated and these are widely used in genetic mapping, but these enzymes are few in number, are limited to the recognition of G+C-rich sequences, and cleave at sites that tend to be highly clustered. Recently, endonucleases encoded by group I introns have been discovered that might have greater than 12 base-pair specificity, but again, these are few in number.

Allele specific oligonucleotide (ASO): If the change is not in a recognition sequence, then allele-specific oligonucleotides (ASOs), can be designed to hybridize in proximity to the mutated nucleotide, such that a primer extension or ligation event can bused as the indicator of a match or a mis-match. Hybridization with radioactively labeled allelic specific oligonucleotides (ASO) also has been applied to the detection of specific point mutations. The method is based on the differences in the melting temperature of short DNA fragments differing by a single nucleotide. Stringent hybridization and washing conditions can differentiate between mutant and wild-type alleles. The ASO approach applied to PCR products also has been extensively utilized by various researchers to detect and characterize point mutations in ras genes and gsp/gip oncogenes. Because of the presence of various nucleotide changes in multiple positions, the ASO method requires the use of many oligonucleotides to cover all possible oncogenic mutations.

With either of the techniques described above (i.e., RFLP and ASO), the precise location of the suspected mutation must be known in advance of the test. That is to say, they are inapplicable when one needs to detect the presence of a mutation within a gene or sequence of interest.

Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE): Two other methods rely on detecting changes in electrophoretic mobility in response to minor sequence changes. One of these methods, termed “Denaturing Gradient Gel Electrophoresis” (DGGE) is based on the observation that slightly different sequences will display different patterns of local melting when electrophoretically resolved on a gradient gel. In this manner, variants can be distinguished, as differences in melting properties of homoduplexes versus heteroduplexes differing in a single nucleotide can detect the presence of mutations in the target sequences because of the corresponding changes in their electrophoretic mobilities. The fragments to be analyzed, usually PCR products, are “clamped” at one end by a long stretch of G-C base pairs (30-80) to allow complete denaturation of the sequence of interest without complete dissociation of the strands. The attachment of a GC “clamp” to the DNA fragments increases the fraction of mutations that can be recognized by DGGE. Attaching a GC clamp to one primer is critical to ensure that the amplified sequence has a low dissociation temperature. Modifications of the technique have been developed, using temperature gradients, and the method can be also applied to RNA:RNA duplexes.

Limitations on the utility of DGGE include the requirement that the denaturing conditions must be optimized for each type of DNA to be tested. Furthermore, the method requires specialized equipment to prepare the gels and maintain the needed high temperatures during electrophoresis. The expense associated with the synthesis of the clamping tail on one oligonucleotide for each sequence to be tested is also a major consideration. In addition, long running times are required for DGGE. The long running time of DGGE was shortened in a modification of DGGE called constant denaturant gel electrophoresis (CDGEi). CDGE requires that gels be performed under different denaturant conditions in order to reach high efficiency for the detection of mutations.

A technique analogous to DGGE, termed temperature gradient gel electrophoresis (TGGE), uses a thermal gradient rather than a chemical denaturant gradient. TGGE requires the use of specialized equipment which can generate a temperature gradient perpendicularly oriented relative to the electrical field. TGGE can detect mutations in relatively small fragments of DNA therefore scanning of large gene segments requires the use of multiple PCR products prior to running the gel.

Single-Strand Conformation Polymorphism (SSCP): Another common method, called “Single-Strand Conformation Polymorphism” (SSCP) was developed by Hayashi, Sekya and colleagues and is based on the observation that single strands of nucleic acid can take on characteristic conformations in non-denaturing conditions, and these conformations influence electrophoretic mobility. The complementary strands assume sufficiently different structures that one strand may be resolved from the other. Changes in sequences within the fragment will also change the conformation, consequently altering the mobility and allowing this to be used as an assay for sequence variations.

The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that is labeled on both strands, followed by slow electrophoretic separation on a non-denaturing polyacrylamide gel, so that intra-molecular interactions can form and not be disturbed during the run. This technique is extremely sensitive to variations in gel composition and temperature. A serious limitation of this method is the relative difficulty encountered in comparing data generated in different laboratories, under apparently similar conditions.

Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technique combines components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing reaction is performed using one dideoxy terminator and then the reaction products are electrophoresed on nondenaturing polyacrylamide gels to detect alterations in mobility of the termination segments as in SSCP analysis. While ddF is an improvement over SSCP in terms of increased sensitivity, ddF requires the use of expensive dideoxynucleotides and this technique is still limited to the analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-300 bases for optimal detection of mutations).

In addition to the above limitations, all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed. For the direct sequencing approach, sequences of greater than 600 base pairs require cloning, with the consequent delays and expense of either deletion sub-cloning or primer walking, in order to cover the entire fragment. SSCP and DGGE have even more severe size limitations. Because of reduced sensitivity to sequence changes, these methods are not considered suitable for larger fragments. Although SSCP is reportedly able to detect 90% of single-base substitutions within a 200 base-pair fragment, the detection drops to less than 50% for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases as the length of the fragment reaches 500 base-pairs. The ddF technique, as a combination of direct sequencing and SSCP, is also limited by the relatively small size of the DNA that can be screened.

According to a presently preferred embodiment of the present invention the step of searching for any of the nucleic acid sequences described here, in tumor cells or in cells derived from a cancer patient is effected by any suitable technique, including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, Qβ-Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis and dideoxy fingerprinting.

Detection may also optionally be performed with a chip or other such device. The nucleic acid sample which includes the candidate region to be analyzed is preferably isolated, amplified and labeled with a reporter group. This reporter group can be a fluorescent group such as phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station. describe the fabrication of fluidics devices and particularly microcapillary devices, in silicon and glass substrates.

Once the reaction is completed, the chip is inserted into a scanner and patterns of hybridization are detected. The hybridization data is collected, as a signal emitted from the reporter groups already incorporated into the nucleic acid, which is now bound to the probes attached to the chip. Since the sequence and position of each probe immobilized on the chip is known, the identity of the nucleic acid hybridized to a given probe can be determined.

It will be appreciated that when utilized along with automated equipment, the above described detection methods can be used to screen multiple samples for a disease and/or pathological condition both rapidly and easily.

Amino Acid Sequences and Peptides

The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. Polypeptides can be modified, e.g., by the addition of carbohydrate residues to form glycoproteins. The terms “polypeptide,” “peptide” and “protein” include glycoproteins, as well as non-glycoproteins.

Polypeptide products can be biochemically synthesized such as by employing standard solid phase techniques. Such methods include but are not limited to exclusive solid phase synthesis, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry.

Solid phase polypeptide synthesis procedures are well known in the art and further described by John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984).

Synthetic polypeptides can optionally be purified by preparative high performance liquid chromatography [Creighton T. (1983) Proteins, structures and molecular principles. WH Freeman and Co. N.Y.], after which their composition can be confirmed via amino acid sequencing.

In cases where large amounts of a polypeptide are desired, it can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463.

The present invention also encompasses polypeptides encoded by the polynucleotide sequences of the present invention, as well as polypeptides according to the amino acid sequences described herein. The present invention also encompasses homologues of these polypeptides, such homologues can be at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95% or more say 100% homologous to the amino acid sequences set forth below, as can be determined using BlastP software of the National Center of Biotechnology Information (NCBI) using default parameters, optionally and preferably including the following: filtering on (this option filters repetitive or low-complexity sequences from the query using the Seg (protein) program), scoring matrix is BLOSUM62 for proteins, word size is 3, E value is 10, gap costs are 11, 1 (initialization and extension), and number of alignments shown is 50. Optionally and preferably, nucleic acid sequence homology/identity may be determined by using BlastN software of the National Center of Biotechnology Information (NCBI) using default parameters, which preferably include using the DUST filter program, and also preferably include having an E value of 10, filtering low complexity sequences and a word size of 11. Finally, the present invention also encompasses fragments of the above described polypeptides and polypeptides having mutations, such as deletions, insertions or substitutions of one or more amino acids, either naturally occurring or artificially induced, either randomly or in a targeted fashion.

It will be appreciated that peptides identified according the present invention may be degradation products, synthetic peptides or recombinant peptides as well as peptidomimetics, typically, synthetic peptides and peptoids and semipeptoids which are peptide analogs, which may have, for example, modifications rendering the peptides more stable while in a body or more capable of penetrating into cells. Such modifications include, but are not limited to N terminus modification, C terminus modification, peptide bond modification, including, but not limited to, CH2-NH, CH2-S, CH2-S═O, O═C—NH, CH2-O, CH2-CH2, S═C—NH, CH═CH or CF═CH, backbone modifications, and residue modification. Methods for preparing peptidomimetic compounds are well known in the art and are specified. Further details in this respect are provided hereinunder.

Peptide bonds (—CO—NH—) within the peptide may be substituted, for example, by N-methylated bonds (—N(CH3)-CO—), ester bonds (—C(R)H—C—O—O—C(R)—N—), ketomethylen bonds (—CO—CH2-), α-aza bonds (—NH—N(R)—CO—), wherein R is any alkyl, e.g., methyl, carba bonds (—CH2-NH—), hydroxyethylene bonds (—CH(OH)—CH2-), thioamide bonds (—CS—NH—), olefinic double bonds (—CH═CH—), retro amide bonds (—NH—CO—), peptide derivatives (—N(R)—CH2-CO—), wherein R is the “normal” side chain, naturally presented on the carbon atom.

These modifications can occur at any of the bonds along the peptide chain and even at several (2-3) at the same time.

Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted for synthetic non-natural acid such as Phenylglycine, TIC, naphthylelanine (Nol), ring-methylated derivatives of Phe, halogenated derivatives of Phe or o-methyl-Tyr.

In addition to the above, the peptides of the present invention may also include one or more modified amino acids or one or more non-amino acid monomers (e.g. fatty acids, complex carbohydrates etc).

As used herein in the specification and in the claims section below the term “amino acid” or “amino acids” is understood to include the 20 naturally occurring amino acids; those amino acids often modified post-translationally in vivo, including, for example, hydroxyproline, phosphoserine and phosphothreonine; and other unusual amino acids including, but not limited to, 2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine, nor-leucine and ornithine. Furthermore, the term “amino acid” includes both D- and L-amino acids.

TABLE A

Table A: non-conventional or modified amino acids

which can be used with the present invention.

Non-conventional amino acid
Code
Non-conventional amino acid
Code

α-aminobutyric acid
Abu
L-N-methylalanine
Nmala

α-amino-α-methylbutyrate
Mgabu
L-N-methylarginine
Nmarg

aminocyclopropane-
Cpro
L-N-methylasparagine
Nmasn

Carboxylate

L-N-methylaspartic acid
Nmasp

aminoisobutyric acid
Aib
L-N-methylcysteine
Nmcys

aminonorbomyl-
Norb
L-N-methylglutamine
Nmgin

Carboxylate

L-N-methylglutamic acid
Nmglu

Cyclohexylalanine
Chexa
L-N-methylhistidine
Nmhis

Cyclopentylalanine
Cpen
L-N-methylisolleucine
Nmile

D-alanine
Dal
L-N-methylleucine
Nmleu

D-arginine
Darg
L-N-methyllysine
Nmlys

D-aspartic acid
Dasp
L-N-methylmethionine
Nmmet

D-cysteine
Dcys
L-N-methylnorleucine
Nmnle

D-glutamine
Dgln
L-N-methylnorvaline
Nmnva

D-glutamic acid
Dglu
L-N-methylornithine
Nmorn

D-histidine
Dhis
L-N-methylphenylalanine
Nmphe

D-isoleucine
Dile
L-N-methylproline
Nmpro

D-leucine
Dleu
L-N-methylserine
Nmser

D-lysine
Dlys
L-N-methylthreonine
Nmthr

D-methionine
Dmet
L-N-methyltryptophan
Nmtrp

D-ornithine
Dorn
L-N-methyltyrosine
Nmtyr

D-phenylalanine
Dphe
L-N-methylvaline
Nmval

D-proline
Dpro
L-N-methylethylglycine
Nmetg

D-serine
Dser
L-N-methyl-t-butylglycine
Nmtbug

D-threonine
Dthr
L-norleucine
Nle

D-tryptophan
Dtrp
L-norvaline
Nva

D-tyrosine
Dtyr
α-methyl-aminoisobutyrate
Maib

D-valine
Dval
α-methyl-γ-aminobutyrate
Mgabu

D-α-methylalanine
Dmala
α-methylcyclohexylalanine
Mchexa

D-α-methylarginine
Dmarg
α-methylcyclopentylalanine
Mcpen

D-α-methylasparagine
Dmasn
α-methyl-α-napthylalanine
Manap

D-α-methylaspartate
Dmasp
α-methylpenicillamine
Mpen

D-α-methylcysteine
Dmcys
N-(4-aminobutyl)glycine
Nglu

D-α-methylglutamine
Dmgln
N-(2-aminoethyl)glycine
Naeg

D-α-methylhistidine
Dmhis
N-(3-aminopropyl)glycine
Norn

D-α-methylisoleucine
Dmile
N-amino-α-methylbutyrate
Nmaabu

D-α-methylleucine
Dmleu
α-napthylalanine
Anap

D-α-methyllysine
Dmlys
N-benzylglycine
Nphe

D-α-methylmethionine
Dmmet
N-(2-carbamylethyl)glycine
Ngln

D-α-methylornithine
Dmorn
N-(carbamylmethyl)glycine
Nasn

D-α-methylphenylalanine
Dmphe
N-(2-carboxyethyl)glycine
Nglu

D-α-methylproline
Dmpro
N-(carboxymethyl)glycine
Nasp

D-α-methylserine
Dmser
N-cyclobutylglycine
Ncbut

D-α-methylthreonine
Dmthr
N-cycloheptylglycine
Nchep

D-α-methyltryptophan
Dmtrp
N-cyclohexylglycine
Nchex

D-α-methyltyrosine
Dmty
N-cyclodecylglycine
Ncdec

D-α-methylvaline
Dmval
N-cyclododeclglycine
Ncdod

D-α-methylalnine
Dnmala
N-cyclooctylglycine
Ncoct

D-α-methylarginine
Dnmarg
N-cyclopropylglycine
Ncpro

D-α-methylasparagine
Dnmasn
N-cycloundecylglycine
Ncund

D-α-methylasparatate
Dnmasp
N-(2,2-diphenylethyl)glycine
Nbhm

D-α-methylcysteine
Dnmcys
N-(3,3-diphenylpropyl)glycine
Nbhe

D-N-methylleucine
Dnmleu
N-(3-indolylyethyl) glycine
Nhtrp

D-N-methyllysine
Dnmlys
N-methyl-γ-aminobutyrate
Nmgabu

N-methylcyclohexylalanine
Nmchexa
D-N-methylmethionine
Dnmmet

D-N-methylornithine
Dnmorn
N-methylcyclopentylalanine
Nmcpen

N-methylglycine
Nala
D-N-methylphenylalanine
Dnmphe

N-methylaminoisobutyrate
Nmaib
D-N-methylproline
Dnmpro

N-(1-methylpropyl)glycine
Nile
D-N-methylserine
Dnmser

N-(2-methylpropyl)glycine
Nile
D-N-methylserine
Dnmser

N-(2-methylpropyl)glycine
Nleu
D-N-methylthreonine
Dnmthr

D-N-methyltryptophan
Dnmtrp
N-(1-methylethyl)glycine
Nva

D-N-methyltyrosine
Dnmtyr
N-methyla-napthylalanine
Nmanap

D-N-methylvaline
Dnmval
N-methylpenicillamine
Nmpen

γ-aminobutyric acid
Gabu
N-(p-hydroxyphenyl)glycine
Nhtyr

L-t-butylglycine
Tbug
N-(thiomethyl)glycine
Ncys

L-ethylglycine
Etg
penicillamine
Pen

L-homophenylalanine
Hphe
L-α-methylalanine
Mala

L-α-methylarginine
Marg
L-α-methylasparagine
Masn

L-α-methylaspartate
Masp
L-α-methyl-t-butylglycine
Mtbug

L-α-methylcysteine
Mcys
L-methylethylglycine
Metg

L-α-methylglutamine
Mgln
L-α-methylglutamate
Mglu

L-α-methylhistidine
Mhis
L-α-methylhomo phenylalanine
Mhphe

L-α-methylisoleucine
Mile
N-(2-methylthioethyl)glycine
Nmet

D-N-methylglutamine
Dnmgln
N-(3-guanidinopropyl)glycine
Narg

D-N-methylglutamate
Dnmglu
N-(1-hydroxyethyl)glycine
Nthr

D-N-methylhistidine
Dnmhis
N-(hydroxyethyl)glycine
Nser

D-N-methylisoleucine
Dnmile
N-(imidazolylethyl)glycine
Nhis

D-N-methylleucine
Dnmleu
N-(3-indolylyethyl)glycine
Nhtrp

D-N-methyllysine
Dnmlys
N-methyl-γ-aminobutyrate
Nmgabu

N-methylcyclohexylalanine
Nmchexa
D-N-methylmethionine
Dnmmet

D-N-methylornithine
Dnmorn
N-methylcyclopentylalanine
Nmcpen

N-methylglycine
Nala
D-N-methylphenylalanine
Dnmphe

N-methylaminoisobutyrate
Nmaib
D-N-methylproline
Dnmpro

N-(1-methylpropyl)glycine
Nile
D-N-methylserine
Dnmser

N-(2-methylpropyl)glycine
Nleu
D-N-methylthreonine
Dnmthr

D-N-methyltryptophan
Dnmtrp
N-(1-methylethyl)glycine
Nval

D-N-methyltyrosine
Dnmtyr
N-methyla-napthylalanine
Nmanap

D-N-methylvaline
Dnmval
N-methylpenicillamine
Nmpen

γ-aminobutyric acid
Gabu
N-(p-hydroxyphenyl)glycine
Nhtyr

L-t-butylglycine
Tbug
N-(thiomethyl)glycine
Ncys

L-ethylglycine
Etg
penicillamine
Pen

L-homophenylalanine
Hphe
L-α-methylalanine
Mala

L-α-methylarginine
Marg
L-α-methylasparagine
Masn

L-α-methylaspartate
Masp
L-α-methyl-t-butylglycine
Mtbug

L-α-methylcysteine
Mcys
L-methylethylglycine
Metg

L-α-methylglutamine
Mgln
L-α-methylglutamate
Mglu

L-α-methylhistidine
Mhis
L-α-methylhomophenylalanine
Mhphe

L-α-methylisoleucine
Mile
N-(2-methylthioethyl)glycine
Nmet

L-α-methylleucine
Mleu
L-α-methyllysine
Mlys

L-α-methylmethionine
Mmet
L-α-methylnorleucine
Mnle

L-α-methylnorvaline
Mnva
L-α-methylornithine
Morn

L-α-methylphenylalanine
Mphe
L-α-methylproline
Mpro

L-α-methylserine
mser
L-α-methylthreonine
Mthr

L-α-methylvaline
Mtrp
L-α-methyltyrosine
Mtyr

L-α-methylleucine
Mval Nnbhm
L-N-methylhomophenylalanine
Nmhphe

N-(N-(2,2-diphenylethyl)

N-(N-(3,3-diphenylpropyl)

carbamylmethyl-glycine
Nnbhm
carbamylmethyl(1)glycine
Nnbhe

1-carboxy-1-(2,2-diphenyl
Nmbc

ethylamino)cyclopropane

Since the peptides of the present invention are preferably utilized in diagnostics which require the peptides to be in soluble form, the peptides of the present invention preferably include one or more non-natural or natural polar amino acids, including but not limited to serine and threonine which are capable of increasing peptide solubility due to their hydroxyl-containing side chain.

The peptides of the present invention are preferably utilized in a linear form, although it will be appreciated that in cases where cyclicization does not severely interfere with peptide characteristics, cyclic forms of the peptide can also be utilized.

The peptides of present invention can be biochemically synthesized such as by using standard solid phase techniques. These methods include exclusive solid phase synthesis well known in the art, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry.

Synthetic peptides can be purified by preparative high performance liquid chromatography and the composition of which can be confirmed via amino acid sequencing.

In cases where large amounts of the peptides of the present invention are desired, the peptides of the present invention can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463 and also as described above.

Antibodies

“Antibody” refers to a polypeptide ligand that is preferably substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, which specifically binds and recognizes an epitope (e.g., an antigen). The recognized immunoglobulin genes include the kappa and lambda light chain constant region genes, the alpha, gamma, delta, epsilon and mu heavy chain constant region genes, and the myriad-immunoglobulin variable region genes. Antibodies exist, e.g., as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. This includes, e.g., Fab′ and F(ab)′₂fragments. The term “antibody,” as used herein, also includes antibody fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies. It also includes polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, or single chain antibodies. “Fc” portion of an antibody refers to that portion of an immunoglobulin heavy chain that comprises one or more heavy chain constant region domains, CH1, CH2 and CH3, but does not include the heavy chain variable region.

The functional fragments of antibodies, such as Fab, F(ab′)2, and Fv that are capable of binding to macrophages, are described as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fab′, the fragment of an antibody molecule that can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab′ fragments are obtained per antibody molecule; (3) (Fab′)₂, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab′)2 is a dimer of two Fab′ fragments held together by two disulfide bonds; (4) Fv, defined as a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (5) Single chain antibody (“SCA”), a genetically engineered molecule containing the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule.

Methods of producing polyclonal and monoclonal antibodies as well as fragments thereof are well known in the art (See for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988, incorporated herein by reference).

Antibody fragments according to the present invention can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli or mammalian cells (e.g. Chinese hamster ovary cell culture or other protein expression systems) of DNA encoding the fragment. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(ab′)2. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab′ monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab′ fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647, and references contained therein, which patents are hereby incorporated by reference in their entirety. See also Porter, R. R. [Biochem. J. 73: 119-126 (1959)]. Other methods of cleaving antibodies, such as separation of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody.

Fv fragments comprise an association of VH and VL chains. This association may be noncovalent, as described in Inbar et al. [Proc. Nat'l Acad. Sci. USA 69:2659-62 (19720]. Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross-linked by chemicals such as glutaraldehyde. Preferably, the Fv fragments comprise VH and VL chains connected by a peptide linker. These single-chain antigen binding proteins (sFv) are prepared by constructing a structural gene comprising DNA sequences encoding the VH and VL domains connected by an oligonucleotide. The structural gene is inserted into an expression vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing sFvs are described, for example, by [Whitlow and Filpula, Methods 2: 97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et al., Bio/Technology 11:1271-77 (1993); and U.S. Pat. No. 4,946,778, which is hereby incorporated by reference in its entirety.

Another form of an antibody fragment is a peptide coding for a single complementarity-determining region (CDR). CDR peptides (“minimal recognition units”) can be obtained by constructing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from RNA of antibody-producing cells. See, for example, Larrick and Fry [Methods, 2: 106-10 (1991)].

Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′) or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)].

Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991)]. Similarly, human antibodies can be made by introduction of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368 812-13 (1994); Fishwild et al., Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995).

Preferably, the antibody of this aspect of the present invention specifically binds at least one epitope of the polypeptide variants of the present invention. As used herein, the term “epitope” refers to any antigenic determinant on an antigen to which the paratope of an antibody binds.

Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics.

Optionally, a unique epitope may be created in a variant due to a change in one or more post-translational modifications, including but not limited to glycosylation and/or phosphorylation, as described below. Such a change may also cause a new epitope to be created, for example through removal of glycosylation at a particular site.

An epitope according to the present invention may also optionally comprise part or all of a unique sequence portion of a variant according to the present invention in combination with at least one other portion of the variant which is not contiguous to the unique sequence portion in the linear polypeptide itself, yet which are able to form an epitope in combination. One or more unique sequence portions may optionally combine with one or more other non-contiguous portions of the variant (including a portion which may have high homology to a portion of the known protein) to form an epitope.

Immunoassays

In another embodiment of the present invention, an immunoassay can be used to qualitatively or quantitatively detect and analyze markers in a sample. This method comprises: providing an antibody that specifically binds to a marker; contacting a sample with the antibody; and detecting the presence of a complex of the antibody bound to the marker in the sample.

To prepare an antibody that specifically binds to a marker, purified protein markers can be used. Antibodies that specifically bind to a protein marker can be prepared using any suitable methods known in the art.

After the antibody is provided, a marker can be detected and/or quantified using any of a number of well recognized immunological binding assays. Useful assays include, for example, an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay (ELISA), a radioimmune assay (RIA), a Western blot assay, or a slot blot assay see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). Generally, a sample obtained from a subject can be contacted with the antibody that specifically binds the marker.

Optionally, the antibody can be fixed to a solid support to facilitate washing and subsequent isolation of the complex, prior to contacting the antibody with a sample. Examples of solid supports include but are not limited to glass or plastic in the form of, e.g., a microtiter plate, a stick, a bead, or a microbead. Antibodies can also be attached to a solid support.

After incubating the sample with antibodies, the mixture is washed and the antibody-marker complex formed can be detected. This can be accomplished by incubating the washed mixture with a detection reagent. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.

Throughout the assays, incubation and/or washing steps may be required after each combination of reagents. Incubation steps can vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time will depend upon the assay format, marker, volume of solution, concentrations and the like. Usually the assays will be carried out at ambient temperature, although they can be conducted over a range of temperatures, such as 10° C. to 40° C.

The immunoassay can be used to determine a test amount of a marker in a sample from a subject. First, a test amount of a marker in a sample can be detected using the immunoassay methods described above. If a marker is present in the sample, it will form an antibody-marker complex with an antibody that specifically binds the marker under suitable incubation conditions described above. The amount of an antibody-marker complex can optionally be determined by comparing to a standard. As noted above, the test amount of marker need not be measured in absolute units, as long as the unit of measurement can be compared to a control amount and/or signal.

Preferably used are antibodies which specifically interact with the polypeptides of the present invention and not with wild type proteins or other isoforms thereof, for example. Such antibodies are directed, for example, to the unique sequence portions of the polypeptide variants of the present invention, including but not limited to bridges, heads, tails and insertions described in greater detail below. Preferred embodiments of antibodies according to the present invention are described in greater detail with regard to the section entitled “Antibodies”.

Radio-immunoassay (RIA): In one version, this method involves precipitation of the desired substrate and in the methods detailed hereinbelow, with a specific antibody and radiolabelled antibody binding protein (e.g., protein A labeled with I¹²⁵) immobilized on a precipitable carrier such as agarose beads. The number of counts in the precipitated pellet is proportional to the amount of substrate.

In an alternate version of the RIA, a labeled substrate and an unlabelled antibody binding protein are employed. A sample containing an unknown amount of substrate is added in varying amounts. The decrease in precipitated counts from the labeled substrate is proportional to the amount of substrate in the added sample.

Enzyme linked immunosorbent assay (ELISA): This method involves fixation of a sample (e.g., fixed cells or a proteinaceous solution) containing a protein substrate to a surface such as a well of a microtiter plate. A substrate specific antibody coupled to an enzyme is applied and allowed to bind to the substrate. Presence of the antibody is then detected and quantitated by a calorimetric reaction employing the enzyme coupled to the antibody. Enzymes commonly employed in this method include horseradish peroxidase and alkaline phosphatase. If well calibrated and within the linear range of response, the amount of substrate present in the sample is proportional to the amount of color produced. A substrate standard is generally employed to improve quantitative accuracy.

Western blot: This method involves separation of a substrate from other protein by means of an acrylamide gel followed by transfer of the substrate to a membrane (e.g., nylon or PVDF). Presence of the substrate is then detected by antibodies specific to the substrate, which are in turn detected by antibody binding reagents. Antibody binding reagents may be, for example, protein A, or other antibodies. Antibody binding reagents may be radiolabelled or enzyme linked as described hereinabove. Detection may be by autoradiography, colorimetric reaction or chemiluminescence. This method allows both quantitation of an amount of substrate and determination of its identity by a relative position on the membrane which is indicative of a migration distance in the acrylamide gel during electrophoresis.

Immunohistochemical analysis: This method involves detection of a substrate in situ in fixed cells by substrate specific antibodies. The substrate specific antibodies may be enzyme linked or linked to fluorophores. Detection is by microscopy and subjective evaluation. If enzyme linked antibodies are employed, a colorimetric reaction may be required.

Fluorescence activated cell sorting (FACS): This method involves detection of a substrate in situ in cells by substrate specific antibodies. The substrate specific antibodies are linked to fluorophores. Detection is by means of a cell sorting machine which reads the wavelength of light emitted from each cell as it passes through a light beam. This method may employ two or more antibodies simultaneously.

Radio-Imaging Methods

These methods include but are not limited to, positron emission tomography (PET) single photon emission computed tomography (SPECT). Both of these techniques are non-invasive, and can be used to detect and/or measure a wide variety of tissue events and/or functions, such as detecting cancerous cells for example. Unlike PET, SPECT can optionally be used with two labels simultaneously. SPECT has some other advantages as well, for example with regard to cost and the types of labels that can be used. For example, U.S. Pat. No. 6,696,686 describes the use of SPECT for detection of breast cancer, and is hereby incorporated by reference as if fully set forth herein.

Display Libraries

According to still another aspect of the present invention there is provided a display library comprising a plurality of display vehicles (such as phages, viruses or bacteria) each displaying at least 6, at least 7, at least 8, at least 9, at least 10, 10-15, 12-17, 15-20, 15-30 or 20-50 consecutive amino acids derived from the polypeptide sequences of the present invention.

Methods of constructing such display libraries are well known in the art. Such methods are described in, for example, Young A C, et al., “The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes” J Mol Biol 1997 Dec. 12; 274(4):622-34; Giebel L B et al. “Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities” Biochemistry 1995 Nov. 28; 34(47):15430-5; Davies E L et al., “Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes” J Immunol Methods 1995 Oct. 12; 186(1):125-35; Jones C R T al. “Current trends in molecular recognition and bioseparation” J Chromatogr A 1995 Jul. 14; 707(1):3-22; Deng S J et al. “Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries” Proc Natl Acad Sci USA 1995 May 23; 92(11):4992-6; and Deng S J et al. “Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display” J Biol Chem 1994 Apr. 1; 269(13):9533-8, which are incorporated herein by reference.

The following sections relate to Candidate Marker Examples (first section) and to Experimental Data for these Marker Examples (second section).

It should be noted that Table numbering is restarted within each section.

Candidate Marker Examples Section

This Section relates to Examples of sequences according to the present invention, including illustrative methods of selection thereof.

Description of the Methodology Undertaken to Uncover the Biomolecular Sequences of the Present Invention

Human ESTs and cDNAs were obtained from GenBank versions 136 (Jun. 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gb136.release.notes); NCBI genome assembly of April 2003; RefSeq sequences from June 2003; Genbank version 139 (December 2003); Human Genome from NCBI (Build 34) (from October 2003); and RefSeq sequences from December 2003; and from the LifeSeq library of Incyte Corporation (Wilmington, Del., USA; ESTs only). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section and the human mRNA sequences from the primate (GBPRI) section were used; also the human nucleotide RefSeq mRNA sequences were used (see for example www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html and for a reference to the EST section, see www.ncbi.nlm.nih.gov/dbEST/; a general reference to dbEST, the EST database in GenBank, may be found in Boguski et al, Nat. Genet. 1993 August; 4(4):332-3; all of which are hereby incorporated by reference as if fully set forth herein).

Novel splice variants were predicted using the LEADS clustering and assembly system as described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); U.S. Pat. No. 6,625,545; and U.S. patent application Ser. No. 10/426,002, published as US20040101876 on May 27, 2004; all of which are hereby incorporated by reference as if fully set forth herein. Briefly, the software cleans the expressed sequences from repeats, vectors and immunoglobulins. It then aligns the expressed sequences to the genome taking alternatively splicing into account and clusters overlapping expressed sequences into “clusters” that represent genes or partial genes.

These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel) platform. The GeneCarta platform includes a rich pool of annotations, sequence information (particularly of spliced sequences), chromosomal information, alignments, and additional information such as SNPs, gene ontology terms, expression profiles, functional analyses, detailed domain structures, known and predicted proteins and detailed homology reports.

A brief explanation is provided with regard to the method of selecting the candidates. However, it should noted that this explanation is provided for descriptive purposes only, and is not intended to be limiting in any way. The potential markers were identified by a computational process that was designed to find genes and/or their splice variants that are over-expressed in tumor tissues, by using databases of expressed sequences. Various parameters related to the information in the EST libraries, determined according to a manual classification process, were used to assist in locating genes and/or splice variants thereof that are over-expressed in cancerous tissues. The detailed description of the selection method is presented in Example 1 below. The cancer biomarkers selection engine and the following wet validation stages are schematically summarized in FIG. 1.

Example 1
Identification of Differentially Expressed Gene Products
Algorithm

In order to distinguish between differentially expressed gene products and constitutively expressed genes (i.e., house keeping genes ) an algorithm based on an analysis of frequencies was configured. A specific algorithm for identification of transcripts over expressed in cancer is described hereinbelow.

Dry Analysis

Library annotation—EST libraries are manually classified according to:

(i) Tissue origin

(ii) Biological source—Examples of frequently used biological sources for construction of EST libraries include cancer cell-lines; normal tissues; cancer tissues; fetal tissues; and others such as normal cell lines and pools of normal cell-lines, cancer cell-lines and combinations thereof. A specific description of abbreviations used below with regard to these tissues/cell lines etc is given above.

(iii) Protocol of library construction—various methods are known in the art for library construction including normalized library construction; non-normalized library construction; subtracted libraries; ORESTES and others. It will be appreciated that at times the protocol of library construction is not indicated.

The following rules are followed:

EST libraries originating from identical biological samples are considered as a single library.

EST libraries which included above-average levels of contamination, such as DNA contamination for example, were eliminated. The presence of such contamination was determined as follows. For each library, the number of unspliced ESTs that are not fully contained within other spliced sequences was counted. If the percentage of such sequences (as compared to all other sequences) was at least 4 standard deviations above the average for all libraries being analyzed, this library was tagged as being contaminated and was eliminated from further consideration in the below analysis (see also Sorek, R. & Safer, H. M. A novel algorithm for computational identification of contaminated EST libraries. Nucleic Acids Res 31, 1067-74 (2003) for further details).

Clusters (genes) having at least five sequences including at least two sequences from the tissue of interest were analyzed. Splice variants were identified by using the LEADS software package as described above.

Example 2
Identification of Genes Over Expressed in Cancer

Two different scoring algorithms were developed.

Libraries score—candidate sequences which are supported by a number of cancer libraries, are more likely to serve as specific and effective diagnostic markers.

The basic algorithm—for each cluster the number of cancer and normal libraries contributing sequences to the cluster was counted. Fisher exact test was used to check if cancer libraries are significantly over-represented in the cluster as compared to the total number of cancer and normal libraries.

Library counting: Small libraries (e.g., less than 1000 sequences) were excluded from consideration unless they participate in the cluster. For this reason, the total number of libraries is actually adjusted for each cluster.

Clones no. score—Generally, when the number of ESTs is much higher in the cancer libraries relative to the normal libraries it might indicate actual over-expression.

The Algorithm—

Clone counting: For counting EST clones each library protocol class was given a weight based on our belief of how much the protocol reflects actual expression levels:

(i) non-normalized: 1

(ii) normalized: 0.2

(iii) all other classes: 0.1

Clones number score—The total weighted number of EST clones from cancer libraries was compared to the EST clones from normal libraries. To avoid cases where one library contributes to the majority of the score, the contribution of the library that gives most clones for a given cluster was limited to 2 clones.

The score was computed as

$\frac{\frac{c + 1}{C}}{\frac{n + 1}{N}}$

where:

c—weighted number of “cancer” clones in the cluster.

C—weighted number of clones in all “cancer” libraries.

n—weighted number of “normal” clones in the cluster.

N—weighted number of clones in all “normal” libraries.

Clones number score significance—Fisher exact test was used to check if EST clones from cancer libraries are significantly over-represented in the cluster as compared to the total number of EST clones from cancer and normal libraries.

Two search approaches were used to find either general cancer-specific candidates or tumor specific candidates.

- Libraries/sequences originating from tumor tissues are counted as well as libraries originating from cancer cell-lines (“normal” cell-lines were ignored).
- Only libraries/sequences originating from tumor tissues are counted

Example 3
Identification of Tissue Specific Genes

For detection of tissue specific clusters, tissue libraries/sequences were compared to the total number of libraries/sequences in cluster. Similar statistical tools to those described in above were employed to identify tissue specific genes. Tissue abbreviations are the same as for cancerous tissues, but are indicated with the header “normal tissue”.

The algorithm—for each tested tissue T and for each tested cluster the following were examined:

1. Each cluster includes at least 2 libraries from the tissue T. At least 3 clones (weighed—as described above) from tissue T in the cluster; and

2. Clones from the tissue T are at least 40% from all the clones participating in the tested cluster

Fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant.

Example 4
Identification of Splice Variants Over Expressed in Cancer of Clusters which are not Over Expressed in Cancer

Cancer-specific splice variants containing a unique region were identified.

Identification of unique sequence regions in splice variants

A Region is defined as a group of adjacent exons that always appear or do not appear together in each splice variant.

A “segment” (sometimes referred also as “seg” or “node”) is defined as the shortest contiguous transcribed region without known splicing inside.

Only reliable ESTs were considered for region and segment analysis. An EST was defined as unreliable if:

(i) Unspliced;

(ii) Not covered by RNA;

(iii) Not covered by spliced ESTs; and

(iv) Alignment to the genome ends in proximity of long poly-A stretch or starts in proximity of long poly-T stretch.

Only reliable regions were selected for further scoring. Unique sequence regions were considered reliable if:

(i) Aligned to the genome; and

(ii) Regions supported by more than 2 ESTs.

The Algorithm

Each unique sequence region divides the set of transcripts into 2 groups:

(i) Transcripts containing this region
(group TA).

(ii) Transcripts not containing this region
(group TB).

The set of EST clones of every cluster is divided into 3 groups:

(i) Supporting (originating from) transcripts of group TA (S1).

(ii) Supporting transcripts of group TB (S2).

(iii) Supporting transcripts from both groups (S3).

Library and clones number scores described above were given to S1 group.

Fisher Exact Test P-values were used to check if:

S1 is significantly enriched by cancer EST clones compared to S2; and

S1 is significantly enriched by cancer EST clones compared to cluster background (S1+S2+S3).

Identification of unique sequence regions and division of the group of transcripts accordingly is illustrated in FIG. 2. Each of these unique sequence regions corresponds to a segment, also termed herein a “node”. Region 1: common to all transcripts, thus it is not considered; Region 2: specific to Transcript 1: T_—1 unique regions (2+6) against T_—2+3 unique regions (3+4); Region 3: specific to Transcripts 2+3: T_—2+3 unique regions (3+4) against T1 unique regions (2+6); Region 4: specific to Transcript 3: T_—3 unique regions (4) against T1+2 unique regions (2+5+6); Region 5: specific to Transcript 1+2: T_—1+2 unique regions (2+5+6) against T3 unique regions (4); Region 6: specific to Transcript 1: same as region 2.

Example 5
Identification of Cancer Specific Splice Variants of Genes Over Expressed in Cancer

A search for EST supported (no mRNA) regions for genes of:

(i) known cancer markers

(ii) Genes shown to be over-expressed in cancer in published micro-array experiments.

Reliable EST supported-regions were defined as supported by minimum of one of the following:

(i) 3 spliced ESTs; or

(ii) 2 spliced ESTs from 2 libraries;

(iii) 10 unspliced ESTs from 2 libraries, or

(iv) 3 libraries.

Actual Marker Examples

The following examples relate to specific actual marker examples.

Experimental Examples Section

This Section relates to Examples describing experiments involving these sequences, and illustrative, non-limiting examples of methods, assays and uses thereof. The materials and experimental procedures are explained first, as all experiments used them as a basis for the work that was performed.

The markers of the present invention were tested with regard to their expression in various cancerous and non-cancerous tissue samples. A description of the samples used in the panel is provided in Tables 1 and 1_—1 below. A description of the samples used in the normal tissue panel is provided in Tables 2 and 2_—2 below. Tests were then performed as described in the “Materials and Experimental Procedures” section below. The key for the is listed in tables 1_—1_—1.

TABLE 1

Tissue samples in testing panel

COLON PANEL

sample name
Lot No.
tissue
source
pathology
Grade
gender/age

58-B-Adeno G1
A609152
Colon
biochain
Adenocarcinoma
1
M/73

59-B-Adeno G1
A609059
Colon
biochain
Adenocarcinoma, Ulcer
1
M/58

14-CG-Polypoid Adeno G1 D-C
CG-222 (2)
Rectum
Ichilov
Well polypoid adeocarcinoma Duke's C

F/49

17-CG-Adeno G1-2
CG-163
Rectum
Ichilov
Adenocarcinoma
2
M/73

10-CG-Adeno G1-2 D-B2
CG-311
Sigmod co
Ichilov
Adenocarcinoma Astler-Coller B2.
1-2
M/88

11-CG-Adeno G1-2 D-C2
CG-337
Colon
Ichilov
Adenocarcinoma Astler-Coller C2.
1-2
NA

6-CG-Adeno G1-2 D-C2
CG-303 (3)
Colon
Ichilov
Adenocarcinoma Astler-Coller C2.
1-2
F/77

5-CG-Adeno G2
CG-308
Colon Sign
Ichilov
Adenocarcinoma.
2
F/80

16-CG-Adeno G2
CG-278C
colon
Ichilov
Adenocarcinoma
2
F/60

56-B-Adeno G2
A609148
Colon
biochain
Adenocarcinoma
2
F48

61-B-Adeno G2
A606258
Colon
biochain
Adenocarcinoma, Ulcer
2
M/41

60-B-Adeno G2
A609058
Colon
biochain
Adenocarcinoma, Ulcer
2
M/67

22-CG-Adeno G2 D-B
CG-229C
Colon
Ichilov
Adenocarcinoma Duke's B
2
F/55

1-CG-Adeno G2 D-B2
CG-335
Cecum
Ichilov
Adenocarcinoma Dukes B2.
2
F/66

12-CG-Adeno G2 D-B2
CG-340
Colon Sign
Ichilov
Adenocarcinoma Astler-Coller B2.
2
M/66

28-CG-Adeno G2 D-B2
CG-284
sigma
Ichilov
Adenocarcinoma Duke's B2
2
F/72

2-CG-Adeno G2 D-C2
CG-307 X2
Cecum
Ichilov
Adenocarcinoma Astler-Coller C2.
2
F/89

9-CG-Adeno G2 D-D
CG-297 X2
Rectum
Ichilov
Adenocarcinoma Dukes D.
2
M/62

13-CG-Adeno G2 D-D
CG-290 X2
Rectosigm
Ichilov
Adenocarcinoma Dukes D.
2
M/47

26-CG-Adeno G2 D-D
CG-283
sigma
Ichilov
Colonic adenocarcinoma Duke's D
2
F/63

4-CG-Adeno G3
CG-276
Colon
Ichilov
Carcinoma.
3
M/64

53-B-Adeno G3
A609161
Colon
biochain
Adenocarcinoma
3
F/53

54-B-Adeno G3
A609142
Colon
biochain
Adenocarcinoma
3
M/53

55-B-Adeno G3
A609144
Colon
biochain
Adenocarcinoma
3
M/68

57-B-Adeno G3
A609150
Colon
biochain
Adenocarcinoma
3
F/45

72-CG-Adeno G3
CG-309
colon
Ichilov
Adenocarcinoma
3
F/88

20-CG-Adeno G3 D-B2
CG-249
Colon
Ichilov
Ulcerated adenocarcinoma Duke's B2
3
M/36

7-CG-Adeno D-A
CG-235
Rectum
Ichilov
Adenocarcinoma intramucosal Duke's A.

F/66

23-CG-Adeno D-C
CG-282
sigma
Ichilov
Mucinus adenocarcinoma Astler Coller C

M/51

3-CG-Muc adeno D-D
CG-224
Colon
Ichilov
Mucinois adenocarcinoma Duke's D

M/48

18-CG-Adeno
CG-22C
Colon
Ichilov
Adenocarcinoma

NA

19-CG-Adeno
CG-19C (1)
Colon
Ichilov
Adenocarcinoma

NA

21-CG-Adeno
CG-18C
Colon
Ichilov
Adenocarcinoma

NA

24-CG-Adeno
CG-12 (2)
Colon
Ichilov
Adenocarcinoma

NA

25-CG-Adeno
CG-2
Colon
Ichilov
Adenocarcinoma

NA

27-CG-Adeno
CG-4
Colon
Ichilov
Adenocarcinoma

NA

8-CG-diverticolosis, diverticulitis
CG-291
Wall of sig
Ichilov
Diverticolosis and diverticulitis of the Colon

F/65

46-CG-Crohn's disease
CG-338C
Cecum
Ichilov
Crohn's disease

M/22

47-CG-Crohn's disease
CG-338AC
Colon
Ichilov
Crohn's disease.

M/22

42-CG-N M20
CG-249N
Colon
Ichilov
Normal

M/36

43-CG-N M8
CG-291N
Wall of sig
Ichilov
Normal

F/65

44-CG-N M21
CG-18N
Colon
Ichilov
Normal

NA

45-CG-N M11
CG-337N
Colon
Ichilov
Normal

M/75

49-CG-N M14
CG-222N
Rectum
Ichilov
Normal

F/49

50-CG-N M5
CG-308N
Sigma
Ichilov
Within normal limits

F/80

51-CG-N M26
CG-283N
Sigma
Ichilov
Normal

F/63

41-B-N
A501156
Colon
biochain
Normal PM

M/78

52-CG-N
CG-309TR
Colon
Ichilov
Within normal limits

F/88

62-B-N
A608273
Colon
biochain
Normal PM

M/66

63-B-N
A609260
Colon
biochain
Normal PM

M/61

64-B-N
A609261
Colon
biochain
Normal PM

F/68

65-B-N
A607115
Colon
biochain
Normal PM

M/24

66-B-N
A609262
Colon
biochain
Normal PM

M/58

67-B-N
A406029
Colon
biochain
Normal PM (Pool of 10)

69-B-N
A411078
Colon
biochain
Normal PM (Pool of 10)

F&M

70-Cl-N
1110101
Colon
clontech
Normal PM (Pool of 3)

71-Am-N
071P10B
Colon
Ambion
Normal (IC BLEED)

F/34

15-CG-Adeno D-A
CG-235
Rectum
Ichilov
Adenocarcinoma intramucosal Duke's A.

F/66

indicates data missing or illegible when filed

TABLE 1_1

Colon cancer testing panel

sample_id

(GCI)/

case id

(Asterand)/
TISSUE ID

lot
(GCI)/

no.
specimen
Sample

Source/
sample
(old
ID
ID

Diag
Specimen

Tissue
Delivery
name
samples
(Asterand)
(Asterand)
Diag
remarks
location
Gr
TNM

CC
Asterand
1-As-
18036
31312
31312B1
Aden

Cec
3
TXN0M0

AdenS0

CC
GCI
2-GC-
4QDH8
4QDH8ADT

Aden

Dis C

Adeno

SI

CC
Ichilov
3-(7)-
CG-235

Al

Rectum
UN

Ic-

Adeno

SI

CC
GCI
4-GC-
NTAI8
NTAI8AOU

Aden

Cec

Adeno

SI

CC
GCI
5-GC-
ARA7P
ARA7PAQA

Aden

Ret,

Adeno

Low

SI

Ant

CC
Ichilov
6-(20)-
CG-249

UA

3

Ic-

Adeno

SIIA

CC
GCI
7-GC-
AFTS6
AFTS6AP6

Aden

Adeno

SIIA

CC
GCI
8-GC-
5CYDK
5CYDKACS

Aden

Adeno

SIIA

CC
GCI
9-GC-
XKSLS
XKSLSAF7

Aden

Adeno

SIIA

CC
GCI
10-
B4RU8
B4RU8A8Q

Aden

GC-

Adeno

SIIA

CC
GCI
11-
HB8EY
HB8EYA8I

Aden

GC-

Adeno

SIIA

CC
Ichilov
12-
CG-229C

Aden

2

(22)-

Adeno

SII

CC
GCI
13-
X8C7X
X8C7XATL

Aden

GC-

Adeno

SIIA

CC
GCI
14-
HCP6K
HCP6KA8Z

Aden

GC-

Adeno

SIIA

CC
GCI
15-
ZX4X7
ZX4X7AXA

Aden

GC-

Adeno

SIIA

CC
Asterand
16-As-
17915
31176
31176A1
Aden

2-3
T3N0M0

Adeno

SIIA

CC
Ichilov
17-(1)-
CG-335

Aden

Cec
2

Ic-

Adeno

SIIA

CC
Asterand
19-As-
12772
18885
18885A1
Aden

rectum
2
T3NXM0

Adeno

SIIA

CC
GCI
20-
JFYXP
JFYXPAMP

Aden

GC-

Adeno

SIIA

CC
GCI
21-
OJXW9
OJXW9ASR

Aden

GC-

Adeno

SIIA

CC
Ichilov
22-
CG-284

Aden

sigma
2

(28)-

Ic-

Adeno

SIIA

CC
Ichilov
23-
CG-311

Aden

Sig
1-2

(10)-

Col

Ic-

Adeno

SIIA

CC
Ichilov
24-
CG-222

WP

Rectum

(14)-
(2)

Aden

Ic-

Adeno

SIII

CC
Ichilov
25-
CG-282

MA

sigma
UN

(23)-

Ic-

Adeno

SIII

CC
GCI
26-
OTPI7
OTPI7AWY

Aden

GC-

Adeno

SIII

CC
GCI
27-
IG9NK
IG9NKAD3

MA

GC-

Adeno

SIII

CC
GCI
28-
53OM7
53OM7AGL

Aden

GC-

Adeno

SIII

CC
GCI
29-
BLUW6
BLUW6A6Y

Aden

GC-

Adeno

SIII

CC
GCI
30-
VZ6QA
VZ6QAAFA

Aden

RECTUM

GC-

Adeno

SIII

CC
Ichilov
31-(6)-
CG-303

Aden

1-2

Ic-
(3)

Adeno

SIII

CC
Ichilov
32-(2)-
CG-307

Aden

Cecum
2

Ic-

Adeno

SIII

CC
Ichilov
33-
CG-337

Aden

1-2

(11)-

Ic-

Adeno

SIII

CC
Asterand
34-As-
18462
40971
40971A1
TA

Sig
2
TXN2M0

Adeno

Col

SIIIC

CC
Ichilov
35-
CG-290

Aden

Rect
2

(13)-

Col

Ic-

Adeno

SIV

CC
GCI
36-
7D7QV
7D7QVAE6

Aden

GC-

Adeno

SIV

CC
GCI
37-
38U4V
38U4VAA4

Aden

GC-

Adeno

SIV

CC
Ichilov
38-(9)-
CG-297

Aden

Rectum
2

Ic-

Adeno

SIV

CC
Ichilov
71-
CG-278C

Aden

2

(16)-

Ic-

Adeno

CC
Ichilov
72-(4)-
CG-276

Carc

3

Ic-

Adeno

CC
Ichilov
73-
CG-163

Aden

Rectum
2

(17)-

Ic-

Adeno

CC
Ichilov
74-(5)-
CG-308

Aden

Col
2

Ic-

Sig

Adeno

CC
Ichilov
75-
CG-309

Aden

3

(72)-

Ic-

Adeno

CC
Ichilov
76-
CG-22C

Aden

UN

(18)-

Ic-

Adeno

CC
Ichilov
78-
CG-18C

Aden

UN

(21)-

Ic-

Adeno

CC
Ichilov
79-
CG-12

Aden

UN

(24)-

Ic-

Adeno

CC
Ichilov
80-
CG-2

Aden

UN

(25)-

Ic-

Adeno

CC
biochain
82-
A606258

Aden,

2

(61)-

Ulcer

Bc-

Adeno

CC
biochain
83-
A609150

Aden

3

(57)-

Bc-

Adeno

CC
biochain
84-
A609148

Aden

2

(56)-

Bc-

Adeno

CC
biochain
85-
A609161

Aden

3

(53)-

Bc-

Adeno

CC
biochain
86-
A609142

Aden

3

(54)-

Bc-

Adeno

CC
biochain
87-
A609059

Aden,

1

(59)-

Ulcer

Bc-

Adeno

CC
biochain
88-
A609058

Aden,

2

(60)-

Ulcer

Bc-

Adeno

CC
biochain
89-
A609144

Aden

3

(55)-

Bc-

Adeno

CC
biochain
90-
A609152

Aden

1

(58)-

Bc-

Adeno

CB
GCI
40-
IG3OY
IG3OYN7S

TS

RT Col

GC-

Aden

Ben

CB
GCI
41-
GKIEY
GKIEYAV4

TS

Prox T

GC-

Aden

Col

Ben

HGD

CN
GCI
42-
AGVTC
AGVTCNK7

NC
DIV

GC-N

PS

CN
Asterand
43-As-
8956
9153
9153B1
NC

N PS

CN
GCI
44-
IG3OY
IG3OYN7S

NC

RT Col

GC-N

PS

CN
GCI
45-
K9OYX
K9OYXN4F

NC
Divs
LT Col

GC-N

w/F DIV

PS

CN
Asterand
46-As-
23024
74445
74445B1
NC
Chr

N PS

Divs

CN
Asterand
47-As-
23049
71410
71410B2
NC
Chr

N PS

Divs

CN
GCI
48-
G7JJX
G7JJXAX7

NC
Divs
Sig

GC-N

w/
Col

PS

DIV . . .

CN
Asterand
49-As-
22900
74446
74446B1
NC
AD

N PS

w/AF

CN
GCI
50-
XVPZ2
XVPZ2NDD

NC
Div

GC-N

PS

CN
GCI
51-
CDSUV
CDSUVNR3

NC
CU

GC-N

PS

CN
GCI
52-
GP5KH
GP5KHAOC

NC
Div

GC-N

PS

CN
GCI
53-
YUZNR
YUZNRNDN

NC
Divs
Sig

GC-N

Col

PS

CN
GCI
54-
28QN6
28QN6NI1

NC
TS
RT Col

GC-N

Aden

PS

CN
GCI
55-
GV6N8
GV6N8NG9

NC
Divs,

GC-N

PA

PS

CN
GCI
56-
ZJ17R
ZJ17RNIH

NC
Tub
RT Col

GC-N

Aden

PS

CN
GCI
57-
2EEBJ
2EEBJN2Q

NC
Div/Chr

GC-N

Infl

PS

CN
GCI
58-
68IX5
68IX5N1H

NC
Chr Div
LT Col

GC-N

PS

CN
GCI
59-
9GEGL
9GEGLN1V

NC
Ext Divs
Sig

GC-N

Col

PS

CN
GCI
60-
PKU8O
PKU8OAJ3

NC
Divs,
Sig

GC-N

Chr
Col

PS

Div . . .

CN
Asterand
61-As-
22903
74452
74452B1
NC
MU

N PS

w/MI

CN
Asterand
62-As-
16364
31802
31802B1
NC
UC

N PS

CN
biochain
63-
A607115

N-PM
PM

(65)-

Bc-N

PM

CN
Ambion
64-
071P10B

N-PM
PM

(71)-

Am-N

PM

CN
biochain
65-
A609262

N-PM
PM

(66)-

Bc-N

PM

CN
biochain
66-
A609260

N-PM
PM

(63)-

Bc-N

PM

CN
biochain
67-
A608273

N-PM
PM

(62)-

Bc-N

PM

CN
biochain
68-
A609261

N-PM
PM

(64)-

Bc-N

PM

CN
biochain
69-
A501156

N-PM
PM

(41)-

Bc-N

PM

CN
biochain
70-
A406029 +

N-PM
PM

(67)-
A411078

P10

Bc-N

PM

Dr.

Alcohol
per
Alc.
Recovery
Exc.

Tissue
CS
CS2
Tumor %
Gender
age
Ethnic B
Status
day
Dur.
Type
Y.

CC
0

80
F
43
CAU
NU

Auto
2004

CC
I
Duke A
85
F
44
WCAU
Y
4

Surg

CC
I
Duke A

F
66

CC
I
Duke
80
M
53
WCAU
Y
—

Surg

B1

CC
I
Duke
70
F
70
WCAU
Y
0

Surg

B1

CC
IIA
Duke

M
36

B2

CC
IIA
Duke
75
M
39
WCAU
N
0

Surg

B2

CC
IIA
Duke
65
M
44
WCAU
N
—

Surg

B2

CC
IIA
Duke
65
M
48
WCAU
Y
10

Surg

B2

CC
IIA
Duke
65
F
50
WCAU
N
—

Surg

B2

CC
IIA
Duke
65
M
53
WCAU
N
—

Surg

B2

CC
II
Duke B

F
55

CC
IIA
Duke
90
M
56
WCAU
N
—

Surg

B2

CC
IIA
Duke
80
M
58
WCAU
Y
4

Surg

B2.

CC
IIA
Duke
90
M
60
WCAU
Y
5

Surg

B2

CC
IIA
Duke
60
F
64
CAU
occ
1
21-30
Auto
2004

B2

drink/
years

week

CC
IIA
Duke

F
66

B2

CC
IIA
Duke
60
F
67
CAU
NU

Surg
2004

B2

CC
IIA
Duke
60
F
68
WCAU
Y
—

Surg

B2

CC
IIA
Duke
90
F
69
WCAU
N
—

Surg

B2

CC
IIA
Duke

F
72

B2

CC
e
Duke

M
88

IIA
B2

CC
III
Duke C

F
49

CC
III
Duke C

M
51

CC
III
Duke
70
F
54
WCAU
N
—

Surg

C2

CC
III
Duke
90
F
54
WCAU
N
—

Surg

C2

CC
III
Duke
75
F
61
WCAU
N
—

Surg

C2

CC
III
Duke
85
F
64
WCAU
N
—

Surg

C2

CC
III
Duke
60
M
67
WCAU
Y
14

Surg

C2

CC
III
Duke

F
77

C2.

CC
III
Duke

F
89

C2.

CC
III
Duke

NA
NA

C2.

CC
IIIC

76
F
68
CAU
NU

Surg
2005

CC
IV
Duke

M
47

D.

CC
IV
Duke D
80
F
52
WCAU
Y
3

Surg

CC
IV
Duke D
85
F
53
WCAU

Surg

CC
IV
Duke

M
62

D.

CC

UN
50
F
60

CC

UN
75
M
64

CC

UN

M
73

CC

UN

F
80

CC

UN

F
88

CC

UN

NA
NA

CC

UN

NA
NA

CC

UN

NA
NA

CC

UN

NA
NA

CC

UN

M
41

CC

UN

F
45

CC

UN
40
F
48

CC

UN

F
53

CC

UN

M
53

CC

UN

M
58

CC

UN

M
67

CC

UN

M
68

CC

UN

M
73

CB

F
48
WCAU
Y
1

Surg

CB

F
75
WCAU
N
—

Surg

CN

0
M
45
WCAU
N
—

Surg

CN

0
F
46
CAU
NU

Surg
2002

CN

0
F
48
WCAU
Y
1

Surg

CN

0
F
50
WCAU
N
—

Surg

CN

0
F
52
CAU
Occ

Surg
2005

CN

0
F
52
CAU
occ

Surg
2005

CN

0
M
52
WCAU
N
—

Surg

CN

0
M
54
CAU
Cur U

Surg
2005

CN

0
F
55
WCAU
N
—

Surg

CN

0
M
55
WCAU
N
—

Surg

CN

0
F
57
WCAU
Y
6

Surg

CN

0
F
57
WCAU
Y
1

Surg

CN

0
M
59
WCAU
Y
42

Surg

CN

0
F
61
WCAU
Y
3

Surg

CN

0
M
61
WCAU
Y
—

Surg

CN

0
F
66
WCAU
Y
4

Surg

CN

0
F
66
WCAU
N
—

Surg

CN

0
M
68
WCAU
N
—

Surg

CN

0
F
69
WCAU
N
—

Surg

CN

0
M
71
CAU
Occ

Surg
2005

CN

0
F
74
WCAU
Occ

Surg
2004

CN

M
24

CN

F
34

CN

M
58

CN

M
61

CN

M
66

CN

F
68

CN

M
78

CN

F&M
M

(26-78)

&F

(53-77).

TABLE 1_1_1

Key
Full Name

CC
Colon Cancer

CB
Colon Benign

CN
Colon Normal

WT
Weight

HT
Height

Aden
Adenocarcinoma

AI
Adenocarcinoma intramucosal

UA
Ulcerated adenocarcinoma

WP Aden
Well polypoid adeocarcinoma

MA
Mucinus adenocarcinoma

TA
Tubular adenocarcinoma

Carc
Carcinoma

TS Aden
TUBULOVILLOUS ADENOMA

TS Aden HGD
TUBULOVILLOUS ADENOMA

with HIGH GRADE DYSPLASIA

NC
Normal Colon

N-PM
Normal PM

N-PM P10
Normal PM (Pool 10)

Diag
Diagnosis

Div
DIVERTICULITIS

Divs w/F DIV
Diverticulosis with Focal DIVERTICULITIS

Chr Divs
Chronic diverticulosis

Divs w/DIV . . .
DIVERTICULOSIS WITH DIVERTICULITIS

AND FOCAL ABSCESS FORMATION; NO

MALIGNANCY

AD w/AF
Acute diverticulitis with abscess formation

CU
CECAL ULCERATION

Divs, PA
DIVERTICULOSIS AND PERICOLIC ABSCESS

Tub Aden
TUBULAR ADENOMA

Div/Chr Infl
DIVERTICULOSIS/CHRONIC INFLAMMATION

Chr Div
CHRONIC DIVERTICULITIS

Ext Divs
EXTENSIVE DIVERTICULOSIS

Divs, Chr Div . . .
DIVERTICULOSIS AND

CHRONIC DIVERTICULITIS,

SEROSAL FIBROSIS AND CHRONIC

SEROSITIS

MU w/MI
Mucosal ulceration with mural inflammation

UC
Ulcerative colitis

Cec
cecum

Dis C
DISTAL COLON

Ret, Low Ant
RETROSIGMOID, LOW ANTERIOR

Rect Col
Rectosigmoidal colon

Sig col
Sigmod colon

Col Sig
Colon Sigma

RT Col
RIGHT COLON

Prox T Col
PROXIMAL TRANSVERSE COLON

LT Col
Left Colon

Gr
Grade

CS
Cancer Stage

Ethnic B
Ethnic background

NU
Never Used

Occ
Occasion

Cur U
Current use

Dr. per day
Drinks per day

Alc. Dur.
Alcohol Duration

Auto.
Autopsy

Surg.
Surgical

Exc. Y.
Excision Year

TABLE 2

Tissue samples in normal panel:

Lot no.
Source
Tissue
Pathology
Sex/Age

1-Am-Colon (C71)
071P10B
Ambion
Colon
PM
F/43

2-B-Colon (C69)
A411078
Biochain
Colon
PM-Pool of 10
M&F

3-Cl-Colon (C70)
1110101
Clontech
Colon
PM-Pool of 3
M&F

4-Am-Small Intestine
091P0201A
Ambion
Small Intestine
PM
M/75

5-B-Small Intestine
A501158
Biochain
Small Intestine
PM
M/63

6-B-Rectum
A605138
Biochain
Rectum
PM
M/25

7-B-Rectum
A610297
Biochain
Rectum
PM
M/24

8-B-Rectum
A610298
Biochain
Rectum
PM
M/27

9-Am-Stomach
110P04A
Ambion
Stomach
PM
M/16

10-B-Stomach
A501159
Biochain
Stomach
PM
M/24

11-B-Esophagus
A603814
Biochain
Esophagus
PM
M/26

12-B-Esophagus
A603813
Biochain
Esophagus
PM
M/41

13-Am-Pancreas
071P25C
Ambion
Pancreas
PM
M/25

14-CG-Pancreas
CG-255-2
Ichilov
Pancreas
PM
M/75

15-B-Lung
A409363
Biochain
Lung
PM
F/26

16-Am-Lung (L93)
111P0103A
Ambion
Lung
PM
F/61

17-B-Lung (L92)
A503204
Biochain
Lung
PM
M/28

18-Am-Ovary (O47)
061P43A
Ambion
Ovary
PM
F/16

19-B-Ovary (O48)
A504087
Biochain
Ovary
PM
F/51

20-B-Ovary (O46)
A504086
Biochain
Ovary
PM
F/41

21-Am-Cervix
101P0101A
Ambion
Cervix
PM
F/40

22-B-Cervix
A408211
Biochain
Cervix
PM
F/36

23-B-Cervix
A504089
Biochain
Cervix
PM-Pool of 5
M&F

24-B-Uterus
A411074
Biochain
Uterus
PM-Pool of 10
M&F

25-B-Uterus
A409248
Biochain
Uterus
PM
F/43

26-B-Uterus
A504090
Biochain
Uterus
PM-Pool of 5
M&F

27-B-Bladder
A501157
Biochain
Bladder
PM
M/29

28-Am-Bladder
071P02C
Ambion
Bladder
PM
M/20

29-B-Bladder
A504088
Biochain
Bladder
PM-Pool of 5
M&F

30-Am-Placenta
021P33A
Ambion
Placenta
PB
F/33

31-B-Placenta
A410165
Biochain
Placenta
PB
F/26

32-B-Placenta
A411073
Biochain
Placenta
PB-Pool of 5
M&F

33-B-Breast (B59)
A607155
Biochain
Breast
PM
F/36

34-Am-Breast (B63)
26486
Ambion
Breast
PM
F/43

35-Am-Breast (B64)
23036
Ambion
Breast
PM
F/57

36-Cl-Prostate (P53)
1070317
Clontech
Prostate
PB-Pool of 47
M&F

37-Am-Prostate (P42)
061P04A
Ambion
Prostate
PM
M/47

38-Am-Prostate (P59)
25955
Ambion
Prostate
PM
M/62

39-Am-Testis
111P0104A
Ambion
Testis
PM
M/25

40-B-Testis
A411147
Biochain
Testis
PM
M/74

41-Cl-Testis
1110320
Clontech
Testis
PB-Pool of 45
M&F

42-CG-Adrenal
CG-184-10
Ichilov
Adrenal
PM
F/81

43-B-Adrenal
A610374
Biochain
Adrenal
PM
F/83

44-B-Heart
A411077
Biochain
Heart
PB-Pool of 5
M&F

45-CG-Heart
CG-255-9
Ichilov
Heart
PM
M/75

46-CG-Heart
CG-227-1
Ichilov
Heart
PM
F/36

47-Am-Liver
081P0101A
Ambion
Liver
PM
M/64

48-CG-Liver
CG-93-3
Ichilov
Liver
PM
F/19

49-CG-Liver
CG-124-4
Ichilov
Liver
PM
F/34

50-Cl-BM
1110932
Clontech
Bone Marrow
PM-Pool of 8
M&F

51-CGEN-Blood
WBC#5
CGEN
Blood

M

52-CGEN-Blood
WBC#4
CGEN
Blood

M

53-CGEN-Blood
WBC#3
CGEN
Blood

M

54-CG-Spleen
CG-267
Ichilov
Spleen
PM
F/25

55-CG-Spleen
111P0106B
Ambion
Spleen
PM
M/25

56-CG-Spleen
A409246
Biochain
Spleen
PM
F/12

56-CG-Thymus
CG-98-7
Ichilov
Thymus
PM
F/28

58-Am-Thymus
101P0101A
Ambion
Thymus
PM
M/14

59-B-Thymus
A409278
Biochain
Thymus
PM
M/28

60-B-Thyroid
A610287
Biochain
Thyroid
PM
M/27

61-B-Thyroid
A610286
Biochain
Thyroid
PM
M/24

62-CG-Thyroid
CG-119-2
Ichilov
Thyroid
PM
F/66

63-Cl-Salivary Gland
1070319
Clontech
Salivary Gland
PM-Pool of 24
M&F

64-Am-Kidney
111P0101B
Ambion
Kidney
PM-Pool of 14
M&F

65-Cl-Kidney
1110970
Clontech
Kidney
PM-Pool of 14
M&F

66-B-Kidney
A411080
Biochain
Kidney
PM-Pool of 5
M&F

67-CG-Cerebellum
CG-183-5
Ichilov
Cerebellum
PM
M/74

68-CG-Cerebellum
CG-212-5
Ichilov
Cerebellum
PM
M/54

69-B-Brain
A411322
Biochain
Brain
PM
M/28

70-Cl-Brain
1120022
Clontech
Brain
PM-Pool of 2
M&F

71-B-Brain
A411079
Biochain
Brain
PM-Pool of 2
M&F

72-CG-Brain
CG-151-1
Ichilov
Brain
PM
F/86

73-Am-Skeletal Muscle
101P013A
Ambion
Skeletal Muscle
PM
F/28

74-Cl-Skeletal Muscle
1061038
Clontech
Skeletal Muscle
PM-Pool of 2
M&F

TABLE 1_5

Tissue samples in normal panel:

Sample id(GCI)/
Tissue id (GCI)/
Sample id

case id
Specimen id
(Asterand)/RNA id

sample name
Source
(Asterand) Lot no.
(Asternd)
(GCI)

1-(7)-Bc-Rectum
Biochain
A610297

2-(8)-Bc-Rectum
Biochain
A610298

3-GC-Colon
GCI
CDSUV
CDSUVNR3

4-As-Colon
Asterand
16364
31802
31802B1

5-As-Colon
Asterand
22900
74446
74446B1

6-GC-Small bowl
GCI
V9L7D
V9L7DN6Z

7-GC-Small bowl
GCI
M3GVT
M3GVTN5R

8-GC-Small bowl
GCI
196S2
196S2AJN

9-(9)-Am-Stomach
Ambion
110P04A

10-(10)-Bc-Stomach
Biochain
A501159

11-(11)-Bc-Esoph
Biochain
A603814

12-(12)-Bc-Esoph
Biochain
A603813

13-As-Panc
Asterand
8918
9442
9442C1

14-As-Panc
Asterand
10082
11134
11134B1

15-(48)-Ic-Liver
Ichilov
CG-93-3

16-As-Liver
Asterand
7916
7203
7203B1

17-(28)-Am-Bladder
Ambion
071P02C

18-(29)-Bc-Bladder
Biochain
A504088

19-(64)-Am-Kidney
Ambion
111P0101B

20-(65)-Cl-Kidney
Clontech
1110970

21-(66)-Bc-Kidney
Biochain
A411080

22-GC-Kidney
GCI
N1EVZ
N1EVZN91

23-GC-Kidney
GCI
BMI6W
BMI6WN9F

24-(42)-Ic-Adrenal
Ichilov
CG-184-10

25-(43)-Bc-Adrenal
Biochain
A610374

26-(16)-Am-Lung
Ambion
111P0103A

27-(17)-Bc-Lung
Biochain
A503204

28-As-Lung
Asterand
9078
9275
9275B1

29-As-Lung
Asterand
6692
6161
6161A1

30-As-Lung
Asterand
7900
7180
7180F1

31-(75)-GC-Ovary
GCI
L629FRV1

32-(76)-GC-Ovary
GCI
DWHTZRQX

33-(77)-GC-Ovary
GCI
FDPL9NJ6

34-(78)-GC-Ovary
GCI
GWXUZN5M

35-(21)-Am-Cerix
Ambion
101P0101A

36-GC-cervix
GCI
E2P2N
E2P2NAP4

37-(24)-Bc-Uterus
Biochain
A411074

38-(26)-Bc-Uterus
Biochain
A504090

39-(30)-Am-Placen
Ambion
021P33A

40-(32)-Bc-Placen
Biochain
A411073

41-GC-Breast
GCI
DHLR1

42-GC-Breast
GCI
TG6J6

43-GC-Breast
GCI
E6UDD
E6UDDNCF

44-(38)-Am-Prostate
Ambion
25955

45-Bc-Prostate
Biochain
A609258

46-As-Testis
Asterand
13071
19567
19567B1

47-As-Testis
Asterand
19671
42120
42120A1

48-GC-Artery
GCI
7FUUP
7FUUPAMP

49-GC-Artery
GCI
YGTVY
YGTVYAIN

50-Th-Blood-PBMC
Tel-Hashomer
52497

51-Th-Blood-PBMC
Tel-Hashomer
31055

52-Th-Blood-PBMC
Tel-Hashomer
31058

53-(54)-Ic-Spleen
Ichilov
CG-267

54-(55)-Ic-Spleen
Ichilov
111P0106B

55-(57)-Ic-Thymus
Ichilov
CG-98-7

56-(58)-Am-Thymus
Ambion
101P0101A

57-(60)-Bc-Thyroid
Biochain
A610287

58-(62)-Ic-Thyroid
Ichilov
CG-119-2

59-Gc-Sali gland
GCI
NNSMV
NNSMVNJC

60-(67)-Ic-Cerebellum
Ichilov
CG-183-5

61-(68)-Ic-Cerebellum
Ichilov
CG-212-5

62-(69)-Bc-Brain
Biochain
A411322

63-(71)-Bc-Brain
Biochain
A411079

64-(72)-Ic-Brain
Ichilov
CG-151-1

65-(44)-Bc-Heart
Biochain
A411077

66-(46)-Ic-Heart
Ichilov
CG-227-1

67-(45)-Ic-Heart
Ichilov
CG-255-9

(Fibrotic)

68-GC-Skel Mus
GCI
T8YZS
T8YZSN7O

69-GC-Skel Mus
GCI
Q3WKA
Q3WKANCJ

70-As-Skel Mus
Asterand
8774
8235
8235G1

71-As-Skel Mus
Asterand
8775
8244
8244A1

72-As-Skel Mus
Asterand
10937
12648
12648C1

73-As-Skel Mus
Asterand
6692
6166
6166A1

Materials and Experimental Procedures

RNA preparation—RNA was obtained from Clontech (Franklin Lakes, N.J. USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, Calif. 94545 USA www.biochain.com), ABS (Wilmington, Del. 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, Tex. 78744 USA, http://www.ambion.com). Alternatively, RNA was generated from tissue samples using TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion) and purified using RNeasy columns (Qiagen).

RT PCR—Purified RNA (1 μg) was mixed with 150 ng Random Hexamer primers (Invitrogen) and 500 μM dNTP in a total volume of 15.6 μl. The mixture was incubated for 5 min at 65° C. and then quickly chilled on ice. Thereafter, 5 μl of 5× SuperscriptII first strand buffer (Invitrogen), 2.4 μl 0.1M DTT and 40 units RNasin (Promega) were added, and the mixture was incubated for 10 min at 25° C., followed by further incubation at 42° C. for 2 min. Then, 1 μl (200 units) of SuperscriptII (Invitrogen) was added and the reaction (final volume of 25 μl) was incubated for 50 min at 42° C. and then inactivated at 70° C. for 15 min. The resulting cDNA was diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8).

Real-Time RT-PCR analysis—cDNA (5 μl), prepared as described above, was used as a template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied Biosystem) with specific primers and UNG Enzyme (Eurogentech or ABI or Roche). The amplification was effected as follows: 50° C. for 2 min, 95° C. for 10 min, and then 40 cycles of 95° C. for 15 sec, followed by 60° C. for 1 min. Detection was performed by using the PE Applied Biosystem SDS 7000. The cycle in which the reactions achieved a threshold level (Ct) of fluorescence was registered and was used to calculate the relative transcript quantity in the RT reactions. The relative quantity was calculated using the equation Q=efficiencŷ^−Ct. The efficiency of the PCR reaction was calculated from a standard curve, created by using serial dilutions of several reverse transcription (RT) reactions. To minimize inherent differences in the RT reaction, the resulting relative quantities were normalized to normalization factor calculated in one of the following methods as indicated in the text:

Method 1—the geometric mean of the relative quantities of the selected housekeeping (HSKP) genes was used as normalization factor.

Method 2—The expression of several housekeeping (HSKP) genes was checked on every panel. The relative quantity (Q) of each housekeeping gene in each sample, calculated as described above, was divided by the median quantity of this gene in all panel samples to obtain the “relative Q rel to MED”. Then, for each sample the median of the “relative Q rel to MED” of the selected housekeeping genes was calculated and served as normalization factor of this sample for further calculations. Schematic summary of quantitative real-time PCR analysis is presented in FIG. 3. As shown, the x-axis shows the cycle number. The CT=Threshold Cycle point, which is the cycle that the amplification curve crosses the fluorescence threshold that was set in the experiment. This point is a calculated cycle number in which PCR products signal is above the background level (passive dye ROX) and still in the Geometric/Exponential phase (as shown, once the level of fluorescence crosses the measurement threshold, it has a geometrically increasing phase, during which measurements are most accurate, followed by a linear phase and a plateau phase; for quantitative measurements, the latter two phases do not provide accurate measurements). The y-axis shows the normalized reporter fluorescence. It should be noted that this type of analysis provides relative quantification.

Unless defined otherwise, the normalization of the Real-Time RT-PCR analysis results described herein was carried out according to method 1 above.

The sequences of the housekeeping genes measured in all the examples on tissue testing panel were as follows:

PBGD (GenBank Accession No. BC019323)

(SEQ ID NO:1576),

PBGD Forward primer (SEQ ID NO: 529):

TGAGAGTGATTCGCGTGGG

PBGD Reverse primer (SEQ ID NO: 530):

CCAGGGTACGAGGCTTTCAAT

PBGD-amplicon (SEQ ID NO: 531):

TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAG

ACGGACAGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG

HPRT1 (GenBank Accession No. NM_000194)

(SEQ ID NO: 1577),

HPRT1 Forward primer (SEQ ID NO: 532):

TGACACTGGCAAAACAATGCA

HPRT1 Reverse primer (SEQ ID NO: 533):

GGTCCTTTTCACCAGCAAGCT

HPRT1-amplicon (SEQ ID NO: 612):

TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATA

ATCCAAAGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC

G6PD (GenBank Accession No. NM_000402)

(SEQ ID NO:1578)

G6PD Forward primer (SEQ ID NO: 613):

gaggccgtcaccaagaacat

G6PD Reverse primer (SEQ ID NO: 614):

ggacagccggtcagagctc

G6PD-amplicon (SEQ ID NO: 615):

gaggccgtcaccaagaacattcacgagtcctgcatgagccagataggctg

gaaccgcatcatcgtggagaagcccttcgggagggacctgcagagctctg

accggctgtcc

RPS27A (GenBank Accession No. NM_002954)

(SEQ ID NO:1579)

RPS27A Forward primer (SEQ ID NO: 642):

CTGGCAAGCAGCTGGAAGAT

RPS27A Reverse primer (SEQ ID NO:1260):

TTTCTTAGCACCACCACGAAGTC

RPS27A-amplicon (SEQ ID NO: 1261):

CTGGCAAGCAGCTGGAAGATGGACGTACTTTGTCTGACTACAATATTCAA

AAGGAGTCTACTCTTCATCTTGTGTTGAGACTTCGTGGTGGTGCTAAGAA

A

The sequences of the housekeeping genes measured in all the examples on normal tissue panel were as follows:

RPL19 (GenBank Accession No. NM_000981)

(SEQ ID NO: 1580),

RPL19 Forward primer (SEQ ID NO: 1262):

TGGCAAGAAGAAGGTCTGGTTAG

RPL19 Reverse primer (SEQ ID NO: 1263):

TGATCAGCCCATCTTTGATGAG

RPL19 amplicon (SEQ ID NO: 1264):

TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCA

ATGCCAACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATC

A

TATA box (GenBank Accession No. NM_003194)

(SEQ ID NO: 1581),

TATA box Forward primer (SEQ ID NO: 1265):

CGGTTTGCTGCGGTAATCAT

TATA box Reverse primer (SEQ ID NO: 1266):

TTTCTTGCTGCCAGTCTGGAC

TATA box amplicon (SEQ ID NO: 1267):

CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACT

GATTTTCAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAAC

AGTCCAGACTGGCAGCAAGAAA

Ubiquitin (GenBank Accession No. BC000449)

(SEQ ID NO: 1582)

Uhiquitin Forward primer (SEQ ID NO: 1268):

ATTTGGGTCGCGGTTCTTG

Ubiquitin Reverse primer (SEQ ID NO: 1269):

TGCCTTGACATTCTCGATGGT

Ubiquitin amplicon (SEQ ID NO: 1270):

ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAA

TGCAGATCTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG T

TGAGCCCAGTGACACCATCGAGAATGTCAAGGCA

SDHA (GenBank Accession No. NM_004168)

(SEQ ID NO: 1583)

SDHA Forward primer (SEQ ID NO: 1271):

TGGGAACAAGAGGGCATCTG

SDHA Reverse primer (SEQ ID NO: 1272):

CCACCACTGCATCAAATTCATG

SDHA-amplicon (SEQ ID NO: 1273):

TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGT

ATCCAGTAGTGGATCATGAATTTGATGCAGTGGTGG

Oligonucleotide-Based Micro-Array Experiment Protocol—

Microarray Fabrication

Microarrays (chips) were printed by pin deposition using the MicroGrid II MGII 600 robot from BioRobtics Limited (Cambridge, UK). 50-mer oligonucleotides target sequences were designed by Compugen Ltd (Tel-Aviv, Ill.) as described by A. Shoshan et al, “Optical technologies and informatics”, Proceedings of SPIE. Vol 4266, pp. 86-95 (2001). The designed oligonucleotides were synthesized and purified by desalting with the Sigma-Genosys system (The Woodlands, Tex., US) and all of the oligonucleotides were joined to a C6 amino-modified linker at the 5′ end, or being attached directly to CodeLink slides (Cat #25-6700-01. Amersham Bioscience, Piscataway, N.J., US). The 50-mer oligonucleotides, forming the target sequences, were first suspended in Ultra-pure DDW (Cat # 01-866-1A Kibbutz Beit-Haemek, Israel) to a concentration of 50 μM. Before printing the slides, the oligonucleotides were resuspended in 300 mM sodium phosphate (pH 8.5) to final concentration of 150 mM and printed at 35-40% relative humidity at 21° C.

Each slide contained a total of 9792 features in 32 subarrays. Of these features, 4224 features were sequences of interest according to the present invention and negative controls that were printed in duplicate. An additional 288 features (96 target sequences printed in triplicate) contained housekeeping genes from Human Evaluation Library2, Compugen Ltd, Israel. Another 384 features are E. coli spikes 1-6, which are oligos to E-Coli genes which are commercially available in the Array Control product (Array control-sense oligo spots, Ambion Inc. Austin, Tex. Cat #1781, Lot #112K06).

Post-Coupling Processing of Printed Slides

After the spotting of the oligonucleotides to the glass (CodeLink) slides, the slides were incubated for 24 hours in a sealed saturated NaCl humidification chamber (relative humidity 70-75%).

Slides were treated for blocking of the residual reactive groups by incubating them in blocking solution at 50° C. for 15 minutes (10 ml/slide of buffer containing 0.1M Tris, 50 mM ethanolamine, 0.1% SDS). The slides were then rinsed twice with Ultra-pure DDW (double distilled water). The slides were then washed with wash solution (10 ml/slide. 4×SSC, 0.1% SDS)) at 50° C. for 30 minutes on the shaker. The slides were then rinsed twice with Ultra-pure DDW, followed by drying by centrifugation for 3 minutes at 800 rpm.

Next, in order to assist in automatic operation of the hybridization protocol, the slides were treated with Ventana Discovery hybridization station barcode adhesives. The printed slides were loaded on a Bio-Optica (Milan, Italy) hematology staining device and were incubated for 10 minutes in 50 ml of 3-Aminopropyl Triethoxysilane (Sigma A3648 lot #122K589). Excess fluid was dried and slides were then incubated for three hours in 20 mm/Hg in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding Calif.).

The following protocol was then followed with the Genisphere 900-RP (random primer), with mini elute columns on the Ventana Discovery HybStation™, to perform the microarray experiments. Briefly, the protocol was performed as described with regard to the instructions and information provided with the device itself. The protocol included cDNA synthesis and labeling. cDNA concentration was measured with the TBS-380 (Turner Biosystems. Sunnyvale, Calif.) PicoFlour, which is used with the OliGreen ssDNA Quantitation reagent and kit.

Hybridization was performed with the Ventana Hybridization device, according to the provided protocols (Discovery Hybridization Station Tuscon Ariz.).

The slides were then scanned with GenePix 4000B dual laser scanner from Axon Instruments Inc, and analyzed by GenePix Pro 5.0 software.

Schematic summary of the oligonucleotide based microarray fabrication and the experimental flow is presented in FIGS. 4 and 5.

Briefly, as shown in FIG. 4, DNA oligonucleotides at 25 uM were deposited (printed) onto Amersham ‘CodeLink’ glass slides generating a well defined ‘spot’. These slides are covered with a long-chain, hydrophilic polymer chemistry that creates an active 3-D surface that covalently binds the DNA oligonucleotides 5′-end via the C6-amine modification. This binding ensures that the full length of the DNA oligonucleotides is available for hybridization to the cDNA and also allows lower background, high sensitivity and reproducibility.

FIG. 5 shows a schematic method for performing the microarray experiments. It should be noted that stages on the left-hand or right-hand side may optionally be performed in any order, including in parallel, until stage 4 (hybridization). Briefly, on the left-hand side, the target oligonucleotides are being spotted on a glass microscope slide (although optionally other materials could be used) to form a spotted slide (stage 1). On the right hand side, control sample RNA and cancer sample RNA are Cy3 and Cy5 labeled, respectively (stage 2), to form labeled probes. It should be noted that the control and cancer samples come from corresponding tissues (for example, normal prostate tissue and cancerous prostate tissue). Furthermore, the tissue from which the RNA was taken is indicated below in the specific examples of data for particular clusters, with regard to overexpression of an oligonucleotide from a “chip” (microarray), as for example “prostate” for chips in which prostate cancerous tissue and normal tissue were tested as described above. In stage 3, the probes are mixed. In stage 4, hybridization is performed to form a processed slide. In stage 5, the slide is washed and scanned to form an image file, followed by data analysis in stage 6.

Description for Cluster M85491

Cluster M85491 features 2 transcript(s) and 11 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

M85491_PEA_1_T16
1

M85491_PEA_1_T20
2

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

M85491_PEA_1_node_0
89

M85491_PEA_1_node_13
90

M85491_PEA_1_node_21
91

M85491_PEA_1_node_23
92

M85491_PEA_1_node_24
93

M85491_PEA_1_node_8
94

M85491_PEA_1_node_9
95

M85491_PEA_1_node_10
96

M85491_PEA_1_node_18
97

M85491_PEA_1_node_19
98

M85491_PEA_1_node_6
99

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

M85491_PEA_1_P13
534

M85491_PEA_1_P14
535

These sequences are variants of the known protein Ephrin type-B receptor 2 [precursor] (SwissProt accession identifier EPB2_HUMAN; known also according to the synonyms EC 2.7.1.112; Tyrosine-protein kinase receptor EPH-3; DRT; Receptor protein-tyrosine kinase HEK5; ERK), SEQ ID NO: 616, referred to herein as the previously known protein.

Protein Ephrin type-B receptor 2 [precursor] is known or believed to have the following function(s): Receptor for members of the ephrin-B family. The sequence for protein Ephrin type-B receptor 2 [precursor] is given at the end of the application, as “Ephrin type-B receptor 2 [precursor] amino acid sequence” (SEQ ID NO:616). Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on

amino acid sequence
Comment

671
A -> R./FTId = VAR_004162.

1-20
MALRRLGAALLLLPLLAAVE ->

MWVPVLALPVCTYA

923
E -> 22K

956
L -> 22V

958
V -> 22L

154
G -> 22D

476
K -> 22KQ

495-496
Missing

532
E -> 22D

568
R -> 22RR

589
M -> 22I

788
I -> 22F

853
S -> 22A

Protein Ephrin type-B receptor 2 [precursor] (SEQ ID NO:616) localization is believed to be Type I membrane protein.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein amino acid phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; neurogenesis, which are annotation(s) related to Biological Process; protein tyrosine kinase; receptor; transmembrane-ephrin receptor; ATP binding; transferase, which are annotation(s) related to Molecular Function; and integral membrane protein, which are annotation(s) related to Cellular Component.

The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

Cluster M85491 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 6 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bladder
0

Bone
0

Brain
10

Colon
31

epithelial
10

general
12

Kidney
0

Liver
0

Lung
5

Breast
8

Muscle
5

Ovary
36

pancreas
10

Skin
0

stomach
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
5.4e−01
6.0e−01
3.2e−01
2.5
4.6e−01
1.9

Bone
1
2.8e−01
1
1.0
7.0e−01
1.8

Brain
3.4e−01
3.6e−01
1.2e−01
2.9
1.8e−02
2.7

Colon
3.4e−02
5.7e−02
8.2e−02
2.8
2.0e−01
2.1

epithelial
1.7e−03
3.5e−03
2.0e−03
2.8
1.1e−02
2.2

general
4.8e−04
5.2e−04
6.7e−04
2.3
1.3e−03
1.9

Kidney
4.3e−01
3.7e−01
1
1.1
7.0e−01
1.5

Liver
1
4.5e−01
1
1.0
6.9e−01
1.5

Lung
2.2e−01
2.7e−01
6.9e−02
3.6
3.4e−02
3.6

Breast
8.2e−01
7.3e−01
6.9e−01
1.2
6.8e−01
1.2

Muscle
9.2e−01
4.8e−01
1
0.8
1.5e−01
3.2

Ovary
8.5e−01
7.3e−01
9.0e−01
0.7
6.7e−01
1.0

pancreas
5.5e−01
2.0e−01
6.7e−01
1.2
3.5e−01
1.8

Skin
2.9e−01
4.7e−01
1.4e−01
7.0
6.4e−01
1.6

stomach
1.5e−01
3.2e−01
1
1.0
8.0e−01
1.3

As noted above, cluster M85491 features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ephrin type-B receptor 2 [precursor]. A description of each variant protein according to the present invention is now provided.

Variant protein M85491_PEA_—1_P13 (SEQ ID NO:534) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M85491_PEA_—1_T16 (SEQ ID NO:1). An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M85491_PEA_—1_P13 (SEQ ID NO:534) and EPB2_HUMAN (SEQ ID NO:616):

1. An isolated chimeric polypeptide encoding for M85491_PEA_—1_P13 (SEQ ID NO:534), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQ NNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVD TIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETL SGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQ GDEACTHCPINSRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSGG REDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAVNGVTDQSPFSPQF ASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEK corresponding to amino acids 1-476 of EPB2_HUMAN (SEQ ID NO:616), which also corresponds to amino acids 1-476 of M85491_PEA_—1_P13 (SEQ ID NO:534), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:1480) corresponding to amino acids 477-496 of M85491_PEA_—1_P13 (SEQ ID NO:534), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M85491_PEA_—1_P13 (SEQ ID NO:534), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:1480) in M85491_PEA_—1_P13 (SEQ ID NO:534).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M85491_PEA_—1_P13 (SEQ ID NO:534) is encoded by the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA_—1_T16 (SEQ ID NO:1) is shown in bold; this coding portion starts at position 143 and ends at position 1630. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA_—1_P13 (SEQ ID NO:534) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

799
G -> A
Yes

1066
C -> T
Yes

1519
A -> G
Yes

1872
C -> T
Yes

2044
T -> C
Yes

2156
G -> A
Yes

2606
C -> A
Yes

2637
G -> C
Yes

Variant protein M85491_PEA_—1_P14 (SEQ ID NO:535) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M85491_PEA_—1_T20 (SEQ ID NO:2). An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M85491_PEA_—1_P14 (SEQ ID NO:535) and EPB2_HUMAN (SEQ ID NO:616):

1. An isolated chimeric polypeptide encoding for M85491_PEA_—1_P14 (SEQ ID NO:535), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQ NNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVD TIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETL SGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:616), which also corresponds to amino acids 1-270 of M85491_PEA_—1_P14 (SEQ ID NO:535), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:1481) corresponding to amino acids 271-301 of M85491_PEA_—1_P14 (SEQ ID NO:535), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M85491_PEA_—1_P14 (SEQ ID NO:535), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:1481) in M85491_PEA_—1_P14 (SEQ ID NO:535). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein M85491_PEA_—1_P14 (SEQ ID NO:535) is encoded by the following transcript(s): M85491_PEA_—1_T20 (SEQ ID NO:2), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA_—1_T20 (SEQ ID NO:2) is shown in bold; this coding portion starts at position 143 and ends at position 1045. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA_—1_P14 (SEQ ID NO:535) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

799
G -> A
Yes

1135
T -> C
Yes

1160
T -> C
Yes

1172
A -> C
Yes

1176
T -> A
Yes

As noted above, cluster M85491 features 11 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster M85491_PEA_—1_node_—0 (SEQ ID NO:89) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1) and M85491_PEA_—1_T20 (SEQ ID NO:2). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment starting
Segment ending

Transcript name
position
position

M85491_PEA_1_T16 (SEQ ID
1
203

NO: 1)

M85491_PEA_1_T20 (SEQ ID
1
203

NO: 2)

Segment cluster M85491_PEA_—1_node_—13 (SEQ ID NO:90) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T20 (SEQ ID NO:2). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment starting
Segment ending

Transcript name
position
position

M85491_PEA_1_T20 (SEQ ID
954
1182

NO: 2)

Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment, shown in Table 11.

TABLE 11

Oligonucleotides related to this segment

Overexpressed
Chip

Oligonucleotide name
in cancers
reference

M85491_0_0_25999
colorectal cancer
Colon

(SEQ ID NO: 1398)

Segment cluster M85491_PEA_—1_node_—21 (SEQ. ID NO:91) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment

Transcript name
starting position
Segment ending position

M85491_PEA_1_T16
1110
1445

(SEQ ID NO: 1)

Segment cluster M85491_PEA_—1_node_—23 (SEQ ID NO:92) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment

Transcript name
starting position
Segment ending position

M85491_PEA_1_T16
1446
1570

(SEQ ID NO: 1)

Segment cluster M85491_PEA_—1_node_—24 (SEQ ID NO:93) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment

Transcript name
starting position
Segment ending position

M85491_PEA_1_T16
1571
2875

(SEQ ID NO: 1)

Segment cluster M85491_PEA_—1_node_—8 (SEQ ID NO:94) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1) and M85491_PEA_—1_T20 (SEQ ID NO:2). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

M85491_PEA_1_T16 (SEQ ID NO: 1)
269
672

M85491_PEA_1_T20 (SEQ ID NO: 2)
269
672

TABLE 16

Oligonucleotides related to this segment

Oligonucleotide name
Overexpressed in cancers
Chip reference

M85491_0_14_0
colorectal cancer
Colon

(SEQ ID NO: 1399)

Segment cluster M85491_PEA_—1_node_—9 (SEQ ID NO:95) according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1) and M85491_PEA_—1_T20 (SEQ ID NO:2). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

M85491_PEA_1_T16 (SEQ ID NO: 1)
673
856

M85491_PEA_1_T20 (SEQ ID NO: 2)
673
856

According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

Segment cluster M85491_PEA_—1_node_—10 (SEQ ID NO:96) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1) and M85491_PEA_—1_T20 (SEQ ID NO:2). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

M85491_PEA_1_T16 (SEQ ID NO: 1)
857
953

M85491_PEA_1_T20 (SEQ ID NO: 2)
857
953

Segment cluster M85491_PEA_—1_node_—18 (SEQ ID NO:97) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment

Transcript name
starting position
Segment ending position

M85491_PEA_1_T16
954
1044

(SEQ ID NO: 1)

Segment cluster M85491_PEA_—1_node_—19 (SEQ ID NO:98) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

Transcript name
starting position
Segment ending position

M85491_PEA_1_T16
1045
1109

(SEQ ID NO: 1)

Segment cluster M85491_PEA_—1_node_—6 (SEQ ID NO:99) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_—1_T16 (SEQ ID NO:1) and M85491_PEA_—1_T20 (SEQ ID NO:2). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

M85491_PEA_1_T16 (SEQ ID NO: 1)
204
268

M85491_PEA_1_T20 (SEQ ID NO: 2)
204
268

Variant Protein Alignment to the Previously Known Protein:

Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by or according to seg24, M85491seg24 amplicon (SEQ ID NO:1276) and M85491seg24F (SEQ ID NO:1274) and M85491seg24R (SEQ ID NO:1275) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon —PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261) was measured similarly. For each RT (RT-PCR) sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 7 is a histogram showing over expression of the above-indicated Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts in cancerous colon samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.

As is evident from FIG. 7, the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1, “Tissue samples in testing panel”). Notably over-expression of at least 3 fold was found in 13 out of 37 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by the above amplicon(s) in colon cancer samples versus the normal tissue samples was determined by T test as 6.83E-04 Threshold of 3 fold over expression was found to differentiate between cancer and normal samples with P value of 2.66E-02 in as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: M85491seg24F forward primer (SEQ ID NO:1274); and M85491seg24R reverse primer (SEQ ID NO:1275).

The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: M85491seg24 (SEQ ID NO:1276).

M85491seg24F-

(SEQ ID NO: 1274)

GGCGTCTTTCTCCCTCTGAAC

M85491seg24R-

(SEQ ID NO: 1275)

GTCCCATTCTGGGTGCTGTG

M85491seg24-

(SEQ ID NO: 1276)

GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGT

GAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGC

ACCCAGAATGGGAC

Expression of Ephrin Type-B Receptor 2 Precursor (EC 2.7.1.112) (Tyrosine-Protein Kinase Receptor EPH-3) M85491 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name M85491Seg24 (SEQ. ID NO:1276) in Different Normal Tissues.

Expression of Ephrin type-B receptor 2 precursor transcripts detectable by or according to M85491 seg24 amplicon(s) (SEQ ID NO:1276) and M85491 seg24F (SEQ ID NO:1274) and M85491 seg24R (SEQ ID NO:1275) was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon-Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 Table 2 Tissue samples in normal panel), to obtain a value of relative expression of each sample relative to median of the lung samples.

The results are described in FIG. 8, presenting the histogram showing the expression of M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 (SEQ ID NO:1276) in different normal tissues.

Forward primer (SEQ ID NO: 1274):

GGCGTCTTTCTCCCTCTGAAC

Reverse primer (SEQ ID NO: 1275):

GTCCCATTCTGGGTGCTGTG

Amplicon (SEQ ID NO: 1276):

GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGT

GAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGC

ACCCAGAATGGGAC

Description for Cluster T10888

Cluster T10888 features 4 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

T10888_PEA_1_T1
3

T10888_PEA_1_T4
4

T10888_PEA_1_T5
5

T10888_PEA_1_T6
6

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

T10888_PEA_1_node_11
100

T10888_PEA_1_node_12
101

T10888_PEA_1_node_17
102

T10888_PEA_1_node_4
103

T10888_PEA_1_node_6
104

T10888_PEA_1_node_7
105

T10888_PEA_1_node_9
106

T10888_PEA_1_node_15
107

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

T10888_PEA_1_P2
536

T10888_PEA_1_P4
537

T10888_PEA_1_P5
538

T10888_PEA_1_P6
539

These sequences are variants of the known protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SwissProt accession identifier CEA6_HUMAN; known also according to the synonyms Normal cross-reacting antigen; Nonspecific crossreacting antigen; CD66c antigen), SEQ ID NO: 617, referred to herein as the previously known protein.

The sequence for protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617) is given at the end of the application, as “Carcinoembryonic antigen-related cell adhesion molecule 6 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

138
F -> L

239
V -> G

Protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617) localization is believed to be Attached to the membrane by a GPI-anchor.

The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Immunostimulant. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Imaging agent; Anticancer; Immunostimulant; Immunoconjugate; Monoclonal antibody, murine; Antisense therapy; antibody.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: signal transduction; cell-cell signaling, which are annotation(s) related to Biological Process; and integral plasma membrane protein, which are annotation(s) related to Cellular Component.

Cluster T10888 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 9 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bladder
0

Colon
107

epithelial
52

general
22

head and neck
40

lung
237

breast
0

pancreas
32

prostate
12

stomach
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
5.4e−01
3.4e−01
5.6e−01
1.8
4.6e−01
1.9

colon
1.2e−01
1.7e−01
2.8e−05
3.7
7.9e−04
2.8

epithelial
3.3e−02
2.1e−01
2.8e−20
2.8
4.8e−10
1.9

general
3.3e−05
2.2e−03
1.9e−44
4.9
4.6e−27
3.3

head and neck
4.6e−01
4.3e−01
1
0.8
7.5e−01
1.0

lung
7.6e−01
8.2e−01
8.9e−01
0.6
1
0.3

breast
3.7e−02
4.1e−02
1.5e−01
3.3
3.1e−01
2.4

pancreas
2.6e−01
2.4e−01
8.6e−23
2.8
1.5e−19
4.5

prostate
9.1e−01
9.3e−01
4.1e−02
1.2
1.0e−01
1.0

stomach
4.5e−02
5.6e−02
5.1e−04
4.1
4.7e−04
6.3

As noted above, cluster T10888 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617). A description of each variant protein according to the present invention is now provided.

Variant protein T10888_PEA_—1_P2 (SEQ ID NO:536) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA_—1_T1 (SEQ ID NO:3). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T10888_PEA_—1_P2 (SEQ ID NO:536) and CEA6_HUMAN (SEQ ID NO:617):

1. An isolated chimeric polypeptide encoding for T10888_PEA_—1_P2 (SEQ ID NO:536), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQNRIGYSWYKGE RVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYP ELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGS YECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQEL FIPNITVNNSGSYMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1-319 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-319 of T10888_PEA_—1_P2 (SEQ ID NO:536), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP (SEQ ID NO:1482) corresponding to amino acids 320-324 of T10888_PEA_—1_P2 (SEQ ID NO:536), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA_—1_P2 (SEQ ID NO:536), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP (SEQ ID NO:1482) in T10888_PEA_—1_P2 (SEQ ID NO:536).

Variant protein T10888_PEA_—1_P2 (SEQ ID NO:536) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P2 (SEQ ID NO:536) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

13
V ->
No

232
N -> D
No

324
P ->
No

63
I ->
No

92
G ->
No

Variant protein T10888_PEA_—1_P2 (SEQ ID NO:536) is encoded by the following transcript(s): T10888_PEA_—1_T1 (SEQ ID NO:3), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_—1_T1 (SEQ ID NO:3) is shown in bold; this coding portion starts at position 151 and ends at position 1122. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P2 (SEQ ID NO:536) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

119
C -> T
No

120
A -> T
No

1062
A -> G
Yes

1120
C ->
No

1297
G -> T
Yes

1501
A -> G
Yes

1824
G -> A
No

2036
A -> C
No

2036
A -> G
No

2095
A -> C
No

2242
A -> C
No

2245
A -> C
No

189
C ->
No

2250
A -> T
Yes

2339
C -> A
Yes

276
G -> A
Yes

338
T ->
No

424
G ->
No

546
A -> G
No

702
C -> T
No

844
A -> G
No

930
C -> T
Yes

Variant protein T10888_PEA_—1_P4 (SEQ ID NO:537) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA_—1_T4 (SEQ ID NO:4). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T10888_PEA_—1_P4 (SEQ ID NO:537) and CEA6_HUMAN (SEQ ID NO:617):

1. An isolated chimeric polypeptide encoding for T10888_PEA_—1_P4 (SEQ ID NO:537), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQNRIGYSWYKGE RVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYP ELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGS YECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-234 of T10888_PEA_—1_P4 (SEQ ID NO:537), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1483) corresponding to amino acids 235-256 of T10888_PEA_—1_P4 (SEQ ID NO:537), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA_—1_P4 (SEQ ID NO:537) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1483) in T10888_PEA_—1_P4 (SEQ ID NO:537).

Comparison Report Between T10888_PEA_—1_P4 (SEQ ID NO:537) and Q13774 (SEQ ID NO:1382):

1. An isolated chimeric polypeptide encoding for T10888_PEA_—1_P4 (SEQ ID NO:537), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQNRIGYSWYKGE RVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYP ELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGS YECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of Q13774 (SEQ ID NO:1382), which also corresponds to amino acids 1-234 of T10888_PEA_—1_P4 (SEQ ID NO:537), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1483) corresponding to amino acids 235-256 of T10888_PEA_—1_P4 (SEQ ID NO:537), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA_—1_P4 (SEQ ID NO:537), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1483) in T10888_PEA_—1_P4 (SEQ ID NO:537).

Variant protein T10888_PEA_—1_P4 (SEQ ID NO:537) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P4 (SEQ ID NO:537) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

13
V ->
No

232
N -> D
No

63
I ->
No

92
G ->
No

Variant protein T10888_PEA_—1_P4 (SEQ ID NO:537) is encoded by the following transcript(s): T10888_PEA_—1_T4 (SEQ ID NO:4), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_—1_T4 (SEQ ID NO:4) is shown in bold; this coding portion starts at position 151 and ends at position 918. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P4 (SEQ ID NO:537) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

119
C -> T
No

120
A -> T
No

978
C ->
No

1155
G -> T
Yes

1359
A -> G
Yes

1682
G -> A
No

1894
A -> C
No

1894
A -> G
No

1953
A -> C
No

2100
A -> C
No

2103
A -> C
No

2108
A -> T
Yes

189
C ->
No

2197
C -> A
Yes

276
G -> A
Yes

338
T ->
No

424
G ->
No

546
A -> G
No

702
C -> T
No

844
A -> G
No

958
G ->
No

Variant protein T10888_PEA_—1_P5 (SEQ ID NO:538) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA_—1_T5 (SEQ ID NO:5). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T10888_PEA_—1_P5 (SEQ ID NO:538) and CEA6_HUMAN (SEQ ID NO:617):

1. An isolated chimeric polypeptide encoding for T10888_PEA_—1_P5 (SEQ ID NO:538), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQNRIGYSWYKGE RVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYP ELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGS YECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQEL FIPNITVNNSGSYMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1-320 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-320 of T10888_PEA_—1_P5 (SEQ ID NO:538), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFFVVFCFLISHV (SEQ ID NO:1484) corresponding to amino acids 321-390 of T10888_PEA_—1_P5 (SEQ ID NO:538), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA_—1_P5 (SEQ ID NO:538), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFFVVFCFLISHV (SEQ ID NO:1484) in T10888_PEA_—1_P5 (SEQ ID NO:538).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

Variant protein T10888_PEA_—1_P5 (SEQ ID NO:538) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P5 (SEQ ID NO:538) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

13
V ->
No

232
N -> D
No

63
I ->
No

92
G ->
No

Variant protein T10888_PEA_—1_P5 (SEQ ID NO:538) is encoded by the following transcript(s): T10888_PEA_—1_T5 (SEQ ID NO:5), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_—1_T5 (SEQ ID NO:5) is shown in bold; this coding portion starts at position 151 and ends at position 1320. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P5 (SEQ ID NO:538) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

119
C -> T
No

120
A -> T
No

1062
A -> G
Yes

1943
C -> A
Yes

2609
C -> T
Yes

2647
C -> G
No

2701
C -> T
Yes

2841
T -> C
Yes

189
C ->
No

276
G -> A
Yes

338
T ->
No

424
G ->
No

546
A -> G
No

702
C -> T
No

844
A -> G
No

930
C -> T
Yes

Variant protein T10888_PEA_—1_P6 (SEQ ID NO:539) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA_—1_T6 (SEQ ID NO:6). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:617)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application.

Comparison Report Between T10888_PEA_—1_P6 (SEQ ID NO:539) and CEA6_HUMAN (SEQ ID NO:617):

1. An isolated chimeric polypeptide encoding for T10888_PEA_—1_P6 (SEQ ID NO:539), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQNRIGYSWYKGE RVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVY corresponding to amino acids 1-141 of CEA6_HUMAN (SEQ ID NO:617), which also corresponds to amino acids 1-141 of T10888_PEA_—1_P6 (SEQ ID NO:539), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI (SEQ ID NO:1485) corresponding to amino acids 142-183 of T10888_PEA_—1_P6 (SEQ ID NO:539), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T10888_PEA_—1_P6 (SEQ ID NO:539), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI (SEQ ID NO:1485) in T10888_PEA_—1_P6 (SEQ ID NO:539).

Variant protein T10888_PEA_—1_P6 (SEQ ID NO:539) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P6 (SEQ ID NO:539) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

13
V ->
No

63
I ->
No

92
G ->
No

Variant protein T10888_PEA_—1_P6 (SEQ ID NO:539) is encoded by the following transcript(s): T10888_PEA_—1_T6 (SEQ ID NO:6), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_—1_T6 (SEQ ID NO:6) is shown in bold; this coding portion starts at position 151 and ends at position 699. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_—1_P6 (SEQ ID NO:539) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

119
C -> T
No

120
A -> T
No

189
C ->
No

276
G -> A
Yes

338
T ->
No

424
G ->
No

546
A -> G
No

As noted above, cluster T10888 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T10888_PEA_—1_node_—11 (SEQ ID NO:100) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T1 (SEQ ID NO:3) and T10888_PEA_—1_T5 (SEQ ID NO:5). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T10888_PEA_1_T1 (SEQ ID NO: 3)
854
1108

T10888_PEA_1_T5 (SEQ ID NO: 5)
854
1108

Segment cluster T10888_PEA_—1_node_—12 (SEQ ID NO:101) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T5 (SEQ ID NO:5). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T10888_PEA_1_T5 (SEQ ID NO: 5)
1109
3004

Segment cluster T10888_PEA_—1_node_—17 (SEQ ID NO:102) according to the present invention is supported by 160 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T1 (SEQ ID NO:3) and T10888_PEA_—1_T4 (SEQ ID NO:4). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T10888_PEA_1_T1 (SEQ ID NO: 3)
1109
2518

T10888_PEA_1_T4 (SEQ ID NO: 4)
967
2376

Segment cluster T10888_PEA_—1_node_—4 (SEQ ID NO:103) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T1 (SEQ ID NO:3), T10888_PEA_—1_T4 (SEQ ID NO:4), T10888_PEA_—1_T5 (SEQ ID NO:5) and T10888_PEA_—1_T6 (SEQ ID NO:6). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T10888_PEA_1_T1 (SEQ ID NO: 3)
1
214

T10888_PEA_1_T4 (SEQ ID NO: 4)
1
214

T10888_PEA_1_T5 (SEQ ID NO: 5)
1
214

T10888_PEA_1_T6 (SEQ ID NO: 6)
1
214

Segment cluster T10888_PEA_—1_node_—6 (SEQ ID NO:104) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T1 (SEQ ID NO:3), T10888_PEA_—1_T4 (SEQ ID NO:4), T10888_PEA_—1_T5 (SEQ ID NO:5) and T10888_PEA_—1_T6 (SEQ ID NO:6). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

T10888_PEA_1_T1 (SEQ ID NO: 3)
215
574

T10888_PEA_1_T4 (SEQ ID NO: 4)
215
574

T10888_PEA_1_T5 (SEQ ID NO: 5)
215
574

T10888_PEA_1_T6 (SEQ ID NO: 6)
215
574

Segment cluster T10888_PEA_—1_node_—7 (SEQ ID NO:105) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T6 (SEQ ID NO:6). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

T10888_PEA_1_T6 (SEQ ID NO: 6)
575
1410

Segment cluster T10888_PEA_—1_node_—9 (SEQ ID NO:106) according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T1 (SEQ ID NO:3), T10888_PEA_—1_T4 (SEQ ID NO:4) and T10888_PEA_—1_T5 (SEQ ID NO:5). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

T10888_PEA_1_T1 (SEQ ID NO: 3)
575
853

T10888_PEA_1_T4 (SEQ ID NO: 4)
575
853

T10888_PEA_1_T5 (SEQ ID NO: 5)
575
853

Segment cluster T10888_PEA_—1_node_—15 (SEQ ID NO:107) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_—1_T4 (SEQ ID NO:4). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

T10888_PEA_1_T4 (SEQ ID NO: 4)
854
966

Variant Protein Alignment to the Previously Known Protein:

Expression of CEA6_HUMAN Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 (T10888)] Transcripts which are Detectable by Amplicon as Depicted in Sequence Name [T10888 junc11-17] (SEQ ID NO: 1279) in Normal and Cancerous Colon Tissues

Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to junc11-17 [node(s)/edge], T10888 junc11-17 amplicon (SEQ ID NO: 1279) and junc11-17 primers (SEQ ID NO: 1277-1278) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 10 is a histogram showing over expression of the above-indicated CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts in cancerous colon samples relative to the normal samples. As is evident from FIG. 10, the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”, above). Notably an over-expression of at least 3 fold was found in 15 out of 36 adenocarcinoma samples

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in colon cancer samples versus the normal tissue samples was determined by T test as 5.36E-03.

Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 7.41E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T10888junc11-17F forward primer (SEQ ID NO: 1277); and T10888junc11-17R reverse primer (SEQ ID NO: 1278).

Forward:-

(SEQ ID NO: 1277)

CCAGCAATCCACACAAGAGCT

Reverse-

(SEQ ID NO: 1278)

CAGGGTCTGGTCCAATCAGAG

Amplicon-

(SEQ ID NO: 1279)

CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATA

GCGGATCCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGG

ACCACAGTCACGATGATCACAGTCTCTGATTGGACCAGACCCTG

Expression of CEA6_HUMAN Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 T10888 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name T10888 junc11-17 (SEQ ID NO: 1282) in Different Normal Tissues

Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to T10888 junc11-17 amplicon (SEQ ID NO: 1282) and T10888 junc11-17F (SEQ ID NO: 1280) and T10888 junc11-17R (SEQ ID NO: 1281) was measured by real time PCR. In parallel the expression of four housekeeping genes —RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO:1267), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon—Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20 Table 2 Tissue samples in normal panel), to obtain a value of relative expression of each sample relative to median of the ovary samples.

The results are described in FIG. 11, presenting the histogram showing the expression of T10888 transcripts, which are detectable by amplicon as depicted in sequence name T10888junc11-17 (SEQ ID NO: 1282) in different normal tissues.

Forward primer (SEQ ID NO: 1280):

CCAGCAATCCACACAAGAGCT

Reverse primer (SEQ ID NO: 1281):

CAGGGTCTGGTCCAATCAGAG

Amplicon (SEQ ID NO: 1282):

CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATA

GCGGATCCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGG

ACCACAGTCACGATGATCACAGTCTCTGATTGGACCAGACCCTG

Description for Cluster H14624

Cluster H14624 features 1 transcript(s) and 15 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

H14624_T20
7

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

H14624_node_0
108

H14624_node_16
109

H14624_node_3
110

H14624_node_10
111

H14624_node_11
112

H14624_node_12
113

H14624_node_13
114

H14624_node_14
115

H14624_node_15
116

H14624_node_4
117

H14624_node_5
118

H14624_node_6
119

H14624_node_7
120

H14624_node_8
121

H14624_node_9
122

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

H14624_P15
540

Cluster H14624 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 12 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: colorectal cancer, epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors and pancreas carcinoma.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

adrenal
0

bladder
410

bone
71

brain
42

colon
6

epithelial
91

general
74

head and neck
0

kidney
0

lung
30

breast
949

ovary
7

pancreas
2

prostate
94

stomach
3

Thyroid
128

uterus
54

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
4.2e−01
4.6^e−01
4.6e−01
2.2
5.3e−01
1.9

bladder
5.4e−01
6.0e−01
1.2e−02
1.6
2.2e−01
1.0

bone
4.9e−01
8.5^e−01
1.8e−01
1.3
7.5e−01
0.6

brain
4.7e−01
7.0^e−01
6.3e−05
2.3
9.4e−03
1.4

colon
4.4e−02
9.9^e−02
4.5e−03
5.4
2.0e−02
3.9

epithelial
7.7e−03
3.6e−01
1.5e−11
2.0
2.9e−02
1.1

general
5.1e−03
5.9^e−01
8.3e−21
2.2
1.5e−04
1.2

head and neck
1.4e−01
2.8^e−01
4.6e−01
2.2
7.5e−01
1.3

kidney
6.5e−01
7.2^e−01
5.8e−01
1.7
7.0e−01
1.4

lung
6.1e−02
1.4e−01
3.3e−05
5.8
8.1e−03
2.9

breast
2.4e−01
4.1e−01
1
0.3
1
0.2

ovary
8.5e−01
7.3^e−01
6.8e−01
1.2
1.6e−01
1.6

pancreas
7.5e−03
4.9^e−02
1.2e−21
22.4
2.4e−16
15.1

prostate
8.3e−01
8.9e−01
7.2e−01
0.8
8.8e−01
0.6

stomach
4.6e−01
8.5^e−01
1.0e−03
2.7
1.1e−01
1.4

Thyroid
7.0e−01
7.0^e−01
5.9e−01
1.0
5.9e−01
1.0

uterus
4.1e−01
7.3^e−01
2.3e−01
1.2
6.2e−01
0.7

As noted above, cluster H14624 features 1 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein H14624_P15 (SEQ ID NO:540) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H14624_T20 (SEQ ID NO:7). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between H14624_P15 (SEQ ID NO:540) and Q9HAP5 (SEQ ID NO:1384) (SEQ ID NO:1384):

1. An isolated chimeric polypeptide encoding for H14624_P15 (SEQ ID NO:540), comprising a first amino acid sequence being at least 90% homologous to MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKE VLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDML ECDRFPQDNDLCIPLASSDHLLPATEE corresponding to amino acids 1-167 of Q9HAP5 (SEQ ID NO:1384), which also corresponds to amino acids 1-167 of H14624_P15 (SEQ ID NO:540), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKPSLLLPHSLLG (SEQ ID NO:1486) corresponding to amino acids 168-180 of H14624_P15 (SEQ ID NO:540), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of H14624_P15 (SEQ ID NO:540), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKPSLLLPHSLLG (SEQ ID NO:1486) in H14624_P15 (SEQ ID NO:540).

Variant protein H14624_P15 (SEQ ID NO:540) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H14624_P15 (SEQ ID NO:540) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

11
L ->
No

170
P -> S
Yes

28
F ->
No

29
G ->
No

38
S ->
No

45
A -> V
Yes

60
L ->
No

Variant protein H14624_P15 (SEQ ID NO:540) is encoded by the following transcript(s): H14624_T20 (SEQ ID NO:7), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H14624_T20 (SEQ ID NO:7) is shown in bold; this coding portion starts at position 857 and ends at position 1396. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H14624_P15 (SEQ ID NO:540) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

389
A -> G
No

476
C -> T
No

969
G ->
No

988
G -> T
Yes

990
C -> T
Yes

1034
C ->
No

1168
C -> T
Yes

1364
C -> T
Yes

488
T -> C
No

819
C -> G
Yes

851
C ->
No

887
C ->
No

922
G -> A
Yes

934
C -> T
Yes

938
T ->
No

943
C ->
No

As noted above, cluster H14624 features 15 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster H14624_node_—0 (SEQ ID NO:108) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1
573

Segment cluster H14624_node_—16 (SEQ ID NO:109) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1359
1745

Segment cluster H14624_node_—3 (SEQ ID NO:110) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
574
822

Segment cluster H14624_node_—10 (SEQ ID NO:111) according to the present invention can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1070
1079

Segment cluster H14624_node_—11 (SEQ ID NO:112) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1080
1114

Segment cluster H14624_node_—12 (SEQ ID NO:113) according to the present invention can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1115
1135

Segment cluster H14624_node_—13 (SEQ ID NO:114) according to the present invention is supported by 124 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1136
1227

Segment cluster H14624_node_—14 (SEQ ID NO:115) according to the present invention is supported by 114 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1228
1287

Segment cluster H14624_node_—15 (SEQ ID NO:115) according to the present invention is supported by 124 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1288
1358

Segment cluster H14624_node_—4 (SEQ ID NO:117) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
823
892

Segment cluster H14624_node_—5 (SEQ ID NO:118) according to the present invention can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
893
903

Segment cluster H14624_node_—6 (SEQ ID NO:119) according to the present invention can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
904
927

Segment cluster H14624_node_—7 (SEQ ID NO:120) according to the present invention can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
928
934

Segment cluster H14624_node_—8 (SEQ ID NO:121) according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
935
1014

Segment cluster H14624_node_—9 (SEQ ID NO:122) according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20 (SEQ ID NO:7). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H14624_T20 (SEQ ID NO: 7)
1015
1069

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster H53626

Cluster H53626 features 2 transcript(s) and 20 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

H53626_PEA_1_T15
8

H53626_PEA_1_T16
9

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

H53626_PEA_1_node_15
123

H53626_PEA_1_node_22
124

H53626_PEA_1_node_25
125

H53626_PEA_1_node_26
126

H53626_PEA_1_node_27
127

H53626_PEA_1_node_34
128

H53626_PEA_1_node_35
129

H53626_PEA_1_node_36
130

H53626_PEA_1_node_11
131

H53626_PEA_1_node_12
132

H53626_PEA_1_node_16
133

H53626_PEA_1_node_19
134

H53626_PEA_1_node_20
135

H53626_PEA_1_node_24
136

H53626_PEA_1_node_28
137

H53626_PEA_1_node_29
138

H53626_PEA_1_node_30
139

H53626_PEA_1_node_31
140

H53626_PEA_1_node_32
141

H53626_PEA_1_node_33
142

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

H53626_PEA_1_P4
541

H53626_PEA_1_P5
542

Cluster H53626 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 13 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and myosarcoma.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

Adrenal
4

Bone
239

Brain
39

Colon
0

Epithelial
12

General
18

head and neck
0

Kidney
8

Lung
26

Breast
8

Muscle
0

Ovary
7

Pancreas
10

Prostate
8

Skin
0

Stomach
73

Thyroid
0

Uterus
0

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
6.4^e−01
4.2e−01
2.1e−01
3.1
1.3e−02
4.1

bone
5.8^e−01
8.1e−01
9.8e−01
0.3
1
0.3

Brain
2.8^e−01
3.3e−01
8.7e−01
0.7
9.4e−01
0.5

Colon
2.3^e−01
1.4e−01
1
1.2
4.6e−01
1.9

epithelial
7.2^e−02
3.7e−03
5.8e−02
1.6
1.4e−08
4.3

general
2.7e−03
1.8e−05
7.8e−04
1.6
8.2e−13
3.0

Head and neck
2.1^e−01
3.3e−01
0.0e+00
0.0
0.0e+00
0.0

Kidney
7.3e−01
5.8e−01
5.8e−01
1.3
4.0e−02
2.0

lung
8.4e−01
5.8e−01
7.9e−01
0.8
3.7e−02
2.0

Breast
6.5^e−01
2.7e−01
6.9e−01
1.2
7.8e−02
1.9

Muscle
1
2.9e−01
1
1.0
3.5e−03
4.1

Ovary
6.7e−01
5.6e−01
1.5e−01
1.7
7.0e−02
2.7

pancreas
2.3e−01
2.0e−01
3.9e−01
1.9
8.2e−02
2.3

prostate
9.0^e−01
9.0e−01
6.7e−01
1.1
1.3e−01
1.9

skin
1
4.4e−01
1
1.0
4.1e−01
2.1

stomach
9.0^e−01
3.4e−01
1
0.3
6.1e−01
0.9

Thyroid
2.4e−01
2.4e−01
1
1.1
1
1.1

Uterus
2.1^e−01
2.4e−01
2.9e−01
2.5
2.6e−01
2.2

As noted above, cluster H53626 features 2 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein H53626_PEA_—1_P4 (SEQ ID NO:541) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H53626_PEA_—1_T15 (SEQ ID NO:8). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between H53626_PEA_—1_P4 (SEQ ID NO:541) and Q8N441 (SEQ ID NO:1385):

1. An isolated chimeric polypeptide encoding for H53626_PEA_—1_P4 (SEQ ID NO:541), comprising a first amino acid sequence being at least 90% homologous to MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTI HSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPA SQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLK NLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCKVRSDVKPVIQ WLKRVEYGAEGRHNSTIDVGGQKFVVLPTGDVWSRPDGSYLNKLLITRARQDDAGMYICLGANTMGYSF RSAFLTVLP corresponding to amino acids 1-357 of Q8N441 (SEQ ID NO:1385), which also corresponds to amino acids 1-357 of H53626_PEA_—1_P4 (SEQ ID NO:541), second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAEGGQPRGTVSTAPGMGLGCSPGLCVGVP LPTSFPLALA (SEQ ID NO:1487) corresponding to amino acids 358-437 of H53626_PEA_—1_P4 (SEQ ID NO:541), and a third amino acid sequence being at least 90% homologous to DPKPPGPPVASSSSATSLPWPVVIGIPAGAVFILGTLLLWLCQAQKKPCTPAPAPPLPGHRPPGTARDRSGD KDLPSLAALSAGPGVGLCEEHGSPAAPQHLLGPGPVAGPKLYPKLYTDIHTHTHTHSHTHSHVEGKVHQH IHYQC corresponding to amino acids 358-504 of Q8N441 (SEQ ID NO:1385), which also corresponds to amino acids 438-584 of H53626_PEA_—1_P4 (SEQ ID NO:541), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of H53626_PEA_—1_P4 (SEQ ID NO:541) comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAEGGQPRGTVSTAPGMGLGCSPGLCVGVP LPTSFPLALA (SEQ ID NO:1487), corresponding to H53626_PEA_—1_P4 (SEQ ID NO:541).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

Variant protein H53626_PEA_—1_P4 (SEQ ID NO:541) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_—1_P4 (SEQ ID NO:541) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

193
R -> L
Yes

300
G ->
No

319
Y -> H
No

442
P -> Q
Yes

504
R -> L
Yes

521
G ->
No

544
P -> L
Yes

573
E -> G
No

Variant protein H53626_PEA_—1_P4 (SEQ ID NO:541) is encoded by the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H53626_PEA_—1_T15 (SEQ ID NO:8) is shown in bold; this coding portion starts at position 17 and ends at position 1768. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_—1_P4 (SEQ ID NO:541) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

76
G -> A
Yes

340
G -> T
No

1647
C -> T
Yes

1734
A -> G
No

1797
G ->
No

1948
A -> G
Yes

2193
C -> T
Yes

2308
C -> T
Yes

2333
C -> G
Yes

2648
C -> T
Yes

2649
G -> A
Yes

2765
C -> T
Yes

594
G -> T
Yes

2972
G -> A
Yes

3027
C -> G
Yes

907
T -> C
Yes

916
C ->
No

971
T -> C
No

1135
G -> A
Yes

1341
C -> A
Yes

1527
G -> T
Yes

1579
C ->
No

Variant protein H53626_PEA_—1_P5 (SEQ ID NO:542) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H53626_PEA_—1_T16 (SEQ ID NO:9). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between H53626_PEA_—1_P5 (SEQ ID NO:542) and Q9H4D7 (SEQ ID NO:1386):

1. An isolated chimeric polypeptide encoding for H53626_PEA_—1_P5 (SEQ ID NO:542), comprising a first amino acid sequence being at least 90% homologous to MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTI HSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPA SQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLK NLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK corresponding to amino acids 1-269 of Q9H4D7 (SEQ ID NO:1386), which also corresponds to amino acids 1-269 of H53626_PEA_—1_P5 (SEQ ID NO:542), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAE TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTS TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA CMHTHARTRAP (SEQ ID NO:1488) corresponding to amino acids 270-490 of H53626_PEA_—1_P5 (SEQ ID NO:542), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of H53626_PEA_—1_P5 (SEQ ID NO:542), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAE TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTS TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA CMHTHARTRAP (SEQ ID NO:1488) in H53626_PEA_—1_P5 (SEQ ID NO:542).

Comparison Report Between H53626_PEA_—1_P5 (SEQ ID NO:542) and Q8N441 (SEQ ID NO:1385):

1. An isolated chimeric polypeptide encoding for H53626_PEA_—1_P5 (SEQ ID NO:542), comprising a first amino acid sequence being at least 90% homologous to MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTI HSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPA SQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLK NLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK corresponding to amino acids 1-269 of Q8N441 (SEQ ID NO:1385), which also corresponds to amino acids 1-269 of H53626_PEA_—1_P5 (SEQ ID NO:542), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAE TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTS TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA CMHTHARTRAP (SEQ ID NO:1488) corresponding to amino acids 270-490 of H53626_PEA_—1_P5 (SEQ ID NO:542), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Variant protein H53626_PEA_—1_P5 (SEQ ID NO:542) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_—1_P5 (SEQ ID NO:542) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

193
R -> L
Yes

274
Q -> K
Yes

336
A -> S
Yes

353
A ->
No

376
Q -> *
Yes

405
R -> G
No

426
G ->
No

476
Y -> C
Yes

Variant protein H53626_PEA_—1_P5 (SEQ ID NO:542) is encoded by the following transcript(s): H53626_PEA_—1_T16 (SEQ ID NO:9), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H53626_PEA_—1_T16 (SEQ ID NO:9) is shown in bold; this coding portion starts at position 17 and ends at position 1486. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_—1_P5 (SEQ ID NO:542) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

76
G -> A
Yes

340
G -> T
No

1688
C -> T
Yes

1803
C -> T
Yes

1828
C -> G
Yes

2143
C -> T
Yes

2144
G -> A
Yes

2260
C -> T
Yes

2467
G -> A
Yes

2522
C -> G
Yes

594
G -> T
Yes

836
C -> A
Yes

1022
G -> T
Yes

1074
C ->
No

1142
C -> T
Yes

1229
A -> G
No

1292
G ->
No

1443
A -> G
Yes

As noted above, cluster H53626 features 20 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster H53626_PEA_—1_node_—15 (SEQ ID NO:123) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ
96
343

ID NO: 8)

H53626_PEA_1_T16 (SEQ
96
343

ID NO: 9)

Segment cluster H53626_PEA_—1_node_—22 (SEQ ID NO:124) according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
450
734

NO: 8)

H53626_PEA_1_T16 (SEQ ID
450
734

NO: 9)

Segment cluster H53626_PEA_—1_node_—25 (SEQ ID NO:125) according to the present invention is supported by 41 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
824
1088

NO: 8)

Segment cluster H53626_PEA_—1_node_—26 (SEQ ID NO:126) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
1089
1328

NO: 8)

TABLE 15

Oligonucleotides related to this segment

Overexpressed

Oligonucleotide name
in cancers
Chip reference

H53626_0_0_8391 (SEQ ID
colorectal cancer
Colon

NO: 1401)

Segment cluster H53626_PEA_—1_node_—27 (SEQ ID NO:127) according to the present invention is supported by 106 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
1329
2228

NO: 8)

H53626_PEA_1_T16 (SEQ ID
824
1723

NO: 9)

Segment cluster H53626_PEA_—1_node_—34 (SEQ ID NO:128) according to the present invention is supported by 121 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
2507
2977

NO: 8)

H53626_PEA_1_T16 (SEQ ID
2002
2472

NO: 9)

Segment cluster H53626_PEA_—1_node_—35 (SEQ ID NO:129) according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
2978
3148

NO: 8)

H53626_PEA_1_T16 (SEQ ID
2473
2643

NO: 9)

Segment cluster H53626_PEA_—1_node_—36 (SEQ ID NO:130) according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
3149
3322

NO: 8)

H53626_PEA_1_T16 (SEQ ID
2644
2817

NO: 9)

Segment cluster H53626_PEA_—1_node_—11 (SEQ ID NO:131) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
1
55

NO: 8)

H53626_PEA_1_T16 (SEQ ID
1
55

NO: 9)

Segment cluster H53626_PEA_—1_node_—12 (SEQ ID NO:132) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
56
95

NO: 8)

H53626_PEA_1_T16 (SEQ ID
56
95

NO: 9)

Segment cluster H53626_PEA_—1_node_—16 (SEQ ID NO:133) according to the present invention can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

H53626_PEA_1_T15 (SEQ ID
344
368

NO: 8)

H53626_PEA_1_T16 (SEQ ID
344
368

NO: 9)

Segment cluster H53626_PEA_—1_node_—19 (SEQ ID NO:134) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
369
419

H53626_PEA_1_T16 (SEQ ID NO: 9)
369
419

Segment cluster H53626_PEA_—1_node_—20 (SEQ ID NO:13b) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
420
449

H53626_PEA_1_T16 (SEQ ID NO: 9)
420
449

Segment cluster H53626_PEA_—1_node_—24 (SEQ ID NO:136) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
735
823

H53626_PEA_1_T16 (SEQ ID NO: 9)
735
823

Segment cluster H53626_PEA_—1_node_—28 (SEQ ID NO:137) according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
2229
2306

H53626_PEA_1_T16 (SEQ ID NO: 9)
1724
1801

Segment cluster H53626_PEA_—1_node_—29 (SEQ ID NO:138) according to the present invention is supported by 73 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
2307
2396

H53626_PEA_1_T16 (SEQ ID NO: 9)
1802
1891

Segment cluster H53626_PEA_—1_node_—30 (SEQ ID NO:139) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
2397
2442

H53626_PEA_1_T16 (SEQ ID NO: 9)
1892
1937

Segment cluster H53626_PEA_—1_node_—31 (SEQ ID NO:140) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
2443
2469

H53626_PEA_1_T16 (SEQ ID NO: 9)
1938
1964

Segment cluster H53626_PEA_—1_node_—32 (SEQ ID NO:141) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
2470
2498

H53626_PEA_1_T16 (SEQ ID NO: 9)
1965
1993

Segment cluster H53626_PEA_—1_node_—33 (SEQ ID NO:142) according to the present invention can be found in the following transcript(s): H53626_PEA_—1_T15 (SEQ ID NO:8) and H53626_PEA_—1_T16 (SEQ ID NO:9). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

H53626_PEA_1_T15 (SEQ ID NO: 8)
2499
2506

H53626_PEA_1_T16 (SEQ ID NO: 9)
1994
2001

Expression of Homo sapiens Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) H53626 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name H53626 junc24-27F1R3 (SEQ ID NO: 1285) in Normal and Cancerous Colon Tissues.

Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to junc24-27, H53626 junc24-27F1R3 amplicon (SEQ ID NO: 1285) and H53626 junc24-27F1 (SEQ ID NO: 1283) and H53626 junc24-27R3 (SEQ ID NO: 1284) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon —PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), and G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3 above, “Tissue sample in colon cancer testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 14 is a histogram showing over expression of the above-indicated Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts in cancerous colon samples relative to the normal samples. As is evident from FIG. 14, the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 3, “Tissue sample in colon cancer testing panel”). Notably an over-expression of at least 5 fold was found in 13 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H53626 junc24-27F1 forward primer (SEQ ID NO: 1283); and H53626 junc24-27R3 reverse primer (SEQ ID NO: 1284).

Forward primer (SEQ ID NO: 1283):

GTCCTTCCAGTGCAAGACCCA

Reverse primer (SEQ ID NO: 1284):

TGGGCCTGGCAAAGCC

Amplicon (SEQ ID NO: 1285):

GTCCTTCCAGTGCAAGACCCAAAACCGCCAGGGCCACCTGTGGCCTCCTC

GTCCTCGGCCACTAGCCTGCCGTGGCCCGTGGTCATCGGCATCCCAGCCG

GCGCTGTCTTCATCCTGGGCACCCTGCTCCTGTGGCTTTGCCAGGCCCA

Expression of Homo sapiens Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) H53626 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name H53626 Seg25 (SEQ ID NO: 1288) in Normal and Cancerous Colon Tissues.

Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to seg25, H53626 seg25 amplicon (SEQ ID NO: 1288) and H53626 seg25F (SEQ ID NO: 1286) and H53626 seg25R (SEQ ID NO: 1287) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3 above, “Tissue samples in colon cancer testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 15 is a histogram showing over expression of the above-indicated Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts in cancerous colon samples relative to the normal samples. As is evident from FIG. 15, the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by the above amplicon was higher in a few cancer samples than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 3, “Tissue samples in colon cancer testing panel”). Notably an over-expression of at least 5 fold was found in 6 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H53626 seg25F forward primer (SEQ ID NO: 1286); and H53626 seg25R reverse primer (SEQ ID NO: 1287).

Forward primer (SEQ ID NO: 1286):

CCGACGGCTCCTACCTCAA

Reverse primer (SEQ ID NO: 1287):

GGAAGCTGTAGCCCATGGTGT

Amplicon (SEQ ID NO: 1288):

CCGACGGCTCCTACCTCAATAAGCTGCTCATCACCCGTGCCCGCCAGGAC

GATGCGGGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTT

CC

It should be noted that the variant expression pattern was found to be similar to the expression pattern of the wild-type (previously known) transcript. However, in some cases (as for colon cancer) overexpression of the variant (for example H53626_FGF-RL_T16 transcript) seems to be higher than that the of previously known transcript.

Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 amplicon (SEQ ID NO: 1288) and H53626 seg25F (SEQ ID NO: 1286) and H53626 seg25R (SEQ ID NO: 1287) was measured by real time PCR. In parallel the expression of four housekeeping genes: RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon—Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 Table 2 above, “Tissue samples in normal panel”), to obtain a value of relative expression of each sample relative to median of the lung samples.

The results are presented in FIG. 71, showing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 amplicon(s) (SEQ ID NO: 1288) and H53626 seg25F (SEQ ID NO: 1286) and H53626 seg25R (SEQ ID NO: 1287) in different normal tissues.

Expression of Homo sapiens Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) H53626 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name H53626 junc24-27F1R3 (SEQ ID NO: 1285) in Different Normal Tissues

Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 junc24-27F1R3 amplicon (SEQ ID NO:1285) and H53626 junc24-27F1 (SEQ ID NO:1283) and H53626 junc24-27R3 (SEQ ID NO:1284) was measured by real time PCR. In parallel the expression of four housekeeping genes —RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon-Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 Table 2 above, “Tissue samples in normal panel”), to obtain a value of relative expression of each sample relative to median of the lung samples.

The results are presented in FIG. 72, showing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 (SEQ ID NO: 1285) amplicon(s) and H53626 seg25F (SEQ ID NO: 1283) and H53626 junc24-27F1R3 (SEQ ID NO: 1284) in different normal tissues.

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster HSENA78

Cluster HSENA78 features 1 transcript(s) and 7 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HSENA78_T5
10

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HSENA78_node_0
143

HSENA78_node_2
144

HSENA78_node_6
145

HSENA78_node_9
146

HSENA78_node_3
147

HSENA78_node_4
148

HSENA78_node_8
149

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

HSENA78_P2
543

These sequences are variants of the known protein Small inducible cytokine B5 precursor (SwissProt accession identifier SZ05_HUMAN; known also according to the synonyms CXCL5; Epithelial-derived neutrophil activating protein 78; Neutrophil-activating peptide ENA-78), SEQ ID NO: 618, referred to herein as the previously known protein.

Protein Small inducible cytokine B5 precursor (SEQ ID NO:618) is known or believed to have the following function(s): Involved in neutrophil activation. The sequence for protein Small inducible cytokine B5 precursor is given at the end of the application, as “Small inducible cytokine B5 precursor amino acid sequence”. Protein Small inducible cytokine B5 precursor localization is believed to be Secreted.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: chemotaxis; signal transduction; cell-cell signaling; positive control of cell proliferation, which are annotation(s) related to Biological Process; and chemokine, which are annotation(s) related to Molecular Function.

Cluster HSENA78 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 16 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and lung malignant tumors.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

colon
0

epithelial
2

general
38

kidney
0

lung
3

breast
8

skin
0

stomach
36

uterus
4

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

colon
2.6e−01
3.3e−01
1.7e−01
2.7
2.7e−01
2.2

epithelial
2.5e−01
9.0e−02
3.2e−03
4.1
8.5e−07
5.5

general
8.4e−01
7.2e−01
1
0.3
1
0.4

kidney
1
7.2e−01
1
1.0
1.7e−01
1.9

lung
8.5e−01
4.8e−01
4.1e−01
1.9
4.0e−05
3.8

breast
9.5e−01
8.7e−01
1
0.8
6.8e−01
1.2

skin
2.9e−01
4.7e−01
1.4e−01
7.0
6.4e−01
1.6

stomach
5.0e−01
4.3e−01
7.5e−01
1.0
4.3e−01
1.3

uterus
7.1e−01
8.5e−01
6.6e−01
1.3
8.0e−01
1.0

As noted above, cluster HSENA78 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Small inducible cytokine B5 precursor (SEQ ID NO:618). A description of each variant protein according to the present invention is now provided.

Variant protein HSENA78_P2 (SEQ ID NO:543) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSENA78_T5 (SEQ ID NO:10). An alignment is given to the known protein (Small inducible cytokine B5 precursor (SEQ ID NO:618)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSENA78_P2 (SEQ ID NO:543) and SZ05_HUMAN (SEQ ID NO:618):

1. An isolated chimeric polypeptide encoding for HSENA78_P2 (SEQ ID NO:543), comprising a first amino acid sequence being at least 90% homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHPKMISNLQVFAIG PQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN (SEQ ID NO:618), which also corresponds to amino acids 1-81 of HSENA78_P2 (SEQ ID NO:543).

Variant protein HSENA78_P2 (SEQ ID NO:543) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSENA78_P2 (SEQ ID NO:543) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

80
V ->
No

81
V ->
No

Variant protein HSENA78_P2 (SEQ ID NO:543) is encoded by the following transcript(s): HSENA78_T5 (SEQ ID NO:10), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSENA78_T5 (SEQ ID NO:10) is shown in bold; this coding portion starts at position 149 and ends at position 391. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSENA78_P2 (SEQ ID NO:543) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

92
C -> T
Yes

144
C -> T
No

1151
A -> T
Yes

1389
T -> C
No

1867
C -> G
Yes

145
C -> T
No

181
C -> T
Yes

316
G -> A
Yes

388
G ->
No

390
T ->
No

605
T ->
No

972
C -> T
Yes

1105
A -> G
Yes

As noted above, cluster HSENA78 features 7 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSENA78_node_—0 (SEQ ID NO:143) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8

Segment location on transcripts

Segment

Transcript name
Segment starting position
ending position

HSENA78_T5 (SEQ ID
1
257

NO: 10)

Segment cluster HSENA78_node_—2 (SEQ ID NO:144) according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Transcript name
Segment starting position
Segment ending position

HSENA78_T5
258
390

(SEQ ID NO: 10)

Segment cluster HSENA78_node_—6 (SEQ ID NO:145) according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment

starting

Transcript name
position
Segment ending position

HSENA78_T5 (SEQ ID NO: 10)
585
2370

Segment cluster HSENA78_node_—9 (SEQ ID NO:146) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment

starting

Transcript name
position
Segment ending position

HSENA78_T5 (SEQ ID NO: 10)
2394
2546

Segment cluster HSENA78_node_—3 (SEQ ID NO:147) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment

starting

Transcript name
position
Segment ending position

HSENA78_T5 (SEQ ID NO: 10)
391
500

Segment cluster HSENA78_node_—4 (SEQ ID NO:148) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment

starting

Transcript name
position
Segment ending position

HSENA78_T5 (SEQ ID NO: 10)
501
584

Segment cluster HSENA78_node_—8 (SEQ ID NO:149) according to the present invention can be found in the following transcript(s): HSENA78_T5 (SEQ ID NO:10). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment

starting

Transcript name
position
Segment ending position

HSENA78_T5 (SEQ ID NO: 10)
2371
2393

Microarray (chip) data is also available for this gene as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment with regard to colon cancer, shown in Table 15.

TABLE 15

Oligonucleotides related to this gene

Overexpressed
Chip

Oligonucleotide name
in cancers
reference

HSENA78_0_1_0 (SEQ ID NO: 1402)
Colon cancer
Colon

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster HUMGROG5

Cluster HUMGROG5 features 4 transcript(s) and 18 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMGROG5_PEA_1_T3
11

HUMGROG5_PEA_1_T4
12

HUMGROG5_PEA_1_T6
13

HUMGROG5_PEA_1_T9
14

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMGROG5_PEA_1_node_18
150

HUMGROG5_PEA_1_node_19
151

HUMGROG5_PEA_1_node_21
152

HUMGROG5_PEA_1_node_23
153

HUMGROG5_PEA_1_node_6
154

HUMGROG5_PEA_1_node_10
155

HUMGROG5_PEA_1_node_11
156

HUMGROG5_PEA_1_node_12
157

HUMGROG5_PEA_1_node_13
158

HUMGROG5_PEA_1_node_14
159

HUMGROG5_PEA_1_node_15
160

HUMGROG5_PEA_1_node_16
161

HUMGROG5_PEA_1_node_17
162

HUMGROG5_PEA_1_node_20
163

HUMGROG5_PEA_1_node_22
164

HUMGROG5_PEA_1_node_7
165

HUMGROG5_PEA_1_node_8
166

HUMGROG5_PEA_1_node_9
167

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

HUMGROG5_PEA_1_P2
544

HUMGROG5_PEA_1_P3
545

HUMGROG5_PEA_1_P7
546

HUMGROG5_PEA_1_P12
547

These sequences are variants of the known protein Macrophage inflammatory protein-2-beta precursor (SwissProt accession identifier MI2B_HUMAN; known also according to the synonyms MIP2-beta; CXCL3; Growth regulated protein gamma; GRO-gamma), SEQ ID NO: 619, referred to herein as the previously known protein.

Protein Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619) is known or believed to have the following function(s): May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. The sequence for protein Macrophage inflammatory protein-2-beta precursor is given at the end of the application, as “Macrophage inflammatory protein-2-beta precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

27-28
AA -> G

Protein Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619) localization is believed to be Secreted.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: chemokine, which are annotation(s) related to Molecular Function; and extracellular space, which are annotation(s) related to Cellular Component.

As noted above, cluster HUMGROG5 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619). A description of each variant protein according to the present invention is now provided.

Variant protein HUMGROG5_PEA_—1_P2 (SEQ ID NO:544) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGROG5_PEA_—1_T3 (SEQ ID NO:11). An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMGROG5_PEA_—1_P2 (SEQ ID NO:544) and MI2B_HUMAN (SEQ ID NO:619):

1. An isolated chimeric polypeptide encoding for HUMGROG5_PEA_—1_P2 (SEQ ID NO:544), comprising a first amino acid sequence being at least 90% homologous to MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQGIHLKNIQSVNVRSPGPHCA QTEV corresponding to amino acids 1-74 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 1-74 of HUMGROG5_PEA_—1_P2 (SEQ ID NO:544).

Variant protein HUMGROG5_PEA_—1_P2 (SEQ ID NO:544) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P2 (SEQ ID NO:544) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5

Amino acid mutations

SNP position(s) on amino
Alternative

acid sequence
amino acid(s)
Previously known SNP?

3
H -> R
Yes

33
A ->
No

Variant protein HUMGROG5_PEA_—1_P2 (SEQ ID NO:544) is encoded by the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_—1_T3 (SEQ ID NO:11) is shown in bold; this coding portion starts at position 196 and ends at position 420. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P2 (SEQ ID NO:544) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

203
A -> G
Yes

292
G ->
No

1062
A -> G
Yes

1294
A -> G
Yes

1764
A -> G
Yes

1901
A -> T
Yes

Variant protein HUMGROG5_PEA_—1_P3 (SEQ ID NO:545) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGROG5_PEA_—1_T4 (SEQ ID NO:12). An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMGROG5_PEA_—1_P3 (SEQ ID NO:545) and MI2B_HUMAN (SEQ ID NO:619):

1. An isolated chimeric polypeptide encoding for HUMGROG5_PEA_—1_P3 (SEQ ID NO:545), comprising a first amino acid sequence being at least 90% homologous to MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQGIHLKNIQSVNVRSPGPHCA QTEVIATLKNGKKACLNPASPMVQKIIEKILNK corresponding to amino acids 1-103 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 1-103 of HUMGROG5_PEA_—1_P3 (SEQ ID NO:545). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMGROG5_PEA_—1_P3 (SEQ ID NO:545) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P3 (SEQ ID NO:545) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

3
H -> R
Yes

33
A ->
No

Variant protein HUMGROG5_PEA_—1_P3 (SEQ ID NO:545) is encoded by the following transcript(s): HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_—1_T4 (SEQ ID NO:12) is shown in bold; this coding portion starts at position 196 and ends at position 504. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P3 (SEQ ID NO:545) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

203
A -> G
Yes

292
G ->
No

949
A -> G
Yes

1181
A -> G
Yes

1651
A -> G
Yes

1788
A -> T
Yes

Variant protein HUMGROG5_PEA_—1_P7 (SEQ ID NO:546) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMGROG5_PEA_—1_P7 (SEQ ID NO:546) and MI2B_HUMAN (SEQ ID NO:619):

1. An isolated chimeric polypeptide encoding for HUMGROG5_PEA_—1_P7 (SEQ ID NO:546), comprising a first amino acid sequence being at least 90% homologous to MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQGIHLKNIQSVN corresponding to amino acids 1-61 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 1-61 of HUMGROG5_PEA_—1_P7 (SEQ ID NO:546), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHTQEWEESLSQPRIPHGSENHRKDTEQGEHQLTGEK (SEQ ID NO:1489) corresponding to amino acids 62-98 of HUMGROG5_PEA_—1_P7 (SEQ ID NO:546), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMGROG5_PEA_—1_P7 (SEQ ID NO:546), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHTQEWEESLSQPRIPHGSENHRKDTEQGEHQLTGEK (SEQ ID NO:1489) in HUMGROG5_PEA_—1_P7 (SEQ ID NO:546).

Variant protein HUMGROG5_PEA_—1_P7 (SEQ ID NO:546) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P7 (SEQ ID NO:546) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

3
H -> R
Yes

33
A ->
No

Variant protein HUMGROG5_PEA_—1_P7 (SEQ ID NO:546) is encoded by the following transcript(s): HUMGROG5_PEA_—1_T9 (SEQ ID NO:14), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_—1_T9 (SEQ ID NO:14) is shown in bold; this coding portion starts at position 196 and ends at position 489. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P7 (SEQ ID NO:546) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

203
A -> G
Yes

292
G ->
No

793
A -> G
Yes

930
A -> T
Yes

Variant protein HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGROG5_PEA_—1_T6 (SEQ ID NO:13). An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor (SEQ ID NO:619)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) and MI2B_HUMAN (SEQ ID NO:619):

1. An isolated chimeric polypeptide encoding for HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MHKKGSPILGSHTARVAGTSPPALPLLAQLPDASAEPHGPRHALRRPQQSPAPAGGAAAPAPGGRQPARS RWVPAPWGPRAGRGWGGRPAPTAPLNQRVYSSL (SEQ ID NO:1490) corresponding to amino acids 1-103 of HUMGROG5_PEA_—1_P12 (SEQ ID NO:547), and a second amino acid sequence being at least 90% homologous to GASVVTELRCQCLQTLQGIHLKNIQSVNVRSPGPHCAQTEVIATLKNGKKACLNPASPMVQKIIEKILNKGS TN corresponding to amino acids 34-107 of MI2B_HUMAN (SEQ ID NO:619), which also corresponds to amino acids 104-177 of HUMGROG5_PEA_—1_P12 (SEQ ID NO:547), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MHKKGSPILGSHTARVAGTSPPALPLLAQLPDASAEPHGPRHALRRPQQSPAPAGGAAAPAPGGRQPARS RWVPAPWGPRAGRGWGGRPAPTAPLNQRVYSSL (SEQ ID NO:1490) of HUMGROG5_PEA_—1_P12 (SEQ ID NO:547).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

70
S ->
No

Variant protein HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) is encoded by the following transcript(s): HUMGROG5_PEA_—1_T6 (SEQ ID NO:13), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) is shown in bold; this coding portion starts at position 84 and ends at position 614. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_—1_P12 (SEQ ID NO:547) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

203
A -> G
Yes

292
G ->
No

932
A -> G
Yes

1069
A -> T
Yes

As noted above, cluster HUMGROG5 features 18 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMGROG5_PEA_—1_node_—18 (SEQ ID NO:150) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11) and HUMGROG5_PEA_—1_T4 (SEQ ID NO:12). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
617
1433

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
504
1320

TABLE 14

Oligonucleotides related to this segment

Oligonucleotide name
Overexpressed in cancers
Chip reference

HUMGROG5_0_0_16626
colorectal cancer
Colon

(SEQ ID NO: 1403)

Segment cluster HUMGROG5_PEA_—1_node_—19 (SEQ ID NO:151) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
1434
1593

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
1321
1480

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
602
761

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
463
622

Segment cluster HUMGROG5_PEA_—1_node_—21 (SEQ ID NO:152) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
1607
1782

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
1494
1669

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
775
950

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
636
811

Segment cluster HUMGROG5_PEA_—1_node_—23 (SEQ ID NO:153) according to the present invention is supported by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
1796
2131

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
1683
2018

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
964
1299

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
825
1160

Segment cluster HUMGROG5_PEA_—1_node_—6 (SEQ ID NO:154) according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
1
222

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
1
222

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
1
222

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
1
222

Segment cluster HUMGROG5_PEA_—1_node_—10 (SEQ ID NO:155) according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
296
315

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
296
315

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
394
413

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
296
315

Segment cluster HUMGROG5_PEA_—1_node_—11 (SEQ ID NO:156) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
316
378

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
316
378

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
414
476

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
316
378

Segment cluster HUMGROG5_PEA_—1_node_—12 (SEQ ID NO:157) according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12) and HUMGROG5_PEA_—1_T6 (SEQ ID NO:13). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
379
399

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
379
399

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
477
497

Segment cluster HUMGROG5_PEA_—1_node_—13 (SEQ ID NO:158) according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12) and HUMGROG5_PEA_—1_T6 (SEQ ID NO:13). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
400
419

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
400
419

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
498
517

Segment cluster HUMGROG5_PEA_—1_node_—14 (SEQ ID NO:159) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
420
451

Segment cluster HUMGROG5_PEA_—1_node_—15 (SEQ ID NO:160) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
452
499

Segment cluster HUMGROG5_PEA_—1_node_—16 (SEQ ID NO:161) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11). Table. 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
500
532

Segment cluster HUMGROG5_PEA_—1_node_—17 (SEQ ID NO:162) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
533
616

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
420
503

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
518
601

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
379
462

Segment cluster HUMGROG5_PEA_—1_node_—20 (SEQ ID NO:163) according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
1594
1606

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
1481
1493

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
762
774

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
623
635

Segment cluster HUMGROG5_PEA_—1_node_—22 (SEQ ID NO:164) according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
1783
1795

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
1670
1682

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
951
963

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
812
824

Segment cluster HUMGROG5_PEA_—1_node_—7 (SEQ ID NO:165) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
223
270

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
223
270

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
223
270

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
223
270

Segment cluster HUMGROG5_PEA_—1_node_—8 (SEQ ID NO:166) according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_—1_T3 (SEQ ID NO:11), HUMGROG5_PEA_—1_T4 (SEQ ID NO:12), HUMGROG5_PEA_—1_T6 (SEQ ID NO:13) and HUMGROG5_PEA_—1_T9 (SEQ ID NO:14). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMGROG5_PEA_1_T3 (SEQ ID NO: 11)
271
295

HUMGROG5_PEA_1_T4 (SEQ ID NO: 12)
271
295

HUMGROG5_PEA_1_T6 (SEQ ID NO: 13)
271
295

HUMGROG5_PEA_1_T9 (SEQ ID NO: 14)
271
295

Segment cluster HUMGROG5_PEA_—1_node_—9 (SEQ ID NO:167) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_—1_T6 (SEQ ID NO:13). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMGROG5_PEA_1_T6 (SEQ ID
296
393

NO: 13)

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster HUMODCA

Cluster HUMODCA features 1 transcript(s) and 17 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMODCA_T17
15

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMODCA_node_1
168

HUMODCA_node_25
169

HUMODCA_node_32
170

HUMODCA_node_36
171

HUMODCA_node_39
172

HUMODCA_node_41
173

HUMODCA_node_0
174

HUMODCA_node_10
175

HUMODCA_node_12
176

HUMODCA_node_13
177

HUMODCA_node_2
178

HUMODCA_node_27
179

HUMODCA_node_3
180

HUMODCA_node_30
181

HUMODCA_node_34
182

HUMODCA_node_38
183

HUMODCA_node_40
184

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

HUMODCA_P9
548

These sequences are variants of the known protein Ornithine decarboxylase (SwissProt accession identifier DCOR_HUMAN; known also according to the synonyms EC 4.1.1.17; ODC), SEQ ID NO: 620, referred to herein as the previously known protein.

Protein Ornithine decarboxylase (SEQ ID NO:620) is known or believed to have the following function(s): Polyamine biosynthesis; first (rate-limiting) step. The sequence for protein Ornithine decarboxylase is given at the end of the application, as “Ornithine decarboxylase amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

415
Q -> E

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: polyamine biosynthesis, which are annotation(s) related to Biological Process; and ornithine decarboxylase; lyase, which are annotation(s) related to Molecular Function.

Cluster HUMODCA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 17 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, colorectal cancer, epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

Adrenal
120

Bladder
82

Bone
161

Brain
53

colon
0

epithelial
107

general
94

head and neck
10

kidney
114

liver
107

lung
120

lymph nodes
165

breast
61

bone marrow
156

muscle
55

ovary
36

pancreas
102

prostate
140

skin
188

stomach
109

T cells
278

Thyroid
128

uterus
118

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
8.3e−01
7.8e−01
1
0.2
8.5e−01
0.7

bladder
5.4e−01
5.1e−01
6.2e−01
1.1
5.0e−01
1.1

bone
8.3e−01
3.2e−01
1
0.2
8.4e−01
0.7

brain
2.6e−01
3.8e−02
6.5e−04
2.8
8.7e−10
3.6

colon
2.2e−02
5.8e−03
1.5e−03
6.9
6.7e−05
9.9

epithelial
6.4e−02
2.7e−03
1.4e−03
1.5
1.6e−12
2.1

general
1.3e−03
5.4e−08
1.9e−08
1.7
1.4e−39
2.6

head and neck
1.7e−01
1.7e−01
1
1.2
7.5e−01
1.3

kidney
7.7e−01
7.6e−01
7.1e−01
0.8
6.6e−01
0.9

liver
7.3e−01
5.7e−01
1
0.3
2.4e−01
1.2

lung
7.8e−01
5.8e−01
7.6e−01
0.6
7.3e−04
1.7

lymph nodes
3.9e−01
2.5e−01
1.8e−01
1.1
1.4e−04
2.1

breast
7.8e−01
4.7e−01
7.7e−01
0.8
6.4e−01
1.0

bone marrow
3.4e−01
2.6e−01
2.8e−01
2.1
1.6e−01
1.2

muscle
8.5e−01
6.1e−01
1
0.2
7.1e−05
1.0

ovary
1.7e−01
9.3e−02
3.8e−01
1.7
2.2e−02
2.6

pancreas
2.2e−01
3.2e−01
5.7e−02
1.6
6.6e−03
1.5

prostate
5.0e−01
4.9e−01
3.8e−02
1.9
4.5e−02
1.7

skin
6.2e−01
5.8e−01
5.4e−02
0.9
1.5e−02
0.5

stomach
4.2e−01
2.6e−01
3.7e−01
0.7
7.3e−03
2.3

T cells
1
1
5.5e−01
1.5
8.1e−01
0.9

Thyroid
8.3e−02
8.3e−02
5.9e−01
1.3
5.9e−01
1.3

uterus
4.2e−01
2.4e−01
1.6e−01
1.2
4.9e−02
1.7

As noted above, cluster HUMODCA features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ornithine decarboxylase (SEQ ID NO:620). A description of each variant protein according to the present invention is now provided.

Variant protein HUMODCA_P9 (SEQ ID NO:548) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMODCA_T17 (SEQ ID NO:15). An alignment is given to the known protein (Ornithine decarboxylase (SEQ ID NO:620)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMODCA_P9 (SEQ ID NO:548) and DCOR_HUMAN (SEQ ID NO:620):

1. An isolated chimeric polypeptide encoding for HUMODCA_P9 (SEQ ID NO:548), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO:1491) corresponding to amino acids 1-29 of HUMODCA_P9 (SEQ ID NO:548), and a second amino acid sequence being at least 90% homologous to LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 151-461 of DCOR_HUMAN (SEQ ID NO:620), which also corresponds to amino acids 30-340 of HUMODCA_P9 (SEQ ID NO:548), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of HUMODCA_P9 (SEQ ID NO:548), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO:1491) of HUMODCA_P9 (SEQ ID NO:548).

Comparison Report Between HUMODCA_P9 (SEQ ID NO:548) and AAA59968 (SEQ ID NO:1387):

1. An isolated chimeric polypeptide encoding for HUMODCA_P9 (SEQ ID NO:548), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO:1491) corresponding to amino acids 1-29 of HUMODCA_P9 (SEQ ID NO:548), and a second amino acid sequence being at least 90% homologous to LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 40-350 of AAA59968 (SEQ ID NO:1387), which also corresponds to amino acids 30-340 of HUMODCA_P9 (SEQ ID NO:548), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Comparison Report Between HUMODCA_P9 (SEQ ID NO:548) and AAH14562 (SEQ ID NO:1388):

1. An isolated chimeric polypeptide encoding for HUMODCA_P9 (SEQ ID NO:548), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO:1491) corresponding to amino acids 1-29 of HUMODCA_P9 (SEQ ID NO:548), and a second amino acid sequence being at least 90% homologous to LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 86-396 of AAH14562 (SEQ ID NO:1388), which also corresponds to amino acids 30-340 of HUMODCA_P9 (SEQ ID NO:548), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Variant protein HUMODCA_P9 (SEQ ID NO:548) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMODCA_P9 (SEQ ID NO:548) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

150
I -> S
No

150
I -> V
No

262
F -> L
No

263
E ->
No

263
E -> G
No

30
L ->
No

301
N ->
No

301
N -> K
No

309
E -> K
No

312
D -> N
No

323
E -> K
No

329
H -> P
No

174
I ->
No

34
I ->
No

59
L ->
No

70
V ->
No

86
T ->
No

86
T -> N
No

90
A ->
No

94
A ->
No

97
V ->
No

97
V -> G
No

198
N -> D
No

200
G ->
No

3
S ->
No

207
C -> G
No

207
C -> R
No

223
P ->
No

262
F ->
No

Variant protein HUMODCA_P9 (SEQ ID NO:548) is encoded by the following transcript(s): HUMODCA_T17 (SEQ ID NO:15), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMODCA_T17 (SEQ ID NO:15) is shown in bold; this coding portion starts at position 528 and ends at position 1547. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMODCA_P9 (SEQ ID NO:548) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

28
C -> G
Yes

210
C ->
No

536
T ->
No

615
T ->
No

628
T ->
No

703
T ->
No

736
T ->
No

784
C ->
No

784
C -> A
No

797
A ->
No

797
A -> T
No

808
C ->
No

217
C ->
No

817
T ->
No

817
T -> G
No

869
C -> T
Yes

975
A -> G
No

976
T -> G
No

1048
T ->
No

1119
A -> G
No

1127
C ->
No

1127
C -> G
No

1146
T -> C
No

366
G -> C
No

1146
T -> G
No

1194
C ->
No

1283
T -> C
Yes

1311
T ->
No

1311
T -> C
No

1315
A ->
No

1315
A -> G
No

1430
C ->
No

1430
C -> A
No

1433
C -> G
No

366
G -> T
No

1433
C -> T
Yes

1452
G -> A
No

1461
G -> A
No

1494
G -> A
No

1513
A -> C
No

1632
T ->
No

1673
C ->
No

1739
T ->
No

1739
T -> G
No

1742
T -> C
No

447
G -> A
Yes

1786
C ->
No

1786
C -> G
No

1832
T -> C
Yes

1877
C -> T
No

464
T -> G
Yes

473
A -> G
Yes

506
G -> A
Yes

521
T ->
No

As noted above, cluster HUMODCA features 17 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMODCA_node_—1 (SEQ ID NO:168) according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
118
256

Segment cluster HUMODCA_node_—25 (SEQ ID NO:169) according to the present invention is supported by 190 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
614
748

Segment cluster HUMODCA_node_—32 (SEQ ID NO:170) according to the present invention is supported by 249 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
915
1077

Segment cluster HUMODCA_node_—36 (SEQ ID NO:171) according to the present invention is supported by 348 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1191
1405

Segment cluster HUMODCA_node_—39 (SEQ ID NO:172) according to the present invention is supported by 297 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1461
1633

Segment cluster HUMODCA_node_—41 (SEQ ID NO:173) according to the present invention is supported by 230 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1728
1893

Segment cluster HUMODCA_node_—0 (SEQ ID NO:174) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1
117

Segment cluster HUMODCA_node_—10 (SEQ ID NO:175) according to the present invention is supported by 107 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
385
494

Segment cluster HUMODCA_node_—12 (SEQ ID NO:176) according to the present invention is supported by 132 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
495
586

Segment cluster HUMODCA_node_—13 (SEQ ID NO:177) according to the present invention is supported by 126 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
587
613

Segment cluster HUMODCA_node_—2 (SEQ ID NO:178) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
257
328

Segment cluster HUMODCA_node_—27 (SEQ ID NO:179) according to the present invention is supported by 185 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
749
830

Segment cluster HUMODCA_node_—3 (SEQ ID NO:180) according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
329
384

Segment cluster HUMODCA_node_—30 (SEQ ID NO:181) according to the present invention is supported by 196 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
831
914

Segment cluster HUMODCA_node_—34 (SEQ ID NO:182) according to the present invention is supported by 259 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1078
1190

Segment cluster HUMODCA_node_—38 (SEQ ID NO:183) according to the present invention is supported by 272 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1406
1460

Segment cluster HUMODCA_node_—40 (SEQ ID NO:184) according to the present invention is supported by 239 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17 (SEQ ID NO:15). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMODCA_T17 (SEQ ID NO: 15)
1634
1727

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster R00299

Cluster R00299 features 1 transcript(s) and 12 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

R00299_T2
16

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

R00299_node_2
185

R00299_node_30
186

R00299_node_10
187

R00299_node_14
188

R00299_node_15
189

R00299_node_20
190

R00299_node_23
191

R00299_node_25
192

R00299_node_28
193

R00299_node_31
194

R00299_node_5
195

R00299_node_9
196

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

R00299_P3
549

These sequences are variants of the known protein Tescalcin (SwissProt accession identifier TESC_HUMAN; known also according to the synonyms TSC), SEQ ID NO: 621, referred to herein as the previously known protein.

Protein Tescalcin is known or believed to have the following function: Binds calcium. The sequence for protein Tescalcin (SEQ ID NO:621) is given at the end of the application, as “Tescalcin amino acid sequence”.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: calcium binding, which are annotation(s) related to Molecular Function.

Cluster R00299 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 18 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: lung malignant tumors.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

bone
0

Colon
0

epithelial
11

general
11

Liver
0

lung
10

lymph nodes
22

bone marrow
31

ovary
0

pancreas
14

prostate
16

stomach
76

T cells
0

Thyroid
0

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bone
1
6.7e−01
1
1.0
7.0e−01
1.4

colon
5.0e−02
5.3e−02
2.4e−01
2.8
2.1e−01
2.8

epithelial
7.7e−02
9.5e−02
4.0e−01
1.3
6.1e−03
1.9

general
2.3e−01
2.6e−01
5.3e−01
1.0
2.6e−04
1.9

liver
1
4.5e−01
1
1.0
6.9e−01
1.5

lung
4.9e−01
2.7e−01
6.5e−01
1.7
5.6e−04
3.8

lymph nodes
8.5e−01
8.7e−01
1
0.5
2.0e−01
1.1

bone marrow
8.6e−01
8.5e−01
1
0.5
2.3e−01
1.4

ovary
4.0e−01
4.4e−01
1
1.1
1
1.1

pancreas
7.2e−01
6.9e−01
6.7e−01
1.0
3.5e−01
1.5

prostate
8.7e−01
9.1e−01
6.7e−01
1.0
7.5e−01
0.9

stomach
6.6e−01
7.5e−01
1
0.4
6.7e−01
0.7

T cells
1
6.7e−01
1
1.0
5.2e−01
1.8

Thyroid
1.8e−01
1.8e−01
6.7e−01
1.6
6.7e−01
1.6

As noted above, cluster R00299 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Tescalcin (SEQ ID NO:621). A description of each variant protein according to the present invention is now provided.

Variant protein R00299_P3 (SEQ ID NO:549) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R00299_T2 (SEQ ID NO:16). An alignment is given to the known protein (Tescalcin (SEQ ID NO:621)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R00299_P3 (SEQ ID NO:549) and Q9NWT9 (SEQ ID NO:1389):

1. An isolated chimeric polypeptide encoding for R00299_P3 (SEQ ID NO:549), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO:1492) corresponding to amino acids 1-44 of R00299_P3 (SEQ ID NO:549), second amino acid sequence being at least 90% homologous to SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLADEINFEDFLTIMS YFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNV corresponding to amino acids 74-191 of Q9NWT9 (SEQ ID NO:1389), which also corresponds to amino acids 45-162 of R00299_P3 (SEQ ID NO:549), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNME TMALCH (SEQ ID NO:1493) corresponding to amino acids 163-238 of R00299_P3 (SEQ ID NO:549), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R00299_P3 (SEQ ID NO:549), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO:1492) of R00299_P3 (SEQ ID NO:549).

3. An isolated polypeptide encoding for a tail of R00299_P3 (SEQ ID NO:549), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNME TMALCH (SEQ ID NO:1493) in R00299_P3 (SEQ ID NO:549).

Comparison Report Between R00299_P3 (SEQ ID NO:549) and TESC_HUMAN (SEQ ID NO:621):

1. An isolated chimeric polypeptide encoding for R00299_P3 (SEQ ID NO:549), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO:1492) corresponding to amino acids 1-44 of R00299_P3 (SEQ ID NO:549), and a second amino acid sequence being at least 90% homologous to SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLADEINFEDFLTIMS YFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNVVEELLSGNPHIEKESARSIADGAMME AASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH corresponding to amino acids 21-214 of TESC_HUMAN (SEQ ID NO:621), which also corresponds to amino acids 45-238 of R00299_P3 (SEQ ID NO:549), wherein said first and second amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein R00299_P3 (SEQ ID NO:549) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R00299_P3 (SEQ ID NO:549) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

120
R -> G
No

120
R -> W
No

Variant protein R00299_P3 (SEQ ID NO:549) is encoded by the following transcript(s): R00299_T2 (SEQ ID NO:16), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript

R00299_T2 (SEQ ID NO:16) is shown in bold; this coding portion starts at position 142 and ends at position 855. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R00299_P3 (SEQ ID NO:549) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

177
C -> A
Yes

499
C -> G
No

499
C -> T
No

900
G -> T
Yes

916
G ->
No

969
G ->
No

969
G -> A
No

987
A -> C
No

As noted above, cluster R00299 features 12 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster R00299_node_—2 (SEQ ID NO:185) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
1
271

Segment cluster R00299_node_—30 (SEQ ID NO:186) according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
790
961

Segment cluster R00299_node_—10 (SEQ ID NO:187) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
346
422

Segment cluster R00299_node_—14 (SEQ ID NO:188) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
423
537

Segment cluster R00299_node_—15 (SEQ ID NO:189) according to the present invention can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
538
562

Segment cluster R00299_node_—20 (SEQ ID NO:190) according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
563
624

Segment cluster R00299_node_—23 (SEQ ID NO:191) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
625
732

Segment cluster R00299_node_—25 (SEQ ID NO:192) according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
733
780

Segment cluster R00299_node_—28 (SEQ ID NO:193) according to the present invention can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
781
789

Segment cluster R00299_node_—31 (SEQ ID NO:194) according to the present invention is supported by 48 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
962
1069

Segment cluster R00299_node_—5 (SEQ ID NO:195) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
272
341

Segment cluster R00299_node_—9 (SEQ ID NO:196) according to the present invention can be found in the following transcript(s): R00299_T2 (SEQ ID NO:16). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

R00299_T2 (SEQ ID NO: 16)
342
345

Microarray (chip) data is also available for this gene as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotide was found to hit this segment with regard to colon cancer, shown in Table 20.

TABLE 20

Oligonucleotide related to this gene

Overexpressed

Oligonucleotide name
in cancers
Chip reference

R00299_0_8_0 (SEQ ID NO: 1404)
Colon cancer
Colon

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster Z19178

Cluster Z19178 features 2 transcript(s) and 15 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

Z19178_PEA_1_T5
17

Z19178_PEA_1_T9
18

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

Z19178_PEA_1_node_15
197

Z19178_PEA_1_node_17
198

Z19178_PEA_1_node_2
199

Z19178_PEA_1_node_22
200

Z19178_PEA_1_node_23
201

Z19178_PEA_1_node_24
202

Z19178_PEA_1_node_10
203

Z19178_PEA_1_node_11
204

Z19178_PEA_1_node_14
205

Z19178_PEA_1_node_18
206

Z19178_PEA_1_node_19
207

Z19178_PEA_1_node_3
208

Z19178_PEA_1_node_4
209

Z19178_PEA_1_node_5
210

Z19178_PEA_1_node_9
211

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

Z19178_PEA_1_P5
550

Z19178_PEA_1_P6
551

These sequences are variants of the known protein Skeletal muscle LIM-protein 2 (SwissProt accession identifier SLI2_HUMAN; known also according to the synonyms SLIM 2; Four and a half LIM domains protein 3; FHL-3), SEQ ID NO: 622, referred to herein as the previously known protein.

The sequence for protein Skeletal muscle LIM-protein 2 is given at the end of the application, as “Skeletal muscle LIM-protein 2 amino acid sequence” (SEQ ID NO: 622).

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: muscle development, which are annotation(s) related to Biological Process.

The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.chlsprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

As noted above, cluster Z19178 features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Skeletal muscle LIM-protein 2 (SEQ ID NO:622). A description of each variant protein according to the present invention is now provided.

Variant protein Z19178_PEA_—1_P5 (SEQ ID NO:550) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z19178_PEA_—1_T5 (SEQ ID NO:17). An alignment is given to the known protein (Skeletal muscle LIM-protein 2 (SEQ ID NO:622)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z19178_PEA_—1_P5 (SEQ ID NO:550) and Q96C98 (SEQ ID NO:1390):

1. An isolated chimeric polypeptide encoding for Z19178_PEA_—1_P5 (SEQ ID NO:550), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVRLQSAASPAARSA PAWPGPQELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCSACGETV (SEQ ID NO:1494) corresponding to amino acids 1-130 of Z19178_PEA_—1_P5 (SEQ ID NO:550), and a second amino acid sequence being at least 90% homologous to MPGSRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKFAPRCARCSKTLTQGGVTYR DQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHH NCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP corresponding to amino acids 1-172 of Q96C98 (SEQ ID NO:1390), which also corresponds to amino acids 131-302 of Z19178_PEA_—1_P5 (SEQ ID NO:550), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of Z19178_PEA_—1_P5 (SEQ ID NO:550), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVRLQSAASPAARSA PAWPGPQELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCSACGETV (SEQ ID NO:1494) of Z19178_PEA_—1_P5 (SEQ ID NO:550).

Comparison Report Between Z19178_PEA_—1_P5 (SEQ ID NO:550) and Q9BVA2 (SEQ ID NO:1391):

1. An isolated chimeric polypeptide encoding for Z19178_PEA_L_P5 (SEQ ID NO:550), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVRLQSAASPAARSA PAWPGPQ corresponding to amino acids 1-74 of Z19178_PEA_—1_P5 (SEQ ID NO:550), and a second amino acid sequence being at least 90% homologous to ELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCSACGETVMPGSRKLEYGGQTW HEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKFAPRCARCSKTLTQGGVTYRDQPWHRECLVCTGC QTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQ GFVPDGDQVLCQGCSQAGP corresponding to amino acids 53-280 of Q9BVA2 (SEQ ID NO:1391), which also corresponds to amino acids 75-302 of Z19178_PEA_—1_P5 (SEQ ID NO:550), wherein said first and second amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein Z19178_PEA_—1_P5 (SEQ ID NO:550) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 4, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_—1_P5 (SEQ ID NO:550) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 4

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

247
K ->
No

278
T -> N
No

Variant protein Z19178_PEA_—1_P5 (SEQ ID NO:550) is encoded by the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z19178_PEA_—1_T5 (SEQ ID NO:17) is shown in bold; this coding portion starts at position 1 and ends at position 907. The transcript also has the following SNPs as listed in Table 5 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_—1_P5 (SEQ ID NO:550) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

607
G -> A
Yes

742
G ->
No

834
C -> A
No

1082
C -> G
Yes

1089
T -> A
Yes

1110
C -> T
Yes

1236
C -> T
Yes

1326
C -> T
No

1450
C -> T
No

1523
C -> T
No

Variant protein Z19178_PEA_—1_P6 (SEQ ID NO:551) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z19178_PEA_—1_T9 (SEQ ID NO:18). An alignment is given to the known protein (Skeletal muscle LIM-protein 2 (SEQ ID NO:622)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z19178_PEA_—1_P6 (SEQ ID NO:551) and Q96C98 (SEQ ID NO:1390):

1. An isolated chimeric polypeptide encoding for Z19178_PEA_—1_P6 (SEQ ID NO:551), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL (SEQ ID NO:1495) corresponding to amino acids 1-34 of Z19178_PEA_—1_P6 (SEQ ID NO:551), and a second amino acid sequence being at least 90% homologous to TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYV SFEDRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP corresponding to amino acids 60-172 of Q96C98 (SEQ ID NO:1390), which also corresponds to amino acids 35-147 of Z19178_PEA_—1_P6 (SEQ ID NO:551), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of Z19178_PEA_—1_P6 (SEQ ID NO:551), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL (SEQ ID NO:1495) of Z19178_PEA_—6 (SEQ ID NO:551).

Comparison Report Between Z19178_PEA_—1_P6 (SEQ ID NO:551) and Q9BVA2 (SEQ ID NO:1391):

1. An isolated chimeric polypeptide encoding for Z19178_PEA_—1_P6 (SEQ ID NO:551), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL (SEQ ID NO:1495) corresponding to amino acids 1-34 of Z19178_PEA_—1_P6 (SEQ ID NO:551), and a second amino acid sequence being at least 90% homologous to TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYV SFEDRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP corresponding to amino acids 168-280 of Q9BVA2 (SEQ ID NO:1391), which also corresponds to amino acids 35-147 of Z19178_PEA_—1_P6 (SEQ ID NO:551), wherein said first and second amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein Z19178_PEA_—1_P6 (SEQ ID NO:551) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_—1_P6 (SEQ ID NO:551) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

123
T -> N
No

92
K ->
No

Variant protein Z19178_PEA_—1_P6 (SEQ ID NO:551) is encoded by the following transcript(s): Z19178_PEA_—1_T9 (SEQ ID NO:18), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z19178_PEA_—1_T9 (SEQ ID NO:18) is shown in bold; this coding portion starts at position 379 and ends at position 819. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_—1_P6 (SEQ ID NO:551) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

519
G -> A
Yes

654
G ->
No

746
C -> A
No

994
C -> G
Yes

1001
T -> A
Yes

1022
C -> T
Yes

1148
C -> T
Yes

1238
C -> T
No

1362
C -> T
No

1435
C -> T
No

As noted above, cluster Z19178 features 15 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z19178_PEA_—1_node_—15 (SEQ ID NO:197) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
449
568

Segment cluster Z19178_PEA_—1_node_—17 (SEQ ID NO:198) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T19 (SEQ ID NO:18). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
569
699

Z19178_PEA_1_T9 (SEQ ID NO: 18)
481
611

Segment cluster Z19178_PEA_—1_node_—2 (SEQ ID NO:199) according to the present invention is supported by 43 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
1
217

Z19178_PEA_1_T9 (SEQ ID NO: 18)
1
217

Segment cluster Z19178_PEA_—1_node_—22 (SEQ ID NO:200) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
756
1000

Z19178_PEA_1_T9 (SEQ ID NO: 18)
668
912

Segment cluster Z19178_PEA_—1_node_—23 (SEQ ID NO:201) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T19 (SEQ ID NO:18). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
1001
1404

Z19178_PEA_1_T9 (SEQ ID NO: 18)
913
1316

Segment cluster Z19178_PEA_—1_node_—24 (SEQ ID NO:202) according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
1405
1554

Z19178_PEA_1_T9 (SEQ ID NO: 18)
1317
1466

Segment cluster Z19178_PEA_—1_node_—10 (SEQ ID NO:203) according to the present invention is supported by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T19 (SEQ ID NO:18). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
277
325

Z19178_PEA_1_T9 (SEQ ID NO: 18)
359
407

Segment cluster Z19178_PEA_—1_node_—11 (SEQ ID NO:204) according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T19 (SEQ ID NO:18). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
326
398

Z19178_PEA_1_T9 (SEQ ID NO: 18)
408
480

Segment cluster Z19178_PEA_—1_node_—14 (SEQ ID NO:205) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
399
448

Segment cluster Z19178_PEA_—1_node_—18 (SEQ ID NO:206) according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
700
751

Z19178_PEA_1_T9 (SEQ ID NO: 18)
612
663

Segment cluster Z19178_PEA_—1_node_—19 (SEQ ID NO:207) according to the present invention can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T19 (SEQ ID NO:18). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
752
755

Z19178_PEA_1_T9 (SEQ ID NO: 18)
664
667

Segment cluster Z19178_PEA_—1_node_—3 (SEQ ID NO:208) according to the present invention can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
218
223

Z19178_PEA_1_T9 (SEQ ID NO: 18)
218
223

Segment cluster Z19178_PEA_—1_node_—4 (SEQ ID NO:209) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T9 (SEQ ID NO: 18)
224
266

Segment cluster Z19178_PEA_—1_node_—5 (SEQ ID NO:210) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T9 (SEQ ID NO: 18)
267
305

Segment cluster Z19178_PEA_—1_node_—9 (SEQ ID NO:211) according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_—1_T5 (SEQ ID NO:17) and Z19178_PEA_—1_T9 (SEQ ID NO:18). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z19178_PEA_1_T5 (SEQ ID NO: 17)
224
276

Z19178_PEA_1_T9 (SEQ ID NO: 18)
306
358

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster S67314

Cluster S67314 features 4 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

S67314_PEA_1_T4
19

S67314_PEA_1_T5
20

S67314_PEA_1_T6
21

S67314_PEA_1_T7
22

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

S67314_PEA_1_node_0
212

S67314_PEA_1_node_11
213

S67314_PEA_1_node_13
214

S67314_PEA_1_node_15
215

S67314_PEA_1_node_17
216

S67314_PEA_1_node_4
217

S67314_PEA_1_node_10
218

S67314_PEA_1_node_3
219

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

S67314_PEA_1_P4
552

S67314_PEA_1_P5
553

S67314_PEA_1_P6
554

S67314_PEA_1_P7
555

These sequences are variants of the known protein Fatty acid-binding protein, heart (SwissProt accession identifier FABH_HUMAN; known also according to the synonyms H-FABP; Muscle fatty acid-binding protein; M-FABP; Mammary-derived growth inhibitor; MDGI), SEQ ID NO: 623, referred to herein as the previously known protein.

Protein Fatty acid-binding protein (SEQ ID NO:623), heart is known or believed to have the following function(s): FABP are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. The sequence for protein Fatty acid-binding protein, heart is given at the end of the application, as “Fatty acid-binding protein, heart amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

1
V -> A

104
L -> K

124
C -> S

129
E -> Q

Protein Fatty acid-binding protein (SEQ ID NO:623), heart localization is believed to be Cytoplasmic.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: negative control of cell proliferation, which are annotation(s) related to Biological Process; and lipid binding, which are annotation(s) related to Molecular Function.

As noted above, cluster S67314 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Fatty acid-binding protein (SEQ ID NO:623), heart. A description of each variant protein according to the present invention is now provided.

Variant protein S67314_PEA_—1_P4 (SEQ ID NO:552) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_—1_T4 (SEQ ID NO:19).

An alignment is given to the known protein (Fatty acid-binding protein (SEQ ID NO:623), heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between S67314_PEA_—1_P4 (SEQ ID NO:552) and FABH_HUMAN (SEQ ID NO:623):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P4 (SEQ ID NO:552), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEF DETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of S67314_PEA_—1_P4 (SEQ ID NO:552), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGLTQAGTQILPYRL HDCGQITFSKCNCKTGINNTNLVGLLGSL (SEQ ID NO:1496) corresponding to amino acids 117-215 of S67314_PEA_—1_P4 (SEQ ID NO:552), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of S67314_PEA_—1_P4 (SEQ ID NO:552), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGLTQAGTQILPYRL HDCGQITFSKCNCKTGINNTNLVGLLGSL (SEQ ID NO:1496) in S67314_PEA_—1_P4 (SEQ ID NO:552).

Comparison Report Between S67314_PEA_—1_P4 (SEQ ID NO:552) and AAP35373 (SEQ ID NO:1392):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P4 (SEQ ID NO:552), comprising a first amino acid sequence being at least 90% homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEF DETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of S67314_PEA_—1_P4 (SEQ ID NO:552), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGLTQAGTQILPYRL HDCGQITFSKCNCKTGINNTNLVGLLGSL (SEQ ID NO:1496) corresponding to amino acids 117-215 of S67314_PEA_—1_P4 (SEQ ID NO:552), wherein said first and second amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein S67314_PEA_—1_P4 (SEQ ID NO:552) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P4 (SEQ ID NO:552) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

53
K -> R
Yes

Variant protein S67314_PEA_—1_P4 (SEQ ID NO:552) is encoded by the following transcript(s): S67314_PEA_—1_T4 (SEQ ID NO:19), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_—1_T4 (SEQ ID NO:19) is shown in bold; this coding portion starts at position 925 and ends at position 1569. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P4 (SEQ ID NO:552) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

580
T -> C
Yes

1082
A -> G
Yes

1670
A -> C
Yes

Variant protein S67314_PEA_—1_P5 (SEQ ID NO:553) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_—1_T5 (SEQ ID NO:20). An alignment is given to the known protein (Fatty acid-binding protein (SEQ ID NO:623), heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between S67314_PEA_—1_P5 (SEQ ID NO:553) and FABH_HUMAN (SEQ ID NO:623):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P5 (SEQ ID NO:553), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEF DETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of S67314_PEA_—1_P5 (SEQ ID NO:553), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVGKSIV (SEQ ID NO:1497) corresponding to amino acids 117-178 of S67314_PEA_—1_P5 (SEQ ID NO:553), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of S67314_PEA_—1_P5 (SEQ ID NO:553), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVGKSIV (SEQ ID NO:1497) in S67314_PEA_—1_P5 (SEQ ID NO:553).

Comparison Report Between S67314_PEA_—1_P5 (SEQ ID NO:553) and AAP35373 (SEQ ID NO:1392):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P5 (SEQ ID NO:553), comprising a first amino acid sequence being at least 90% homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEF DETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of S67314_PEA_—1_P5 (SEQ ID NO:553), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVGKSIV (SEQ ID NO:1497) corresponding to amino acids 117-178 of S67314_PEA_—1_P5 (SEQ ID NO:553), wherein said first and second amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein S67314_PEA_—1_P5 (SEQ ID NO:553) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P5 (SEQ ID NO:553) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

53
K -> R
Yes

Variant protein S67314_PEA_—1_P5 (SEQ ID NO:553) is encoded by the following transcript(s): S67314_PEA_—1_T5 (SEQ ID NO:20), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_—1_T5 (SEQ ID NO:20) is shown in bold; this coding portion starts at position 925 and ends at position 1458. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P5 (SEQ ID NO:553) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

580
T -> C
Yes

1082
A -> G
Yes

1326
A -> G
Yes

Variant protein S67314_PEA_—1_P6 (SEQ ID NO:554) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_—1_T6 (SEQ ID NO:21). An alignment is given to the known protein (Fatty acid-binding protein (SEQ ID NO:623), heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between S67314_PEA_—1_P6 (SEQ ID NO:554) and FABH_HUMAN (SEQ ID NO:623):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P6 (SEQ ID NO:554), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEF DETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1-116 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-116 of S67314_PEA_—1_P6 (SEQ ID NO:554), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MEKLQLRNVK (SEQ ID NO:1498) corresponding to amino acids 117-126 of S67314_PEA_—1_P6 (SEQ ID NO:554), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of S67314_PEA_—1_P6 (SEQ ID NO:554), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MEKLQLRNVK (SEQ ID NO:1498) in S67314_PEA_—1_P6 (SEQ ID NO:554).

Comparison Report Between S67314_PEA_—1_P6 (SEQ ID NO:554) and AAP35373 (SEQ ID NO:1392):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P6 (SEQ ID NO:554), comprising a first amino acid sequence being at least 90% homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEF DETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1-116 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-116 of S67314_PEA_—1_P6 (SEQ ID NO:554), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MEKLQLRNVK (SEQ ID NO:1498) corresponding to amino acids 117-126 of S67314_PEA_—1_P6 (SEQ ID NO:554), wherein said first and second amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein S67314_PEA_—1_P6 (SEQ ID NO:554) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P6 (SEQ ID NO:554) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

53
K -> R
Yes

Variant protein S67314_PEA_—1_P6 (SEQ ID NO:554) is encoded by the following transcript(s): S67314_PEA_—1_T6 (SEQ ID NO:21), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_—1_T6 (SEQ ID NO:21) is shown in bold; this coding portion starts at position 925 and ends at position 1302. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P6 (SEQ ID NO:554) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

580
T -> C
Yes

1082
A -> G
Yes

1444
T -> C
Yes

Variant protein S67314_PEA_—1_P7 (SEQ ID NO:555) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_—1_T7 (SEQ ID NO:22). An alignment is given to the known protein (Fatty acid-binding protein (SEQ ID NO:623), heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between S67314_PEA_—1_P7 (SEQ ID NO:555) and FABH_HUMAN (SEQ ID NO:623):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P7 (SEQ ID NO:555), comprising a first amino acid sequence being at least 90% homologous to MVDAFLGTWKLVDSKNFDDYMKSL corresponding to amino acids 1-24 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 1-24 of S67314_PEA_—1_P7 (SEQ ID NO:555), second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AHILITFPLPS (SEQ ID NO:1499) corresponding to amino acids 25-35 of S67314_PEA_—1_P7 (SEQ ID NO:555), and a third amino acid sequence being at least 90% homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQ KWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding to amino acids 25-133 of FABH_HUMAN (SEQ ID NO:623), which also corresponds to amino acids 36-144 of S67314_PEA_—1_P7 (SEQ ID NO:555), wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of S67314_PEA_—1_P7 (SEQ ID NO:555) comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AHILITFPLPS (SEQ ID NO:1499), corresponding to S67314_PEA_—1_P7 (SEQ ID NO:555).

Comparison Report Between S67314_PEA_—1_P7 (SEQ ID NO:555) and AAP35373 (SEQ ID NO:1392):

1. An isolated chimeric polypeptide encoding for S67314_PEA_—1_P7 (SEQ ID NO:555), comprising a first amino acid sequence being at least 90% homologous to MVDAFLGTWKLVDSKNFDDYMKSL corresponding to amino acids 1-24 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 1-24 of S67314_PEA_—1_P7 (SEQ ID NO:555), second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AHILITFPLPS (SEQ ID NO:1499) corresponding to amino acids 25-35 of S67314_PEA_—1_P7 (SEQ ID NO:555), and a third amino acid sequence being at least 90% homologous to GVGFATRQVASMTKPTTHEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQ KWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding to amino acids 25-133 of AAP35373 (SEQ ID NO:1392), which also corresponds to amino acids 36-144 of S67314_PEA_—1_P7 (SEQ ID NO:555), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein S67314_PEA_—1_P7 (SEQ ID NO:555) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P7 (SEQ ID NO:555) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

64
K -> R
Yes

Variant protein S67314_PEA_—1_P7 (SEQ ID NO:555) is encoded by the following transcript(s): S67314_PEA_—1_T7 (SEQ ID NO:22), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_—1_T7 (SEQ ID NO:22) is shown in bold; this coding portion starts at position 925 and ends at position 1356. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_—1_P7 (SEQ ID NO:555) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

580
T -> C
Yes

1115
A -> G
Yes

2772
G -> A
Yes

2896
C -> A
Yes

2918
G -> C
Yes

3003
A -> G
Yes

3074
T -> G
Yes

1344
T -> C
Yes

1522
-> T
No

1540
-> A
No

1540
-> T
No

1578
G -> A
Yes

1652
G -> A
Yes

2263
G -> A
Yes

2605
T -> C
Yes

As noted above, cluster S67314 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster S67314_PEA_—1_node_—0 (SEQ ID NO:212) according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T4 (SEQ ID NO:19), S67314_PEA_—1_T5 (SEQ ID NO:20), S67314_PEA_—1_T6 (SEQ ID NO:21) and S67314_PEA_—1_T7 (SEQ ID NO:22). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T4 (SEQ ID NO: 19)
1
997

S67314_PEA_1_T5 (SEQ ID NO: 20)
1
997

S67314_PEA_1_T6 (SEQ ID NO: 21)
1
997

S67314_PEA_1_T7 (SEQ ID NO: 22)
1
997

Segment cluster S67314_PEA_—1_node_—11 (SEQ ID NO:213) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T4 (SEQ ID NO:19). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T4 (SEQ ID NO: 19)
1273
2110

Segment cluster S67314_PEA_—1_node_—13 (SEQ ID NO:214) according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T7 (SEQ ID NO:22). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T7 (SEQ ID NO: 22)
1306
3531

Segment cluster S67314_PEA_—1_node_—15 (SEQ ID NO:215) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T5 (SEQ ID NO:20). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T5 (SEQ ID NO: 20)
1273
1733

Segment cluster S67314_PEA_—1_node_—17 (SEQ ID NO:216) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T6 (SEQ ID NO:21). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T6 (SEQ ID NO: 21)
1273
1822

TABLE 18

Oligonucleotides related to this segment

Overexpressed
Chip

Oligonucleotide name
in cancers
reference

S67314_0_0_744 (SEQ ID NO: 1406)
colorectal cancer
Colon

As a general note, oligonucleotide S67314_—0_—0_—741 (SEQ ID NO:1405) was overexpressed in colon cancer; this oligonucleotide maps to at least one part of this cluster.

Segment cluster S67314_PEA_—1_node_—4 (SEQ ID NO:217) according to the present invention is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T4 (SEQ ID NO:19), S67314_PEA_—1_T5 (SEQ ID NO:20), S67314_PEA_—1_T6 (SEQ ID NO:21) and S67314_PEA_—1_T7 (SEQ ID NO:22). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T4 (SEQ ID NO: 19)
998
1170

S67314_PEA_1_T5 (SEQ ID NO: 20)
998
1170

S67314_PEA_1_T6 (SEQ ID NO: 21)
998
1170

S67314_PEA_1_T7 (SEQ ID NO: 22)
1031
1203

Segment cluster S67314_PEA_—1_node_—10 (SEQ ID NO:218) according to the present invention is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T4 (SEQ ID NO:19), S67314_PEA_—1_T5 (SEQ ID NO:20), S67314_PEA_—1_T6 (SEQ ID NO:21) and S67314_PEA_—1_T7 (SEQ ID NO:22). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T4 (SEQ ID NO: 19)
1171
1272

S67314_PEA_1_T5 (SEQ ID NO: 20)
1171
1272

S67314_PEA_1_T6 (SEQ ID NO: 21)
1171
1272

S67314_PEA_1_T7 (SEQ ID NO: 22)
1204
1305

Segment cluster S67314_PEA_—1_node_—3 (SEQ ID NO:219) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_—1_T7 (SEQ ID NO:22). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

S67314_PEA_1_T7 (SEQ ID NO: 22)
998
1030

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster Z44808

Cluster Z44808 features 5 transcript(s) and 21 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

Z44808_PEA_1_T11
23

Z44808_PEA_1_T4
24

Z44808_PEA_1_T5
25

Z44808_PEA_1_T8
26

Z44808_PEA_1_T9
27

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

Z44808_PEA_1_node_0
220

Z44808_PEA_1_node_16
221

Z44808_PEA_1_node_2
222

Z44808_PEA_1_node_24
223

Z44808_PEA_1_node_32
224

Z44808_PEA_1_node_33
225

Z44808_PEA_1_node_36
226

Z44808_PEA_1_node_37
227

Z44808_PEA_1_node_41
228

Z44808_PEA_1_node_11
229

Z44808_PEA_1_node_13
230

Z44808_PEA_1_node_18
231

Z44808_PEA_1_node_22
232

Z44808_PEA_1_node_26
233

Z44808_PEA_1_node_30
234

Z44808_PEA_1_node_34
235

Z44808_PEA_1_node_35
236

Z44808_PEA_1_node_39
237

Z44808_PEA_1_node_4
238

Z44808_PEA_1_node_6
239

Z44808_PEA_1_node_8
240

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

Z44808_PEA_1_P5
556

Z44808_PEA_1_P6
557

Z44808_PEA_1_P7
558

Z44808_PEA_1_P11
559

These sequences are variants of the known protein SPARC related modular calcium-binding protein 2 precursor (SwissProt accession identifier SMO2_HUMAN; known also according to the synonyms Secreted modular calcium-binding protein 2; SMOC-2; Smooth muscle-associated protein 2; SMAP-2; MSTP117), SEQ ID NO: 624, referred to herein as the previously known protein.

Protein SPARC related modular calcium-binding protein 2 precursor is known or believed to have the following function(s): calcium binding . The sequence for protein SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624) is given at the end of the application, as “SPARC related modular calcium-binding protein 2 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on

amino acid sequence
Comment

169-170
KT -> TR

212
S -> P

429-466
TPRGHAESTSNRQPRKQG -> RSKRNL

434
A -> V

439
N -> Y

Protein SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624) localization is believed to be Secreted (Probable).

Cluster Z44808 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 19 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: colorectal cancer, lung cancer and pancreas carcinoma.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bladder
123

bone
304

brain
18

colon
0

epithelial
40

general
37

kidney
2

lung
0

breast
61

ovary
116

pancreas
0

prostate
128

stomach
36

uterus
195

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
6.8e−01
7.6e−01
7.7e−01
0.8
9.1e−01
0.6

bone
7.0e−01
8.8e−01
9.9e−01
0.3
1
0.2

brain
6.8e−01
7.2e−01
3.0e−02
2.6
1.7e−01
1.6

colon
9.2e−03
1.3e−02
1.2e−01
3.6
1.6e−01
3.1

epithelial
2.1e−02
4.0e−01
1.0e−04
1.9
2.7e−01
1.0

general
2.6e−02
7.2e−01
4.9e−07
1.9
3.0e−01
1.0

kidney
7.3e−01
8.1e−01
1
1.0
1
1.0

lung
4.0e−03
1.8e−02
8.0e−04
12.2
2.1e−02
6.0

breast
4.8e−01
6.1e−01
9.8e−02
2.0
3.9e−01
1.2

ovary
8.1e−01
8.3e−01
9.1e−01
0.6
9.7e−01
0.5

pancreas
1.2e−01
2.1e−01
1.0e−03
6.5
5.9e−03
4.6

prostate
8.4e−01
8.9e−01
9.0e−01
0.6
9.8e−01
0.4

stomach
5.0e−01
8.7e−01
9.6e−04
1.5
1.9e−01
0.8

uterus
6.7e−01
7.9e−01
9.2e−01
0.5
1
0.3

As noted above, cluster Z44808 features 5 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624). A description of each variant protein according to the present invention is now provided.

Variant protein Z44808_PEA_—1_P5 (SEQ ID NO:556) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z44808_PEA_—1_T4 (SEQ ID NO:24). An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z44808_PEA_—1_P5 (SEQ ID NO:556) and SMO2_HUMAN (SEQ ID NO:624):

1. An isolated chimeric polypeptide encoding for Z44808_PEA_—1_P5 (SEQ ID NO:556), comprising a first amino acid sequence being at least 90% homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE DGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1-441 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-441 of Z44808_PEA_—1_P5 (SEQ ID NO:556), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DAMVVSSRPKATTHRKSRTLSRR (SEQ ID NO:1500) corresponding to amino acids 442-464 of Z44808_PEA_—1_P5 (SEQ ID NO:556), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z44808_PEA_—1_P5 (SEQ ID NO:556), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DAMVVSSRPKATTHRKSRTLSRR (SEQ ID NO:1500) in Z44808_PEA_—1_P5 (SEQ ID NO:556).

Variant protein Z44808_PEA_—1_P5 (SEQ ID NO:556) is encoded by the following transcript(s): Z44808_PEA_—1_T4 (SEQ ID NO:24), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z44808_PEA_—1_T4 (SEQ ID NO:24) is shown in bold; this coding portion starts at position 586 and ends at position 1977. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P5 (SEQ ID NO:556) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

549
A -> G
No

648
T -> G
No

4403
G -> T
No

4456
G -> A
Yes

4964
G -> C
Yes

1025
C ->
No

1677
T -> C
No

2691
C -> T
Yes

3900
T -> C
No

3929
G -> A
Yes

4099
G -> T
Yes

4281
T -> C
No

4319
G -> C
Yes

Variant protein Z44808_PEA_—1_P6 (SEQ ID NO:557) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z44808_PEA_—1_T5 (SEQ ID NO:25). An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z44808_PEA_—1_P6 (SEQ ID NO:557) and SMO2_HUMAN (SEQ ID NO:624):

1. An isolated chimeric polypeptide encoding for Z44808_PEA_—1_P6 (SEQ ID NO:557), comprising a first amino acid sequence being at least 90% homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE DGKADTKKRH corresponding to amino acids 1-428 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-428 of Z44808_PEA_—1_P6 (SEQ ID NO:557), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RSKRNL (SEQ ID NO:1501) corresponding to amino acids 1-428 of Z44808_PEA_—1_P6 (SEQ ID NO:557), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z44808_PEA_—1_P6 (SEQ ID NO:557), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RSKRNL (SEQ ID NO:1501) in Z44808_PEA_—1_P6 (SEQ ID NO:557).

Variant protein Z44808_PEA_—1_P6 (SEQ ID NO:557) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P6 (SEQ ID NO:557) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

147
A ->
No

Variant protein Z44808_PEA_—1_P6 (SEQ ID NO:557) is encoded by the following transcript(s): Z44808_PEA_—1_T5 (SEQ ID NO:25), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z44808_PEA_—1_T5 (SEQ ID NO:25) is shown in bold; this coding portion starts at position 586 and ends at position 1887. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P6 (SEQ ID NO:557) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

549
A -> G
No

648
T -> G
No

2866
G -> A
Yes

3374
G -> C
Yes

1025
C ->
No

1677
T -> C
No

2310
T -> C
No

2339
G -> A
Yes

2509
G -> T
Yes

2691
T -> C
No

2729
G -> C
Yes

2813
G -> T
No

Variant protein Z44808_PEA_—1_P7 (SEQ ID NO:558) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z44808_PEA_—1_T9 (SEQ ID NO:27). An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z44808_PEA_—1_P7 (SEQ ID NO:558) and SMO2_HUMAN (SEQ ID NO:624):

1. An isolated chimeric polypeptide encoding for Z44808_PEA_—1_P7 (SEQ ID NO:558), comprising a first amino acid sequence being at least 90% homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE DGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1-441 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-441 of Z44808_PEA_—1_P7 (SEQ ID NO:558), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLWLRGKVSFYCF (SEQ ID NO:1502) corresponding to amino acids 442-454 of Z44808_PEA_—1_P7 (SEQ ID NO:558), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z44808_PEA_—1_P7 (SEQ ID NO:558), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLWLRGKVSFYCF (SEQ ID NO:1502) in Z44808_PEA_—1_P7 (SEQ ID NO:558).

Variant protein Z44808_PEA_—1_P7 (SEQ ID NO:558) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P7 (SEQ ID NO:558) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

147
A ->
No

Variant protein Z44808_PEA_—1_P7 (SEQ ID NO:558) is encoded by the following transcript(s): Z44808_PEA_—1_T9 (SEQ ID NO:27), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z44808_PEA_—1_T9 (SEQ ID NO:27) is shown in bold; this coding portion starts at position 586 and ends at position 1947. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P7 (SEQ ID NO:558) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

549
A -> G
No

648
T -> G
No

1025
C ->
No

1677
T -> C
No

2169
C -> A
Yes

Variant protein Z44808_PEA_—1_P11 (SEQ ID NO:559) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z44808_PEA_—1_T11 (SEQ ID NO:23). The identification of this transcript was performed using a non-EST based method for identification of alternative splicing, described in the following reference: “Sorek R et al., Genome Res. (2004) 14:1617-23.” An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor (SEQ ID NO:624)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z44808_PEA_—1_P11 (SEQ ID NO:559) and SMO2_HUMAN (SEQ ID NO:624):

1. An isolated chimeric polypeptide encoding for Z44808_PEA_—1_P11 (SEQ ID NO:559), comprising a first amino acid sequence being at least 90% homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR PISGTAVAHKTPRCPGSVNEKLPQREGTGKT corresponding to amino acids 1-170 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 1-170 of Z44808_PEA_—1_P11 (SEQ ID NO:559), and a second amino acid sequence being at least 90% homologous to DIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGY CWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVH AASDPSSSSGRLSEPDPSHTLEERVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCD VNNDKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG corresponding to amino acids 188-446 of SMO2_HUMAN (SEQ ID NO:624), which also corresponds to amino acids 171-429 of Z44808_PEA_—1_P11 (SEQ ID NO:559), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of Z44808_PEA_—1_P11 (SEQ ID NO:559) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TD, having a structure as follows: a sequence starting from any of amino acid numbers 170−x to 170; and ending at any of amino acid numbers 171+((n−2)−x), in which x varies from 0 to n−2.

Variant protein Z44808_PEA_—1_P11 (SEQ ID NO:559) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P11 (SEQ ID NO:559) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

147
A ->
No

Variant protein Z44808_PEA_—1_P11 (SEQ ID NO:559) is encoded by the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z44808_PEA_—1_T11 (SEQ ID NO:23) is shown in bold; this coding portion starts at position 586 and ends at position 1872. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_—1_P11 (SEQ ID NO:559) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

549
A -> G
No

648
T -> G
No

2720
G -> A
Yes

3228
G -> C
Yes

1025
C ->
No

1626
T -> C
No

2164
T -> C
No

2193
G -> A
Yes

2363
G -> T
Yes

2545
T -> C
No

2583
G -> C
Yes

2667
G -> T
No

As noted above, cluster Z44808 features 21 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z44808_PEA_—1_node_—0 (SEQ ID NO:220) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1
669

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1
669

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1
669

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1
669

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1
669

Segment cluster Z44808_PEA_—1_node_—16 (SEQ ID NO:221) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1172
1358

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1223
1409

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1223
1409

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1223
1409

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1223
1409

Segment cluster Z44808_PEA_—1_node_—2 (SEQ ID NO:222) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
670
841

Z44808_PEA_1_T4 (SEQ ID NO: 24)
670
841

Z44808_PEA_1_T5 (SEQ ID NO: 25)
670
841

Z44808_PEA_1_T8 (SEQ ID NO: 26)
670
841

Z44808_PEA_1_T9 (SEQ ID NO: 27)
670
841

Segment cluster Z44808_PEA_—1_node_—24 (SEQ ID NO:223) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1545
1819

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1596
1870

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1596
1870

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1596
1870

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1596
1870

Segment cluster Z44808_PEA_—1_node_—32 (SEQ ID NO:224) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T4 (SEQ ID NO:24) and Z44808_PEA_—1_T8 (SEQ ID NO:26). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1909
3593

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1909
2397

Segment cluster Z44808_PEA_—1_node_—33 (SEQ ID NO:225) according to the present invention is supported by 133 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24) and Z44808_PEA_—1_T5 (SEQ ID NO:25). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1858
2734

Z44808_PEA_1_T4 (SEQ ID NO: 24)
3594
4470

Z44808_PEA_1_T5 (SEQ ID NO: 25)
2004
2880

Segment cluster Z44808_PEA_—1_node_—36 (SEQ ID NO:226) according to the present invention is supported by 117 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24) and Z44808_PEA_—1_T5 (SEQ ID NO:25). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
2829
3080

Z44808_PEA_1_T4 (SEQ ID NO: 24)
4565
4816

Z44808_PEA_1_T5 (SEQ ID NO: 25)
2975
3226

Segment cluster Z44808_PEA_—1_node_—37 (SEQ ID NO:227) according to the present invention is supported by 120 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24) and Z44808_PEA_—1_T5 (SEQ ID NO:25). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
3081
3429

Z44808_PEA_1_T4 (SEQ ID NO: 24)
4817
5165

Z44808_PEA_1_T5 (SEQ ID NO: 25)
3227
3575

Segment cluster Z44808_PEA_—1_node_—41 (SEQ ID NO:228) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1974
2206

Segment cluster Z44808_PEA_—1_node_—11 (SEQ ID NO:229) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1097
1147

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1097
1147

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1097
1147

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1097
1147

Segment cluster Z44808_PEA_—1_node_—13 (SEQ ID NO:230) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1097
1171

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1148
1222

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1148
1222

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1148
1222

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1148
1222

Segment cluster Z44808_PEA_—1_node_—18 (SEQ ID NO:231) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1359
1441

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1410
1492

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1410
1492

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1410
1492

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1410
1492

Segment cluster Z44808_PEA_—1_node_—22 (SEQ ID NO:232) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1442
1544

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1493
1595

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1493
1595

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1493
1595

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1493
1595

TABLE 28

Oligonucleotides related to this segment

Overexpressed

Oligonucleotide name
in cancers
Chip reference

Z44808_0_8_0 (SEQ ID NO: 1407)
Lung squamous
LUN

cell carcinoma

Segment cluster Z44808_PEA_—1_node_—26 (SEQ ID NO:233) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T5 (SEQ ID NO:25). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1871
1965

Segment cluster Z44808_PEA_—1_node_—30 (SEQ ID NO:234) according to the present invention is supported by 44 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1820
1857

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1871
1908

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1966
2003

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1871
1908

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1871
1908

Segment cluster Z44808_PEA_—1_node_—34 (SEQ ID NO:235) according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24) and Z44808_PEA_—1_T5 (SEQ ID NO:25). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
2735
2809

Z44808_PEA_1_T4 (SEQ ID NO: 24)
4471
4545

Z44808_PEA_1_T5 (SEQ ID NO: 25)
2881
2955

Segment cluster Z44808_PEA_—1_node_—35 (SEQ ID NO:236) according to the present invention can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24) and Z44808_PEA_—1_T5 (SEQ ID NO:25). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
2810
2828

Z44808_PEA_1_T4 (SEQ ID NO: 24)
4546
4564

Z44808_PEA_1_T5 (SEQ ID NO: 25)
2956
2974

Segment cluster Z44808_PEA_—1_node_—39 (SEQ ID NO:237) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1909
1973

Segment cluster Z44808_PEA_—1_node_—4 (SEQ ID NO:238) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25) Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
842
948

Z44808_PEA_1_T4 (SEQ ID NO: 24)
842
948

Z44808_PEA_1_T5 (SEQ ID NO: 25)
842
948

Z44808_PEA_1_T8 (SEQ ID NO: 26)
842
948

Z44808_PEA_1_T9 (SEQ ID NO: 27)
842
948

Segment cluster Z44808_PEA_—1_node_—6 (SEQ ID NO:239) according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
949
1048

Z44808_PEA_1_T4 (SEQ ID NO: 24)
949
1048

Z44808_PEA_1_T5 (SEQ ID NO: 25)
949
1048

Z44808_PEA_1_T8 (SEQ ID NO: 26)
949
1048

Z44808_PEA_1_T9 (SEQ ID NO: 27)
949
1048

Segment cluster Z44808_PEA_—1_node_—8 (SEQ ID NO:240) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_—1_T11 (SEQ ID NO:23), Z44808_PEA_—1_T4 (SEQ ID NO:24), Z44808_PEA_—1_T5 (SEQ ID NO:25), Z44808_PEA_—1_T8 (SEQ ID NO:26) and Z44808_PEA_—1_T9 (SEQ ID NO:27). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

Z44808_PEA_1_T11 (SEQ ID NO: 23)
1049
1096

Z44808_PEA_1_T4 (SEQ ID NO: 24)
1049
1096

Z44808_PEA_1_T5 (SEQ ID NO: 25)
1049
1096

Z44808_PEA_1_T8 (SEQ ID NO: 26)
1049
1096

Z44808_PEA_1_T9 (SEQ ID NO: 27)
1049
1096

Variant Protein Alignment to the Previously Known Protein:

Expression of SMO2_HUMAN SPARC Related Modular Calcium-Binding Protein 2 Precursor (Secreted Modular Calcium-Binding Protein 2) (SMOC-2) (Smooth Muscle-Associated Protein 2) Z44808 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name Z44808junc8-11 (SEQ ID NO: 1291) in Normal and Cancerous Colon Tissues

Expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts detectable by or according to junc8-11, Z44808junc8-11 amplicon (SEQ ID NO: 1291) and primers Z44808junc8-11 (SEQ ID NO: 1289) and Z44808junc8-11R (SEQ ID NO: 1290) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 32 is a histogram showing over expression of the above-indicated SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts in cancerous colon samples relative to the normal samples.

As is evident from FIG. 32, the expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts detectable by the above amplicon in cancer samples was higher in a few samples than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 4 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z44808junc8-11F forward primer (SEQ ID NO: 1289); and Z44808junc8-11R reverse primer (SEQ ID NO: 1290).

Primers:

Forward primer Z44808junc8-11F (SEQ ID NO: 1289):

GAAGGCACAGGAAAAACAGATATTG

Reverse primer Z44808junc8-11R (SEQ ID NO: 1290):

TGGTGCTCTTGGTCACAGGAT

Amplicon Z44808junc8-11 (SEQ ID NO: 1291):

GAAGGCACAGGAAAAACAGATATTGCATCACGTTACCCTACCCTTTGGAC

TGAACAGGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTCAT

CCTGTGACCAAGAGCACCA

Expression of SMO2_HUMAN SPARC Related Modular Calcium-Binding Protein 2 Precursor (Secreted Modular Calcium-Binding Protein 2) (SMOC-2) (Smooth Muscle-Associated Protein 2) Z44808 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name Z44808 junc8-11 (SEQ ID NO: 1291) in Different Normal Tissues

Expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts detectable by or according to Z44808 junc8-11 amplicon (SEQ ID NO: 1291) and primers: Z44808 junc8-11F (SEQ ID NO: 1289) and Z44808 junc8-11R (SEQ ID NO: 1290) was measured by real time PCR. In parallel the expression of four housekeeping genes —RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO:1267), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon-Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2, “Tissue samples in normal panel”), to obtain a value of relative expression of each sample relative to median of the ovary samples.

The results are shown in FIG. 39, demonstrating the expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808 junc8-11 (SEQ ID NO: 1291) in different normal tissues.

Description for Cluster Z25299

Cluster Z25299 features 5 transcript(s) and 11 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

Z25299_PEA_2_T1
28

Z25299_PEA_2_T2
29

Z25299_PEA_2_T3
30

Z25299_PEA_2_T6
31

Z25299_PEA_2_T9
32

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

Z25299_PEA_2_node_20
241

Z25299_PEA_2_node_21
242

Z25299_PEA_2_node_23
243

Z25299_PEA_2_node_24
244

Z25299_PEA_2_node_8
245

Z25299_PEA_2_node_12
246

Z25299_PEA_2_node_13
247

Z25299_PEA_2_node_14
248

Z25299_PEA_2_node_17
249

Z25299_PEA_2_node_18
250

Z25299_PEA_2_node_19
251

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

Z25299_PEA_2_P2
560

Z25299_PEA_2_P3
561

Z25299_PEA_2_P7
562

Z25299_PEA_2_P10
563

These sequences are variants of the known protein Antileukoproteinase 1 precursor (SwissProt accession identifier ALK1_HUMAN; known also according to the synonyms ALP; HUSI-1; Seminal proteinase inhibitor; Secretory leukocyte protease inhibitor; BLPI; Mucus proteinase inhibitor; MPI; WAP four-disulfide core domain protein 4; Protease inhibitor WAP4), SEQ ID NO: 625, referred to herein as the previously known protein.

Protein Antileukoproteinase 1 precursor (SEQ ID NO:625) is known or believed to have the following function(s): Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues. The sequence for protein Antileukoproteinase 1 precursor is given at the end of the application, as “Antileukoproteinase 1 precursor amino acid sequence”. Protein Antileukoproteinase 1 precursor localization is believed to be Secreted.

It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Elastase inhibitor; Tryptase inhibitor. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anti-inflammatory; Antiasthma.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: proteinase inhibitor; serine protease inhibitor, which are annotation(s) related to Molecular Function.

Cluster Z25299 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 20 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, a mixture of malignant tumors from different tissues and ovarian carcinoma.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

Bladder
82

Bone
6

Brain
0

colon
37

epithelial
145

general
73

head and neck
638

kidney
26

liver
68

lung
465

breast
52

ovary
0

pancreas
20

prostate
36

skin
215

stomach
219

uterus
113

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
8.2e−01
8.5e−01
9.2e−01
0.6
9.7e−01
0.5

bone
5.5e−01
7.3e−01
4.0e−01
2.1
4.9e−01
1.5

brain
8.8e−02
1.5e−01
2.3e−03
7.7
1.2e−02
4.8

colon
3.3e−01
2.8e−01
4.2e−01
1.6
4.2e−01
1.5

epithelial
2.5e−01
7.6e−01
3.8e−01
1.0
1
0.6

general
6.4e−03
2.5e−01
1.7e−06
1.6
5.2e−01
0.9

head and neck
3.6e−01
5.9e−01
7.6e−01
0.6
1
0.3

kidney
7.4e−01
8.4e−01
2.1e−01
2.1
4.2e−01
1.4

liver
4.1e−01
9.1e−01
4.2e−02
3.2
6.4e−01
0.8

lung
7.6e−01
8.3e−01
9.8e−01
0.5
1
0.3

breast
5.0e−01
5.5e−01
9.8e−02
1.6
3.4e−01
1.1

ovary
3.7e−02
3.0e−02
6.9e−03
6.1
4.9e−03
5.6

pancreas
3.8e−01
3.6e−01
3.6e−01
1.7
3.9e−01
1.5

prostate
9.1e−01
9.2e−01
8.9e−01
0.5
9.4e−01
0.5

skin
6.0e−01
8.1e−01
9.3e−01
0.4
1
0.1

stomach
3.0e−01
8.1e−01
9.1e−01
0.6
1
0.3

uterus
1.6e−01
1.3e−01
3.2e−02
1.6
3.0e−01
1.1

As noted above, cluster Z25299 features 5 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Antileukoproteinase 1 precursor (SEQ ID NO:625). A description of each variant protein according to the present invention is now provided.

Variant protein Z25299_PEA_—2_P2 (SEQ ID NO:560) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25299_PEA_—2_T1 (SEQ ID NO:28). An alignment is given to the known protein (Antileukoproteinase 1 precursor (SEQ ID NO:625)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z25299_PEA_—2_P2 (SEQ ID NO:560) and ALK1_HUMAN (SEQ ID NO:625):

1. An isolated chimeric polypeptide encoding for Z25299_PEA_—2_P2 (SEQ ID NO:560), comprising a first amino acid sequence being at least 90% homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI KCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK corresponding to amino acids 1-131 of ALK1_HUMAN (SEQ ID NO:625), which also corresponds to amino acids 1-131 of Z25299_PEA_—2_P2 (SEQ ID NO:560), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKQGMRAH (SEQ ID NO:1503) corresponding to amino acids 132-139 of Z25299_PEA_—2_P2 (SEQ ID NO:560), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z25299_PEA_—2_P2 (SEQ ID NO:560), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKQGMRAH (SEQ ID NO:1503) in Z25299_PEA_—2_P2 (SEQ ID NO:560).

Variant protein Z25299_PEA_—2_P2 (SEQ ID NO:560) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P2 (SEQ ID NO:560) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

136
M -> T
Yes

20
P ->
No

43
C -> R
No

48
K -> N
No

83
R -> K
No

84
R -> W
No

Variant protein Z25299_PEA_—2_P2 (SEQ ID NO:560) is encoded by the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_—2_T1 (SEQ ID NO:28) is shown in bold; this coding portion starts at position 124 and ends at position 540. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P2 (SEQ ID NO:560) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

122
C -> T
No

123
C -> T
No

530
T -> C
Yes

989
C -> T
Yes

1127
C -> T
Yes

1162
A -> C
Yes

1180
A -> C
Yes

1183
A -> C
Yes

1216
A -> C
Yes

1262
G -> A
Yes

183
T ->
No

250
T -> C
No

267
A -> C
No

267
A -> G
No

339
C -> T
Yes

371
G -> A
No

373
A -> T
No

435
C -> T
No

Variant protein Z25299_PEA_—2_P3 (SEQ ID NO:561) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25299_PEA_—2_T2 (SEQ ID NO:29). An alignment is given to the known protein (Antileukoproteinase 1 precursor (SEQ ID NO:625)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z25299_PEA_—2_P3 (SEQ ID NO:561) and ALK1_HUMAN (SEQ ID NO:625):

1. An isolated chimeric polypeptide encoding for Z25299_PEA_—2_P3 (SEQ ID NO:561), comprising a first amino acid sequence being at least 90% homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI KCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK corresponding to amino acids 1-131 of ALK1_HUMAN (SEQ ID NO:625), which also corresponds to amino acids 1-131 of Z25299_PEA_—2_P3 (SEQ ID NO:561), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEKRHHKQLRDQEVDPLEMRRHSAG (SEQ ID NO:1504) corresponding to amino acids 132-156 of Z25299_PEA_—2_P3 (SEQ ID NO:561), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z25299_PEA_—2_P3 (SEQ ID NO:561), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEKRHHKQLRDQEVDPLEMRRHSAG (SEQ ID NO:1504) in Z25299_PEA_—2_P3 (SEQ ID NO:561).

Variant protein Z25299_PEA_—2_P3 (SEQ ID NO:561) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P3 (SEQ ID NO:561) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

20
P ->
No

43
C -> R
No

48
K -> N
No

83
R -> K
No

84
R -> W
No

Variant protein Z25299_PEA_—2_P3 (SEQ ID NO:561) is encoded by the following transcript(s): Z25299_PEA_—2_T2 (SEQ ID NO:29), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_—2_T2 (SEQ ID NO:29) is shown in bold; this coding portion starts at position 124 and ends at position 591. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P3 (SEQ ID NO:561) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

122
C -> T
No

123
C -> T
No

183
T ->
No

250
T -> C
No

267
A -> C
No

267
A -> G
No

339
C -> T
Yes

371
G -> A
No

373
A -> T
No

435
C -> T
No

Variant protein Z25299_PEA_—2_P7 (SEQ ID NO:562) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25299_PEA_—2_T6 (SEQ ID NO:31). An alignment is given to the known protein (Antileukoproteinase 1 precursor (SEQ ID NO:625)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z25299_PEA_—2_P7 (SEQ ID NO:562) and ALK1_HUMAN (SEQ ID NO:625):

1. An isolated chimeric polypeptide encoding for Z25299_PEA_—2_P7 (SEQ ID NO:562), comprising a first amino acid sequence being at least 90% homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI KCLDPVDTPNP corresponding to amino acids 1-81 of ALK1_HUMAN (SEQ ID NO:625), which also corresponds to amino acids 1-81 of Z25299_PEA_—2_P7 (SEQ ID NO:562), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RGSLGSAQ (SEQ ID NO:1505) corresponding to amino acids 82-89 of Z25299_PEA_—2_P7 (SEQ ID NO:562), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z25299_PEA_—2_P7 (SEQ ID NO:562), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RGSLGSAQ (SEQ ID NO:1505) in Z25299_PEA_—2_P7 (SEQ ID NO:562).

Variant protein Z25299_PEA_—2_P7 (SEQ ID NO:562) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P7 (SEQ ID NO:562) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

20
P ->
No

43
C -> R
No

48
K -> N
No

82
R -> S
No

Variant protein Z25299_PEA_—2_P7 (SEQ ID NO:562) is encoded by the following transcript(s): Z25299_PEA_—2_T6 (SEQ ID NO:31), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_—2_T6 (SEQ ID NO:31) is shown in bold; this coding portion starts at position 124 and ends at position 390. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P7 (SEQ ID NO:562) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

122
C -> T
No

123
C -> T
No

576
A -> C
Yes

594
A -> C
Yes

597
A -> C
Yes

630
A -> C
Yes

676
G -> A
Yes

183
T ->
No

250
T -> C
No

267
A -> C
No

267
A -> G
No

339
C -> T
Yes

369
A -> T
No

431
C -> T
No

541
C -> T
Yes

Variant protein Z25299_PEA_—2_P10 (SEQ ID NO:563) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25299_PEA_—2_T9 (SEQ ID NO:32). An alignment is given to the known protein (Antileukoproteinase 1 precursor (SEQ ID NO:625)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z25299_PEA_—2_P10 (SEQ ID NO:563) and ALK1_HUMAN (SEQ ID NO:625):

1. An isolated chimeric polypeptide encoding for Z25299_PEA_—2_P10 (SEQ ID NO:563), comprising a first amino acid sequence being at least 90% homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI KCLDPVDTPNPT corresponding to amino acids 1-82 of ALK1_HUMAN (SEQ ID NO:625), which also corresponds to amino acids 1-82 of Z25299_PEA_—2_P10 (SEQ ID NO:563).

Variant protein Z25299_PEA_—2_P10 (SEQ ID NO:563) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P10 (SEQ ID NO:563) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

20
P ->
No

43
C -> R
No

48
K -> N
No

Variant protein Z25299_PEA_—2_P10 (SEQ ID NO:563) is encoded by the following transcript(s): Z25299_PEA_—2_T9 (SEQ ID NO:32), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_—2_T9 (SEQ ID NO:32) is shown in bold; this coding portion starts at position 124 and ends at position 369. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_—2_P10 (SEQ ID NO:563) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

122
C -> T
No

123
C -> T
No

451
A -> C
Yes

484
A -> C
Yes

530
G -> A
Yes

183
T ->
No

250
T -> C
No

267
A -> C
No

267
A -> G
No

339
C -> T
Yes

395
C -> T
Yes

430
A -> C
Yes

448
A -> C
Yes

As noted above, cluster Z25299 features 11 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z25299_PEA_—2_node_—20 (SEQ ID NO:241) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
518
1099

Segment cluster Z25299_PEA_—2_node_—21 (SEQ ID NO:242) according to the present invention is supported by 162 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T6 (SEQ ID NO:31) and Z25299_PEA_—2_T9 (SEQ ID NO:32). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
1100
1292

Z25299_PEA_2_T6 (SEQ ID NO: 31)
514
706

Z25299_PEA_2_T9 (SEQ ID NO: 32)
368
560

Segment cluster Z25299_PEA_—2_node_—23 (SEQ ID NO:243) according to the present invention is invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T2 (SEQ ID NO:29). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z25299_PEA_2_T2 (SEQ ID NO: 29)
518
707

Segment cluster Z25299_PEA_—2_node_—24 (SEQ ID NO:244) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T2 (SEQ ID NO:29) and Z25299_PEA_—2_T3 (SEQ ID NO:30). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T2 (SEQ ID NO: 29)
708
886

Z25299_PEA_2_T3 (SEQ ID NO: 30)
518
696

Segment cluster Z25299_PEA_—2_node_—8 (SEQ ID NO:245) according to the present invention is supported by 218 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29), Z25299_PEA_—2_T3 (SEQ ID NO:30), Z25299_PEA_—2_T6 (SEQ ID NO:31) and Z25299_PEA_—2_T9 (SEQ ID NO:32). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
1
208

Z25299_PEA_2_T2 (SEQ ID NO: 29)
1
208

Z25299_PEA_2_T3 (SEQ ID NO: 30)
1
208

Z25299_PEA_2_T6 (SEQ ID NO: 31)
1
208

Z25299_PEA_2_T9 (SEQ ID NO: 32)
1
208

Segment cluster Z25299_PEA_—2_node_—12 (SEQ ID NO:246) according to the present invention is supported by 228 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29), Z25299_PEA_—2_T3 (SEQ ID NO:30), Z25299_PEA_—2_T6 (SEQ ID NO:31) and Z25299_PEA_—2_T9 (SEQ ID NO:32). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
209
245

Z25299_PEA_2_T2 (SEQ ID NO: 29)
209
245

Z25299_PEA_2_T3 (SEQ ID NO: 30)
209
245

Z25299_PEA_2_T6 (SEQ ID NO: 31)
209
245

Z25299_PEA_2_T9 (SEQ ID NO: 32)
209
245

Segment cluster Z25299_PEA_—2_node_—13 (SEQ ID NO:247) according to the present invention is supported by 246 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29), Z25299_PEA_—2_T3 (SEQ ID NO:30) Z25299_PEA_—2_T6 (SEQ ID NO:31) and Z25299_PEA_—2_T9 (SEQ ID NO:32). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
246
357

Z25299_PEA_2_T2 (SEQ ID NO: 29)
246
357

Z25299_PEA_2_T3 (SEQ ID NO: 30)
246
357

Z25299_PEA_2_T6 (SEQ ID NO: 31)
246
357

Z25299_PEA_2_T9 (SEQ ID NO: 32)
246
357

Segment cluster Z25299_PEA_—2_node_—14 (SEQ ID NO:248) according to the present invention can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29), Z25299_PEA_—2_T3 (SEQ ID NO:30), Z25299_PEA_—2_T6 (SEQ ID NO:31) and Z25299_PEA_—2_T9 (SEQ ID NO:32). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
358
367

Z25299_PEA_2_T2 (SEQ ID NO: 29)
358
367

Z25299_PEA_2_T3 (SEQ ID NO: 30)
358
367

Z25299_PEA_2_T6 (SEQ ID NO: 31)
358
367

Z25299_PEA_2_T9 (SEQ ID NO: 32)
358
367

Segment cluster Z25299_PEA_—2_node_—17 (SEQ ID NO:249) according to the present invention can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29) and Z25299_PEA_—2_T3 (SEQ ID NO:30). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
368
371

Z25299_PEA_2_T2 (SEQ ID NO: 29)
368
371

Z25299_PEA_2_T3 (SEQ ID NO: 30)
368
371

Segment cluster Z25299_PEA_—2_node_—18 (SEQ ID NO:250) according to the present invention is supported by 221 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29), Z25299_PEA_—2_T3 (SEQ ID NO:30) and Z25299_PEA_—2_T6 (SEQ ID NO:31). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
372
427

Z25299_PEA_2_T2 (SEQ ID NO: 29)
372
427

Z25299_PEA_2_T3 (SEQ ID NO: 30)
372
427

Z25299_PEA_2_T6 (SEQ ID NO: 31)
368
423

Segment cluster Z25299_PEA_—2_node_—19 (SEQ ID NO:251) according to the present invention is supported by 197 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_—2_T1 (SEQ ID NO:28), Z25299_PEA_—2_T2 (SEQ ID NO:29), Z25299_PEA_—2_T3 (SEQ ID NO:30) and Z25299_PEA_—2_T6 (SEQ ID NO:31). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

Segment starting
ending

Transcript name
position
position

Z25299_PEA_2_T1 (SEQ ID NO: 28)
428
517

Z25299_PEA_2_T2 (SEQ ID NO: 29)
428
517

Z25299_PEA_2_T3 (SEQ ID NO: 30)
428
517

Z25299_PEA_2_T6 (SEQ ID NO: 31)
424
513

Variant Protein Alignment to the Previously Known Protein:

Expression of Secretory Leukocyte Protease Inhibitor Acid-Stable Proteinase Inhibitor with Strong Affinities for Trypsin, Chymotrypsin, Elastase, and Cathepsin G
Z25299 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name Z25299 seg20 (SEQ ID NO:1294), Were Examined for Expression in Normal and Cancerous Colon Tissues

Transcripts detectable by or according to seg20, Z25299 seg20 amplicon (SEQ ID NO: 1294) and Z25299 seg20F (SEQ ID NO: 1292) and Z25299 seg20R (SEQ ID NO: 1293) primers were measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above Tissue samples in testing panel), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 21 is a histogram showing over expression of the above-indicated variant.

Transcript expression in cancerous colon samples relative to the normal samples are shown.

As is evident from FIG. 21, transcripts detectable by the above amplicon(s) in cancer samples were significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1 Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 7 out of 36 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of this variant was determined.

Transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples were determined by T test as 6.98E-02.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.33E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z25299 seg20F forward primer (SEQ ID NO: 1292); and Z25299 seg20R reverse primer (SEQ ID NO: 1293).

Forward primer (SEQ ID NO: 1292):

CTCCTGAACCCTACTCCAAGCA

Reverse primer (SEQ ID NO: 1293):

CAGGCGATCCTATGGAAATCC

Amplicon (SEQ ID NO: 1294):

CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCCTTGTCCTTT

CAAGAGAACTGTTCTCCAGGTCTCAGGGCCAGGATTTCCATAGGATCGCC

TG

Expression of Secretory Leukocyte Protease Inhibitor Acid-Stable Proteinase Inhibitor with Strong Affinities for Trypsin, Chymotrypsin, Elastase, and Cathepsin G. May Prevent Elastase-Mediated Damage to Oral and Possibly Other Mucosal Tissues Z25299 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name Z25299Seg20 (SEQ ID NO: 1294) in Different Normal Tissues

Expression of Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues transcripts detectable by or according to Z25299seg20 amplicon (SEQ ID NO: 1294) and primers: Z25299seg20F (SEQ ID NO: 1294) and Z25299seg20R (SEQ ID NO: 1294) was measured by real time PCR. In parallel the expression of four housekeeping genes —RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon (SEQ ID NO: 1267)), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon-Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon (SEQ ID NO: 1273)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2, “Tissue samples on normal panel”), to obtain a value of relative expression of each sample relative to median of the ovary samples.

Forward primer (SEQ ID NO: 1292):

CTCCTGAACCCTACTCCAAGCA

Reverse primer (SEQ ID NO: 1293):

CAGGCGATCCTATGGAAATCC

Amplicon (SEQ ID NO: 1294):

CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCCTTGTCCTTC

AAGAGAACTGTTCTCCAGGTCTCAGGGCCAGGATTTCCATAGGATCGCCT

G

The results are demonstrated in FIG. 22, showing the expression of Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues Z25299 transcripts which are detectable by amplicon as depicted in sequence name Z25299seg20 (SEQ ID NO: 1294) in different normal tissues.

Description for Cluster HUMF5A

Cluster HUMF5A features 3 transcript(s) and 33 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMF5A_PEA_1_T1
33

HUMF5A_PEA_1_T3
34

HUMF5A_PEA_1_T7
35

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMF5A_PEA_1_node_0
252

HUMF5A_PEA_1_node_4
253

HUMF5A_PEA_1_node_6
254

HUMF5A_PEA_1_node_8
255

HUMF5A_PEA_1_node_10
256

HUMF5A_PEA_1_node_12
257

HUMF5A_PEA_1_node_14
258

HUMF5A_PEA_1_node_18
259

HUMF5A_PEA_1_node_21
260

HUMF5A_PEA_1_node_22
261

HUMF5A_PEA_1_node_24
262

HUMF5A_PEA_1_node_26
263

HUMF5A_PEA_1_node_27
264

HUMF5A_PEA_1_node_29
265

HUMF5A_PEA_1_node_35
266

HUMF5A_PEA_1_node_37
267

HUMF5A_PEA_1_node_39
268

HUMF5A_PEA_1_node_47
269

HUMF5A_PEA_1_node_50
270

HUMF5A_PEA_1_node_53
271

HUMF5A_PEA_1_node_56
272

HUMF5A_PEA_1_node_60
273

HUMF5A_PEA_1_node_2
274

HUMF5A_PEA_1_node_16
275

HUMF5A_PEA_1_node_31
276

HUMF5A_PEA_1_node_32
277

HUMF5A_PEA_1_node_33
278

HUMF5A_PEA_1_node_41
279

HUMF5A_PEA_1_node_43
280

HUMF5A_PEA_1_node_45
281

HUMF5A_PEA_1_node_51
282

HUMF5A_PEA_1_node_57
283

HUMF5A_PEA_1_node_59
284

TABLE 3

Proteins of interest

SEQ

Protein Name
ID NO:
Corresponding Transcript(s)

HUMF5A_PEA_1_P3
564
HUMF5A_PEA_1_T1 (SEQ ID

NO: 33)

HUMF5A_PEA_1_P4
565
HUMF5A_PEA_1_T3 (SEQ ID

NO: 34)

HUMF5A_PEA_1_P8
566
HUMF5A_PEA_1_T7 (SEQ ID

NO: 35)

These sequences are variants of the known protein Coagulation factor V precursor (SwissProt accession identifier FA5_HUMAN; known also according to the synonyms Activated protein C cofactor), SEQ ID NO: 626, referred to herein as the previously known protein.

Protein Coagulation factor V precursor (SEQ ID NO:626) is known or believed to have the following function(s): Coagulation factor V is a cofactor that participates with factor Xa to activate prothrombin to thrombin. The sequence for protein Coagulation factor V precursor is given at the end of the application, as “Coagulation factor V precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s)

on amino

acid sequence
Comment

107
D -> H (in dbSNP: 6019). /FTId = VAR_013886.

334
R -> G (in APCR; Hong Kong). /FTId = VAR_013620.

334
R -> T (in APCR; Cambridge). /FTId = VAR_013621.

413
M -> T (in dbSNP: 6033). /FTId = VAR_013887.

513
R -> K (in dbSNP: 6020). /FTId = VAR_013622.

534
R -> Q (in APCR; Leiden; dbSNP: 6025).

/FTId = VAR_001213.

809
P -> S (in dbSNP: 6031). /FTId = VAR_013888.

817
N -> T (in dbSNP: 6018). /FTId = VAR_013889.

858
K -> R (in dbSNP: 4524). /FTId = VAR_001214.

865
H -> R (in dbSNP: 4525). /FTId = VAR_001215.

925
K -> E (in dbSNP: 6032). /FTId = VAR_013890.

1146
H -> Q (in dbSNP: 6005). /FTId = VAR_013891.

1285
L -> I (in dbSNP: 1046712). /FTId = VAR_013892.

1327
H -> R (in dbSNP: 1800595). /FTId = VAR_013893.

1530
E -> A (in dbSNP: 6007). /FTId = VAR_013894.

1685
T -> S (in dbSNP: 6011). /FTId = VAR_013895.

1749
L -> V (in dbSNP: 6034). /FTId = VAR_013896.

1764
V -> M (in dbSNP: 6030). /FTId = VAR_013897.

1820
M -> I (in dbSNP: 6026). /FTId = VAR_013898.

2102
R -> H (in APCR). /FTId = VAR_017329.

2222
D -> G (in dbSNP: 6027). /FTId = VAR_013899.

2213
T -> A

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cell adhesion; blood coagulation, which are annotation(s) related to Biological Process; and blood coagulation factor; copper binding, which are annotation(s) related to Molecular Function.

As noted above, cluster HUMF5A features 3 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Coagulation factor V precursor (SEQ ID NO:626). A description of each variant protein according to the present invention is now provided.

Variant protein HUMF5A_PEA_—1_P3 (SEQ ID NO:564) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMF5A_PEA_—1_T1 (SEQ ID NO:33). An alignment is given to the known protein (Coagulation factor V precursor (SEQ ID NO:626)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMF5A_PEA_—1_P3 (SEQ ID NO:564) and FA5_HUMAN_V1 (SEQ ID NO 627):

1. An isolated chimeric polypeptide encoding for HUMF5A_PEA_—1_P3 (SEQ ID NO:564), comprising a first amino acid sequence being at least 90% homologous to MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLSVTSFKKIVYREY EPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDA VAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLL FAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVS AITLVSATSTTANMTVGPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRREMKRWEYFIA AEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNPNMKEDGILGPIIRA QVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTEN DAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCE NPDEVKRDDPKFYESNIMSTINGYVPESITTLGFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTL TLFPMRGESVTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPESTVMATRKMHD RLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEEFNLTALALENGTEFVSSNTDIIVGSNYSSPSNIS KFTVNNLAEPQKAPSHQQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLLSLGAGEF RSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGSPSGMRPWEDLPSQDTGSPSRMRPWK DPPSDLLLLKQSNSSKILVGRWHLASEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQS GHPKFPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHPLRSEAYNTFSERRLKHS LVLHKSNETSLPTDLNQTLPSMDFGWIASLPDHNQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQM HSTSDPSHRSSSPELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELSQTNLSPDLSHTT LSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLSLDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLS LDFSQTNLSPELSHMTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSPALGQMPLSP DPSHTTLSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQIPLTPDLDQMTLSPDLGETDLSPNFGQMSLSPD LSQVTLSPDISDTTLLPDLSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLNDTFLSKEF NPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPYKTDVRTNINSSRDPDNIAAWYLRSNNGNR RNYYIAAEEISWDYSEFVQRETDIEDSDDIPEDTTYKK corresponding to amino acids 1-1617 of FA5_HUMAN_V1 (SEQ ID NO:627), which also corresponds to amino acids 1-1617 of HUMF5A_PEA_—1_P3 (SEQ ID NO:564), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GSMKSISEFLVLLSELKWMMLSKFVLKI (SEQ ID NO:1506) corresponding to amino acids 1618-1645 of HUMF5A_PEA_—1_P3 (SEQ ID NO:564), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMF5A_PEA_—1_P3 (SEQ ID NO:564), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GSMKSISEFLVLLSELKWMMLSKFVLKI (SEQ ID NO:1506) in HUMF5A_PEA_—1_P3 (SEQ ID NO:564).

It should be noted that the known protein sequence (FA5_HUMAN (SEQ ID NO:626)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for FA5_HUMAN_V1 (SEQ ID NO:627). These changes were previously known to occur and are listed in the table below.

TABLE 5

Changes to FA5_HUMAN_V1 (SEQ ID NO: 627)

SNP position(s) on amino

acid sequence
Type of change

859
variant

866
variant

Variant protein HUMF5A_PEA_—1_P3 (SEQ ID NO:564) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_—1_P3 (SEQ ID NO:564) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

15
G -> S
Yes

107
D -> H
Yes

413
M -> T
Yes

513
R -> K
Yes

534
R -> Q
Yes

781
S -> R
Yes

809
P -> S
Yes

817
N -> T
Yes

858
R -> K
Yes

865
R -> H
Yes

915
T -> S
Yes

925
K -> E
Yes

969
N -> S
Yes

980
R -> L
Yes

1146
H -> Q
Yes

1169
D ->
No

1285
L -> I
Yes

1327
H -> R
Yes

1397
L -> F
Yes

1404
P -> S
Yes

1530
E -> A
Yes

Variant protein HUMF5A_PEA_—1_P3 (SEQ ID NO:564) is encoded by the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMF5A_PEA_—1_T1 (SEQ ID NO:33) is shown in bold; this coding portion starts at position 183 and ends at position 5117. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_—1_P3 (SEQ ID NO:564) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

16
C -> T
Yes

225
G -> A
Yes

419
A -> G
Yes

501
G -> C
Yes

587
G -> A
Yes

734
G -> T
Yes

746
G -> C
Yes

951
C -> T
Yes

998
C -> T
Yes

1420
T -> C
Yes

1424
A -> G
Yes

1562
C -> T
Yes

1720
G -> A
Yes

1783
G -> A
Yes

1898
G -> A
Yes

2102
C -> T
Yes

2108
C -> A
Yes

2390
T -> C
Yes

2417
C -> T
Yes

2471
A -> G
Yes

2483
G -> A
Yes

2525
T -> G
Yes

2607
C -> T
Yes

2632
A -> C
Yes

2755
G -> A
Yes

2776
G -> A
Yes

2925
A -> T
Yes

2955
A -> G
Yes

3088
A -> G
Yes

3121
G -> T
Yes

3437
A -> G
Yes

3620
C -> G
Yes

3686
A -> C
Yes

3688
A ->
No

3689
T ->
No

3764
C -> T
Yes

3986
T -> C
Yes

4035
C -> A
Yes

4130
C -> T
Yes

4162
A -> G
Yes

4277
C -> T
Yes

4371
C -> T
Yes

4392
C -> T
Yes

4771
A -> C
Yes

5152
A -> G
Yes

5184
C -> G
Yes

5375
C -> G
Yes

5420
G -> A
Yes

5590
G -> A
Yes

6573
T -> C
Yes

6684
A -> G
Yes

6795
A -> G
Yes

Variant protein HUMF5A_PEA_—1_P4 (SEQ ID NO:565) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMF5A_PEA_—1_T3 (SEQ ID NO:34). An alignment is given to the known protein (Coagulation factor V precursor (SEQ ID NO:626)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMF5A_PEA_—1_P4 (SEQ ID NO:565) and FA5_HUMAN_V1 (SEQ ID NO:627):

1. An isolated chimeric polypeptide encoding for HUMF5A_PEA_—1_P4 (SEQ ID NO:565), comprising a first amino acid sequence being at least 90% homologous to MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLSVTSFKKIVYREY EPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDA VAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLL FAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVS AITLVSATSTTANMTVGPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFIA AEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNPNMKEDGILGPIIRA QVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTEN DAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCE NPDEVKRDDPKFYESNIMSTINGYVPESITTLGFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTL TLFPMRGESVTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPESTVMATRKMHD RLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEEFNLTALALENGTEFVSSNTDIIVGSNYSSPSNIS KFTVNNLAEPQKAPSHQQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLLSLGAGEF RSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGSPSGMRPWEDLPSQDTGSPSRMRPWK DPPSDLLLLKQSNSSKILVGRWHLASEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQS GHPKFPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHPLRSEAYNTFSERRLKHS LVLHKSNETSLPTDLNQTLPSMDFGWIASLPDHNQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQM HSTSDPSHRSSSPELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELSQTNLSPDLSHTT LSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLSLDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLS LDFSQTNLSPELSHMTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSPALGQMPLSP DPSHTTLSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQIPLTPDLDQMTLSPDLGETDLSPNFGQMSLSPD LSQVTLSPDISDTTLLPDLSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLNDTFLSKEF NPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPYKTDVRTNINSSRDPDNIAAWYLRSNNGNR RNYYIAAEEISWDYSEFVQRETDIEDSDDIPEDTTYKKVVFRKYLDSTFTKRDPRGEYEEHLGILGPIIRAEV DDVIQVRFKNLASRPYSLHAHGLSYEKSSEGKTYEDDSPEWFKEDNAVQPNSSYTYVWHATERSGPESPG SACRAWAYYSAVNPEKDIHSGLIGPLLICQKGILHKDSNMPVDMREFVLLFMTFDEKKSWYYEKKSRSSW RLTSSEMKKSHEFHAINGMIYSLPGLKMYEQEWVRLHLLNIGGSQDIHVVHFHGQTLLENGNKQHQLGV WPLLPGSFKTLEMKASKPGWWLLNTEVGENQRAGMQTPFLIMDRDCRMPMGLSTGIISDSQIKASEFLGY WEPRLARLNNGGSYNAWSVEKLAAEFASKPWIQVDMQKEVIITGIQTQGAKHYLKSCYTTEFYVAYSSN QINWQIFKGNSTRNVMYFNGNSDASTIKENQFDPPIVARYIRISPTRAYNRPTLRLELQGCE corresponding to amino acids 1-2062 of FA5_HUMAN_V1 (SEQ ID NO:627), which also corresponds to amino acids 1-2062 of HUMF5A_PEA_—1_P4 (SEQ ID NO:565), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVPHPWVWKMER (SEQ ID NO:1507) corresponding to amino acids 2063-2074 of HUMF5A_PEA_—1_P4 (SEQ ID NO:565), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMF5A_PEA_—1_P4 (SEQ ID NO:565), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVPHPWVWKMER (SEQ ID NO:1507) in HUMF5A_PEA_—1_P4 (SEQ ID NO:565).

TABLE 8

Changes to FA5_HUMAN_V1 (SEQ ID NO: 627)

SNP position(s) on amino

acid sequence
Type of change

859
variant

866
variant

Variant protein HUMF5A_PEA_—1_P4 (SEQ ID NO:565) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_—1_P4 (SEQ ID NO:565) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

15
G -> S
Yes

107
D -> H
Yes

413
M -> T
Yes

513
R -> K
Yes

534
R -> Q
Yes

781
S -> R
Yes

809
P -> S
Yes

817
N -> T
Yes

858
R -> K
Yes

865
R -> H
Yes

915
T -> S
Yes

925
K -> E
Yes

969
N -> S
Yes

980
R -> L
Yes

1146
H -> Q
Yes

1169
D ->
No

1285
L -> I
Yes

1327
H -> R
Yes

1397
L -> F
Yes

1404
P -> S
Yes

1530
E -> A
Yes

1685
T -> S
Yes

1749
L -> V
Yes

1764
V -> M
Yes

1820
M -> I
Yes

Variant protein HUMF5A_PEA_—1_P4 (SEQ ID NO:565) is encoded by the following transcript(s): HUMF5A_PEA_—1_T3 (SEQ ID NO:34), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMF5A_PEA_—1_T3 (SEQ ID NO:34) is shown in bold; this coding portion starts at position 183 and ends at position 6404. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_—1_P4 (SEQ ID NO:565) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

16
C -> T
Yes

225
G -> A
Yes

419
A -> G
Yes

501
G -> C
Yes

587
G -> A
Yes

734
G -> T
Yes

746
G -> C
Yes

951
C -> T
Yes

998
C -> T
Yes

1420
T -> C
Yes

1424
A -> G
Yes

1562
C -> T
Yes

1720
G -> A
Yes

1783
G -> A
Yes

1898
G -> A
Yes

2102
C -> T
Yes

2108
C -> A
Yes

2390
T -> C
Yes

2417
C -> T
Yes

2471
A -> G
Yes

2483
G -> A
Yes

2525
T -> G
Yes

2607
C -> T
Yes

2632
A -> C
Yes

2755
G -> A
Yes

2776
G -> A
Yes

2925
A -> T
Yes

2955
A -> G
Yes

3088
A -> G
Yes

3121
G -> T
Yes

3437
A -> G
Yes

3620
C -> G
Yes

3686
A -> C
Yes

3688
A ->
No

3689
T ->
No

3764
C -> T
Yes

3986
T -> C
Yes

4035
C -> A
Yes

4130
C -> T
Yes

4162
A -> G
Yes

4277
C -> T
Yes

4371
C -> T
Yes

4392
C -> T
Yes

4771
A -> C
Yes

5204
A -> G
Yes

5236
C -> G
Yes

5427
C -> G
Yes

5472
G -> A
Yes

5642
G -> A
Yes

6618
T -> C
Yes

6729
A -> G
Yes

6840
A -> G
Yes

Variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMF5A_PEA_—1_T7 (SEQ ID NO:35). An alignment is given to the known protein (Coagulation factor V precursor (SEQ ID NO:626)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMF5A_PEA_—1_P8 (SEQ ID NO:566) and FA5_HUMAN (SEQ ID NO:626):

1. An isolated chimeric polypeptide encoding for HUMF5A_PEA_—1_P8 (SEQ ID NO:566), comprising a first amino acid sequence being at least 90% homologous to MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLSVTSFKKIVYREY EPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDA VAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLL FAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVS AITLVSATSTTANMTVGPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFIA AEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNPNMKEDGILGPIIRA QVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTEN DAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCE NPDEVKRDDPKFYESNIMS corresponding to amino acids 1-587 of FA5_HUMAN (SEQ ID NO:626), which also corresponds to amino acids 1-587 of HUMF5A_PEA_—1_P8 (SEQ ID NO:566), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SKSEYYFCSSVFHSCG (SEQ ID NO:1508) corresponding to amino acids 588-603 of HUMF5A_PEA_—1_P8 (SEQ ID NO:566), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMF5A_PEA_—1_P8 (SEQ ID NO:566), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SKSEYYFCSSVFHSCG (SEQ ID NO:1508) in HUMF5A_PEA_—1_P8 (SEQ ID NO:566).

Variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

15
G -> S
Yes

107
D -> H
Yes

413
M -> T
Yes

513
R -> K
Yes

534
R -> Q
Yes

The glycosylation sites of variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566), as compared to the known protein Coagulation factor V precursor (SEQ ID NO:626), are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 12

Glycosylation site(s)

Position(s) on known amino
Present in
Position

acid sequence
variant protein?
in variant protein?

821
no

554
yes
554

1703
no

741
no

55
yes
55

297
yes
297

752
no

468
yes
468

460
yes
460

1559
no

782
no

1479
no

938
no

776
no

760
no

1103
no

1499
no

1106
no

977
no

2010
no

239
yes
239

1074
no

2209
no

1083
no

51
yes
51

382
yes
382

The phosphorylation sites of variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566), as compared to the known protein Coagulation factor V precursor (SEQ ID NO:626), are described in Table 13 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 13

Phosphorylation site(s)

Position(s) on known amino acid

sequence
Present in variant protein?

724
no

726
no

1543
no

1538
no

693
no

1593
no

1522
no

Variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566) is encoded by the following transcript(s): HUMF5A_PEA_—1_T7 (SEQ ID NO:35), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMF5A_PEA_—1_T7 (SEQ ID NO:35) is shown in bold; this coding portion starts at position 183 and ends at position 1991. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_—1_P8 (SEQ ID NO:566) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

16
C -> T
Yes

225
G -> A
Yes

419
A -> G
Yes

501
G -> C
Yes

587
G -> A
Yes

734
G -> T
Yes

746
G -> C
Yes

951
C -> T
Yes

998
C -> T
Yes

1420
T -> C
Yes

1424
A -> G
Yes

1562
C -> T
Yes

1720
G -> A
Yes

1783
G -> A
Yes

1898
G -> A
Yes

2088
G -> A
Yes

2095
G -> A
Yes

As noted above, cluster HUMF5A features 33 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMF5A_PEA_—1_node_—0 (SEQ ID NO:252) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1
340

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1
340

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1
340

Segment cluster HUMF5A_PEA_—1_node_—4 (SEQ ID NO:253) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
433
555

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
433
555

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
433
555

Segment cluster HUMF5A_PEA_—1_node_—6 (SEQ ID NO:254) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
556
768

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
556
768

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
556
768

Segment cluster HUMF5A_PEA_—1_node_—8 (SEQ ID NO:255) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
769
912

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
769
912

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
769
912

Segment cluster HUMF5A_PEA_—1_node_—10 (SEQ ID NO:256) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
913
1134

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
913
1134

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
913
1134

Segment cluster HUMF5A_PEA_—1_node_—12 (SEQ ID NO:257) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1135
1300

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1135
1300

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1135
1300

Segment cluster HUMF5A_PEA_—1_node_—14 (SEQ ID NO:258) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1301
1478

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1301
1478

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1301
1478

Segment cluster HUMF5A_PEA_—1_node_—18 (SEQ ID NO:259) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1579
1793

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1579
1793

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1579
1793

Segment cluster HUMF5A_PEA_—1_node_—21 (SEQ ID NO:260) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1794
1944

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1794
1944

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1794
1944

Segment cluster HUMF5A_PEA_—1_node_—22 (SEQ ID NO:261) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1945
2097

Segment cluster HUMF5A_PEA_—1_node_—24 (SEQ ID NO:262) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1945
2157

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1945
2157

Segment cluster HUMF5A_PEA_—1_node_—26 (SEQ ID NO:263) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
2158
3766

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
2158
3766

Segment cluster HUMF5A_PEA_—1_node_—27 (SEQ ID NO:264) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
3767
3936

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
3767
3936

Segment cluster HUMF5A_PEA_—1_node_—29 (SEQ ID NO:265) according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
3937
4978

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
3937
4978

Segment cluster HUMF5A_PEA_—1_node_—35 (SEQ ID NO:266) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5102
5338

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5154
5390

Segment cluster HUMF5A_PEA_—1_node_—37 (SEQ ID NO:267) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5339
5549

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5391
5601

Segment cluster HUMF5A_PEA_—1_node_—39 (SEQ ID NO:268) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5550
5729

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5602
5781

Segment cluster HUMF5A_PEA_—1_node_—47 (SEQ ID NO:269) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6023
6178

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6075
6230

Segment cluster HUMF5A_PEA_—1_node_—50 (SEQ ID NO:270) according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6179
6316

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6231
6368

Segment cluster HUMF5A_PEA_—1_node_—53 (SEQ ID NO:271) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6324
6475

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6369
6520

Segment cluster HUMF5A_PEA_—1_node_—56 (SEQ ID NO:272) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6476
6611

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6521
6656

Segment cluster HUMF5A_PEA_—1_node_—60 (SEQ ID NO:273) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6666
6951

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6711
6996

Segment cluster HUMF5A_PEA_—1_node_—2 (SEQ ID NO:274) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
341
432

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
341
432

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
341
432

Segment cluster HUMF5A_PEA_—1_node_—16 (SEQ ID NO:275) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33), HUMF5A_PEA_—1_T3 (SEQ ID NO:34) and HUMF5A_PEA_—1_T7 (SEQ ID NO:35). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
1479
1578

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
1479
1578

HUMF5A_PEA_1_T7 (SEQ ID NO: 35)
1479
1578

Segment cluster HUMF5A_PEA_—1_node_—31 (SEQ ID NO:276) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
4979
5033

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
4979
5033

Segment cluster HUMF5A_PEA_—1_node_—32 (SEQ ID NO:277) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5034
5085

Segment cluster HUMF5A_PEA_—1_node_—33 (SEQ ID NO:278) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5034
5101

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5086
5153

Segment cluster HUMF5A_PEA_—1_node_—41 (SEQ ID NO:279) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5730
5846

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5782
5898

Segment cluster HUMF5A_PEA_—1_node_—43 (SEQ ID NO:280) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5847
5918

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5899
5970

Segment cluster HUMF5A_PEA_—1_node_—45 (SEQ ID NO:281) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
5919
6022

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
5971
6074

Segment cluster HUMF5A_PEA_—1_node_—51 (SEQ ID NO:282) according to the present invention can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMF5A_PEA_1_T1
6317
6323

(SEQ ID NO: 33)

Segment cluster HUMF5A_PEA_—1_node_—57 (SEQ ID NO:283) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6612
6658

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6657
6703

Segment cluster HUMF5A_PEA_—1_node_—59 (SEQ ID NO:284) according to the present invention can be found in the following transcript(s): HUMF5A_PEA_—1_T1 (SEQ ID NO:33) and HUMF5A_PEA_—1_T3 (SEQ ID NO:34). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

HUMF5A_PEA_1_T1 (SEQ ID NO: 33)
6659
6665

HUMF5A_PEA_1_T3 (SEQ ID NO: 34)
6704
6710

Variant Protein Alignment to the Previously Known Protein:

PBGD-amplicon, SEQ ID NO:531HPRT1-amplicon, SEQ ID NO:612HPRT1-amplicon, SEQ ID NO:615RPS27A amplicon, SEQ ID NO:1261

Description for Cluster HUMANK

Cluster HUMANK features 8 transcript(s) and 22 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMANK_T3
36

HUMANK_T13
37

HUMANK_T23
38

HUMANK_T24
39

HUMANK_T26
40

HUMANK_T27
41

HUMANK_T28
42

HUMANK_T35
43

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMANK_node_91
285

HUMANK_node_92
286

HUMANK_node_93
287

HUMANK_node_100
288

HUMANK_node_108
289

HUMANK_node_113
290

HUMANK_node_115
291

HUMANK_node_117
292

HUMANK_node_119
293

HUMANK_node_120
294

HUMANK_node_94
295

HUMANK_node_95
296

HUMANK_node_98
297

HUMANK_node_99
298

HUMANK_node_102
299

HUMANK_node_103
300

HUMANK_node_104
301

HUMANK_node_105
302

HUMANK_node_106
303

HUMANK_node_112
304

HUMANK_node_114
305

HUMANK_node_116
306

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HUMANK_P12
567
HUMANK_T13 (SEQ ID NO: 37)

HUMANK_P21
568
HUMANK_T26 (SEQ ID NO: 40)

HUMANK_P22
569
HUMANK_T27 (SEQ ID NO: 41)

HUMANK_P23
570
HUMANK_T28 (SEQ ID NO: 42)

HUMANK_P27
571
HUMANK_T35 (SEQ ID NO: 43)

HUMANK_P29
572
HUMANK_T3 (SEQ ID NO: 36)

HUMANK_P33
573
HUMANK_T23 (SEQ ID NO: 38)

HUMANK_P34
574
HUMANK_T24 (SEQ ID NO: 39)

These sequences are variants of the known protein Ankyrin 1 (SwissProt accession identifier ANK1_HUMAN; known also according to the synonyms Erythrocyte ankyrin; Ankyrin R), SEQ ID NO: 628, referred to herein as the previously known protein.

Protein Ankyrin 1 (SEQ ID NO:628) is known or believed to have the following function(s): Attach integral membrane proteins to cytoskeletal elements; bind to the erythrocyte membrane protein band 4.2, to Na—K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. The sequence for protein Ankyrin 1 is given at the end of the application, as “Ankyrin 1 amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s)

on amino

acid sequence
Comment

20
R -> T. /FTId = VAR_000595.

462
V -> I (in HS). /FTId = VAR_000596.

618
R -> H (in Brueggen). /FTId = VAR_000597.

749
V -> A. /FTId = VAR_000598.

844
D -> E. /FTId = VAR_000599.

1285
E -> D. /FTId = VAR_000601.

1391
S -> T. /FTId = VAR_000600.

1591
D -> N (in Duesseldorf). /FTId = VAR_000602.

1698
R -> D. /FTId = VAR_000603.

229
A -> S

1545
V -> I

Protein Ankyrin 1 (SEQ ID NO:628) localization is believed to be Cytoplasmic surface of erythrocytic plasma membrane.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: exocytosis; cytoskeleton organization and biogenesis; signal transduction, which are annotation(s) related to Biological Process; structural protein; structural protein of cytoskeleton; cytoskeletal adaptor, which are annotation(s) related to Molecular Function; and cytoskeleton; plasma membrane; actin cytoskeleton; basolateral plasma membrane, which are annotation(s) related to Cellular Component.

Cluster HUMANK can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 23 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

Bladder
0

Brain
41

Epithelial
2

General
20

head and neck
0

Kidney
0

bone marrow
62

Muscle
225

Ovary
0

Pancreas
4

prostate
8

uterus
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
5.4e−01
6.0e−01
5.6e−01
1.8
6.8e−01
1.5

brain
8.9e−01
8.9e−01
1
0.1
1
0.2

epithelial
1.0e−01
1.7e−01
1.8e−03
3.8
1.8e−02
2.6

general
9.1e−01
9.5e−01
9.3e−01
0.5
1
0.4

head and neck
4.3e−01
2.8e−01
1
1.1
7.5e−01
1.4

kidney
6.5e−01
7.2e−01
5.8e−01
1.7
7.0e−01
1.4

bone marrow
7.1e−01
8.4e−01
1
0.3
9.0e−01
0.6

muscle
5.4e−01
6.2e−01
1
0.1
1
0.2

ovary
3.8e−01
4.2e−01
6.9e−02
2.4
1.6e−01
1.9

pancreas
5.5e−01
2.0e−01
4.2e−01
1.7
1.5e−01
2.6

prostate
9.1e−01
9.3e−01
6.7e−01
1.1
7.5e−01
1.0

uterus
4.7e−01
6.4e−01
6.6e−01
1.5
8.0e−01
1.2

As noted above, cluster HUMANK features 8 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ankyrin 1 (SEQ ID NO:628). A description of each variant protein according to the present invention is now provided.

Variant protein HUMANK_P12 (SEQ ID NO:567) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T13 (SEQ ID NO:37). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P12 (SEQ ID NO:567) and AAH07930 (SEQ ID NO 631):

1. An isolated chimeric polypeptide encoding for HUMANK_P12 (SEQ ID NO:567), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 1-123 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-123 of HUMANK_P12 (SEQ ID NO:567), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP (SEQ ID NO:1509) corresponding to amino acids 124-156 of HUMANK_P12 (SEQ ID NO:567), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P12 (SEQ ID NO:567), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP (SEQ ID NO:1509) in HUMANK_P12 (SEQ ID NO:567).

Comparison Report Between HUMANK_P12 (SEQ ID NO:567) and ANK1_HUMAN_V1 (SEQ ID NO 629):

1. An isolated chimeric polypeptide encoding for HUMANK_P12 (SEQ ID NO:567), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LK (SEQ ID NO:1510) corresponding to amino acids 1-73 of HUMANK_P12 (SEQ ID NO:567), and a second amino acid sequence being at least 90% homologous to GNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEEVTVEGPLEDPSELEVDIDYFMK HSKDHTSTPNP (SEQ ID NO:1509) corresponding to amino acids 1799-1881 of ANK1_HUMAN_V1 (SEQ ID NO:629), which also corresponds to amino acids 74-156 of HUMANK_P12 (SEQ ID NO:567), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of HUMANK_P12 (SEQ ID NO:567), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LK (SEQ ID NO:1510) of HUMANK_P12 (SEQ ID NO:567).

It should be noted that the known protein sequence (ANK1_HUMAN (SEQ ID NO:628)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for ANK1_HUMAN_V1 (SEQ ID NO:629). These changes were previously known to occur and are listed in the table below.

TABLE 7

Changes to ANK1_HUMAN_V1 (SEQ ID NO: 629)

SNP position(s) on amino

acid sequence
Type of change

1
init_met

Comparison Report Between HUMANK_P12 (SEQ ID NO:567) and Q8N604 (SEQ ID NO: 630):

1. An isolated chimeric polypeptide encoding for HUMANK_P12 (SEQ ID NO:567), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P12 (SEQ ID NO:567), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P12 (SEQ ID NO:567), a second amino acid sequence being at least 90% homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEEV corresponding to amino acids 54-124 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-124 of HUMANK_P12 (SEQ ID NO:567), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP corresponding to amino acids 125-156 of HUMANK_P12 (SEQ ID NO:567), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P12 (SEQ ID NO:567), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP in HUMANK_P12 (SEQ ID NO:567).

Variant protein HUMANK_P12 (SEQ ID NO:567) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P12 (SEQ ID NO:567) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

12
L -> P
No

63
T -> P
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P12 (SEQ ID NO:567) is encoded by the following transcript(s): HUMANK_T13 (SEQ ID NO:37), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T13 (SEQ ID NO:37) is shown in bold; this coding portion starts at position 2053 and ends at position 2520. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P12 (SEQ ID NO:567) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2533
-> C
No

2533
-> T
No

2733
A ->
No

2733
A -> C
No

2742
A -> C
No

2772
A -> C
No

2796
A ->
No

2796
A -> C
No

2890
C -> T
No

3305
-> G
No

3306
-> C
No

4118
T -> A
Yes

4175
-> T
No

4228
G ->
No

4603
G -> T
Yes

5012
T ->
No

Variant protein HUMANK_P21 (SEQ ID NO:568) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T26 (SEQ ID NO:40). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P21 (SEQ ID NO:568) and AAH07930 (SEQ ID NO: 631):

1. An isolated chimeric polypeptide encoding for HUMANK_P21 (SEQ ID NO:568), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 1-123 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-123 of HUMANK_P21 (SEQ ID NO:568), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1511) corresponding to amino acids 124-169 of HUMANK_P21 (SEQ ID NO:568), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P21 (SEQ ID NO:568), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VTVEGPLEDPSELEVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1511) in HUMANK_P21 (SEQ ID NO:568).

Comparison Report Between HUMANK_P21 (SEQ ID NO:568) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P21 (SEQ ID NO:568), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P21 (SEQ ID NO:568), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P21 (SEQ ID NO:568), a second amino acid sequence being at least 90% homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHE corresponding to amino acids 54-122 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-122 of HUMANK_P21 (SEQ ID NO:568), a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EVTVEGPLEDPSEL (SEQ ID NO:1512) corresponding to amino acids 123-136 of HUMANK_P21 (SEQ ID NO:568), and a fourth amino acid sequence being at least 90% homologous to EVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 123-155 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 137-169 of HUMANK_P21 (SEQ ID NO:568), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of HUMANK_P21 (SEQ ID NO:568), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for EVTVEGPLEDPSEL (SEQ ID NO:1512), corresponding to HUMANK_P21 (SEQ ID NO:568).

Variant protein HUMANK_P21 (SEQ ID NO:568) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P21 (SEQ ID NO:568) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

12
L -> P
No

63
T -> P
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P21 (SEQ ID NO:568) is encoded by the following transcript(s): HUMANK_T26 (SEQ ID NO:40), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T26 (SEQ ID NO:40) is shown in bold; this coding portion starts at position 2053 and ends at position 2559. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P21 (SEQ ID NO:568) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2635
-> C
No

2635
-> T
No

2835
A ->
No

2835
A -> C
No

2844
A -> C
No

2874
A -> C
No

2898
A ->
No

2898
A -> C
No

2992
C -> T
No

3407
-> G
No

3408
-> C
No

4220
T -> A
Yes

4277
-> T
No

4330
G ->
No

4705
G -> T
Yes

5114
T ->
No

Variant protein HUMANK_P22 (SEQ ID NO:569) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T27 (SEQ ID NO:41). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P22 (SEQ ID NO:569) and AAH07930 (SEQ ID NO:631):

1. An isolated chimeric polypeptide encoding for HUMANK_P22 (SEQ ID NO:569), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 1-123 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-123 of HUMANK_P22 (SEQ ID NO:569), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVDIDYFMKHSKVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1513) corresponding to amino acids 124-180 of HUMANK_P22 (SEQ ID NO:569), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P22 (SEQ ID NO:569), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VTVEGPLEDPSELEVDIDYFMKHSKVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1513) in HUMANK_P22 (SEQ ID NO:569).

Comparison Report Between HUMANK_P22 (SEQ ID NO:569) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P22 (SEQ ID NO:569), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P22 (SEQ ID NO:569), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P22 (SEQ ID NO:569), a second amino acid sequence being at least 90% homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 54-123 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-123 of HUMANK_P22 (SEQ ID NO:569), a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVDIDYFMKHSK (SEQ ID NO:1514) corresponding to amino acids 124-148 of HUMANK_P22 (SEQ ID NO:569), and a fourth amino acid sequence being at least 90% homologous to VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1517) corresponding to amino acids 124-155 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 149-180 of HUMANK_P22 (SEQ ID NO:569), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of HUMANK_P22 (SEQ ID NO:569), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for VTVEGPLEDPSELEVDIDYFMKHSK (SEQ ID NO:1514), corresponding to HUMANK_P22 (SEQ ID NO:569).

Variant protein HUMANK_P22 (SEQ ID NO:569) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P22 (SEQ ID NO:569) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

12
L -> P
No

63
T -> P
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P22 (SEQ ID NO:569) is encoded by the following transcript(s): HUMANK_T27 (SEQ ID NO:41), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T27 (SEQ ID NO:41) is shown in bold; this coding portion starts at position 2053 and ends at position 2592. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P22 (SEQ ID NO:569) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2668
-> C
No

2668
-> T
No

2868
A ->
No

2868
A -> C
No

2877
A -> C
No

2907
A -> C
No

2931
A ->
No

2931
A -> C
No

3025
C -> T
No

3440
-> G
No

3441
-> C
No

4253
T -> A
Yes

4310
-> T
No

4363
G ->
No

4738
G -> T
Yes

5147
T ->
No

Variant protein HUMANK_P23 (SEQ ID NO:570) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T28 (SEQ ID NO:42). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P23 (SEQ ID NO:570) and AAH07930 (SEQ ID NO:631):

1. An isolated chimeric polypeptide encoding for HUMANK_P23 (SEQ ID NO:570), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LKGNEFQNIPGEQVTEEQFTDEQGNUVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 1-123 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-123 of HUMANK_P23 (SEQ ID NO:570), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEDHTSTPNP (SEQ ID NO:1515) corresponding to amino acids 124-145 of HUMANK_P23 (SEQ ID NO:570), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P23 (SEQ ID NO:570), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VTVEGPLEDPSELEDHTSTPNP (SEQ ID NO:1515) in HUMANK_P23 (SEQ ID NO:570).

Comparison Report Between HUMANK_P23 (SEQ ID NO:570) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P23 (SEQ ID NO:570), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P23 (SEQ ID NO:570), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P23 (SEQ ID NO:570), a second amino acid sequence being at least 90% homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEEV corresponding to amino acids 54-124 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-124 of HUMANK_P23 (SEQ ID NO:570), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TVEGPLEDPSELEDHTSTPNP corresponding to amino acids 125-145 of HUMANK_P23 (SEQ ID NO:570), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P23 (SEQ ID NO:570), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TVEGPLEDPSELEDHTSTPNP in HUMANK_P23 (SEQ ID NO:570).

Variant protein HUMANK_P23 (SEQ ID NO:570) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P23 (SEQ ID NO:570) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

12
L -> P
No

63
T -> P
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P23 (SEQ ID NO:570) is encoded by the following transcript(s): HUMANK_T28 (SEQ ID NO:42), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T28 (SEQ ID NO:42) is shown in bold; this coding portion starts at position 2053 and ends at position 2487. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P23 (SEQ ID NO:570) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2500
-> C
No

2500
-> T
No

2700
A ->
No

2700
A -> C
No

2709
A -> C
No

2739
A -> C
No

2763
A ->
No

2763
A -> C
No

2857
C -> T
No

3272
-> G
No

3273
-> C
No

4085
T -> A
Yes

4142
-> T
No

4195
G ->
No

4570
G -> T
Yes

4979
T ->
No

Variant protein HUMANK_P27 (SEQ ID NO:571) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T35 (SEQ ID NO:43). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P27 (SEQ ID NO:571) and AAH07930 (SEQ ID NO:631):

1. An isolated chimeric polypeptide encoding for HUMANK_P27 (SEQ ID NO:571), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETISTRVVRRRVF LKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 1-101 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-101 of HUMANK_P27 (SEQ ID NO:571), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAECSPLCWGEAGGLEAKRW (SEQ ID NO:1516) corresponding to amino acids 102-122 of HUMANK_P27 (SEQ ID NO:571), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P27 (SEQ ID NO:571), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VGAECSPLCWGEAGGLEAKRW (SEQ ID NO:1516) in HUMANK_P27 (SEQ ID NO:571).

Comparison Report Between HUMANK_P27 (SEQ ID NO:571) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P27 (SEQ ID NO:571), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P27 (SEQ ID NO:571), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P27 (SEQ ID NO:571), a second amino acid sequence being at least 90% homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 54-101 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-101 of HUMANK_P27 (SEQ ID NO:571), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAECSPLCWGEAGGLEAKRW (SEQ ID NO:1516) corresponding to amino acids 102-122 of HUMANK_P27 (SEQ ID NO:571), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

Variant protein HUMANK_P27 (SEQ ID NO:571) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P27 (SEQ ID NO:571) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

12
L -> P
No

63
T -> P
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P27 (SEQ ID NO:571) is encoded by the following transcript(s): HUMANK_T35 (SEQ ID NO:43), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T35 (SEQ ID NO:43) is shown in bold; this coding portion starts at position 2053 and ends at position 2418. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P27 (SEQ ID NO:571) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

Variant protein HUMANK_P29 (SEQ ID NO:572) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T3 (SEQ ID NO:36). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P29 (SEQ ID NO:572) and AAH07930 (SEQ ID NO:631):

1. An isolated chimeric polypeptide encoding for HUMANK_P29 (SEQ ID NO:572), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETIS corresponding to amino acids 1-62 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-62 of HUMANK_P29 (SEQ ID NO:572), a bridging amino acid P corresponding to amino acid 63 of HUMANK_P29 (SEQ ID NO:572), a second amino acid sequence being at least 90% homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 64-123 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 64-123 of HUMANK_P29 (SEQ ID NO:572), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1517) corresponding to amino acids 124-155 of HUMANK_P29 (SEQ ID NO:572), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P29 (SEQ ID NO:572), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1517) in HUMANK_P29 (SEQ ID NO:572).

Comparison Report Between HUMANK_P29 (SEQ ID NO:572) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P29 (SEQ ID NO:572), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P29 (SEQ ID NO:572), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P29 (SEQ ID NO:572), a second amino acid sequence being at least 90% homologous to LSDDEETIS corresponding to amino acids 54-62 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-62 of HUMANK_P29 (SEQ ID NO:572), a bridging amino acid P corresponding to amino acid 63 of HUMANK_P29 (SEQ ID NO:572), and a third amino acid sequence being at least 90% homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEEVELRGSGLQPDL IEGRKGAQIVKRASLKRGKQ corresponding to amino acids 64-155 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 64-155 of HUMANK_P29 (SEQ ID NO:572), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order.

Variant protein HUMANK_P29 (SEQ ID NO:572) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 18, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P29 (SEQ ID NO:572) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

12
L -> P
No

63
P -> T
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P29 (SEQ ID NO:572) is encoded by the following transcript(s): HUMANK_T3 (SEQ ID NO:36), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T3 (SEQ ID NO:36) is shown in bold; this coding portion starts at position 2053 and ends at position 2517. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P29 (SEQ ID NO:572) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2593
-> C
No

2593
-> T
No

2793
A ->
No

2793
A -> C
No

2802
A -> C
No

2832
A -> C
No

2856
A ->
No

2856
A -> C
No

2950
C -> T
No

3242
G -> T
Yes

3244
C -> A
Yes

3245
T -> A
Yes

3246
C -> T
Yes

3379
-> G
No

3380
-> C
No

4192
T -> A
Yes

4249
-> T
No

4302
G ->
No

4677
G -> T
Yes

5086
T ->
No

Variant protein HUMANK_P33 (SEQ ID NO:573) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T23 (SEQ ID NO:38). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P33 (SEQ ID NO:573) and AAH07930 (SEQ ID NO:631):

1. An isolated chimeric polypeptide encoding for HUMANK_P33 (SEQ ID NO:573), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETIS corresponding to amino acids 1-62 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-62 of HUMANK_P33 (SEQ ID NO:573), a bridging amino acid P corresponding to amino acid 63 of HUMANK_P33 (SEQ ID NO:573), a second amino acid sequence being at least 90% homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64-101 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 64-101 of HUMANK_P33 (SEQ ID NO:573), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DHTSTPNP (SEQ ID NO:1518) corresponding to amino acids 102-109 of HUMANK_P33 (SEQ ID NO:573), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P33 (SEQ ID NO:573), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DHTSTPNP (SEQ ID NO:1518) in HUMANK_P33 (SEQ ID NO:573).

Comparison Report Between HUMANK_P33 (SEQ ID NO:573) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P33 (SEQ ID NO:573), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P33 (SEQ ID NO:573), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P33 (SEQ ID NO:573), a second amino acid sequence being at least 90% homologous to LSDDEETIS corresponding to amino acids 54-62 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-62 of HUMANK_P33 (SEQ ID NO:573), a bridging amino acid P corresponding to amino acid 63 of HUMANK_P33 (SEQ ID NO:573), a third amino acid sequence being at least 90% homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64-101 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 64-101 of HUMANK_P33 (SEQ ID NO:573), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DHTSTPNP (SEQ ID NO:1518) corresponding to amino acids 102-109 of HUMANK_P33 (SEQ ID NO:573), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

Variant protein HUMANK_P33 (SEQ ID NO:573) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P33 (SEQ ID NO:573) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

12
L -> P
No

63
P -> T
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P33 (SEQ ID NO:573) is encoded by the following transcript(s): HUMANK_T23 (SEQ ID NO:38), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T23 (SEQ ID NO:38) is shown in bold; this coding portion starts at position 2053 and ends at position 2379. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P33 (SEQ ID NO:573) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2392
-> C
No

2392
-> T
No

2592
A ->
No

2592
A -> C
No

2601
A -> C
No

2631
A -> C
No

2655
A ->
No

2655
A -> C
No

2749
C -> T
No

3164
-> G
No

3165
-> C
No

3977
T -> A
Yes

4034
-> T
No

4087
G ->
No

4462
G -> T
Yes

4871
T ->
No

Variant protein HUMANK_P34 (SEQ ID NO:574) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T24 (SEQ ID NO:39). An alignment is given to the known protein (Ankyrin 1 (SEQ ID NO:628)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMANK_P34 (SEQ ID NO:574) and AAH07930 (SEQ ID NO:631):

1. An isolated chimeric polypeptide encoding for HUMANK_P34 (SEQ ID NO:574), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEETIS corresponding to amino acids 1-62 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 1-62 of HUMANK_P34 (SEQ ID NO:574), a bridging amino acid P corresponding to amino acid 63 of HUMANK_P34 (SEQ ID NO:574), a second amino acid sequence being at least 90% homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64-101 of AAH07930 (SEQ ID NO:631), which also corresponds to amino acids 64-101 of HUMANK_P34 (SEQ ID NO:574), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1517) corresponding to amino acids 102-133 of HUMANK_P34 (SEQ ID NO:574), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMANK_P34 (SEQ ID NO:574), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1517) in HUMANK_P34 (SEQ ID NO:574).

Comparison Report Between HUMANK_P34 (SEQ ID NO:574) and Q8N604 (SEQ ID NO:630):

1. An isolated chimeric polypeptide encoding for HUMANK_P34 (SEQ ID NO:574), comprising a first amino acid sequence being at least 90% homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1-52 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 1-52 of HUMANK_P34 (SEQ ID NO:574), a bridging amino acid G corresponding to amino acid 53 of HUMANK_P34 (SEQ ID NO:574), a second amino acid sequence being at least 90% homologous to LSDDEETIS corresponding to amino acids 54-62 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 54-62 of HUMANK_P34 (SEQ ID NO:574), a bridging amino acid P corresponding to amino acid 63 of HUMANK_P34 (SEQ ID NO:574), a third amino acid sequence being at least 90% homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64-101 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 64-101 of HUMANK_P34 (SEQ ID NO:574), and a fourth amino acid sequence being at least 90% homologous to VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ (SEQ ID NO:1517) corresponding to amino acids 124-155 of Q8N604 (SEQ ID NO:630), which also corresponds to amino acids 102-133 of HUMANK_P34 (SEQ ID NO:574), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMANK_P34 (SEQ ID NO:574), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KV, having a structure as follows: a sequence starting from any of amino acid numbers 101−x to 101; and ending at any of amino acid numbers 102+((n−2)−x), in which x varies from 0 to n−2.

Variant protein HUMANK_P34 (SEQ ID NO:574) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 22, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P34 (SEQ ID NO:574) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

12
L -> P
No

63
P -> T
No

82
G ->
No

82
G -> V
No

89
Q -> P
No

Variant protein HUMANK_P34 (SEQ ID NO:574) is encoded by the following transcript(s): HUMANK_T24 (SEQ ID NO:39), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T24 (SEQ ID NO:39) is shown in bold; this coding portion starts at position 2053 and ends at position 2451. The transcript also has the following SNPs as listed in Table 23 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK_P34 (SEQ ID NO:574) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

1603
C -> T
No

1969
A -> G
No

2005
-> G
No

2014
C -> A
No

2087
T -> C
No

2238
C -> A
No

2239
A -> C
No

2297
G ->
No

2297
G -> T
No

2318
A -> C
No

2527
-> C
No

2527
-> T
No

2727
A ->
No

2727
A -> C
No

2736
A -> C
No

2766
A -> C
No

2790
A ->
No

2790
A -> C
No

2884
C -> T
No

3299
-> G
No

3300
-> C
No

4112
T -> A
Yes

4169
-> T
No

4222
G ->
No

4597
G -> T
Yes

5006
T ->
No

As noted above, cluster HUMANK features 22 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMANK_node_—91 (SEQ ID NO:285) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
1
1543

HUMANK_T13 (SEQ ID NO: 37)
1
1543

HUMANK_T23 (SEQ ID NO: 38)
1
1543

HUMANK_T24 (SEQ ID NO: 39)
1
1543

HUMANK_T26 (SEQ ID NO: 40)
1
1543

HUMANK_T27 (SEQ ID NO: 41)
1
1543

HUMANK_T28 (SEQ ID NO: 42)
1
1543

HUMANK_T35 (SEQ ID NO: 43)
1
1543

Segment cluster HUMANK_node_—92 (SEQ ID NO:286) according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
1544
1928

HUMANK_T13 (SEQ ID NO: 37)
1544
1928

HUMANK_T23 (SEQ ID NO: 38)
1544
1928

HUMANK_T24 (SEQ ID NO: 39)
1544
1928

HUMANK_T26 (SEQ ID NO: 40)
1544
1928

HUMANK_T27 (SEQ ID NO: 41)
1544
1928

HUMANK_T28 (SEQ ID NO: 42)
1544
1928

HUMANK_T35 (SEQ ID NO: 43)
1544
1928

Segment cluster HUMANK_node_—93 (SEQ ID NO:287) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
1929
2178

HUMANK_T13 (SEQ ID NO: 37)
1929
2178

HUMANK_T23 (SEQ ID NO: 38)
1929
2178

HUMANK_T24 (SEQ ID NO: 39)
1929
2178

HUMANK_T26 (SEQ ID NO: 40)
1929
2178

HUMANK_T27 (SEQ ID NO: 41)
1929
2178

HUMANK_T28 (SEQ ID NO: 42)
1929
2178

HUMANK_T35 (SEQ ID NO: 43)
1929
2178

Segment cluster HUMANK_node_—100 (SEQ ID NO:288) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T35 (SEQ ID NO:43). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T35 (SEQ ID NO: 43)
2356
2490

Segment cluster HUMANK_node_—108 (SEQ ID NO:289) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40) and HUMANK_T27 (SEQ ID NO:41). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2422
2556

HUMANK_T24 (SEQ ID NO: 39)
2356
2490

HUMANK_T26 (SEQ ID NO: 40)
2464
2598

HUMANK_T27 (SEQ ID NO: 41)
2497
2631

Segment cluster HUMANK_node_—113 (SEQ ID NO:290) according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2596
2735

HUMANK_T13 (SEQ ID NO: 37)
2536
2675

HUMANK_T23 (SEQ ID NO: 38)
2395
2534

HUMANK_T24 (SEQ ID NO: 39)
2530
2669

HUMANK_T26 (SEQ ID NO: 40)
2638
2777

HUMANK_T27 (SEQ ID NO: 41)
2671
2810

HUMANK_T28 (SEQ ID NO: 42)
2503
2642

Segment cluster HUMANK_node_—115 (SEQ ID NO:291) according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK T28 (SEQ ID NO:42). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2821
3234

HUMANK_T13 (SEQ ID NO: 37)
2761
3174

HUMANK_T23 (SEQ ID NO: 38)
2620
3033

HUMANK_T24 (SEQ ID NO: 39)
2755
3168

HUMANK_T26 (SEQ ID NO: 40)
2863
3276

HUMANK_T27 (SEQ ID NO: 41)
2896
3309

HUMANK_T28 (SEQ ID NO: 42)
2728
3141

Segment cluster HUMANK_node_—117 (SEQ ID NO:292) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
3249
4438

HUMANK_T13 (SEQ ID NO: 37)
3175
4364

HUMANK_T23 (SEQ ID NO: 38)
3034
4223

HUMANK_T24 (SEQ ID NO: 39)
3169
4358

HUMANK_T26 (SEQ ID NO: 40)
3277
4466

HUMANK_T27 (SEQ ID NO: 41)
3310
4499

HUMANK_T28 (SEQ ID NO: 42)
3142
4331

Segment cluster HUMANK_node_—119 (SEQ ID NO:293) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
4439
4797

HUMANK_T13 (SEQ ID NO: 37)
4365
4723

HUMANK_T23 (SEQ ID NO: 38)
4224
4582

HUMANK_T24 (SEQ ID NO: 39)
4359
4717

HUMANK_T26 (SEQ ID NO: 40)
4467
4825

HUMANK_T27 (SEQ ID NO: 41)
4500
4858

HUMANK_T28 (SEQ ID NO: 42)
4332
4690

Segment cluster HUMANK_node_—120 (SEQ ID NO:294) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
4798
5100

HUMANK_T13 (SEQ ID NO: 37)
4724
5026

HUMANK_T23 (SEQ ID NO: 38)
4583
4885

HUMANK_T24 (SEQ ID NO: 39)
4718
5020

HUMANK_T26 (SEQ ID NO: 40)
4826
5128

HUMANK_T27 (SEQ ID NO: 41)
4859
5161

HUMANK_T28 (SEQ ID NO: 42)
4691
4993

Segment cluster HUMANK_node_—94 (SEQ ID NO:295) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2179
2240

HUMANK_T13 (SEQ ID NO: 37)
2179
2240

HUMANK_T23 (SEQ ID NO: 38)
2179
2240

HUMANK_T24 (SEQ ID NO: 39)
2179
2240

HUMANK_T26 (SEQ ID NO: 40)
2179
2240

HUMANK_T27 (SEQ ID NO: 41)
2179
2240

HUMANK_T28 (SEQ ID NO: 42)
2179
2240

HUMANK_T35 (SEQ ID NO: 43)
2179
2240

Segment cluster HUMANK_node_—95 (SEQ ID NO:296) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2241
2271

HUMANK_T13 (SEQ ID NO: 37)
2241
2271

HUMANK_T23 (SEQ ID NO: 38)
2241
2271

HUMANK_T24 (SEQ ID NO: 39)
2241
2271

HUMANK_T26 (SEQ ID NO: 40)
2241
2271

HUMANK_T27 (SEQ ID NO: 41)
2241
2271

HUMANK_T28 (SEQ ID NO: 42)
2241
2271

HUMANK_T35 (SEQ ID NO: 43)
2241
2271

Segment cluster HUMANK_node_—98 (SEQ ID NO:297) according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2272
2348

HUMANK_T13 (SEQ ID NO: 37)
2272
2348

HUMANK_T23 (SEQ ID NO: 38)
2272
2348

HUMANK_T24 (SEQ ID NO: 39)
2272
2348

HUMANK_T26 (SEQ ID NO: 40)
2272
2348

HUMANK_T27 (SEQ ID NO: 41)
2272
2348

HUMANK_T28 (SEQ ID NO: 42)
2272
2348

HUMANK_T35 (SEQ ID NO: 43)
2272
2348

Segment cluster HUMANK_node_—99 (SEQ ID NO:298) according to the present invention can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41), HUMANK_T28 (SEQ ID NO:42) and HUMANK_T35 (SEQ ID NO:43). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2349
2355

HUMANK_T13 (SEQ ID NO: 37)
2349
2355

HUMANK_T23 (SEQ ID NO: 38)
2349
2355

HUMANK_T24 (SEQ ID NO: 39)
2349
2355

HUMANK_T26 (SEQ ID NO: 40)
2349
2355

HUMANK_T27 (SEQ ID NO: 41)
2349
2355

HUMANK_T28 (SEQ ID NO: 42)
2349
2355

HUMANK_T35 (SEQ ID NO: 43)
2349
2355

Segment cluster HUMANK_node_—102 (SEQ ID NO:299) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2356
2387

HUMANK_T13 (SEQ ID NO: 37)
2356
2387

HUMANK_T26 (SEQ ID NO: 40)
2356
2387

HUMANK_T27 (SEQ ID NO: 41)
2356
2387

HUMANK_T28 (SEQ ID NO: 42)
2356
2387

Segment cluster HUMANK_node_—103 (SEQ ID NO:300) according to the present invention can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2388
2409

HUMANK_T13 (SEQ ID NO: 37)
2388
2409

HUMANK_T26 (SEQ ID NO: 40)
2388
2409

HUMANK_T27 (SEQ ID NO: 41)
2388
2409

HUMANK_T28 (SEQ ID NO: 42)
2388
2409

Segment cluster HUMANK_node_—104 (SEQ ID NO:301) according to the present invention can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2410
2421

HUMANK_T13 (SEQ ID NO: 37)
2410
2421

HUMANK_T26 (SEQ ID NO: 40)
2410
2421

HUMANK_T27 (SEQ ID NO: 41)
2410
2421

HUMANK_T28 (SEQ ID NO: 42)
2410
2421

Segment cluster HUMANK_node_—105 (SEQ ID NO:302) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T13 (SEQ ID NO:37), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T13 (SEQ ID NO: 37)
2422
2463

HUMANK_T26 (SEQ ID NO: 40)
2422
2463

HUMANK_T27 (SEQ ID NO: 41)
2422
2463

HUMANK_T28 (SEQ ID NO: 42)
2422
2463

Segment cluster HUMANK_node_—106 (SEQ ID NO:303) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T13 (SEQ ID NO:37) and HUMANK_T27 (SEQ ID NO:41). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T13 (SEQ ID NO: 37)
2464
2496

HUMANK_T27 (SEQ ID NO: 41)
2464
2496

Segment cluster HUMANK_node_—112 (SEQ ID NO:304) according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK T24 (SEQ ID NO:39), HUMANK T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2557
2595

HUMANK_T13 (SEQ ID NO: 37)
2497
2535

HUMANK_T23 (SEQ ID NO: 38)
2356
2394

HUMANK_T24 (SEQ ID NO: 39)
2491
2529

HUMANK_T26 (SEQ ID NO: 40)
2599
2637

HUMANK_T27 (SEQ ID NO: 41)
2632
2670

HUMANK_T28 (SEQ ID NO: 42)
2464
2502

Segment cluster HUMANK_node_—114 (SEQ ID NO:305) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36), HUMANK_T13 (SEQ ID NO:37), HUMANK_T23 (SEQ ID NO:38), HUMANK_T24 (SEQ ID NO:39), HUMANK_T26 (SEQ ID NO:40), HUMANK_T27 (SEQ ID NO:41) and HUMANK_T28 (SEQ ID NO:42). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
2736
2820

HUMANK_T13 (SEQ ID NO: 37)
2676
2760

HUMANK_T23 (SEQ ID NO: 38)
2535
2619

HUMANK_T24 (SEQ ID NO: 39)
2670
2754

HUMANK_T26 (SEQ ID NO: 40)
2778
2862

HUMANK_T27 (SEQ ID NO: 41)
2811
2895

HUMANK_T28 (SEQ ID NO: 42)
2643
2727

Segment cluster HUMANK_node_—116 (SEQ ID NO:306) according to the present invention can be found in the following transcript(s): HUMANK_T3 (SEQ ID NO:36). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMANK_T3 (SEQ ID NO: 36)
3235
3248

Variant Protein Alignment to the Previously Known Protein:

Description for Cluster Z39819

Cluster Z39819 features 1 transcript(s) and 10 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

Z39819_PEA_1_T2
44

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

Z39819_PEA_1_node_2
307

Z39819_PEA_1_node_6
308

Z39819_PEA_1_node_10
309

Z39819_PEA_1_node_14
310

Z39819_PEA_1_node_16
311

Z39819_PEA_1_node_21
312

Z39819_PEA_1_node_3
313

Z39819_PEA_1_node_8
314

Z39819_PEA_1_node_12
315

Z39819_PEA_1_node_19
316

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

Z39819_PEA_1_P6
575
Z39819_PEA_1_T2 (SEQ ID

NO: 44)

These sequences are variants of the known protein GDNF family receptor alpha 2 precursor (SwissProt accession identifier GFR2_HUMAN; known also according to the synonyms GFR-alpha 2; Neurturin receptor alpha; NTNR-alpha; NRTNR-alpha; TGF-beta related neurotrophic factor receptor 2; GDNF receptor beta; GDNFR-beta; RET ligand 2), SEQ ID NO:632, referred to herein as the previously known protein.

Protein GDNF family receptor alpha 2 precursor (SEQ ID NO:632) is known or believed to have the following function(s): Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor. The sequence for protein GDNF family receptor alpha 2 precursor is given at the end of the application, as “GDNF family receptor alpha 2 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

6
V -> A

462
Q -> L

Protein GDNF family receptor alpha 2 precursor (SEQ ID NO:632) localization is believed to be attached to the membrane by a GPI-anchor (By similarity).

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: transmembrane receptor protein tyrosine kinase signaling pathway, which are annotation(s) related to Biological Process; and receptor; glial cell line-derived neurotrophic factor receptor, which are annotation(s) related to Molecular Function.

As noted above, cluster Z39819 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein GDNF family receptor alpha 2 precursor (SEQ ID NO:632). A description of each variant protein according to the present invention is now provided.

Variant protein Z39819_PEA_—1_P6 (SEQ ID NO:575) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z39819_PEA_—1_T2 (SEQ ID NO:44). An alignment is given to the known protein (GDNF family receptor alpha 2 precursor (SEQ ID NO:632)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between Z39819_PEA_—1_P6 (SEQ ID NO:575) and GFR2_HUMAN (SEQ ID NO:632):

1. An isolated chimeric polypeptide encoding for Z39819_PEA_—1_P6 (SEQ ID NO:575), comprising a first amino acid sequence being at least 90% homologous to MILANVFCLFFFL corresponding to amino acids 1-13 of GFR2_HUMAN (SEQ ID NO:632), which also corresponds to amino acids 1-13 of Z39819_PEA_—1_P6 (SEQ ID NO:575), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GPRAPRLAPPSGLCPGQ (SEQ ID NO:1520) corresponding to amino acids 14-30 of Z39819_PEA_—1_P6 (SEQ ID NO:575), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of Z39819_PEA_—1_P6 (SEQ ID NO:575), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GPRAPRLAPPSGLCPGQ (SEQ ID NO:1520) in Z39819_PEA_—1_P6 (SEQ ID NO:575).

The glycosylation sites of variant protein Z39819_PEA_—1_P6 (SEQ ID NO:575), as compared to the known protein GDNF family receptor alpha 2 precursor (SEQ ID NO:632), are described in Table 5 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 5

Glycosylation site(s)

Position(s) on known amino acid

sequence
Present in variant protein?

413
No

357
No

52
No

Variant protein Z39819_PEA_—1_P6 (SEQ ID NO:575) is encoded by the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z39819_PEA_—1_T2 (SEQ ID NO:44) is shown in bold; this coding portion starts at position 715 and ends at position 804. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z39819_PEA_—1_P6 (SEQ ID NO:575) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

633
C -> G
No

1088
T -> G
No

1114
G -> C
No

1120
G -> C
No

1372
C ->
No

1380
C ->
No

1872
C -> T
No

2058
A -> T
Yes

2090
G -> T
Yes

2161
T -> C
No

2165
A ->
No

2165
A -> C
No

2256
C -> A
No

As noted above, cluster Z39819 features 10 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z39819_PEA_—1_node_—2 (SEQ ID NO:307) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 7 below describes the starting and ending position of this segment on each transcript.

TABLE 7

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
1
679

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—6 (SEQ ID NO:308) according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 8 below describes the starting and ending position of this segment on each transcript.

TABLE 8

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
755
1028

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—10 (SEQ ID NO:309) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
1113
1467

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—14 (SEQ ID NO:310) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
1578
1718

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—16 (SEQ ID NO:311) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
1719
1891

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—21 (SEQ ID NO:312) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
1946
3332

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—3 (SEQ ID NO:313) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

Z39819_PEA_1_T2
680
754

(SEQ ID NO: 44)

Segment cluster Z39819_PEA_—1_node_—8 (SEQ ID NO:314) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z39819_PEA_1_T2 (SEQ ID NO: 44)
1029
1112

Segment cluster Z39819_PEA_—1_node_—12 (SEQ ID NO:315) according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z39819_PEA_1_T2 (SEQ ID NO: 44)
1468
1577

Segment cluster Z39819_PEA_—1_node_—19 (SEQ ID NO:316) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_—1_T2 (SEQ ID NO:44). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z39819_PEA_1_T2 (SEQ ID NO: 44)
1892
1945

Variant Protein Alignment to the Previously Known Protein:

Sequence name: GFR2_HUMAN (SEQ ID NO: 632)

Sequence documentation:

Alignment of: Z39819_PEA_1 PG (SEQ ID NO: 575) × GFR2_HUMAN (SEQ ID

NO: 632) . .

Alignment segment 1/1:

Quality:
146.00
Escore:
0

Matching length:
26
Total length:
26

Matching Percent Similarity:
69.23
Matching Percent Identity:
69.23

Total Percent Similarity:
69.23
Total Percent Identity:
69.23

Gaps:
0

Alignment:

Description for Cluster HUMCA1XIA

Cluster HUMCA1XIA features 4 transcript(s) and 46 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMCA1XIA_T16
45

HUMCA1XIA_T17
46

HUMCA1XIA_T19
47

HUMCA1XIA_T20
48

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMCA1XIA_node_0
317

HUMCA1XIA_node_2
318

HUMCA1XIA_node_4
319

HUMCA1XIA_node_6
320

HUMCA1XIA_node_8
321

HUMCA1XIA_node_9
322

HUMCA1XIA_node_18
323

HUMCA1XIA_node_54
324

HUMCA1XIA_node_55
325

HUMCA1XIA_node_92
326

HUMCA1XIA_node_11
327

HUMCA1XIA_node_15
328

HUMCA1XIA_node_19
329

HUMCA1XIA_node_21
330

HUMCA1XIA_node_23
331

HUMCA1XIA_node_25
332

HUMCA1XIA_node_27
333

HUMCA1XIA_node_29
334

HUMCA1XIA_node_31
335

HUMCA1XIA_node_33
336

HUMCA1XIA_node_35
337

HUMCA1XIA_node_37
338

HUMCA1XIA_node_39
339

HUMCA1XIA_node_41
340

HUMCA1XIA_node_43
341

HUMCA1XIA_node_45
342

HUMCA1XIA_node_47
343

HUMCA1XIA_node_49
344

HUMCA1XIA_node_51
345

HUMCA1XIA_node_57
346

HUMCA1XIA_node_59
347

HUMCA1XIA_node_62
348

HUMCA1XIA_node_64
349

HUMCA1XIA_node_66
350

HUMCA1XIA_node_68
351

HUMCA1XIA_node_70
352

HUMCA1XIA_node_72
353

HUMCA1XIA_node_74
354

HUMCA1XIA_node_76
355

HUMCA1XIA_node_78
356

HUMCA1XIA_node_81
357

HUMCA1XIA_node_83
358

HUMCA1XIA_node_85
359

HUMCA1XIA_node_87
360

HUMCA1XIA_node_89
361

HUMCA1XIA_node_91
362

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HUMCA1XIA_P14
576
HUMCA1XIA_T16 (SEQ ID

NO: 45)

HUMCA1XIA_P15
577
HUMCA1XIA_T17 (SEQ ID

NO: 46)

HUMCA1XIA_P16
578
HUMCA1XIA_T19 (SEQ ID

NO: 47)

HUMCA1XIA_P17
579
HUMCA1XIA_T20 (SEQ ID

NO: 48)

These sequences are variants of the known protein Collagen alpha 1 (SwissProt accession identifier CA1B_HUMAN; known also according to the synonyms XI), SEQ ID NO: 633, referred to herein as the previously known protein.

Protein Collagen alpha 1 (SEQ ID NO:633) is known or believed to have the following function(s): May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils. The sequence for protein Collagen alpha 1 is given at the end of the application, as “Collagen alpha 1 amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on

amino acid sequence
Comment

625
G -> V (in STL2). /FTId = VAR_013583.

676
G -> R (in STL2; overlapping phenotype

with Marshall syndrome). /FTId = VAR_013584.

921-926
Missing (in STL2; overlapping phenotype

with Marshall syndrome). /FTId = VAR_013585.

1313-1315
Missing (in STL2; overlapping phenotype

with Marshall syndrome). /FTId = VAR_013586.

1516
G -> V (in STL2; overlapping phenotype

with Marshall syndrome). /FTId = VAR_013587.

941-944
KDGL -> RMGC

986
Y -> H

1074
R -> P

1142
G -> D

1218
M -> W

1758
T -> A

1786
S -> N

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cartilage condensation; vision; hearing; cell-cell adhesion; extracellular matrix organization and biogenesis, which are annotation(s) related to Biological Process; extracellular matrix structural protein; extracellular matrix protein, adhesive, which are annotation(s) related to Molecular Function; and extracellular matrix; collagen; collagen type XI, which are annotation(s) related to Cellular Component.

Cluster HUMCA1XIA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 24 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

adrenal
0

Bone
207

brain
13

colon
0

epithelial
11

general
11

Head and neck
0

kidney
0

Lung
0

breast
8

pancreas
0

stomach
73

uterus
9

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
4.2e−01
1.9e−01
9.6e−02
3.4
8.2e−02
3.6

bone
2.4e−01
6.3e−01
7.7e−10
4.3
5.3e−03
1.6

brain
5.0e−01
6.9e−01
1.8e−01
2.1
4.2e−01
1.3

colon
1.3e−02
2.9e−02
2.4e−01
3.0
3.5e−01
2.4

epithelial
3.9e−04
3.2e−03
1.3e−03
2.3
1.8e−02
1.7

general
5.6e−05
1.6e−03
9.5e−17
4.5
1.1e−09
2.8

head and neck
1.2e−01
2.1e−01
1
1.3
1
1.1

kidney
6.5e−01
7.2e−01
3.4e−01
2.4
4.9e−01
1.9

lung
5.3e−02
9.1e−02
5.5e−05
7.3
5.0e−03
4.0

breast
4.3e−01
5.6e−01
6.9e−01
1.4
8.2e−01
1.1

pancreas
3.3e−01
1.8e−01
4.2e−01
2.4
1.5e−01
3.7

stomach
5.0e−01
6.1e−01
6.9e−01
1.0
6.7e−01
0.8

uterus
7.1e−01
7.0e−01
6.6e−01
1.1
6.4e−01
1.1

As noted above, cluster HUMCA1XIA features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Collagen alpha 1 (SEQ ID NO:633). A description of each variant protein according to the present invention is now provided.

Variant protein HUMCA1XIA_P14 (SEQ ID NO:576) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T16 (SEQ ID NO:45). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:633)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCA1XIA_P14 (SEQ ID NO:576) and CA1B_HUMAN_V5 (SEQ ID NO 634):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P14 (SEQ ID NO:576), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE DGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQ GPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVKGADGVRGLKG SKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPG YPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGP PGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERG HPGPPGPPGEQGLPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP V corresponding to amino acids 1-1056 of CA1B_HUMAN_V5 (SEQ ID NO:634), which also corresponds to amino acids 1-1056 of HUMCA1XIA_P14 (SEQ ID NO:576), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:1521) corresponding to amino acids 1057-1081 of HUMCA1XIA_P14 (SEQ ID NO:576), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCA1XIA_P14 (SEQ ID NO:576), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:1521) in HUMCA1XIA_P14 (SEQ ID NO:576).

It should be noted that the known protein sequence (CA1B_HUMAN (SEQ ID NO:633)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CA1B_HUMAN_V5 (SEQ ID NO:634). These changes were previously known to occur and are listed in the table below.

TABLE 7

Changes to CA1B_HUMAN_V5(SEQ ID NO: 634)

SNP position(s) on amino

acid sequence
Type of change

987
conflict

Variant protein HUMCA1XIA_P14 (SEQ ID NO:576) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P14 (SEQ ID NO:576) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

8
W -> G
Yes

46
D -> E
Yes

559
G -> S
Yes

832
G -> *
Yes

986
H -> Y
Yes

1061
I -> M
Yes

1070
V -> A
Yes

Variant protein HUMCA1XIA_P14 (SEQ ID NO:576) is encoded by the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T16 (SEQ ID NO:45) is shown in bold; this coding portion starts at position 319 and ends at position 3561. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P14 (SEQ ID NO:576) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

157
A -> G
No

241
T -> A
Yes

340
T -> G
Yes

456
T -> G
Yes

1993
G -> A
Yes

2812
G -> T
Yes

3274
C -> T
Yes

3282
C -> T
Yes

3501
A -> G
Yes

3527
T -> C
Yes

Variant protein HUMCA1XIA_P15 (SEQ ID NO:577) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T17 (SEQ ID NO:46). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:633)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCA1XIA_P15 (SEQ ID NO:577) and CA1B_HUMAN (SEQ ID NO:633):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P15 (SEQ ID NO:577), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE DGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQ GPIGPPGEK corresponding to amino acids 1-714 of CA1B_HUMAN (SEQ ID NO:633), which also corresponds to amino acids 1-714 of HUMCA1XIA_P15 (SEQ ID NO:577), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCCNLSFGILIPLQK (SEQ ID NO:1522) corresponding to amino acids 715-729 of HUMCA1XIA_P15 (SEQ ID NO:577), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCA1XIA_P15 (SEQ ID NO:577), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK (SEQ ID NO:1522) in HUMCA1XIA_P15 (SEQ ID NO:577).

Variant protein HUMCA1XIA_P15 (SEQ ID NO:577) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P15 (SEQ ID NO:577) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

8
W -> G
Yes

46
D -> E
Yes

559
G -> S
Yes

The glycosylation sites of variant protein HUMCA1XIA_P15 (SEQ ID NO:577), as compared to the known protein Collagen alpha 1 (SEQ ID NO:633), are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 11

Glycosylation site(s)

Position(s) on known amino acid

sequence
Present in variant protein?

1640
no

Variant protein HUMCA1XIA_P15 (SEQ ID NO:577) is encoded by the following transcript(s): HUMCA1XIA_T17 (SEQ ID NO:46), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T17 (SEQ ID NO:46) is shown in bold; this coding portion starts at position 319 and ends at position 2505. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P15 (SEQ ID NO:577) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

157
A -> G
No

241
T -> A
Yes

340
T -> G
Yes

456
T -> G
Yes

1993
G -> A
Yes

2473
C -> T
Yes

Variant protein HUMCA1XIA_P16 (SEQ ID NO:578) according to the present invention has amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T19 (SEQ ID NO:47). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:633)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCA1XIA_P16 (SEQ ID NO:578) and CA1B_HUMAN (SEQ ID NO:633):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P16 (SEQ ID NO:578), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE DGEIGPRGLPGEA corresponding to amino acids 1-648 of CA1B_HUMAN (SEQ ID NO:633), which also corresponds to amino acids 1-648 of HUMCA1XIA_P16 (SEQ ID NO:578), a second amino acid sequence being at least 90% homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667-714 of CA1B HUMAN (SEQ ID NO:633), which also corresponds to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID NO:578), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:1523) corresponding to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID NO:578), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMCA1XIA_P16 (SEQ ID NO:578), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648−x to 648; and ending at any of amino acid numbers 649+((n−2)−x), in which x varies from 0 to n−2.

3. An isolated polypeptide encoding for a tail of HUMCA1XIA_P16 (SEQ ID NO:578), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:1523) in HUMCA1XIA_P16 (SEQ ID NO:578).

Variant protein HUMCA1XIA_P16 (SEQ ID NO:578) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P16 (SEQ ID NO:578) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

8
W -> G
Yes

46
D -> E
Yes

559
G -> S
Yes

The glycosylation sites of variant protein HUMCA1XIA_P16 (SEQ ID NO:578), as compared to the known protein Collagen alpha 1 (SEQ ID NO:633), are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 14

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

1640
no

Variant protein HUMCA1XIA_P16 (SEQ ID NO:578) is encoded by the following transcript(s): HUMCA1XIA_T19 (SEQ ID NO:47), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T19 (SEQ ID NO:47) is shown in bold; this coding portion starts at position 319 and ends at position 2532. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P16 (SEQ ID NO:578) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

157
A -> G
No

241
T -> A
Yes

340
T -> G
Yes

456
T -> G
Yes

1993
G -> A
Yes

2606
C -> A
Yes

2677
T -> G
Yes

2849
C -> T
Yes

Variant protein HUMCA1XIA_P17 (SEQ ID NO:579) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCA1XIA_T20 (SEQ ID NO:48). An alignment is given to the known protein (Collagen alpha 1 (SEQ ID NO:633)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCA1XIA_P17 (SEQ ID NO:579) and CA1B_HUMAN (SEQ ID NO:633):

1. An isolated chimeric polypeptide encoding for HUMCA1XIA_P17 (SEQ ID NO:579), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids 1-260 of CA1B_HUMAN (SEQ ID NO:633), which also corresponds to amino acids 1-260 of HUMCA1XIA_P17 (SEQ ID NO:579), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSTRPEKVFVFQ (SEQ ID NO:1524) corresponding to amino acids 261-273 of HUMCA1XIA_P17 (SEQ ID NO:579), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCA1XIA_P17 (SEQ ID NO:579), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSTRPEKVFVFQ (SEQ ID NO:1524) in HUMCA1XIA_P17 (SEQ ID NO:579).

Variant protein HUMCA1XIA_P17 (SEQ ID NO:579) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P17 (SEQ ID NO:579) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

8
W -> G
Yes

46
D -> E
Yes

The glycosylation sites of variant protein HUMCA1XIA_P17 (SEQ ID NO:579), as compared to the known protein Collagen alpha 1 (SEQ ID NO:633), are described in Table 17 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 17

Glycosylation site(s)

Position(s) on known
Present in

amino acid sequence
variant protein?

1640
no

Variant protein HUMCA1XIA_P17 (SEQ ID NO:579) is encoded by the following transcript(s): HUMCA1XIA_T20 (SEQ ID NO:48), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_T20 (SEQ ID NO:48) is shown in bold; this coding portion starts at position 319 and ends at position 1137. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA_P17 (SEQ ID NO:579) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

157
A -> G
No

241
T -> A
Yes

340
T -> G
Yes

456
T -> G
Yes

1150
A -> C
Yes

As noted above, cluster HUMCA1XIA features 46 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMCA1XIA_node_—0 (SEQ ID NO:317) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46), HUMCA1XIA_T19 (SEQ ID NO:47) and HUMCA1XIA_T20 (SEQ ID NO:48). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1
424

HUMCA1XIA_T17 (SEQ ID NO: 46)
1
424

HUMCA1XIA_T19 (SEQ ID NO: 47)
1
424

HUMCA1XIA_T20 (SEQ ID NO: 48)
1
424

Segment cluster HUMCA1XIA_node_—2 (SEQ ID NO:318) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46), HUMCA1XIA_T19 (SEQ ID NO:47) and HUMCA1XIA_T20 (SEQ ID NO:48). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
425
592

HUMCA1XIA_T17 (SEQ ID NO: 46)
425
592

HUMCA1XIA_T19 (SEQ ID NO: 47)
425
592

HUMCA1XIA_T20 (SEQ ID NO: 48)
425
592

Segment cluster HUMCA1XIA_node_—4 (SEQ ID NO:319) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46), HUMCA1XIA_T19 (SEQ ID NO:47) and HUMCA1XIA_T20 (SEQ ID NO:48). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
593
806

HUMCA1XIA_T17 (SEQ ID NO: 46)
593
806

HUMCA1XIA_T19 (SEQ ID NO: 47)
593
806

HUMCA1XIA_T20 (SEQ ID NO: 48)
593
806

TABLE 22

Oligonucleotides related to this segment

Overexpressed
Chip

Oligonucleotide name
in cancers
reference

HUMCA1XIA_0_18_0
colorectal cancer
Colon

(SEQ ID NO: 1412)

Segment cluster HUMCA1XIA_node_—6 (SEQ ID NO:320) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46), HUMCA1XIA_T19 (SEQ ID NO:47) and HUMCA1XIA_T20 (SEQ ID NO:48). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
807
969

HUMCA1XIA_T17 (SEQ ID NO: 46)
807
969

HUMCA1XIA_T19 (SEQ ID NO: 47)
807
969

HUMCA1XIA_T20 (SEQ ID NO: 48)
807
969

TABLE 24

Oligonucleotides related to this segment

Chip

Oligonucleotide name
Overexpressed in cancers
reference

HUMCA1XIA_0_18_0
breast malignant tumors
BRS

(SEQ ID NO: 1412)

HUMCA1XIA_0_18_0
colorectal cancer
Colon

(SEQ ID NO: 1412)

HUMCA1XIA_0_18_0
lung malignant tumors
LUN

(SEQ ID NO: 1412)

Segment cluster HUMCA1XIA_node_—8 (SEQ ID NO:321) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46), HUMCA1XIA_T19 (SEQ ID NO:47) and HUMCA1XIA_T20 (SEQ ID NO:48). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
970
1098

HUMCA1XIA_T17 (SEQ ID NO: 46)
970
1098

HUMCA1XIA_T19 (SEQ ID NO: 47)
970
1098

HUMCA1XIA_T20 (SEQ ID NO: 48)
970
1098

Segment cluster HUMCA1XIA_node_—9 (SEQ ID NO:322) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T20 (SEQ ID NO:48). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T20 (SEQ ID NO: 48)
1099
1271

Segment cluster HUMCA1XIA_node_—18 (SEQ ID NO:323) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1309
1522

HUMCA1XIA_T17 (SEQ ID NO: 46)
1309
1522

HUMCA1XIA_T19 (SEQ ID NO: 47)
1309
1522

Segment cluster HUMCA1XIA_node_—54 (SEQ ID NO:324) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T19 (SEQ ID NO:47). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T19 (SEQ ID NO: 47)
2407
2836

Segment cluster HUMCA1XIA_node_—55 (SEQ ID NO:325) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T17 (SEQ ID NO: 46)
2461
2648

HUMCA1XIA_T19 (SEQ ID NO: 47)
2837
3475

Segment cluster HUMCA1XIA_node_—92 (SEQ ID NO:326) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3487
3615

Segment cluster HUMCA1XIA_node_—11 (SEQ ID NO:327) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1099
1215

HUMCA1XIA_T17 (SEQ ID NO: 46)
1099
1215

HUMCA1XIA_T19 (SEQ ID NO: 47)
1099
1215

Segment cluster HUMCA1XIA_node_—15 (SEQ ID NO:328) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1216
1308

HUMCA1XIA_T17 (SEQ ID NO: 46)
1216
1308

HUMCA1XIA_T19 (SEQ ID NO: 47)
1216
1308

Segment cluster HUMCA1XIA_node_—19 (SEQ ID NO:329) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1523
1563

HUMCA1XIA_T17 (SEQ ID NO: 46)
1523
1563

HUMCA1XIA_T19 (SEQ ID NO: 47)
1523
1563

Segment cluster HUMCA1XIA_node_—21 (SEQ ID NO:330) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1564
1626

HUMCA1XIA_T17 (SEQ ID NO: 46)
1564
1626

HUMCA1XIA_T19 (SEQ ID NO: 47)
1564
1626

Segment cluster HUMCA1XIA_node_—23 (SEQ ID NO:331) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1627
1668

HUMCA1XIA_T17 (SEQ ID NO: 46)
1627
1668

HUMCA1XIA_T19 (SEQ ID NO: 47)
1627
1668

Segment cluster HUMCA1XIA_node_—25 (SEQ ID NO:332) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1669
1731

HUMCA1XIA_T17 (SEQ ID NO: 46)
1669
1731

HUMCA1XIA_T19 (SEQ ID NO: 47)
1669
1731

Segment cluster HUMCA1XIA_node_—27 (SEQ ID NO:333) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1732
1806

HUMCA1XIA_T17 (SEQ ID NO: 46)
1732
1806

HUMCA1XIA_T19 (SEQ ID NO: 47)
1732
1806

Segment cluster HUMCA1XIA_node_—29 (SEQ ID NO:334) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1807
1890

HUMCA1XIA_T17 (SEQ ID NO: 46)
1807
1890

HUMCA1XIA_T19 (SEQ ID NO: 47)
1807
1890

Segment cluster HUMCA1XIA_node_—31 (SEQ ID NO:335) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1891
1947

HUMCA1XIA_T17 (SEQ ID NO: 46)
1891
1947

HUMCA1XIA_T19 (SEQ ID NO: 47)
1891
1947

Segment cluster HUMCA1XIA_node_—33 (SEQ ID NO:336) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
1948
2001

HUMCA1XIA_T17 (SEQ ID NO: 46)
1948
2001

HUMCA1XIA_T19 (SEQ ID NO: 47)
1948
2001

Segment cluster HUMCA1XIA_node_—35 (SEQ ID NO:337) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2002
2055

HUMCA1XIA_T17 (SEQ ID NO: 46)
2002
2055

HUMCA1XIA_T19 (SEQ ID NO: 47)
2002
2055

Segment cluster HUMCA1XIA_node_—37 (SEQ ID NO:338) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2056
2109

HUMCA1XIA_T17 (SEQ ID NO: 46)
2056
2109

HUMCA1XIA_T19 (SEQ ID NO: 47)
2056
2109

Segment cluster HUMCA1XIA_node_—39 (SEQ ID NO:339) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2110
2163

HUMCA1XIA_T17 (SEQ ID NO: 46)
2110
2163

HUMCA1XIA_T19 (SEQ ID NO: 47)
2110
2163

Segment cluster HUMCA1XIA_node_—41 (SEQ ID NO:340) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2164
2217

HUMCA1XIA_T17 (SEQ ID NO: 46)
2164
2217

HUMCA1XIA_T19 (SEQ ID NO: 47)
2164
2217

Segment cluster HUMCA1XIA_node_—43 (SEQ ID NO:341) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2218
2262

HUMCA1XIA_T17 (SEQ ID NO: 46)
2218
2262

HUMCA1XIA_T19 (SEQ ID NO: 47)
2218
2262

Segment cluster HUMCA1XIA_node_—45 (SEQ ID NO:342) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45) and HUMCA1XIA_T17 (SEQ ID NO:46). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2263
2316

HUMCA1XIA_T17 (SEQ ID NO: 46)
2263
2316

Segment cluster HUMCA1XIA_node_—47 (SEQ ID NO:343) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2317
2361

HUMCA1XIA_T17 (SEQ ID NO: 46)
2317
2361

HUMCA1XIA_T19 (SEQ ID NO: 47)
2263
2307

Segment cluster HUMCA1XIA_node_—49 (SEQ ID NO:344) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2362
2415

HUMCA1XIA_T17 (SEQ ID NO: 46)
2362
2415

HUMCA1XIA_T19 (SEQ ID NO: 47)
2308
2361

Segment cluster HUMCA1XIA_node_—51 (SEQ ID NO:345) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45), HUMCA1XIA_T17 (SEQ ID NO:46) and HUMCA1XIA_T19 (SEQ ID NO:47). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2416
2460

HUMCA1XIA_T17 (SEQ ID NO: 46)
2416
2460

HUMCA1XIA_T19 (SEQ ID NO: 47)
2362
2406

Segment cluster HUMCA1XIA_node_—57 (SEQ ID NO:346) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2461
2514

Segment cluster HUMCA1XIA_node_—59 (SEQ ID NO:347) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2515
2559

Segment cluster HUMCA1XIA_node_—62 (SEQ ID NO:348) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2560
2613

Segment cluster HUMCA1XIA_node_—64 (SEQ ID NO:349) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2614
2658

Segment cluster HUMCA1XIA_node_—66 (SEQ ID NO:350) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2659
2712

Segment cluster HUMCA1XIA_node_—68 (SEQ ID NO:351) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2713
2820

Segment cluster HUMCA1XIA_node_—70 (SEQ ID NO:352) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2821
2874

Segment cluster HUMCA1XIA_node_—72 (SEQ ID NO:353) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2875
2928

Segment cluster HUMCA1XIA_node_—74 (SEQ ID NO:354) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2929
2973

Segment cluster HUMCA1XIA_node_—76 (SEQ ID NO:355) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
2974
3027

Segment cluster HUMCA1XIA_node_—78 (SEQ ID NO:356) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3028
3072

Segment cluster HUMCA1XIA_node_—81 (SEQ ID NO:357) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3073
3126

Segment cluster HUMCA1XIA_node_—83 (SEQ ID NO:358) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3127
3180

Segment cluster HUMCA1XIA_node_—85 (SEQ ID NO:359) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3181
3234

Segment cluster HUMCA1XIA_node_—87 (SEQ ID NO:360) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3235
3342

Segment cluster HUMCA1XIA_node_—89 (SEQ ID NO:361) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3343
3432

Segment cluster HUMCA1XIA_node_—91 (SEQ ID NO:362) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:45). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCA1XIA_T16 (SEQ ID NO: 45)
3433
3486

Variant Protein Alignment to the Previously Known Protein:

Sequence name: CA1B_HUMAN_V5 (SEQ ID NO: 634)

Sequence documentation:

Alignment of: HUMCA1XIA_P14 (SEQ ID NO: 576) × CA1B_HUMAN_V5 (SEQ ID

NO: 634)

Alignment segment 1/1:

Quality:
10456.00
Escore:
0

Matching length:
1058
Total length:
1058

Matching Percent Similarity:
99.91
Matching Percent Identity:
99.91

Total Percent Similarity:
99.91
Total Percent Identity:
99.91

Gaps:
0

Alignment:

Sequence name: CA1B_HUMAN (SEQ ID NO: 633)

Sequence documentation:

Alignment of:

HUMCA1XIA_P15 (SEQ ID NO: 577) × CA1B_HUMAN (SEQ ID NO: 633)

Alignment segment 1/1:

Quality:
7073.00
Escore:
0

Matching length:
714
Total length:
714

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: CA1B_HUMAN (SEQ ID NO: 633)

Sequence documentation:

Alignment of:

HUMCA1XIA_P16 (SEQ ID NO: 578) × CA1B_HUMAN (SEQ ID NO: 633)

Alignment segment 1/1:

Quality:
6795.00
Escore:
0

Matching length:
696
Total length:
714

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
97.48
Total Percent Identity:
97.48

Gaps:
1

Alignment:

Sequence name: CA1B HUMAN (SEQ ID NO: 633)

Sequence documentation:

Alignment of:

HUMCA1XIA_P17 (SEQ ID NO: 579) × CA1B_HUMAN (SEQ ID NO: 633)

Alignment segment 1/1:

Quality:
2561.00
Escore:
0

Matching length:
260
Total length:
260

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Experimental Results for Seg55 Amplicon Expression in Cancerous Colon Tissue

Expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by or according to seg55—HUMCA1XIA_seg55 amplicon (SEQ ID NO:1586) and primers HUMCA1XIA_seg55F (SEQ ID NO: 1584) and HUMCA1XIA_seg55R (SEQ ID NO:1585) was measured by real time PCR. Non-detected sample no. 63 was assigned Ct value of 41 and was calculated accordingly. In parallel the expression of several housekeeping genes —HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO: 1577); amplicon—HPRT1-amplicon (SEQ ID NO: 612)), PBGD (GenBank Accession No. BC019323 (SEQ ID NO: 1576); amplicon—PBGD-amplicon (SEQ ID NO: 531)), and G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO: 1578); G6PD amplicon (SEQ ID NO: 615)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the normalization factor calculated from the expression of these house keeping genes as described in normalization method 2 in the “materials and methods” section. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal samples (sample numbers 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 and 55, Table 1_—1 above), to obtain a value of fold up-regulation for each sample relative to median of the normal samples.

FIG. 77 is a histogram showing over expression of the above-indicated Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts in cancerous Colon samples relative to the normal samples.

As is evident from FIG. 77, the expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (sample numbers 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 and 55, Table 1_—1 above). Notably an over-expression of at least 5 fold was found in 18 out of 37 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by the above amplicon in Colon cancer samples versus the normal tissue samples was determined by T test as 3.33e-005.

Threshold of 5 fold over expression was found to differentiate between cancer and normal samples with P value of 2.58e-006 as checked by exact Fisher test.

The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCA1XIA_seg55F (SEQ ID NO: 1584) forward primer; and HUMCA1XIA_seg55R (SEQ ID NO: 1585) reverse primer.

Forward Primer

(HUMCA1XIA_seg55F (SEQ ID NO: 1584)):

>HUMCA1XIA_seg55F

(SEQ ID NO: 1584)

TTCTCATAGTATTCCATTGATTGGGTA

Reverse Primer

(HUMCA1XIA_seg55R (SEQ ID NO: 1585)):

>HUMCA1XIA_seg55R

(SEQ ID NO: 1585)

CACCGGTATGGAGAATAGCGA

Amplicon (HUMCA1XIA_seg55) (SEQ ID NO: 1586):

>HUMCA1XIA_seg55

(SEQ ID NO: 1586)

TTCTCATAGTATTCCATTGATTGGGTATACCAGGTTCTGTTTACTTTTAC

TTGGCAGTTGATAGAATAGGTGTAGTTTATACTTTTTCGCTATTCTCCAT

ACCGGTG

Experimental Results for Seg55 Amplicon Expression in Normal Tissue

Expression of Homo sapiens collagen, type XI, alpha 1 (COL11 A1) transcripts detectable by or according to seg55—HUMCA1XIA_seg55 amplicon (SEQ ID NO: 1586) and primers HUMCA1XIA_seg55F (SEQ ID NO: 1584) and HUMCA1XIA_seg55R (SEQ ID NO: 1585) was measured by real time PCR. In parallel the expression of several housekeeping genes—SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO: 1583); amplicon —SDHA-amplicon (SEQ ID NO: 1273)), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO: 1582); amplicon—Ubiquitin-amplicon (SEQ ID NO: 1270)) and TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO: 1581); TATA amplicon (SEQ ID NO: 1267)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the normalization factor calculated from the expression of these house keeping genes as described in normalization method 2 in the “materials and methods” section. The normalized quantity of each RT sample was then divided by the median of the quantities of the colon samples (sample numbers 3, 4 and 5, Table 2_—1 above), to obtain a value of relative expression of each sample relative to median of the colon samples.

Results are shown in FIG. 78. Low expression was seen in all normal tissues, although a certain level of expression was seen in brain tissue samples.

Expression of Homo sapiens Collagen, Type XI, Alpha 1 (COL11A1) HUMCA1XIA Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HUMCA1XIA_Seg54-55F2R2 (SEQ ID NO: 1589) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by or according to seg54-55F2R2—HUMCA1XIA_seg54-55F2R2 (SEQ ID NO: 1589) amplicon and primers HUMCA1XIA_seg54-55F2 (SEQ ID NO: 1587) and HUMCA1XIA_seg54-55R2 (SEQ ID NO: 1588) was measured by real time PCR. Non-detected samples (sample(s) no. 28, 36 and 63) were assigned Ct value of 41 and were calculated accordingly. In parallel the expression of several housekeeping genes —HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO: 1577); amplicon—HPRT1-amplicon (SEQ ID NO: 612)), PBGD (GenBank Accession No. BC019323 (SEQ ID NO: 1576); amplicon—PBGD-amplicon (SEQ ID NO: 531)), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO: 1579); RPS27A amplicon (SEQ ID NO: 1261)) and G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO: 1578); G6PD amplicon (SEQ ID NO: 615)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the normalization factor calculated from the expression of these house keeping genes as described in normalization method 2 in the “materials and methods” section. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal samples (sample numbers 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 and 55, Table 1_—1 above), to obtain a value of fold up-regulation for each sample relative to median of the normal samples.

FIG. 79 is a histogram showing over expression of the above-indicated Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts in cancerous Colon samples relative to the normal samples.

As is evident from FIG. 79, the expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (sample numbers 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 and 55, Table 1_—1 above). Notably an over-expression of at least 5 fold was found in 27 out of 55 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 5 fold over expression was found to differentiate between cancer and normal samples with P value of 5.09e-007 as checked by exact Fisher test.

The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCA1XIA_seg54-55F2 (SEQ ID NO: 1587) forward primer; and HUMCA1XIA_seg54-55R2 (SEQ ID NO: 1588) reverse primer.

Forward Primer

(HUMCA1XIA_seg54-55F2 (SEQ ID NO: 1587)):

>HUMCA1XIA_seg54-55F2

(SEQ ID MO: 1587)

TCGAAGTGTAATTTAAATACTATAAATATTCCCTT

Reverse Primer

(HUMCA1XIA_seg54-55R2 (SEQ ID NO: 1588)):

>HUMCA1XIA_seg54-55R2

(SEQ ID NO: 1588)

GGAAACATGGACTGAATATTAACACG

Amplicon

(HUMCA1XIA_seg54-55F2R2 (SEQ ID NO: 1589)):

>HUMCA1XIA_seg54-55F2R2

(SEQ ID NO: 1589)

TCGAAGTGTAATTTAAATACTATAAATATTCCCTTGTTTTAAGTGTACAA

GTGAATTATTTTTACTAAATTTACAGATGTGCTGCAATCTAAGTTTCGGA

ATACTTATACCACTCCAGAAATAATCCTCGTGTTAATATTCAGTCCATGT

TTCC

Expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by or according to seg54-55F2R2—HUMCA1XIA_seg54-55F2R2 amplicon (SEQ ID NO: 1589) and primers HUMCA1XIA_seg54-55F2 (SEQ ID NO: 1587) and HUMCA1XIA_seg54-55R2 (SEQ ID NO: 1588) was measured by real time PCR. Non-detected samples (samples no. 16, 19, 50, 51, 52, 56, 65, 67 and 70) were assigned Ct value of 41 and were calculated accordingly. In parallel the expression of several housekeeping genes—SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO: 1583); amplicon—SDHA-amplicon (SEQ ID NO: 1273)), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO: 1582); amplicon—Ubiquitin-amplicon (SEQ ID NO: 1270)), RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO: 1580); RPL19 amplicon (SEQ ID NO: 1264)) and TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO: 1581); TATA amplicon (SEQ ID NO: 1267)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the normalization factor calculated from the expression of these house keeping genes as described in normalization method 2 in the “materials and methods” section. The normalized quantity of each RT sample was then divided by the median of the quantities of the colon samples (sample numbers 3, 4 and 5, Table 2_—1 above), to obtain a value of relative expression of each sample relative to median of the colon samples.

Forward Primer

(HUMCA1XIA_seg54-55F2 (SEQ ID NO: 1587)):

>HUMCA1XIA_seg54-55F2

(SEQ ID NO: 1587)

TCGAAGTGTAATTTAAATACTATAAATATTCCCTT

Reverse Primer

(HUMCA1XIA_seg54-55R2 (SEQ ID NO: 1588)):

>HUMCA1XIA_seg54-55R2

(SEQ ID NO: 1588)

GGAAACATGGACTGAATATTAACACG

Amplicon

(HUMCA1XIA_seg54-55F2R2) (SEQ ID NO: 1589):

>HUMCA1XIA_seg54-55F2R2

(SEQ ID NO: 1589)

TCGAAGTGTAATTTAAATACTATAAATATTCCCTTGTTTTAAGTGTACAA

GTGAATTATTTTTACTAAATTTACAGATGTGCTGCAATCTAAGTTTCGGA

ATACTTATACCACTCCAGAAATAATCCTCGTGTTAATATTCAGTCCATGT

TTCC

The results are shown in FIG. 80, demonstrating expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) HUMCA1XIA transcripts which are detectable by amplicon as depicted in sequence name HUMCA1XIA_seg54-55F2R2 (SEQ ID NO: 1589) in different normal tissues.

Expression of Homo sapiens Collagen, Type XI, Alpha 1 (COL11A1) HUMCA1XIA Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HUMCA1XIA_Seg52-56F1R1 (SEQ ID NO: 1592) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens collagen, type XI, alpha 1 (COL11A1) transcripts detectable by or according to seg52-56F1R1—HUMCA1XIA_seg52-56F1R1 (SEQ ID NO: 1592) amplicon and primers HUMCA1XIA_seg52-56F1 (SEQ ID NO: 1590) and HUMCA1XIA_seg52-56R1 (SEQ ID NO: 1591) was measured by real time PCR. In parallel the expression of several housekeeping genes —HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO: 1577); amplicon—HPRT1-amplicon (SEQ ID NO: 612)), PBGD (GenBank Accession No. BC019323 (SEQ ID NO: 1576); amplicon—PBGD-amplicon (SEQ ID NO: 531)), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO: 1579); RPS27A amplicon (SEQ ID NO: 1261)) and G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO: 1578); G6PD amplicon (SEQ ID NO: 615)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the normalization factor calculated from the expression of these house keeping genes as described in normalization method 2 in the “materials and methods” section. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal samples (sample numbers 42-70, Table 1_—1 above), to obtain a value of fold differential expression for each sample relative to median of the normal samples.

In one experiment that was carried out no differential expression in the cancerous samples relative to the normal samples was observed.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCA1XIA_seg52-56F1 (SEQ ID NO: 1590) forward primer; and HUMCA1XIA_seg52-56R1 (SEQ ID NO: 1591) reverse primer.

Forward Primer

(HUMCA1XIA_seg52-56F1 (SEQ ID NO: 1590)):

>HUMCA1XIA_seg52-56F1

(SEQ ID NO: 1590)

GGTCTTCCTGGTCCACAAGGT

Reverse Primer

(HUMCA1XIA_seg52-56R1 (SEQ ID NO: 1591)):

>HUMCA1XIA_seg52-56R1

(SEQ ID NO: 1591)

GAATATTAACACGAGGATTATTTCTGGAG

Amplicon

(HUMCA1XIA_seg52-56F1R1 (SEQ ID NO: 1592)):

>HUMCA1XIA_seg52-5GF1R1

(SEQ ID NO: 1592)

GGTCTTCCTGGTCCACAAGGTCCAATTGGTCCTCCTGGTGAAAAAATGTG

CTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCGT

GTTAATATTC

Description for Cluster HSS100PCB

Cluster HSS100PCB features 1 transcript(s) and 3 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HSS100PCB_T1
49

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HSS100PCB_node_3
363

HSS100PCB_node_4
364

HSS100PCB_node_5
365

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HSS100PCB_P3
580
HSS100PCB_T1 (SEQ ID NO: 49)

These sequences are variants of the known protein S-100P protein (SwissProt accession identifier S10P_HUMAN), SEQ ID NO: 635, referred to herein as the previously known protein.

The sequence for protein S-100P protein (SEQ ID NO:635) is given at the end of the application, as “S-100P protein amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

32
E -> T

44
F -> E

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: calcium binding; protein binding, which are annotation(s) related to Molecular Function.

Cluster HSS100PCB can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 25 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bladder
41

colon
37

epithelial
38

general
22

kidney
0

liver
0

Lung
18

breast
0

bone marrow
0

ovary
0

pancreas
0

prostate
46

stomach
553

uterus
13

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
3.3e−01
2.9e−01
2.9e−02
2.8
3.5e−02
2.8

colon
3.0e−01
1.9e−01
5.2e−01
1.2
2.4e−01
1.7

epithelial
4.7e−02
1.6e−02
2.0e−01
1.2
6.1e−02
1.3

general
1.1e−03
6.8e−05
1.4e−02
1.5
4.9e−04
1.7

kidney
6.5e−01
7.2e−01
5.8e−01
1.7
7.0e−01
1.4

liver
9.1e−01
4.9e−01
1
1.0
7.7e−02
2.1

lung
6.8e−01
7.3e−01
2.2e−02
2.9
1.3e−01
1.7

breast
2.8e−01
3.2e−01
4.7e−01
2.0
6.8e−01
1.5

bone marrow
1
6.7e−01
1
1.0
2.8e−01
2.8

ovary
2.6e−01
3.0e−01
4.7e−01
2.0
5.9e−01
1.7

pancreas
3.3e−01
4.4e−01
7.6e−02
3.7
1.5e−01
2.8

prostate
9.1e−01
9.3e−01
5.8e−01
0.6
7.6e−01
0.5

stomach
3.7e−01
3.2e−01
1
0.1
1
0.3

uterus
9.4e−01
7.0e−01
1
0.6
4.1e−01
1.1

As noted above, cluster HSS100PCB features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein S-100P protein (SEQ ID NO:635). A description of each variant protein according to the present invention is now provided.

Variant protein HSS100PCB_P3 (SEQ ID NO:580) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSS100PCB_T1 (SEQ ID NO:49). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HSS100PCB_P3 (SEQ ID NO:580) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCB_P3 (SEQ ID NO:580) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on amino

Previously known

acid sequence
Alternative amino acid(s)
SNP?

1
M -> R
Yes

11
M -> L
Yes

20
L -> F
Yes

Variant protein HSS100PCB_P3 (SEQ ID NO:580) is encoded by the following transcript(s): HSS100PCB_T1 (SEQ ID NO:49), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSS100PCB_T1 (SEQ ID NO:49) is shown in bold; this coding portion starts at position 1057 and ends at position 1533. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCB_P3 (SEQ ID NO:580) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on nucleotide

Previously known

sequence
Alternative nucleic acid
SNP?

52
C -> T
Yes

107
A -> C
Yes

458
C -> T
Yes

468
A -> G
Yes

648
C -> T
Yes

846
C -> G
Yes

882
G -> A
Yes

960
C -> T
No

965
C -> T
Yes

1058
T -> G
Yes

1087
A -> C
Yes

1114
C -> T
Yes

1968
G -> A
Yes

1971
C -> T
Yes

2010
C -> A
Yes

2099
G ->
No

As noted above, cluster HSS100PCB features 3 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSS100PCB_node_—3 (SEQ ID NO:363) according to the present invention is supported by 16 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1 (SEQ ID NO:49). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSS100PCB_T1 (SEQ ID NO: 49)
1
1133

Segment cluster HSS100PCB_node_—4 (SEQ ID NO:364) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1 (SEQ ID NO:49). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSS100PCB_T1 (SEQ ID NO: 49)
1134
1923

TABLE 11

Oligonucleotides related to this segment

Oligonucleotide name
Overexpressed in cancers
Chip reference

HSS100PCB_0_0_12280
colorectal cancer
Colon

(SEQ ID NO: 1413)

Segment cluster HSS100PCB_node_—5 (SEQ ID NO:365) according to the present invention is supported by 141 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_T1 (SEQ ID NO:49). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSS100PCB_T1 (SEQ ID NO: 49)
1924
2201

Description for Cluster HUMPHOSLIP

Cluster HUMPHOSLIP features 7 transcript(s) and 53 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMPHOSLIP_PEA_2_T6
50

HUMPHOSLIP_PEA_2_T7
51

HUMPHOSLIP_PEA_2_T14
52

HUMPHOSLIP_PEA_2_T16
53

HUMPHOSLIP_PEA_2_T17
54

HUMPHOSLIP_PEA_2_T18
55

HUMPHOSLIP_PEA_2_T19
56

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMPHOSLIP_PEA_2_node_0
366

HUMPHOSLIP_PEA_2_node_19
367

HUMPHOSLIP_PEA_2_node_34
368

HUMPHOSLIP_PEA_2_node_68
369

HUMPHOSLIP_PEA_2_node_70
370

HUMPHOSLIP_PEA_2_node_75
371

HUMPHOSLIP_PEA_2_node_2
372

HUMPHOSLIP_PEA_2_node_3
373

HUMPHOSLIP_PEA_2_node_4
374

HUMPHOSLIP_PEA_2_node_6
375

HUMPHOSLIP_PEA_2_node_7
376

HUMPHOSLIP_PEA_2_node_8
377

HUMPHOSLIP_PEA_2_node_9
378

HUMPHOSLIP_PEA_2_node_14
379

HUMPHOSLIP_PEA_2_node_15
380

HUMPHOSLIP_PEA_2_node_16
381

HUMPHOSLIP_PEA_2_node_17
382

HUMPHOSLIP_PEA_2_node_23
383

HUMPHOSLIP_PEA_2_node_24
384

HUMPHOSLIP_PEA_2_node_25
385

HUMPHOSLIP_PEA_2_node_26
386

HUMPHOSLIP_PEA_2_node_29
387

HUMPHOSLIP_PEA_2_node_30
388

HUMPHOSLIP_PEA_2_node_33
389

HUMPHOSLIP_PEA_2_node_36
390

HUMPHOSLIP_PEA_2_node_37
391

HUMPHOSLIP_PEA_2_node_39
392

HUMPHOSLIP_PEA_2_node_40
393

HUMPHOSLIP_PEA_2_node_41
394

HUMPHOSLIP_PEA_2_node_42
395

HUMPHOSLIP_PEA_2_node_44
396

HUMPHOSLIP_PEA_2_node_45
397

HUMPHOSLIP_PEA_2_node_47
398

HUMPHOSLIP_PEA_2_node_51
399

HUMPHOSLIP_PEA_2_node_52
400

HUMPHOSLIP_PEA_2_node_53
401

HUMPHOSLIP_PEA_2_node_54
402

HUMPHOSLIP_PEA_2_node_55
403

HUMPHOSLIP_PEA_2_node_58
404

HUMPHOSLIP_PEA_2_node_59
405

HUMPHOSLIP_PEA_2_node_60
406

HUMPHOSLIP_PEA_2_node_61
407

HUMPHOSLIP_PEA_2_node_62
408

HUMPHOSLIP_PEA_2_node_63
409

HUMPHOSLIP_PEA_2_node_64
410

HUMPHOSLIP_PEA_2_node_65
411

HUMPHOSLIP_PEA_2_node_66
412

HUMPHOSLIP_PEA_2_node_67
413

HUMPHOSLIP_PEA_2_node_69
414

HUMPHOSLIP_PEA_2_node_71
415

HUMPHOSLIP_PEA_2_node_72
416

HUMPHOSLIP_PEA_2_node_73
417

HUMPHOSLIP_PEA_2_node_74
418

TABLE 3

Proteins of interest

SEQ

ID

Protein Name
NO:
Corresponding Transcript(s)

HUMPHOSLIP_PEA_2_P10
581
HUMPHOSLIP_PEA_2_T17

(SEQ ID NO: 54)

HUMPHOSLIP_PEA_2_P12
582
HUMPHOSLIP_PEA_2_T19

(SEQ ID NO: 56)

HUMPHOSLIP_PEA_2_P30
583
HUMPHOSLIP_PEA_2_T6

(SEQ ID NO: 50)

HUMPHOSLIP_PEA_2_P31
584
HUMPHOSLIP_PEA_2_T7

(SEQ ID NO: 51)

HUMPHOSLIP_PEA_2_P33
585
HUMPHOSLIP_PEA_2_T14

(SEQ ID NO: 52)

HUMPHOSLIP_PEA_2_P34
586
HUMPHOSLIP_PEA_2_T16

(SEQ ID NO: 53)

HUMPHOSLIP_PEA_2_P35
587
HUMPHOSLIP_PEA_2_T18

(SEQ ID NO: 55)

These sequences are variants of the known protein Phospholipid transfer protein precursor (SwissProt accession identifier PLTP_HUMAN; known also according to the synonyms Lipid transfer protein II), SEQ ID NO: 636, referred to herein as the previously known protein.

Protein Phospholipid transfer protein precursor (SEQ ID NO:636) is known or believed to have the following function(s): Converts HDL into larger and smaller particles. May play a key role in extracellular phospholipid transport and modulation of hdl particles. The sequence for protein Phospholipid transfer protein precursor is given at the end of the application, as “Phospholipid transfer protein precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s)

on amino

acid sequence
Comment

282
R -> Q. /FTId = VAR_017020.

372
R -> H. /FTId = VAR_017021.

380
R -> W (in dbSNP: 6065903). /FTId = VAR_017022.

444
F -> L (in dbSNP: 1804161). /FTId = VAR_012073.

487
T -> K (in dbSNP: 1056929). /FTId = VAR_012074.

18
E -> V

Protein Phospholipid transfer protein precursor (SEQ ID NO:636) localization is believed to be secreted.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: lipid metabolism; lipid transport, which are annotation(s) related to Biological Process; lipid binding, which are annotation(s) related to Molecular Function; and extracellular, which are annotation(s) related to Cellular Component.

For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously described. The following oligonucleotides were found to hit this cluster (in relation to colon cancer) but not other segments/transcripts below, shown in Table 5.

TABLE 5

Oligonucleotides related to this cluster

Oligonucleotide name
Overexpressed in cancers
Chip reference

HUMPHOSLIP_0_0_18458
colorectal cancer
Colon

(SEQ ID NO: 1414)

AS noted above, cluster HUMPHOSLIP features/transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Phospholipid transfer protein precursor (SEQ ID NO:636). A description of each variant protein according to the present invention is now provided.

Variant protein HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54). An alignment is given to the known protein (Phospholipid transfer protein precursor (SEQ ID NO:636)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) and PLTP_HUMAN (SEQ ID NO:636):

1. An isolated chimeric polypeptide encoding for HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) comprising a first amino acid sequence being at least 90% homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGBIFYYNISE corresponding to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-67 of HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581), and a second amino acid sequence being at least 90% homologous to KVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVGIDYSLMKDPVASTSNLDMD FRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLDMLL RATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPPDQPEVQLSSMTMDARLSAK MALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHE VVTNHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV corresponding to amino acids 163-493 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 68-398 of HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EK, having a structure as follows: a sequence starting from any of amino acid numbers 67−x to 67; and ending at any of amino acid numbers 68+((n−2)−x), in which x varies from 0 to n−2.

Variant protein HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

16
H -> R
Yes

18
E -> V
Yes

113
S -> F
Yes

118
V ->
No

140
R ->
No

140
R -> P
No

150
N ->
No

160
P ->
No

201
P ->
No

274
M ->
No

285
R -> W
Yes

292
Q ->
No

315
L -> *
No

330
M -> I
Yes

349
F -> L
Yes

392
T -> K
Yes

The glycosylation sites of variant protein HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581), as compared to the known protein Phospholipid transfer protein precursor (SEQ ID NO:636), are described in Table 7 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 7

Glycosylation site(s)

Position(s) on known
Precent in
Position in

amino acid sequence
variant protein?
variant protein?

94
No

143
No

64
Yes
64

245
Yes
150

398
Yes
303

117
No

Variant protein HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54) is shown in bold; this coding portion starts at position 276 and ends at position 1469. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P10 (SEQ ID NO:581) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

431
G -> A
Yes

551
C -> T
Yes

613
C -> T
Yes

628
T ->
No

694
G ->
No

694
G -> C
No

723
A ->
No

753
C ->
No

876
C ->
No

1037
C -> T
Yes

1097
G ->
No

1128
C -> T
Yes

1149
C ->
No

1219
T -> A
No

1230
C -> T
Yes

1265
G -> C
Yes

1322
T -> A
Yes

1450
C -> A
Yes

1469
C -> T
No

1549
C -> T
Yes

1565
A -> G
No

1565
A -> T
No

1630
A -> G
Yes

1654
T -> A
No

1731
G -> T
Yes

1864
G -> A
Yes

1893
G -> T
Yes

2073
G -> A
Yes

2269
C -> T
Yes

2325
G -> T
Yes

2465
C -> T
Yes

2566
C -> T
Yes

2881
A -> G
No

Variant protein HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). An alignment is given to the known protein (Phospholipid transfer protein precursor (SEQ ID NO:636)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) and PLTP_HUMAN (SEQ ID NO:636):

1. An isolated chimeric polypeptide encoding for HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) comprising a first amino acid sequence being at least 90% homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVG IDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAG ALQLLLVGDKVPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPP DQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLN corresponding to amino acids 1-427 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-427 of HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKAGV (SEQ ID NO:1525) corresponding to amino acids 428-432 of HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKAGV (SEQ ID NO:1525) in HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582).

Variant protein HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

16
H -> R
Yes

18
E -> V
Yes

81
D -> H
Yes

124
S -> Y
Yes

160
T ->
No

160
T -> N
No

208
S -> F
Yes

213
V ->
No

235
R -> P
No

235
R ->
No

245
N ->
No

255
P ->
No

296
P ->
No

369
M ->
No

380
R -> W
Yes

387
Q ->
No

410
L -> *
No

425
M -> I
Yes

The glycosylation sites of variant protein HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582), as compared to the known protein Phospholipid transfer protein precursor (SEQ ID NO:636), are described in Table 10 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 10

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

94
Yes
94

143
Yes
143

64
Yes
64

245
Yes
245

398
Yes
398

117
Yes
117

Variant protein HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56) is shown in bold; this coding portion starts at position 276 and ends at position 1571. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P12 (SEQ ID NO:582) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

431
G -> A
Yes

516
G -> C
Yes

644
G -> A
Yes

646
C -> A
Yes

754
C ->
No

754
C -> A
No

836
C -> T
Yes

898
C -> T
Yes

913
T ->
No

979
G ->
No

979
G -> C
No

1008
A ->
No

1038
C ->
No

1161
C ->
No

1322
C -> T
Yes

1382
G ->
No

1413
C -> T
Yes

1434
C ->
No

1504
T -> A
No

1515
C -> T
Yes

1550
G -> C
Yes

1690
T -> A
Yes

1818
C -> A
Yes

1837
C -> T
No

1917
C -> T
Yes

1933
A -> G
No

1933
A -> T
No

1998
A -> G
Yes

2022
T -> A
No

2099
G -> T
Yes

2232
G -> A
Yes

2261
G -> T
Yes

2441
G -> A
Yes

2637
C -> T
Yes

2693
G -> T
Yes

2833
C -> T
Yes

2934
C -> T
Yes

3249
A -> G
No

Variant protein HUMPHOSLIP_PEA_—2_P30 (SEQ ID NO:583) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMPHOSLIP_PEA_—2_P30 (SEQ ID NO:583) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P30 (SEQ ID NO:583) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

16
H -> R
Yes

18
E -> V
Yes

37
R -> Q
Yes

Variant protein HUMPHOSLIP_PEA_—2_P30 (SEQ ID NO:583) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50) is shown in bold; this coding portion starts at position 276 and ends at position 431. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P30 (SEQ ID NO:583) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

385
G -> A
Yes

470
G -> C
Yes

598
G -> A
Yes

600
C -> A
Yes

708
C ->
No

708
C -> A
No

790
C -> T
Yes

852
C -> T
Yes

867
T ->
No

933
G ->
No

933
G -> C
No

962
A ->
No

992
C ->
No

1115
C ->
No

1276
C -> T
Yes

1336
G ->
No

1367
C -> T
Yes

1388
C ->
No

1458
T -> A
No

1469
C -> T
Yes

1504
G -> C
Yes

1561
T -> A
Yes

1689
C -> A
Yes

1708
C -> T
No

1788
C -> T
Yes

1804
A -> G
No

1804
A -> T
No

1869
A -> G
Yes

1893
T -> A
No

1970
G -> T
Yes

2103
G -> A
Yes

2132
G -> T
Yes

2312
G -> A
Yes

2508
C -> T
Yes

2564
G -> T
Yes

2704
C -> T
Yes

2805
C -> T
Yes

3120
A -> G
No

Variant protein HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51). An alignment is given to the known protein (Phospholipid transfer protein precursor (SEQ ID NO:636)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) and PLTP_HUMAN (SEQ ID NO:636):

1. An isolated chimeric polypeptide encoding for HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) comprising a first amino acid sequence being at least 90% homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISE corresponding to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-67 of HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PGLERGADKFPVVGGSSLFLALDLTLRPPVG (SEQ ID NO:1526) corresponding to amino acids 68-98 of HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PGLERGADKFPVVGGSSLFLALDLTLRPPVG (SEQ ID NO:1526) in HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584).

Variant protein HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

16
H -> R
Yes

18
E -> V
Yes

The glycosylation sites of variant protein HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584), as compared to the known protein Phospholipid transfer protein precursor (SEQ ID NO:636), are described in Table 15 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 15

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

94
No

143
No

64
Yes
64

245
No

398
No

117
No

Variant protein HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51) is shown in bold; this coding portion starts at position 276 and ends at position 569. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P31 (SEQ ID NO:584) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

431
G -> A
Yes

608
G -> C
Yes

736
G -> A
Yes

738
C -> A
Yes

846
C ->
No

846
C -> A
No

928
C -> T
Yes

990
C -> T
Yes

1005
T ->
No

1071
G ->
No

1071
G -> C
No

1100
A ->
No

1130
C ->
No

1253
C ->
No

1414
C -> T
Yes

1474
G ->
No

1505
C -> T
Yes

1526
C ->
No

1596
T -> A
No

1607
C -> T
Yes

1642
G -> C
Yes

1699
T -> A
Yes

1827
C -> A
Yes

1846
C -> T
No

1926
C -> T
Yes

1942
A -> G
No

1942
A -> T
No

2007
A -> G
Yes

2031
T -> A
No

2108
G -> T
Yes

2241
G -> A
Yes

2270
G -> T
Yes

2450
G -> A
Yes

2646
C -> T
Yes

2702
G -> T
Yes

2842
C -> T
Yes

2943
C -> T
Yes

3258
A -> G
No

Variant protein HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52). An alignment is given to the known protein (Phospholipid transfer protein precursor (SEQ ID NO:636)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) and PLTP_HUMAN (SEQ ID NO:636):

1. An isolated chimeric polypeptide encoding for HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) comprising a first amino acid sequence being at least 90% homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQ corresponding to amino acids 1-183 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-183 of HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWAATGRRVARVGMLSL (SEQ ID NO:1527) corresponding to amino acids 184-200 of HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWAATGRRVARVGMLSL (SEQ ID NO:1527) in HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585).

Variant protein HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

16
H -> R
Yes

18
E -> V
Yes

81
D -> H
Yes

124
S -> Y
Yes

160
T ->
No

160
T -> N
No

The glycosylation sites of variant protein HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585), as compared to the known protein Phospholipid transfer protein precursor (SEQ ID NO:636), are described in Table 18 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 18

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

94
Yes
94

143
Yes
143

64
Yes
64

245
No

398
No

117
Yes
117

Variant protein HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52) is shown in bold; this coding portion starts at position 276 and ends at position 875. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P33 (SEQ ID NO:585) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

431
G -> A
Yes

516
G -> C
Yes

644
G -> A
Yes

646
C -> A
Yes

754
C ->
No

754
C -> A
No

921
C -> T
Yes

983
C -> T
Yes

998
T ->
No

1064
G ->
No

1064
G -> C
No

1093
A ->
No

1123
C ->
No

1246
C ->
No

1407
C -> T
Yes

1467
G ->
No

1498
C -> T
Yes

1519
C ->
No

1589
T -> A
No

1600
C -> T
Yes

1635
G -> C
Yes

1692
T -> A
Yes

1820
C -> A
Yes

1839
C -> T
No

1919
C -> T
Yes

1935
A -> G
No

1935
A -> T
No

2000
A -> G
Yes

2024
T -> A
No

2101
G -> T
Yes

2234
G -> A
Yes

2263
G -> T
Yes

2443
G -> A
Yes

2639
C -> T
Yes

2695
G -> T
Yes

2835
C -> T
Yes

2936
C -> T
Yes

3251
A -> G
No

Variant protein HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53). An alignment is given to the known protein (Phospholipid transfer protein precursor (SEQ ID NO:636)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) and PLTP_HUMAN (SEQ ID NO:636):

1. An isolated chimeric polypeptide encoding for HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) comprising a first amino acid sequence being at least 90% homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPV corresponding to amino acids 1-205 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-205 of HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LWTSLLALTIPS (SEQ ID NO:1528) corresponding to amino acids 206-217 of HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LWTSLLALTIPS (SEQ ID NO:1528) in HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586).

Variant protein HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
kn own SNP?

16
H -> R
Yes

18
E -> V
Yes

81
D -> H
Yes

124
S -> Y
Yes

160
T ->
No

160
T -> N
No

211
L ->
No

The glycosylation sites of variant protein HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586), as compared to the known protein Phospholipid transfer protein precursor (SEQ ID NO:636), are described in Table 21 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 21

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

94
Yes
94

143
Yes
143

64
Yes
64

245
No

398
No

117
Yes
117

Variant protein HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53) is shown in bold; this coding portion starts at position 276 and ends at position 926. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P34 (SEQ ID NO:586) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

431
G -> A
Yes

516
G -> C
Yes

644
G -> A
Yes

646
C -> A
Yes

754
C ->
No

754
C -> A
No

836
C -> T
Yes

891
C -> T
Yes

906
T ->
No

972
G ->
No

972
G -> C
No

1001
A ->
No

1031
C ->
No

1154
C ->
No

1315
C -> T
Yes

1375
G ->
No

1406
C -> T
Yes

1427
C ->
No

1497
T -> A
No

1508
C -> T
Yes

1543
G -> C
Yes

1600
T -> A
Yes

1728
C -> A
Yes

1747
C -> T
No

1827
C -> T
Yes

1843
A -> G
No

1843
A -> T
No

1908
A -> G
Yes

1932
T -> A
No

2009
G -> T
Yes

2142
G -> A
Yes

2171
G -> T
Yes

2351
G -> A
Yes

2547
C -> T
Yes

2603
G -> T
Yes

2743
C -> T
Yes

2844
C -> T
Yes

3159
A -> G
No

Variant protein HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55). An alignment is given to the known protein (Phospholipid transfer protein precursor (SEQ ID NO:636)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) and PLTP_HUMAN (SEQ ID NO:636):

1. An isolated chimeric polypeptide encoding for HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) comprising a first amino acid sequence being at least 90% homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWF corresponding to amino acids 1-109 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 1-109 of HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587), a second amino acid sequence bridging amino acid sequence comprising of L, a third amino acid sequence being at least 90% homologous to KVYDFLSTFITSGMRFLLNQQ corresponding to amino acids 163-183 of PLTP_HUMAN (SEQ ID NO:636), which also corresponds to amino acids 111-131 of HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWAATGRRVARVGMLSL (SEQ ID NO:1527) corresponding to amino acids 132-148 of HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise

FLK having a structure as follows (numbering according to HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587)): a sequence starting from any of amino acid numbers 109−x to 109; and ending at any of amino acid numbers 111+((n−2)−x), in which x varies from 0 to n−2.

3. An isolated polypeptide encoding for a tail of HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWAATGRRVARVGMLSL (SEQ ID NO:1527) in HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587).

Variant protein HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

16
H -> R
Yes

18
E -> V
Yes

81
D -> H
Yes

The glycosylation sites of variant protein HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587), as compared to the known protein Phospholipid transfer protein precursor (SEQ ID NO:636), are described in Table 24 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 24

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

94
Yes
94

143
No

64
Yes
64

245
No

398
No

117
No

Variant protein HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) is encoded by the following transcript(s): HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) is shown in bold; this coding portion starts at position 276 and ends at position 719. The transcript also has the following SNPs as listed in Table 25 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP_PEA_—2_P35 (SEQ ID NO:587) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

174
G -> T
No

175
A -> T
No

322
A -> G
Yes

328
A -> T
Yes

431
G -> A
Yes

516
G -> C
Yes

765
C -> T
Yes

827
C -> T
Yes

842
T ->
No

908
G ->
No

908
G -> C
No

937
A ->
No

967
C ->
No

1090
C ->
No

1251
C -> T
Yes

1311
G ->
No

1342
C -> T
Yes

1363
C ->
No

1433
T -> A
No

1444
C -> T
Yes

1479
G -> C
Yes

1536
T -> A
Yes

1664
C -> A
Yes

1683
C -> T
No

1763
C -> T
Yes

1779
A -> G
No

1779
A -> T
No

1844
A -> G
Yes

1868
T -> A
No

1945
G -> T
Yes

2078
G -> A
Yes

2107
G -> T
Yes

2287
G -> A
Yes

2483
C -> T
Yes

2539
G -> T
Yes

2679
C -> T
Yes

2780
C -> T
Yes

3095
A -> G
No

As noted above, cluster HUMPHOSLIP features 53 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMPHOSLIP_PEA_—2_node_—0 (SEQ ID NO:366) according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1
264

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1
264

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1
264

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1
264

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1
264

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1
264

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1
264

Segment cluster HUMPHOSLIP_PEA_—2_node_—19 (SEQ ID NO:367) according to the present invention is supported by 186 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
559
714

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
697
852

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
605
760

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
605
760

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
605
760

Segment cluster HUMPHOSLIP_PEA_—2_node_—34 (SEQ ID NO:368) according to the present invention is supported by 191 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
971
1111

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1109
1249

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1102
1242

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1010
1150

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
732
872

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
946
1086

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1017
1157

Segment cluster HUMPHOSLIP_PEA_—2_node_—68 (SEQ ID NO:369) according to the present invention is supported by 131 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1867
2285

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2005
2423

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1998
2416

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1906
2324

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1628
2046

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1842
2260

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1996
2414

Segment cluster HUMPHOSLIP_PEA_—2_node_—70 (SEQ ID NO:370) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2298
2529

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2436
2667

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2429
2660

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2337
2568

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2059
2290

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2273
2504

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2427
2658

Segment cluster HUMPHOSLIP_PEA_—2_node_—75 (SEQ ID NO:371) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2846
3125

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2984
3263

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2977
3256

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2885
3164

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2607
2886

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2821
3100

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2975
3254

Segment cluster HUMPHOSLIP_PEA_—2_node_—2 (SEQ ID NO:372) according to the present invention is supported by 159 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
265
337

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
265
337

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
265
337

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
265
337

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
265
337

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
265
337

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
265
337

Segment cluster HUMPHOSLIP_PEA_—2_node_—3 (SEQ ID NO:373) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51) (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53) (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
338
355

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
338
355

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
338
355

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
338
355

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
338
355

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
338
355

Segment cluster HUMPHOSLIP_PEA_—2_node_—4 (SEQ ID NO:374) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
356
375

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
356
375

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
356
375

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
356
375

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
356
375

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
356
375

Segment cluster HUMPHOSLIP_PEA_—2_node_—6 (SEQ ID NO:375) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
376
383

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
376
383

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
376
383

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
376
383

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
376
383

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
376
383

Segment cluster HUMPHOSLIP_PEA_—2_node_—7 (SEQ ID NO:376) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
338
343

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
384
389

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
384
389

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
384
389

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
384
389

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
384
389

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
384
389

Segment cluster HUMPHOSLIP_PEA_—2_node_—8 (SEQ ID NO:377) according to the present invention is supported by 171 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
334
378

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
390
424

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
390
424

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
390
424

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
390
424

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
390
424

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
390
424

Segment cluster HUMPHOSLIP_PEA_—2_node_—9 (SEQ ID NO:378) according to the present invention is supported by 168 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
379
429

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
425
475

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
425
475

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
425
475

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
425
475

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
425
475

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
425
475

Segment cluster HUMPHOSLIP_PEA_—2_node_—14 (SEQ ID NO:379) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
476
567

Segment cluster HUMPHOSLIP_PEA_—2_node_—15 (SEQ ID NO:380) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
430
445

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
568
583

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
476
491

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
476
491

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
476
491

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
476
491

Segment cluster HUMPHOSLIP_PEA_—2_node_—16 (SEQ ID NO:381) according to the present invention is supported by 179 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
446
534

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
584
672

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
492
580

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
492
580

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
492
580

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
492
580

Segment cluster HUMPHOSLIP_PEA_—2_node_—17 (SEQ ID NO:382) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
535
558

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
673
696

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
581
604

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
581
604

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
581
604

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
581
604

Segment cluster HUMPHOSLIP_PEA_—2_node_—23 (SEQ ID NO:383) according to the present invention is supported by 168 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
715
766

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
853
904

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
761
812

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
761
812

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
476
527

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
605
656

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
761
812

Segment cluster HUMPHOSLIP_PEA_—2_node_—24 (SEQ ID NO:384) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
767
778

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
905
916

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
813
824

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
813
824

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
528
539

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
657
668

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
813
824

Segment cluster HUMPHOSLIP_PEA_—2_node_—25 (SEQ ID NO:385) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52) and HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
825
909

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
669
753

Segment cluster HUMPHOSLIP_PEA_—2_node_—26 (SEQ ID NO:386) according to the present invention is supported by 163 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
779
842

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
917
980

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
910
973

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
825
888

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
540
603

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
754
817

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
825
888

Segment cluster HUMPHOSLIP_PEA_—2_node_—29 (SEQ ID NO:387) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
843
849

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
981
387

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
974
980

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
604
610

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
818
824

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
889
895

Segment cluster HUMPHOSLIP_PEA_—2_node_—30 (SEQ ID NO:388) according to the present invention is supported by 181 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
850
934

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
988
1072

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
981
1065

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
889
973

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
611
695

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
825
909

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
896
980

Segment cluster HUMPHOSLIP_PEA_—2_node_—33 (SEQ ID NO:389) according to the present invention is supported by 173 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
935
970

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1073
1108

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1066
1101

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
974
1009

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
696
731

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
910
945

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
981
1016

Segment cluster HUMPHOSLIP_PEA_—2_node_—36 (SEQ ID NO:390) according to the present invention is supported by 163 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1112
1156

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1250
1294

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1243
1287

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1151
1195

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
873
917

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1087
1131

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1158
1202

Segment cluster HUMPHOSLIP_PEA_—2_node_—37 (SEQ ID NO:391) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1157
1171

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1295
1309

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1288
1302

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1196
1210

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
918
932

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1132
1146

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1203
1217

Segment cluster HUMPHOSLIP_PEA_—2_node_—39 (SEQ ID NO:392) according to the present invention is supported by 166 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1172
1201

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1310
1339

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1303
1332

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1211
1240

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
933
962

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1147
1176

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1218
1247

Segment cluster HUMPHOSLIP_PEA_—2_node_—40 (SEQ ID NO:393) according to the present invention is supported by 199 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1202
1288

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1340
1426

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1333
1419

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1241
1327

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
963
1049

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1177
1263

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1248
1334

Segment cluster HUMPHOSLIP_PEA_—2_node_—41 (SEQ ID NO:394) according to the present invention is supported by 186 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1289
1318

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1427
1456

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1420
1449

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1328
1357

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1050
1079

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1264
1293

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1335
1364

Segment cluster HUMPHOSLIP_PEA_—2_node_—42 (SEQ ID NO:395) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1319
1336

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1457
1474

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1450
1467

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1358
1375

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1080
1097

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1294
1311

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1365
1382

Segment cluster HUMPHOSLIP_PEA_—2_node_—44 (SEQ ID NO:396) according to the present invention is supported by 185 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1337
1363

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1475
1501

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1468
1494

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1376
1402

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1098
1124

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1312
1338

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1383
1409

Segment cluster HUMPHOSLIP_PEA_—2_node_—45 (SEQ ID NO:397) according to the present invention is supported by 197 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1364
1404

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1502
1542

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1495
1535

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1403
1443

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1125
1165

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1339
1379

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1410
1450

Segment cluster HUMPHOSLIP_PEA_—2_node_—47 (SEQ ID NO:398) according to the present invention is supported by 223 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1405
1447

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1543
1585

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1536
1578

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1444
1486

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1166
1208

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1380
1422

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1451
1493

Segment cluster HUMPHOSLIP_PEA_—2_node_—51 (SEQ ID NO:399) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1448
1462

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1586
1600

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1579
1593

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1487
1501

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1209
1223

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1423
1437

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1494
1508

Segment cluster HUMPHOSLIP_PEA_—2_node_—52 (SEQ ID NO:400) according to the present invention is supported by 235 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1463
1511

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1601
1649

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1594
1642

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1502
1550

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1224
1272

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1438
1486

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1509
1557

Segment cluster HUMPHOSLIP_PEA_—2_node_—53 (SEQ ID NO:401) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1558
1640

Segment cluster HUMPHOSLIP_PEA_—2_node_—54 (SEQ ID NO:402) according to the present invention is supported by 236 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1512
1552

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1650
1690

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1643
1683

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1551
1591

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1273
1313

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1487
1527

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1641
1681

Segment cluster HUMPHOSLIP_PEA_—2_node_—55 (SEQ ID NO:403) according to the present invention is supported by 232 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1553
1588

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1691
1726

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1684
1719

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1592
1627

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1314
1349

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1528
1563

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1682
1717

Segment cluster HUMPHOSLIP_PEA_—2_node_—58 (SEQ ID NO:404) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1589
1612

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1727
1750

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1720
1743

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1628
1651

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1350
1373

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1564
1587

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1718
1741

Segment cluster HUMPHOSLIP_PEA_—2_node_—59 (SEQ ID NO:405) according to the present invention is supported by 230 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1613
1648

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1751
1786

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1744
1779

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1652
1687

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1374
1409

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1588
1623

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1742
1777

Segment cluster HUMPHOSLIP_PEA_—2_node_—60 (SEQ ID NO:406) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1649
1671

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1787
1809

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1780
1802

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1688
1710

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1410
1432

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1624
1646

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1778
1800

Segment cluster HUMPHOSLIP_PEA_—2_node_—61 (SEQ ID NO:407) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50) (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54) (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1672
1680

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1810
1818

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1803
1811

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1711
1719

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1433
1441

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1647
1655

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1801
1809

Segment cluster HUMPHOSLIP_PEA_—2_node_—62 (SEQ ID NO:408) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1681
1703

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1819
1841

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1812
1834

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1720
1742

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1442
1464

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1656
1678

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1810
1832

Segment cluster HUMPHOSLIP_PEA_—2_node_—63 (SEQ ID NO:409) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 69 below describes the starting and ending position of this segment on each transcript.

TABLE 69

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1704
1727

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1842
1865

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1835
1858

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1743
1766

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1465
1488

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1679
1702

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1833
1856

Segment cluster HUMPHOSLIP_PEA_—2_node_—64 (SEQ ID NO:410) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1728
1734

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1866
1872

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1859
1865

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1767
1773

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1489
1495

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1703
1709

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1857
1863

Segment cluster HUMPHOSLIP_PEA_—2_node_—65 (SEQ ID NO:411) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1735
1754

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1873
1892

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1866
1885

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1774
1793

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1496
1515

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1710
1729

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1864
1883

Segment cluster HUMPHOSLIP_PEA_—2_node_—66 (SEQ ID NO:412) according to the present invention is supported by 180 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1755
1844

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1893
1982

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1886
1975

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1794
1883

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1516
1605

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1730
1819

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1884
1973

Segment cluster HUMPHOSLIP_PEA_—2_node_—67 (SEQ ID NO:413) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 73 below describes the starting and ending position of this segment on each transcript.

TABLE 73

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
1845
1866

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
1983
2004

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
1976
1997

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
1884
1905

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
1606
1627

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
1820
1841

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
1974
1995

Segment cluster HUMPHOSLIP_PEA_—2_node_—69 (SEQ ID NO:414) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 74 below describes the starting and ending position of this segment on each transcript.

TABLE 74

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2286
2297

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2424
2435

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2417
2428

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2325
2336

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2047
2058

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2261
2272

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2415
2426

Segment cluster HUMPHOSLIP_PEA_—2_node_—71 (SEQ ID NO:415) according to the present invention can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 75 below describes the starting and ending position of this segment on each transcript.

TABLE 75

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2530
2542

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2668
2680

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2661
2673

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2569
2581

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2291
2303

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2505
2517

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2659
2671

Segment cluster HUMPHOSLIP_PEA_—2_node_—72 (SEQ ID NO:416) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 76 below describes the starting and ending position of this segment on each transcript.

TABLE 76

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2543
2647

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2681
2785

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2674
2778

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2582
2686

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2304
2408

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2518
2622

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2672
2776

Segment cluster HUMPHOSLIP_PEA_—2_node_—73 (SEQ ID NO:417) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 77 below describes the starting and ending position of this segment on each transcript.

TABLE 77

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2648
2755

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2786
2893

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2779
2886

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2687
2794

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2409
2516

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2623
2730

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2777
2884

Segment cluster HUMPHOSLIP_PEA_—2_node_—74 (SEQ ID NO:418) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP_PEA_—2_T6 (SEQ ID NO:50), HUMPHOSLIP_PEA_—2_T7 (SEQ ID NO:51), HUMPHOSLIP_PEA_—2_T14 (SEQ ID NO:52), HUMPHOSLIP_PEA_—2_T16 (SEQ ID NO:53), HUMPHOSLIP_PEA_—2_T17 (SEQ ID NO:54), HUMPHOSLIP_PEA_—2_T18 (SEQ ID NO:55) and HUMPHOSLIP_PEA_—2_T19 (SEQ ID NO:56). Table 78 below describes the starting and ending position of this segment on each transcript.

TABLE 78

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 50)
2756
2845

HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 51)
2894
2983

HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 52)
2887
2976

HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 53)
2795
2884

HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 54)
2517
2606

HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 55)
2731
2820

HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 56)
2885
2974

Variant Protein Alignment to the Previously Known Protein:

Sequence name: PLTP_HUMAN (SEQ ID NO: 636)

Sequence documentation:

Alignment of:

HUMPHOSLIP_PEA_2_P10 (SEQ ID NO: 581) × PLTP_HUMAN (SEQ ID

NO: 636) . .

Alignment segment 1/1:

Quality:
3716.00
Escore:
0

Matching length:
398
Total length:
493

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
80.73
Total Percent Identity:
80.73

Gaps:
1

Alignment:

Sequence name: PLTP_HUMAN (SEQ ID NO: 636)

Sequence documentation:

Alignment of:

HUMPHOSLIP_PEA_2_P12 (SEQ ID NO: 582) × PLTP_HUMAN (SEQ ID

NO: 636) . .

Alignment segment 1/1:

Quality:
4101.00
Escore:
0

Matching length:
427
Total length:
427

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: PLTP HUMAN (SEQ ID NO: 636)

Sequence documentation:

Alignment of:

HUMPHOSLIP_PEA_2_P31 (SEQ ID NO: 584) × PLTP_HUMAN (SEQ ID

NO: 636) . .

Alignment segment 1/1:

Quality:
639.00
Escore:
0

Matching length:
67
Total length:
67

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: PLTP_HUMAN (SEQ ID NO: 636)

Sequence documentation:

Alignment of:

HUMPHOSLIP_PEA_2_P33 (SEQ ID NO: 585) × PLTP_HUMAN (SEQ ID

NO: 636) . .

Alignment segment 1/1:

Quality:
1767.00
Escore:
0

Matching length:
184
Total length:
184

Matching Percent Similarity:
100.00
Matching Percent Identity:
99.46

Total Percent Similarity:
100.00
Total Percent Identity:
99.46

Gaps:
0

Alignment:

Sequence name: PLTP_HUMAN (SEQ ID NO: 636)

Sequence documentation:

Alignment of:

HUMPHOSLIP_PEA_2_P34 (SEQ ID NO: 586) × PLTP_HUMAN (SEQ ID

NO: 636) . .

Alignment segment 1/1:

Quality:
1971.00
Escore:
0

Matching length:
205
Total length:
205

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: PLTP_HUMAN (SEQ ID NO: 636)

Sequence documentation:

Alignment of:

HUMPHOSLIP_PEA_2_P35 (SEQ ID NO: 587) × PLTP HUMAN (SEQ ID

NO: 636) . .

Alignment segment 1/1:

Quality:
1158.00
Escore:
0

Matching length:
132
Total length:
184

Matching Percent Similarity:
100.00
Matching Percent Identity:
98.48

Total Percent Similarity:
71.74
Total Percent Identity:
70.65

Gaps:
1

Alignment:

Description for Cluster D11853

Cluster D11853 features 18 transcript(s) and 31 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

D11853_PEA_1_T1
57

D11853_PEA_1_T3
58

D11853_PEA_1_T7
59

D11853_PEA_1_T8
60

D11853_PEA_1_T9
61

D11853_PEA_1_T10
62

D11853_PEA_1_T13
63

D11853_PEA_1_T14
64

D11853_PEA_1_T15
65

D11853_PEA_1_T16
66

D11853_PEA_1_T17
67

D11853_PEA_1_T19
68

D11853_PEA_1_T21
69

D11853_PEA_1_T23
70

D11853_PEA_1_T24
71

D11853_PEA_1_T25
72

D11853_PEA_1_T26
73

D11853_PEA_1_T27
74

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

D11853_PEA_1_node_3
419

D11853_PEA_1_node_6
420

D11853_PEA_1_node_9
421

D11853_PEA_1_node_17
422

D11853_PEA_1_node_21
423

D11853_PEA_1_node_22
424

D11853_PEA_1_node_23
425

D11853_PEA_1_node_25
426

D11853_PEA_1_node_26
427

D11853_PEA_1_node_27
428

D11853_PEA_1_node_30
429

D11853_PEA_1_node_32
430

D11853_PEA_1_node_0
431

D11853_PEA_1_node_1
432

D11853_PEA_1_node_2
433

D11853_PEA_1_node_4
434

D11853_PEA_1_node_5
435

D11853_PEA_1_node_7
436

D11853_PEA_1_node_8
437

D11853_PEA_1_node_10
438

D11853_PEA_1_node_12
439

D11853_PEA_1_node_13
440

D11853_PEA_1_node_14
441

D11853_PEA_1_node_15
442

D11853_PEA_1_node_16
443

D11853_PEA_1_node_18
444

D11853_PEA_1_node_19
445

D11853_PEA_1_node_20
446

D11853_PEA_1_node_24
447

D11853_PEA_1_node_28
448

D11853_PEA_1_node_29
449

TABLE 3

Proteins of interest

SEQ ID

Protein Name
NO:
Corresponding Transcript(s)

D11853_PEA_1_P1
588
D11853_PEA_1_T1 (SEQ ID

NO: 57)

D11853_PEA_1_P2
589
D11853_PEA_1_T3 (SEQ ID

NO: 58)

D11853_PEA_1_P7
590
D11853_PEA_1_T10 (SEQ ID

NO: 62)

D11853_PEA_1_P9
591
D11853_PEA_1_T13 (SEQ ID

NO: 63)

D11853_PEA_1_P10
592
D11853_PEA_1_T14 (SEQ ID

NO: 64)

D11853_PEA_1_P11
593
D11853_PEA_1_T15 (SEQ ID

NO: 65)

D11853_PEA_1_P12
594
D11853_PEA_1_T16 (SEQ ID

NO: 66); D11853_PEA_1_T23

(SEQ ID NO: 70)

D11853_PEA_1_P14
595
D11853_PEA_1_T19 (SEQ ID

NO: 68)

D11853_PEA_1_P16
596
D11853_PEA_1_T24 (SEQ ID

NO: 71)

D11853_PEA_1_P18
597
D11853_PEA_1_T26 (SEQ ID

NO: 73)

D11853_PEA_1_P19
598
D11853_PEA_1_T27 (SEQ ID

NO: 74)

D11853_PEA_1_P20
599
D11853_PEA_1_T7 (SEQ ID

NO: 59); D11853_PEA_1_T17

(SEQ ID NO: 67);

D11853_PEA_1_T25 (SEQ ID

NO: 72)

D11853_PEA_1_P21
600
D11853_PEA_1_T8 (SEQ ID

NO: 60)

D11853_PEA_1_P22
601
D11853_PEA_1_T9 (SEQ ID

NO: 61)

D11853_PEA_1_P24
602
D11853_PEA_1_T21 (SEQ ID

NO: 69)

These sequences are variants of the known protein Membrane associated protein SLP-2 (SwissProt accession identifier Q9UJZ1; known also according to the synonyms Stomatin-like protein 2; Stomatin-like 2; Hypothetical protein FLJ14499), SEQ ID NO: 637, referred to herein as the previously known protein.

The sequence for protein Membrane associated protein SLP-2 (SEQ ID NO:637) is given at the end of the application, as “Membrane associated protein SLP-2 amino acid sequence”.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: ligand, which are annotation(s) related to Molecular Function; and cytoskeleton; membrane, which are annotation(s) related to Cellular Component.

Cluster D11853 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 26 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, colorectal cancer and a mixture of malignant tumors from different tissues.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

adrenal
160

bladder
82

Bone
71

brain
70

colon
31

epithelial
106

general
88

head and neck
0

kidney
71

liver
53

lung
108

lymph nodes
107

breast
158

bone marrow
0

muscle
94

ovary
131

pancreas
113

prostate
106

skin
193

stomach
73

Thyroid
0

uterus
140

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
7.4e−01
6.9e−01
9.5e−01
0.4
7.1e−01
0.7

bladder
7.0e−01
6.6e−01
6.2e−01
1.1
7.1e−01
1.0

bone
4.9e−01
6.3e−01
7.9e−01
0.9
2.1e−01
1.1

brain
7.4e−02
2.0e−02
1.0e−01
1.5
5.2e−12
3.2

colon
2.6e−03
5.7e−04
9.9e−03
4.3
1.3e−02
4.0

epithelial
3.2e−01
2.5e−02
3.3e−01
1.0
9.1e−08
1.8

general
4.9e−02
2.3e−04
3.6e−03
1.3
1.4e−23
2.2

head and neck
2.1e−01
1.1e−01
1
1.1
4.2e−01
2.0

kidney
8.6e−01
8.8e−01
9.7e−01
0.4
8.1e−01
0.6

liver
5.2e−01
9.1e−02
1
0.5
1.0e−01
2.4

lung
7.1e−01
7.3e−01
8.9e−01
0.6
1.3e−01
0.9

lymph nodes
5.9e−01
6.6e−01
4.1e−01
1.3
6.0e−01
0.9

breast
1.9e−01
1.5e−01
2.6e−01
1.0
1.4e−01
1.3

bone marrow
4.3e−01
2.5e−01
1
3.3
1.5e−01
4.0

muscle
6.7e−01
5.1e−01
1
0.2
1.6e−02
0.7

ovary
6.3e−01
4.9e−01
6.9e−01
0.9
2.8e−01
1.0

pancreas
2.2e−01
1.7e−01
3.8e−02
0.9
5.5e−05
1.6

prostate
8.7e−01
8.3e−01
8.3e−01
0.7
1.8e−01
1.0

skin
5.0e−01
4.9e−01
6.9e−01
0.8
3.3e−02
0.9

stomach
5.2e−01
3.9e−01
1
0.4
2.0e−01
1.5

Thyroid
4.6e−01
4.6e−01
1
1.2
1
1.2

uterus
6.1e−01
3.6e−01
1.7e−01
1.0
1.2e−01
1.3

As noted above, cluster D11853 features 18 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Membrane associated protein SLP-2 (SEQ ID NO:637). A description of each variant protein according to the present invention is now provided.

Variant protein D11853_PEA_—1_P1 (SEQ ID NO:588) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T1 (SEQ ID NO:57). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P1 (SEQ ID NO:588) and Q9P042 (SEQ ID NO 639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P1 (SEQ ID NO:588), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P1 (SEQ ID NO:588), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of D11853_PEA_—1_P1 (SEQ ID NO:588), a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_—1_P1 (SEQ ID NO:588), and a third amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDA AASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGT DASLDEELDRVKMS corresponding to amino acids 189-342 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 203-356 of D11853_PEA_—1_P1 (SEQ ID NO:588), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P1 (SEQ ID NO:588), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P1 (SEQ ID NO:588).

Comparison Report Between D11853_PEA_—1_P1 (SEQ ID NO:588) and BAC85377 (SEQ ID NO 640):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P1 (SEQ ID NO:588), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1-109 of D11853_PEA_—1_P1 (SEQ ID NO:588), a second amino acid sequence being at least 90% homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKD IHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLA KAKAKAEAIRILAAALTQH corresponding to amino acids 1-159 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 110-268 of D11853_PEA_—1_P1 (SEQ ID NO:588), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRD VQGTDASLDEELDRVKMS corresponding to amino acids 269-356 of D11853_PEA_—1_P1 (SEQ ID NO:588), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P1 (SEQ ID NO:588), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P1 (SEQ ID NO:588).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P1 (SEQ ID NO:588), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRD VQGTDASLDEELDRVKMS in D11853_PEA_—1_P1 (SEQ ID NO:588).

Comparison Report Between D11853_PEA_—1_P1 (SEQ ID NO:588) and Q96FY2 (SEQ ID NO: 638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P1 (SEQ ID NO:588), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P1 (SEQ ID NO:588), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P1 (SEQ ID NO:588), and a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERR KRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHN GDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDV QGTDASLDEELDRVKMS corresponding to amino acids 130-356 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-356 of D11853_PEA_—1_P1 (SEQ ID NO:588), wherein said first amino acid sequence, bridging amino acid and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P1 (SEQ ID NO:588) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P1 (SEQ ID NO:588) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

206
E -> K
No

230
E -> K
No

230
E -> Q
No

235
E ->
No

235
E -> D
No

239
Q -> P
No

244
A -> G
No

244
A ->
No

267
Q -> H
No

278
V -> G
No

284
S -> N
No

284
S -> T
No

299
P ->
No

299
P -> A
No

326
G ->
No

329
D -> N
No

340
Q ->
No

Variant protein D11853_PEA_—1_P1 (SEQ ID NO:588) is encoded by the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T1 (SEQ ID NO:57) is shown in bold; this coding portion starts at position 108 and ends at position 1175. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P1 (SEQ ID NO:588) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously known

nucleotide sequence
nucleic acid
SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

723
G -> A
No

795
G -> A
No

795
G -> C
No

812
A ->
No

812
A -> C
No

823
A -> C
No

838
C ->
No

838
C -> G
No

908
A -> C
No

932
A -> C
No

940
T -> G
No

958
G -> A
No

958
G -> C
No

966
-> C
No

966
-> T
No

973
-> G
No

1002
C ->
No

1002
C -> G
No

1033
-> G
No

1083
G ->
No

1092
G -> A
No

1112
C -> T
No

1127
G ->
No

1208
G -> A
No

1211
A ->
No

1211
A -> C
No

1257
T ->
No

1260
T -> C
No

1260
T -> G
No

1297
T -> C
Yes

Variant protein D11853_PEA_—1_P2 (SEQ ID NO:589) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T3 (SEQ ID NO:58). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P2 (SEQ ID NO:589) and Q9P042 (SEQ ID NO: 639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P2 (SEQ ID NO:589), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of D11853_PEA_—1_P2 (SEQ ID NO:589), a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_—1_P2 (SEQ ID NO:589), a third amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDA AASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQ corresponding to amino acids 189-297 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 203-311 of D11853_PEA_—1_P2 (SEQ ID NO:589) and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRAL (SEQ ID NO:1533) corresponding to amino acids 312-315 of D11853_PEA_—1_P2 (SEQ ID NO:589), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P2 (SEQ ID NO:589).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRAL (SEQ ID NO:1533) in D11853_PEA_—1_P2 (SEQ ID NO:589).

Comparison Report Between D11853_PEA_—1_P2 (SEQ ID NO:589) and BAC85377 (SEQ ID NO: 640):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1-109 of D11853_PEA_—1_P2 (SEQ ID NO:589), a second amino acid sequence being at least 90% homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKD IHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLA KAKAKAEAIRILAAALTQH corresponding to amino acids 1-159 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 110-268 of D11853_PEA_—1_P2 (SEQ ID NO:589), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQVRAL corresponding to amino acids 269-315 of D11853_PEA_—1_P2 (SEQ ID NO:589), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P2 (SEQ ID NO:589).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQVRAL in D11853_PEA_—1_P2 (SEQ ID NO:589).

Comparison Report Between D11853_PEA_—1_P2 (SEQ ID NO:589) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P2 (SEQ ID NO:589), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P2 (SEQ ID NO:589), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERR KRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHN GDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQ corresponding to amino acids 130-311 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-311 of D11853_PEA_—1_P2 (SEQ ID NO:589), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRAL (SEQ ID NO:1533) corresponding to amino acids 312-315 of D11853_PEA_—1_P2 (SEQ ID NO:589), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRAL (SEQ ID NO:1533) in D11853_PEA_—1_P2 (SEQ ID NO:589).

Comparison Report Between D11853_PEA_—1_P2 (SEQ ID NO:589) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P2 (SEQ ID NO:589), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRES AINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQIINGDAAASLTVAEQY VSAFSKLAKDSNTILLPSNPGDVTSMVAQ corresponding to amino acids 1-311 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-311 of D11853_PEA_—1_P2 (SEQ ID NO:589), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRAL (SEQ ID NO:1533) corresponding to amino acids 312-315 of D11853_PEA_—1_P2 (SEQ ID NO:589), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P2 (SEQ ID NO:589) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P2 (SEQ ID NO:589) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

206
E -> K
No

230
E -> Q
No

230
E -> K
No

235
E -> D
No

235
E ->
No

239
Q -> P
No

244
A ->
No

244
A -> G
No

267
Q -> H
No

278
V -> G
No

284
S -> T
No

284
S -> N
No

299
P -> A
No

299
P ->
No

Variant protein D11853_PEA_—1_P2 (SEQ ID NO:589) is encoded by the following transcript(s): D11853_PEA_—1_T3 (SEQ ID NO:58), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T3 (SEQ ID NO:58) is shown in bold; this coding portion starts at position 108 and ends at position 1052. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P2 (SEQ ID NO:589) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on
Alternative
Previously known

nucleotide sequence
nucleic acid
SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

723
G -> A
No

795
G -> A
No

795
G -> C
No

812
A ->
No

812
A -> C
No

823
A -> C
No

838
C ->
No

838
C -> G
No

908
A -> C
No

932
A -> C
No

940
T -> G
No

958
G -> A
No

958
G -> C
No

966
-> C
No

966
-> T
No

973
-> G
No

1002
C ->
No

1002
C -> G
No

1033
-> G
No

1066
C -> T
No

1508
G ->
No

1517
G -> A
No

1537
C -> T
No

1552
G ->
No

1633
G -> A
No

1636
A ->
No

1636
A -> C
No

1682
T ->
No

1685
T -> C
No

1685
T -> G
No

1722
T -> C
Yes

Variant protein D11853_PEA_—1_P7 (SEQ ID NO:590) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T10 (SEQ ID NO:62). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P7 (SEQ ID NO:590) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P7 (SEQ ID NO:590), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of D11853_PEA_—1_P7 (SEQ ID NO:590), a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_—1_P7 (SEQ ID NO:590), a third amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 189-254 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 203-268 of D11853_PEA_—1_P7 (SEQ ID NO:590), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) corresponding to amino acids 269-290 of D11853_PEA_—1_P7 (SEQ ID NO:590), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P7 (SEQ ID NO:590).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) in D11853_PEA_—1_P7 (SEQ ID NO:590).

Comparison Report Between D11853_PEA_—1_P7 (SEQ ID NO:590) and BAC85377 (SEQ ID NO:640):

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P7 (SEQ ID NO:590).

Comparison Report Between D11853_PEA_—1_P7 (SEQ ID NO:590) and Q96FY2 (SEQ ID NO 638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P7 (SEQ ID NO:590), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P7 (SEQ ID NO:590), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERR KRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 130-268 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-268 of D11853_PEA_—1_P7 (SEQ ID NO:590), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) corresponding to amino acids 269-290 of D11853_PEA_—1_P7 (SEQ ID NO:590), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) in D11853_PEA_—1_P7 (SEQ ID NO:590).

Comparison Report Between D11853_PEA_—1_P7 (SEQ ID NO:590) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P7 (SEQ ID NO:590), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRES AINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 1-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-268 of D11853_PEA_—1_P7 (SEQ ID NO:590), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) corresponding to amino acids 269-290 of D11853_PEA_—1_P7 (SEQ ID NO:590), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM: Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P7 (SEQ ID NO:590) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P7 (SEQ ID NO:590) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

206
E -> K
No

230
E -> K
No

230
E -> Q
No

235
E ->
No

235
E -> D
No

239
Q -> P
No

244
A ->
No

244
A -> G
No

267
Q -> H
No

Variant protein D11853_PEA_—1_P7 (SEQ ID NO:590) is encoded by the following transcript(s): D11853_PEA_—1_T10 (SEQ ID NO:62), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T10 (SEQ ID NO:62) is shown in bold; this coding portion starts at position 108 and ends at position 977. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P7 (SEQ ID NO:590) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

723
G -> A
No

795
G -> A
No

795
G -> C
No

812
A ->
No

812
A -> C
No

823
A -> C
No

838
C ->
No

838
C -> G
No

908
A -> C
No

1137
A -> C
No

1145
T -> G
No

1163
G -> A
No

1163
G -> C
No

1171
-> C
No

1171
-> T
No

1178
-> G
No

1207
C ->
No

1207
C -> G
No

1238
-> G
No

1288
G ->
No

1297
G -> A
No

1317
C -> T
No

1332
G ->
No

1413
G -> A
No

1416
A ->
No

1416
A -> C
No

1462
T ->
No

1465
T -> C
No

1465
T -> G
No

1502
T -> C
Yes

Variant protein D11853_PEA_—1_P9 (SEQ ID NO:591) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T13 (SEQ ID NO:63). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P9 (SEQ ID NO:591) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P9 (SEQ ID NO:591), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of D11853_PEA_—1_P9 (SEQ ID NO:591), a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_—1_P9 (SEQ ID NO:591), a third amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 189-226 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 203-240 of D11853_PEA_—1_P9 (SEQ ID NO:591), a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P9 (SEQ ID NO:591), and a fifth amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVA QAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 227-342 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 282-397 of D11853_PEA_—1_P9 (SEQ ID NO:591), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P9 (SEQ ID NO:591).

3. An isolated polypeptide encoding for an edge portion of D11853_PEA_—1_P9 (SEQ ID NO:591) comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538), corresponding to D11853_PEA_—1_P9 (SEQ ID NO:591).

Comparison Report Between D11853_PEA_—1_P9 (SEQ ID NO:591) and BAC85377 (SEQ ID NO:640):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1-109 of D11853_PEA_—1_P9 (SEQ ID NO:591), a second amino acid sequence being at least 90% homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKD IHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 1-131 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 110-240 of D11853_PEA_—1_P9 (SEQ ID NO:591), a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P9 (SEQ ID NO:591), a fourth amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 132-159 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 282-309 of D11853_PEA_—1_P9 (SEQ ID NO:591), and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRD VQGTDASLDEELDRVKMS (SEQ ID NO:1531) corresponding to amino acids 310-397 of D11853_PEA_—1_P9 (SEQ ID NO:591), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P9 (SEQ ID NO:591).

3. An isolated polypeptide encoding for an edge portion of D11853_PEA_—1_P9 (SEQ ID NO:591), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538), corresponding to D11853_PEA_—1_P9 (SEQ ID NO:591).

4. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRD VQGTDASLDEELDRVKMS (SEQ ID NO:1531) in D11853_PEA_—1_P9 (SEQ ID NO:591).

Comparison Report Between D11853_PEA_—1_P9 (SEQ ID NO:591) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P9 (SEQ ID NO:591), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P9 (SEQ ID NO:591), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERR KRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 130-240 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-240 of D11853_PEA_—1_P9 (SEQ ID NO:591), a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P9 (SEQ ID NO:591), and a fourth amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVA QAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 241-356 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 282-397 of D11853_PEA_—1_P9 (SEQ ID NO:591), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of D11853_PEA_—1_P9 (SEQ ID NO:591) comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538), corresponding to D11853_PEA_—1_P9 (SEQ ID NO:591).

Comparison Report Between D11853_PEA_—1_P9 (SEQ ID NO:591) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P9 (SEQ ID NO:591), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRES AINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 1-240 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-240 of D11853_PEA_—1_P9 (SEQ ID NO:591), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P9 (SEQ ID NO:591), and a third amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVA QAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 241-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 282-397 of D11853_PEA_—1_P9 (SEQ ID NO:591), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P9 (SEQ ID NO:591) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P9 (SEQ ID NO:591) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

206
E -> K
No

230
E -> K
No

230
E -> Q
No

235
E ->
No

235
E -> D
No

239
Q -> P
No

285
A -> G
No

285
A ->
No

308
Q -> H
No

319
V -> G
No

325
S -> N
No

325
S -> T
No

340
P ->
No

340
P -> A
No

367
G ->
No

370
D -> N
No

381
Q ->
No

Variant protein D11853_PEA_—1_P9 (SEQ ID NO:591) is encoded by the following transcript(s): D11853_PEA_—1_T13 (SEQ ID NO:63), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T13 (SEQ ID NO:63) is shown in bold; this coding portion starts at position 108 and ends at position 1298. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P9 (SEQ ID NO:591) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

723
G -> A
No

795
G -> A
No

795
G -> C
No

812
A ->
No

812
A -> C
No

823
A -> C
No

961
C ->
No

961
C -> G
No

1031
A -> C
No

1055
A -> C
No

1063
T -> G
No

1081
G -> A
No

1081
G -> C
No

1089
-> C
No

1089
-> T
No

1096
-> G
No

1125
C ->
No

1125
C -> G
No

1156
-> G
No

1206
G ->
No

1215
G -> A
No

1235
C -> T
No

1250
G ->
No

1331
G -> A
No

1334
A ->
No

1334
A -> C
No

1380
T ->
No

1383
T -> C
No

1383
T -> G
No

1420
T -> C
Yes

Variant protein D11853_PEA_—1_P10 (SEQ ID NO:592) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T14 (SEQ ID NO:64). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P10 (SEQ ID NO:592) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P10 (SEQ ID NO:592), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of D11853_PEA_—1_P10 (SEQ ID NO:592), a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_—1_P10 (SEQ ID NO:592), a third amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 189-254 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 269-313 of D11853_PEA_—1_P10 (SEQ ID NO:592), and a fourth amino acid sequence being at least 90% homologous to AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS (SEQ ID NO:1540) corresponding to amino acids 298-342 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 269-313 of D11853_PEA_—1_P10 (SEQ ID NO:592), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P10 (SEQ ID NO:592).

3. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P10 (SEQ ID NO:592) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268−x to 268; and ending at any of amino acid numbers 269+((n−2)−x), in which x varies from 0 to n−2.

Comparison Report Between D11853_PEA_—1_P10 (SEQ ID NO:592) and BAC85377 (SEQ ID NO:640):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1-109 of D11853_PEA_—1_P10 (SEQ ID NO:592), a second amino acid sequence being at least 90% homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKD IHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLA KAKAKAEAIRILAAALTQH corresponding to amino acids 1-159 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 110-268 of D11853_PEA_—1_P10 (SEQ ID NO:592), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS (SEQ ID NO:1540) corresponding to amino acids 269-313 of D11853_PEA_—1_P10 (SEQ ID NO:592), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEWINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P10 (SEQ ID NO:592).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS (SEQ ID NO:1540) in D11853_PEA_—1_P10 (SEQ ID NO:592).

Comparison Report Between D11853_PEA_—1_P10 (SEQ ID NO:592) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P10 (SEQ ID NO:592), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P10 (SEQ ID NO:592), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERR KRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 130-268 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-268 of D11853_PEA_—1_P10 (SEQ ID NO:592), and a third amino acid sequence being at least 90% homologous to AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS (SEQ ID NO:1540) corresponding to amino acids 312-356 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 269-313 of D11853_PEA_—1_P10 (SEQ ID NO:592), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P10 (SEQ ID NO:592) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268−x to 268; and ending at any of amino acid numbers 269+((n−2)−x), in which x varies from 0 to n−2.

Comparison Report Between D11853_PEA_—1_P10 (SEQ ID NO:592) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P10 (SEQ ID NO:592), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRES AINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 1-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-268 of D11853_PEA_—1_P10 (SEQ ID NO:592), and a second amino acid sequence being at least 90% homologous to AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS (SEQ ID NO:1540) corresponding to amino acids 312-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 269-313 of D11853_PEA_—1_P10 (SEQ ID NO:592), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P10 (SEQ ID NO:592) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P10 (SEQ ID NO:592) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

206
E -> K
No

230
E -> K
No

230
E -> Q
No

235
E ->
No

235
E -> D
No

239
Q -> P
No

244
A ->
No

244
A -> G
No

267
Q -> H
No

283
G ->
No

286
D -> N
No

297
Q ->
No

Variant protein D11853_PEA_—1_P10 (SEQ ID NO:592) is encoded by the following transcript(s): D11853_PEA_—1_T14 (SEQ ID NO:64), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T14 (SEQ ID NO:64) is shown in bold; this coding portion starts at position 108 and ends at position 1046. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P10 (SEQ ID NO:592) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

723
G -> A
No

795
G -> A
No

795
G -> C
No

812
A ->
No

812
A -> C
No

823
A -> C
No

838
C ->
No

838
C -> G
No

908
A -> C
No

954
G ->
No

963
G -> A
No

983
C -> T
No

998
G ->
No

1079
G -> A
No

1082
A ->
No

1082
A -> C
No

1128
T ->
No

1131
T -> C
No

1131
T -> G
No

1168
T -> C
Yes

Variant protein D11853_PEA_—1_P11 (SEQ ID NO:593) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T15 (SEQ ID NO:65). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P11 (SEQ ID NO:593) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P11 (SEQ ID NO:593), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-201 of D11853_PEA_—1_P11 (SEQ ID NO:593), a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_—1_P11 (SEQ ID NO:593), a third amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 189-226 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 203-240 of D11853_PEA_—1_P11 (SEQ ID NO:593), a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P11 (SEQ ID NO:593), a fifth amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 227-254 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 282-309 of D11853_PEA_—1_P11 (SEQ ID NO:593), and a sixth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) corresponding to amino acids 310-331 of D11853_PEA_—1_P11 (SEQ ID NO:593), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence, fifth amino acid sequence and sixth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P11 (SEQ ID NO:593).

3. An isolated polypeptide encoding for an edge portion of D11853_PEA_—1_P11 (SEQ ID NO:593) comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538), corresponding to D11853_PEA_—1_P11 (SEQ ID NO:593).

4. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) in D11853_PEA_—1_P11 (SEQ ID NO:593).

Comparison Report Between D11853_PEA_—1_P11 (SEQ ID NO:593) and BAC85377 (SEQ ID NO:640):

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P11 (SEQ ID NO:593).

Comparison Report Between D11853_PEA_—1_P11 (SEQ ID NO:593) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P11 (SEQ ID NO:593), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P11 (SEQ ID NO:593), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERR KRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 130-240 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-240 of D11853_PEA_—1_P11 (SEQ ID NO:593), a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P11 (SEQ ID NO:593), a fourth amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 241-268 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 282-309 of D11853_PEA_—1_P11 (SEQ ID NO:593), and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) corresponding to amino acids 310-331 of D11853_PEA_—1_P11 (SEQ ID NO:593), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of D11853_PEA_—1_P11 (SEQ ID NO:593), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538), corresponding to D11853_PEA_—1_P11 (SEQ ID NO:593).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) in D11853_PEA_—1_P11 (SEQ ID NO:593).

Comparison Report Between D11853_PEA_—1_P11 (SEQ ID NO:593) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P11 (SEQ ID NO:593), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRES AINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 1-240 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-240 of D11853_PEA_—1_P11 (SEQ ID NO:593), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538) corresponding to amino acids 241-281 of D11853_PEA_—1_P11 (SEQ ID NO:593), a third amino acid sequence being at least 90% homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 241-268 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 282-309 of D11853_PEA_—1_P11 (SEQ ID NO:593), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA (SEQ ID NO:1535) corresponding to amino acids 310-331 of D11853_PEA_—1_P11 (SEQ ID NO:593), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of D11853_PEA_—1_P11 (SEQ ID NO:593) comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL (SEQ ID NO:1538), corresponding to D11853_PEA_—1_P11 (SEQ ID NO:593).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P11 (SEQ ID NO:593) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P11 (SEQ ID NO:593) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

206
E -> K
No

230
E -> K
No

230
E -> Q
No

235
E ->
No

235
E -> D
No

239
Q -> P
No

285
A ->
No

285
A -> G
No

308
Q -> H
No

Variant protein D11853_PEA_—1_P11 (SEQ ID NO:593) is encoded by the following transcript(s): D11853_PEA_—1_T15 (SEQ ID NO:65), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T15 (SEQ ID NO:65) is shown in bold; this coding portion starts at position 108 and ends at position 1100. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P11 (SEQ ID NO:593) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide seqence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

723
G -> A
No

795
G -> A
No

795
G -> C
No

812
A ->
No

812
A -> C
No

823
A -> C
No

961
C ->
No

961
C -> G
No

1031
A -> C
No

1260
A -> C
No

1268
T -> G
No

1286
G -> A
No

1286
G -> C
No

1294
-> C
No

1294
-> T
No

1301
-> G
No

1330
C ->
No

1330
C -> G
No

1361
-> G
No

1411
G ->
No

1420
G -> A
No

1440
C -> T
No

1455
G ->
No

1536
G -> A
No

1539
A ->
No

1539
A -> C
No

1585
T ->
No

1588
T -> C
No

1588
T -> G
No

1625
T -> C
Yes

Variant protein D11853_PEA_—1_P12 (SEQ ID NO:594) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T16 (SEQ ID NO:66). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P12 (SEQ ID NO:594) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P12 (SEQ ID NO:594), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P12 (SEQ ID NO:594), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR corresponding to amino acids 13-134 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-148 of D11853_PEA_—1_P12 (SEQ ID NO:594), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP (SEQ ID NO:1545) corresponding to amino acids 149-183 of D11853_PEA_—1_P12 (SEQ ID NO:594), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P12 (SEQ ID NO:594), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P12 (SEQ ID NO:594).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P12 (SEQ ID NO:594), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP (SEQ ID NO:1545) in D11853_PEA_—1_P12 (SEQ ID NO:594).

Comparison Report Between D11853_PEA_—1_P12 (SEQ ID NO:594) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P12 (SEQ ID NO:594), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P12 (SEQ ID NO:594), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P12 (SEQ ID NO:594), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFR corresponding to amino acids 130-148 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-148 of D11853_PEA_—1_P12 (SEQ ID NO:594), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP (SEQ ID NO:1545) corresponding to amino acids 149-183 of D11853_PEA_—1_P12 (SEQ ID NO:594), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P12 (SEQ ID NO:594), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP (SEQ ID NO:1545) in D11853_PEA_—1_P12 (SEQ ID NO:594).

Comparison Report Between D11853_PEA_—1_P12 (SEQ ID NO:594) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P12 (SEQ ID NO:594), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFR corresponding to amino acids 1-148 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-148 of D11853_PEA_—1_P12 (SEQ ID NO:594), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP (SEQ ID NO:1545) corresponding to amino acids 149-183 of D11853_PEA_—1_P12 (SEQ ID NO:594), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P12 (SEQ ID NO:594) is encoded by the following transcript(s): D11853_PEA_—1_T16 (SEQ ID NO:66), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T16 (SEQ ID NO:66) is shown in bold; this coding portion starts at position 108 and ends at position 656. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P12 (SEQ ID NO:594) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide seqence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

789
A -> C
No

789
A -> G
No

790
G ->
No

790
G -> A
No

809
C -> G
No

816
A -> C
No

872
G -> A
No

944
G -> A
No

944
G -> C
No

961
A ->
No

961
A -> C
No

972
A -> C
No

987
C ->
No

987
C -> G
No

1057
A -> C
No

1081
A -> C
No

1089
T -> G
No

1107
G -> A
No

1107
G -> C
No

1115
-> C
No

1115
-> T
No

1122
-> G
No

1151
C ->
No

1151
C -> G
No

1182
-> G
No

1232
G ->
No

1241
G -> A
No

1261
C -> T
No

1276
G ->
No

1357
G -> A
No

1360
A ->
No

1360
A -> C
No

1406
T ->
No

1409
T -> C
No

1409
T -> G
No

1446
T -> C
Yes

Variant protein D11853_PEA_—1_P14 (SEQ ID NO:595) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T19 (SEQ ID NO:68). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P14 (SEQ ID NO:595) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P14 (SEQ ID NO:595), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P14 (SEQ ID NO:595), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCW GIRCLRYEIKDIHVPPRVKESMQMQV corresponding to amino acids 13-180 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-194 of D11853_PEA_—1_P14 (SEQ ID NO:595), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG (SEQ ID NO:1547) corresponding to amino acids 195-220 of D11853_PEA_—1_P14 (SEQ ID NO:595), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P14 (SEQ ID NO:595), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P14 (SEQ ID NO:595).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P14 (SEQ ID NO:595), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG (SEQ ID NO:1547) in D11853_PEA_—1_P14 (SEQ ID NO:595).

Comparison Report Between D11853_PEA_—1_P14 (SEQ ID NO:595) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P14 (SEQ ID NO:595), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P14 (SEQ ID NO:595), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P14 (SEQ ID NO:595), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQV corresponding to amino acids 130-194 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-194 of D11853_PEA_—1_P14 (SEQ ID NO:595), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG (SEQ ID NO:1547) corresponding to amino acids 195-220 of D11853_PEA_—1_P14 (SEQ ID NO:595), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P14 (SEQ ID NO:595), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG (SEQ ID NO:1547) in D11853_PEA_—1_P14 (SEQ ID NO:595).

Comparison Report Between D11853_PEA_—1_P14 (SEQ ID NO:595) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P14 (SEQ ID NO:595), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQV corresponding to amino acids 1-194 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-194 of D11853_PEA_—1_P14 (SEQ ID NO:595), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG (SEQ ID NO:1547) corresponding to amino acids 195-220 of D11853_PEA_—1_P14 (SEQ ID NO:595), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P14 (SEQ ID NO:595) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 19, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P14 (SEQ ID NO:595) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

178
K ->
No

178
K -> R
No

178
K -> T
No

185
R -> G
No

187
K -> T
No

Variant protein D11853_PEA_—1_P14 (SEQ ID NO:595) is encoded by the following transcript(s): D11853_PEA_—1_T19 (SEQ ID NO:68), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T19 (SEQ ID NO:68) is shown in bold; this coding portion starts at position 108 and ends at position 767. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P14 (SEQ ID NO:595) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

640
A -> C
No

640
A -> G
No

641
G ->
No

641
G -> A
No

660
C -> G
No

667
A -> C
No

867
G -> A
No

939
G -> A
No

939
G -> C
No

956
A ->
No

956
A -> C
No

967
A -> C
No

982
C ->
No

982
C -> G
No

1052
A -> C
No

1076
A -> C
No

1084
T -> G
No

1102
G -> A
No

1102
G -> C
No

1110
-> C
No

1110
-> T
No

1117
-> G
No

1146
C ->
No

1146
C -> G
No

1177
-> G
No

1227
G ->
No

1236
G -> A
No

1256
C -> T
No

1271
G ->
No

1352
G -> A
No

1355
A ->
No

1355
A -> C
No

1401
T ->
No

1404
T -> C
No

1404
T -> G
No

1441
T -> C
Yes

Variant protein D11853_PEA_—1_P16 (SEQ ID NO:596) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T24 (SEQ ID NO:71). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P16 (SEQ ID NO:596) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P16 (SEQ ID NO:596), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR corresponding to amino acids 13-134 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-148 of D11853_PEA_—1_P16 (SEQ ID NO:596), a third amino acid sequence being at least 90% homologous to VEAERRKR corresponding to amino acids 180-187 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 149-156 of D11853_PEA_—1_P16 (SEQ ID NO:596), a bridging amino acid A corresponding to amino acid 157 of D11853_PEA_—1_P16 (SEQ ID NO:596), and a fourth amino acid sequence being at least 90% homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDA AASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGT DASLDEELDRVKMS corresponding to amino acids 189-342 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 158-311 of D11853_PEA_—1_P16 (SEQ ID NO:596), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, bridging amino acid and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P16 (SEQ ID NO:596).

3. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P16 (SEQ ID NO:596) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148−x to 148; and ending at any of amino acid numbers 149+((n−2)−x), in which x varies from 0 to n−2.

Comparison Report Between D11853_PEA_—1_P16 (SEQ ID NO:596) and BAC85377 (SEQ ID NO:640):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1-109 of D11853_PEA_—1_P16 (SEQ ID NO:596), a second amino acid sequence being at least 90% homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR corresponding to amino acids 1-39 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 110-148 of D11853_PEA_—1_P16 (SEQ ID NO:596), a third amino acid sequence being at least 90% homologous to VEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAA ALTQH corresponding to amino acids 85-159 of BAC85377 (SEQ ID NO:640), which also corresponds to amino acids 149-223 of D11853_PEA_—1_P16 (SEQ ID NO:596), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRD VQGTDASLDEELDRVKMS (SEQ ID NO:1531) corresponding to amino acids 224-311 of D11853_PEA_—1_P16 (SEQ ID NO:596), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_—1_P16 (SEQ ID NO:596).

4. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRD VQGTDASLDEELDRVKMS (SEQ ID NO:1531) in D11853_PEA_—1_P16 (SEQ ID NO:596).

Comparison Report Between D11853_PEA_—1_P16 (SEQ ID NO:596) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P16 (SEQ ID NO:596), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P16 (SEQ ID NO:596), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFR corresponding to amino acids 130-148 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-148 of D11853_PEA_—1_P16 (SEQ ID NO:596), and a third amino acid sequence being at least 90% homologous to VEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAA ALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSS GSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 194-356 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 149-311 of D11853_PEA_—1_P16 (SEQ ID NO:596), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P16 (SEQ ID NO:596) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148−x to 148; and ending at any of amino acid numbers 149+((n−2)−x), in which x varies from 0 to n−2.

Comparison Report Between D11853_PEA_—1_P16 (SEQ ID NO:596) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFR corresponding to amino acids 1-148 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-148 of D11853_PEA_—1_P16 (SEQ ID NO:596), and a second amino acid sequence being at least 90% homologous to VEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAA ALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSS GSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 194-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 149-311 of D11853_PEA_—1_P16 (SEQ ID NO:596), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P16 (SEQ ID NO:596), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148−x to 148; and ending at any of amino acid numbers 149+((n−2)−x), in which x varies from 0 to n−2.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P16 (SEQ ID NO:596) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 21, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P16 (SEQ ID NO:596) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

161
E -> K
No

185
E -> K
No

185
E -> Q
No

190
E ->
No

190
E -> D
No

194
Q -> P
No

199
A ->
No

199
A -> G
No

222
Q -> H
No

233
V -> G
No

239
S -> N
No

239
S -> T
No

254
P ->
No

254
P -> A
No

281
G ->
No

284
D -> N
No

295
Q ->
No

Variant protein D11853_PEA_—1_P16 (SEQ ID NO:596) is encoded by the following transcript(s): D11853_PEA_—1_T24 (SEQ ID NO:71), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T24 (SEQ ID NO:71) is shown in bold; this coding portion starts at position 108 and ends at position 1040. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P16 (SEQ ID NO:596) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

588
G -> A
No

660
G -> A
No

660
G -> C
No

677
A ->
No

677
A -> C
No

688
A -> C
No

703
C ->
No

703
C -> G
No

773
A -> C
No

797
A -> C
No

805
T -> G
No

823
G -> A
No

823
G -> C
No

831
-> C
No

831
-> T
No

838
-> G
No

867
C ->
No

867
C -> G
No

898
-> G
No

948
G ->
No

957
G -> A
No

977
C -> T
No

992
G ->
No

1073
G -> A
No

1076
A ->
No

1076
A -> C
No

1122
T ->
No

1125
T -> C
No

1125
T -> G
No

1162
T -> C
Yes

Variant protein D11853_PEA_—1_P18 (SEQ ID NO:597) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T26 (SEQ ID NO:73). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P18 (SEQ ID NO:597) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P18 (SEQ ID NO:597), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P18 (SEQ ID NO:597), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASI corresponding to amino acids 13-143 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-157 of D11853_PEA_—1_P18 (SEQ ID NO:597), and a third amino acid sequence being at least 90% homologous to VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 295-342 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 158-205 of D11853_PEA_—1_P18 (SEQ ID NO:597), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P18 (SEQ ID NO:597), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P18 (SEQ ID NO:597).

3. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P18 (SEQ ID NO:597) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157−x to 157; and ending at any of amino acid numbers 158+((n−2)−x), in which x varies from 0 to n−2.

Comparison Report Between D11853_PEA_—1_P18 (SEQ ID NO:597) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P18 (SEQ ID NO:597), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P18 (SEQ ID NO:597), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P18 (SEQ ID NO:597), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLSLDKVFRERESLNASI corresponding to amino acids 130-157 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-157 of D11853_PEA_—1_P18 (SEQ ID NO:597), and a third amino acid sequence being at least 90% homologous to VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 309-356 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 158-205 of D11853_PEA_—1_P18 (SEQ ID NO:597), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_—1_P18 (SEQ ID NO:597) comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157−x to 157; and ending at any of amino acid numbers 158+((n−2)−x), in which x varies from 0 to n−2.

Comparison Report Between D11853_PEA_—1_P18 (SEQ ID NO:597) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P18 (SEQ ID NO:597), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS LDKVFRERESLNASI corresponding to amino acids 1-157 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-157 of D11853_PEA_—1_P18 (SEQ ID NO:597), and a second amino acid sequence being at least 90% homologous to VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 309-356 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 158-205 of D11853_PEA_—1_P18 (SEQ ID NO:597), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P18 (SEQ ID NO:597) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P18 (SEQ ID NO:597) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

175
G ->
No

178
D -> N
No

189
Q ->
No

Variant protein D11853_PEA_—1_P18 (SEQ ID NO:597) is encoded by the following transcript(s): D11853_PEA_—1_T26 (SEQ ID NO:73), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T26 (SEQ ID NO:73) is shown in bold; this coding portion starts at position 108 and ends at position 722. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P18 (SEQ ID NO:597) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

630
G ->
No

639
G -> A
No

659
C -> T
No

674
G ->
No

755
G -> A
No

758
A ->
No

758
A -> C
No

804
T ->
No

807
T -> C
No

807
T -> G
No

844
T -> C
Yes

Variant protein D11853_PEA_—1_P19 (SEQ ID NO:598) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T27 (SEQ ID NO:74). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more, alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P19 (SEQ ID NO:598) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P19 (SEQ ID NO:598), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P19 (SEQ ID NO:598), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVT LQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS corresponding to amino acids 13-128 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-142 of D11853_PEA_—1_P19 (SEQ ID NO:598), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SRLTLQWEQQRCPGYRCKS (SEQ ID NO:1552) corresponding to amino acids 143-161 of D11853_PEA_—1_P19 (SEQ ID NO:598), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P19 (SEQ ID NO:598), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P19 (SEQ ID NO:598).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P19 (SEQ ID NO:598), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SRLTLQWEQQRCPGYRCKS (SEQ ID NO:1552) in D11853_PEA_—1_P19 (SEQ ID NO:598).

Comparison Report Between D11853_PEA_—1_P19 (SEQ ID NO:598) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P19 (SEQ ID NO:598), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQ corresponding to amino acids 1-128 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-128 of D11853_PEA_—1_P19 (SEQ ID NO:598), a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_—1_P19 (SEQ ID NO:598), a second amino acid sequence being at least 90% homologous to AQTTMRSELGKLS corresponding to amino acids 130-142 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 130-142 of D11853_PEA_—1_P19 (SEQ ID NO:598), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SRLTLQWEQQRCPGYRCKS (SEQ ID NO:1552) corresponding to amino acids 143-161 of D11853_PEA_—1_P19 (SEQ ID NO:598), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P19 (SEQ ID NO:598), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SRLTLQWEQQRCPGYRCKS (SEQ ID NO:1552) in D11853_PEA_—1_P19 (SEQ ID NO:598).

Comparison Report Between D11853_PEA_—1_P19 (SEQ ID NO:598) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P19 (SEQ ID NO:598), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEWINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS corresponding to amino acids 1-142 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-142 of D11853_PEA_—1_P19 (SEQ ID NO:598), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SRLTLQWEQQRCPGYRCKS (SEQ ID NO:1552) corresponding to amino acids 143-161 of D11853_PEA_—1_P19 (SEQ ID NO:598), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P19 (SEQ ID NO:598) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 25, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P19 (SEQ ID NO:598) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25

Amino acid mutations

SNP Position(s)

on amino acid
Alternative
Previously

sequence
amine acid(s)
known SNP?

25
P ->
No

32
L ->
No

144
R -> K
No

151
Q -> *
No

156
G ->
No

Variant protein D11853_PEA_—1_P19 (SEQ ID NO:598) is encoded by the following transcript(s): D11853_PEA_—1_T27 (SEQ ID NO:74), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T27 (SEQ ID NO:74) is shown in bold; this coding portion starts at position 108 and ends at position 590. The transcript also has the following SNPs as listed in Table 26 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P19 (SEQ ID NO:598) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

538
G -> A
No

558
C -> T
No

573
G ->
No

654
G -> A
No

657
A ->
No

657
A -> C
No

703
T ->
No

706
T -> C
No

706
T -> G
No

743
T -> C
Yes

Variant protein D11853_PEA_—1_P20 (SEQ ID NO:599) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T17 (SEQ ID NO:67) and D11853_PEA_—1_T25 (SEQ ID NO:72). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P20 (SEQ ID NO:599) is encoded by the following transcript(s): D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T17 (SEQ ID NO:67) and D11853_PEA_—1_T25 (SEQ ID NO:72), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript D11853_PEA_—1_T7 (SEQ ID NO:59) is shown in bold; this coding portion starts at position 108 and ends at position 287. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P20 (SEQ ID NO:599) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

406
C ->
No

408
G ->
No

411
-> C
No

427
T ->
No

1357
A -> C
No

1357
A -> G
No

1358
G ->
No

1358
G -> A
No

1377
C -> G
No

1384
A -> C
No

1440
G -> A
No

1512
G -> A
No

1512
G -> C
No

1529
A ->
No

1529
A -> C
No

1540
A -> C
No

1555
C ->
No

1555
C -> G
No

1625
A -> C
No

1649
A -> C
No

1657
T -> G
No

1675
G -> A
No

1675
G -> C
No

1683
-> C
No

1683
-> T
No

1690
-> G
No

1719
C ->
No

1719
C -> G
No

1750
-> G
No

1800
G ->
No

1809
G -> A
No

1829
C -> T
No

1844
G ->
No

1925
G -> A
No

1928
A ->
No

1928
A -> C
No

1974
T ->
No

1977
T -> C
No

1977
T -> G
No

2014
T -> C
Yes

The coding portion of transcript D11853_PEA_—1_T17 (SEQ ID NO:67) is shown in bold; this coding portion starts at position 108 and ends at position 287. The transcript also has the following SNPs as listed in Table 28 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P20 (SEQ ID NO:599) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 28

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

406
C ->
No

408
G ->
No

411
-> C
No

427
T ->
No

1357
A -> C
No

1357
A -> G
No

1358
G ->
No

1358
G -> A
No

1377
C -> G
No

1384
A -> C
No

1440
G -> A
No

1512
G -> A
No

1512
G -> C
No

1529
A ->
No

1529
A -> C
No

1540
A -> C
No

1555
C ->
No

1555
C -> G
No

1625
A -> C
No

1649
A -> C
No

1657
T -> G
No

1675
G -> A
No

1675
G -> C
No

1683
-> C
No

1683
-> T
No

1690
-> G
No

1719
C ->
No

1719
C -> G
No

1750
-> G
No

1800
G ->
No

1809
G -> A
No

1829
C -> T
No

1844
G ->
No

1925
G -> A
No

1928
A ->
No

1928
A -> C
No

1974
T ->
No

1977
T -> C
No

1977
T -> G
No

2014
T -> C
Yes

The coding portion of transcript D11853_PEA_—1_T25 (SEQ ID NO:72) is shown in bold; this coding portion starts at position 108 and ends at position 287. The transcript also has the following SNPs as listed in Table 29 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P20 (SEQ ID NO:599) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

406
C ->
No

408
G ->
No

411
-> C
No

427
T ->
No

1489
A -> C
No

1489
A -> G
No

1490
G ->
No

1490
G -> A
No

1509
C -> G
No

1516
A -> C
No

1572
G -> A
No

1644
G -> A
No

1644
G -> C
No

1661
A ->
No

1661
A -> C
No

1672
A -> C
No

1687
C ->
No

1687
C -> G
No

1757
A -> C
No

1986
A -> C
No

1994
T -> G
No

2012
G -> A
No

2012
G -> C
No

2020
-> C
No

2020
-> T
No

2027
-> G
No

2056
C ->
No

2056
C -> G
No

2087
-> G
No

2120
C -> T
No

2562
G ->
No

2571
G -> A
No

2591
C -> T
No

2606
G ->
No

2687
G -> A
No

2690
A ->
No

2690
A -> C
No

2736
T ->
No

2739
T -> C
No

2739
T -> G
No

2776
T -> C
Yes

Variant protein D11853_PEA_—1_P21 (SEQ ID NO:600) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T8 (SEQ ID NO:60). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P21 (SEQ ID NO:600) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P21 (SEQ ID NO:600), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEP corresponding to amino acids 1-61 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-61 of D11853_PEA_—1_P21 (SEQ ID NO:600), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT (SEQ ID NO:1553) corresponding to amino acids 62-102 of D11853_PEA_—1_P21 (SEQ ID NO:600), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P21 (SEQ ID NO:600), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT (SEQ ID NO:1553) in D11853_PEA_—1_P21 (SEQ ID NO:600).

Comparison Report Between D11853_PEA_—1_P21 (SEQ ID NO:600) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P21 (SEQ ID NO:600), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEP corresponding to amino acids 1-61 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-61 of D11853_PEA_—1_P21 (SEQ ID NO:600), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT (SEQ ID NO:1553) corresponding to amino acids 62-102 of D11853_PEA_—1_P21 (SEQ ID NO:600), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P21 (SEQ ID NO:600) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 30, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P21 (SEQ ID NO:600) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 30

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

Variant protein D11853_PEA_—1_P21 (SEQ ID NO:600) is encoded by the following transcript(s): D11853_PEA_—1_T8 (SEQ ID NO:60), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T8 (SEQ ID NO:60) is shown in bold; this coding portion starts at position 108 and ends at position 413. The transcript also has the following SNPs as listed in Table 31 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P21 (SEQ ID NO:600) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 31

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

1131
A -> C
No

1131
A -> G
No

1132
G ->
No

1132
G -> A
No

1151
C -> G
No

1158
A -> C
No

1214
G -> A
No

1286
G -> A
No

1286
G -> C
No

1303
A ->
No

1303
A -> C
No

1314
A -> C
No

1329
C ->
No

1329
C -> G
No

1399
A -> C
No

1423
A -> C
No

1431
T -> G
No

1449
G -> A
No

1449
G -> C
No

1457
-> C
No

1457
-> T
No

1464
-> G
No

1493
C ->
No

1493
C -> G
No

1524
-> G
No

1574
G ->
No

1583
G -> A
No

1603
C -> T
No

1618
G ->
No

1699
G -> A
No

1702
A ->
No

1702
A -> C
No

1748
T ->
No

1751
T -> C
No

1751
T -> G
No

1788
T -> C
Yes

Variant protein D11853_PEA_—1_P22 (SEQ ID NO:601) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T9 (SEQ ID NO:61). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P22 (SEQ ID NO:601) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P22 (SEQ ID NO:601), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P22 (SEQ ID NO:601), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEP corresponding to amino acids 13-47 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-61 of D11853_PEA_—1_P22 (SEQ ID NO:601), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELLLFWACSMC (SEQ ID NO:1555) corresponding to amino acids 62-72 of D11853_PEA_—1_P22 (SEQ ID NO:601), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P22 (SEQ ID NO:601), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P22 (SEQ ID NO:601).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P22 (SEQ ID NO:601), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELLLFWACSMC (SEQ ID NO:1555) in D11853_PEA_—1_P22 (SEQ ID NO:601).

Comparison Report Between D11853_PEA_—1_P22 (SEQ ID NO:601) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P22 (SEQ ID NO:601), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEP corresponding to amino acids 1-61 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-61 of D11853_PEA_—1_P22 (SEQ ID NO:601), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELLLFWACSMC (SEQ ID NO:1555) corresponding to amino acids 62-72 of D11853_PEA_—1_P22 (SEQ ID NO:601), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P22 (SEQ ID NO:601), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELLLFWACSMC (SEQ ID NO:1555) in D11853_PEA_—1_P22 (SEQ ID NO:601).

Comparison report between D11853_PEA_—1_P22 (SEQ ID NO:601) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P22 (SEQ ID NO:601), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEP corresponding to amino acids 1-61 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-61 of D11853_PEA_—1_P22 (SEQ ID NO:601), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELLLFWACSMC (SEQ ID NO:1555) corresponding to amino acids 62-72 of D11853_PEA_—1_P22 (SEQ ID NO:601), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P22 (SEQ ID NO:601) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 32, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P22 (SEQ ID NO:601) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 32

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

Variant protein D11853_PEA_—1_P22 (SEQ ID NO:601) is encoded by the following transcript(s): D11853_PEA_—1_T9 (SEQ ID NO:61), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T9 (SEQ ID NO:61) is shown in bold; this coding portion starts at position 108 and ends at position 323. The transcript also has the following SNPs as listed in Table 33 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P22 (SEQ ID NO:601) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 33

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

757
A -> C
No

757
A -> G
No

758
G ->
No

758
G -> A
No

777
C -> G
No

784
A -> C
No

840
G -> A
No

912
G -> A
No

912
G -> C
No

929
A ->
No

929
A -> C
No

940
A -> C
No

955
C ->
No

955
C -> G
No

1025
A -> C
No

1049
A -> C
No

1057
T -> G
No

1075
G -> A
No

1075
G -> C
No

1083
-> C
No

1083
-> T
No

1090
-> G
No

1119
C ->
No

1119
C -> G
No

1150
-> G
No

1200
G ->
No

1209
G -> A
No

1229
C -> T
No

1244
G ->
No

1325
G -> A
No

1328
A ->
No

1328
A -> C
No

1374
T ->
No

1377
T -> C
No

1377
T -> G
No

1414
T -> C
Yes

Variant protein D11853_PEA_—1_P24 (SEQ ID NO:602) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_—1_T21 (SEQ ID NO:69). An alignment is given to the known protein (Membrane associated protein SLP-2 (SEQ ID NO:637)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between D11853_PEA_—1_P24 (SEQ ID NO:602) and Q9P042 (SEQ ID NO:639):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P24 (SEQ ID NO:602), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) corresponding to amino acids 1-26 of D11853_PEA_—1_P24 (SEQ ID NO:602), a second amino acid sequence being at least 90% homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL corresponding to amino acids 13-80 of Q9P042 (SEQ ID NO:639), which also corresponds to amino acids 27-94 of D11853_PEA_—1_P24 (SEQ ID NO:602), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTGVPECQHCGCHQPSC (SEQ ID NO:1557) corresponding to amino acids 95-111 of D11853_PEA_—1_P24 (SEQ ID NO:602), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of D11853_PEA_—1_P24 (SEQ ID NO:602), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR (SEQ ID NO:1530) of D11853_PEA_—1_P24 (SEQ ID NO:602).

3. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P24 (SEQ ID NO:602), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GTGVPECQHCGCHQPSC (SEQ ID NO:1557) in D11853_PEA_—1_P24 (SEQ ID NO:602).

Comparison Report Between D11853_PEA_—1_P24 (SEQ ID NO:602) and Q96FY2 (SEQ ID NO:638):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P24 (SEQ ID NO:602), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTL corresponding to amino acids 1-94 of Q96FY2 (SEQ ID NO:638), which also corresponds to amino acids 1-94 of D11853_PEA_—1_P24 (SEQ ID NO:602), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTGVPECQHCGCHQPSC (SEQ ID NO:1557) corresponding to amino acids 95-111 of D11853_PEA_—1_P24 (SEQ ID NO:602), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of D11853_PEA_—1_P24 (SEQ ID NO:602), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GTGVPECQHCGCHQPSC (SEQ ID NO:1557) in D11853_PEA_—1_P24 (SEQ ID NO:602).

Comparison Report Between D11853_PEA_—1_P24 (SEQ ID NO:602) and Q9UJZ1 (SEQ ID NO:637):

1. An isolated chimeric polypeptide encoding for D11853_PEA_—1_P24 (SEQ ID NO:602), comprising a first amino acid sequence being at least 90% homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLD RIRYVQSLKEIVINVPEQSAVTL corresponding to amino acids 1-94 of Q9UJZ1 (SEQ ID NO:637), which also corresponds to amino acids 1-94 of D11853_PEA_—1_P24 (SEQ ID NO:602), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTGVPECQHCGCHQPSC (SEQ ID NO:1557) corresponding to amino acids 95-111 of D11853_PEA_—1_P24 (SEQ ID NO:602), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein D11853_PEA_—1_P24 (SEQ ID NO:602) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 34, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P24 (SEQ ID NO:602) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 34

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

25
P ->
No

32
L ->
No

Variant protein D11853_PEA_—1_P24 (SEQ ID NO:602) is encoded by the following transcript(s): D11853_PEA_—1_T21 (SEQ ID NO:69), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_—1_T21 (SEQ ID NO:69) is shown in bold; this coding portion starts at position 108 and ends at position 440. The transcript also has the following SNPs as listed in Table 35 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_—1_P24 (SEQ ID NO:602) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 35

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

180
C ->
No

182
G ->
No

185
-> C
No

201
T ->
No

479
A -> C
No

479
A -> G
No

480
G ->
No

480
G -> A
No

499
C -> G
No

506
A -> C
No

562
G -> A
No

634
G -> A
No

634
G -> C
No

651
A ->
No

651
A -> C
No

662
A -> C
No

677
C ->
No

677
C -> G
No

747
A -> C
No

771
A -> C
No

779
T -> G
No

797
G -> A
No

797
G -> C
No

805
-> C
No

805
-> T
No

812
-> G
No

841
C ->
No

841
C -> G
No

872
-> G
No

922
G ->
No

931
G -> A
No

951
C -> T
No

966
G ->
No

1047
G -> A
No

1050
A ->
No

1050
A -> C
No

1096
T ->
No

1099
T -> C
No

1099
T -> G
No

1136
T -> C
Yes

As noted above, cluster D11853 features 31 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster D11853_PEA_—1_node_—3 (SEQ ID NO:419) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T17 (SEQ ID NO:67) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T7 (SEQ ID NO: 59)
153
378

D11853_PEA_1_T17 (SEQ ID NO: 67)
153
378

D11853_PEA_1_T25 (SEQ ID NO: 72)
153
378

Segment cluster D11853_PEA_—1_node_—6 (SEQ ID NO:420) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T17 (SEQ ID NO:67) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T7 (SEQ ID NO: 59)
517
890

D11853_PEA_1_T8 (SEQ ID NO: 60)
291
664

D11853_PEA_1_T17 (SEQ ID NO: 67)
517
890

D11853_PEA_1_T25 (SEQ ID NO: 72)
517
890

Segment cluster D11853_PEA_—1_node_—9 (SEQ ID NO:421) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T25 (SEQ ID NO:72). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T25 (SEQ ID NO: 72)
1108
1239

Segment cluster D11853_PEA_—1_node_—17 (SEQ ID NO:422) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T16 (SEQ ID NO:66) and D11853_PEA_—1_T23 (SEQ ID NO:70). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T16 (SEQ ID NO: 66)
552
700

D11853_PEA_1_T23 (SEQ ID NO: 70)
552
700

Segment cluster D11853_PEA_—1_node_—21 (SEQ ID NO:423) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T19 (SEQ ID NO:68) and D11853_PEA_—1_T23 (SEQ ID NO:70). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T19 (SEQ ID NO: 68)
687
830

D11853_PEA_1_T23 (SEQ ID NO: 70)
836
979

Segment cluster D11853_PEA_—1_node_—22 (SEQ ID NO:424) according to the present invention is supported by 287 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T17 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T19 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
687
831

D11853_PEA_1_T3 (SEQ ID NO: 58)
687
831

D11853_PEA_1_T7 (SEQ ID NO: 59)
1404
1548

D11853_PEA_1_T8 (SEQ ID NO: 60)
1178
1322

D11853_PEA_1_T9 (SEQ ID NO: 61)
804
948

D11853_PEA_1_T10 (SEQ ID NO: 62)
687
831

D11853_PEA_1_T13 (SEQ ID NO: 63)
687
831

D11853_PEA_1_T14 (SEQ ID NO: 64)
687
831

D11853_PEA_1_T15 (SEQ ID NO: 65)
687
831

D11853_PEA_1_T16 (SEQ ID NO: 66)
836
980

D11853_PEA_1_T17 (SEQ ID NO: 67)
1404
1548

D11853_PEA_1_T19 (SEQ ID NO: 68)
831
975

D11853_PEA_1_T21 (SEQ ID NO: 69)
526
670

D11853_PEA_1_T23 (SEQ ID NO: 70)
980
1124

D11853_PEA_1_T24 (SEQ ID NO: 71)
552
696

D11853_PEA_1_T25 (SEQ ID NO: 72)
1536
1680

Segment cluster D11853_PEA_—1_node_—23 (SEQ ID NO:425) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T13 (SEQ ID NO:63) and D11853_PEA_—1_T15 (SEQ ID NO:65). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T13 (SEQ ID NO: 63)
832
954

D11853_PEA_1_T15 (SEQ ID NO: 65)
832
954

Segment cluster D11853_PEA_—1_node_—25 (SEQ ID NO:426) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T15 (SEQ ID NO:65) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T10 (SEQ ID NO: 62)
912
1116

D11853_PEA_1_T15 (SEQ ID NO: 65)
1035
1239

D11853_PEA_1_T25 (SEQ ID NO: 72)
1761
1965

Segment cluster D11853_PEA_—1_node_—26 (SEQ ID NO:427) according to the present invention is supported by 290 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
912
1040

D11853_PEA_1_T3 (SEQ ID NO: 58)
912
1040

D11853_PEA_1_T7 (SEQ ID NO: 59)
1629
1757

D11853_PEA_1_T8 (SEQ ID NO: 60)
1403
1531

D11853_PEA_1_T9 (SEQ ID NO: 61)
1029
1157

D11853_PEA_1_T10 (SEQ ID NO: 62)
1117
1245

D11853_PEA_1_T13 (SEQ ID NO: 63)
1035
1163

D11853_PEA_1_T15 (SEQ ID NO: 65)
1240
1368

D11853_PEA_1_T16 (SEQ ID NO: 66)
1061
1189

D11853_PEA_1_T17 (SEQ ID NO: 67)
1629
1757

D11853_PEA_1_T19 (SEQ ID NO: 68)
1056
1184

D11853_PEA_1_T21 (SEQ ID NO: 69)
751
879

D11853_PEA_1_T23 (SEQ ID NO: 70)
1205
1333

D11853_PEA_1_T24 (SEQ ID NO: 71)
777
905

D11853_PEA_1_T25 (SEQ ID NO: 72)
1966
2094

Segment cluster D11853_PEA_—1_node_—27 (SEQ ID NO:428) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T3 (SEQ ID NO:58) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T3 (SEQ ID NO: 58)
1041
1460

D11853_PEA_1_T25 (SEQ ID NO: 72)
2095
2514

Segment cluster D11853_PEA_—1_node_—30 (SEQ ID NO:429) according to the present invention is supported by 249 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
1088
1207

D11853_PEA_1_T3 (SEQ ID NO: 58)
1513
1632

D11853_PEA_1_T7 (SEQ ID NO: 59)
1805
1924

D11853_PEA_1_T8 (SEQ ID NO: 60)
1579
1698

D11853_PEA_1_T9 (SEQ ID NO: 61)
1205
1324

D11853_PEA_1_T10 (SEQ ID NO: 62)
1293
1412

D11853_PEA_1_T13 (SEQ ID NO: 63)
1211
1330

D11853_PEA_1_T14 (SEQ ID NO: 64)
959
1078

D11853_PEA_1_T15 (SEQ ID NO: 65)
1416
1535

D11853_PEA_1_T16 (SEQ ID NO: 66)
1237
1356

D11853_PEA_1_T17 (SEQ ID NO: 67)
1805
1924

D11853_PEA_1_T19 (SEQ ID NO: 68)
1232
1351

D11853_PEA_1_T21 (SEQ ID NO: 69)
927
1046

D11853_PEA_1_T23 (SEQ ID NO: 70)
1381
1500

D11853_PEA_1_T24 (SEQ ID NO: 71)
953
1072

D11853_PEA_1_T25 (SEQ ID NO: 72)
2567
2686

D11853_PEA_1_T26 (SEQ ID NO: 73)
635
754

D11853_PEA_1_T27 (SEQ ID NO: 74)
534
653

Segment cluster D11853_PEA_—1_node_—32 (SEQ ID NO:430) according to the present invention is supported by 215 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
1208
1437

D11853_PEA_1_T3 (SEQ ID NO: 58)
1633
1745

D11853_PEA_1_T7 (SEQ ID NO: 59)
1925
2037

D11853_PEA_1_T8 (SEQ ID NO: 60)
1699
1811

D11853_PEA_1_T9 (SEQ ID NO: 61)
1325
1437

D11853_PEA_1_T10 (SEQ ID NO: 62)
1413
1525

D11853_PEA_1_T13 (SEQ ID NO: 63)
1331
1443

D11853_PEA_1_T14 (SEQ ID NO: 64)
1079
1191

D11853_PEA_1_T15 (SEQ ID NO: 65)
1536
1648

D11853_PEA_1_T16 (SEQ ID NO: 66)
1357
1469

D11853_PEA_1_T17 (SEQ ID NO: 67)
1925
2154

D11853_PEA_1_T19 (SEQ ID NO: 68)
1352
1464

D11853_PEA_1_T21 (SEQ ID NO: 69)
1047
1159

D11853_PEA_1_T23 (SEQ ID NO: 70)
1501
1613

D11853_PEA_1_T24 (SEQ ID NO: 71)
1073
1185

D11853_PEA_1_T25 (SEQ ID NO: 72)
2687
2799

D11853_PEA_1_T26 (SEQ ID NO: 73)
755
984

D11853_PEA_1_T27 (SEQ ID NO: 74)
654
766

Segment cluster D11853_PEA_—1_node_—0 (SEQ ID NO:431) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
1
41

D11853_PEA_1_T3 (SEQ ID NO: 58)
1
41

D11853_PEA_1_T7 (SEQ ID NO: 59)
1
41

D11853_PEA_1_T8 (SEQ ID NO: 60)
1
41

D11853_PEA_1_T9 (SEQ ID NO: 61)
1
41

D11853_PEA_1_T10 (SEQ ID NO: 62)
1
41

D11853_PEA_1_T13 (SEQ ID NO: 63)
1
41

D11853_PEA_1_T14 (SEQ ID NO: 64)
1
41

D11853_PEA_1_T15 (SEQ ID NO: 65)
1
41

D11853_PEA_1_T16 (SEQ ID NO: 66)
1
41

D11853_PEA_1_T17 (SEQ ID NO: 67)
1
41

D11853_PEA_1_T19 (SEQ ID NO: 68)
1
41

D11853_PEA_1_T21 (SEQ ID NO: 69)
1
41

D11853_PEA_1_T23 (SEQ ID NO: 70)
1
41

D11853_PEA_1_T24 (SEQ ID NO: 71)
1
41

D11853_PEA_1_T25 (SEQ ID NO: 72)
1
41

D11853_PEA_1_T26 (SEQ ID NO: 73)
1
41

D11853_PEA_1_T27 (SEQ ID NO: 74)
1
41

Segment cluster D11853_PEA_—1_node_—1 (SEQ ID NO:432) according to the present invention is supported by 158 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
42
110

D11853_PEA_1_T3 (SEQ ID NO: 58)
42
110

D11853_PEA_1_T7 (SEQ ID NO: 59)
42
110

D11853_PEA_1_T8 (SEQ ID NO: 60)
42
110

D11853_PEA_1_T9 (SEQ ID NO: 61)
42
110

D11853_PEA_1_T10 (SEQ ID NO: 62)
42
110

D11853_PEA_1_T13 (SEQ ID NO: 63)
42
110

D11853_PEA_1_T14 (SEQ ID NO: 64)
42
110

D11853_PEA_1_T15 (SEQ ID NO: 65)
42
110

D11853_PEA_1_T16 (SEQ ID NO: 66)
42
110

D11853_PEA_1_T17 (SEQ ID NO: 67)
42
110

D11853_PEA_1_T19 (SEQ ID NO: 68)
42
110

D11853_PEA_1_T21 (SEQ ID NO: 69)
42
110

D11853_PEA_1_T23 (SEQ ID NO: 70)
42
110

D11853_PEA_1_T24 (SEQ ID NO: 71)
42
110

D11853_PEA_1_T25 (SEQ ID NO: 72)
42
110

D11853_PEA_1_T26 (SEQ ID NO: 73)
42
110

D11853_PEA_1_T27 (SEQ ID NO: 74)
42
110

Segment cluster D11853_PEA_—1_node_—2 (SEQ ID NO:433) according to the present invention is supported by 247 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
111
152

D11853_PEA_1_T3 (SEQ ID NO: 58)
111
152

D11853_PEA_1_T7 (SEQ ID NO: 59)
111
152

D11853_PEA_1_T8 (SEQ ID NO: 60)
111
152

D11853_PEA_1_T9 (SEQ ID NO: 61)
111
152

D11853_PEA_1_T10 (SEQ ID NO: 62)
111
152

D11853_PEA_1_T13 (SEQ ID NO: 63)
111
152

D11853_PEA_1_T14 (SEQ ID NO: 64)
111
152

D11853_PEA_1_T15 (SEQ ID NO: 65)
111
152

D11853_PEA_1_T16 (SEQ ID NO: 66)
111
152

D11853_PEA_1_T17 (SEQ ID NO: 67)
111
152

D11853_PEA_1_T19 (SEQ ID NO: 68)
111
152

D11853_PEA_1_T21 (SEQ ID NO: 69)
111
152

D11853_PEA_1_T23 (SEQ ID NO: 70)
111
152

D11853_PEA_1_T24 (SEQ ID NO: 71)
111
152

D11853_PEA_1_T25 (SEQ ID NO: 72)
111
152

D11853_PEA_1_T26 (SEQ ID NO: 73)
111
152

D11853_PEA_1_T27 (SEQ ID NO: 74)
111
152

Segment cluster D11853_PEA_—1_node_—4 (SEQ ID NO:434) according to the present invention is supported by 258 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
153
185

D11853_PEA_1_T3 (SEQ ID NO: 58)
153
185

D11853_PEA_1_T7 (SEQ ID NO: 59)
379
411

D11853_PEA_1_T8 (SEQ ID NO: 60)
153
185

D11853_PEA_1_T9 (SEQ ID NO: 61)
153
185

D11853_PEA_1_T10 (SEQ ID NO: 62)
153
185

D11853_PEA_1_T13 (SEQ ID NO: 63)
153
185

D11853_PEA_1_T14 (SEQ ID NO: 64)
153
185

D11853_PEA_1_T15 (SEQ ID NO: 65)
153
185

D11853_PEA_1_T16 (SEQ ID NO: 66)
153
185

D11853_PEA_1_T17 (SEQ ID NO: 67)
379
411

D11853_PEA_1_T19 (SEQ ID NO: 68)
153
185

D11853_PEA_1_T21 (SEQ ID NO: 69)
153
185

D11853_PEA_1_T23 (SEQ ID NO: 70)
153
185

D11853_PEA_1_T24 (SEQ ID NO: 71)
153
185

D11853_PEA_1_T25 (SEQ ID NO: 72)
379
411

D11853_PEA_1_T26 (SEQ ID NO: 73)
153
185

D11853_PEA_1_T27 (SEQ ID NO: 74)
153
185

Segment cluster D11853_PEA_—1_node_—5 (SEQ ID NO:435) according to the present invention is supported by 291 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
186
290

D11853_PEA_1_T3 (SEQ ID NO: 58)
186
290

D11853_PEA_1_T7 (SEQ ID NO: 59)
412
516

D11853_PEA_1_T8 (SEQ ID NO: 60)
186
290

D11853_PEA_1_T9 (SEQ ID NO: 61)
186
290

D11853_PEA_1_T10 (SEQ ID NO: 62)
186
290

D11853_PEA_1_T13 (SEQ ID NO: 63)
186
290

D11853_PEA_1_T14 (SEQ ID NO: 64)
186
290

D11853_PEA_1_T15 (SEQ ID NO: 65)
186
290

D11853_PEA_1_T16 (SEQ ID NO: 66)
186
290

D11853_PEA_1_T17 (SEQ ID NO: 67)
412
516

D11853_PEA_1_T19 (SEQ ID NO: 68)
186
290

D11853_PEA_1_T21 (SEQ ID NO: 69)
186
290

D11853_PEA_1_T23 (SEQ ID NO: 70)
186
290

D11853_PEA_1_T24 (SEQ ID NO: 71)
186
290

D11853_PEA_1_T25 (SEQ ID NO: 72)
412
516

D11853_PEA_1_T26 (SEQ ID NO: 73)
186
290

D11853_PEA_1_T27 (SEQ ID NO: 74)
186
290

Segment cluster D11853_PEA_—1_node_—7 (SEQ ID NO:436) according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T17 (SEQ ID NO:67) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T7 (SEQ ID NO: 59)
891
1007

D11853_PEA_1_T8 (SEQ ID NO: 60)
665
781

D11853_PEA_1_T9 (SEQ ID NO: 61)
291
407

D11853_PEA_1_T17 (SEQ ID NO: 67)
891
1007

D11853_PEA_1_T25 (SEQ ID NO: 72)
891
1007

Segment cluster D11853_PEA_—1_node_—8 (SEQ ID NO:437) according to the present invention is supported by 304 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
291
390

D11853_PEA_1_T3 (SEQ ID NO: 58)
291
390

D11853_PEA_1_T7 (SEQ ID NO: 59)
1008
1107

D11853_PEA_1_T8 (SEQ ID NO: 60)
782
881

D11853_PEA_1_T9 (SEQ ID NO: 61)
408
507

D11853_PEA_1_T10 (SEQ ID NO: 62)
291
390

D11853_PEA_1_T13 (SEQ ID NO: 63)
291
390

D11853_PEA_1_T14 (SEQ ID NO: 64)
291
390

D11853_PEA_1_T15 (SEQ ID NO: 65)
291
390

D11853_PEA_1_T16 (SEQ ID NO: 66)
291
390

D11853_PEA_1_T17 (SEQ ID NO: 67)
1008
1107

D11853_PEA_1_T19 (SEQ ID NO: 68)
291
390

D11853_PEA_1_T21 (SEQ ID NO: 69)
291
390

D11853_PEA_1_T23 (SEQ ID NO: 70)
291
390

D11853_PEA_1_T24 (SEQ ID NO: 71)
291
390

D11853_PEA_1_T25 (SEQ ID NO: 72)
1008
1107

D11853_PEA_1_T26 (SEQ ID NO: 73)
291
390

D11853_PEA_1_T27 (SEQ ID NO: 74)
291
390

Segment cluster D11853_PEA_—1_node_—10 (SEQ ID NO:438) according to the present invention is supported by 237 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
391
449

D11853_PEA_1_T3 (SEQ ID NO: 58)
391
449

D11853_PEA_1_T7 (SEQ ID NO: 59)
1108
1166

D11853_PEA_1_T8 (SEQ ID NO: 60)
882
940

D11853_PEA_1_T9 (SEQ ID NO: 61)
508
566

D11853_PEA_1_T10 (SEQ ID NO: 62)
391
449

D11853_PEA_1_T13 (SEQ ID NO: 63)
391
449

D11853_PEA_1_T14 (SEQ ID NO: 64)
391
449

D11853_PEA_1_T15 (SEQ ID NO: 65)
391
449

D11853_PEA_1_T16 (SEQ ID NO: 66)
391
449

D11853_PEA_1_T17 (SEQ ID NO: 67)
1108
1166

D11853_PEA_1_T19 (SEQ ID NO: 68)
391
449

D11853_PEA_1_T23 (SEQ ID NO: 70)
391
449

D11853_PEA_1_T24 (SEQ ID NO: 71)
391
449

D11853_PEA_1_T25 (SEQ ID NO: 72)
1240
1298

D11853_PEA_1_T26 (SEQ ID NO: 73)
391
449

D11853_PEA_1_T27 (SEQ ID NO: 74)
391
449

Segment cluster D11853_PEA_—1_node_—12 (SEQ ID NO:439) according to the present invention is supported by 239 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
450
482

D11853_PEA_1_T3 (SEQ ID NO: 58)
450
482

D11853_PEA_1_T7 (SEQ ID NO: 59)
1167
1199

D11853_PEA_1_T8 (SEQ ID NO: 60)
941
973

D11853_PEA_1_T9 (SEQ ID NO: 61)
567
599

D11853_PEA_1_T10 (SEQ ID NO: 62)
450
482

D11853_PEA_1_T13 (SEQ ID NO: 63)
450
482

D11853_PEA_1_T14 (SEQ ID NO: 64)
450
482

D11853_PEA_1_T15 (SEQ ID NO: 65)
450
482

D11853_PEA_1_T16 (SEQ ID NO: 66)
450
482

D11853_PEA_1_T17 (SEQ ID NO: 67)
1167
1199

D11853_PEA_1_T19 (SEQ ID NO: 68)
450
482

D11853_PEA_1_T23 (SEQ ID NO: 70)
450
482

D11853_PEA_1_T24 (SEQ ID NO: 71)
450
482

D11853_PEA_1_T25 (SEQ ID NO: 72)
1299
1331

D11853_PEA_1_T26 (SEQ ID NO: 73)
450
482

D11853_PEA_1_T27 (SEQ ID NO: 74)
450
482

Segment cluster D11853_PEA_—1_node_—13 (SEQ ID NO:440) according to the present invention can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62) D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
483
495

D11853_PEA_1_T3 (SEQ ID NO: 58)
483
495

D11853_PEA_1_T7 (SEQ ID NO: 59)
1200
1212

D11853_PEA_1_T8 (SEQ ID NO: 60)
974
986

D11853_PEA_1_T9 (SEQ ID NO: 61)
600
612

D11853_PEA_1_T10 (SEQ ID NO: 62)
483
495

D11853_PEA_1_T13 (SEQ ID NO: 63)
483
495

D11853_PEA_1_T14 (SEQ ID NO: 64)
483
495

D11853_PEA_1_T15 (SEQ ID NO: 65)
483
495

D11853_PEA_1_T16 (SEQ ID NO: 66)
483
495

D11853_PEA_1_T17 (SEQ ID NO: 67)
1200
1212

D11853_PEA_1_T19 (SEQ ID NO: 68)
483
495

D11853_PEA_1_T23 (SEQ ID NO: 70)
483
495

D11853_PEA_1_T24 (SEQ ID NO: 71)
483
495

D11853_PEA_1_T25 (SEQ ID NO: 72)
1332
1344

D11853_PEA_1_T26 (SEQ ID NO: 73)
483
495

D11853_PEA_1_T27 (SEQ ID NO: 74)
483
495

Segment cluster D11853_PEA_—1_node_—14 (SEQ ID NO:441) according to the present invention can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
496
511

D11853_PEA_1_T3 (SEQ ID NO: 58)
496
511

D11853_PEA_1_T7 (SEQ ID NO: 59)
1213
1228

D11853_PEA_1_T8 (SEQ ID NO: 60)
987
1002

D11853_PEA_1_T9 (SEQ ID NO: 61)
613
628

D11853_PEA_1_T10 (SEQ ID NO: 62)
496
511

D11853_PEA_1_T13 (SEQ ID NO: 63)
496
511

D11853_PEA_1_T14 (SEQ ID NO: 64)
496
511

D11853_PEA_1_T15 (SEQ ID NO: 65)
496
511

D11853_PEA_1_T16 (SEQ ID NO: 66)
496
511

D11853_PEA_1_T17 (SEQ ID NO: 67)
1213
1228

D11853_PEA_1_T19 (SEQ ID NO: 68)
496
511

D11853_PEA_1_T23 (SEQ ID NO: 70)
496
511

D11853_PEA_1_T24 (SEQ ID NO: 71)
496
511

D11853_PEA_1_T25 (SEQ ID NO: 72)
1345
1360

D11853_PEA_1_T26 (SEQ ID NO: 73)
496
511

D11853_PEA_1_T27 (SEQ ID NO: 74)
496
511

Segment cluster D11853_PEA_—1_node_—15 (SEQ ID NO:442) according to the present invention can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72), D11853_PEA_—1_T26 (SEQ ID NO:73) and D11853_PEA_—1_T27 (SEQ ID NO:74). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
512
533

D11853_PEA_1_T3 (SEQ ID NO: 58)
512
533

D11853_PEA_1_T7 (SEQ ID NO: 59)
1229
1250

D11853_PEA_1_T8 (SEQ ID NO: 60)
1003
1024

D11853_PEA_1_T9 (SEQ ID NO: 61)
629
650

D11853_PEA_1_T10 (SEQ ID NO: 62)
512
533

D11853_PEA_1_T13 (SEQ ID NO: 63)
512
533

D11853_PEA_1_T14 (SEQ ID NO: 64)
512
533

D11853_PEA_1_T15 (SEQ ID NO: 65)
512
533

D11853_PEA_1_T16 (SEQ ID NO: 66)
512
533

D11853_PEA_1_T17 (SEQ ID NO: 67)
1229
1250

D11853_PEA_1_T19 (SEQ ID NO: 68)
512
533

D11853_PEA_1_T23 (SEQ ID NO: 70)
512
533

D11853_PEA_1_T24 (SEQ ID NO: 71)
512
533

D11853_PEA_1_T25 (SEQ ID NO: 72)
1361
1382

D11853_PEA_1_T26 (SEQ ID NO: 73)
512
533

D11853_PEA_1_T27 (SEQ ID NO: 74)
512
533

Segment cluster D11853_PEA_—1_node_—16 (SEQ ID NO:443) according to the present invention can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72) and D11853_PEA_—1_T26 (SEQ ID NO:73). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
534
551

D11853_PEA_1_T3 (SEQ ID NO: 58)
534
551

D11853_PEA_1_T7 (SEQ ID NO: 59)
1251
1268

D11853_PEA_1_T8 (SEQ ID NO: 60)
1025
1042

D11853_PEA_1_T9 (SEQ ID NO: 61)
651
668

D11853_PEA_1_T10 (SEQ ID NO: 62)
534
551

D11853_PEA_1_T13 (SEQ ID NO: 63)
534
551

D11853_PEA_1_T14 (SEQ ID NO: 64)
534
551

D11853_PEA_1_T15 (SEQ ID NO: 65)
534
551

D11853_PEA_1_T16 (SEQ ID NO: 66)
534
551

D11853_PEA_1_T17 (SEQ ID NO: 67)
1251
1268

D11853_PEA_1_T19 (SEQ ID NO: 68)
534
551

D11853_PEA_1_T23 (SEQ ID NO: 70)
534
551

D11853_PEA_1_T24 (SEQ ID NO: 71)
534
551

D11853_PEA_1_T25 (SEQ ID NO: 72)
1383
1400

D11853_PEA_1_T26 (SEQ ID NO: 73)
534
551

Segment cluster D11853_PEA_—1_node_—18 (SEQ ID NO:444) according to the present invention is supported by 230 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T25 (SEQ ID NO:72) and D11853_PEA_—1_T26 (SEQ ID NO:73). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
552
582

D11853_PEA_1_T3 (SEQ ID NO: 58)
552
582

D11853_PEA_1_T7 (SEQ ID NO: 59)
1269
1299

D11853_PEA_1_T8 (SEQ ID NO: 60)
1043
1073

D11853_PEA_1_T9 (SEQ ID NO: 61)
669
699

D11853_PEA_1_T10 (SEQ ID NO: 62)
552
582

D11853_PEA_1_T13 (SEQ ID NO: 63)
552
582

D11853_PEA_1_T14 (SEQ ID NO: 64)
552
582

D11853_PEA_1_T15 (SEQ ID NO: 65)
552
582

D11853_PEA_1_T16 (SEQ ID NO: 66)
701
731

D11853_PEA_1_T17 (SEQ ID NO: 67)
1269
1299

D11853_PEA_1_T19 (SEQ ID NO: 68)
552
582

D11853_PEA_1_T21 (SEQ ID NO: 69)
391
421

D11853_PEA_1_T23 (SEQ ID NO: 70)
701
731

D11853_PEA_1_T25 (SEQ ID NO: 72)
1401
1431

D11853_PEA_1_T26 (SEQ ID NO: 73)
552
582

Segment cluster D11853_PEA_—1_node_—19 (SEQ ID NO:445) according to the present invention can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
583
587

D11853_PEA_1_T3 (SEQ ID NO: 58)
583
587

D11853_PEA_1_T7 (SEQ ID NO: 59)
1300
1304

D11853_PEA_1_T8 (SEQ ID NO: 60)
1074
1078

D11853_PEA_1_T9 (SEQ ID NO: 61)
700
704

D11853_PEA_1_T10 (SEQ ID NO: 62)
583
587

D11853_PEA_1_T13 (SEQ ID NO: 63)
583
587

D11853_PEA_1_T14 (SEQ ID NO: 64)
583
587

D11853_PEA_1_T15 (SEQ ID NO: 65)
583
587

D11853_PEA_1_T16 (SEQ ID NO: 66)
732
736

D11853_PEA_1_T17 (SEQ ID NO: 67)
1300
1304

D11853_PEA_1_T19 (SEQ ID NO: 68)
583
587

D11853_PEA_1_T21 (SEQ ID NO: 69)
422
426

D11853_PEA_1_T23 (SEQ ID NO: 70)
732
736

D11853_PEA_1_T25 (SEQ ID NO: 72)
1432
1436

Segment cluster D11853_PEA_—1_node_—20 (SEQ ID NO:446) according to the present invention is supported by 257 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
588
686

D11853_PEA_1_T3 (SEQ ID NO: 58)
588
686

D11853_PEA_1_T7 (SEQ ID NO: 59)
1305
1403

D11853_PEA_1_T8 (SEQ ID NO: 60)
1079
1177

D11853_PEA_1_T9 (SEQ ID NO: 61)
705
803

D11853_PEA_1_T10 (SEQ ID NO: 62)
588
686

D11853_PEA_1_T13 (SEQ ID NO: 63)
588
686

D11853_PEA_1_T14 (SEQ ID NO: 64)
588
686

D11853_PEA_1_T15 (SEQ ID NO: 65)
588
686

D11853_PEA_1_T16 (SEQ ID NO: 66)
737
835

D11853_PEA_1_T17 (SEQ ID NO: 67)
1305
1403

D11853_PEA_1_T19 (SEQ ID NO: 68)
588
686

D11853_PEA_1_T21 (SEQ ID NO: 69)
427
525

D11853_PEA_1_T23 (SEQ ID NO: 70)
737
835

D11853_PEA_1_T25 (SEQ ID NO: 72)
1437
1535

Segment cluster D11853_PEA_—1_node_—24 (SEQ ID NO:447) according to the present invention is supported by 254 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71) and D11853_PEA_—1_T25 (SEQ ID NO:72). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
832
911

D11853_PEA_1_T3 (SEQ ID NO: 58)
832
911

D11853_PEA_1_T7 (SEQ ID NO: 59)
1549
1628

D11853_PEA_1_T8 (SEQ ID NO: 60)
1323
1402

D11853_PEA_1_T9 (SEQ ID NO: 61)
949
1028

D11853_PEA_1_T10 (SEQ ID NO: 62)
832
911

D11853_PEA_1_T13 (SEQ ID NO: 63)
955
1034

D11853_PEA_1_T14 (SEQ ID NO: 64)
832
911

D11853_PEA_1_T15 (SEQ ID NO: 65)
955
1034

D11853_PEA_1_T16 (SEQ ID NO: 66)
981
1060

D11853_PEA_1_T17 (SEQ ID NO: 67)
1549
1628

D11853_PEA_1_T19 (SEQ ID NO: 68)
976
1055

D11853_PEA_1_T21 (SEQ ID NO: 69)
671
750

D11853_PEA_1_T23 (SEQ ID NO: 70)
1125
1204

D11853_PEA_1_T24 (SEQ ID NO: 71)
697
776

D11853_PEA_1_T25 (SEQ ID NO: 72)
1681
1760

Segment cluster D11853_PEA_—1_node_—28 (SEQ ID NO:448) according to the present invention can be found in the following transcript(s): D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T25 (SEQ ID NO:72) and D11853_PEA_—1_T26 (SEQ ID NO:73). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T3 (SEQ ID NO: 58)
1461
1465

D11853_PEA_1_T25 (SEQ ID NO: 72)
2515
2519

D11853_PEA_1_T26 (SEQ ID NO: 73)
583
587

Segment cluster D11853_PEA_—1_node_—29 (SEQ ID NO:449) according to the present invention is supported by 248 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_—1_T1 (SEQ ID NO:57), D11853_PEA_—1_T3 (SEQ ID NO:58), D11853_PEA_—1_T7 (SEQ ID NO:59), D11853_PEA_—1_T8 (SEQ ID NO:60), D11853_PEA_—1_T9 (SEQ ID NO:61), D11853_PEA_—1_T10 (SEQ ID NO:62), D11853_PEA_—1_T13 (SEQ ID NO:63), D11853_PEA_—1_T14 (SEQ ID NO:64), D11853_PEA_—1_T15 (SEQ ID NO:65), D11853_PEA_—1_T16 (SEQ ID NO:66), D11853_PEA_—1_T17 (SEQ ID NO:67), D11853_PEA_—1_T19 (SEQ ID NO:68), D11853_PEA_—1_T21 (SEQ ID NO:69), D11853_PEA_—1_T23 (SEQ ID NO:70), D11853_PEA_—1_T24 (SEQ ID NO:71), D11853_PEA_—1_T25 (SEQ ID NO:72) and D11853_PEA_—1_T26 (SEQ ID NO:73). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

D11853_PEA_1_T1 (SEQ ID NO: 57)
1041
1087

D11853_PEA_1_T3 (SEQ ID NO: 58)
1466
1512

D11853_PEA_1_T7 (SEQ ID NO: 59)
1758
1804

D11853_PEA_1_T8 (SEQ ID NO: 60)
1532
1578

D11853_PEA_1_T9 (SEQ ID NO: 61)
1158
1204

D11853_PEA_1_T10 (SEQ ID NO: 62)
1246
1292

D11853_PEA_1_T13 (SEQ ID NO: 63)
1164
1210

D11853_PEA_1_T14 (SEQ ID NO: 64)
912
958

D11853_PEA_1_T15 (SEQ ID NO: 65)
1369
1415

D11853_PEA_1_T16 (SEQ ID NO: 66)
1190
1236

D11853_PEA_1_T17 (SEQ ID NO: 67)
1758
1804

D11853_PEA_1_T19 (SEQ ID NO: 68)
1185
1231

D11853_PEA_1_T21 (SEQ ID NO: 69)
880
926

D11853_PEA_1_T23 (SEQ ID NO: 70)
1334
1380

D11853_PEA_1_T24 (SEQ ID NO: 71)
906
952

D11853_PEA_1_T25 (SEQ ID NO: 72)
2520
2566

D11853_PEA_1_T26 (SEQ ID NO: 73)
588
634

Variant Protein Alignment to the Previously Known Protein:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P1 (SEQ ID NO: 588) × Q9P042 (SEQ ID NO: 639) . .

Alignment segment 1/1:

Quality:
3115.00
Escore:
0

Matching length:
330
Total length:
330

Matching Percent Similarity:
99.70
Matching Percent Identity:
99.70

Total Percent Similarity:
99.70
Total Percent Identity:
99.70

Gaps:
0

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P1 (SEQ ID NO: 588) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
1512.00
Escore:
0

Matching length:
159
Total length:
159

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P1 (SEQ ID NO: 588) × Q96FY2 (SEQ ID NO: 638) . .

Alignment segment 1/1:

Quality:
3343.00
Escore:
0

Matching length:
356
Total length:
356

Matching Percent Similarity:
99.72
Matching Percent Identity:
99.72

Total Percent Similarity:
99.72
Total Percent Identity:
99.72

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P2 (SEQ ID NO: 589) × Q9P042 (SEQ ID NO: 639) . .

Alignment segment 1/1:

Quality:
2691.00
Escore:
0

Matching length:
285
Total length:
285

Matching Percent Similarity:
99.65
Matching Percent Identity:
99.65

Total Percent Similarity:
99.65
Total Percent Identity:
99.65

Gaps:
0

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P2 (SEQ ID NO: 589) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
1512.00
Escore:
0

Matching length:
159
Total length:
159

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P2 (SEQ ID NO: 589) × Q96FY2 (SEQ ID NO: 638) . .

Alignment segment 1/1:

Quality:
2919.00
Escore:
0

Matching length:
311
Total length:
311

Matching Percent Similarity:
99.68
Matching Percent Identity:
99.68

Total Percent Similarity:
99.68
Total Percent Identity:
99.68

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P2 (SEQ ID NO: 589) × Q9UJZ1 (SEQ ID NO: 637) . .

Alignment segment 1/1:

Quality:
2934.00
Escore:
0

Matching length:
311
Total length:
311

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P7 (SEQ ID NO: 590) × Q9P042 (SEQ ID NO: 639) . .

Alignment segment 1/1:

Quality:
2290.00
Escore:
0

Matching length:
242
Total length:
242

Matching Percent Similarity:
99.59
Matching Percent Identity:
99.59

Total Percent Similarity:
99.59
Total Percent Identity:
99.59

Gaps:
0

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P7 (SEQ ID NO: 590) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
1724.00
Escore:
0

Matching length:
181
Total length:
181

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P7 (SEQ ID NO: 590) × Q96FY2 (SEQ ID NO: 638) . .

Alignment segment 1/1:

Quality:
2518.00
Escore:
0

Matching length:
268
Total length:
268

Matching Percent Similarity:
99.63
Matching Percent Identity:
99.63

Total Percent Similarity:
99.63
Total Percent Identity:
99.63

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P7 (SEQ ID NO: 590) × Q9UJZ1 (SEQ ID NO: 637) . .

Alignment segment 1/1:

Quality:
2533.00
Escore:
0

Matching length:
268
Total length:
268

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P9 (SEQ ID NO: 591) × Q9P042 (SEQ ID NO: 639) . .

Alignment segment 1/1:

Quality:
3015.00
Escore:
0

Matching length:
330
Total length:
371

Matching Percent Similarity:
99.70
Matching Percent Identity:
99.70

Total Percent Similarity:
88.68
Total Percent Identity:
88.68

Gaps:
1

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P9 (SEQ ID NO: 591) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
1412.00
Escore:
0

Matching length:
159
Total length:
200

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
79.50
Total Percent Identity:
79.50

Gaps:
1

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P9 (SEQ ID NO: 591) × Q96FY2 (SEQ ID NO: 638) . .

Alignment segment 1/1:

Quality:
3243.00
Escore:
0

Matching length:
356
Total length:
397

Matching Percent Similarity:
99.72
Matching Percent Identity:
99.72

Total Percent Similarity:
89.42
Total Percent Identity:
89.42

Gaps:
1

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P9 (SEQ ID NO: 591) × Q9UJZ1 (SEQ ID NO: 637) . .

Alignment segment 1/1:

Quality:
3258.00
Escore:
0

Matching length:
356
Total length:
397

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
89.67
Total Percent Identity:
89.67

Gaps:
1

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P10 (SEQ ID NO: 592) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
2614.00
Escore:
0

Matching length:
287
Total length:
330

Matching Percent Similarity:
99.65
Matching Percent Identity:
99.65

Total Percent Similarity:
86.67
Total Percent Identity:
86.67

Gaps:
1

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P10 (SEQ ID NO: 592) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
1515.00
Escore:
0

Matching length:
162
Total length:
162

Matching Percent Similarity:
98.77
Matching Percent Identity:
98.77

Total Percent Similarity:
98.77
Total Percent Identity:
98.77

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P10 (SEQ ID NO: 592) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
2842.00
Escore:
0

Matching length:
313
Total length:
356

Matching Percent Similarity:
99.68
Matching Percent Identity:
99.68

Total Percent Similarity:
87.64
Total Percent Identity:
87.64

Gaps:
1

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P10 (SEQ ID NO: 592) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
2857.00
Escore:
0

Matching length:
313
Total length:
356

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
87.92
Total Percent Identity:
87.92

Gaps:
1

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P11 (SEQ ID NO: 593) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
2190.00
Escore:
0

Matching length:
242
Total length:
283

Matching Percent Similarity:
99.59
Matching Percent Identity:
99.59

Total Percent Similarity:
85.16
Total Percent Identity:
85.16

Gaps:
1

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P11 (SEQ ID NO: 593) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
1624.00
Escore:
0

Matching length:
181
Total length:
222

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
81.53
Total Percent Identity:
81.53

Gaps:
1

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P11 (SEQ ID NO: 593) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
2418.00
Escore:
0

Matching length:
268
Total length:
309

Matching Percent Similarity:
99.63
Matching Percent Identity:
99.63

Total Percent Similarity:
86.41
Total Percent Identity:
86.41

Gaps:
1

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P11 (SEQ ID NO: 593) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
2433.00
Escore:
0

Matching length:
268
Total length:
309

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
86.73
Total Percent Identity:
86.73

Gaps:
1

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P12 (SEQ ID NO: 594) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
1167.00
Escore:
0

Matching length:
122
Total length:
122

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P12 (SEQ ID NO: 594) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
1385.00
Escore:
0

Matching length:
148
Total length:
148

Matching Percent Similarity:
99.32
Matching Percent Identity:
99.32

Total Percent Similarity:
99.32
Total Percent Identity:
99.32

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P12 (SEQ ID NO: 594) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
1400.00
Escore:
0

Matching length:
148
Total length:
148

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P14 (SEQ ID NO: 595) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
1628.00
Escore:
0

Matching length:
170
Total length:
170

Matching Percent Similarity:
99.41
Matching Percent Identity:
99.41

Total Percent Similarity:
99.41
Total Percent Identity:
99.41

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P14 (SEQ ID NO: 595) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
1846.00
Escore:
0

Matching length:
196
Total length:
196

Matching Percent Similarity:
98.98
Matching Percent Identity:
98.98

Total Percent Similarity:
98.98
Total Percent Identity:
98.98

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P14 (SEQ ID NO: 595) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
1861.00
Escore:
0

Matching length:
196
Total length:
196

Matching Percent Similarity:
99.49
Matching Percent Identity:
99.49

Total Percent Similarity:
99.49
Total Percent Identity:
99.49

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P16 (SEQ ID NO: 596) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
2564.00
Escore:
0

Matching length:
285
Total length:
330

Matching Percent Similarity:
99.65
Matching Percent Identity:
99.65

Total Percent Similarity:
86.06
Total Percent Identity:
86.06

Gaps:
1

Alignment:

Sequence name: BAC85377 (SEQ ID NO: 640)

Sequence documentation:

Alignment of:

D11853_PEA_1_P16 (SEQ ID NO: 596) × BAC85377 (SEQ ID NO: 640)

Alignment segment 1/1:

Quality:
961.00
Escore:
0

Matching length:
114
Total length:
159

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
71.70
Total Percent Identity:
71.70

Gaps:
1

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P16 (SEQ ID NO: 596) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
2792.00
Escore:
0

Matching length:
311
Total length:
356

Matching Percent Similarity:
99.68
Matching Percent Identity:
99.68

Total Percent Similarity:
87.08
Total Percent Identity:
87.08

Gaps:
1

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P16 (SEQ ID NO: 596) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
2807.00
Escore:
0

Matching length:
311
Total length:
356

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
87.36
Total Percent Identity:
87.36

Gaps:
1

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P18 (SEQ ID NO: 597) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
1601.00
Escore:
0

Matching length:
179
Total length:
330

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
54.24
Total Percent Identity:
54.24

Gaps:
1

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P18 (SEQ ID NO: 597) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
1819.00
Escore:
0

Matching length:
205
Total length:
356

Matching Percent Similarity:
99.51
Matching Percent Identity:
99.51

Total Percent Similarity:
57.30
Total Percent Identity:
57.30

Gaps:
1

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P18 (SEQ ID NO: 597) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
1834.00
Escore:
0

Matching length:
205
Total length:
356

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
57.58
Total Percent Identity:
57.58

Gaps:
1

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P19 (SEQ ID NO: 598) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
1110.00
Escore:
0

Matching length:
116
Total length:
116

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P19 (SEQ ID NO: 598) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
1328.00
Escore:
0

Matching length:
142
Total length:
142

Matching Percent Similarity:
99.30
Matching Percent Identity:
99.30

Total Percent Similarity:
99.30
Total Percent Identity:
99.30

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P19 (SEQ ID NO: 598) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
1343.00
Escore:
0

Matching length:
142
Total length:
142

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1 P21 (SEQ ID NO: 600) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
587.00
Escore:
0

Matching length:
68
Total length:
68

Matching Percent Similarity:
95.59
Matching Percent Identity:
92.65

Total Percent Similarity:
95.59
Total Percent Identity:
92.65

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P21 (SEQ ID NO: 600) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
587.00
Escore:
0

Matching length:
68
Total length:
68

Matching Percent Similarity:
95.59
Matching Percent Identity:
92.65

Total Percent Similarity:
95.59
Total Percent Identity:
92.65

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P22 (SEQ ID NO: 601) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
348.00
Escore:
0

Matching length:
37
Total length:
37

Matching Percent Similarity:
97.30
Matching Percent Identity:
97.30

Total Percent Similarity:
97.30
Total Percent Identity:
97.30

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P22 (SEQ ID NO: 601) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
581.00
Escore:
0

Matching length:
63
Total length:
63

Matching Percent Similarity:
98.41
Matching Percent Identity:
98.41

Total Percent Similarity:
98.41
Total Percent Identity:
98.41

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P22 (SEQ ID NO: 601) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
581.00
Escore:
0

Matching length:
63
Total length:
63

Matching Percent Similarity:
98.41
Matching Percent Identity:
98.41

Total Percent Similarity:
98.41
Total Percent Identity:
98.41

Gaps:
0

Alignment:

Sequence name: Q9P042 (SEQ ID NO: 639)

Sequence documentation:

Alignment of:

D11853_PEA_1_P24 (SEQ ID NO: 602) × Q9P042 (SEQ ID NO: 639)

Alignment segment 1/1:

Quality:
650.00
Escore:
0

Matching length:
68
Total length:
68

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q96FY2 (SEQ ID NO: 638)

Sequence documentation:

Alignment of:

D11853_PEA_1_P24 (SEQ ID NO: 602) × Q96FY2 (SEQ ID NO: 638)

Alignment segment 1/1:

Quality:
883.00
Escore:
0

Matching length:
94
Total length:
94

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9UJZ1 (SEQ ID NO: 637)

Sequence documentation:

Alignment of:

D11853_PEA_1_P24 (SEQ ID NO: 602) × Q9UJZ1 (SEQ ID NO: 637)

Alignment segment 1/1:

Quality:
883.00
Escore:
0

Matching length:
94
Total length:
94

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Description for Cluster R11723

Cluster R11723 features 6 transcript(s) and 26 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

R11723_PEA_1_T15
75

R11723_PEA_1_T17
76

R11723_PEA_1_T19
77

R11723_PEA_1_T20
78

R11723_PEA_1_T5
79

R11723_PEA_1_T6
80

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

R11723_PEA_1_node_13
450

R11723_PEA_1_node_16
451

R11723_PEA_1_node_19
452

R11723_PEA_1_node_2
453

R11723_PEA_1_node_22
454

R11723_PEA_1_node_31
455

R11723_PEA_1_node_10
456

R11723_PEA_1_node_11
457

R11723_PEA_1_node_15
458

R11723_PEA_1_node_18
459

R11723_PEA_1_node_20
460

R11723_PEA_1_node_21
461

R11723_PEA_1_node_23
462

R11723_PEA_1_node_24
463

R11723_PEA_1_node_25
464

R11723_PEA_1_node_26
465

R11723_PEA_1_node_27
466

R11723_PEA_1_node_28
467

R11723_PEA_1_node_29
468

R11723_PEA_1_node_3
469

R11723_PEA_1_node_30
470

R11723_PEA_1_node_4
471

R11723_PEA_1_node_5
472

R11723_PEA_1_node_6
473

R11723_PEA_1_node_7
474

R11723_PEA_1_node_8
475

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:

R11723_PEA_1_P2
603

R11723_PEA_1_P6
604

R11723_PEA_1_P7
605

R11723_PEA_1_P13
606

R11723_PEA_1_P10
607

Cluster R11723 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the right hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 27 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

adrenal
0

brain
30

epithelial
3

general
17

Head and neck
0

kidney
0

Lung
0

breast
0

ovary
0

pancreas
10

skin
0

uterus
0

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
4.2e−01
4.6e−01
4.6e−01
2.2
5.3e−01
1.9

brain
2.2e−01
2.0e−01
1.2e−02
2.8
5.0e−02
2.0

epithelial
3.0e−05
6.3e−05
1.8e−05
6.3
3.4e−06
6.4

general
7.2e−03
4.0e−02
1.3e−04
2.1
1.1e−03
1.7

head and neck
1
5.0e−01
1
1.0
7.5e−01
1.3

kidney
1.5e−01
2.4e−01
4.4e−03
5.4
2.8e−02
3.6

lung
1.2e−01
1.6e−01
1
1.6
1
1.3

breast
5.9e−01
4.4e−01
1
1.1
6.8e−01
1.5

ovary
1.6e−02
1.3e−02
1.0e−01
3.8
7.0e−02
3.5

pancreas
5.5e−01
2.0e−01
3.9e−01
1.9
1.4e−01
2.7

skin
1
4.4e−01
1
1.0
1.9e−02
2.1

uterus
1.5e−02
5.4e−02
1.9e−01
3.1
1.4e−01
2.5

As noted above, cluster R11723 features 6 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein R11723_PEA_—1_P2 (SEQ ID NO:603) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA_—1_T6 (SEQ ID NO:80). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein R11723_PEA_—1_P2 (SEQ ID NO:603) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P2 (SEQ ID NO:603) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

107
H -> P
Yes

70
G ->
No

70
G -> C
No

Variant protein R11723_PEA_—1_P2 (SEQ ID NO:603) is encoded by the following transcript(s): R11723_PEA_—1_T6 (SEQ ID NO:80), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA_—1_T6 (SEQ ID NO:80) is shown in bold; this coding portion starts at position 1716 and ends at position 2051. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P2 (SEQ ID NO:603) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on necleotide
Alternative

sequence
nucleic acid
Previously known SNP?

1231
C -> T
Yes

1278
G -> C
Yes

1923
G ->
No

1923
G -> T
No

2035
A -> C
Yes

2048
A -> C
No

2057
A -> G
Yes

Variant protein R11723_PEA_—1_P6 (SEQ ID NO:604) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA_—1_T15 (SEQ ID NO:75). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R11723_PEA_—1_P6 (SEQ ID NO:604) and Q8IXM0 (SEQ ID NO:1393):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P6 (SEQ ID NO:604), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS CASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR (SEQ ID NO:1558) corresponding to amino acids 1-110 of R11723_PEA_—1_P6 (SEQ ID NO:604), and a second amino acid sequence being at least 90% homologous to MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLG FGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 1-112 of Q8IXM0, which also corresponds to amino acids 111-222 of R11723_PEA_—1_P6 (SEQ ID NO:604), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R11723_PEA_—1_P6 (SEQ ID NO:604), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS CASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR (SEQ ID NO:1558) of R11723_PEA_—1_P6 (SEQ ID NO:604).

Comparison Report Between R11723_PEA_—1_P6 (SEQ ID NO:604) and Q96AC2 (SEQ ID NO:1394):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P6 (SEQ ID NO:604), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS CASSAACLIASAG corresponding to amino acids 1-83 of Q96AC2, which also corresponds to amino acids 1-83 of R11723_PEA_—1_P6 (SEQ ID NO:604), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM RTQ (SEQ ID NO:1559) corresponding to amino acids 84-222 of R11723_PEA_—1_P6 (SEQ ID NO:604) wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA_—1_P6 (SEQ ID NO:604), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM RTQ SEQ ID NO:1559) in R11723_PEA_—1_P6 (SEQ ID NO:604).

Comparison Report Between R11723_PEA_—1_P6 (SEQ ID NO:604) and Q8N2G4 (SEQ ID NO:1395):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P6 (SEQ ID NO:604), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS CASSAACLIASAG corresponding to amino acids 1-83 of Q8N2G4, which also corresponds to amino acids 1-83 of R11723_PEA_—1_P6 (SEQ ID NO:604), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM RTQ SEQ ID NO:1559) corresponding to amino acids 84-222 of R11723_PEA_—1_P6 (SEQ ID NO:604), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Comparison Report Between R11723_PEA_—1_P6 (SEQ ID NO:604) and BAC85518 (SEQ ID NO:1396):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P6 (SEQ ID NO:604), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS CASSAACLIASAG corresponding to amino acids 24-106 of BAC85518 (SEQ ID NO:1396), which also corresponds to amino acids 1-83 of R11723_PEA_—1_P6 (SEQ ID NO:604), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM RTQ SEQ ID NO:1559) corresponding to amino acids 84-222 of R11723_PEA_—1_P6 (SEQ ID NO:604), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Variant protein R11723_PEA_—1_P6 (SEQ ID NO:604) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P6 (SEQ ID NO:604) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

180
G ->
No

180
G -> C
No

217
H -> P
Yes

Variant protein R11723_PEA_—1_P6 (SEQ ID NO:604) is encoded by the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA_—1_T15 (SEQ ID NO:75) is shown in bold; this coding portion starts at position 434 and ends at position 1099. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P6 (SEQ ID NO:604) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

971
G ->
No

971
G -> T
No

1083
A -> C
Yes

1096
A -> C
No

1105
A -> G
Yes

Variant protein R11723_PEA_—1_P7 (SEQ ID NO:605) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA_—1_T17 (SEQ ID NO:76). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R11723_PEA_—1_P7 (SEQ ID NO:605) and Q96AC2 (SEQ ID NO: 1394):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG corresponding to amino acids 1-64 of Q96AC2 (SEQ ID NO: 1394), which also corresponds to amino acids 1-64 of R11723_PEA_—1_P7 (SEQ ID NO:605), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1560) corresponding to amino acids 65-93 of R11723_PEA_—1_P7 (SEQ ID NO:605), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1560) in R11723_PEA_—1_P7 (SEQ ID NO:605).

Comparison Report Between R11723_PEA_—1_P7 (SEQ ID NO:605) and Q8N2G4 (SEQ ID NO: 1395):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG corresponding to amino acids 1-64 of Q8N2G4 (SEQ ID NO: 1395), which also corresponds to amino acids 1-64 of R11723_PEA_—1_P7 (SEQ ID NO:605), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1560) corresponding to amino acids 65-93 of R11723_PEA_—1_P7 (SEQ ID NO:605), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Comparison Report Between R11723_PEA_—1_P7 (SEQ ID NO:605) and BAC85273 (SEQ ID NO:1397):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG (SEQ ID NO:1561) corresponding to amino acids 1-5 of R11723_PEA_—1_P7 (SEQ ID NO:605), second amino acid sequence being at least 90% homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG corresponding to amino acids 22-80 of BAC85273 (SEQ ID NO:1397), which also corresponds to amino acids 6-64 of R11723_PEA_—1_P7 (SEQ ID NO:605), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1560) corresponding to amino acids 65-93 of R11723_PEA_—1_P7 (SEQ ID NO:605), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG (SEQ ID NO:1561) of R11723_PEA_—1_P7 (SEQ ID NO:605).

3. An isolated polypeptide encoding for a tail of R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1560) in R11723_PEA_—1_P7 (SEQ ID NO:605).

Comparison Report Between R11723_PEA_—1_P7 (SEQ ID NO:605) and BAC85518 (SEQ ID NO:1396):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P7 (SEQ ID NO:605), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG corresponding to amino acids 24-87 of BAC85518 (SEQ ID NO:1396), which also corresponds to amino acids 1-64 of R11723_PEA_—1_P7 (SEQ ID NO:605), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO:1560) corresponding to amino acids 65-93 of R11723_PEA_—1_P7 (SEQ ID NO:605), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Variant protein R11723_PEA_—1_P7 (SEQ ID NO:605) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P7 (SEQ ID NO:605) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

67
C -> S
Yes

Variant protein R11723_PEA_—1_P7 (SEQ ID NO:605) is encoded by the following transcript(s): R11723_PEA_—1_T17 (SEQ ID NO:76), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA_—1_T17 (SEQ ID NO:76) is shown in bold; this coding portion starts at position 434 and ends at position 712. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P7 (SEQ ID NO:605) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

625
G -> T
Yes

633
G -> C
Yes

1303
C -> T
Yes

Variant protein R11723_PEA_—1_P13 (SEQ ID NO:606) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA_—1_T19 (SEQ ID NO:77) and R11723_PEA_—1_T5 (SEQ ID NO:79). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R11723_PEA_—1_P13 (SEQ ID NO:606) and Q96AC2 (SEQ ID NO: 1394):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P13 (SEQ ID NO:606), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO: 1394), which also corresponds to amino acids 1-63 of R11723_PEA_—1_P13 (SEQ ID NO:606), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1562) corresponding to amino acids 64-84 of R11723_PEA_—1_P13 (SEQ ID NO:606), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA_—1_P13 (SEQ ID NO:606), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1562) in R11723_PEA_—1_P13 (SEQ ID NO:606).

Variant protein R11723_PEA_—1_P13 (SEQ ID NO:606) is encoded by the following transcript(s): R11723_PEA_—1_T19 (SEQ ID NO:77), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA_—1_T19 (SEQ ID NO:77) is shown in bold; this coding portion starts at position 434 and ends at position 685. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P13 (SEQ ID NO:606) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

778
G -> T
Yes

786
G -> C
Yes

1456
C -> T
Yes

Variant protein R11723_PEA_—1_P10 (SEQ ID NO:607) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA_—1_T20 (SEQ ID NO:78). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R11723_PEA_—1_P10 (SEQ ID NO:607) and Q96AC2 (SEQ ID NO: 1394):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO: 1394), which also corresponds to amino acids 1-63 of R11723_PEA_—1_P10 (SEQ ID NO:607), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1563) corresponding to amino acids 64-90 of R11723_PEA_—1_P10 (SEQ ID NO:607), wherein said first and second amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1563) in R11723_PEA_—1_P10 (SEQ ID NO:607).

Comparison Report Between R11723_PEA_—1_P10 (SEQ ID NO:607) and Q8N2G4 (SEQ ID NO: 1395):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 1-63 of Q8N2G4 (SEQ ID NO: 1395), which also corresponds to amino acids 1-63 of R11723_PEA_—1_P10 (SEQ ID NO:607), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1563) corresponding to amino acids 64-90 of R11723_PEA_—1_P10 (SEQ ID NO:607), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Comparison Report Between R11723_PEA_—1_P10 (SEQ ID NO:607) and BAC85273 (SEQ ID NO:1397) (SEQ ID NO:1397):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG (SEQ ID NO:1561) corresponding to amino acids 1-5 of R11723_PEA_—1_P10 (SEQ ID NO:607), second amino acid sequence being at least 90% homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 22-79 of BAC85273 (SEQ ID NO:1397), which also corresponds to amino acids 6-63 of R11723_PEA_—1_P10 (SEQ ID NO:607), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1563) corresponding to amino acids 64-90 of R11723_PEA_—1_P10 (SEQ ID NO:607), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG (SEQ ID NO:1561) of R11723_PEA_—1_P10 (SEQ ID NO:607).

3. An isolated polypeptide encoding for a tail of R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1563) in R11723_PEA_—1_P10 (SEQ ID NO:607).

Comparison Report Between R11723_PEA_—1_P10 (SEQ ID NO:607) and BAC85518 (SEQ ID NO:1396):

1. An isolated chimeric polypeptide encoding for R11723_PEA_—1_P10 (SEQ ID NO:607), comprising a first amino acid sequence being at least 90% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 24-86 of BAC85518 (SEQ ID NO:1396), which also corresponds to amino acids 1-63 of R11723_PEA_—1_P10 (SEQ ID NO:607), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO:1563) corresponding to amino acids 64-90 of R11723_PEA_—1_P10 (SEQ ID NO:607), wherein said first and second amino acid sequences are contiguous and in a sequential order.

Variant protein R11723_PEA_—1_P10 (SEQ ID NO:607) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P10 (SEQ ID NO:607) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

66
V -> F
Yes

Variant protein R11723_PEA_—1_P10 (SEQ ID NO:607) is encoded by the following transcript(s): R11723_PEA_—1_T20 (SEQ ID NO:78), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA_—1_T20 (SEQ ID NO:78) is shown in bold; this coding portion starts at position 434 and ends at position 703. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_—1_P10 (SEQ ID NO:607) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

629
G -> T
Yes

637
G -> C
Yes

1307
C -> T
Yes

As noted above, cluster R11723 features 26 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster R11723_PEA_—1_node_—13 (SEQ ID NO:450) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T19 (SEQ ID NO: 77)
624
776

R11723_PEA_1_T5 (SEQ ID NO: 79)
624
776

R11723_PEA_1_T6 (SEQ ID NO: 80)
658
810

Segment cluster R11723_PEA_—1_node_—16 (SEQ ID NO:451) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77) and R11723_PEA_—1_T20 (SEQ ID NO:78). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T17 (SEQ ID NO: 76)
624
1367

R11723_PEA_1_T19 (SEQ ID NO: 77)
777
1520

R11723_PEA_1_T20 (SEQ ID NO: 78)
628
1371

Segment cluster R11723_PEA_—1_node_—19 (SEQ ID NO:452) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T5 (SEQ ID NO: 79)
835
1008

R11723_PEA_1_T6 (SEQ ID NO: 80)
869
1042

Segment cluster R11723_PEA_—1_node_—2 (SEQ ID NO:453) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
1
309

R11723_PEA_1_T17 (SEQ ID NO: 76)
1
309

R11723_PEA_1_T19 (SEQ ID NO: 77)
1
309

R11723_PEA_1_T20 (SEQ ID NO: 78)
1
309

R11723_PEA_1_T5 (SEQ ID NO: 79)
1
309

R11723_PEA_1_T6 (SEQ ID NO: 80)
1
309

Segment cluster R11723_PEA_—1_node_—22 (SEQ ID NO:454) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T5 (SEQ ID NO: 79)
1083
1569

R11723_PEA_1_T6 (SEQ ID NO: 80)
1117
1603

Segment cluster R11723_PEA_—1_node_—31 (SEQ ID NO:455) according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 20 below describes the starting and ending position of this segment on each transcript (it should be noted that these transcripts show alternative polyadenylation).

TABLE 20

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
1060
1295

R11723_PEA_1_T5 (SEQ ID NO: 79)
1978
2213

R11723_PEA_1_T6 (SEQ ID NO: 80)
2012
2247

Segment cluster R11723_PEA_—1_node_—10 (SEQ ID NO:456) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
486
529

R11723_PEA_1_T17 (SEQ ID NO: 76)
486
529

R11723_PEA_1_T19 (SEQ ID NO: 77)
486
529

R11723_PEA_1_T20 (SEQ ID NO: 78)
486
529

R11723_PEA_1_T5 (SEQ ID NO: 79)
486
529

R11723_PEA_1_T6 (SEQ ID NO: 80)
520
563

Segment cluster R11723_PEA_—1_node_—11 (SEQ ID NO:457) according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
530
623

R11723_PEA_1_T17 (SEQ ID NO: 76)
530
623

R11723_PEA_1_T19 (SEQ ID NO: 77)
530
623

R11723_PEA_1_T20 (SEQ ID NO: 78)
530
623

R11723_PEA_1_T5 (SEQ ID NO: 79)
530
623

R11723_PEA_1_T6 (SEQ ID NO: 80)
564
657

Segment cluster R11723_PEA_—1_node_—15 (SEQ ID NO:458) according to the present invention can be found in the following transcript(s): R11723_PEA_—1_T20 (SEQ ID NO:78). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T20 (SEQ ID NO: 78)
624
627

Segment cluster R11723_PEA_—1_node_—18 (SEQ ID NO:459) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
624
681

R11723_PEA_1_T5 (SEQ ID NO: 79)
777
834

R11723_PEA_1_T6 (SEQ ID NO: 80)
811
868

Segment cluster R11723_PEA_—1_node_—20 (SEQ ID NO:460) according to the present invention can be found in the following transcript(s): R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T5 (SEQ ID NO: 79)
1009
1019

R11723_PEA_1_T6 (SEQ ID NO: 80)
1043
1053

Segment cluster R11723_PEA_—1_node_—21 (SEQ ID NO:461) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T5 (SEQ ID NO: 79)
1020
1082

R11723_PEA_1_T6 (SEQ ID NO: 80)
1054
1116

Segment cluster R11723_PEA_—1_node_—23 (SEQ ID NO:462) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T5 (SEQ ID NO: 79)
1570
1599

R11723_PEA_1_T6 (SEQ ID NO: 80)
1604
1633

Segment cluster R11723_PEA_—1_node_—24 (SEQ ID NO:463) according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
682
765

R11723_PEA_1_T5 (SEQ ID NO: 79)
1600
1683

R11723_PEA_1_T6 (SEQ ID NO: 80)
1634
1717

Segment cluster R11723_PEA_—1_node_—25 (SEQ ID NO:464) according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
766
791

R11723_PEA_1_T5 (SEQ ID NO: 79)
1684
1709

R11723_PEA_1_T6 (SEQ ID NO: 80)
1718
1743

Segment cluster R11723_PEA_—1_node_—26 (SEQ ID NO:465) according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
792
904

R11723_PEA_1_T5 (SEQ ID NO: 79)
1710
1822

R11723_PEA_1_T6 (SEQ ID NO: 80)
1744
1856

Segment cluster R11723_PEA_—1_node_—27 (SEQ ID NO:466) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723=PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
905
986

R11723_PEA_1_T5 (SEQ ID NO: 79)
1823
1904

R11723_PEA_1_T6 (SEQ ID NO: 80)
1857
1938

Segment cluster R11723_PEA_—1_node_—28 (SEQ ID NO:467) according to the present invention can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
987
1010

R11723_PEA_1_T5 (SEQ ID NO: 79)
1905
1928

R11723_PEA_1_T6 (SEQ ID NO: 80)
1939
1962

Segment cluster R11723_PEA_—1_node_—29 (SEQ ID NO:468) according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
1011
1038

R11723_PEA_1_T5 (SEQ ID NO: 79)
1929
1956

R11723_PEA_1_T6 (SEQ ID NO: 80)
1963
1990

Segment cluster R11723_PEA_—1_node_—3 (SEQ ID NO:469) according to the present invention can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
310
319

R11723_PEA_1_T17 (SEQ ID NO: 76)
310
319

R11723_PEA_1_T19 (SEQ ID NO: 77)
310
319

R11723_PEA_1_T20 (SEQ ID NO: 78)
310
319

R11723_PEA_1_T5 (SEQ ID NO: 79)
310
319

R11723_PEA_1_T6 (SEQ ID NO: 80)
310
319

Segment cluster R11723_PEA_—1_node_—30 (SEQ ID NO:470) according to the present invention can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
1039
1059

R11723_PEA_1_T5 (SEQ ID NO: 79)
1957
1977

R11723_PEA_1_T6 (SEQ ID NO: 80)
1991
2011

Segment cluster R11723_PEA_—1_node_—4 (SEQ ID NO:471) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
320
371

R11723_PEA_1_T17 (SEQ ID NO: 76)
320
371

R11723_PEA_1_T19 (SEQ ID NO: 77)
320
371

R11723_PEA_1_T20 (SEQ ID NO: 78)
320
371

R11723_PEA_1_T5 (SEQ ID NO: 79)
320
371

R11723_PEA_1_T6 (SEQ ID NO: 80)
320
371

Segment cluster R11723_PEA_—1_node_—5 (SEQ ID NO:472) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
372
414

R11723_PEA_1_T17 (SEQ ID NO: 76)
372
414

R11723_PEA_1_T19 (SEQ ID NO: 77)
372
414

R11723_PEA_1_T20 (SEQ ID NO: 78)
372
414

R11723_PEA_1_T5 (SEQ ID NO: 79)
372
414

R11723_PEA_1_T6 (SEQ ID NO: 80)
372
414

Segment cluster R11723_PEA_—1_node_—6 (SEQ ID NO:473) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
415
446

R11723_PEA_1_T17 (SEQ ID NO: 76)
415
446

R11723_PEA_1_T19 (SEQ ID NO: 77)
415
446

R11723_PEA_1_T20 (SEQ ID NO: 78)
415
446

R11723_PEA_1_T5 (SEQ ID NO: 79)
415
446

R11723_PEA_1_T6 (SEQ ID NO: 80)
415
446

Segment cluster R11723_PEA_—1_node_—7 (SEQ ID NO:474) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T15 (SEQ ID NO:75), R11723_PEA_—1_T17 (SEQ ID NO:76), R11723_PEA_—1_T19 (SEQ ID NO:77), R11723_PEA_—1_T20 (SEQ ID NO:78), R11723_PEA_—1_T5 (SEQ ID NO:79) and R11723_PEA_—1_T6 (SEQ ID NO:80). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

R11723_PEA_1_T15 (SEQ ID NO: 75)
447
485

R11723_PEA_1_T17 (SEQ ID NO: 76)
447
485

R11723_PEA_1_T19 (SEQ ID NO: 77)
447
485

R11723_PEA_1_T20 (SEQ ID NO: 78)
447
485

R11723_PEA_1_T5 (SEQ ID NO: 79)
447
485

R11723_PEA_1_T6 (SEQ ID NO: 80)
447
485

Segment cluster R11723_PEA_—1_node_—8 (SEQ ID NO:475) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_—1_T6 (SEQ ID NO:80). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment

starting
Segment ending

Transcript name
position
position

R11723_PEA_1_T6 (SEQ ID NO: 80)
486
519

It should be noted that the variants of this cluster are variants of the hypothetical protein PSEC0181 (SEQ ID NO:1395) (referred to herein as “PSEC”). Furthermore, use of the known protein (WT protein) for detection of ovarian cancer, alone or in combination with one or more variants of this cluster and/or of any other cluster and/or of any known marker, also comprises an embodiment of the present invention.

It should be noted that the nucleotide transcript sequence of known protein (PSEC, also referred to herein as the “wild type” or WT protein) feature at least one SNP that appears to affect the coding region, in addition to certain silent SNPs. This SNP does not have an effect on the R11723_PEA_—1_T5 (SEQ ID NO:79) splice variant sequence): “G->” resulting in a missing nucleotide (affects amino acids from position 91 onwards). The missing nucleotide creates a frame shift, resulting in a new protein. This SNP was not previously identified and is supported by 5 ESTs out of ˜70 ESTs in this exon.

Expression of R1723 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name R11723 Seg13 (SEQ ID NO:1297) in Normal and Cancerous Colon Tissues.

Expression of transcripts detectable by or according to seg13, R11723 seg13 amplicon (SEQ ID NO: 1297) and R11723 seg13F (SEQ ID NO: 1295) and R11723 seg13R (SEQ ID NO: 1296) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3, above: “Tissue samples in colon cancer testing panel”), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

FIG. 28 is a histogram showing differential expression of the above-indicated transcripts in cancerous colon samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.

As is evident from FIG. 28, the expression of transcripts detectable by the above amplicon in a few cancer samples was higher by more than 5 fold than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 3: “Tissue samples in colon cancer testing panel”). However, the expression of transcripts detectable by the above amplicon in a several other cancer samples was lower than in the non-cancerous samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R11723 seg13F forward primer (SEQ ID NO: 1295); and R11723 seg13R reverse primer (SEQ ID NO: 1296).

(SEQ ID NO: 1295)

R11723seg13F-ACACTAAAAGAACAAACACCTTGCTC

(SEQ ID NO: 1296)

R11723seg13R-TCCTCAGAAGGCACATGAAAGA

R11723seg13-amplicon (SEQ ID NO: 1297):

ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAG

CAGTTGACCACTTAGTTCTCAAGAAGCAAGTATCTCTTTCATGTGCCTTC

TGAGGA

Expression of R11723 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name R11723 junc11-18 (SEQ ID NO: 1300) in Normal and Cancerous Colon Tissues.

Expression of transcripts detectable by or according to junc11-18, R11723 junc11-18 amplicon (SEQ ID NO: 1300) and R11723 junc11-18F (SEQ ID NO: 1298) and R11723 junc11-18R (SEQ ID NO: 1299) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3, above: “Tissue samples in colon cancer testing panel”), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

FIG. 29 is a histogram showing differential expression of the above-indicated transcripts in a few cancerous colon samples relative to the normal samples (Sample Nos. 41, 52, 62-67, 69-71 Table 3: “Tissue samples in colon cancer testing panel”).

As is evident from FIG. 29, the expression of transcripts detectable by the above amplicon in a few cancer samples was higher by more than 5 fold than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1: “Tissue samples in colon cancer testing panel”). However, the expression of transcripts detectable by the above amplicon in a several other cancer samples was lower than in the non-cancerous samples Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R11723 junc11-18F forward primer (SEQ ID NO: 1298); and R11723 junc11-18R reverse primer (SEQ ID NO: 1299).

(SEQ ID NO: 1298)

R11723junc11-18F-AGTGATGGAGCAAAGTGCCG

(SEQ ID NO: 1299)

R11723 junc11-18R-CAGCAGCTGATGCAAACTGAG

(SEQ ID NO: 1300)

R11723 junc11-18 amplicon

AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCAT

CAGCGGCCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCA

GGGAAACTGAACTCAGTTTGCATCAGCTGCTG

Expression of R11723 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name R11723Seg13 (SEQ ID NO: 1297) in different normal tissues.

Expression of R11723 transcripts detectable by or according to R11723seg13 amplicon (SEQ ID NO: 1297) and R11723seg13F (SEQ ID NO: 1295), R11723seg13R (SEQ ID NO: 1296) was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon—Ubiquitin-amplicon, SEQ ID NO:1270) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples to obtain a value of relative expression of each sample relative to median of the ovary samples.

The results are described in FIG. 30, presenting the histogram showing the expression of R11723 transcripts, detectable by amplicon depicted in sequence name R11723seg13 (SEQ ID NO: 1297) in different normal tissues.

Expression of R11723 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name R11723 junc11-18 (SEQ ID NO: 1300) in Different Normal Tissues.

Expression of R11723 transcripts detectable by or according to R11723seg13 amplicon (SEQ ID NO: 1300) and R11723 junc11-18F (SEQ ID NO:1298), R11723 junc11-18R (SEQ ID NO:1299) was measured by real time PCR. In parallel the expression of four housekeeping genes—RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon—Ubiquitin-amplicon, SEQ ID NO:1270) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples to obtain a value of relative expression of each sample relative to median of the ovary samples.

The results are described in FIG. 31, presenting the histogram showing the expression of R11723 transcripts, detectable by amplicon depicted in sequence name R11723 junc11-18 (SEQ ID NO: 1300) in different normal tissues.

(SEQ ID NO: 1298)

R11723junc11-18F-AGTGATGGAGCAAAGTGCCG

(SEQ ID NO: 1299)

R11723junc11-18R-CAGCAGCTGATGCAAACTGAG

(SEQ ID NO: 1300)

R11723junc11-18 amplicon-AGTGATGGAGCAAAGTGCCGGGATC

ATGTACCGCAAGTCCTGTGCATCATCAGCGGCCTGTCTCATCGCCTCTGC

CGGGTACCAGTCCTTCTGCTCCCCAGGGAAACTGAACTCAGTTTGCATCA

GCTGCTG

It was found that the known protein (wild type) transcript expression pattern for the above cluster (PSEC) is similar to the variant expression pattern, except that in some cases (such as ovarian cancer) the variant overexpression in cancer was found to be higher.

Variant Protein Alignment to the Previously Known Protein:

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8IXMO

Sequence documentation:

Alignment of: R11723_PEA_1_P6 (SEQ ID NO:604) × Q8IXMO (SEQ ID NO:1393) ..

Alignment segment 1/1:

Quality:
1128.00
Escore:
0

Matching length:
112
Total length:
112

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q9GAC2

Sequence documentation:

Alignment of: R11723_PEA_1_P6 (SEQ ID NO:604) × Q96AC2 (SEQ ID NO:1394) ..

Alignment segment 1/1:

Quality:
835.00
Escore:
0

Matching length:
83
Total length:
83

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8N2G4

Sequence documentation:

Alignment of: R11723_PEA_1_PG (SEQ ID NO:604) × Q8N2G4 (SEQ ID NO:1395)

Alignment segment 1/1:

Quality:
835.00
Escore:
0

Matching length:
83
Total length:
83

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:BAC85518 (SEQ ID NO: 1396)

Sequence documentation:

Alignment of: R11723_PEA_1_P6 (SEQ ID NO:604) × BAC85518 (SEQ ID NO:1396)

Alignment segment 1/1:

Quality:
835.00
Escore:
0

Matching length:
83
Total length:
83

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:Q96AC2 (SEQ ID NO:1394)

Sequence documentation:

Alignment of: R11723_PEA_1_P7 (SEQ ID NO:605) × Q96AC2 (SEQ ID NO:1394)

Alignment segment 1/1:

Quality:
654.00
Escore:
0

Matching length:
64
Total length:
64

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:Q8N2G4 (SEQ ID NO:1395)

Sequence documentation:

Alignment of: R11723_PEA_1_P7 (SEQ ID NO:605) × Q8N2G4 (SEQ ID NO:1395) ..

Alignment segment 1/1:

Quality:
654.00
Escore:
0

Matching length:
64
Total length:
64

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:BAC85273 (SEQ ID NO:1397)

Sequence documentation:

Alignment of: R11723_PEA_1_P7 (SEQ ID NO:605) × BAC85273 (SEQ ID MO:1397)

Alignment segment 1/1:

Quality:
600.00
Escore:
0

Matching length:
59
Total length:
59

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/VXjdF1zdBX/bexTxTh0Th:BAC85518 (SEQ ID NO: 1396)

Sequence documentation:

Alignment of: R11723_PEA_1_P7 (SEQ ID NO:605) × BAC85518 (SEQ ID NO:1396)

Alignment segment 1/1:

Quality:
654.00
Escore:
0

Matching length:
64
Total length:
64

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q96AC2 (SEQ ID NO: 1394)

Sequence documentation:

Alignment of: R11723_PEA_1_P10 (SEQ ID NO:607) × Q96AC2 (SEQ ID NO:1394) ..

Alignment segment 1/1:

Quality:
645.00
Escore:
0

Matching length:
63
Total length:
63

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q8N2G4 (SEQ ID NO:1395)

Sequence documentation:

Alignment of: R11723_PEA_1_P10 (SEQ ID NO:607) × Q8N2G4 (SEQ ID NO:1395) ..

Alignment segment 1/1:

Quality:
645.00
Escore:
0

Matching length:
63
Total length:
63

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:BAC85273 (SEQ ID NO:1397)

Sequence documentation:

Alignment of: R11723_PEA_1_P10 (SEQ ID NO:607) × BAC85273 (SEQ ID NO:1397) ..

Alignment segment 1/1:

Quality:
591.00
Escore:
0

Matching length:
58
Total length:
58

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:BAC85518 (SEQ ID NO:1396)

Sequence documentation:

Alignment of: R11723_PEA_1_P10 (SEQ ID NO:607) × BAC85518 (SEQ ID NO:1396) ..

Alignment segment 1/1:

Quality:
645.00
Escore:
0

Matching length:
63
Total length:
63

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Alignment of: R11723_PEA_1_P13 (SEQ ID NO:606) × Q96AC2 (SEQ ID NO:1394) ..

Alignment segment 1/1:

Quality:
645.00
Escore:
0

Matching length:
63
Total length:
63

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Description for Cluster M77903

Cluster M77903 features 4 transcript(s) and 29 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

M77903_T11
81

M77903_T12
82

M77903_T34
83

M77903_T36
84

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

M77903_node_2
476

M77903_node_13
477

M77903_node_16
478

M77903_node_18
479

M77903_node_35
480

M77903_node_36
481

M77903_node_37
482

M77903_node_38
483

M77903_node_40
484

M77903_node_44
485

M77903_node_46
486

M77903_node_47
487

M77903_node_48
488

M77903_node_49
489

M77903_node_51
490

M77903_node_52
491

M77903_node_1
492

M77903_node_5
493

M77903_node_9
494

M77903_node_10
495

M77903_node_11
496

M77903_node_12
497

M77903_node_15
498

M77903_node_17
499

M77903_node_20
500

M77903_node_28
501

M77903_node_34
502

M77903_node_41
503

M77903_node_42
504

TABLE 3

Proteins of interest

SEQ ID

Protein Name
NO:
Corresponding Transcript(s)

M77903_P4
608
M77903_T11 (SEQ ID NO: 81)

M77903_P5
609
M77903_T12 (SEQ ID NO: 82)

M77903_P15
610
M77903_T34 (SEQ ID NO: 83)

M77903_P16
611
M77903_T36 (SEQ ID NO: 84)

These sequences are variants of the known protein Translocon-associated protein, alpha subunit precursor (SwissProt accession identifier SSRA_HUMAN; known also according to the synonyms TRAP-alpha; Signal sequence receptor alpha subunit; SSR-alpha), SEQ ID NO: 641, referred to herein as the previously known protein.

Protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor is known or believed to have the following function(s): TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocation apparatus after completion of the translocation process or may function as a membrane-bound chaperone facilitating folding of translocated proteins. The sequence for protein Translocon-associated protein, alpha subunit precursor is given at the end of the application, as “Translocon-associated protein, alpha subunit precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on

amino acid sequence
Comment

28
L -> S

130
Y -> H

Protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor localization is believed to be Type I membrane protein. Endoplasmic reticulum.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: co-translational membrane targeting; positive control of cell proliferation, which are annotation(s) related to Biological Process; signal sequence receptor; calcium binding, which are annotation(s) related to Molecular Function; and endoplasmic reticulum; integral membrane protein, which are annotation(s) related to Cellular Component.

Cluster M77903 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 33 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: ovarian carcinoma and uterine malignancies.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

Adrenal
120

Bladder
123

Bone
129

Colon
31

Epithelial
124

General
129

head and neck
263

Kidney
118

Liver
107

Lung
147

Lymph nodes
126

Breast
211

bone marrow
251

Muscle
109

Ovary
3

Pancreas
144

Prostate
142

Skin
163

Stomach
183

T cells
278

Thyroid
128

Uterus
81

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
3.8e−01
2.8e−01
4.1e−01
1.4
2.4e−01
1.6

bladder
3.7e−01
4.1e−01
1.6e−01
1.8
3.0e−01
1.4

Bone
2.0e−01
2.4e−01
7.7e−01
1.0
6.6e−01
0.9

Brain
5.9e−01
5.5e−01
8.4e−01
0.7
7.9e−01
0.8

Colon
7.0e−02
1.1e−02
6.1e−02
2.9
2.5e−02
3.2

epithelial
4.2e−02
5.8e−02
1.3e−01
1.2
4.7e−01
1.0

general
4.0e−02
2.0e−02
6.1e−01
1.0
8.9e−01
0.9

head and neck
4.5e−01
4.6e−01
1
0.4
9.0e−01
0.5

kidney
6.5e−01
7.6e−01
2.8e−01
1.2
5.3e−01
0.9

Liver
5.3e−01
5.8e−01
1
0.4
9.1e−01
0.6

Lung
6.1e−01
7.3e−01
3.7e−01
1.2
7.0e−01
0.9

Lymph nodes
2.4e−01
5.8e−01
7.1e−01
0.9
8.7e−01
0.6

breast
8.0e−01
8.3e−01
9.9e−01
0.4
9.1e−01
0.5

bone marrow
7.5e−01
6.8e−01
1
0.1
9.5e−01
0.5

muscle
4.0e−01
2.6e−01
6.2e−01
1.5
8.3e−01
0.7

Ovary
7.8e−03
8.7e−03
1.0e−02
5.8
3.1e−02
4.4

pancreas
5.6e−01
6.6e−01
7.8e−01
0.6
8.6e−01
0.6

prostate
4.5e−01
4.3e−01
6.2e−01
0.9
4.3e−01
0.8

Skin
4.9e−01
5.3e−01
3.6e−01
1.4
9.3e−01
0.4

stomach
2.9e−01
5.5e−01
7.5e−01
0.6
9.4e−01
0.5

T cells
6.7e−01
5.0e−01
5.5e−01
1.5
5.7e−01
1.1

Thyroid
5.7e−01
5.7e−01
7.4e−01
1.1
7.4e−01
1.1

uterus
7.4e−03
2.5e−02
4.6e−01
1.1
6.0e−01
0.9

As noted above, cluster M77903 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor. A description of each variant protein according to the present invention is now provided.

Variant protein M77903_P4 (SEQ ID NO:608) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903_T11 (SEQ ID NO:81). An alignment is given to the known protein (Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M77903_P4 (SEQ ID NO:608) and SSRA_HUMAN (SEQ ID NO:641):

1. An isolated chimeric polypeptide encoding for M77903_P4 (SEQ ID NO:608), comprising a first amino acid sequence being at least 90% homologous to MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDEPTDLVEDKEEED VSGEPEASPSADTTILFVKGEDFPANNIVKFLVGFTNKGTEDFIVESLDASFRYPQDYQFYIQNFTALPLNTV VPPQRQATFEYSFIPAEPMGGRPFGLVINLNYKDLNGNVFQDAVFNQTVTVIEREDGLDGET corresponding to amino acids 1-207 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-207 of M77903_P4 (SEQ ID NO:608), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRDPYRK (SEQ ID NO:1565) corresponding to amino acids 208-214 of M77903_P4 (SEQ ID NO:608), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M77903_P4 (SEQ ID NO:608), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRDPYRK (SEQ ID NO:1565) in M77903_P4 (SEQ ID NO:608).

Variant protein M77903_P4 (SEQ ID NO:608) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P4 (SEQ ID NO:608) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

6
R -> G
No

24
G ->
No

28
L -> S
Yes

48
E -> G
No

54
A -> T
Yes

58
E -> K
No

63
D ->
No

89
F ->
No

116
I -> M
No

130
Y -> H
No

130
Y -> N
No

178
K ->
No

The glycosylation sites of variant protein M77903_P4 (SEQ ID NO:608), as compared to the known protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor, are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 8

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

191
Yes
191

136
Yes
136

Variant protein M77903_P4 (SEQ ID NO:608) is encoded by the following transcript(s): M77903_T11 (SEQ ID NO:81), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M77903_T11 (SEQ ID NO:81) is shown in bold; this coding portion starts at position 200 and ends at position 841. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P4 (SEQ ID NO:608) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
knowns SNP?

72
G -> T
Yes

120
C -> G
No

147
G -> C
Yes

215
C -> G
No

271
C ->
No

282
T -> C
Yes

342
A -> G
No

359
G -> A
Yes

371
G -> A
No

388
T ->
No

464
T ->
No

547
T -> C
No

547
T -> G
No

587
T -> A
No

587
T -> C
No

731
A ->
No

927
A ->
No

1117
T ->
No

1118
G ->
No

1296
T -> A
Yes

1324
T ->
No

1326
T ->
No

1408
T -> G
No

1450
T -> G
No

1660
C ->
No

1664
C -> T
Yes

1665
T ->
No

1797
T ->
No

1802
T ->
No

1913
G -> A
Yes

1985
T ->
No

2168
A -> G
Yes

2205
T -> C
Yes

2466
A -> C
No

2466
A -> G
Yes

2535
T -> G
Yes

2597
T ->
No

2648
T -> C
No

2720
A -> T
No

2738
G -> A
Yes

2782
C -> T
Yes

2790
C ->
No

2861
C -> T
No

2931
T -> G
No

3043
T -> G
No

3103
T -> G
No

3120
T -> G
No

3125
T -> G
No

3500
A -> C
Yes

3566
A -> G
Yes

5060
G -> A
Yes

5156
-> T
No

5533
G -> C
No

5789
G -> A
Yes

5866
T -> C
Yes

6591
C -> T
Yes

6619
G -> A
Yes

6905
A -> T
Yes

6922
G -> C
Yes

7046
C -> G
Yes

7319
A -> G
Yes

7706
C -> T
Yes

7894
G -> A
Yes

8099
C -> G
Yes

8324
T -> C
No

8555
T -> C
Yes

8627
G -> T
Yes

8644
T -> C
Yes

8704
T -> C
No

8781
C -> T
Yes

8787
C -> T
Yes

8827
C -> T
No

8847
T -> C
No

8847
T -> G
No

8909
G -> A
No

8947
G -> A
Yes

8960
T -> C
Yes

9096
T -> C
No

9096
T -> G
No

9207
A -> G
No

9424
T -> C
Yes

9516
A ->
No

9596
C -> T
Yes

Variant protein M77903_P5 (SEQ ID NO:609) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903_T12 (SEQ ID NO:82). An alignment is given to the known protein (Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M77903_P5 (SEQ ID NO:609) and SSRA_HUMAN (SEQ ID NO:641):

1. An isolated chimeric polypeptide encoding for M77903_P5 (SEQ ID NO:609), comprising a first amino acid sequence being at least 90% homologous to MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDEPTDLVEDKEEED VSGEPEASPSADTTILFVKGEDFPANNIVKFLVGFTNKGTEDFIVESLDASFRYPQDYQFYIQNFTALPLNTV VPPQRQATFEYSFIPAEPMGGRPFGLVINLNYKDLNGNVFQDAVFNQTVTVIEREDGLDGET corresponding to amino acids 1-207 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-207 of M77903_P5 (SEQ ID NO:609).

Variant protein M77903_P5 (SEQ ID NO:609) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P5 (SEQ ID NO:609) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s)

on amino acid
Alternative amino
Previously

sequence
acid(s)
known SNP?

6
R -> G
No

24
G ->
No

28
L -> S
Yes

48
E -> G
No

54
A -> T
Yes

58
E -> K
No

63
D ->
No

89
F ->
No

116
I -> M
No

130
Y -> H
No

130
Y -> N
No

178
K ->
No

The glycosylation sites of variant protein M77903_P5 (SEQ ID NO:609), as compared to the known protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor, are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 11

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

191
Yes
191

136
Yes
136

Variant protein M77903_P5 (SEQ ID NO:609) is encoded by the following transcript(s): M77903_T12 (SEQ ID NO:82), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M77903_T12 (SEQ ID NO:82) is shown in bold; this coding portion starts at position 200 and ends at position 820. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P5 (SEQ ID NO:609) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

72
G -> T
Yes

120
C -> G
No

147
G -> C
Yes

215
C -> G
No

271
C ->
No

282
T -> C
Yes

342
A -> G
No

359
G -> A
Yes

371
G -> A
No

388
T ->
No

464
T ->
No

547
T -> C
No

547
T -> G
No

587
T -> A
No

587
T -> C
No

731
A ->
No

833
A ->
No

1023
T ->
No

1024
G ->
No

1202
T -> A
Yes

1230
T ->
No

1232
T ->
No

1314
T -> G
No

1356
T -> G
No

1566
C ->
No

1570
C -> T
Yes

1571
T ->
No

1703
T ->
No

1708
T ->
No

1819
G -> A
Yes

1891
T ->
No

2074
A -> G
Yes

2111
T -> C
Yes

2372
A -> C
No

2372
A -> G
Yes

2441
T -> G
Yes

2503
T ->
No

2554
T -> C
No

2626
A -> T
No

2644
G -> A
Yes

2688
C -> T
Yes

2696
C ->
No

2767
C -> T
No

2837
T -> G
No

2949
T -> G
No

3009
T -> G
No

3026
T -> G
No

3031
T -> G
No

3406
A -> C
Yes

3472
A -> G
Yes

4966
G -> A
Yes

5062
-> T
No

5439
G -> C
No

5695
G -> A
Yes

5772
T -> C
Yes

6497
C -> T
Yes

6525
G -> A
Yes

6811
A -> T
Yes

6828
G -> C
Yes

6952
C -> G
Yes

7225
A -> G
Yes

7612
C -> T
Yes

7800
G -> A
Yes

8005
C -> G
Yes

8230
T -> C
No

8461
T -> C
Yes

8533
G -> T
Yes

8550
T -> C
Yes

8610
T -> C
No

8687
C -> T
Yes

8693
C -> T
Yes

8733
C -> T
No

8753
T -> C
No

8753
T -> G
No

8815
G -> A
No

8853
G -> A
Yes

8866
T -> C
Yes

9002
T -> C
No

9002
T -> G
No

9113
A -> G
No

9330
T -> C
Yes

9422
A ->
No

9502
C -> T
Yes

Variant protein M77903_P15 (SEQ ID NO:610) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903_T34 (SEQ ID NO:83). An alignment is given to the known protein (Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M77903_P15 (SEQ ID NO:610) and SSRA_HUMAN (SEQ ID NO:641):

1. An isolated chimeric polypeptide encoding for M77903_P15 (SEQ ID NO:610), comprising a first amino acid sequence being at least 90% homologous to MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDEPTDLVEDKEEED VSGEPEASPSADTTILFVKGEDFPANNIVKFLVGFTNKGTEDFIVESLDASFRYPQDYQFYIQNFTALPLNTV VPPQRQATFEYSFIPAEPMGGRPFGLVINLNYKDLN corresponding to amino acids 1-181 of SSRA_HUMAN (SEQ ID NO:641), which also corresponds to amino acids 1-181 of M77903_P15 (SEQ ID NO:610), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSSKPSFCLS (SEQ ID NO:1566) corresponding to amino acids 182-192 of M77903_P15 (SEQ ID NO:610), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M77903_P15 (SEQ ID NO:610), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSSKPSFCLS (SEQ ID NO:1566) in M77903_P15 (SEQ ID NO:610).

Variant protein M77903_P15 (SEQ ID NO:610) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P15 (SEQ ID NO:610) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

6
R -> G
No

24
G ->
No

28
L -> S
Yes

48
E -> G
No

54
A -> T
Yes

58
E -> K
No

63
D ->
No

89
F ->
No

116
I -> M
No

130
Y -> H
No

130
Y -> N
No

178
K ->
No

The glycosylation sites of variant protein M77903_P15 (SEQ ID NO:610), as compared to the known protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor, are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 14

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

191
No

136
Yes
136

Variant protein M77903_P15 (SEQ ID NO:610) is encoded by the following transcript(s): M77903_T34 (SEQ ID NO:83), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M77903_T34 (SEQ ID NO:83) is shown in bold; this coding portion starts at position 200 and ends at position 775. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P15 (SEQ ID NO:610) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

72
G -> T
Yes

120
C -> G
No

147
G -> C
Yes

215
C -> G
No

271
C ->
No

282
T -> C
Yes

342
A -> G
No

359
G -> A
Yes

371
G -> A
No

388
T ->
No

464
T ->
No

547
T -> C
No

547
T -> G
No

587
T -> A
No

587
T -> C
No

731
A ->
No

Variant protein M77903_P16 (SEQ ID NO:611) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903_T36 (SEQ ID NO:84). An alignment is given to the known protein (Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M77903_P16 (SEQ ID NO:611) and SSRA_HUMAN (SEQ ID NO:641):

1. An isolated chimeric polypeptide encoding for M77903_P16 (SEQ ID NO:611), comprising a first amino acid sequence being at least 90% homologous to MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDEPTDLVEDKEEED VSGEPEASPSADTTILFVKGE corresponding to amino acids 1-93 of SSRA_HUMAN (SEQ ID NO:641) which also corresponds to amino acids 1-93 of M77903_P16 (SEQ ID NO:611), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GNTEVLVLIQM (SEQ ID NO:1567) corresponding to amino acids 94-104 of M77903_P16 (SEQ ID NO:611), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of M77903_P16 (SEQ ID NO:611), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GNTEVLVLIQM (SEQ ID NO:1567) in M77903_P16 (SEQ ID NO:611).

Variant protein M77903_P16 (SEQ ID NO:611) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P16 (SEQ ID NO:611) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

6
R -> G
No

24
G ->
No

28
L -> S
Yes

48
E -> G
No

54
A -> T
Yes

58
E -> K
No

63
D ->
No

89
F ->
No

The glycosylation sites of variant protein M77903_P16 (SEQ ID NO:611), as compared to the known protein Translocon-associated protein (SEQ ID NO:641), alpha subunit precursor, are described in Table 17 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 17

Glycosylation site(s)

Position(s) on known amino acid

sequence
Present in variant protein?

191
No

136
No

Variant protein M77903_P16 (SEQ ID NO:611) is encoded by the following transcript(s): M77903_T36 (SEQ ID NO:84), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M77903_T36 (SEQ ID NO:84) is shown in bold; this coding portion starts at position 200 and ends at position 511. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P16 (SEQ ID NO:611) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

72
G -> T
Yes

120
C -> G
No

147
G -> C
Yes

215
C -> G
No

271
C ->
No

282
T -> C
Yes

342
A -> G
No

359
G -> A
Yes

371
G -> A
No

388
T ->
No

464
T ->
No

527
G -> A
Yes

597
C -> T
Yes

As noted above, cluster M77903 features 29 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster M77903_node_—2 (SEQ ID NO:476) according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
118
278

M77903_T12 (SEQ ID NO: 82)
118
278

M77903_T34 (SEQ ID NO: 83)
118
278

M77903_T36 (SEQ ID NO: 84)
118
278

Segment cluster M77903_node_—13 (SEQ ID NO:477) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T36 (SEQ ID NO:84). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T36 (SEQ ID NO: 84)
480
629

Segment cluster M77903_node_—16 (SEQ ID NO:478) according to the present invention is supported by 149 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82) and M77903_T34 (SEQ ID NO:83). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
523
683

M77903_T12 (SEQ ID NO: 82)
523
683

M77903_T34 (SEQ ID NO: 83)
523
683

Segment cluster M77903_node_—18 (SEQ ID NO:479) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T34 (SEQ ID NO:83). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T34 (SEQ ID NO: 83)
743
935

Segment cluster M77903_node_—35 (SEQ ID NO:480) according to the present invention is supported by 145 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
978
1162

M77903_T12 (SEQ ID NO: 82)
884
1068

Segment cluster M77903_node_—36 (SEQ ID NO:481) according to the present invention is supported by 173 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
1163
1571

M77903_T12 (SEQ ID NO: 82)
1069
1477

Segment cluster M77903_node_—37 (SEQ ID NO:482) according to the present invention is supported by 128 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
1572
1913

M77903_T12 (SEQ ID NO: 82)
1478
1819

Segment cluster M77903_node_—38 (SEQ ID NO:483) according to the present invention is supported by 152 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
1914
2411

M77903_T12 (SEQ ID NO: 82)
1820
2317

Segment cluster M77903_node_—40 (SEQ ID NO:484) according to the present invention is supported by 186 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
2412
2923

M77903_T12 (SEQ ID NO: 82)
2318
2829

Segment cluster M77903_node_—44 (SEQ ID NO:485) according to the present invention is supported by 122 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
3079
3826

M77903_T12 (SEQ ID NO: 82)
2985
3732

Segment cluster M77903_node_—46 (SEQ ID NO:486) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
3827
4196

M77903_T12 (SEQ ID NO: 82)
3733
4102

Segment cluster M77903_node_—47 (SEQ ID NO:487) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
4197
5182

M77903_T12 (SEQ ID NO: 82)
4103
5088

Segment cluster M77903_node_—48 (SEQ ID NO:488) according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
5183
6133

M77903_T12 (SEQ ID NO: 82)
5089
6039

Segment cluster M77903_node_—49 (SEQ ID NO:489) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
6134
6319

M77903_T12 (SEQ ID NO: 82)
6040
6225

Segment cluster M77903_node_—51 (SEQ ID NO:490) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
6320
7542

M77903_T12 (SEQ ID NO: 82)
6226
7448

Segment cluster M77903_node_—52 (SEQ ID NO:491) according to the present invention is supported by 160 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
7543
9702

M77903_T12 (SEQ ID NO: 82)
7449
9608

Segment cluster M77903_node_—1 (SEQ ID NO:492) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
1
117

M77903_T12 (SEQ ID NO: 82)
1
117

M77903_T34 (SEQ ID NO: 83)
1
117

M77903_T36 (SEQ ID NO: 84)
1
117

Segment cluster M77903_node_—5 (SEQ ID NO:493) according to the present invention is supported by 154 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
279
391

M77903_T12 (SEQ ID NO: 82)
279
391

M77903_T34 (SEQ ID NO: 83)
279
391

M77903_T36 (SEQ ID NO: 84)
279
391

Segment cluster M77903_node_—9 (SEQ ID NO:494) according to the present invention can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
392
395

M77903_T12 (SEQ ID NO: 82)
392
395

M77903_T34 (SEQ ID NO: 83)
392
395

M77903_T36 (SEQ ID NO: 84)
392
395

Segment cluster M77903_node_—10 (SEQ ID NO:495) according to the present invention is supported by 148 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
396
468

M77903_T12 (SEQ ID NO: 82)
396
468

M77903_T34 (SEQ ID NO: 83)
396
468

M77903_T36 (SEQ ID NO: 84)
396
468

Segment cluster M77903_node_—11 (SEQ ID NO:496) according to the present invention can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
469
473

M77903_T12 (SEQ ID NO: 82)
469
473

M77903_T34 (SEQ ID NO: 83)
469
473

M77903_T36 (SEQ ID NO: 84)
469
473

Segment cluster M77903_node_—12 (SEQ ID NO:497) according to the present invention can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82), M77903_T34 (SEQ ID NO:83) and M77903_T36 (SEQ ID NO:84). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
474
479

M77903_T12 (SEQ ID NO: 82)
474
479

M77903_T34 (SEQ ID NO: 83)
474
479

M77903_T36 (SEQ ID NO: 84)
474
479

Segment cluster M77903_node_—15 (SEQ ID NO:498) according to the present invention is supported by 129 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82) and M77903_T34 (SEQ ID NO:83). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
480
522

M77903_T12 (SEQ ID NO: 82)
480
522

M77903_T34 (SEQ ID NO: 83)
480
522

Segment cluster M77903_node_—17 (SEQ ID NO:499) according to the present invention is supported by 141 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81), M77903_T12 (SEQ ID NO:82) and M77903_T34 (SEQ ID NO:83). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
684
742

M77903_T12 (SEQ ID NO: 82)
684
742

M77903_T34 (SEQ ID NO: 83)
684
742

Segment cluster M77903_node_—20 (SEQ ID NO:500) according to the present invention is supported by 134 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
743
819

M77903_T12 (SEQ ID NO: 82)
743
819

Segment cluster M77903_node_—28 (SEQ ID NO:501) according to the present invention is supported by 134 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
820
913

Segment cluster M77903_node_—34 (SEQ ID NO:502) according to the present invention is supported by 134 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
914
977

M77903_T12 (SEQ ID NO: 82)
820
883

Segment cluster M77903_node_—41 (SEQ ID NO:503) according to the present invention is supported by 119 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
2924
2984

M77903_T12 (SEQ ID NO: 82)
2830
2890

Segment cluster M77903_node_—42 (SEQ ID NO:504) according to the present invention is supported by 123 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M77903_T11 (SEQ ID NO:81) and M77903_T12 (SEQ ID NO:82). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M77903_T11 (SEQ ID NO: 81)
2985
3078

M77903_T12 (SEQ ID NO: 82)
2891
2984

Variant Protein Alignment to the Previously Known Protein:

Sequence name: SSRA_HUMAN (SEQ ID NO:641)

Sequence documentation:

Alignment of: M77903_P4 (SEQ ID NO:608) × SSRA_HUMAN (SEQ ID NO:641) ..

Alignment segment 1/1:

Quality:
1991.00
Escore:
0

Matching length:
208
Total length:
208

Matching Percent Similarity:
100.00
Matching Percent Identity:
99.52

Total Percent Similarity:
100.00
Total Percent Identity:
99.52

Gaps:
0

Alignment:

Sequence name: SSRA_HUMAN (SEQ ID NO:641)

Sequence documentation:

Alignment of: M77903_P5 (SEQ ID NO:609) × SSRA_HUMAN (SEQ ID NO:641) ..

Alignment segment 1/1:

Quality:
1987.00
Escore:
0

Matching length:
207
Total length:
207

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: SSRA_HUMAN (SEQ ID NO:641)

Sequence documentation:

Alignment of: M77903_P15 (SEQ ID NO:610) × SSRA_HUMAN (SEQ ID 110:641) ..

Alignment segment 1/1:

Quality:
1741.00
Escore:
0

Matching length:
181
Total length:
181

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: SSRA_HUMAN (SEQ ID NO:641)

Sequence documentation:

Alignment of: M77903_P16 (SEQ ID NO:611) × SSRA_HUMAN (SEQ ID NO:641) ..

Alignment segment 1/1:

Quality:
869.00
Escore:
0

Matching length:
93
Total length:
93

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Expression of SSRA_HUMAN: SSR-Alpha M77903 Transcripts, which are Detectable by Amplicon, as Depicted in Sequence Name M77903Seg18 (SEQ ID NO: 1303) in Normal and Cancerous Colon Tissues.

Transcripts detectable by or according to M77903seg18 amplicon (SEQ ID NO:1303) and M77903seg18F (SEQ ID NO: 1301) and M77903seg18R (SEQ ID NO: 1302) primers were measured by real time PCR. In parallel the expression of four housekeeping genes: PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), and, G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1 Tissue samples in testing panel), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 34 is a histogram showing over expression of the above-indicated SSRA_HUMAN: SSR-alpha transcripts in cancerous colon samples relative to the normal samples.

As is evident from FIG. 34, the expression of SSRA_HUMAN: SSR-alpha transcripts detectable by the above amplicon(s) in a few cancer samples was higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1 Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 5 out of 37 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: M77903seg18F forward primer (SEQ ID NO: 1301); and M77903seg18R reverse primer (SEQ ID NO: 1302).

M77903seg18F

(SEQ ID NO: 1301)

CGGTGACGTTGTTTAATAGAATATATCTGT

M77903seg18R

(SEQ ID NO: 1302)

AAGAAACGTGCAATTTATCTTTGCT

M77903seg18 amplicon

(SEQ ID NO: 1303)

CGGTGACGTTGTTTAATAGAATATATCTGTTCATTCAGTTGCCTGTTTTG

TGGTTGAACCTGTGATAGCCACCAGGGAAGCAAAGATAAATTGCACGTTT

CTT

As can be seen from FIGS. 35 and 36, for cluster M77903, amplicon name: M77903 junc20-34-35, and M77903 junc20-28, respectively, low over expression was observed in one experiment carried out with colon.

Expression of SSRA_HUMAN
Translocon-Associated Protein, Alpha Subunit (Trap-Alpha Signal Sequence Receptor Alpha SubunitSSR-Alpha) M77903 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name M77903junc20-28 (SEQ ID NO: 1306) in Normal and Cancerous Colon Tissues

Expression of SSRA_HUMAN: Translocon-associated protein, alpha subunit (TRAP-alpha Signal sequence receptor alpha subunitSSR-alpha ) transcripts detectable by or according to junc20-28, M77903junc20-28 amplicon (SEQ ID NO: 1306) and primers M77903junc20-28F (SEQ ID NO: 1304) and M77903junc20-28R (SEQ ID NO: 1305) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 35 is a histogram showing over expression of the above-indicated SSRA_HUMAN: Translocon-associated protein, alpha subunit TRAP-alpha Signal sequence receptor alpha subunitSSR-alpha transcripts in cancerous colon samples relative to the normal samples.

As is evident from FIG. 35, the expression of the above-indicated SSRA_HUMAN: Translocon-associated protein, alpha subunit TRAP-alpha Signal sequence receptor alpha subunitSSR-alpha transcripts detectable by the above amplicon in cancer samples was higher in a few samples than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 4 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: M77903junc20-28F forward primer (SEQ ID NO: 1304); and M77903junc20-28R reverse primer (SEQ ID NO: 1305).

Primers:

Forward primer M77903junc20-28F (SEQ ID NO: 1304):

GGCAATGTATTCCAAGATGCAG

Reverse primer M77903junc20-28R (SEQ ID NO: 1305):

TCTGTATGGGTCTCTTACGGTTTCT

Amplicon M77903junc20-28 (SEQ ID NO: 1306):

GGCAATGTATTCCAGATGCAGTCTTCAATCAAACAGTTACAGTTATTGAA

AGAGAGGATGGGTTAGATGGAGAAACCGTAAGAGACCCATACAGA

Expression of SSRA_HUMAN
Translocon-Associated Protein, Alpha Subunit Trap-Alpha Signal Sequence Receptor Alpha SubunitSSR-AlphaM77903 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name M77903junc20-34-35 (SEQ ID NO: 1309) in Normal and Cancerous Colon Tissues

Expression of SSRA_HUMAN: Translocon-associated protein, alpha subunit TRAP-alpha Signal sequence receptor alpha subunitSSR-alpha transcripts detectable by or according to junc20-34-35, M77903junc20-34-35 amplicon (SEQ ID NO: 1309) and primers M77903junc20-34-35F (SEQ ID NO: 1307) and M77903junc20-34-35R (SEQ ID NO: 1308) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 36 is a histogram showing over expression of the above-indicated SSRA_HUMAN: Translocon-associated protein, alpha subunit TRAP-alpha Signal sequence receptor alpha subunit SSR-alpha transcripts in cancerous colon samples relative to the normal samples.

As is evident from FIG. 36, the expression of SSRA_HUMAN: Translocon-associated protein, alpha subunit, TRAP-alpha Signal sequence receptor alpha subunitSSR-alpha transcripts detectable by the above amplicon in cancer samples was higher in a few samples than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”). Notably an over-expression of at least 10 fold was found in 7 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: M77903junc20-34-35F forward primer (SEQ ID NO: 1307); and M77903junc20-34-35R reverse primer (SEQ ID NO: 1308).

Primers:

Forward primer M77903junc20-34-35F (SEQ ID NO:

1307):

ATGGGTTAGATGGAGAAACATAAAGCT

Reverse primer M77903junc20-34-35R (SEQ ID NO:

1308):

TGCACAAAGGAACATTTACTCATCA

Amplicon M77903junc20-34-35 (SEQ ID NO: 1309):

ATGGGTTAGATGGAGAAACATAAAGCTTCACCAAGAAGGTTGCCCAGGAA

ACGGGCACAGAAGAGATCAGTGGGATCTGATGAGTAAATGTTCCTTTGTG

CA

Combined expression of 6 Sequences (M85491seg24 (SEQ ID NO: 1276), M77903 seg18 (SEQ ID NO: 1303), M77903junc20-28 (SEQ ID NO: 1306), Z44808 junc8-11 (SEQ ID NO: 1291), Z25299 seg 20 (SEQ ID NO: 1294) and HSKITCR seg3 (SEQ ID NO: 1309)) in Normal and Cancerous Colon Tissues

Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3), SSRA_HUMAN, SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2), Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor and KIT_HUMAN; mast/stem cell growth factor receptor SCFR; Proto-oncogene tyrosine-protein kinase Kit; v-kit; CD117 antigen transcripts detectable by or according to M85491seg24 (SEQ ID NO: 1276), M77903 seg18 (SEQ ID NO: 1303), M77903junc20-28 (SEQ ID NO: 1306), Z44808 junc8-11 (SEQ ID NO: 1291), Z25299 seg 20 (SEQ ID NO: 1294) and HSKITCR seg3 (SEQ ID NO: 1309) amplicons and M85491seg24F (SEQ ID NO: 1274), M85491seg24R (SEQ ID NO: 1275), M77903 seg18F (SEQ ID NO: 1301), M77903 seg18R (SEQ ID NO: 1302), M77903junc20-28F (SEQ ID NO: 1304), M77903junc20-28R (SEQ ID NO: 1305), Z44808 junc8-11 (SEQ ID NO: 1289), Z44808 junc8-11R (SEQ ID NO: 1290), Z25299 seg 20F (SEQ ID NO: 1292), Z25299 seg 20R (SEQ ID NO: 1293), HSKITCR seg3F (SEQ ID NO: 1307) and HSKITCR seg3R (SEQ ID NO: 1308) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615) and RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261) was measured similarly. For each RT sample, the expression of the above amplicons was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample of each amplicon was then divided by the median of the quantities of the normal post-mortem (PM) samples detected for the same amplicon (Sample Nos. 41, 52, 62-67, 69-71 Table 3, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. The reciprocal of this ratio was calculated for HSKITCR seg3 (SEQ ID NO: 1309), to obtain a value of fold down-regulation for each sample relative to median of the normal PM samples. The expression of HSKITCR transcripts which can be detected by the HSKITCR seg3 (SEQ ID NO: 1309), is described also in the patent application “NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS”, attorney reference number XXXXX, by the same inventors, filed on the same date ans incorporated herein by reference.

FIGS. 37-38 are histograms showing differential expression of the above-indicated transcripts in cancerous colon samples relative to the normal samples, in different combinations. The number and percentage of samples that exhibit at least 5 fold differential of at least one of the sequences, out of the total number of samples tested is indicated in the bottom.

As is evident from FIGS. 37-38, differential expression of at least 5 fold in at least one of the sequences was found in 29 out of 36 adenocarcinoma samples in the combinations of 6 transcripts, and in 13 out of 36 adenocarcinoma samples in the combinations of 5 transcripts.

Statistical analysis was applied to verify the significance of these results, as described below. Threshold of 5 fold differential expression of at least one of the amplicons was found to differentiate between cancer and normal samples as checked by exact fisher test.

The above values demonstrate statistical significance of the results.

Description for Cluster HSSTROL3

Cluster HSSTROL3 features 6 transcript(s) and 16 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HSSTROL3_T5
85

HSSTROL3_T8
86

HSSTROL3_T9
87

HSSTROL3_T10
88

HSSTROL3_T11
505

HSSTROL3_T12
506

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HSSTROL3_node_6
507

HSSTROL3_node_10
508

HSSTROL3_node_13
509

HSSTROL3_node_15
510

HSSTROL3_node_19
511

HSSTROL3_node_21
512

HSSTROL3_node_24
513

HSSTROL3_node_25
514

HSSTROL3_node_26
515

HSSTROL3_node_28
516

HSSTROL3_node_29
517

HSSTROL3_node_11
518

HSSTROL3_node_17
519

HSSTROL3_node_18
520

HSSTROL3_node_20
521

HSSTROL3_node_27
522

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HSSTROL3_P4
524
HSSTROL3_T5 (SEQ ID NO: 85)

HSSTROL3_P5
525
HSSTROL3_T8 (SEQ ID NO: 86);

HSSTROL3_T9 (SEQ ID NO: 87)

HSSTROL3_P7
526
HSSTROL3_T10 (SEQ ID NO: 88)

HSSTROL3_P8
527
HSSTROL3_T11 (SEQ ID NO: 505)

HSSTROL3_P9
528
HSSTROL3_T12 (SEQ ID NO: 506)

These sequences are variants of the known protein Stromelysin-3 precursor (SwissProt accession identifier MM11_HUMAN; known also according to the synonyms EC 3.4.24.-; Matrix metalloproteinase-11; MMP-11; ST3; SL-3), SEQ ID NO: 523, referred to herein as the previously known protein.

Protein Stromelysin-3 precursor (SEQ ID NO:523) is known or believed to have the following function(s): May play an important role in the progression of epithelial malignancies. The sequence for protein Stromelysin-3 precursor is given at the end of the application, as “Stromelysin-3 precursor amino acid sequence”.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: proteolysis and peptidolysis; developmental processes; morphogenesis, which are annotation(s) related to Biological Process; stromelysin 3; calcium binding; zinc binding; hydrolase, which are annotation(s) related to Molecular Function; and extracellular matrix, which are annotation(s) related to Cellular Component.

Cluster HSSTROL3 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 75 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carinoma.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

adrenal
0

bladder
0

brain
1

colon
63

epithelial
33

general
13

head and neck
101

kidney
0

lung
11

breast
8

ovary
14

pancreas
0

prostate
2

skin
99

Thyroid
0

uterus
181

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
1
4.6e−01
1
1.0
5.3e−01
1.9

bladder
2.7e−01
3.4e−01
3.3e−03
4.9
2.1e−02
3.3

brain
3.5e−01
2.6e−01
1
1.7
3.3e−01
2.8

colon
7.7e−02
1.5e−01
3.1e−01
1.4
5.2e−01
1.0

epithelial
1.2e−04
1.2e−02
1.3e−06
2.7
4.6e−02
1.4

general
5.4e−09
3.1e−05
1.8e−16
5.0
3.1e−07
2.6

head and neck
4.6e−01
4.3e−01
1
0.6
9.4e−01
0.7

kidney
2.5e−01
3.5e−01
1.1e−01
4.0
2.4e−01
2.8

lung
1.8e−01
4.5e−01
1.9e−01
2.7
5.1e−01
1.4

breast
2.0e−01
3.4e−01
7.3e−02
3.3
2.5e−01
2.0

ovary
2.6e−01
3.2e−01
2.2e−02
2.0
7.0e−02
1.6

pancreas
9.5e−02
1.8e−01
1.8e−04
7.8
1.6e−03
5.5

prostate
8.2e−01
7.8e−01
4.5e−01
1.8
5.6e−01
1.5

skin
5.2e−01
5.8e−01
7.1e−01
0.8
1
0.3

Thyroid
2.9e−01
2.9e−01
1
1.1
1
1.1

uterus
4.2e−01
8.0e−01
7.5e−01
0.6
9.9e−01
0.4

AS noted above, cluster HSSTROL3 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Stromelysin-3 precursor (SEQ ID NO:523). A description of each variant protein according to the present invention is now provided.

Variant protein HSSTROL3_P4 (SEQ ID NO:524) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T5 (SEQ ID NO:85). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:523)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSSTROL3_P4 (SEQ ID NO:524) and MM11_HUMAN (SEQ ID NO:523):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P4 (SEQ ID NO:524), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 1-163 of HSSTROL3_P4 (SEQ ID NO:524), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4 (SEQ ID NO:524), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLG PAPLTELGLVRFPVHAALVWGPEKNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDA DG corresponding to amino acids 165-445 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 165-445 of HSSTROL3_P4 (SEQ ID NO:524), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:1568) corresponding to amino acids 446-496 of HSSTROL3_P4 (SEQ ID NO:524), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P4 (SEQ ID NO:524), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:1568) in HSSTROL3_P4 (SEQ ID NO:524).

Variant protein HSSTROL3_P4 (SEQ ID NO:524) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P4 (SEQ ID NO:524) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on
Alternative
Previously known

amino acid sequence
amino acid(s)
SNP?

38
V -> A
Yes

104
R -> P
Yes

214
A ->
No

323
Q -> H
Yes

Variant protein HSSTROL3_P4 (SEQ ID NO:524) is encoded by the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T5 (SEQ ID NO:85) is shown in bold; this coding portion starts at position 24 and ends at position 1511. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P4 (SEQ ID NO:524) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

136
T -> C
Yes

334
G -> C
Yes

663
G ->
No

699
-> T
No

992
G -> C
Yes

1528
A -> G
Yes

1710
A -> G
Yes

2251
A -> G
Yes

2392
C ->
No

2444
C -> A
Yes

2470
A -> T
Yes

2687
-> G
No

2696
-> G
No

2710
C ->
No

2729
-> A
No

2755
T -> C
No

2813
A ->
No

2813
A -> C
No

2963
A ->
No

2963
A -> C
No

2993
T -> C
Yes

3140
-> T
No

Variant protein HSSTROL3_P5 (SEQ ID NO:525) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T8 (SEQ ID NO:86) and HSSTROL3_T9 (SEQ ID NO:87). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:523)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSSTROL3_P5 (SEQ ID NO:525) and MM11_HUMAN (SEQ ID NO:523):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P5 (SEQ ID NO:525), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 1-163 of HSSTROL3_P5 (SEQ ID NO:525), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5 (SEQ ID NO:525), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQ corresponding to amino acids 165-358 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 165-358 of HSSTROL3_P5 (SEQ ID NO:525), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:1569) corresponding to amino acids 359-382 of HSSTROL3_P5 (SEQ ID NO:525), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P5 (SEQ ID NO:525), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:1569) in HSSTROL3_P5 (SEQ ID NO:525).

Variant protein HSSTROL3_P5 (SEQ ID NO:525) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:525) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

38
V -> A
Yes

104
R -> P
Yes

214
A ->
No

323
Q -> H
Yes

Variant protein HSSTROL3_P5 (SEQ ID NO:525) is encoded by the following transcript(s): HSSTROL3_T8 (SEQ ID NO:86) and HSSTROL3_T9 (SEQ ID NO:87), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript HSSTROL3_T8 (SEQ ID NO:86) is shown in bold; this coding portion starts at position 24 and ends at position 1169. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:525) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

136
T -> C
Yes

334
G -> C
Yes

663
G ->
No

699
-> T
No

992
G -> C
Yes

1903
C ->
No

1955
C -> A
Yes

1981
A -> T
Yes

2198
-> G
No

2207
-> G
No

2221
C ->
No

2240
-> A
No

2266
T -> C
No

2324
A ->
No

2324
A -> C
No

2474
A ->
No

2474
A -> C
No

2504
T -> C
Yes

2651
-> T
No

The coding portion of transcript HSSTROL3_T9 (SEQ ID NO:87) is shown in bold; this coding portion starts at position 24 and ends at position 1169. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:525) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

136
T -> C
Yes

334
G -> C
Yes

663
G ->
No

699
-> T
No

992
G -> C
Yes

1666
A -> G
Yes

1848
A -> G
Yes

2389
A -> G
Yes

2530
C ->
No

2582
C -> A
Yes

2608
A -> T
Yes

2825
-> G
No

2834
-> G
No

2848
C ->
No

2867
-> A
No

2893
T -> C
No

2951
A ->
No

2951
A -> C
No

3101
A ->
No

3101
A -> C
No

3131
T -> C
Yes

3278
-> T
No

Variant protein HSSTROL3_P7 (SEQ ID NO:526) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T10 (SEQ ID NO:88). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:523)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSSTROL3_P7 (SEQ ID NO:526) and MM11_HUMAN (SEQ ID NO:523):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P7 (SEQ ID NO:526), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 1-163 of HSSTROL3_P7 (SEQ ID NO:526), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7 (SEQ ID NO:526), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 165-359 of HSSTROL3_P7 (SEQ ID NO:526), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:1570) corresponding to amino acids 360-370 of HSSTROL3_P7 (SEQ ID NO:526), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P7 (SEQ ID NO:526), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:1570) in HSSTROL3_P7 (SEQ ID NO:526).

Variant protein HSSTROL3_P7 (SEQ ID NO:526) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P7 (SEQ ID NO:526) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

38
V -> A
Yes

104
R -> P
Yes

214
A ->
No

323
Q -> H
Yes

Variant protein HSSTROL3_P7 (SEQ ID NO:526) is encoded by the following transcript(s): HSSTROL3_T10 (SEQ ID NO:88), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T10 (SEQ ID NO:88) is shown in bold; this coding portion starts at position 24 and ends at position 1133. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P7 (SEQ ID NO:526) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

136
T -> C
Yes

334
G -> C
Yes

663
G ->
No

699
-> T
No

992
G -> C
Yes

1386
A -> G
Yes

1568
A -> G
Yes

2109
A -> G
Yes

2250
C ->
No

2302
C -> A
Yes

2328
A -> T
Yes

2545
-> G
No

2554
-> G
No

2568
C ->
No

2587
-> A
No

2613
T -> C
No

2671
A ->
No

2671
A -> C
No

2821
A ->
No

2821
A -> C
No

2851
T -> C
Yes

2998
-> T
No

Variant protein HSSTROL3_P8 (SEQ ID NO:527) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T11 (SEQ ID NO:505). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:523)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSSTROL3_P8 (SEQ ID NO:527) and MM11_HUMAN (SEQ ID NO:523):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P8 (SEQ ID NO:527), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 1-163 of HSSTROL3_P8 (SEQ ID NO:527), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P8 (SEQ ID NO:527), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE corresponding to amino acids 165-286 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 165-286 of HSSTROL3_P8 (SEQ ID NO:527), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRPCLPVPLLLCWPL (SEQ ID NO:1571) corresponding to amino acids 287-301 of HSSTROL3_P8 (SEQ ID NO:527), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSSTROL3_P8 (SEQ ID NO:527), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRPCLPVPLLLCWPL (SEQ ID NO:1571) in HSSTROL3_P8 (SEQ ID NO:527).

Variant protein HSSTROL3_P8 (SEQ ID NO:527) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P8 (SEQ ID NO:527) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

38
V -> A
Yes

104
R -> P
Yes

214
A ->
No

Variant protein HSSTROL3_P8 (SEQ ID NO:527) is encoded by the following transcript(s): HSSTROL3_T11 (SEQ ID NO:505), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T11 (SEQ ID NO:505) is shown in bold; this coding portion starts at position 24 and ends at position 926. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P8 (SEQ ID NO:527) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

136
T -> C
Yes

334
G -> C
Yes

663
G ->
No

699
-> T
No

935
G -> A
Yes

948
G -> A
Yes

1084
G -> C
Yes

1557
C ->
No

1609
C -> A
Yes

1635
A -> T
Yes

1852
-> G
No

1861
-> G
No

1875
C ->
No

1894
-> A
No

1920
T -> C
No

1978
A ->
No

1978
A -> C
No

2128
A ->
No

2128
A -> C
No

2158
T -> C
Yes

2305
-> T
No

Variant protein HSSTROL3_P9 (SEQ ID NO:528) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSSTROL3_T12 (SEQ ID NO:506). An alignment is given to the known protein (Stromelysin-3 precursor (SEQ ID NO:523)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSSTROL3_P9 (SEQ ID NO:528) and MM11_HUMAN (SEQ ID NO:523):

1. An isolated chimeric polypeptide encoding for HSSTROL3_P9 (SEQ ID NO:528), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR PASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1-96 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 1-96 of HSSTROL3_P9 (SEQ ID NO:528), a second amino acid sequence being at least 90% homologous to RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 113-163 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 97-147 of HSSTROL3_P9 (SEQ ID NO:528), a bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9 (SEQ ID NO:528), a third amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:523), which also corresponds to amino acids 149-343 of HSSTROL3_P9 (SEQ ID NO:528), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:1570) corresponding to amino acids 344-354 of HSSTROL3_P9 (SEQ ID NO:528), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HSSTROL3_P9 (SEQ ID NO:528), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96−x to 96; and ending at any of amino acid numbers 97+((n−2)−x), in which x varies from 0 to n−2.

3. An isolated polypeptide encoding for a tail of HSSTROL3_P9 (SEQ ID NO:528), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:1570) in HSSTROL3_P9 (SEQ ID NO:528).

Variant protein HSSTROL3_P9 (SEQ ID NO:528) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P9 (SEQ ID NO:528) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

38
V -> A
Yes

198
A ->
No

307
Q -> H
Yes

Variant protein HSSTROL3_P9 (SEQ ID NO:528) is encoded by the following transcript(s): HSSTROL3_T12 (SEQ ID NO:506), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSSTROL3_T12 (SEQ ID NO:506) is shown in bold; this coding portion starts at position 24 and ends at position 1085. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSSTROL3_P9 (SEQ ID NO:528) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

136
T -> C
Yes

615
G ->
No

651
-> T
No

944
G -> C
Yes

1275
C ->
No

1327
C -> A
Yes

1353
A -> T
Yes

1570
-> G
No

1579
-> G
No

1593
C ->
No

1612
-> A
No

1638
T -> C
No

1696
A ->
No

1696
A -> C
No

1846
A ->
No

1846
A -> C
No

1876
T -> C
Yes

2023
-> T
No

As noted above, cluster HSSTROL3 features 16 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSSTROL3_node_—6 (SEQ ID NO:507) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
1
131

HSSTROL3_T8 (SEQ ID NO: 86)
1
131

HSSTROL3_T9 (SEQ ID NO: 87)
1
131

HSSTROL3_T10 (SEQ ID NO: 88)
1
131

HSSTROL3_T11 (SEQ ID NO: 505)
1
131

HSSTROL3_T12 (SEQ ID NO: 506)
1
131

Segment cluster HSSTROL3_node_—10 (SEQ ID NO:508) according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
132
313

HSSTROL3_T8 (SEQ ID NO: 86)
132
313

HSSTROL3_T9 (SEQ ID NO: 87)
132
313

HSSTROL3_T10 (SEQ ID NO: 88)
132
313

HSSTROL3_T11 (SEQ ID NO: 505)
132
313

HSSTROL3_T12 (SEQ ID NO: 506)
132
313

Segment cluster HSSTROL3_node_—13 (SEQ ID NO:509) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
362
505

HSSTROL3_T8 (SEQ ID NO: 86)
362
505

HSSTROL3_T9 (SEQ ID NO: 87)
362
505

HSSTROL3_T10 (SEQ ID NO: 88)
362
505

HSSTROL3_T11 (SEQ ID NO: 505)
362
505

HSSTROL3_T12 (SEQ ID NO: 506)
314
457

Segment cluster HSSTROL3_node_—15 (SEQ ID NO:510) according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
506
639

HSSTROL3_T8 (SEQ ID NO: 86)
506
639

HSSTROL3_T9 (SEQ ID NO: 87)
506
639

HSSTROL3_T10 (SEQ ID NO: 88)
506
639

HSSTROL3_T11 (SEQ ID NO: 505)
506
639

HSSTROL3_T12 (SEQ ID NO: 506)
458
591

Segment cluster HSSTROL3_node_—19 (SEQ ID NO:511) according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
699
881

HSSTROL3_T8 (SEQ ID NO: 86)
699
881

HSSTROL3_T9 (SEQ ID NO: 87)
699
881

HSSTROL3_T10 (SEQ ID NO: 88)
699
881

HSSTROL3_T11 (SEQ ID NO: 505)
699
881

HSSTROL3_T12 (SEQ ID NO: 506)
651
833

Segment cluster HSSTROL3_node_—21 (SEQ ID NO:512) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
882
1098

HSSTROL3_T8 (SEQ ID NO: 86)
882
1098

HSSTROL3_T9 (SEQ ID NO: 87)
882
1098

HSSTROL3_T10 (SEQ ID NO: 88)
882
1098

HSSTROL3_T11 (SEQ ID NO: 505)
974
1190

HSSTROL3_T12 (SEQ ID NO: 506)
834
1050

Segment cluster HSSTROL3_node_—24 (SEQ ID NO:513) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T8 (SEQ ID NO:86) and HSSTROL3_T9 (SEQ ID NO:87). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T8 (SEQ ID NO: 86)
1099
1236

HSSTROL3_T9 (SEQ ID NO: 87)
1099
1236

Segment cluster HSSTROL3_node_—25 (SEQ ID NO:514) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T8 (SEQ ID NO:86). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T8 (SEQ ID NO: 86)
1237
1536

Segment cluster HSSTROL3_node_—26 (SEQ ID NO: 515) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87) and HSSTROL3_T11 (SEQ ID NO:505). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
1099
1240

HSSTROL3_T8 (SEQ ID NO: 86)
1537
1678

HSSTROL3_T9 (SEQ ID NO: 87)
1237
1378

HSSTROL3_T11 (SEQ ID NO: 505)
1191
1332

Segment cluster HSSTROL3_node_—28 (SEQ ID NO:516) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T9 (SEQ ID NO:87) and HSSTROL3_T10 (SEQ ID NO:88). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
1357
2283

HSSTROL3_T9 (SEQ ID NO: 87)
1495
2421

HSSTROL3_T10 (SEQ ID NO: 88)
1215
2141

Segment cluster HSSTROL3_node_—29 (SEQ ID NO:517) according to the present invention is supported by 109 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
2284
3194

HSSTROL3_T8 (SEQ ID NO: 86)
1795
2705

HSSTROL3_T9 (SEQ ID NO: 87)
2422
3332

HSSTROL3_T10 (SEQ ID NO: 88)
2142
3052

HSSTROL3_T11 (SEQ ID NO: 505)
1449
2359

HSSTROL3_T12 (SEQ ID NO: 506)
1167
2077

Segment cluster HSSTROL3_node_—11 (SEQ ID NO:518) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88) and HSSTROL3_T11 (SEQ ID NO:505). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
314
361

HSSTROL3_T8 (SEQ ID NO: 86)
314
361

HSSTROL3_T9 (SEQ ID NO: 87)
314
361

HSSTROL3_T10 (SEQ ID NO: 88)
314
361

HSSTROL3_T11 (SEQ ID NO: 505)
314
361

Segment cluster HSSTROL3_node_—17 (SEQ ID NO:519) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
640
680

HSSTROL3_T8 (SEQ ID NO: 86)
640
680

HSSTROL3_T9 (SEQ ID NO: 87)
640
680

HSSTROL3_T10 (SEQ ID NO: 88)
640
680

HSSTROL3_T11 (SEQ ID NO: 505)
640
680

HSSTROL3_T12 (SEQ ID NO: 506)
592
632

Segment cluster HSSTROL3_node_—18 (SEQ ID NO:520) according to the present invention can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
681
698

HSSTROL3_T8 (SEQ ID NO: 86)
681
698

HSSTROL3_T9 (SEQ ID NO: 87)
681
698

HSSTROL3_T10 (SEQ ID NO: 88)
681
698

HSSTROL3_T11 (SEQ ID NO: 505)
681
698

HSSTROL3_T12 (SEQ ID NO: 506)
633
650

Segment cluster HSSTROL3_node_—20 (SEQ ID NO:521) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T11 (SEQ ID NO:505). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T11 (SEQ ID NO: 505)
882
973

Segment cluster HSSTROL3_node_—27 (SEQ ID NO:522) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSSTROL3_T5 (SEQ ID NO:85), HSSTROL3_T8 (SEQ ID NO:86), HSSTROL3_T9 (SEQ ID NO:87), HSSTROL3_T10 (SEQ ID NO:88), HSSTROL3_T11 (SEQ ID NO:505) and HSSTROL3_T12 (SEQ ID NO:506). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HSSTROL3_T5 (SEQ ID NO: 85)
1241
1356

HSSTROL3_T8 (SEQ ID NO: 86)
1679
1794

HSSTROL3_T9 (SEQ ID NO: 87)
1379
1494

HSSTROL3_T10 (SEQ ID NO: 88)
1099
1214

HSSTROL3_T11 (SEQ ID NO: 505)
1333
1448

HSSTROL3_T12 (SEQ ID NO: 506)
1051
1166

Variant Protein Alignment to the Previously Known Protein:

Sequence name: MM11_HUMAN (SEQ ID NO:523)

Sequence documentation:

Alignment of: HSSTROL3_P4 (SEQ ID NO:524) × M11_HUMAN (SEQ ID NO:523) ..

Alignment segment 1/1:

Quality:
4444.00
Escore:
0

Matching length:
445
Total length:
445

Matching Percent Similarity:
99.78
Matching Percent Identity:
99.78

Total Percent Similarity:
99.78
Total Percent Identity:
99.78

Gaps:
0

Alignment:

Sequence name: MM11_HUMAN (SEQ ID NO:523)

Sequence documentation:

Alignment of: HSSTROL3_P5 (SEQ ID NO:525) × MM11_HUMAN (SEQ ID NO:523) ..

Alignment segment 1/1:

Quality:
3566.00
Escore:
0

Matching length:
358
Total length:
358

Matching Percent Similarity:
99.72
Matching Percent Identity:
99.72

Total Percent Similarity:
99.72
Total Percent Identity:
99.72

Gaps:
0

Alignment:

Sequence name: MM11_HUMAN (SEQ ID NO:523)

Sequence documentation:

Alignment of: HSSTROL3_P7 (SEQ ID NO:526) × MM11_HUMAN (SEQ ID NO:523) ..

Alignment segment 1/1:

Quality:
3575.00
Escore:
0

Matching length:
359
Total length:
359

Matching Percent Similarity:
99.72
Matching Percent Identity:
99.72

Total Percent Similarity:
99.72
Total Percent Identity:
99.72

Gaps:
0

Alignment:

Sequence name: MM11_HUMAN (SEQ ID NO:523)

Sequence documentation:

Alignment of: HSSTROL3_P8 (SEQ ID NO:527) × MM11_HUMAN (SEQ ID NO:523) ..

Alignment segment 1/1:

Quality:
2838.00
Escore:
0

Matching length:
286
Total length:
286

Matching Percent Similarity:
99.65
Matching Percent Identity:
99.65

Total Percent Similarity:
99.65
Total Percent Identity:
99.65

Gaps:
0

Alignment:

Sequence name: MM11_HUMAN (SEQ ID NO:523)

Sequence documentation:

Alignment of: HSSTROL3_P9 (SEQ ID NO:528) × MM11_HUMAN (SEQ ID NO:523) ..

Alignment segment 1/1:

Quality:
3316.00
Escore:
0

Matching length:
343
Total length:
359

Matching Percent Similarity:
99.71
Matching Percent Identity:
99.71

Total Percent Similarity:
95.26
Total Percent Identity:
95.26

Gaps:
1

Alignment:

Expression of Homo sapiens Matrix Metalloproteinase 11 (Stromelysin 3) (MMP11) HSSTROL3 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 junc21-27 (SEQ ID NO:1312) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts detectable by or according to junc21-27, HSSTROL3 junc21-27 amplicon (SEQ ID NO:1312) and primers HSSTROL3 junc21-27F (SEQ ID NO:1310) and HSSTROL3 junc21-27R (SEQ ID NO:1311) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 73 is a histogram showing over expression of the above-indicated Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts in cancerous colon samples relative to the normal samples.

As is evident from FIG. 73, the expression of Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts detectable by the above amplicon(s) in cancer samples was higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 6 fold was found in 14 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL3 junc21-27F forward primer (SEQ ID NO:1310); and HSSTROL3 junc21-27R reverse primer (SEQ ID NO:1311).

Primers:

Forward primer HSSTROL3 junc21-27F (SEQ ID NO:

1310):

ACATTTGGTTCTTCCAAGGGACTAC

Reverse primer HSSTROL3 junc21-27R (SEQ ID NO:

1311):

TCGATCTCAGAGGGCACCC

Amplicon HSSTROL3 junc21-27 (SEQ ID NO:1312):

ACATTTGGTTCTTCCAAGGGACTACTGGCGTTTCCACCCCAGCACCCGGC

GTGTAGACAGTCCCGTGCCCCGCAGGGCCACTGACTGGAGAGGGGTGCCC

TCTGAGATCGA

Expression of Homo sapiens Matrix Metalloproteinase 11 (Stromelysin 3) (MMP11) HSSTROL3 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 Seg25 (SEQ ID NO: 1315) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts detectable by or according to seg25, amplicon (SEQ ID NO: 1315) and primers HSSTROL3 seg25F (SEQ ID NO: 1313) and HSSTROL3 seg25R (SEQ ID NO: 1314) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); HPRT1-amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”, above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 74 is a histogram showing over expression of the above-indicated Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts in cancerous colon samples relative to the normal samples.

As is evident from FIG. 74, the expression of Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts detectable by the above amplicon(s) was higher in a few cancer samples than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 5 out of 36 adenocarcinoma samples.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL3 seg25F forward primer (SEQ ID NO: 1313); and HSSTROL3 seg25R reverse primer (SEQ ID NO: 1314).

Primers:

Forward primer HSSTROL3 seg25F (SEQ ID NO: 1313):

CACTGCCCCAGCTTATGCC

Reverse primer HSSTROL3 seg25R (SEQ ID NO: 1314):

CTCTCCCAGCCTCAGTTTCCT

Amplicon HSSTROL3 seg25 (SEQ ID NO: 1315):

CACTGCCCCAGCTTATCCCAGGCCTCCCGCTTCCCTCTGCGGGTGGGGTG

CTGAGCAGGCATTATTGGCCTGCATGTTTTACTGATGAGGAAACTGAGGC

TGGGAGAG

Expression of Homo sapiens Matrix Metalloproteinase 11 (Stromelysin 3) (MMP11) HSSTROL3 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 Seg24 (SEQ ID NO: 1318) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts detectable by or according to seg24, HSSTROL3 seg24 amplicon (SEQ ID NO: 1318) and primers HSSTROL3 seg24F (SEQ ID NO: 1316) and HSSTROL3 seg24R (SEQ ID NO: 1317) was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon —PBGD-amplicon, SEQ ID NO: 531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO: 612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO: 1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSSTROL3 seg24F forward primer (SEQ ID NO: 1316); and HSSTROL3 seg24R reverse primer (SEQ ID NO: 1317).

Primers:

Forward primer HSSTROL3 seg24F (SEQ ID NO: 1316):

ATTTCCATCCTCAACTGGCAGA

Reverse primer HSSTROL3 seg24R (SEQ ID NO: 1317):

TGCCCTGGAACCCACG

Amp1icon HSSTROL3 seg24 (SEQ ID NO: 1318):

ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTGGAGCATTGCAGATGCC

AGGGACTTCACAAATGAAGGCACAGCATGGGAAACCTGCGTGGGTTCCAG

GGCA

Expression of Stromelysin-3 Precursor (Matrix Metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3 Seg24 (SEQ ID NO: 1318) in Different Normal Tissues

Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3 transcripts detectable by or according to HSSTROL3 seg24 amplicon (SEQ ID NO: 1318) and HSSTROL3 seg24F (SEQ ID NO: 1316) and HSSTROL3 seg24R (SEQ ID NO: 1317) was measured by real time PCR. In parallel the expression of four housekeeping genes UBC (GenBank Accession No. BC000449 (SEQ ID NO:1582); amplicon—Ubiquitin-amplicon, SEQ ID NO: 1270) and SDHA (GenBank Accession No. NM_—004168 (SEQ ID NO:1583); amplicon—SDHA-amplicon, SEQ ID NO: 1273), RPL19 (GenBank Accession No. NM_—000981 (SEQ ID NO:1580); RPL19 amplicon, SEQ ID NO: 1264), TATA box (GenBank Accession No. NM_—003194 (SEQ ID NO:1581); TATA amplicon, SEQ ID NO: 1267) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 above), to obtain a value of relative expression of each sample relative to median of the lung samples.

Primers:

Forward primer HSSTROL3 seg24F (SEQ ID NO: 1316):

ATTTCCATCCTCAACTGGCAGA

Reverse primer HSSTROL3 seg24R (SEQ ID NO: 1317):

TGCCCTGGAACCCACG

Amplicon HSSTROL3 seg24 (SEQ ID NO: 1318):

ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTGGAGCATTGCAGATGCC

AGGGACTTCACAAATGAAGGCACAGCATGGGAAACCTGCGTGGGTTCCAG

GGCA

The results are presented in FIG. 76, showing the expression of Stromelysin-3 HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 in different normal tissues.

Description for Cluster AA583399

Cluster AA583399 features 16 transcript(s) and 20 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript name
SEQ ID NO:

AA583399_PEA_1_T0
643

AA583399_PEA_1_T1
644

AA583399_PEA_1_T2
645

AA583399_PEA_1_T3
646

AA583399_PEA_1_T4
647

AA583399_PEA_1_T5
648

AA583399_PEA_1_T6
649

AA583399_PEA_1_T7
650

AA583399_PEA_1_T8
651

AA583399_PEA_1_T9
652

AA583399_PEA_1_T10
653

AA583399_PEA_1_T11
654

AA583399_PEA_1_T12
655

AA583399_PEA_1_T15
656

AA583399_PEA_1_T16
657

AA583399_PEA_1_T17
658

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

AA583399_PEA_1_node_0
659

AA583399_PEA_1_node_3
660

AA583399_PEA_1_node_9
661

AA583399_PEA_1_node_10
662

AA583399_PEA_1_node_12
663

AA583399_PEA_1_node_14
664

AA583399_PEA_1_node_21
665

AA583399_PEA_1_node_24
666

AA583399_PEA_1_node_25
667

AA583399_PEA_1_node_29
668

AA583399_PEA_1_node_1
669

AA583399_PEA_1_node_2
670

AA583399_PEA_1_node_4
671

AA583399_PEA_1_node_5
672

AA583399_PEA_1_node_6
673

AA583399_PEA_1_node_7
674

AA583399_PEA_1_node_8
675

AA583399_PEA_1_node_11
676

AA583399_PEA_1_node_19
677

AA583399_PEA_1_node_27
678

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

AA583399_PEA_1_P3
683
AA583399_PEA_1_T1 (SEQ ID NO: 644);

AA583399_PEA_1_T6 (SEQ ID NO: 649);

AA583399_PEA_1_T9 (SEQ ID NO: 652)

AA583399_PEA_1_P2
684
AA583399_PEA_1_T3 (SEQ ID NO: 646);

AA583399_PEA_1_T4 (SEQ ID NO: 647);

AA583399_PEA_1_T5 (SEQ ID NO: 648)

AA583399_PEA_1_P4
685
AA583399_PEA_1_T7 (SEQ ID NO: 650)

AA583399_PEA_1_P5
686
AA583399_PEA_1_T8 (SEQ ID NO: 651)

AA583399_PEA_1_P6
687
AA583399_PEA_1_T12 (SEQ ID NO: 655);

AA583399_PEA_1_T16 (SEQ ID NO: 657)

AA583399_PEA_1_P8
688
AA583399_PEA_1_T17 (SEQ ID NO: 658)

AA583399_PEA_1_P10
689
AA583399_PEA_1_T0 (SEQ ID NO: 643)

AA583399_PEA_1_P11
690
AA583399_PEA_1_T2 (SEQ ID NO: 645)

AA583399_PEA_1_P12
691
AA583399_PEA_1_T10 (SEQ ID NO: 653);

AA583399_PEA_1_T11 (SEQ ID NO: 654)

AA583399_PEA_1_P14
692
AA583399_PEA_1_T15 (SEQ ID NO: 656)

These sequences are variants of the known protein Myeloma overexpressed gene protein (SwissProt accession identifier MYEO_HUMAN; known also according to the synonyms Oncogene in multiple myeloma), SEQ ID NO: 679, referred to herein as the previously known protein.

The sequence for protein Myeloma overexpressed gene protein (SEQ ID NO:679) is given at the end of the application, as “Myeloma overexpressed gene protein amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s)

on amino

acid sequence
Comment

159
A -> V (in dbSNP: 7103126). /FTId = VAR_016603.

198
R -> Q

219
V -> M

271
G -> R

Cluster AA583399 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 40 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and gastric carcinoma.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bone
32

brain
0

colon
0

epithelial
4

general
2

kidney
0

liver
0

lung
2

lymph nodes
0

breast
79

ovary
0

pancreas
0

prostate
0

skin
0

stomach
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bone
9.2e−01
5.8e−01
1
0.5
9.1e−01
0.8

brain
9.8e−01
1.4e−01
1
0.8
2.0e−09
11.1

colon
1.6e−01
7.3e−02
3.4e−01
2.5
2.7e−01
2.7

epithelial
3.0e−03
1.3e−04
1.1e−01
2.3
5.4e−06
4.1

general
1.1e−05
3.2e−10
2.0e−03
4.5
1.1e−17
10.7

kidney
6.5e−01
5.1e−01
1
1.1
7.0e−01
1.5

liver
1
1.3e−01
1
1.0
1.6e−01
2.2

lung
1.7e−01
2.7e−01
1.7e−01
3.5
2.4e−01
2.5

lymph nodes
1
5.7e−01
1
1.0
5.8e−01
1.7

breast
8.8e−01
8.6e−01
9.0e−01
0.5
8.5e−01
0.6

ovary
1.6e−01
1.9e−01
1
1.1
1
1.1

pancreas
3.3e−01
4.4e−01
4.2e−01
2.4
5.3e−01
1.9

prostate
1
7.8e−01
1
1.0
5.6e−01
1.7

skin
1
4.4e−01
1
1.0
6.4e−01
1.6

stomach
3.6e−01
1.3e−01
1
1.1
1.8e−03
3.8

As noted above, cluster AA583399 features 16 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Myeloma overexpressed gene protein (SEQ ID NO:679). A description of each variant protein according to the present invention is now provided.

Variant protein AA583399_PEA_—1_P3 (SEQ ID NO:683) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T1 (SEQ ID NO:644). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide. Variant protein AA583399_PEA_—1_P3 (SEQ ID NO:683) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P3 (SEQ ID NO:683) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

159
V -> A
Yes

198
R -> Q
Yes

219
M -> V
No

271
G -> R
Yes

284
P -> T
Yes

Variant protein AA583399_PEA_—1_P3 (SEQ ID NO:683) is encoded by the following transcript(s): AA583399_PEA_—1_T1 (SEQ ID NO:644), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T1 (SEQ ID NO:644) is shown in bold; this coding portion starts at position 587 and ends at position 1525. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P3 (SEQ ID NO:683) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

380
A -> G
Yes

805
C -> T
Yes

1062
T -> C
Yes

1179
G -> A
Yes

1241
A -> G
No

1397
G -> C
Yes

1436
C -> A
Yes

1653
C -> T
No

1657
T -> G
No

Variant protein AA583399_PEA_—1_P2 (SEQ ID NO:684) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T3 (SEQ ID NO:646). An alignment is given to the known protein (Myeloma overexpressed gene protein (SEQ ID NO:679)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between AA583399_PEA_—1_P2 (SEQ ID NO:684) and MYEO_HUMAN_V1 (SEQ ID NO: 680):

1. An isolated chimeric polypeptide encoding for AA583399_PEA_—1_P2 (SEQ ID NO:684), comprising a first amino acid sequence being at least 90% homologous to MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKGAQTGAGLSQEAE DVDVSRARRVTDAPQGTLCGTGNRNSGSQSARVVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIM WARMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTV VTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59-313 of MYEO_HUMAN_V1 (SEQ ID NO:680), which also corresponds to amino acids 1-255 of AA583399_PEA_—1_P2 (SEQ ID NO:684).

It should be noted that the known protein sequence (MYEO_HUMAN (SEQ ID NO:679)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYEO_HUMAN_V1 (SEQ ID NO:680). These changes were previously known to occur and are listed in the table below.

TABLE 9

Changes to MYEO_HUMAN_V1 (SEQ ID NO: 680)

SNP position(s) on amino

acid sequence
Type of change

160
variant

220
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein AA583399_PEA_—1_P2 (SEQ ID NO:684) is encoded by the following transcript(s): AA583399_PEA_—1_T3 (SEQ ID NO:646), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T3 (SEQ ID NO:646) is shown in bold; this coding portion starts at position 689 and ends at position 1453. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P2 (SEQ ID NO:684) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

380
A -> G
Yes

733
C -> T
Yes

990
T -> C
Yes

1107
G -> A
Yes

1169
A -> G
No

1325
G -> C
Yes

1364
C -> A
Yes

1581
C -> T
No

1585
T -> G
No

Variant protein AA583399_PEA_—1_P4 (SEQ ID NO:685) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T7 (SEQ ID NO:650). An alignment is given to the known protein (Myeloma overexpressed gene protein (SEQ ID NO:679)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between AA583399_PEA_—1_P4 (SEQ ID NO:685) and MYEO_HUMAN_V1 (SEQ ID NO:680):

1. An isolated chimeric polypeptide encoding for AA583399_PEA_—1_P4 (SEQ ID NO:685), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG (SEQ ID NO:1479) corresponding to amino acids 1-27 of AA583399_PEA_—1_P4 (SEQ ID NO:685), and a second amino acid sequence being at least 90% homologous to RNSGSQSARVVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIMWARMDVALRSPGRGLLAGAGALC MTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVEALGGWRMGVRRTGQVGPTM HPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 150-313 of MYEO_HUMAN_V1 (SEQ ID NO:680), which also corresponds to amino acids 28-191 of AA583399_PEA_—1_P4 (SEQ ID NO:685), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of AA583399_PEA_—1_P4 (SEQ ID NO:685), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG (SEQ ID NO:1479) of AA583399_PEA_—1_P4 (SEQ ID NO:685).

TABLE 11

Changes to MYEO_HUMAN_V1 (SEQ ID NO: 680)

SNP position(s) on amino

acid sequence
Type of change

160
variant

220
conflict

Variant protein AA583399_PEA_—1_P4 (SEQ ID NO:685) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P4 (SEQ ID NO:685) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

37
V -> A
Yes

76
R -> Q
Yes

97
M -> V
No

149
G -> R
Yes

162
P -> T
Yes

Variant protein AA583399_PEA_—1_P4 (SEQ ID NO:685) is encoded by the following transcript(s): AA583399_PEA_—1_T7 (SEQ ID NO:650), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T7 (SEQ ID NO:650) is shown in bold; this coding portion starts at position 789 and ends at position 1361. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P4 (SEQ ID NO:685) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

380
A -> G
Yes

898
T -> C
Yes

1015
G -> A
Yes

1077
A -> G
No

1233
G -> C
Yes

1272
C -> A
Yes

1489
C -> T
No

1493
T -> G
No

Variant protein AA583399_PEA_—1_P5 (SEQ ID NO:686) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T8 (SEQ ID NO:651). An alignment is given to the known protein (Myeloma overexpressed gene protein (SEQ ID NO:679)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between AA583399_PEA_—1_P5 (SEQ ID NO:686) and MYEO_HUMAN_V2 (SEQ ID NO: 681):

1. An isolated chimeric polypeptide encoding for AA583399_PEA_—1_P5 (SEQ ID NO:686), comprising a first amino acid sequence being at least 90% homologous to MEIMWARMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGS WLTVVTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 192-313 of MYEO_HUMAN_V2 (SEQ ID NO:681), which also corresponds to amino acids 1-122 of AA583399_PEA_—1_P5 (SEQ ID NO:686).

It should be noted that the known protein sequence (MYEO_HUMAN (SEQ ID NO:679)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYEO_HUMAN_V2 (SEQ ID NO:681). These changes were previously known to occur and are listed in the table below.

TABLE 14

Changes to MYEO_HUMAN_V2 (SEQ ID NO: 681)

SNP position(s) on amino

acid sequence
Type of change

220
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein AA583399_PEA_—1_P5 (SEQ ID NO:686) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P5 (SEQ ID NO:686) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

7
R -> Q
Yes

28
M -> V
No

80
G -> R
Yes

93
P -> T
Yes

Variant protein AA583399_PEA_—1_P5 (SEQ ID NO:686) is encoded by the following transcript(s): AA583399_PEA_—1_T8 (SEQ ID NO:651), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T8 (SEQ ID NO:651) is shown in bold; this coding portion starts at position 849 and ends at position 1214. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P5 (SEQ ID NO:686) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

380
A -> G
Yes

494
C -> T
Yes

751
T -> C
Yes

868
G -> A
Yes

930
A -> G
No

1086
G -> C
Yes

1125
C -> A
Yes

1342
C -> T
No

1346
T -> G
No

Variant protein AA583399_PEA_—1_P6 (SEQ ID NO:687) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T12 (SEQ ID NO:655). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein AA583399_PEA_—1_P6 (SEQ ID NO:687) is encoded by the following transcript(s): AA583399_PEA_—1_T12 (SEQ ID NO:655), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T12 (SEQ ID NO:655) is shown in bold; this coding portion starts at position 39 and ends at position 371. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P6 (SEQ ID NO:687) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

198
A -> G
Yes

538
C -> A
Yes

659
C -> G
Yes

1009
C -> T
Yes

1145
A -> G
Yes

Variant protein AA583399_PEA_—1_P8 (SEQ ID NO:688) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T17 (SEQ ID NO:658). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein AA583399_PEA_—1_P8 (SEQ ID NO:688) is encoded by the following transcript(s): AA583399_PEA_—1_T17 (SEQ ID NO:658), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T17 (SEQ ID NO:658) is shown in bold; this coding portion starts at position 191 and ends at position 400.

Variant protein AA583399_PEA_—1_P10 (SEQ ID NO:689) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T0 (SEQ ID NO:643). An alignment is given to the known protein (Myeloma overexpressed gene protein (SEQ ID NO:679)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between AA583399_PEA_—1_P10 (SEQ ID NO:689) and MYEO_HUMAN_V3 (SEQ ID NO: 682):

1. An isolated chimeric polypeptide encoding for AA583399_PEA_—1_P10 (SEQ ID NO:689), comprising a first amino acid sequence being at least 90% homologous to MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKGAQTGAGLSQEAE DVDVSRARRVTDAPQGTLCGTGNRNSGSQSARAVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIM WAQMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTV VTVEALGRWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59-313 of MYEO_HUMAN_V3 (SEQ ID NO:682), which also corresponds to amino acids 1-255 of AA583399_PEA_—1_P10 (SEQ ID NO:689).

It should be noted that the known protein sequence (MYEO_HUMAN (SEQ ID NO:679)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for MYEO_HUMAN_V3 (SEQ ID NO:682). These changes were previously known to occur and are listed in the table below.

TABLE 18

Changes to MYEO_HUMAN_V3 (SEQ ID NO: 682)

SNP position(s) on amino

acid sequence
Type of change

199
conflict

220
conflict

272
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein AA583399_PEA_—1_P10 (SEQ ID NO:689) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 19, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P10 (SEQ ID NO:689) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

101
A -> V
Yes

140
Q -> R
Yes

161
M -> V
No

213
R -> G
Yes

226
P -> T
Yes

Variant protein AA583399_PEA_—1_P10 (SEQ ID NO:689) is encoded by the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T0 (SEQ ID NO:643) is shown in bold; this coding portion starts at position 857 and ends at position 1621. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P10 (SEQ ID NO:689) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

380
A -> G
Yes

901
C -> T
Yes

1158
T -> C
Yes

1275
G -> A
Yes

1337
A -> G
No

1493
G -> C
Yes

1532
C -> A
Yes

1749
C -> T
No

1753
T -> G
No

Variant protein AA583399_PEA_—1_P11 (SEQ ID NO:690) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T2 (SEQ ID NO:645). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide.

Variant protein AA583399_PEA_—1_P11 (SEQ ID NO:690) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 21, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P11 (SEQ ID NO:690) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

159
A -> V
Yes

198
R -> Q
Yes

219
V -> M
No

271
G -> R
Yes

284
P -> T
Yes

Variant protein AA583399_PEA_—1_P11 (SEQ ID NO:690) is encoded by the following transcript(s): AA583399_PEA_—1_T2 (SEQ ID NO:645), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T2 (SEQ ID NO:645) is shown in bold; this coding portion starts at position 493 and ends at position 1431. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P11 (SEQ ID NO:690) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

380
A -> G
Yes

711
C -> T
Yes

968
T -> C
Yes

1085
G -> A
Yes

1147
A -> G
No

1303
G -> C
Yes

1342
C -> A
Yes

1559
C -> T
No

1563
T -> G
No

Variant protein AA583399_PEA_—1_P12 (SEQ ID NO:691) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T10 (SEQ ID NO:653) and AA583399_PEA_—1_T11 (SEQ ID NO:654). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein AA583399_PEA_—1_P12 (SEQ ID NO:691) is encoded by the following transcript(s): AA583399_PEA_—1_T10 (SEQ ID NO:653) and AA583399_PEA_—1_T11 (SEQ ID NO:654), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript AA583399_PEA_—1_T10 (SEQ ID NO:653) is shown in bold; this coding portion starts at position 191 and ends at position 367. The transcript also has the following SNPs as listed in Table 23 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P12 (SEQ ID NO:691) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

380
A -> G
Yes

The coding portion of transcript AA583399_PEA_—1_T11 (SEQ ID NO:654) is shown in bold; this coding portion starts at position 191 and ends at position 367. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AA583399_PEA_—1_P12 (SEQ ID NO:691) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

380
A -> G
Yes

Variant protein AA583399_PEA_—1_P14 (SEQ ID NO:692) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AA583399_PEA_—1_T15 (SEQ ID NO:656). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein AA583399_PEA_—1_P14 (SEQ ID NO:692) is encoded by the following transcript(s): AA583399_PEA_—1_T15 (SEQ ID NO:656), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AA583399_PEA_—1_T15 (SEQ ID NO:656) is shown in bold; this coding portion starts at position 43 and ends at position 210.

As noted above, cluster AA583399 features 20 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster AA583399_PEA_—1_node_—0 (SEQ ID NO:659) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650), AA583399_PEA_—1_T8 (SEQ ID NO:651), AA583399_PEA_—1_T9 (SEQ ID NO:652), AA583399_PEA_—1_T10 (SEQ ID NO:653), AA583399_PEA_—1_T11 (SEQ ID NO:654) and AA583399_PEA_—1_T17 (SEQ ID NO:658). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
1
355

AA583399_PEA_1_T1 (SEQ ID NO: 644)
1
355

AA583399_PEA_1_T2 (SEQ ID NO: 645)
1
355

AA583399_PEA_1_T3 (SEQ ID NO: 646)
1
355

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1
355

AA583399_PEA_1_T5 (SEQ ID NO: 648)
1
355

AA583399_PEA_1_T6 (SEQ ID NO: 649)
1
355

AA583399_PEA_1_T7 (SEQ ID NO: 650)
1
355

AA583399_PEA_1_T8 (SEQ ID NO: 651)
1
355

AA583399_PEA_1_T9 (SEQ ID NO: 652)
1
355

AA583399_PEA_1_T10 (SEQ ID NO: 653)
1
355

AA583399_PEA_1_T11 (SEQ ID NO: 654)
1
355

AA583399_PEA_1_T17 (SEQ ID NO: 658)
1
355

Segment cluster AA583399_PEA_—1_node_—3 (SEQ ID NO:660) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T4 (SEQ ID NO:647). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T4 (SEQ ID NO: 647)
465
1120

Segment cluster AA583399_PEA_—1_node_—9 (SEQ ID NO:661) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T8 (SEQ ID NO:651) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
872
1131

AA583399_PEA_1_T1 (SEQ ID NO: 644)
776
1035

AA583399_PEA_1_T2 (SEQ ID NO: 645)
682
941

AA583399_PEA_1_T3 (SEQ ID NO: 646)
704
963

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1528
1787

AA583399_PEA_1_T5 (SEQ ID NO: 648)
778
1037

AA583399_PEA_1_T6 (SEQ ID NO: 649)
776
1035

AA583399_PEA_1_T8 (SEQ ID NO: 651)
465
724

AA583399_PEA_1_T9 (SEQ ID NO: 652)
776
1035

Segment cluster AA583399_PEA_—1_node_—10 (SEQ ID NO:662) according to the present invention is supported by 59 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650), AA583399_PEA_—1_T8 (SEQ ID NO:651) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
1132
2389

AA583399_PEA_1_T1 (SEQ ID NO: 644)
1036
2293

AA583399_PEA_1_T2 (SEQ ID NO: 645)
942
2199

AA583399_PEA_1_T3 (SEQ ID NO: 646)
964
2221

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1788
3045

AA583399_PEA_1_T5 (SEQ ID NO: 648)
1038
2295

AA583399_PEA_1_T6 (SEQ ID NO: 649)
1036
2293

AA583399_PEA_1_T7 (SEQ ID NO: 650)
872
2129

AA583399_PEA_1_T8 (SEQ ID NO: 651)
725
1982

AA583399_PEA_1_T9 (SEQ ID NO: 652)
1036
2293

Segment cluster AA583399_PEA_—1_node_—12 (SEQ ID NO:663) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650), AA583399_PEA_—1_T8 (SEQ ID NO:651) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
2412
2519

AA583399_PEA_1_T1 (SEQ ID NO: 644)
2316
2423

AA583399_PEA_1_T2 (SEQ ID NO: 645)
2222
2329

AA583399_PEA_1_T3 (SEQ ID NO: 646)
2244
2351

AA583399_PEA_1_T4 (SEQ ID NO: 647)
3068
3175

AA583399_PEA_1_T5 (SEQ ID NO: 648)
2318
2425

AA583399_PEA_1_T6 (SEQ ID NO: 649)
2316
2589

AA583399_PEA_1_T7 (SEQ ID NO: 650)
2152
2259

AA583399_PEA_1_T8 (SEQ ID NO: 651)
2005
2112

AA583399_PEA_1_T9 (SEQ ID NO: 652)
2294
2401

Segment cluster AA583399_PEA_—1_node_—14 (SEQ ID NO:664) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T12 (SEQ ID NO:655) and AA583399_PEA_—1_T16 (SEQ ID NO:657). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T12 (SEQ ID NO: 655)
1
1179

AA583399_PEA_1_T16 (SEQ ID NO: 657)
1
1179

Segment cluster AA583399_PEA_—1_node_—21 (SEQ ID NO:665) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T10 (SEQ ID NO:653), AA583399_PEA_—1_T11 (SEQ ID NO:654), AA583399_PEA_—1_T12 (SEQ ID NO:655), AA583399_PEA_—1_T15 (SEQ ID NO:656), AA583399_PEA_—1_T16 (SEQ ID NO:657) and AA583399_PEA_—1_T17 (SEQ ID NO:658). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T10 (SEQ ID NO: 653)
465
633

AA583399_PEA_1_T11 (SEQ ID NO: 654)
465
633

AA583399_PEA_1_T12 (SEQ ID NO: 655)
1180
1348

AA583399_PEA_1_T15 (SEQ ID NO: 656)
78
246

AA583399_PEA_1_T16 (SEQ ID NO: 657)
1180
1348

AA583399_PEA_1_T17 (SEQ ID NO: 658)
434
602

Segment cluster AA583399_PEA_—1_node_—24 (SEQ ID NO:666) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T11 (SEQ ID NO:654), AA583399_PEA_—1_T12 (SEQ ID NO:655), AA583399_PEA_—1_T15 (SEQ ID NO:656) and AA583399_PEA_—1_T16 (SEQ ID NO:657). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T11 (SEQ ID NO: 654)
634
757

AA583399_PEA_1_T12 (SEQ ID NO: 655)
1349
1472

AA583399_PEA_1_T15 (SEQ ID NO: 656)
247
370

AA583399_PEA_1_T16 (SEQ ID NO: 657)
1349
1472

Segment cluster AA583399_PEA_—1_node_—25 (SEQ ID NO:667) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T16 (SEQ ID NO:657). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

AA583399_PEA_1_T16 (SEQ ID
1473
1614

NO: 657)

Segment cluster AA583399_PEA_—1_node_—29 (SEQ ID NO:668) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T11 (SEQ ID NO:654), AA583399_PEA_—1_T12 (SEQ ID NO:655) and AA583399_PEA_—1_T15 (SEQ ID NO:656). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T11 (SEQ ID NO: 654)
832
1491

AA583399_PEA_1_T12 (SEQ ID NO: 655)
1547
2206

AA583399_PEA_1_T15 (SEQ ID NO: 656)
445
1104

Segment cluster AA583399_PEA_—1_node_—1 (SEQ ID NO:669) according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650), AA583399_PEA_—1_T8 (SEQ ID NO:651), AA583399_PEA_—1_T9 (SEQ ID NO:652), AA583399_PEA_—1_T10 (SEQ ID NO:653) and AA583399_PEA_—1_T11 (SEQ ID NO:654). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
356
386

AA583399_PEA_1_T1 (SEQ ID NO: 644)
356
386

AA583399_PEA_1_T2 (SEQ ID NO: 645)
356
386

AA583399_PEA_1_T3 (SEQ ID NO: 646)
356
386

AA583399_PEA_1_T4 (SEQ ID NO: 647)
356
386

AA583399_PEA_1_T5 (SEQ ID NO: 648)
356
386

AA583399_PEA_1_T6 (SEQ ID NO: 649)
356
386

AA583399_PEA_1_T7 (SEQ ID NO: 650)
356
386

AA583399_PEA_1_T8 (SEQ ID NO: 651)
356
386

AA583399_PEA_1_T9 (SEQ ID NO: 652)
356
386

AA583399_PEA_1_T10 (SEQ ID NO: 653)
356
386

AA583399_PEA_1_T11 (SEQ ID NO: 654)
356
386

Segment cluster AA583399_PEA_—1_node_—2 (SEQ ID NO:670) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650), AA583399_PEA_—1_T8 (SEQ ID NO:651), AA583399_PEA_—1_T9 (SEQ ID NO:652), AA583399_PEA_—1_T10 (SEQ ID NO:653), AA583399_PEA_—1_T11 (SEQ ID NO:654) and AA583399_PEA_—1_T17 (SEQ ID NO:658). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
387
464

AA583399_PEA_1_T1 (SEQ ID NO: 644)
387
464

AA583399_PEA_1_T2 (SEQ ID NO: 645)
387
464

AA583399_PEA_1_T3 (SEQ ID NO: 646)
387
464

AA583399_PEA_1_T4 (SEQ ID NO: 647)
387
464

AA583399_PEA_1_T5 (SEQ ID NO: 648)
387
464

AA583399_PEA_1_T6 (SEQ ID NO: 649)
387
464

AA583399_PEA_1_T7 (SEQ ID NO: 650)
387
464

AA583399_PEA_1_T8 (SEQ ID NO: 651)
387
464

AA583399_PEA_1_T9 (SEQ ID NO: 652)
387
464

AA583399_PEA_1_T10 (SEQ ID NO: 653)
387
464

AA583399_PEA_1_T11 (SEQ ID NO: 654)
387
464

AA583399_PEA_1_T17 (SEQ ID NO: 658)
356
433

Segment cluster AA583399_PEA_—1_node_—4 (SEQ ID NO:671) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
465
558

AA583399_PEA_1_T1 (SEQ ID NO: 644)
465
558

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1121
1214

AA583399_PEA_1_T6 (SEQ ID NO: 649)
465
558

AA583399_PEA_1_T7 (SEQ ID NO: 650)
465
558

AA583399_PEA_1_T9 (SEQ ID NO: 652)
465
558

Segment cluster AA583399_PEA_—1_node_—5 (SEQ ID NO:672) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
559
632

AA583399_PEA_1_T1 (SEQ ID NO: 644)
559
632

AA583399_PEA_1_T2 (SEQ ID NO: 645)
465
538

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1215
1288

AA583399_PEA_1_T5 (SEQ ID NO: 648)
465
538

AA583399_PEA_1_T6 (SEQ ID NO: 649)
559
632

AA583399_PEA_1_T7 (SEQ ID NO: 650)
559
632

AA583399_PEA_1_T9 (SEQ ID NO: 652)
559
632

Segment cluster AA583399_PEA_—1_node_—6 (SEQ ID NO:673) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
633
727

AA583399_PEA_1_T1 (SEQ ID NO: 644)
633
727

AA583399_PEA_1_T2 (SEQ ID NO: 645)
539
633

AA583399_PEA_1_T3 (SEQ ID NO: 646)
465
559

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1289
1383

AA583399_PEA_1_T5 (SEQ ID NO: 648)
539
633

AA583399_PEA_1_T6 (SEQ ID NO: 649)
633
727

AA583399_PEA_1_T7 (SEQ ID NO: 650)
633
727

AA583399_PEA_1_T9 (SEQ ID NO: 652)
633
727

Segment cluster AA583399_PEA_—1_node_—7 (SEQ ID NO:674) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648) and AA583399_PEA_—1_T7 (SEQ ID NO:650). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
728
823

AA583399_PEA_1_T3 (SEQ ID NO: 646)
560
655

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1384
1479

AA583399_PEA_1_T5 (SEQ ID NO: 648)
634
729

AA583399_PEA_1_T7 (SEQ ID NO: 650)
728
823

Segment cluster AA583399_PEA_—1_node_—8 (SEQ ID NO:675) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650) and AA583399_PEA_—1_T9 (SEQ ID NO:652). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
824
871

AA583399_PEA_1_T1 (SEQ ID NO: 644)
728
775

AA583399_PEA_1_T2 (SEQ ID NO: 645)
634
681

AA583399_PEA_1_T3 (SEQ ID NO: 646)
656
703

AA583399_PEA_1_T4 (SEQ ID NO: 647)
1480
1527

AA583399_PEA_1_T5 (SEQ ID NO: 648)
730
777

AA583399_PEA_1_T6 (SEQ ID NO: 649)
728
775

AA583399_PEA_1_T7 (SEQ ID NO: 650)
824
871

AA583399_PEA_1_T9 (SEQ ID NO: 652)
728
775

Segment cluster AA583399_PEA_—1_node_—11 (SEQ ID NO:676) according to the present invention can be found in the following transcript(s): AA583399_PEA_—1_T0 (SEQ ID NO:643), AA583399_PEA_—1_T1 (SEQ ID NO:644), AA583399_PEA_—1_T2 (SEQ ID NO:645), AA583399_PEA_—1_T3 (SEQ ID NO:646), AA583399_PEA_—1_T4 (SEQ ID NO:647), AA583399_PEA_—1_T5 (SEQ ID NO:648), AA583399_PEA_—1_T6 (SEQ ID NO:649), AA583399_PEA_—1_T7 (SEQ ID NO:650) and AA583399_PEA_—1_T8 (SEQ ID NO:651). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AA583399_PEA_1_T0 (SEQ ID NO: 643)
2390
2411

AA583399_PEA_1_T1 (SEQ ID NO: 644)
2294
2315

AA583399_PEA_1_T2 (SEQ ID NO: 645)
2200
2221

AA583399_PEA_1_T3 (SEQ ID NO: 646)
2222
2243

AA583399_PEA_1_T4 (SEQ ID NO: 647)
3046
3067

AA583399_PEA_1_T5 (SEQ ID NO: 648)
2296
2317

AA583399_PEA_1_T6 (SEQ ID NO: 649)
2294
2315

AA583399_PEA_1_T7 (SEQ ID NO: 650)
2130
2151

AA583399_PEA_1_T8 (SEQ ID NO: 651)
1983
2004

Segment cluster AA583399_PEA_—1_node_—19 (SEQ ID NO:677) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T15 (SEQ ID NO:656). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T15 (SEQ ID NO: 656)
1
77

Segment cluster AA583399_PEA_—1_node_—27 (SEQ ID NO:678) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AA583399_PEA_—1_T11 (SEQ ID NO:654), AA583399_PEA_—1_T12 (SEQ ID NO:655) and AA583399_PEA_—1_T15 (SEQ ID NO:656). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AA583399_PEA_1_T11 (SEQ ID NO: 654)
758
831

AA583399_PEA_1_T12 (SEQ ID NO: 655)
1473
1546

AA583399_PEA_1_T15 (SEQ ID NO: 656)
371
444

Variant Protein Alignment to the Previously Known Protein:

Sequence name: MYEO_HUMAN_V1 (SEQ ID NO:680)

Sequence documentation:

Alignment of: AA583399_PEA_1_P2 (SEQ ID NO:684) × MYEO_HUMAN_V1 (SEQ ID

NO:680) ..

Alignment segment 1/1:

Quality:
2473.00
Escore:
0

Matching length:
255
Total length:
255

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: MYEO_HUMAN_V1 (SEQ ID NO:680)

Sequence documentation:

Alignment of: AA583399_PEA_1_P4 (SEQ ID NO:685) × MYEO_HUMAN_V1 (SEQ ID

NO:680) ..

Alignment segment 1/1:

Quality:
1607.00
Escore:
0

Matching length:
164
Total length:
164

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: MYEO_HUMAN_V2 (SEQ ID NO:681)

Sequence documentation:

Alignment of: AA583399_PEA_1_P5 (SEQ ID NO:686) × MYEO_HUMAN_V2 (SEQ ID

NO:681) ..

Alignment segment 1/1:

Quality:
1206.00
Escore:
0

Matching length:
122
Total length:
122

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: MYEO_HUMAN_V3 (SEQ ID NO:682)

Sequence documentation:

Alignment of: AA583399_PEA_1_P10 (SEQ ID NO:689) × MYEO_HUMAN_V3

(SEQ ID NO:682) ..

Alignment segment 1/1:

Quality:
2475.00
Escore:
0

Matching length:
255
Total length:
255

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Expression of Myeloma Overexpressed Gene (in a Subset of t(11;14) Positive Multiple Myelomas) (MYEOV) AA583399 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name

AA583399seg30-32 (SEQ ID NO:1321) in Normal and Cancerous Colon Tissues

Expression of myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts detectable by or according to seg30-32, AA583399seg30-32 amplicon (SEQ ID NO:1321) and AA583399seg30-32F (SEQ ID NO: 1319) and AA583399seg30-32R(SEQ ID NO: 1320) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 41 is a histogram showing over expression of the above-indicated myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts in cancerous colon samples relative to the normal samples. (Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.) The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 41, the expression of myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 27 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 6.50E-05.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.56E-05 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AA583399seg30-23F forward primer (SEQ ID NO: 1319); and AA583399seg30-32 R reverse primer (SEQ ID NO: 1320). The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: AA583399seg30-32 (SEQ ID NO: 1321). Forward primer

Forward primer (SEQ ID NO: 1319):

TGGAGATTCCTGGTTTAAAGCATT

Reverse primer (SEQ ID NO: 1320):

CCCCAGCTTAGAGCTGCACT

Amplicon (SEQ ID NO: 1321):

TGGAGATTCCTGGTTTAAAGCATTTAAAGCCTCTGTGAAAATTTGCCCAG

GCCAACAACTTCACTTTCCACACTCAGTGCCACGAAGTGCAGCTCTAAGC

TGGGG

Expression of Myeloma Overexpressed Gene (in a Subset of t(11;14) Positive Multiple Myelomas) (MYEOV) AA583399 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name

AA583399seg17 (SEQ ID NO: 1324) in Normal and Cancerous Colon Tissues

Expression of myeloma overexpressed gene (in a subset of t(111;14) positive multiple myelomas) (MYEOV) transcripts detectable by or according to seg17, AA583399seg17 amplicon (SEQ ID NO: 1324) and AA583399seg17F (SEQ ID NO: 1322) AA583399seg17R (SEQ ID NO: 1323) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 42 is a histogram showing over expression of the above-indicated myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts in cancerous colon samples relative to the normal samples. (Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.) The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 42, the expression of myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 22 out of 37 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 3.42E-04 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AA583399seg17F forward primer (SEQ ID NO: 1322); and AA583399seg17 R reverse primer (SEQ ID NO: 1323).

Forward primer (SEQ ID NO: 1322):

CATTCTCCACGCATCAGATGA

Reverse primer (SEQ ID NO: 1323):

ACCATCAGATTGGCAGCATG

Amplicon (SEQ ID NO: 1324):

CATTCTCCACGCATCAGATGATCCTGTGGCCCCTCAGTGCCAGGCCCCAC

TGGCCCTCTGCGCACATCAGTGACTCTGATGTTCTCCCCCACCGCATGCT

GCCAATCTGATGGT

Expression of Myeloma Overexpressed Gene (in a Subset of t(11;14) Positive Multiple Myelomas) (MYEOV) AA583399 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name AA583399Seg1 (SEQ ID NO: 1327) in Normal and Cancerous Colon Tissues

Expression of myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts detectable by or according to seg1, AA583399seg1 amplicon (SEQ ID NO: 1327) and AA583399seg1F (SEQ ID NO: 1325) AA583399seg1R (SEQ ID NO: 1326) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 43 is a histogram showing over expression of the above-indicated myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 43, the expression of myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 23 out of 37 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.97E-04 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AA583399seg1F forward primer (SEQ ID NO: 1325); and AA583399seg1 R reverse primer (SEQ ID NO: 1326).

Forward primer (SEQ ID NO: 1325):

GAATCAGCCCAAAGCCAGG

Reverse primer (SEQ ID NO: 1326):

GCTGGTGAAAGCACTGGGTT

Amplicon (SEQ ID NO: 1327):

GAATCAGCCCAAAGCCAGGCGTCCAGGGTCTCCCTCACCTGAAGCTGACT

TTTTCCCCACCTTGGACAGAGGGCGGGAGATGCCATCCCCACTGAACCCA

GTGCTTTCACCAGC

Description for Cluster AI684092

Cluster AI684092 features 2 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

AI684092_PEA_1_T2
693

AI684092_PEA_1_T3
694

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

AI684092_PEA_1_node_0
695

AI684092_PEA_1_node_2
696

AI684092_PEA_1_node_4
697

AI684092_PEA_1_node_5
698

AI684092_PEA_1_node_6
699

AI684092_PEA_1_node_7
700

AI684092_PEA_1_node_8
701

AI684092_PEA_1_node_9
702

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

AI684092_PEA_1_P1
703
AI684092_PEA_1_T2

(SEQ ID NO: 693)

AI684092_PEA_1_P3
704
AI684092_PEA_1_T3

(SEQ ID NO: 694)

Cluster AI684092 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 44 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

bone
0

brain
0

colon
0

epithelial
0

general
0

kidney
0

lung
0

lymph nodes
0

breast
17

ovary
0

prostate
0

stomach
0

uterus
0

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bone
1
6.7e−01
1
1.0
7.0e−01
1.4

brain
1
1.3e−01
1
1.0
3.8e−03
9.2

colon
1
4.8e−01
1
1.0
5.9e−01
1.6

epithelial
7.2e−02
2.0e−02
4.1e−02
3.9
8.9e−03
4.8

general
3.0e−03
2.0e−04
1.4e−04
8.1
1.2e−06
9.0

kidney
1
7.2e−01
1
1.0
4.9e−01
1.9

lung
1
6.3e−01
1
1.0
6.2e−01
1.6

lymph nodes
3.1e−01
5.7e−01
2.9e−01
3.5
5.8e−01
1.7

breast
8.2e−01
7.3e−01
6.9e−01
1.0
5.6e−01
1.2

ovary
6.2e−01
6.5e−01
6.8e−01
1.5
7.7e−01
1.3

prostate
7.3e−01
7.8e−01
6.7e−01
1.5
7.5e−01
1.3

stomach
3.6e−01
4.7e−01
1
1.0
8.0e−01
1.3

uterus
2.1e−01
4.0e−01
4.4e−01
2.0
6.4e−01
1.5

As noted above, cluster AI684092 features 2 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein AI684092_PEA_—1_P1 (SEQ ID NO:703) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AI684092_PEA_—1_T2 (SEQ ID NO:693). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein AI684092_PEA_—1_P1 (SEQ ID NO:703) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AI684092_PEA_—1_P1 (SEQ ID NO:703) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

137
C -> Y
Yes

160
S -> P
Yes

164
A -> D
Yes

168
S -> R
Yes

175
A -> D
Yes

Variant protein AI684092_PEA_—1_P1 (SEQ ID NO:703) is encoded by the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AI684092_PEA_—1_T2 (SEQ ID NO:693) is shown in bold; this coding portion starts at position 1480 and ends at position 2058. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AI684092_PEA_—1_P1 (SEQ ID NO:703) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

609
G -> A
Yes

807
T -> C
Yes

1284
T -> C
No

1295
T -> G
No

1889
G -> A
Yes

1932
C -> G
Yes

1941
C -> T
Yes

1957
T -> C
Yes

1970
C -> A
Yes

1983
T -> G
Yes

2003
C -> A
Yes

2019
C -> G
Yes

2052
G -> C
Yes

2142
A -> T
Yes

Variant protein AI684092_PEA_—1_P3 (SEQ ID NO:704) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) AI684092_PEA_—1_T3 (SEQ ID NO:694). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein AI684092_PEA_—1_P3 (SEQ ID NO:704) is encoded by the following transcript(s): AI684092_PEA_—1_T3 (SEQ ID NO:694), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript AI684092_PEA_—1_T3 (SEQ ID NO:694) is shown in bold; this coding portion starts at position 28 and ends at position 279. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein AI684092_PEA_—1_P3 (SEQ ID NO:704) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

609
G -> A
Yes

807
T -> C
Yes

1284
T -> C
No

1295
T -> G
No

1571
C -> A
Yes

1584
T -> G
Yes

1604
C -> A
Yes

1620
C -> G
Yes

1653
G -> C
Yes

1743
A -> T
Yes

As noted above, cluster AI684092 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster AI684092_PEA_—1_node_—0 (SEQ ID NO:695) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 9 below describes the starting and ending position of this segment on each transcript.

TABLE 9

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
1
368

AI684092_PEA_1_T3 (SEQ ID NO: 694)
1
368

Segment cluster AI684092_PEA_—1_node_—2 (SEQ ID NO:696) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 10 below describes the starting and ending position of this segment on each transcript.

TABLE 10

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
369
498

AI684092_PEA_1_T3 (SEQ ID NO: 694)
369
498

Segment cluster AI684092_PEA_—1_node_—4 (SEQ ID NO:697) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 11 below describes the starting and ending position of this segment on each transcript.

TABLE 11

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
499
665

AI684092_PEA_1_T3 (SEQ ID NO: 694)
499
665

Segment cluster AI684092_PEA_—1_node_—5 (SEQ ID NO:698) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 12 below describes the starting and ending position of this segment on each transcript.

TABLE 12

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
666
932

AI684092_PEA_1_T3 (SEQ ID NO: 694)
666
932

Segment cluster AI684092_PEA_—1_node_—6 (SEQ ID NO:699) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 13 below describes the starting and ending position of this segment on each transcript.

TABLE 13

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
933
1372

AI684092_PEA_1_T3 (SEQ ID NO: 694)
933
1372

Segment cluster AI684092_PEA_—1_node_—7 (SEQ ID NO:700) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 14 below describes the starting and ending position of this segment on each transcript.

TABLE 14

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
1373
1560

AI684092_PEA_1_T3 (SEQ ID NO: 694)
1373
1560

Segment cluster AI684092_PEA_—1_node_—8 (SEQ ID NO:701) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693). Table 15 below describes the starting and ending position of this segment on each transcript.

TABLE 15

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
1561
1959

Segment cluster AI684092_PEA_—1_node_—9 (SEQ ID NO:702) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): AI684092_PEA_—1_T2 (SEQ ID NO:693) and AI684092_PEA_—1_T3 (SEQ ID NO:694). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

AI684092_PEA_1_T2 (SEQ ID NO: 693)
1960
2195

AI684092_PEA_1_T3 (SEQ ID NO: 694)
1561
1796

Example 1
Expression of AA5315457 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name AA5315457seg8 (SEQ ID NO: 1330) in Normal and Cancerous Colon Tissues

Expression of AA5315457 transcripts detectable by or according to seg8, AA5315457 seg8 amplicon (SEQ ID NO: 1330) and AA5315457F (SEQ ID NO: 1328) AA5315457R (SEQ ID NO: 1329) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 45 is a histogram showing over expression of the above-indicated AA5315457 transcripts in cancerous colon samples relative to the normal samples. (Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.) The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 45, the expression of AA5315457 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1 above, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 10 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of AA5315457 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 1.66E-05.

Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 5.33E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AA5315457F forward primer (SEQ ID NO: 1328); and AA5315457R reverse primer (SEQ ID NO: 1329).

Forward primer (SEQ ID NO: 1328):

CATGGACCCCAGGCAAGTC

Reversr primer (SEQ ID NO: 1329):

CTGTTTAGGGTCGAGGCTGTG

Amplicon (SEQ ID NO: 1330):

CATGGACCCCAGGCAAGTCCCCCCACCCACGCATTTCTAATCATCTGCCC

TGGTTTTGCCTCCTGAGTCTGTTAAGGCTGTGTGCCCCTCATCGAGGCCC

GTCACAGCCTCGACCCTAAACAG

Description for Cluster HUMCACH1A

Cluster HUMCACH1A features 18 transcript(s) and 67 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HUMCACH1A_PEA_1_T0
705

HUMCACH1A_PEA_1_T1
706

HUMCACH1A_PEA_1_T2
707

HUMCACH1A_PEA_1_T3
708

HUMCACH1A_PEA_1_T4
709

HUMCACH1A_PEA_1_T6
710

HUMCACH1A_PEA_1_T7
711

HUMCACH1A_PEA_1_T8
712

HUMCACH1A_PEA_1_T12
713

HUMCACH1A_PEA_1_T13
714

HUMCACH1A_PEA_1_T14
715

HUMCACH1A_PEA_1_T15
716

HUMCACH1A_PEA_1_T16
717

HUMCACH1A_PEA_1_T17
718

HUMCACH1A_PEA_1_T18
719

HUMCACH1A_PEA_1_T19
720

HUMCACH1A_PEA_1_T20
721

HUMCACH1A_PEA_1_T22
722

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMCACH1A_PEA_1_node_2
723

HUMCACH1A_PEA_1_node_5
724

HUMCACH1A_PEA_1_node_9
725

HUMCACH1A_PEA_1_node_11
726

HUMCACH1A_PEA_1_node_14
727

HUMCACH1A_PEA_1_node_16
728

HUMCACH1A_PEA_1_node_27
729

HUMCACH1A_PEA_1_node_30
730

HUMCACH1A_PEA_1_node_33
731

HUMCACH1A_PEA_1_node_41
732

HUMCACH1A_PEA_1_node_43
733

HUMCACH1A_PEA_1_node_45
734

HUMCACH1A_PEA_1_node_47
735

HUMCACH1A_PEA_1_node_55
736

HUMCACH1A_PEA_1_node_57
737

HUMCACH1A_PEA_1_node_70
738

HUMCACH1A_PEA_1_node_72
739

HUMCACH1A_PEA_1_node_74
740

HUMCACH1A_PEA_1_node_86
741

HUMCACH1A_PEA_1_node_92
742

HUMCACH1A_PEA_1_node_94
743

HUMCACH1A_PEA_1_node_103
744

HUMCACH1A_PEA_1_node_104
745

HUMCACH1A_PEA_1_node_106
746

HUMCACH1A_PEA_1_node_109
747

HUMCACH1A_PEA_1_node_113
748

HUMCACH1A_PEA_1_node_114
749

HUMCACH1A_PEA_1_node_116
750

HUMCACH1A_PEA_1_node_119
751

HUMCACH1A_PEA_1_node_121
752

HUMCACH1A_PEA_1_node_123
753

HUMCACH1A_PEA_1_node_125
754

HUMCACH1A_PEA_1_node_128
755

HUMCACH1A_PEA_1_node_0
756

HUMCACH1A_PEA_1_node_3
757

HUMCACH1A_PEA_1_node_7
758

HUMCACH1A_PEA_1_node_23
759

HUMCACH1A_PEA_1_node_26
760

HUMCACH1A_PEA_1_node_32
761

HUMCACH1A_PEA_1_node_35
762

HUMCACH1A_PEA_1_node_37
763

HUMCACH1A_PEA_1_node_39
764

HUMCACH1A_PEA_1_node_49
765

HUMCACH1A_PEA_1_node_51
766

HUMCACH1A_PEA_1_node_53
767

HUMCACH1A_PEA_1_node_58
768

HUMCACH1A_PEA_1_node_60
769

HUMCACH1A_PEA_1_node_62
770

HUMCACH1A_PEA_1_node_64
771

HUMCACH1A_PEA_1_node_66
772

HUMCACH1A_PEA_1_node_68
773

HUMCACH1A_PEA_1_node_76
774

HUMCACH1A_PEA_1_node_77
775

HUMCACH1A_PEA_1_node_79
776

HUMCACH1A_PEA_1_node_81
777

HUMCACH1A_PEA_1_node_84
778

HUMCACH1A_PEA_1_node_88
779

HUMCACH1A_PEA_1_node_90
780

HUMCACH1A_PEA_1_node_96
781

HUMCACH1A_PEA_1_node_98
782

HUMCACH1A_PEA_1_node_100
783

HUMCACH1A_PEA_1_node_101
784

HUMCACH1A_PEA_1_node_107
785

HUMCACH1A_PEA_1_node_111
786

HUMCACH1A_PEA_1_node_117
787

HUMCACH1A_PEA_1_node_124
788

HUMCACH1A_PEA_1_node_126
789

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HUMCACH1A_PEA_1_P2
792
HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705);

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706);

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707);

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708);

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)

HUMCACH1A_PEA_1_P3
793
HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)

HUMCACH1A_PEA_1_P4
794
HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)

HUMCACH1A_PEA_1_P5
795
HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)

HUMCACH1A_PEA_1_P7
796
HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)

HUMCACH1A_PEA_1_P8
797
HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)

HUMCACH1A_PEA_1_P9
798
HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)

HUMCACH1A_PEA_1_P10
799
HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)

HUMCACH1A_PEA_1_P11
800
HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)

HUMCACH1A_PEA_1_P12
801
HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)

HUMCACH1A_PEA_1_P13
802
HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)

HUMCACH1A_PEA_1_P14
803
HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)

HUMCACH1A_PEA_1_P15
804
HUMCACH1A_PEA_1_T20 (SEQ ID NO: 721)

HUMCACH1A_PEA_1_P17
805
HUMCACH1A_PEA_1_T22 (SEQ ID NO: 722)

These sequences are variants of the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SwissProt accession identifier CCAD_HUMAN; known also according to the synonyms Calcium channel, L type, alpha-1 polypeptide, isoform 2), SEQ ID NO: 790, referred to herein as the previously known protein.

Protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790) is known or believed to have the following function(s): Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the “high-voltage activated” (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-aga-IVA). The sequence for protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790) is given at the end of the application, as “Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790) amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

1
M -> MM (in a NIDDM patient).

/FTId = VAR_001497.

576
S -> T

637
C -> S

650
S -> I

918
I -> T

960
M -> I

1289-1290
Missing

1346
F -> S

1433
H -> Y

Protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790) localization is believed to be Integral membrane protein.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: transport; cation transport; calcium ion transport, which are annotation(s) related to Biological Process; calcium binding; dihydropyridine-sensitive calcium channel, which are annotation(s) related to Molecular Function; and voltage-gated calcium channel; integral membrane protein, which are annotation(s) related to Cellular Component.

Cluster HUMCACH1A can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 46 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

adrenal
0

brain
27

colon
0

epithelial
13

general
13

lung
51

ovary
0

pancreas
32

prostate
4

skin
0

stomach
0

uterus
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
6.1e−01
6.6e−01
2.1e−01
3.4
2.9e−01
2.7

brain
8.7e−01
8.9e−01
9.2e−01
0.4
9.8e−01
0.3

colon
1.1e−01
1.1e−01
4.9e−01
2.2
4.6e−01
2.0

epithelial
2.6e−02
2.2e−01
8.8e−03
2.4
2.5e−01
1.3

general
7.1e−03
1.7e−01
4.3e−03
2.0
4.0e−01
1.0

lung
8.7e−01
9.2e−01
9.6e−01
0.6
1
0.3

ovary
6.2e−01
6.5e−01
6.8e−01
1.5
7.7e−01
1.3

pancreas
4.3e−01
6.5e−01
5.0e−01
1.2
7.0e−01
0.9

prostate
3.1e−01
4.7e−01
1.2e−02
4.9
4.2e−02
3.6

skin
1
4.4e−01
1
1.0
6.4e−01
1.6

stomach
3.0e−01
6.7e−01
1.3e−01
3.0
5.1e−01
1.5

uterus
4.7e−01
6.4e−01
6.6e−01
1.5
8.0e−01
1.2

As noted above, cluster HUMCACH1A features 18 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790). A description of each variant protein according to the present invention is now provided.

Variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708) and HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP Position(s) on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

577
I -> M
Yes

809
N ->
No

1038
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708) and HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705) is shown in bold; this coding portion starts at position 512 and ends at position 7054. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP Position on uncleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

6919
C -> T
Yes

7383
A -> G
Yes

7701
A -> G
Yes

8070
C -> T
Yes

8117
T -> A
Yes

8361
T -> C
Yes

8544
G -> A
Yes

8632
A -> C
Yes

8685
A -> G
Yes

9028
G -> A
Yes

9375
G ->
No

9375
G -> A
No

The coding portion of transcript HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706) is shown in bold; this coding portion starts at position 89 and ends at position 6631. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

547
T -> C
Yes

1192
C -> T
Yes

1819
T -> G
Yes

1873
C -> T
No

1958
T -> C
Yes

2514
A ->
No

2848
C -> T
Yes

3201
T -> C
No

3214
C -> T
Yes

6496
C -> T
Yes

6960
A -> G
Yes

7278
A -> G
Yes

7647
C -> T
Yes

7694
T -> A
Yes

7938
T -> C
Yes

8121
G -> A
Yes

8209
A -> C
Yes

8262
A -> G
Yes

8605
G -> A
Yes

8952
G ->
No

8952
G -> A
No

The coding portion of transcript HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707) is shown in bold; this coding portion starts at position 512 and ends at position 7054. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

6919
C -> T
Yes

7383
A -> G
Yes

7701
A -> G
Yes

8070
C -> T
Yes

8117
T -> A
Yes

8361
T -> C
Yes

8544
G -> A
Yes

8632
A -> C
Yes

8685
A -> G
Yes

9028
G -> A
Yes

The coding portion of transcript HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708) is shown in bold; this coding portion starts at position 512 and ends at position 7054. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

6919
C -> T
Yes

7383
A -> G
Yes

7701
A -> G
Yes

8070
C -> T
Yes

The coding portion of transcript HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709) is shown in bold; this coding portion starts at position 512 and ends at position 7054. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P2 (SEQ ID NO:792) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

6919
C -> T
Yes

7383
A -> G
Yes

7701
A -> G
Yes

Variant protein HUMCACH1A_PEA_—1_P3 (SEQ ID NO:793) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P3 (SEQ ID NO:793) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P3 (SEQ ID NO:793) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

577
I -> M
Yes

809
N ->
No

1038
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P3 (SEQ ID NO:793) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710) is shown in bold; this coding portion starts at position 512 and ends at position 6157. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P3 (SEQ ID NO:793) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

6312
G -> A
Yes

7098
C -> T
Yes

7562
A -> G
Yes

7880
A -> G
Yes

8249
C -> T
Yes

8296
T -> A
Yes

8540
T -> C
Yes

8723
G -> A
Yes

8811
A -> C
Yes

8864
A -> G
Yes

9207
G -> A
Yes

9554
G ->
No

9554
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P4 (SEQ ID NO:794) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P4 (SEQ ID NO:794) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 15, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P4 (SEQ ID NO:794) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

577
I -> M
Yes

809
N ->
No

1038
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P4 (SEQ ID NO:794) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711) is shown in bold; this coding portion starts at position 512 and ends at position 7027. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P4 (SEQ ID NO:794) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

6892
C -> T
Yes

7356
A -> G
Yes

7674
A -> G
Yes

8043
C -> T
Yes

8090
T -> A
Yes

8334
T -> C
Yes

8517
G -> A
Yes

8605
A -> C
Yes

8658
A -> G
Yes

9001
G -> A
Yes

9348
G ->
No

9348
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P5 (SEQ ID NO:795) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P5 (SEQ ID NO:795) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P5 (SEQ ID NO:795) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

557
I -> M
Yes

789
N ->
No

1018
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P5 (SEQ ID NO:795) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712) is shown in bold; this coding portion starts at position 512 and ends at position 6994. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P5 (SEQ ID NO:795) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2182
T -> G
Yes

2236
C -> T
No

2321
T -> C
Yes

2877
A ->
No

3211
C -> T
Yes

3564
T -> C
No

3577
C -> T
Yes

6859
C -> T
Yes

7323
A -> G
Yes

7641
A -> G
Yes

8010
C -> T
Yes

8057
T -> A
Yes

8301
T -> C
Yes

8484
G -> A
Yes

8572
A -> C
Yes

8625
A -> G
Yes

8968
G -> A
Yes

9315
G ->
No

9315
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713). An alignment is given to the known protein (Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796) and CCAD_HUMAN_V3 (SEQ ID NO:791):

1. An isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), comprising a first amino acid sequence being at least 90% homologous to MPTSETESVNTENVSGEGENRGCCGSL corresponding to amino acids 466-492 of CCAD_HUMAN_V3 (SEQ ID NO:791), which also corresponds to amino acids 1-27 of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WCWWRRRGAAKAGPSGCRRWG (SEQ ID NO:1573) corresponding to amino acids 28-48 of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), and a third amino acid sequence being at least 90% homologous to QAISKSKLSRRWRRWNRFNRRRCRAAVKSVTFYWLVIVLVFLNTLTISSEHYNQPDWLTQIQDIANKVLL ALFTCEMLVKMYSLGLQAYFVSLFNRFDCFVVCGGITETILVELEIMSPLGISVFRCVRLLRIFKVTRHWTS LSNLVASLLNSMKSIASLLLLLFLFIIIFSLLGMQLFGGKFNFDETQTKRSTFDNFPQALLTVFQILTGEDWN AVMYDGIMAYGGPSSSGMIVCIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEAEEKERKKIARK ESLENKKNNKPEVNQIANSDNKVTIDDYREEDEDKDPYPPCDVPVGEEEEEEEEDEPEVPAGPRPRRISELN MKEKIAPIPEGSAFFILSKTNPIRVGCHKLINHHIFTNLILVFIMLSSAALAAEDPIRSHSFRNTILGYFDYAFT AIFTVEILLKMTTFGAFLHKGAFCRNYFNLLDMLVVGVSLVSFGIQSSAISVVKILRVLRVLRPLRAINRAK GLKHVVQCVFVAIRTIGNIMIVTTLLQFMFACIGVQLFKGKFYRCTDEAKSNPEECRGLFILYKDGDVDSP VVRERIWQNSDFNFDNVLSAMMALFTVSTFEGWPALLYKAIDSNGENIGPIYNHRVEISIFFIIYIIIVAFFM MNIFVGFVIVTFQEQGEKEYKNCELDKNQRQCVEYALKARPLRRYIPKNPYQYKFWYVVNSSPFEYMMF VLIMLNTLCLAMQHYEQSKMFNDAMDILNMVFTGVFTVEMVLKVIAFKPKGYFSDAWNTFDSLIVIGSIID VALSEADPTESENVPVPTATPGNSEESNRISITFFRLFRVMRLVKLLSRGEGIRTLLWTFIKSFQALPYVALLI AMLFFIYAVIGMQMFGKVAMRDNNQINRNNNFQTFPQAVLLLFRCATGEAWQEIMLACLPGKLCDPESD YNPGEEYTCGSNFAIVYFISFYMLCAFLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWSEYDPEAKG RIKHLDVVTLLRRIQPPLGFGKLCPHRVACKRLVAMNMPLNSDGTVMFNATLFALVRTALKIKTEGNLEQ ANEELRAVIKKIWKKTSMKLLDQVVPPAGDDEVTVGKFYATFLIQDYFRKFKKRKEQGLVGKYPAKNTTI ALQAGLRTLHDIGPEIRRAISCDLQDDEPEETKREEEDDVFKRNGALLGNHVNHVNSDRRDSLQQTNTTH RPLHVQRPSIPPASDTEKPLFPPAGNSVCHNHHNHNSIGKQVPTSTNANLNNANMSKAAHGKRPSIGNLEH VSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEEC YEDDSSPTWSRQNYGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSS FNFECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDW TPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSLVEAV LISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVGPLSHRQDYELQDFGPG YSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 494-2161 of CCAD_HUMAN_V3 (SEQ ID NO:791), which also corresponds to amino acids 49-1716 of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for WCWWRRRGAAKAGPSGCRRWG (SEQ ID NO:1573), corresponding to HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796).

3. A bridge portion of HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise L, having a structure as follows (numbering according to HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796)): a sequence starting from any of amino acid numbers 492−x to 492; and ending at any of amino acid numbers 28+((n−2)−x), in which x varies from 0 to n−2.

It should be noted that the known protein sequence (CCAD_HUMAN (SEQ ID NO:790)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CCAD_HUMAN_V3 (SEQ ID NO:791). These changes were previously known to occur and are listed in the table below.

TABLE 19

Changes to CCAD_HUMAN_V3 (SEQ ID NO: 791)

SNP position(s) on amino

acid sequence
Type of change

638
conflict

651
conflict

1347
conflict

1434
conflict

The location or the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

112
I -> M
Yes

344
N ->
No

573
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713) is shown in bold; this coding portion starts at position 240 and ends at position 5387. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P7 (SEQ ID NO:796) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

575
T -> G
Yes

629
C -> T
No

714
T -> C
Yes

1270
A ->
No

1604
C -> T
Yes

1957
T -> C
No

1970
C -> T
Yes

5252
C -> T
Yes

5716
A -> G
Yes

6034
A -> G
Yes

6403
C -> T
Yes

6450
T -> A
Yes

6694
T -> C
Yes

6877
G -> A
Yes

6965
A -> C
Yes

7018
A -> G
Yes

7361
G -> A
Yes

7708
G ->
No

7708
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P8 (SEQ ID NO:797) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P8 (SEQ ID NO:797) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 22, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P8 (SEQ ID NO:797) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

577
I -> M
Yes

809
N ->
No

1038
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P8 (SEQ ID NO:797) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714) is shown in bold; this coding portion starts at position 512 and ends at position 88889. The transcript also has the following SNPs as listed in Table 23 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P8 (SEQ ID NO:797) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

Variant protein HUMCACH1A_PEA_—1_P9 (SEQ ID NO:798) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P9 (SEQ ID NO:798) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 24, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P9 (SEQ ID NO:798) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

577
I -> M
Yes

809
N ->
No

1038
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P9 (SEQ ID NO:798) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) is shown in bold; this coding portion starts at position 512 and ends at position 5386. The transcript also has the following SNPs as listed in Table 25 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P9 (SEQ ID NO:798) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

Variant protein HUMCACH1A_PEA_—1_P10 (SEQ ID NO:799) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P10 (SEQ ID NO:799) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 26, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P10 (SEQ ID NO:799) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

577
I -> M
Yes

809
N ->
No

1038
I -> T
No

Variant protein HUMCACH1A_PEA_—1_P10 (SEQ ID NO:799) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) is shown in bold; this coding portion starts at position 512 and ends at position 88889. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P10 (SEQ ID NO:799) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

3624
T -> C
No

3637
C -> T
Yes

Variant protein HUMCACH1A_PEA_—1_P11 (SEQ ID NO:800) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P11 (SEQ ID NO:800) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 28, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P11 (SEQ ID NO:800) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 28

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

577
I -> M
Yes

809
N ->
No

Variant protein HUMCACH1A_PEA_—1_P11 (SEQ ID NO:800) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717) is shown in bold; this coding portion starts at position 512 and ends at position 88889. The transcript also has the following SNPs as listed in Table 29 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P11 (SEQ ID NO:800) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

2242
T -> G
Yes

2296
C -> T
No

2381
T -> C
Yes

2937
A ->
No

3271
C -> T
Yes

Variant protein HUMCACH1A_PEA_—1_P12 (SEQ ID NO:801) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P12 (SEQ ID NO:801) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718) is shown in bold; this coding portion starts at position 1 and ends at position 2644. The transcript also has the following SNPs as listed in Table 30 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P12 (SEQ ID NO:801) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 30

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

2509
C -> T
Yes

2973
A -> G
Yes

3291
A -> G
Yes

3660
C -> T
Yes

3707
T -> A
Yes

3951
T -> C
Yes

4134
G -> A
Yes

4222
A -> C
Yes

4275
A -> G
Yes

4618
G -> A
Yes

4965
G ->
No

4965
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719). An alignment is given to the known protein (Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802) and CCAD_HUMAN (SEQ ID NO:790):

1. An isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL (SEQ ID NO:1477) corresponding to amino acids 1-47 of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), and a second amino acid sequence being at least 90% homologous to DDEVTVGKFYATFLIQDYFRKFKKRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRRAISCDLQDDEPE ETKREEEDDVFKRNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPLFPPAGNSVCH NHHNHNSIGKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYY ETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSE RPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPHRTALPLH LMQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSS WYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLT IDEMESAASTLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1598-2161 of CCAD_HUMAN (SEQ ID NO:790), which also corresponds to amino acids 48-611 of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL (SEQ ID NO:1477) of HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

The glycosylation sites of variant protein HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), as compared to the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790), are described in Table 31 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 31

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

225
no

155
no

329
no

The phosphorilation sites of variant protein HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802), as compared to the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790), are described in Table 32 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorilation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 32

Phosphorilation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

1475
no

Variant protein HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) is shown in bold; this coding portion starts at position 63 and ends at position 1895. The transcript also has the following SNPs as listed in Table 33 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P13 (SEQ ID NO:802) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 33

Nucleic acid SNPs

SNP position on

nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

1760
C -> T
Yes

2224
A -> G
Yes

2542
A -> G
Yes

2911
C -> T
Yes

2958
T -> A
Yes

3202
T -> C
Yes

3385
G -> A
Yes

3473
A -> C
Yes

3526
A -> G
Yes

3869
G -> A
Yes

4216
G ->
No

4216
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). An alignment is given to the known protein (Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803) and CCAD_HUMAN (SEQ ID NO:790):

1. An isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803), comprising a first amino acid sequence being at least 90% homologous to MSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLPTICREDPEIHGYF RDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRS PRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHST RSWATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNK NSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVG PLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1763-2161 of CCAD_HUMAN (SEQ ID NO:790), which also corresponds to amino acids 1-399 of HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

The glycosylation sites of variant protein HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803), as compared to the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790), are described in Table 34 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 34

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

225
no

155
no

329
no

The phosphorilation sites of variant protein HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803), as compared to the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790), are described in Table 35 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorilation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 35

Phosphorilation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

1475
no

Variant protein HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720) is shown in bold; this coding portion starts at position 1820 and ends at position 3016. The transcript also has the following SNPs as listed in Table 36 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P14 (SEQ ID NO:803) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 36

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

84
G -> T
Yes

542
G -> A
Yes

579
G -> A
Yes

690
A -> G
Yes

890
C -> T
Yes

2881
C -> T
Yes

3345
A -> G
Yes

3663
A -> G
Yes

4032
C -> T
Yes

4079
T -> A
Yes

4323
T -> C
Yes

4506
G -> A
Yes

4594
A -> C
Yes

4647
A -> G
Yes

4990
G -> A
Yes

5337
G ->
No

5337
G -> A
No

Variant protein HUMCACH1A_PEA_—1_P15 (SEQ ID NO:804) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P15 (SEQ ID NO:804) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) is shown in bold; this coding portion starts at position 512 and ends at position 1732. The transcript also has the following SNPs as listed in Table 37 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P15 (SEQ ID NO:804) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 37

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

Variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). An alignment is given to the known protein (Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805) and CCAD_HUMAN (SEQ ID NO:790):

1. An isolated chimeric polypeptide encoding for HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), comprising a first amino acid sequence being at least 90% homologous to MMMMMMMKKMQHQRQQQADHANEANYARGTRLPLSGEGPTSQPNSSKQTVLSWQAAIDAARQAKAA QTMSTSAPPPVGSLSQRKRQQYAKSKKQGNSSNSRPARALFCLSLNNPIRRACISIVEWKPFDIFILLAIFAN CVALAIYIPFPEDDSNSTNHNLEKVEYAFLIIFTVETFLKIIAYGLLLHPNAYVRNGWNLLDFVIVIVGLFSVI LEQLTKETEGGNHSSGKSGGFDVKALRAFRVLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYA IIGLELFIGKMHKTCFFADSDIVAEEDPAPCAFSGNGRQCTANGTECRSGWVGPNGGITNFDNFAFAMLTV FQCITMEGWTDVLYWMNDAMGFELPWVYFVSLVIFGSFFVLNLVLGVLSG corresponding to amino acids 1-407 of CCAD_HUMAN (SEQ ID NO:790), which also corresponds to amino acids 1-407 of HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence HGGSRL (SEQ ID NO:1478) corresponding to amino acids 408-413 of HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence HGGSRL (SEQ ID NO:1478) in HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 38, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 38

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

409
G -> S
No

The glycosylation sites or variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), as compared to the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790), are described in Table 39 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 39

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

225
yes
225

155
yes
155

329
yes
329

The phosphorilation sites of variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805), as compared to the known protein Voltage-dependent L-type calcium channel alpha-1D subunit (SEQ ID NO:790), are described in Table 40 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the phosphorilation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 40

Phosphorilation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

1475
no

Variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805) is encoded by the following transcript(s): HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722) is shown in bold; this coding portion starts at position 512 and ends at position 1750. The transcript also has the following SNPs as listed in Table 41 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCACH1A_PEA_—1_P17 (SEQ ID NO:805) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 41

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

331
T -> A
Yes

422
C -> T
Yes

458
T -> C
Yes

970
T -> C
Yes

1615
C -> T
Yes

1736
G -> A
No

1848
G -> A
No

2004
A -> T
Yes

2006
C -> T
Yes

2020
A ->
Yes

2045
A -> G
Yes

2235
G -> A
Yes

2432
C -> A
Yes

2565
T -> A
Yes

2749
C -> T
Yes

2887
C -> T
Yes

3099
A -> G
Yes

3319
C -> T
Yes

As noted above, cluster HUMCACH1A features 67 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMCACH1A_PEA_—1_node_—2 (SEQ ID NO:723) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1
468

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1
468

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1
468

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1
468

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1
468

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1
468

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1
468

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
1
468

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
1
468

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
1
468

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
1
468

717)

HUMCACH1A_PEA_1_T20 (SEQ ID NO:
1
468

721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO:
1
468

722)

Segment cluster HUMCACH1A_PEA_—1_node_—5 (SEQ ID NO:724) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
579
888

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
156
465

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
579
888

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
579
888

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
579
888

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
579
888

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
579
888

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
579
888

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
579
888

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
579
888

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
579
888

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
579
888

717)

HUMCACH1A_PEA_1_T20 (SEQ ID NO:
579
888

721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO:
579
888

722)

Segment cluster HUMCACH1A_PEA_—1_node_—9 (SEQ ID NO:725) according to the present invention is supported by 0 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
995
1134

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
572
711

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
995
1134

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
995
1134

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
995
1134

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
995
1134

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
995
1134

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
995
1134

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
995
1134

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
995
1134

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
995
1134

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
995
1134

717)

HUMCACH1A_PEA_1_T20 (SEQ ID NO:
995
1134

721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO:
995
1134

722)

Segment cluster HUMCACH1A_PEA_—1_node_—11 (SEQ ID NO:726) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1135
1277

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
712
854

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1135
1277

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1135
1277

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1135
1277

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1135
1277

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1135
1277

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1135
1277

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
1135
1277

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
1135
1277

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
1135
1277

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
1135
1277

717)

HUMCACH1A_PEA_1_T20 (SEQ ID NO:
1135
1277

721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO:
1135
1277

722)

Segment cluster HUMCACH1A_PEA_—1_node_—14 (SEQ ID NO:727) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1278
1430

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
855
1007

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1278
1430

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1278
1430

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1278
1430

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1278
1430

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1278
1430

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1278
1430

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
1278
1430

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
1278
1430

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
1278
1430

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
1278
1430

717)

HUMCACH1A_PEA_1_T20 (SEQ ID NO:
1278
1430

721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO:
1278
1430

722)

Segment cluster HUMCACH1A_PEA_—1_node_—16 (SEQ ID NO:728) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1431
1627

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1008
1204

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1431
1627

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1431
1627

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1431
1627

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1431
1627

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1431
1627

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1431
1627

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
1431
1627

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
1431
1627

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
1431
1627

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
1431
1627

717)

HUMCACH1A_PEA_1_T20 (SEQ ID NO:
1431
1627

721)

HUMCACH1A_PEA_1_T22 (SEQ ID NO:
1431
1627

722)

Segment cluster HUMCACH1A_PEA_—1_node_—27 (SEQ ID NO:729) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCACH1A_PEA_1_T20 (SEQ
1732
1973

ID NO: 721)

Segment cluster HUMCACH1A_PEA_—1_node_—30 (SEQ ID NO:730) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCACH1A_PEA_1_T22 (SEQ
1732
3379

ID NO: 722)

Segment cluster HUMCACH1A_PEA_—1_node_—33 (SEQ ID NO:731) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1732
1901

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1309
1478

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1732
1901

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1732
1901

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1732
1901

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1732
1901

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1732
1901

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1732
1901

HUMCACH1A_PEA_1_T12 (SEQ ID NO:
65
234

713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
1732
1901

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
1732
1901

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
1732
1901

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
1732
1901

717)

Segment cluster HUMCACH1A_PEA_—1_node_—41 (SEQ ID NO:732) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2077
2237

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1654
1814

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2077
2237

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2077
2237

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2077
2237

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2077
2237

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2077
2237

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2017
2177

HUMCACH1A_PEA_1_T12 (SEQ ID NO:
410
570

713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
2077
2237

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
2077
2237

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
2077
2237

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
2077
2237

717)

Segment cluster HUMCACH1A_PEA_—1_node_—43 (SEQ ID NO:733) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2238
2463

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1815
2040

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2238
2463

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2238
2463

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2238
2463

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2238
2463

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2238
2463

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2178
2403

HUMCACH1A_PEA_1_T12 (SEQ ID NO:
571
796

713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
2238
2463

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
2238
2463

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
2238
2463

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
2238
2463

717)

Segment cluster HUMCACH1A_PEA_—1_node_—45 (SEQ ID NO:734) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2464
2671

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2041
2248

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2464
2671

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2464
2671

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2464
2671

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2464
2671

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2464
2671

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2404
2611

HUMCACH1A_PEA_1_T12 (SEQ ID NO:
797
1004

713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
2464
2671

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
2464
2671

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
2464
2671

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
2464
2671

717)

Segment cluster HUMCACH1A_PEA_—1_node_—47 (SEQ ID NO:735) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2672
2792

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2249
2369

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2672
2792

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2672
2792

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2672
2792

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2672
2792

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2672
2792

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2612
2732

HUMCACH1A_PEA_1_T12 (SEQ ID NO:
1005
1125

713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
2672
2792

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
2672
2792

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
2672
2792

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
2672
2792

717)

Segment cluster HUMCACH1A_PEA_—1_node_—55 (SEQ ID NO:736) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3045
3192

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2622
2769

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3045
3192

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3045
3192

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3045
3192

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3045
3192

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3045
3192

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2985
3132

HUMCACH1A_PEA_1_T12 (SEQ ID NO:
1378
1525

713)

HUMCACH1A_PEA_1_T13 (SEQ ID NO:
3045
3192

714)

HUMCACH1A_PEA_1_T14 (SEQ ID NO:
3045
3192

715)

HUMCACH1A_PEA_1_T15 (SEQ ID NO:
3045
3192

716)

HUMCACH1A_PEA_1_T16 (SEQ ID NO:
3045
3192

717)

Segment cluster HUMCACH1A_PEA_—1_node_—57 (SEQ ID NO:737) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3193
3322

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2770
2899

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3193
3322

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3193
3322

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3193
3322

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3193
3322

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3193
3322

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3133
3262

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1526
1655

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3193
3322

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3193
3322

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3193
3322

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
3193
3322

Segment cluster HUMCACH1A_PEA_—1_node_—70 (SEQ ID NO:738) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3739
3885

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3316
3462

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3739
3885

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3739
3885

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3739
3885

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3739
3885

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3739
3885

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3679
3825

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2072
2218

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3739
3885

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3739
3885

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3739
3885

Segment cluster HUMCACH1A_PEA_—1_node_—72 (SEQ ID NO:739) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3886
4087

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3463
3664

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3886
4087

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3886
4087

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3886
4087

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3886
4087

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3886
4087

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3826
4027

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2219
2420

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3886
4087

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3886
4087

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3886
4087

Segment cluster HUMCACH1A_PEA_—1_node_—74 (SEQ ID NO:740) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4088
4246

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3665
3823

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4088
4246

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4088
4246

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4088
4246

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4088
4246

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4088
4246

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4028
4186

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2421
2579

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4088
4246

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4088
4246

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
4088
4246

Segment cluster HUMCACH1A_PEA_—1_node_—86 (SEQ ID NO:741) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4487
4615

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4064
4192

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4487
4615

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4487
4615

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4487
4615

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4487
4615

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4487
4615

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4427
4555

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2820
2948

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4487
4615

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4487
4615

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
77
205

Segment cluster HUMCACH1A_PEA_—1_node_—92 (SEQ ID NO:742) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4774
4933

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4351
4510

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4774
4933

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4774
4933

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4774
4933

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4774
4933

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4774
4933

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4714
4873

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3107
3266

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4774
4933

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4774
4933

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
364
523

Segment cluster HUMCACH1A_PEA_—1_node_—94 (SEQ ID NO:743) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4934
5061

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4511
4638

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4934
5061

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4934
5061

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4934
5061

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4934
5061

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4934
5061

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4874
5001

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3267
3394

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4934
5061

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4934
5061

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
524
651

Segment cluster HUMCACH1A_PEA_—1_node_—103 (SEQ ID NO:744) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment locationon transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T18
1
204

(SEQ ID NO: 719)

Segment cluster HUMCACH1A_PEA_—1_node_—104 (SEQ ID NO:745) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718) and HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5364
5494

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4941
5071

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5364
5494

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5364
5494

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5364
5494

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5364
5494

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5364
5494

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5304
5434

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3697
3827

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5364
5494

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
954
1084

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
205
335

Segment cluster HUMCACH1A_PEA_—1_node_—106 (SEQ ID NO:746) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T19
1
1456

(SEQ ID NO: 720)

Segment cluster HUMCACH1A_PEA_—1_node_—109 (SEQ ID NO:747) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5612
5979

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
5189
5556

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5612
5979

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5612
5979

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5612
5979

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5612
5979

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5612
5979

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5552
5919

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3945
4312

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5612
5979

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1202
1569

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
453
820

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
1574
1941

Segment cluster HUMCACH1A_PEA_—1_node_—113 (SEQ ID NO:748) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
6007
6156

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
5584
5733

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
6007
6156

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
6007
6156

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
6007
6156

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
6007
6156

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5980
6129

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5947
6096

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
4340
4489

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5980
6129

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1597
1746

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
848
997

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
1969
2118

Segment cluster HUMCACH1A_PEA_—1_node_—114 (SEQ ID NO:749) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T6
6157
6335

(SEQ ID NO: 710)

Segment cluster HUMCACH1A_PEA_—1_node_—116 (SEQ ID NO:750) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 69 below describes the starting and ending position of this segment on each transcript.

TABLE 69

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
6157
6320

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
5734
5897

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
6157
6320

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
6157
6320

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
6157
6320

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
6336
6499

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
6130
6293

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
6097
6260

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
4490
4653

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
6130
6293

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1747
1910

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
998
1161

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
2119
2282

Segment cluster HUMCACH1A_PEA_—1_node_—119 (SEQ ID NO:751) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70

Segment location on transcripts

Seg-

ment
Segment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
6321
6442

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
5898
6019

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
6321
6442

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
6321
6442

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
6321
6442

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
6500
6621

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
6294
6415

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
6261
6382

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
4654
4775

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1911
2032

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
1162
1283

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
2283
2404

Segment cluster HUMCACH1A_PEA_—1_node_—12 (SEQ ID NO:752) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
6443
6763

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
6020
6340

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
6443
6763

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
6443
6763

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
6443
6763

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
6622
6942

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
6416
6736

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
6383
6703

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
4776
5096

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
2033
2353

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
1284
1604

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
2405
2725

Segment cluster HUMCACH1A_PEA_—1_node_—123 (SEQ ID NO:753) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
6764
7550

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
6341
7127

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
6764
7550

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
6764
7550

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
6764
7550

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
6943
7729

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
6737
7523

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
6704
7490

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
5097
5883

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
2354
3140

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
1605
2391

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
2726
3512

Segment cluster HUMCACH1A_PEA_—1_node_—125 (SEQ ID NO:754) according to the present invention is supported by 48 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 73 below describes the starting and ending position of this segment on each transcript.

TABLE 73

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
7650
9310

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
7227
8887

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
7650
9310

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
7650
8114

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
7650
7850

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
7829
9489

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
7623
9283

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
7590
9250

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
5983
7643

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
3240
4900

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
2491
4151

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
3612
5272

Segment cluster HUMCACH1A_PEA_—1_node_—128 (SEQ ID NO:755) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707). Table 74 below describes the starting and ending position of this segment on each transcript.

TABLE 74

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCACH1A_PEA_1_T2
9311
9458

(SEQ ID NO: 707)

Segment cluster HUMCACH1A_PEA_—1_node_—0 (SEQ ID NO:756) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706). Table 75 below describes the starting and ending position of this segment on each transcript.

TABLE 75

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCACH1A_PEA_1_T1
1
45

(SEQ ID NO: 706)

Segment cluster HUMCACH1A_PEA_—1_node_—3 (SEQ ID NO:757) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 76 below describes the starting and ending position of this segment on each transcript.

TABLE 76

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
469
578

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
46
155

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
469
578

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
469
578

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
469
578

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
469
578

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
469
578

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
469
578

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
469
578

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
469
578

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
469
578

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
469
578

HUMCACH1A_PEA_1_T20 (SEQ ID NO: 721)
469
578

HUMCACH1A_PEA_1_T22 (SEQ ID NO: 722)
469
578

Segment cluster HUMCACH1A_PEA_—1_node_—7 (SEQ ID NO:758) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717), HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 77 below describes the starting and ending position of this segment on each transcript.

TABLE 77

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
889
994

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
466
571

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
889
994

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
889
994

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
889
994

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
889
994

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
889
994

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
889
994

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
889
994

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
889
994

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
889
994

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
889
994

HUMCACH1A_PEA_1_T20 (SEQ ID NO: 721)
889
994

HUMCACH1A_PEA_1_T22 (SEQ ID NO: 722)
889
994

Segment cluster HUMCACH1A_PEA_—1_node_—23 (SEQ ID NO:759) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712) and HUMCACH1A_PEA_—1_T22 (SEQ ID NO:722). Table 78 below describes the starting and ending position of this segment on each transcript.

TABLE 78

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCACH1A_PEA_1_T8
1628
1731

(SEQ ID NO: 712)

HUMCACH1A_PEA_1_T22
1628
1731

(SEQ ID NO: 722)

Segment cluster HUMCACH1A_PEA_—1_node_—26 (SEQ ID NO:760) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716), HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717) and HUMCACH1A_PEA_—1_T20 (SEQ ID NO:721). Table 79 below describes the starting and ending position of this segment on each transcript.

TABLE 79

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1628
1731

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1205
1308

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1628
1731

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1628
1731

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1628
1731

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1628
1731

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1628
1731

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
1628
1731

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
1628
1731

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
1628
1731

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
1628
1731

HUMCACH1A_PEA_1_T20 (SEQ ID NO: 721)
1628
1731

Segment cluster HUMCACH1A_PEA_—1_node_—32 (SEQ ID NO:761) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713). Table 80 below describes the starting and ending position of this segment on each transcript.

TABLE 80

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCACH1A_PEA_1_T12
1
64

(SEQ ID NO: 713)

Segment cluster HUMCACH1A_PEA_—1_node_—35 (SEQ ID NO:762) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 81 below describes the starting and ending position of this segment on each transcript.

TABLE 81

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1902
1989

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1479
1566

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1902
1989

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1902
1989

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1902
1989

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1902
1989

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1902
1989

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1902
1989

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
235
322

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
1902
1989

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
1902
1989

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
1902
1989

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
1902
1989

Segment cluster HUMCACH1A_PEA_—1_node_—37 (SEQ ID NO:763) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 82 below describes the starting and ending position of this segment on each transcript.

TABLE 82

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
1990
2049

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1567
1626

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
1990
2049

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
1990
2049

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
1990
2049

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
1990
2049

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
1990
2049

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
323
382

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
1990
2049

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
1990
2049

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
1990
2049

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
1990
2049

Segment cluster HUMCACH1A_PEA_—1_node_—39 (SEQ ID NO:764) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 83 below describes the starting and ending position of this segment on each transcript.

TABLE 83

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2050
2076

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
1627
1653

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2050
2076

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2050
2076

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2050
2076

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2050
2076

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2050
2076

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
1990
2016

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
383
409

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
2050
2076

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
2050
2076

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
2050
2076

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
2050
2076

Segment cluster HUMCACH1A_PEA_—1_node_—49 (SEQ ID NO:765) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 84 below describes the starting and ending position of this segment on each transcript.

TABLE 84

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2793
2907

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2370
2484

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2793
2907

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2793
2907

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2793
2907

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2793
2907

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2793
2907

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2733
2847

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1126
1240

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
2793
2907

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
2793
2907

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
2793
2907

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
2793
2907

Segment cluster HUMCACH1A_PEA_—1_node_—51 (SEQ ID NO:766) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 85 below describes the starting and ending position of this segment on each transcript.

TABLE 85

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2908
2977

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2485
2554

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2908
2977

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2908
2977

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2908
2977

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2908
2977

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2908
2977

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2848
2917

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1241
1310

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
2908
2977

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
2908
2977

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
2908
2977

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
2908
2977

Segment cluster HUMCACH1A_PEA_—1_node_—53 (SEQ ID NO:767) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715), HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716) and HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 86 below describes the starting and ending position of this segment on each transcript.

TABLE 86

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
2978
3044

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2555
2621

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
2978
3044

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
2978
3044

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
2978
3044

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
2978
3044

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
2978
3044

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
2918
2984

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1311
1377

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
2978
3044

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
2978
3044

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
2978
3044

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
2978
3044

Segment cluster HUMCACH1A_PEA_—1_node_—58 (SEQ ID NO:768) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T16 (SEQ ID NO:717). Table 87 below describes the starting and ending position of this segment on each transcript.

TABLE 87

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T16 (SEQ ID NO: 717)
3323
3363

Segment cluster HUMCACH1A_PEA_—1_node_—60 (SEQ ID NO:769) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 88 below describes the starting and ending position of this segment on each transcript.

TABLE 88

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3323
3382

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2900
2959

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3323
3382

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3323
3382

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3323
3382

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3323
3382

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3323
3382

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3263
3322

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1656
1715

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3323
3382

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3323
3382

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3323
3382

Segment cluster HUMCACH1A_PEA_—1_node_—62 (SEQ ID NO:770) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 89 below describes the starting and ending position of this segment on each transcript.

TABLE 89

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3383
3489

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
2960
3066

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3383
3489

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3383
3489

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3383
3489

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3383
3489

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3383
3489

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3323
3429

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1716
1822

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3383
3489

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3383
3489

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3383
3489

Segment cluster HUMCACH1A_PEA_—1_node_—64 (SEQ ID NO:771) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 90 below describes the starting and ending position of this segment on each transcript.

TABLE 90

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3490
3577

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3067
3154

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3490
3577

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3490
3577

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3490
3577

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3490
3577

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3490
3577

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3430
3517

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1823
1910

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3490
3577

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3490
3577

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3490
3577

Segment cluster HUMCACH1A_PEA_—1_node_—66 (SEQ ID NO:772) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 91 below describes the starting and ending position of this segment on each transcript.

TABLE 91

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3578
3685

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3155
3262

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3578
3685

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3578
3685

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3578
3685

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3578
3685

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3578
3685

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3518
3625

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
1911
2018

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3578
3685

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3578
3685

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3578
3685

Segment cluster HUMCACH1A_PEA_—1_node_—68 (SEQ ID NO:773) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 92 below describes the starting and ending position of this segment on each transcript.

TABLE 92

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
3686
3738

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3263
3315

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
3686
3738

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
3686
3738

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
3686
3738

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
3686
3738

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
3686
3738

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
3626
3678

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2019
2071

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
3686
3738

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
3686
3738

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
3686
3738

Segment cluster HUMCACH1A_PEA_—1_node_—76 (SEQ ID NO:774) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 93 below describes the starting and ending position of this segment on each transcript.

TABLE 93

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4247
4357

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3824
3934

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4247
4357

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4247
4357

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4247
4357

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4247
4357

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4247
4357

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4187
4297

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2580
2690

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4247
4357

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4247
4357

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
4247
4357

Segment cluster HUMCACH1A_PEA_—1_node_—77 (SEQ ID NO:775) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T15 (SEQ ID NO:716). Table 94 below describes the starting and ending position of this segment on each transcript.

TABLE 94

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T15 (SEQ ID NO: 716)
4358
4400

Segment cluster HUMCACH1A_PEA_—1_node_—79 (SEQ ID NO:776) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714) and HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715). Table 95 below describes the starting and ending position of this segment on each transcript.

TABLE 95

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4358
4441

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
3935
4018

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4358
4441

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4358
4441

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4358
4441

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4358
4441

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4358
4441

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4298
4381

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2691
2774

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4358
4441

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4358
4441

Segment cluster HUMCACH1A_PEA_—1_node_—81 (SEQ ID NO:777) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 96 below describes the starting and ending position of this segment on each transcript.

TABLE 96

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1
31

Segment cluster HUMCACH1A_PEA_—1_node_—84 (SEQ ID NO:778) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 97 below describes the starting and ending position of this segment on each transcript.

TABLE 97

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4442
4486

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4019
4063

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4442
4486

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4442
4486

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4442
4486

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4442
4486

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4442
4486

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4382
4426

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2775
2819

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4442
4486

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4442
4486

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
32
76

Segment cluster HUMCACH1A_PEA_—1_node_—88 (SEQ ID NO:779) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 98 below describes the starting and ending position of this segment on each transcript.

TABLE 98

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4616
4681

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4193
4258

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4616
4681

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4616
4681

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4616
4681

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4616
4681

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4616
4681

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4556
4621

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
2949
3014

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4616
4681

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4616
4681

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
206
271

Segment cluster HUMCACH1A_PEA_—1_node_—90 (SEQ ID NO:780) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 99 below describes the starting and ending position of this segment on each transcript.

TABLE 99

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
4682
4773

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4259
4350

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
4682
4773

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
4682
4773

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
4682
4773

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
4682
4773

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
4682
4773

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
4622
4713

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3015
3106

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
4682
4773

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
4682
4773

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
272
363

Segment cluster HUMCACH1A_PEA_—1_node_—96 (SEQ ID NO:781) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 100 below describes the starting and ending position of this segment on each transcript.

TABLE 100

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5062
5158

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4639
4735

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5062
5158

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5062
5158

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5062
5158

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5062
5158

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5062
5158

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5002
5098

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3395
3491

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5062
5158

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
5062
5158

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
652
748

Segment cluster HUMCACH1A_PEA_—1_node_—98 (SEQ ID NO:782) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 101 below describes the starting and ending position of this segment on each transcript.

TABLE 101

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5159
5261

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4736
4838

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5159
5261

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5159
5261

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5159
5261

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5159
5261

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5159
5261

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5099
5201

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3492
3594

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5159
5261

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
5159
5261

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
749
851

Segment cluster HUMCACH1A_PEA_—1_node_—100 (SEQ ID NO:783) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715) and HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718). Table 102 below describes the starting and ending position of this segment on each transcript.

TABLE 102

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5262
5363

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
4839
4940

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5262
5363

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5262
5363

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5262
5363

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5262
5363

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5262
5363

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5202
5303

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3595
3696

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5262
5363

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
5262
5363

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
852
953

Segment cluster HUMCACH1A_PEA_—1_node_—101 (SEQ ID NO:784) according to the present invention is supported by 0 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T14 (SEQ ID NO:715). Table 103 below describes the starting and ending position of this segment on each transcript.

TABLE 103

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T14 (SEQ ID NO: 715)
5364
5440

Segment cluster HUMCACH1A_PEA_—1_node_—107 (SEQ ID NO:785) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 104 below describes the starting and ending position of this segment on each transcript.

TABLE 104

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5495
5611

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
5072
5188

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5495
5611

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5495
5611

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5495
5611

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5495
5611

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
5495
5611

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5435
5551

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
3828
3944

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
5495
5611

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1085
1201

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
336
452

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
1457
1573

Segment cluster HUMCACH1A_PEA_—1_node_—111 (SEQ ID NO:786) according to the present invention is supported by 0 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 105 below describes the starting and ending position of this segment on each transcript.

TABLE 105

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
5980
6006

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
5557
5583

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
5980
6006

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
5980
6006

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
5980
6006

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
5980
6006

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
5920
5946

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
4313
4339

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
1570
1596

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
821
847

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
1942
1968

Segment cluster HUMCACH1A_PEA_—1_node_—117 (SEQ ID NO:787) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T13 (SEQ ID NO:714). Table 106 below describes the starting and ending position of this segment on each transcript.

TABLE 106

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T13 (SEQ ID NO: 714)
6294
6365

Segment cluster HUMCACH1A_PEA_—1_node_—124 (SEQ ID NO:788) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T2 (SEQ ID NO:707), HUMCACH1A_PEA_—1_T3 (SEQ ID NO:708), HUMCACH1A_PEA_—1_T4 (SEQ ID NO:709), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 107 below describes the starting and ending position of this segment on each transcript.

TABLE 107

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
7551
7649

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
7128
7226

HUMCACH1A_PEA_1_T2 (SEQ ID NO: 707)
7551
7649

HUMCACH1A_PEA_1_T3 (SEQ ID NO: 708)
7551
7649

HUMCACH1A_PEA_1_T4 (SEQ ID NO: 709)
7551
7649

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
7730
7828

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
7524
7622

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
7491
7589

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
5884
5982

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
3141
3239

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
2392
2490

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
3513
3611

Segment cluster HUMCACH1A_PEA_—1_node_—126 (SEQ ID NO:789) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCACH1A_PEA_—1_T0 (SEQ ID NO:705), HUMCACH1A_PEA_—1_T1 (SEQ ID NO:706), HUMCACH1A_PEA_—1_T6 (SEQ ID NO:710), HUMCACH1A_PEA_—1_T7 (SEQ ID NO:711), HUMCACH1A_PEA_—1_T8 (SEQ ID NO:712), HUMCACH1A_PEA_—1_T12 (SEQ ID NO:713), HUMCACH1A_PEA_—1_T17 (SEQ ID NO:718), HUMCACH1A_PEA_—1_T18 (SEQ ID NO:719) and HUMCACH1A_PEA_—1_T19 (SEQ ID NO:720). Table 108 below describes the starting and ending position of this segment on each transcript.

TABLE 108

Segment location on transcripts

Seg-

Segment
ment

starting
ending

Transcript name
position
position

HUMCACH1A_PEA_1_T0 (SEQ ID NO: 705)
9311
9380

HUMCACH1A_PEA_1_T1 (SEQ ID NO: 706)
8888
8957

HUMCACH1A_PEA_1_T6 (SEQ ID NO: 710)
9490
9559

HUMCACH1A_PEA_1_T7 (SEQ ID NO: 711)
9284
9353

HUMCACH1A_PEA_1_T8 (SEQ ID NO: 712)
9251
9320

HUMCACH1A_PEA_1_T12 (SEQ ID NO: 713)
7644
7713

HUMCACH1A_PEA_1_T17 (SEQ ID NO: 718)
4901
4970

HUMCACH1A_PEA_1_T18 (SEQ ID NO: 719)
4152
4221

HUMCACH1A_PEA_1_T19 (SEQ ID NO: 720)
5273
5342

Variant Protein Alignment to the Previously Known Protein:

Sequence name: CCAD_HUMAN_V3 (SEQ ID NO:791)

Sequence documentation:

Alignment of: HUMCACH1A_PEA_1_P7 (SEQ ID NO:796) × CCAD_HUMAN_V3 (SEQ ID

NO:791) ..

Alignment segment 1/1:

Quality:
16625.00
Escore:
0

Matching length:
1696
Total length:
1716

Matching Percent Similarity:
99.94
Matching Percent Identity:
99.94

Total Percent Similarity:
98.78
Total Percent Identity:
98.78

Gaps:
1

Alignment:

Sequence name: CCAD_HUMAN (SEQ ID NO:790)

Sequence documentation:

Alignment of: HUMCACH1A_PEA_1_P13 (SEQ ID NO:802) × OCAD_HUMAN (SEQ ID

NO:790) ..

Alignment segment 1/1:

Quality:
5658.00
Escore:
0

Matching length:
564
Total length:
564

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: CCAD_HUMAN (SEQ ID NO:790)

Sequence documentation:

Alignment of: HUMCACH1A_PEA_1_{— P14 (SEQ ID NO:803) × CCAD}_HUMAN (SEQ ID

NO:790) ..

Alignment segment 1/1:

Quality:
4021.00
Escore:
0

Matching length:
399
Total length:
399

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: CCAD_HUMAN (SEQ ID NO:790)

Sequence documentation:

Alignment of: HUMCACH1A_PEA_1_P17 (SEQ ID NO:805) × CCAD_HUMAN (SEQ ID

NO:790) ..

Alignment segment 1/1:

Quality:
3976.00
Escore:
0

Matching length:
407
Total length:
407

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Expression of Voltage-Dependent L-Type Calcium Channel Alpha-1D Subunit Calcium Channel, L Type, Alpha-1 Polypeptide, Isoform 2 Transcripts which are Detectable by Seg 113, 35, 109, 125, in Normal, and Cancerous Colon Tissues

Expression of Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts detectable by or according to segments 113, 35, 109, 125 was measured with oligonucleotide-based micro-arrays. The results of image intensities for each feature were normalized according to the ninetieth percentile of the image intensities of all the features on the chip. Then, feature image intensities for replicates of the same oligonucleotide on the chip and replicates of the same sample were averaged. Outlying results were discarded.

For every oligonucleotide HUMCACH1A_—0_—3_—14917, HUMCACH1A_—0_—0_—14922, HUMCACH1A_—0_—0_—14924 and HUMCACH1A_—0_—0_—14913 (SEQ ID NOs: 1331, 1332, 1333 and 1334, respectively) the averaged intensity determined for every sample was divided by the averaged intensity of all the normal samples (Sample Nos. 62-66 and 69, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to the averaged normal samples. These data are presented in a histogram bellow (FIG. 47). As is evident from the histogram, the expression of Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts detectable with the above oligonucleotides in cancer samples was higher than in the normal samples.

HUMCACH1A_0_3_14917-

(SEQ ID NO: 1331)

AGAGAATATCACTCCGATGGTCGGTTTCTGACTGTCACGCTAAGGGCAAC

HUMCACH1A_0_0_14922-

(SEQ ID NO: 1332)

GAACACAGAGAACGTCAGCGGTGAAGGCGAGAACCGAGGCTGCTGTGGAA

HUMCACH1A_0_0_14924-

(SEQ ID NO: 1333)

GGCCCAGCATTGGGAACCTTGAGCATGTGTCTGAAAATGGGCATCATTCT

HUMCACH1A_0_0_14913-

(SEQ ID NO: 1334)

GACTCAGGAGATGAACAGCTCCCAACTATTTGCCGGGAAGACCCAGAGAT

Expression of Voltage-Dependent L-Type Calcium Channel Alpha-1D Subunit Calcium Channel, L Type, Alpha-1 Polypeptide, Isoform 2

HUMCACH1A Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HUMCACH1Aseg101 (SEQ ID NO: 1337) in Normal and Cancerous Colon Tissues

Expression of Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts detectable by or according to seg101, HUMCACH1A seg101 amplicon (SEQ ID NO: 1337) and HUMCACH1Aseg101F (SEQ ID NO: 1335), HUMCACH1A seg101R (SEQ ID NO: 1336) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 48 is a histogram showing over expression of the above-indicated Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 48, the expression of Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in II out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 1.02E-03.

Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 3.78E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCACH1Aseg101F forward primer (SEQ ID NO: 1335); and HUMCACH1A seg101R reverse primer (SEQ ID NO: 1336).

Forward primer (SEQ ID NO: 1335):

CAGCAGGAAATTCGGTGTGTC

Reverse primer (SEQ ID NO: 1336):

TCAAGGTTCCCAATGCTGG

Amplicon (SEQ ID NO: 1337):

CAGCAGGAAATTCGGTGTGTCATAACCATCATAACCATAATTCCATAGGA

AAGCAAGTTCCCACCTCAACAAATGCCAATCTCAATAATGCCAATATGTC

CAAAGCTGCCCATGGAAAGCGGCCCAGCATTGGGAACCTTGA

Description for Cluster HUMCEA

Cluster HUMCEA features 10 transcript(s) and 47 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcripts Name
SEQ ID NO:

HUMCEA_PEA_1_T8
806

HUMCEA_PEA_1_T9
807

HUMCEA_PEA_1_T12
808

HUMCEA_PEA_1_T14
809

HUMCEA_PEA_1_T16
810

HUMCEA_PEA_1_T20
811

HUMCEA_PEA_1_T25
812

HUMCEA_PEA_1_T26
813

HUMCEA_PEA_1_T29
814

HUMCEA_PEA_1_T30
815

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HUMCEA_PEA_1_node_0
816

HUMCEA_PEA_1_node_2
817

HUMCEA_PEA_1_node_6
818

HUMCEA_PEA_1_node_11
819

HUMCEA_PEA_1_node_12
820

HUMCEA_PEA_1_node_31
821

HUMCEA_PEA_1_node_36
822

HUMCEA_PEA_1_node_42
823

HUMCEA_PEA_1_node_43
824

HUMCEA_PEA_1_node_44
825

HUMCEA_PEA_1_node_46
826

HUMCEA_PEA_1_node_48
827

HUMCEA_PEA_1_node_63
828

HUMCEA_PEA_1_node_65
829

HUMCEA_PEA_1_node_67
830

HUMCEA_PEA_1_node_3
831

HUMCEA_PEA_1_node_7
832

HUMCEA_PEA_1_node_8
833

HUMCEA_PEA_1_node_9
834

HUMCEA_PEA_1_node_10
835

HUMCEA_PEA_1_node_15
836

HUMCEA_PEA_1_node_16
837

HUMCEA_PEA_1_node_17
838

HUMCEA_PEA_1_node_18
839

HUMCEA_PEA_1_node_19
840

HUMCEA_PEA_1_node_20
841

HUMCEA_PEA_1_node_21
842

HUMCEA_PEA_1_node_22
843

HUMCEA_PEA_1_node_23
844

HUMCEA_PEA_1_node_24
845

HUMCEA_PEA_1_node_27
846

HUMCEA_PEA_1_node_29
847

HUMCEA_PEA_1_node_30
848

HUMCEA_PEA_1_node_33
849

HUMCEA_PEA_1_node_34
850

HUMCEA_PEA_1_node_35
851

HUMCEA_PEA_1_node_45
852

HUMCEA_PEA_1_node_49
853

HUMCEA_PEA_1_node_50
854

HUMCEA_PEA_1_node_51
855

HUMCEA_PEA_1_node_56
856

HUMCEA_PEA_1_node_57
857

HUMCEA_PEA_1_node_58
858

HUMCEA_PEA_1_node_60
859

HUMCEA_PEA_1_node_61
860

HUMCEA_PEA_1_node_62
861

HUMCEA_PEA_1_node_64
862

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HUMCEA_PEA_1_P4
864
HUMCEA_PEA_1_T8

(SEQ ID NO: 806)

HUMCEA_PEA_1_P5
865
HUMCEA_PEA_1_T9

(SEQ ID NO: 807)

HUMCEA_PEA_1_P7
866
HUMCEA_PEA_1_T12

(SEQ ID NO: 808)

HUMCEA_PEA_1_P10
867
HUMCEA_PEA_1_T16

(SEQ ID NO: 810)

HUMCEA_PEA_1_P14
868
HUMCEA_PEA_1_T20

(SEQ ID NO: 811)

HUMCEA_PEA_1_P19
869
HUMCEA_PEA_1_T25

(SEQ ID NO: 812)

HUMCEA_PEA_1_P20
870
HUMCEA_PEA_1_T26

(SEQ ID NO: 813)

These sequences are variants of the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SwissProt accession identifier CEA5_HUMAN; known also according to the synonyms Carcinoembryonic antigen; CEA; Meconium antigen 100; CD66e antigen), SEQ ID NO: 863, referred to herein as the previously known protein.

The sequence for protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863) is given at the end of the application, as “Carcinoembryonic antigen-related cell adhesion molecule 5 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

320
Missing

Protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863) localization is believed to be Attached to the membrane by a GPI-anchor.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: integral plasma membrane protein; membrane, which are annotation(s) related to Cellular Component.

Cluster HUMCEA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 49 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

colon
1175

epithelial
92

general
29

head and neck
81

kidney
0

lung
0

lymph nodes
0

breast
0

pancreas
0

prostate
0

stomach
256

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

colon
2.0e−01
2.7e−01
9.8e−01
0.5
1
0.5

epithelial
2.1e−03
2.7e−02
6.4e−04
1.4
2.1e−01
1.0

general
3.9e−08
8.2e−06
9.2e−18
3.2
1.3e−10
2.2

head and neck
3.4e−01
5.0e−01
2.1e−01
1.8
5.6e−01
0.9

kidney
4.3e−01
5.3e−01
5.8e−01
2.1
7.0e−01
1.6

lung
1.3e−01
2.6e−01
1
1.1
1
1.1

lymph nodes
3.1e−01
5.7e−01
8.1e−02
6.0
3.3e−01
2.5

breast
3.8e−01
1.5e−01
1
1.0
6.8e−01
1.5

pancreas
2.2e−02
2.3e−02
1.4e−08
7.8
7.4e−07
6.4

prostate
5.3e−01
6.0e−01
3.0e−01
2.5
4.2e−01
2.0

stomach
1.5e−01
4.7e−01
8.9e−01
0.6
7.2e−01
0.4

For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously described. The following oligonucleotides were found to hit this cluster but not other segments/transcripts below, shown in Table 7.

TABLE 7

Oligonucleotides related to this cluster

Oligonucleotide name
Overexpressed in cancers
Chip reference

HUMCEA_0_0_15168
lung malignant tumors
LUN

As noted above, cluster HUMCEA features 10 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863). A description of each variant protein according to the present invention is now provided.

Variant protein HUMCEA_PEA_—1_P4 (SEQ ID NO:864) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T8 (SEQ ID NO:806). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCEA_PEA_—1_P4 (SEQ ID NO:864) and CEA5_HUMAN (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P4 (SEQ ID NO:864), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK CETQNPVSARRSDSVILNVL corresponding to amino acids 1-234 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-234 of HUMCEA_PEA_—1_P4 (SEQ ID NO:864), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGG SGSTPYDGRNR (SEQ ID NO:1475) corresponding to amino acids 235-315 of HUMCEA_PEA_—1_P4 (SEQ ID NO:864), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCEA_PEA_—1_P4 (SEQ ID NO:864), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGG SGSTPYDGRNR (SEQ ID NO:1475) in HUMCEA_PEA_—1_P4 (SEQ ID NO:864).

Variant protein HUMCEA_PEA_—1_P4 (SEQ ID NO:864) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P4 (SEQ ID NO:864) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

173
D -> N
No

The glycosylation sites of variant protein HUMCEA_PEA_—1_P4 (SEQ ID NO:864), as compared to the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863), are described in Table 9 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 9

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

197
yes
197

466
no

360
no

288
no

665
no

560
no

650
no

480
no

104
yes
104

580
no

204
yes
204

115
yes
115

208
yes
208

152
yes
152

309
no

432
no

351
no

246
no

182
yes
182

612
no

256
no

508
no

330
no

274
no

292
no

553
no

529
no

375
no

Variant protein HUMCEA_PEA_—1_P4 (SEQ ID NO:864) is encoded by the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T8 (SEQ ID NO:806) is shown in bold; this coding portion starts at position 115 and ends at position 1059. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P4 (SEQ ID NO:864) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

631
G -> A
No

1315
A -> G
No

1380
T -> C
No

1533
C -> A
Yes

1706
G -> A
Yes

2308
T -> C
No

2362
C -> T
No

2455
A ->
No

2504
C -> A
Yes

2558
G ->
No

2623
G ->
No

2639
T -> A
No

2640
T -> A
No

2832
G -> A
Yes

2885
C -> T
No

3396
A -> G
Yes

3562
C -> T
Yes

3753
C -> T
Yes

Variant protein HUMCEA_PEA_—1_P5 (SEQ ID NO:865) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T9 (SEQ ID NO:807). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCEA_PEA_—1_P5 (SEQ ID NO:865) and CEA5_HUMAN (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P5 (SEQ ID NO:865), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK CETQNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFI PNITVNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWW VNNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRP GVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELP KPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVC GIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKI TPNNNGTYACFVSNLATGRNNSIVKSITVS corresponding to amino acids 1-675 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-675 of HUMCEA_PEA_—1_P5 (SEQ ID NO:865), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO:1476) corresponding to amino acids 676-719 of HUMCEA_PEA_—1_P5 (SEQ ID NO:865), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HUMCEA_PEA_—1_P5 (SEQ ID NO:865), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO:1476) in HUMCEA_PEA_—1_P5 (SEQ ID NO:865).

Variant protein HUMCEA_PEA_—1_P5 (SEQ ID NO:865) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P5 (SEQ ID NO:865) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

173
D -> N
No

289
I -> T
No

340
A -> D
Yes

398
E -> K
Yes

647
P ->
No

664
R -> S
Yes

The glycosylation sites of variant protein HUMCEA_PEA_—1_P5 (SEQ ID NO:865), as compared to the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863), are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 12

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

197
yes
197

466
yes
466

360
yes
360

288
yes
288

665
yes
665

560
yes
560

650
yes
650

480
yes
480

104
yes
104

580
yes
580

204
yes
204

115
yes
115

208
yes
208

152
yes
152

309
yes
309

432
yes
432

351
yes
351

246
yes
246

182
yes
182

612
yes
612

256
yes
256

508
yes
508

330
yes
330

274
yes
274

292
yes
292

553
yes
553

529
yes
529

375
yes
375

Variant protein HUMCEA_PEA_—1_P5 (SEQ ID NO:865) is encoded by the following transcript(s): HUMCEA_PEA_—1_T9 (SEQ ID NO:807), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T9 (SEQ ID NO:807) is shown in bold; this coding portion starts at position 115 and ends at position 2271. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P5 (SEQ ID NO:865) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

631
G -> A
No

915
A -> G
No

980
T -> C
No

1133
C -> A
Yes

1306
G -> A
Yes

1908
T -> C
No

1962
C -> T
No

2055
A ->
No

2104
C -> A
Yes

3259
T -> C
Yes

Variant protein HUMCEA_PEA_—1_P7 (SEQ ID NO:866) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T12 (SEQ ID NO:808). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCEA_PEA_—1_P7 (SEQ ID NO:866) and CEA5_HUMAN (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P7 (SEQ ID NO:866), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK CETQNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFI PNITVNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWW VNNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRP GVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELP KPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVC GIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKI TPNNNGTYACFVSNLATGRNNSIVKSITV corresponding to amino acids 1-674 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-674 of HUMCEA_PEA_—1_P7 (SEQ ID NO:866), and a second amino acid sequence being at least 90% homologous to SAGATVGIMIGVLVGVALI corresponding to amino acids 684-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 675-693 of HUMCEA_PEA_—1_P7 (SEQ ID NO:866), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P7 (SEQ ID NO:866), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise VS, having a structure as follows: a sequence starting from any of amino acid numbers 674−x to 674; and ending at any of amino acid numbers 675+((n−2)−x), in which x varies from 0 to n−2.

Variant protein HUMCEA_PEA_—1_P7 (SEQ ID NO:866) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P7 (SEQ ID NO:866) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

173
D -> N
No

289
I -> T
No

340
A -> D
Yes

398
E -> K
Yes

647
P ->
No

664
R -> S
Yes

The glycosylation sites of variant protein HUMCEA_PEA_—1_P7 (SEQ ID NO:866), as compared to the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863), are described in Table 15 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 15

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

197
yes
197

466
yes
466

360
yes
360

288
yes
288

665
yes
665

560
yes
560

650
yes
650

480
yes
480

104
yes
104

580
yes
580

204
yes
204

115
yes
115

208
yes
208

152
yes
152

309
yes
309

432
yes
432

351
yes
351

246
yes
246

182
yes
182

612
yes
612

256
yes
256

508
yes
508

330
yes
330

274
yes
274

292
yes
292

553
yes
553

529
yes
529

375
yes
375

Variant protein HUMCEA_PEA_—1_P7 (SEQ ID NO:866) is encoded by the following transcript(s): HUMCEA_PEA_—1_T12 (SEQ ID NO:808), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T12 (SEQ ID NO:808) is shown in bold; this coding portion starts at position 115 and ends at position 2193. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P7 (SEQ ID NO:866) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

631
G -> A
No

915
A -> G
No

980
T -> C
No

1133
C -> A
Yes

1306
G -> A
Yes

1908
T -> C
No

1962
C -> T
No

2055
A ->
No

2104
C -> A
Yes

2196
G ->
No

2212
T -> A
No

2213
T -> A
No

2405
G -> A
Yes

2458
C -> T
No

2969
A -> G
Yes

3135
C -> T
Yes

3326
C -> T
Yes

Variant protein HUMCEA_PEA_—1_P10 (SEQ ID NO:867) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T16 (SEQ ID NO:810). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCEA_PEA_—1_P10 (SEQ ID NO:867) and CEA5_HUMAN (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P10 (SEQ ID NO:867), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK CETQNPVSARRSDS corresponding to amino acids 1-228 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-228 of HUMCEA_PEA_—1_P10 (SEQ ID NO:867), and a second amino acid sequence being at least 90% homologous to VILNVLYGPDDPTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQA NNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLS NGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPS PQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGV LVGVALI corresponding to amino acids 407-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 229-524 of HUMCEA_PEA_—1_P10 (SEQ ID NO:867), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P10 (SEQ ID NO:867), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SV, having a structure as follows: a sequence starting from any of amino acid numbers 228−x to 228; and ending at any of amino acid numbers 229+((n−2)−x), in which x varies from 0 to n−2.

Variant protein HUMCEA_PEA_—1_P10 (SEQ ID NO:867) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P10 (SEQ ID NO:867) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

173
D -> N
No

469
P ->
No

486
R -> S
Yes

504
G ->
No

The glycosylation sites of variant protein HUMCEA_PEA_—1_P10 (SEQ ID NO:867), as compared to the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863), are described in Table 18 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 18

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

197
yes
197

466
yes
288

360
no

288
no

665
yes
487

560
yes
382

650
yes
472

480
yes
302

104
yes
104

580
yes
402

204
yes
204

115
yes
115

208
yes
208

152
yes
152

309
no

432
yes
254

351
no

246
no

182
yes
182

612
yes
434

256
no

508
yes
330

330
no

274
no

292
no

553
yes
375

529
yes
351

375
no

Variant protein HUMCEA_PEA_—1_P10 (SEQ ID NO:867) is encoded by the following transcript(s): HUMCEA_PEA_—1_T16 (SEQ ID NO:810), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T16 (SEQ ID NO:810) is shown in bold; this coding portion starts at position 115 and ends at position 1686. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P10 (SEQ ID NO:867) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

631
G -> A
No

1374
T -> C
No

1428
C -> T
No

1521
A ->
No

1570
C -> A
Yes

1624
G ->
No

1689
G ->
No

1705
T -> A
No

1706
T -> A
No

1898
G -> A
Yes

1951
C -> T
No

2462
A -> G
Yes

2628
C -> T
Yes

2819
C -> T
Yes

Variant protein HUMCEA_PEA_—1_P14 (SEQ ID NO:868) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T20 (SEQ ID NO:811). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

Variant protein HUMCEA_PEA_—1_P14 (SEQ ID NO:868) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P14 (SEQ ID NO:868) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

173
D -> N
No

289
I -> T
No

340
A -> D
Yes

398
E -> K
Yes

Variant protein HUMCEA_PEA_—1_P14 (SEQ ID NO:868) is encoded by the following transcript(s): HUMCEA_PEA_—1_T20 (SEQ ID NO:811), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T20 (SEQ ID NO:811) is shown in bold; this coding portion starts at position 115 and ends at position 1821. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P14 (SEQ ID NO:868) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

631
G -> A
No

915
A -> G
No

980
T -> C
No

1133
C -> A
Yes

1306
G -> A
Yes

Variant protein HUMCEA_PEA_—1_P19 (SEQ ID NO:869) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T25 (SEQ ID NO:812). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCEA_PEA_—1_P19 (SEQ ID NO:869) and CEA5_HUMAN (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P19 (SEQ ID NO:869), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK CETQNPVSARRSDSVILN corresponding to amino acids 1-232 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-232 of HUMCEA_PEA_—1_P19 (SEQ ID NO:869), and a second amino acid sequence being at least 90% homologous to VLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLA TGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 589-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 233-346 of HUMCEA_PEA_—1_P19 (SEQ ID NO:869), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P19 (SEQ ID NO:869), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise NV, having a structure as follows: a sequence starting from any of amino acid numbers 232−x to 232; and ending at any of amino acid numbers 233+((n−2)−x), in which x varies from 0 to n−2.

Variant protein HUMCEA_PEA_—1_P19 (SEQ ID NO:869) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 22, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P19 (SEQ ID NO:869) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

173
D -> N
No

291
P ->
No

308
R -> S
Yes

326
G ->
No

The glycosylation sites of variant protein HUMCEA_PEA_—1_P19 (SEQ ID NO:869), as compared to the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863), are described in Table 23 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 23

Glycosylation site(s)

Position(s) on

known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

197
yes
197

466
no

360
no

288
no

665
yes
309

560
no

650
yes
294

480
no

104
yes
104

580
no

204
yes
204

115
yes
115

208
yes
208

152
yes
152

309
no

432
no

351
no

246
no

182
yes
182

612
yes
256

256
no

508
no

330
no

274
no

292
no

553
no

529
no

375
no

Variant protein HUMCEA_PEA_—1_P19 (SEQ ID NO:869) is encoded by the following transcript(s): HUMCEA_PEA_—1_T25 (SEQ ID NO:812), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T25 (SEQ ID NO:812) is shown in bold; this coding portion starts at position 115 and ends at position 1152. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P19 (SEQ ID NO:869) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

631
G -> A
No

840
T -> C
No

894
C -> T
No

987
A ->
No

1036
C -> A
Yes

1090
G ->
No

1155
G ->
No

1171
T -> A
No

1172
T -> A
No

1364
G -> A
Yes

1417
C -> T
No

1928
A -> G
Yes

2094
C -> T
Yes

2285
C -> T
Yes

Variant protein HUMCEA_PEA_—1_P20 (SEQ ID NO:870) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCEA_PEA_—1_T26 (SEQ ID NO:813). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HUMCEA_PEA_—1_P20 (SEQ ID NO:870) and CEA5_HUMAN (SEQ ID NO:863):

1. An isolated chimeric polypeptide encoding for HUMCEA_PEA_—1_P20 (SEQ ID NO:870), comprising a first amino acid sequence being at least 90% homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYP corresponding to amino acids 1-142 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 1-142 of HUMCEA_PEA_—1_P20 (SEQ ID NO:870), and a second amino acid sequence being at least 90% homologous to ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARA YVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLF IAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 499-702 of CEA5_HUMAN (SEQ ID NO:863), which also corresponds to amino acids 143-346 of HUMCEA_PEA_—1_P20 (SEQ ID NO:870), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated chimeric polypeptide encoding for an edge portion of HUMCEA_PEA_—1_P20 (SEQ ID NO:870), comprising a polypeptide having a length “n”, wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PE, having a structure as follows: a sequence starting from any of amino acid numbers 142−x to 142; and ending at any of amino acid numbers 143+((n−2)−x), in which x varies from 0 to n−2.

Variant protein HUMCEA_PEA_—1_P20 (SEQ ID NO:870) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 25, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P20 (SEQ ID NO:870) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

63
F -> L
No

80
I -> V
Yes

83
V -> A
Yes

137
Q -> P
Yes

291
P ->
No

308
R -> S
Yes

326
G ->
No

The glycosylation sites of variant protein HUMCEA_PEA_—1_P20 (SEQ ID NO:870), as compared to the known protein Carcinoembryonic antigen-related cell adhesion molecule 5 precursor (SEQ ID NO:863), are described in Table 26 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 26

Glycosylation site(s)

Position(s) on known
Present in
Position

amino acid sequence
variant protein?
in variant protein?

197
no

466
no

360
no

288
no

665
yes
309

560
yes
204

650
yes
294

480
no

104
yes
104

580
yes
224

204
no

115
yes
115

208
no

152
no

309
no

432
no

351
no

246
no

182
no

612
yes
256

256
no

508
yes
152

330
no

274
no

292
no

553
yes
197

529
yes
173

375
no

Variant protein HUMCEA_PEA_—1_P20 (SEQ ID NO:870) is encoded by the following transcript(s): HUMCEA_PEA_—1_T26 (SEQ ID NO:813), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCEA_PEA_—1_T26 (SEQ ID NO:813) is shown in bold; this coding portion starts at position 115 and ends at position 1152. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCEA_PEA_—1_P20 (SEQ ID NO:870) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

49
T ->
No

273
A -> C
Yes

303
T -> G
No

324
T -> C
Yes

352
A -> G
Yes

362
T -> C
Yes

524
A -> C
Yes

840
T -> C
No

894
C -> T
No

987
A ->
No

1036
C -> A
Yes

1090
G ->
No

1155
G ->
No

1171
T -> A
No

1172
T -> A
No

1364
G -> A
Yes

1417
C -> T
No

1928
A -> G
Yes

2094
C -> T
Yes

2285
C -> T
Yes

As noted above, cluster HUMCEA features 47 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HUMCEA_PEA_—1_node_—0 (SEQ ID NO:816) according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811), HUMCEA_PEA_—1_T25 (SEQ ID NO:812) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1
178

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1
178

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1
178

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1
178

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1
178

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1
178

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1
178

Segment cluster HUMCEA_PEA_—1_node_—2 (SEQ ID NO:817) according to the present invention is supported by 83 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811), HUMCEA_PEA_—1_T25 (SEQ ID NO:812) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
179
456

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
179
456

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
179
456

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
179
456

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
179
456

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
179
456

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
179
456

Segment cluster HUMCEA_PEA_—1_node_—6 (SEQ ID NO:818) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T14 (SEQ ID NO:809). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1
1258

Segment cluster HUMCEA_PEA_—1_node_—1 (SEQ ID NO:819) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
818
1217

TABLE 32

Oligonucleotides related to this segment

Overexpressed
Chip

Oligonucleotide name
in cancers
reference

HUMCEA_0_0_96 (SEQ ID NO: 1428)
colorectal cancer
Colon

HUMCEA_0_0_96 (SEQ ID NO: 1428)
lung malignant
LUN

tumors

Segment cluster HUMCEA_PEA_—1_node_—12 (SEQ ID NO:820) according to the present invention is supported by 83 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1218
1472

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
818
1072

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
818
1072

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1538
1792

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
818
1072

Segment cluster HUMCEA_PEA_—1_node_—31 (SEQ ID NO:821) according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1817
2006

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1417
1606

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1417
1606

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2137
2326

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
883
1072

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1417
1606

Segment cluster HUMCEA_PEA_—1_node_—36 (SEQ ID NO:822) according to the present invention is supported by 94 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2159
2285

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1759
1885

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1759
1885

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2479
2605

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1225
1351

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
691
817

Segment cluster HUMCEA_PEA_—1_node_—42 (SEQ ID NO:823) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T29 (SEQ ID NO:814). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
1
136

Segment cluster HUMCEA_PEA_—1_node_—43 (SEQ ID NO:824) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T29 (SEQ ID NO:814). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
137
260

Segment cluster HUMCEA_PEA_—1_node_—44 (SEQ ID NO:825) according to the present invention is supported by 112 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813) and HUMCEA_PEA_—1_T29 (SEQ ID NO:814). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2286
2540

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1886
2140

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1886
2140

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2606
2860

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1352
1606

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
818
1072

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
818
1072

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
261
515

Segment cluster HUMCEA_PEA_—1_node_—46 (SEQ ID NO:826) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T9 (SEQ ID NO:807). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCEA_PEA_1_T9
2174
3347

(SEQ ID NO: 807)

Segment cluster HUMCEA_PEA_—1_node_—48 (SEQ ID NO:827) according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCEA_PEA_1_T30
1
1762

(SEQ ID NO: 815)

Segment cluster HUMCEA_PEA_—1_node_—63 (SEQ ID NO:828) according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2957
3135

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2530
2708

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3277
3455

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
2023
2201

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1489
1667

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1489
1667

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
932
1110

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2185
2363

Segment cluster HUMCEA_PEA_—1_node_—65 (SEQ ID NO:829) according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
3166
3897

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2739
3470

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3486
4217

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
2232
2963

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1698
2429

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1698
2429

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
1141
1872

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2394
3125

Segment cluster HUMCEA_PEA_—1_node_—67 (SEQ ID NO:830) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

HUMCEA_PEA_1_T20
1607
1886

(SEQ ID NO: 811)

Segment cluster HUMCEA_PEA_—1_node_—3 (SEQ ID NO:831) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811), HUMCEA_PEA_—1_T25 (SEQ ID NO:812) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
457
538

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
457
538

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
457
538

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
457
538

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
457
538

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
457
538

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
457
538

Segment cluster HUMCEA_PEA_—1_node_—7 (SEQ ID NO:832) according to the present invention is supported by 73 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811) and HUMCEA_PEA_—1_T25 (SEQ ID NO:812). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
539
642

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
539
642

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
539
642

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1259
1362

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
539
642

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
539
642

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
539
642

Segment cluster HUMCEA_PEA_—1_node_—8 (SEQ ID NO:833) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811) and HUMCEA_PEA_—1_T25 (SEQ ID NO:812). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
643
690

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
643
690

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
643
690

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1363
1410

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
643
690

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
643
690

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
643
690

Segment cluster HUMCEA_PEA_—1_node_—9 (SEQ ID NO:834) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811) and HUMCEA_PEA_—1_T25 (SEQ ID NO:812). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
691
738

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
691
738

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
691
738

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1411
1458

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
691
738

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
691
738

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
691
738

Segment cluster HUMCEA_PEA_—1_node_—10 (SEQ ID NO:835) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T20 (SEQ ID NO:811) and HUMCEA_PEA_—1_T25 (SEQ ID NO:812). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
739
817

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
739
817

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
739
817

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1459
1537

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
739
817

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
739
817

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
739
817

Segment cluster HUMCEA_PEA_—1_node_—15 (SEQ ID NO:836) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1473
1475

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1073
1075

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1073
1075

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1793
1795

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1073
1075

Segment cluster HUMCEA_PEA_—1_node_—16 (SEQ ID NO:837) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1476
1481

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1076
1081

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1076
1081

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1796
1801

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1076
1081

Segment cluster HUMCEA_PEA_—1_node_—17 (SEQ ID NO:838) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1482
1488

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1082
1088

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1082
1088

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1802
1808

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1082
1088

Segment cluster HUMCEA_PEA_—1_node_—18 (SEQ ID NO:839) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1489
1506

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1089
1106

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1089
1106

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1809
1826

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1089
1106

Segment cluster HUMCEA_PEA_—1_node_—19 (SEQ ID NO:840) according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1507
1576

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1107
1176

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1107
1176

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1827
1896

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1107
1176

Segment cluster HUMCEA_PEA_—1_node_—20 (SEQ ID NO:841) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1577
1600

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1177
1200

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1177
1200

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1897
1920

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1177
1200

Segment cluster HUMCEA_PEA_—1_node_—21 (SEQ ID NO:842) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1601
1624

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1201
1224

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1201
1224

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1921
1944

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1201
1224

Segment cluster HUMCEA_PEA_—1_node_—22 (SEQ ID NO:843) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1625
1702

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1225
1302

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1225
1302

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
1945
2022

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1225
1302

Segment cluster HUMCEA_PEA_—1_node_—23 (SEQ ID NO:844) according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1703
1732

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1303
1332

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1303
1332

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2023
2052

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1303
1332

Segment cluster HUMCEA_PEA_—1_node_—24 (SEQ ID NO:845) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1733
1751

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1333
1351

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1333
1351

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2053
2071

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1333
1351

Segment cluster HUMCEA_PEA_—1_node_—27 (SEQ ID NO:846) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1752
1770

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1352
1370

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1352
1370

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2072
2090

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
818
836

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1352
1370

Segment cluster HUMCEA_PEA_—1_node_—29 (SEQ ID NO:847) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1771
1788

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1371
1388

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1371
1388

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2091
2108

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
837
854

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1371
1388

Segment cluster HUMCEA_PEA_—1_node_—30 (SEQ ID NO:848) according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T20 (SEQ ID NO:811). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
1789
1816

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1389
1416

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1389
1416

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2109
2136

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
855
882

HUMCEA_PEA_1_T20 (SEQ ID NO: 811)
1389
1416

Segment cluster HUMCEA_PEA_—1_node_—33 (SEQ ID NO:849) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2007
2028

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1607
1628

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1607
1628

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2327
2348

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1073
1094

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
539
560

Segment cluster HUMCEA_PEA_—1_node_—34 (SEQ ID NO:850) according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2029
2110

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1629
1710

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1629
1710

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2349
2430

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1095
1176

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
561
642

Segment cluster HUMCEA_PEA_—1_node_—35 (SEQ ID NO:851) according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T9 (SEQ ID NO:807), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810) and HUMCEA_PEA_—1_T26 (SEQ ID NO:813). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2111
2158

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
1711
1758

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
1711
1758

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2431
2478

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1177
1224

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
643
690

Segment cluster HUMCEA_PEA_—1_node_—45 (SEQ ID NO:852) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T9 (SEQ ID NO:807). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T9 (SEQ ID NO: 807)
2141
2173

Segment cluster HUMCEA_PEA_—1_node_—49 (SEQ ID NO:853) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
1763
1768

Segment cluster HUMCEA_PEA_—1_node_—50 (SEQ ID NO:854) according to the present invention is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2541
2567

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2861
2887

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1607
1633

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1073
1099

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1073
1099

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
516
542

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
1769
1795

Segment cluster HUMCEA_PEA_—1_node_—51 (SEQ ID NO:855) according to the present invention is supported by 88 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2568
2659

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2141
2232

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2888
2979

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1634
1725

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1100
1191

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1100
1191

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
543
634

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
1796
1887

Segment cluster HUMCEA_PEA_—1_node_—56 (SEQ ID NO:856) according to the present invention is supported by 75 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 69 below describes the starting and ending position of this segment on each transcript.

TABLE 69

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2660
2685

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2233
2258

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
2980
3005

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1726
1751

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1192
1217

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1192
1217

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
635
660

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
1888
1913

Segment cluster HUMCEA_PEA_—1_node_—57 (SEQ ID NO:857) according to the present invention is supported by 82 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2686
2786

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2259
2359

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3006
3106

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1752
1852

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1218
1318

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1218
1318

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
661
761

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
1914
2014

Segment cluster HUMCEA_PEA_—1_node_—58 (SEQ ID NO:858) according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2787
2820

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2360
2393

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3107
3140

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1853
1886

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1319
1352

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1319
1352

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
762
795

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2015
2048

Segment cluster HUMCEA_PEA_—1_node_—60 (SEQ ID NO:859) according to the present invention is supported by 55 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2821
2864

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2394
2437

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3141
3184

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1887
1930

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1353
1396

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1353
1396

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
796
839

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2049
2092

Segment cluster HUMCEA_PEA_—1_node_—61 (SEQ ID NO:860) according to the present invention can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 73 below describes the starting and ending position of this segment on each transcript.

TABLE 73

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2865
2868

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2438
2441

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3185
3188

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1931
1934

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1397
1400

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1397
1400

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
840
843

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2093
2096

Segment cluster HUMCEA_PEA_—1_node_—62 (SEQ ID NO:861) according to the present invention is supported by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 74 below describes the starting and ending position of this segment on each transcript.

TABLE 74

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
2869
2956

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2442
2529

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3189
3276

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
1935
2022

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1401
1488

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1401
1488

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
844
931

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2097
2184

Segment cluster HUMCEA_PEA_—1_node_—64 (SEQ ID NO:862) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCEA_PEA_—1_T8 (SEQ ID NO:806), HUMCEA_PEA_—1_T12 (SEQ ID NO:808), HUMCEA_PEA_—1_T14 (SEQ ID NO:809), HUMCEA_PEA_—1_T16 (SEQ ID NO:810), HUMCEA_PEA_—1_T25 (SEQ ID NO:812), HUMCEA_PEA_—1_T26 (SEQ ID NO:813), HUMCEA_PEA_—1_T29 (SEQ ID NO:814) and HUMCEA_PEA_—1_T30 (SEQ ID NO:815). Table 75 below describes the starting and ending position of this segment on each transcript.

TABLE 75

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HUMCEA_PEA_1_T8 (SEQ ID NO: 806)
3136
3165

HUMCEA_PEA_1_T12 (SEQ ID NO: 808)
2709
2738

HUMCEA_PEA_1_T14 (SEQ ID NO: 809)
3456
3485

HUMCEA_PEA_1_T16 (SEQ ID NO: 810)
2202
2231

HUMCEA_PEA_1_T25 (SEQ ID NO: 812)
1668
1697

HUMCEA_PEA_1_T26 (SEQ ID NO: 813)
1668
1697

HUMCEA_PEA_1_T29 (SEQ ID NO: 814)
1111
1140

HUMCEA_PEA_1_T30 (SEQ ID NO: 815)
2364
2393

Variant Protein Alignment to the Previously Known Protein:

Sequence name: CEA5_HUMAN (SEQ ID NO:863)

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P4 (SEQ ID NO:864) × CEA5_HUMAN (SEQ ID NO:863)

Alignment segment 1/1:

Quality:
2320.00
Escore
0

Matching length:
234
Total length:
234

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: CEA5_HUMAN (SEQ ID NO:863)

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P5 (SEQ ID NO:865) × CEA5_HUMAN (SEQ ID NO:863)

Alignment segment 1/1:

Quality:
6692.00
Escore
0

Matching length:
675
Total length:
675

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Caps:
0

Alignment:

Sequence name: CEA5_HUMAN (SEQ ID NO:863)

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P7 (SEQ ID NO:866) × CEA5_HUMAN (SEQ ID NO:863)

Alignment segment 1/1:

Quality:
6745.00
Escore
0

Matching length:
693
Total length:
702

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
98.72
Total Percent Identity:
98.72

Gaps:
1

Alignment:

Sequence name: CEA5_HUMAN (SEQ ID NO:863)

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P10 (SEQ ID NO:867) × CEA5_HUMAN (SEQ ID NO:863)

Alignment segment 1/1:

Quality:
5057.00
Escore
0

Matching length:
524
Total length:
702

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
74.64
Total Percent Identity:
74.64

Gaps:
1

Alignment:

Sequence name: CEA5_HUMAN (SEQ ID NO:863)

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P19 (SEQ ID NO:869) × CEA5_HUMAN (SEQ ID NO:863)

Alignment segment 1/1:

Quality:
3298.00
Escore
0

Matching length:
346
Total length:
702

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
49.29
Total Percent Identity:
49.29

Gaps:
1

Alignment:

Sequence name: CEA5_HUMAN (SEQ ID NO:863)

Sequence documentation:

Alignment of: HUMCEA_PEA_1_P20 (SEQ ID NO:870) × CEA5_HUMAN (SEQ ID NO:863)

Alignment segment 1/1:

Quality:
3294.00
Escore
0

Matching length:
346
Total length:
702

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
49.29
Total Percent Identity:
49.29

Gaps:
1

Alignment:

Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Transcripts which are Detectable by Seg12 and Seg9, in Normal, and Cancerous Colon Tissues

Expression of Carcinoembryonic antigen-related cell adhesion molecule 5 transcripts detectable by or according to seg12 (SEQ ID NO: 1338) and seg9 (SEQ ID NO: 1339), was measured with oligonucleotide-based micro-arrays. The results of image intensities for each feature were normalized according to the ninetieth percentile of the image intensities of all the features on the chip. Then, feature image intensities for replicates of the same oligonucleotide on the chip and replicates of the same sample were averaged. Outlying results were discarded.

For every oligonucleotide HUMCEA_—0_—0_—96 (seg12, SEQ ID NO: 1338) and HUMCEA_—0_—0_—15168 (seg9, SEQ ID NO: 1339) the averaged intensity determined for every sample was divided by the averaged intensity of all the normal samples (Sample Nos. 62-66 and 69, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to the averaged normal samples. These data are presented in a histogram bellow, in FIG. 50. As is evident from the histogram (FIG. 50), the expression of Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2 transcripts detectable with the above oligonucleotides in cancer samples was higher than in the normal samples.

HUMCEA_0_0_96-

(SEQ ID NO: 1338)

CAAGAGGGGTTTGGCTGAGACTTTAGGATTGTGATTCAGCTTAGAGGGAC

HUMCEA_0_0_15168-

(SEQ ID NO: 1339)

TCCTGCCTGTCACCTGAAGTTCTAGATCATTCCCTGGACTCCACTCTATC

Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 CEACAM5 HUMCEA Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HUMCEA Seg31 (SEQ ID NO: 1342) in Normal and Cancerous Colon Tissues

Expression of CEACAM5 transcripts detectable by or according to seg31, HUMCEA (ver 3.4 T10888) seg31 amplicon (SEQ ID NO: 1342) and HUMCEA seg31-F (SEQ ID NO: 1340) HUMCEA seg31-R (SEQ ID NO: 1341) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 51 is a histogram showing over expression of the above-indicated CEACAM5 transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 51, the expression of CEACAM5 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 9 out of 37 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of CEACAM5 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 6.24E-04. Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 7.42E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCEA seg31F forward primer (SEQ ID NO: 1340); and HUMCEA seg31 R reverse primer (SEQ ID NO: 1341).

Forward primer (SEQ ID NO: 1340):

CGGCCTCCCAAAGTGCT

Reverse primer (SEQ ID NO: 1341):

GGGAAGCTCCTGATTGTAGAAGG

Amplicon (SEQ ID NO: 1342):

CGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCACCCGGCCG

ATTTGGACTTTTTAACACAGGATTGGGACAGGATTCAGAGGGACACTGTG

GCCCTTCTACAATCAGGAGCTTCCC

Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 CEACAM5 HUMCEA Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HUMCEA Seg33 (SEQ ID NO: 1345) in Normal and Cancerous Colon Tissues

Expression of CEACAM5 transcripts detectable by or according to seg33, HUMCEA (ver 3.4 T10888) seg33 amplicon (SEQ ID NO: 1345) and HUMCEA seg33 F (SEQ ID NO: 1343) and HUMCEA seg33 R (SEQ ID NO: 1344) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 52 is a histogram showing over expression of the above-indicated CEACAM5 transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 52, the expression of CEACAM5 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 11 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of CEACAM5 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 4.01E-04. Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 3.78E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCEA seg33F forward primer (SEQ ID NO: 1343); and HUMCEA seg33 R reverse primer (SEQ ID NO: 1344).

Forward primer (SEQ ID NO: 1343):

CTGGAGCATCAGCATCATATTCTG

Reverse primer (SEQ ID NO: 1344):

GAGAGTTGGCCGAGATGGAG

Amplicon (SEQ ID NO: 1345):

CTGGAGCATCAGCATCATATTCTGGGGTGGAGTCTATCTGGTTCTCACCA

AAGAGCCAAGAAGACATTTTCTTTCCCAGTCTGTGTTCCATGGGCACAAG

GAAATCCCAAATTCTATCCTGAGCCCCCTCACTCCATCTCGGCCAACTCT

C

Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 CEACAM5 HUMCEA Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HUMCEA Seg35 (SEQ ID NO: 1348) in Normal and Cancerous Colon Tissues

Expression of CEACAM5 transcripts detectable by or according to seg35, HUMCEA (ver 3.4 T10888) seg35 amplicon (SEQ ID NO: 1348) and HUMCEA seg35 F (SEQ ID NO: 1346) and HUMCEA seg35 R (SEQ ID NO: 1347) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 53 is a histogram showing over expression of the above-indicated CEACAM5 transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 53, the expression of CEACAM5 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 15 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of CEACAM5 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 8.96E-04. Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.27E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HUMCEA seg35F forward primer (SEQ ID NO: 1346); and HUMCEA seg35 R reverse primer (SEQ ID NO: 1347).

Forward primer (SEQ ID NO: 1346):

GAAGCAGAGTCCCCCAGAACT

Reverse primer (SEQ ID NO: 1347):

AAGGCCCAGGCTAGTGCATT

Amplicon (SEQ ID NO: 1348):

GAAGCAGAGTCCCCCAGAACTGGGCTTTTCATTCCCCTGGTGGGAGCCCA

TGAGAAGCGAGTTCTCTGTGCAACGGACTTAGTAAATACAGAATGCACTA

GCCTGGGCCTT

Description for Cluster M78035

Cluster M78035 features 12 transcript(s) and 39 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

M78035_T0
871

M78035_T3
872

M78035_T4
873

M78035_T7
874

M78035_T9
875

M78035_T11
876

M78035_T17
877

M78035_T18
878

M78035_T19
879

M78035_T20
880

M78035_T27
881

M78035_T28
882

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

M78035_node_4
883

M78035_node_6
884

M78035_node_10
885

M78035_node_17
886

M78035_node_18
887

M78035_node_21
888

M78035_node_25
889

M78035_node_33
890

M78035_node_55
891

M78035_node_58
892

M78035_node_60
893

M78035_node_62
894

M78035_node_63
895

M78035_node_64
896

M78035_node_65
897

M78035_node_69
898

M78035_node_71
899

M78035_node_14
900

M78035_node_15
901

M78035_node_20
902

M78035_node_24
903

M78035_node_26
904

M78035_node_28
905

M78035_node_29
906

M78035_node_30
907

M78035_node_31
908

M78035_node_34
909

M78035_node_35
910

M78035_node_37
911

M78035_node_40
912

M78035_node_48
913

M78035_node_49
914

M78035_node_50
915

M78035_node_52
916

M78035_node_53
917

M78035_node_54
918

M78035_node_56
919

M78035_node_57
920

M78035_node_59
921

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

M78035_P2
923
M78035_T0 (SEQ ID NO: 871);

M78035_T17 (SEQ ID NO: 877);

M78035_T18 (SEQ ID NO: 878);

M78035_T19 (SEQ ID NO: 879);

M78035_T20 (SEQ ID NO: 880)

M78035_P4
924
M78035_T3 (SEQ ID NO: 872);

M78035_T4 (SEQ ID NO: 873)

M78035_P6
925
M78035_T7 (SEQ ID NO: 874);

M78035_T9 (SEQ ID NO: 875)

M78035_P8
926
M78035_T11 (SEQ ID NO: 876)

M78035_P18
927
M78035_T27 (SEQ ID NO: 881)

M78035_P19
928
M78035_T28 (SEQ ID NO: 882)

These sequences are variants of the known protein Adenosylhomocysteinase (SwissProt accession identifier SAHH_HUMAN; known also according to the synonyms EC 3.3.1.1; S-adenosyl-L-homocysteine hydrolase; AdoHcyase), SEQ ID NO: 922, referred to herein as the previously known protein.

Protein Adenosylhomocysteinase (SEQ ID NO:922) is known or believed to have the following function(s): Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine. The sequence for protein Adenosylhomocysteinase is given at the end of the application, as “Adenosylhomocysteinase amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

86
D -> N. /FTId = VAR_006934.

Protein Adenosylhomocysteinase (SEQ ID NO:922) localization is believed to be Cytoplasmic.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: one-carbon compound metabolism, which are annotation(s) related to Biological Process; adenosylhomocysteinase; hydrolase, which are annotation(s) related to Molecular Function; and cytoplasm, which are annotation(s) related to Cellular Component.

Cluster M78035 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 54 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, colorectal cancer, epithelial malignant tumors, a mixture of malignant tumors from different tissues, malignant tumors involving the lymph nodes and pancreas carcinoma.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

adrenal
0

bladder
0

bone
97

brain
71

colon
6

epithelial
74

general
72

head and neck
10

kidney
85

liver
48

lung
64

lymph nodes
49

breast
101

bone marrow
62

muscle
57

ovary
36

pancreas
30

prostate
76

skin
204

stomach
109

T cells
0

Thyroid
283

uterus
118

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
1.5e−01
7.0e−02
2.1e−01
3.4
1.5e−01
3.6

bladder
5.4e−01
3.4e−01
5.6e−01
1.8
2.1e−01
2.4

bone
9.2e−01
3.7e−02
1
0.2
2.1e−01
1.4

brain
1.5e−01
2.5e−02
3.8e−03
2.0
1.2e−12
3.7

colon
5.2e−02
2.3e−02
8.0e−02
3.7
2.0e−03
3.9

epithelial
3.1e−02
6.2e−05
1.7e−02
1.5
3.6e−25
3.4

general
6.7e−03
5.9e−10
3.8e−06
1.6
1.3e−66
3.8

head and neck
6.4e−01
2.5e−01
1
0.9
1.3e−01
2.1

kidney
7.6e−01
7.4e−01
2.5e−01
1.3
5.4e−02
1.7

liver
5.5e−02
1.1e−01
4.2e−02
5.1
4.4e−05
2.7

lung
8.0e−01
7.6e−01
6.4e−01
1.1
2.3e−04
2.6

lymph nodes
4.0e−01
1.6e−02
6.3e−01
1.1
2.5e−06
4.7

breast
3.4e−01
2.8e−01
4.3e−01
1.2
1.3e−01
1.3

bone marrow
7.5e−01
5.4e−01
1
0.3
1.9e−01
2.1

muscle
6.3e−01
5.0e−01
4.7e−01
1.6
7.1e−05
1.4

ovary
2.0e−01
1.1e−01
4.9e−01
1.5
3.5e−03
2.7

pancreas
4.5e−02
7.4e−03
2.3e−02
3.0
5.9e−04
3.2

prostate
4.7e−01
3.8e−01
1.4e−01
1.5
3.7e−02
1.6

skin
4.7e−01
5.3e−01
7.2e−01
0.8
6.9e−05
1.2

stomach
1.8e−01
1.7e−02
5.0e−01
1.2
6.2e−03
2.8

T cells
1
6.7e−01
1
1.0
7.2e−01
1.4

Thyroid
6.9e−01
6.9e−01
1
0.5
1
0.5

uterus
7.0e−01
3.4e−01
8.1e−01
0.7
5.6e−02
1.4

As noted above, cluster M178035 features 12 transcripts(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Adenosylhomocysteinase (SEQ ID NO:922). A description of each variant protein according to the present invention is now provided.

Variant protein M78035_P2 (SEQ ID NO:923) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78035_T0 (SEQ ID NO:871), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein M78035_P2 (SEQ ID NO:923) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P2 (SEQ ID NO:923) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

19
R -> H
No

36
R -> L
No

38
R -> W
Yes

65
E -> D
No

74
V -> L
No

77
S ->
No

91
A ->
No

111
L -> P
No

135
L -> I
Yes

206
A ->
No

206
A -> G
No

211
I ->
No

214
K -> R
Yes

226
K ->
No

226
K -> Q
No

265
A ->
No

325
V -> L
No

325
V ->
No

325
V -> G
No

353
H -> Q
No

353
H ->
No

374
T ->
No

383
V -> G
No

383
V ->
No

407
T -> S
No

407
T ->
No

414
A -> T
No

Variant protein M78035_P2 (SEQ ID NO:923) is encoded by the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript M78035_T0 (SEQ ID NO:871) is shown in bold; this coding portion starts at position 132 and ends at position 1427. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P2 (SEQ ID NO:923) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

351
G -> C
No

361
C ->
No

403
C ->
No

463
T -> C
No

476
G -> A
No

482
C -> A
No

506
C -> T
Yes

534
C -> A
Yes

748
C ->
No

748
C -> G
No

763
T ->
No

772
A -> G
Yes

807
A ->
No

807
A -> C
No

925
C ->
No

1016
T -> C
No

1085
G -> A
Yes

1104
G ->
No

1104
G -> T
No

1105
T -> G
No

1190
C ->
No

1190
C -> A
No

1252
C ->
No

1279
T ->
No

1279
T -> G
No

1351
C ->
No

1351
C -> G
No

1371
G -> A
No

1505
C ->
No

1554
C ->
No

1554
C -> G
No

1563
T -> C
No

1573
C ->
No

1573
C -> G
No

1624
C ->
No

1624
C -> A
No

1638
C -> G
No

1664
G ->
No

1664
G -> A
No

1686
T ->
No

1712
T -> C
No

1719
C ->
No

1731
T -> G
Yes

1741
A ->
No

1741
A -> C
No

1755
T ->
No

1775
C ->
No

1775
C -> A
No

1807
T ->
No

1807
T -> G
No

1881
T ->
No

1881
T -> G
No

1937
A ->
No

1937
A -> C
No

1958
C ->
No

1969
-> C
No

1969
-> G
No

2001
A -> C
Yes

2008
A -> C
Yes

2009
C -> G
Yes

2011
G -> C
Yes

2016
G -> T
Yes

2041
C -> T
No

2043
G -> T
No

2047
A -> C
Yes

2084
A -> C
Yes

2086
T ->
No

2109
A -> T
Yes

2153
A -> C
No

2192
T -> C
No

The coding portion of transcript M78035_T17 (SEQ ID NO:877) is shown in bold; this coding portion starts at position 132 and ends at position 1427. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P2 (SEQ ID NO:923) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

351
G -> C
No

361
C ->
No

403
C ->
No

463
T -> C
No

476
G -> A
No

482
C -> A
No

506
C -> T
Yes

534
C -> A
Yes

748
C ->
No

748
C -> G
No

763
T ->
No

772
A -> G
Yes

807
A ->
No

807
A -> C
No

925
C ->
No

1016
T -> C
No

1085
G -> A
Yes

1104
G ->
No

1104
G -> T
No

1105
T -> G
No

1190
C ->
No

1190
C -> A
No

1252
C ->
No

1279
T ->
No

1279
T -> G
No

1351
C ->
No

1351
C -> G
No

1371
G -> A
No

1567
C -> T
Yes

1668
G -> A
Yes

2289
G -> A
Yes

2815
T -> C
Yes

3258
G -> A
No

3260
G -> A
No

The coding portion of transcript M78035_T18 (SEQ ID NO:878) is shown in bold; this coding portion starts at position 132 and ends at position 1427. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P2 (SEQ ID NO:923) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

351
G -> C
No

361
C ->
No

403
C ->
No

463
T -> C
No

476
G -> A
No

482
C -> A
No

506
C -> T
Yes

534
C -> A
Yes

748
C ->
No

748
C -> G
No

763
T ->
No

772
A -> G
Yes

807
A ->
No

807
A -> C
No

925
C ->
No

1016
T -> C
No

1085
G -> A
Yes

1104
G ->
No

1104
G -> T
No

1105
T -> G
No

1190
C ->
No

1190
C -> A
No

1252
C ->
No

1279
T ->
No

1279
T -> G
No

1351
C ->
No

1351
C -> G
No

1371
G -> A
No

1707
C -> T
Yes

1808
G -> A
Yes

2429
G -> A
Yes

2955
T -> C
Yes

3398
G -> A
No

3400
G -> A
No

The coding portion of transcript M78035_T19 (SEQ ID NO:879) is shown in bold; this coding portion starts at position 132 and ends at position 1427. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P2 (SEQ ID NO:923) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

351
G -> C
No

361
C ->
No

403
C ->
No

463
T -> C
No

476
G -> A
No

482
C -> A
No

506
C -> T
Yes

534
C -> A
Yes

748
C ->
No

748
C -> G
No

763
T ->
No

772
A -> G
Yes

807
A ->
No

807
A -> C
No

925
C ->
No

1016
T -> C
No

1085
G -> A
Yes

1104
G ->
No

1104
G -> T
No

1105
T -> G
No

1190
C ->
No

1190
C -> A
No

1252
C ->
No

1279
T ->
No

1279
T -> G
No

1351
C ->
No

1351
C -> G
No

1371
G -> A
No

1569
A -> C
Yes

2440
G -> A
Yes

3110
G -> C
Yes

3323
C -> T
Yes

3630
G -> A
No

The coding portion of transcript M78035_T20 (SEQ ID NO:880) is shown in bold; this coding portion starts at position 132 and ends at position 1427. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P2 (SEQ ID NO:923) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

351
G -> C
No

361
C ->
No

403
C ->
No

463
T -> C
No

476
G -> A
No

482
C -> A
No

506
C -> T
Yes

534
C -> A
Yes

748
C ->
No

748
C -> G
No

763
T ->
No

772
A -> G
Yes

807
A ->
No

807
A -> C
No

925
C ->
No

1016
T -> C
No

1085
G -> A
Yes

1104
G ->
No

1104
G -> T
No

1105
T -> G
No

1190
C ->
No

1190
C -> A
No

1252
C ->
No

1279
T ->
No

1279
T -> G
No

1351
C ->
No

1351
C -> G
No

1371
G -> A
No

1569
A -> C
Yes

2440
G -> A
Yes

2649
G -> C
Yes

2862
C -> T
Yes

3169
G -> A
No

Variant protein M78035_P4 (SEQ ID NO:924) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78035_T3 (SEQ ID NO:872) and M78035_T4 (SEQ ID NO:873). An alignment is given to the known protein (Adenosylhomocysteinase (SEQ ID NO:922)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M78035_P4 (SEQ ID NO:924) and SAHH_HUMAN (SEQ ID NO:922):

1. An isolated chimeric polypeptide encoding for M78035_P4 (SEQ ID NO:924), comprising a first amino acid sequence being at least 90% homologous to MPGLMRMRERYSASKPLKGARIAGCLHMTVETAVLIETLVTLGAEVQWSSCNIFSTQDHAAAAIAKAGIP VYAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMM ANGILKVPAINVNDSVTKSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGA RVIITEIDPINALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVK WLNENAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDK YPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 29-432 of SAHH_HUMAN (SEQ ID NO:922), which also corresponds to amino acids 1-404 of M78035_P4 (SEQ ID NO:924).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein M78035_P4 (SEQ ID NO:924) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P4 (SEQ ID NO:924) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

8
R -> L
No

10
R -> W
Yes

37
E -> D
No

46
V -> L
No

49
S ->
No

63
A ->
No

83
L -> P
No

107
L -> I
Yes

178
A ->
No

178
A -> G
No

183
I ->
No

186
K -> R
Yes

198
K ->
No

198
K -> Q
No

237
A ->
No

297
V -> G
No

297
V -> L
No

297
V ->
No

325
H -> Q
No

325
H ->
No

346
T ->
No

355
V ->
No

355
V -> G
No

379
T ->
No

379
T -> S
No

386
A -> T
No

Variant protein M78035_P4 (SEQ ID NO:924) is encoded by the following transcript(s): M78035_T3 (SEQ ID NO:872) and M78035_T4 (SEQ ID NO:873), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript M78035_T3 (SEQ ID NO:872) is shown in bold; this coding portion starts at position 301 and ends at position 1512. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P4 (SEQ ID NO:924) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

104
A -> G
Yes

272
G -> A
No

282
G -> A
No

323
G -> T
No

328
C -> T
Yes

411
G -> T
No

420
C -> T
No

436
G -> C
No

446
C ->
No

488
C ->
No

548
T -> C
No

561
G -> A
No

567
C -> A
No

591
C -> T
Yes

619
C -> A
Yes

833
C ->
No

833
C -> G
No

848
T ->
No

857
A -> G
Yes

892
A ->
No

892
A -> C
No

1010
C ->
No

1101
T -> C
No

1170
G -> A
Yes

1189
G ->
No

1189
G -> T
No

1190
T -> G
No

1275
C ->
No

1275
C -> A
No

1337
C ->
No

1364
T ->
No

1364
T -> G
No

1436
C ->
No

1436
C -> G
No

1456
G -> A
No

1590
C ->
No

1639
C ->
No

1639
C -> G
No

1648
T -> C
No

1658
C ->
No

1658
C -> G
No

1709
C ->
No

1709
C -> A
No

1723
C -> G
No

1749
G ->
No

1749
G -> A
No

1771
T ->
No

1797
T -> C
No

1804
C ->
No

1816
T -> G
Yes

1826
A ->
No

1826
A -> C
No

1840
T ->
No

1860
C ->
No

1860
C -> A
No

1892
T ->
No

1892
T -> G
No

1966
T ->
No

1966
T -> G
No

2022
A ->
No

2022
A -> C
No

2043
C ->
No

2054
-> C
No

2054
-> G
No

2086
A -> C
Yes

2093
A -> C
Yes

2094
C -> G
Yes

2096
G -> C
Yes

2101
G -> T
Yes

2126
C -> T
No

2128
G -> T
No

2132
A -> C
Yes

2169
A -> C
Yes

2171
T ->
No

2194
A -> T
Yes

2238
A -> C
No

2277
T -> C
No

The coding portion of transcript M78035_T4 (SEQ ID NO:873) is shown in bold; this coding portion starts at position 897 and ends at position 2108. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P4 (SEQ ID NO:924) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

654
G -> A
Yes

868
G -> A
No

878
G -> A
No

919
G -> T
No

924
C -> T
Yes

1007
G -> T
No

1016
C -> T
No

1032
G -> C
No

1042
C ->
No

1084
C ->
No

1144
T -> C
No

1157
G -> A
No

1163
C -> A
No

1187
C -> T
Yes

1215
C -> A
Yes

1429
C ->
No

1429
C -> G
No

1444
T ->
No

1453
A -> G
Yes

1488
A ->
No

1488
A -> C
No

1606
C ->
No

1697
T -> C
No

1766
G -> A
Yes

1785
G ->
No

1785
G -> T
No

1786
T -> G
No

1871
C ->
No

1871
C -> A
No

1933
C ->
No

1960
T ->
No

1960
T -> G
No

2032
C ->
No

2032
C -> G
No

2052
G -> A
No

2186
C ->
No

2235
C ->
No

2235
C -> G
No

2244
T -> C
No

2254
C ->
No

2254
C -> G
No

2305
C ->
No

2305
C -> A
No

2319
C -> G
No

2345
G ->
No

2345
G -> A
No

2367
T ->
No

2393
T -> C
No

2400
C ->
No

2412
T -> G
Yes

2422
A ->
No

2422
A -> C
No

2436
T ->
No

2456
C ->
No

2456
C -> A
No

2488
T ->
No

2488
T -> G
No

2562
T ->
No

2562
T -> G
No

2618
A ->
No

2618
A -> C
No

2639
C ->
No

2650
-> C
No

2650
-> G
No

2682
A -> C
Yes

2689
A -> C
Yes

2690
C -> G
Yes

2692
G -> C
Yes

2697
G -> T
Yes

2722
C -> T
No

2724
G -> T
No

2728
A -> C
Yes

2765
A -> C
Yes

2767
T ->
No

2790
A -> T
Yes

2834
A -> C
No

2873
T -> C
No

Variant protein M78035_P6 (SEQ ID NO:925) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78035_T7 (SEQ ID NO:874) and M78035_T9 (SEQ ID NO:875). An alignment is given to the known protein (Adenosylhomocysteinase (SEQ ID NO:922)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M78035_P6 (SEQ ID NO:925) and SAHH_HUMAN (SEQ ID NO:922):

1. An isolated chimeric polypeptide encoding for M78035_P6 (SEQ ID NO:925), comprising a first amino acid sequence being at least 90% homologous to MILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMANGILKVPAINVNDSVTKSKFDNLYGCRE SLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVIITEIDPINALQAAMEGYEVTTMDEACQ EGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNENAVEKVNIKPQVDRYRLKNGRRIILL AEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDKYPVGVHFLPKKLDEAVAEAHLGKLNVKLT KLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 127-432 of SAHH_HUMAN (SEQ ID NO:922), which also corresponds to amino acids 1-306 of M78035_P6 (SEQ ID NO:925).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein M78035_P6 (SEQ ID NO:925) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P6 (SEQ ID NO:925) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

9
L -> I
Yes

80
A -> G
No

80
A ->
No

85
I ->
No

88
K -> R
Yes

100
K ->
No

100
K -> Q
No

139
A ->
No

199
V ->
No

199
V -> L
No

199
V -> G
No

227
H ->
No

227
H -> Q
No

248
T ->
No

257
V -> G
No

257
V ->
No

281
T -> S
No

281
T ->
No

288
A -> T
No

Variant protein M78035_P6 (SEQ ID NO:925) is encoded by the following transcript(s): M78035_T7 (SEQ ID NO:874) and M78035_T9 (SEQ ID NO:875), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript M78035_T7 (SEQ ID NO:874) is shown in bold; this coding portion starts at position 556 and ends at position 1473. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P6 (SEQ ID NO:925) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

351
G -> C
No

361
C ->
No

403
C ->
No

509
T -> C
No

522
G -> A
No

528
C -> A
No

552
C -> T
Yes

580
C -> A
Yes

794
C ->
No

794
C -> G
No

809
T ->
No

818
A -> G
Yes

853
A ->
No

853
A -> C
No

971
C ->
No

1062
T -> C
No

1131
G -> A
Yes

1150
G ->
No

1150
G -> T
No

1151
T -> G
No

1236
C ->
No

1236
C -> A
No

1298
C ->
No

1325
T ->
No

1325
T -> G
No

1397
C ->
No

1397
C -> G
No

1417
G -> A
No

1551
C ->
No

1600
C ->
No

1600
C -> G
No

1609
T -> C
No

1619
C ->
No

1619
C -> G
No

1670
C ->
No

1670
C -> A
No

1684
C -> G
No

1710
G ->
No

1710
G -> A
No

1732
T ->
No

1758
T -> C
No

1765
C ->
No

1777
T -> G
Yes

1787
A ->
No

1787
A -> C
No

1801
T ->
No

1821
C ->
No

1821
C -> A
No

1853
T ->
No

1853
T -> G
No

1927
T ->
No

1927
T -> G
No

1983
A ->
No

1983
A -> C
No

2004
C ->
No

2015
-> C
No

2015
-> G
No

2047
A -> C
Yes

2054
A -> C
Yes

2055
C -> G
Yes

2057
G -> C
Yes

2062
G -> T
Yes

2087
C -> T
No

2089
G -> T
No

2093
A -> C
Yes

2130
A -> C
Yes

2132
T ->
No

2155
A -> T
Yes

2199
A -> C
No

2238
T -> C
No

The coding portion of transcript M78035_T9 (SEQ ID NO:875) is shown in bold; this coding portion starts at position 768 and ends at position 1685. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P6 (SEQ ID NO:925) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

104
A -> G
Yes

272
G -> A
No

282
G -> A
No

323
G -> T
No

328
C -> T
Yes

411
G -> T
No

420
C -> T
No

609
G -> C
No

619
C ->
No

661
C ->
No

721
T -> C
No

734
G -> A
No

740
C -> A
No

764
C -> T
Yes

792
C -> A
Yes

1006
C ->
No

1006
C -> G
No

1021
T ->
No

1030
A -> G
Yes

1065
A ->
No

1065
A -> C
No

1183
C ->
No

1274
T -> C
No

1343
G -> A
Yes

1362
G ->
No

1362
G -> T
No

1363
T -> G
No

1448
C ->
No

1448
C -> A
No

1510
C ->
No

1537
T ->
No

1537
T -> G
No

1609
C ->
No

1609
C -> G
No

1629
G -> A
No

1763
C ->
No

1812
C ->
No

1812
C -> G
No

1821
T -> C
No

1831
C ->
No

1831
C -> G
No

1882
C ->
No

1882
C -> A
No

1896
C -> G
No

1922
G ->
No

1922
G -> A
No

1944
T ->
No

1970
T -> C
No

1977
C ->
No

1989
T -> G
Yes

1999
A ->
No

1999
A -> C
No

2013
T ->
No

2033
C ->
No

2033
C -> A
No

2065
T ->
No

2065
T -> G
No

2139
T ->
No

2139
T -> G
No

2195
A ->
No

2195
A -> C
No

2216
C ->
No

2227
-> C
No

2227
-> G
No

2259
A -> C
Yes

2266
A -> C
Yes

2267
C -> G
Yes

2269
G -> C
Yes

2274
G -> T
Yes

2299
C -> T
No

2301
G -> T
No

2305
A -> C
Yes

2342
A -> C
Yes

2344
T ->
No

2367
A -> T
Yes

2411
A -> C
No

2450
T -> C
No

Variant protein M78035_P8 (SEQ ID NO:926) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78035_T11 (SEQ ID NO:876). An alignment is given to the known protein (Adenosylhomocysteinase (SEQ ID NO:922)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between M78035_P8 (SEQ ID NO:926) and SAHH_HUMAN (SEQ ID NO:922):

1. An isolated chimeric polypeptide encoding for M78035_P8 (SEQ ID NO:926), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MSDKLPYKV (SEQ ID NO:1474) corresponding to amino acids 1-9 of M78035_P8 (SEQ ID NO:926), and a second amino acid sequence being at least 90% homologous to VYAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMM ANGILKVPAINVNDSVTKSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGA RVIITEIDPINALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVK WLNENAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDK YPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 99-432 of SAHH_HUMAN (SEQ ID NO:922), which also corresponds to amino acids 10-343 of M78035_P8 (SEQ ID NO:926), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of M78035_P8 (SEQ ID NO:926), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MSDKLPYKV (SEQ ID NO:1474) of M78035_P8 (SEQ ID NO:926).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein M78035_P8 (SEQ ID NO:926) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 19, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P8 (SEQ ID NO:926) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

22
L -> P
No

46
L -> I
Yes

117
A ->
No

117
A -> G
No

122
I ->
No

125
K -> R
Yes

137
K ->
No

137
K -> Q
No

176
A ->
No

236
V -> G
No

236
V -> L
No

236
V ->
No

264
H -> Q
No

264
H ->
No

285
T ->
No

294
V ->
No

294
V -> G
No

318
T ->
No

318
T -> S
No

325
A -> T
No

Variant protein M78035_P8 (SEQ ID NO:926) is encoded by the following transcript(s): M78035_T11 (SEQ ID NO:876), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78035_T11 (SEQ ID NO:876) is shown in bold; this coding portion starts at position 132 and ends at position 1160. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P8 (SEQ ID NO:926) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

196
T -> C
No

209
G -> A
No

215
C -> A
No

239
C -> T
Yes

267
C -> A
Yes

481
C ->
No

481
C -> G
No

496
T ->
No

505
A -> G
Yes

540
A ->
No

540
A -> C
No

658
C ->
No

749
T -> C
No

818
G -> A
Yes

837
G ->
No

837
G -> T
No

838
T -> G
No

923
C ->
No

923
C -> A
No

985
C ->
No

1012
T ->
No

1012
T -> G
No

1084
C ->
No

1084
C -> G
No

1104
G -> A
No

1238
C ->
No

1287
C ->
No

1287
C -> G
No

1296
T -> C
No

1306
C ->
No

1306
C -> G
No

1357
C ->
No

1357
C -> A
No

1371
C -> G
No

1397
G ->
No

1397
G -> A
No

1419
T ->
No

1445
T -> C
No

1452
C ->
No

1464
T -> G
Yes

1474
A ->
No

1474
A -> C
No

1488
T ->
No

1508
C ->
No

1508
C -> A
No

1540
T ->
No

1540
T -> G
No

1614
T ->
No

1614
T -> G
No

1670
A ->
No

1670
A -> C
No

1691
C ->
No

1702
-> C
No

1702
-> G
No

1734
A -> C
Yes

1741
A -> C
Yes

1742
C -> G
Yes

1744
G -> C
Yes

1749
G -> T
Yes

1774
C -> T
No

1776
G -> T
No

1780
A -> C
Yes

1817
A -> C
Yes

1819
T ->
No

1842
A -> T
Yes

1886
A -> C
No

1925
T -> C
No

Variant protein M78035_P18 (SEQ ID NO:927) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78035_T27 (SEQ ID NO:881). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein M78035_P18 (SEQ ID NO:927) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 21, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P18 (SEQ ID NO:927) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

19
R -> H
No

36
R -> L
No

38
R -> W
Yes

65
E -> D
No

131
W -> C
No

135
P ->
No

149
P ->
No

Variant protein M78035_P18 (SEQ ID NO:927) is encoded by the following transcript(s): M78035_T27 (SEQ ID NO:881), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78035_T27 (SEQ ID NO:881) is shown in bold; this coding portion starts at position 132 and ends at position 617. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P18 (SEQ ID NO:927) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

8
C -> A
Yes

140
C -> T
No

187
G -> A
No

197
G -> A
No

238
G -> T
No

243
C -> T
Yes

326
G -> T
No

335
C -> T
No

524
G -> C
No

534
C ->
No

576
C ->
No

980
G -> A
Yes

Variant protein M78035_P19 (SEQ ID NO:928) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M78035_T28 (SEQ ID NO:882). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein M78035_P19 (SEQ ID NO:928) is encoded by the following transcript(s): M78035_T28 (SEQ ID NO:882), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M78035_T28 (SEQ ID NO:882) is shown in bold; this coding portion starts at position 585 and ends at position 902. The transcript also has the following SNPs as listed in Table 23 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M78035_P19 (SEQ ID NO:928) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

483
G -> A
Yes

1153
G -> C
Yes

1366
C -> T
Yes

1673
G -> A
No

As noted above, cluster M78035 features 39 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster M78035_node_—4 (SEQ ID NO:883) according to the present invention is supported by 163 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T7 (SEQ ID NO:874), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879), M78035_T20 (SEQ ID NO:880) and M78035_T27 (SEQ ID NO:881). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1
159

M78035_T7 (SEQ ID NO: 874)
1
159

M78035_T11 (SEQ ID NO: 876)
1
159

M78035_T17 (SEQ ID NO: 877)
1
159

M78035_T18 (SEQ ID NO: 878)
1
159

M78035_T19 (SEQ ID NO: 879)
1
159

M78035_T20 (SEQ ID NO: 880)
1
159

M78035_T27 (SEQ ID NO: 881)
1
159

Segment cluster M78035_node_—6 (SEQ ID NO:884) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T4 (SEQ ID NO:873). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T4 (SEQ ID NO: 873)
1
840

Segment cluster M78035_node_—10 (SEQ ID NO:885) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T3 (SEQ ID NO:872) and M78035_T9 (SEQ ID NO:875). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T3 (SEQ ID NO: 872)
1
244

M78035_T9 (SEQ ID NO: 875)
1
244

Segment cluster M78035_node_—17 (SEQ ID NO:886) according to the present invention is supported by 189 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879), M78035_T20 (SEQ ID NO:880) and M78035_T27 (SEQ ID NO:881). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
160
350

M78035_T3 (SEQ ID NO: 872)
245
435

M78035_T4 (SEQ ID NO: 873)
841
1031

M78035_T7 (SEQ ID NO: 874)
160
350

M78035_T9 (SEQ ID NO: 875)
245
435

M78035_T17 (SEQ ID NO: 877)
160
350

M78035_T18 (SEQ ID NO: 878)
160
350

M78035_T19 (SEQ ID NO: 879)
160
350

M78035_T20 (SEQ ID NO: 880)
160
350

M78035_T27 (SEQ ID NO: 881)
160
350

Segment cluster M78035_node_—18 (SEQ ID NO:887) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T9 (SEQ ID NO:875) and M78035_T27 (SEQ ID NO:881). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T9 (SEQ ID NO: 875)
436
608

M78035_T27 (SEQ ID NO: 881)
351
523

Segment cluster M78035_node_—21 (SEQ ID NO:888) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T27 (SEQ ID NO:881). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T27 (SEQ ID NO: 881)
600
998

Segment cluster M78035_node_—25 (SEQ ID NO:889) according to the present invention is supported by 171 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
427
569

M78035_T3 (SEQ ID NO: 872)
512
654

M78035_T4 (SEQ ID NO: 873)
1108
1250

M78035_T7 (SEQ ID NO: 874)
473
615

M78035_T9 (SEQ ID NO: 875)
685
827

M78035_T11 (SEQ ID NO: 876)
160
302

M78035_T17 (SEQ ID NO: 877)
427
569

M78035_T18 (SEQ ID NO: 878)
427
569

M78035_T19 (SEQ ID NO: 879)
427
569

M78035_T20 (SEQ ID NO: 880)
427
569

Segment cluster M78035_node_—33 (SEQ ID NO:890) according to the present invention is supported by 191 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
690
860

M78035_T3 (SEQ ID NO: 872)
775
945

M78035_T4 (SEQ ID NO: 873)
1371
1541

M78035_T7 (SEQ ID NO: 874)
736
906

M78035_T9 (SEQ ID NO: 875)
948
1118

M78035_T11 (SEQ ID NO: 876)
423
593

M78035_T17 (SEQ ID NO: 877)
690
860

M78035_T18 (SEQ ID NO: 878)
690
860

M78035_T19 (SEQ ID NO: 879)
690
860

M78035_T20 (SEQ ID NO: 880)
690
860

Segment cluster M78035_node_—55 (SEQ ID NO:891) according to the present invention is supported by 238 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875) and M78035_T11 (SEQ ID NO:876). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1438
1578

M78035_T3 (SEQ ID NO: 872)
1523
1663

M78035_T4 (SEQ ID NO: 873)
2119
2259

M78035_T7 (SEQ ID NO: 874)
1484
1624

M78035_T9 (SEQ ID NO: 875)
1696
1836

M78035_T11 (SEQ ID NO: 876)
1171
1311

Segment cluster M78035_node_—58 (SEQ ID NO:892) according to the present invention is supported by 273 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875) and M78035_T11 (SEQ ID NO:876). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1663
1813

M78035_T3 (SEQ ID NO: 872)
1748
1898

M78035_T4 (SEQ ID NO: 873)
2344
2494

M78035_T7 (SEQ ID NO: 874)
1709
1859

M78035_T9 (SEQ ID NO: 875)
1921
2071

M78035_T11 (SEQ ID NO: 876)
1396
1546

Segment cluster M78035_node_—60 (SEQ ID NO:893) according to the present invention is supported by 268 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875) and M78035_T11 (SEQ ID NO:876). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1899
2194

M78035_T3 (SEQ ID NO: 872)
1984
2279

M78035_T4 (SEQ ID NO: 873)
2580
2875

M78035_T7 (SEQ ID NO: 874)
1945
2240

M78035_T9 (SEQ ID NO: 875)
2157
2452

M78035_T11 (SEQ ID NO: 876)
1632
1927

Segment cluster M78035_node_—62 (SEQ ID NO:894) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T19 (SEQ ID NO: 879)
1438
2099

M78035_T20 (SEQ ID NO: 880)
1438
2099

Segment cluster M78035_node_—63 (SEQ ID NO:895) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T19 (SEQ ID NO:879), M78035_T20 (SEQ ID NO:880) and M78035_T28 (SEQ ID NO:882). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T19 (SEQ ID NO: 879)
2100
2490

M78035_T20 (SEQ ID NO: 880)
2100
2490

M78035_T28 (SEQ ID NO: 882)
143
533

Segment cluster M78035_node_—64 (SEQ ID NO:896) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T19 (SEQ ID NO:879) and M78035_T28 (SEQ ID NO:882). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T19 (SEQ ID NO: 879)
2491
2951

M78035_T28 (SEQ ID NO: 882)
534
994

Segment cluster M78035_node_—65 (SEQ ID NO:897) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T19 (SEQ ID NO:879), M78035_T20 (SEQ ID NO:880) and M78035_T28 (SEQ ID NO:882). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T19 (SEQ ID NO: 879)
2952
3919

M78035_T20 (SEQ ID NO: 880)
2491
3458

M78035_T28 (SEQ ID NO: 882)
995
1962

Segment cluster M78035_node_—69 (SEQ ID NO:898) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T18 (SEQ ID NO:878). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T18 (SEQ ID NO: 878)
1438
1577

Segment cluster M78035_node_—71 (SEQ ID NO:899) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T17 (SEQ ID NO:877) and M78035_T18 (SEQ ID NO:878). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T17 (SEQ ID NO: 877)
1438
3302

M78035_T18 (SEQ ID NO: 878)
1578
3442

Segment cluster M78035_node_—14 (SEQ ID NO:900) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T28 (SEQ ID NO:882). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T28 (SEQ ID NO: 882)
1
95

Segment cluster M78035_node_—15 (SEQ ID NO:901) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T28 (SEQ ID NO:882). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T28 (SEQ ID NO: 882)
96
142

Segment cluster M78035_node_—20 (SEQ ID NO:902) according to the present invention is supported by 162 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879), M78035_T20 (SEQ ID NO:880) and M78035_T27 (SEQ ID NO:881). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
351
426

M78035_T3 (SEQ ID NO: 872)
436
511

M78035_T4 (SEQ ID NO: 873)
1032
1107

M78035_T7 (SEQ ID NO: 874)
351
426

M78035_T9 (SEQ ID NO: 875)
609
684

M78035_T17 (SEQ ID NO: 877)
351
426

M78035_T18 (SEQ ID NO: 878)
351
426

M78035_T19 (SEQ ID NO: 879)
351
426

M78035_T20 (SEQ ID NO: 880)
351
426

M78035_T27 (SEQ ID NO: 881)
524
599

Segment cluster M78035_node_—24 (SEQ ID NO:903) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T7 (SEQ ID NO:874). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T7 (SEQ ID NO: 874)
427
472

Segment cluster M78035_node_—26 (SEQ ID NO:904) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
570
576

M78035_T3 (SEQ ID NO: 872)
655
661

M78035_T4 (SEQ ID NO: 873)
1251
1257

M78035_T7 (SEQ ID NO: 874)
616
622

M78035_T9 (SEQ ID NO: 875)
828
834

M78035_T11 (SEQ ID NO: 876)
303
309

M78035_T17 (SEQ ID NO: 877)
570
576

M78035_T18 (SEQ ID NO: 878)
570
576

M78035_T19 (SEQ ID NO: 879)
570
576

M78035_T20 (SEQ ID NO: 880)
570
576

Segment cluster M78035_node_—28 (SEQ ID NO:905) according to the present invention is supported by 161 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
577
622

M78035_T3 (SEQ ID NO: 872)
662
707

M78035_T4 (SEQ ID NO: 873)
1258
1303

M78035_T7 (SEQ ID NO: 874)
623
668

M78035_T9 (SEQ ID NO: 875)
835
880

M78035_T11 (SEQ ID NO: 876)
310
355

M78035_T17 (SEQ ID NO: 877)
577
622

M78035_T18 (SEQ ID NO: 878)
577
622

M78035_T19 (SEQ ID NO: 879)
577
622

M78035_T20 (SEQ ID NO: 880)
577
622

Segment cluster M78035_node_—29 (SEQ ID NO:906) according to the present invention is supported by 157 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
623
657

M78035_T3 (SEQ ID NO: 872)
708
742

M78035_T4 (SEQ ID NO: 873)
1304
1338

M78035_T7 (SEQ ID NO: 874)
669
703

M78035_T9 (SEQ ID NO: 875)
881
915

M78035_T11 (SEQ ID NO: 876)
356
390

M78035_T17 (SEQ ID NO: 877)
623
657

M78035_T18 (SEQ ID NO: 878)
623
657

M78035_T19 (SEQ ID NO: 879)
623
657

M78035_T20 (SEQ ID NO: 880)
623
657

Segment cluster M78035_node_—30 (SEQ ID NO:907) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
658
664

M78035_T3 (SEQ ID NO: 872)
743
749

M78035_T4 (SEQ ID NO: 873)
1339
1345

M78035_T7 (SEQ ID NO: 874)
704
710

M78035_T9 (SEQ ID NO: 875)
916
922

M78035_T11 (SEQ ID NO: 876)
391
397

M78035_T17 (SEQ ID NO: 877)
658
664

M78035_T18 (SEQ ID NO: 878)
658
664

M78035_T19 (SEQ ID NO: 879)
658
664

M78035_T20 (SEQ ID NO: 880)
658
664

Segment cluster M78035_node_—31 (SEQ ID NO:908) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
665
689

M78035_T3 (SEQ ID NO: 872)
750
774

M78035_T4 (SEQ ID NO: 873)
1346
1370

M78035_T7 (SEQ ID NO: 874)
711
735

M78035_T9 (SEQ ID NO: 875)
923
947

M78035_T11 (SEQ ID NO: 876)
398
422

M78035_T17 (SEQ ID NO: 877)
665
689

M78035_T18 (SEQ ID NO: 878)
665
689

M78035_T19 (SEQ ID NO: 879)
665
689

M78035_T20 (SEQ ID NO: 880)
665
689

Segment cluster M78035_node_—34 (SEQ ID NO:909) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
861
878

M78035_T3 (SEQ ID NO: 872)
946
963

M78035_T4 (SEQ ID NO: 873)
1542
1559

M78035_T7 (SEQ ID NO: 874)
907
924

M78035_T9 (SEQ ID NO: 875)
1119
1136

M78035_T11 (SEQ ID NO: 876)
594
611

M78035_T17 (SEQ ID NO: 877)
861
878

M78035_T18 (SEQ ID NO: 878)
861
878

M78035_T19 (SEQ ID NO: 879)
861
878

M78035_T20 (SEQ ID NO: 880)
861
878

Segment cluster M78035_node_—35 (SEQ ID NO:910) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
879
897

M78035_T3 (SEQ ID NO: 872)
964
982

M78035_T4 (SEQ ID NO: 873)
1560
1578

M78035_T7 (SEQ ID NO: 874)
925
943

M78035_T9 (SEQ ID NO: 875)
1137
1155

M78035_T11 (SEQ ID NO: 876)
612
630

M78035_T17 (SEQ ID NO: 877)
879
897

M78035_T18 (SEQ ID NO: 878)
879
897

M78035_T19 (SEQ ID NO: 879)
879
897

M78035_T20 (SEQ ID NO: 880)
879
897

Segment cluster M78035_node_—37 (SEQ ID NO:911) according to the present invention is supported by 177 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
898
985

M78035_T3 (SEQ ID NO: 872)
983
1070

M78035_T4 (SEQ ID NO: 873)
1579
1666

M78035_T7 (SEQ ID NO: 874)
944
1031

M78035_T9 (SEQ ID NO: 875)
1156
1243

M78035_T11 (SEQ ID NO: 876)
631
718

M78035_T17 (SEQ ID NO: 877)
898
985

M78035_T18 (SEQ ID NO: 878)
898
985

M78035_T19 (SEQ ID NO: 879)
898
985

M78035_T20 (SEQ ID NO: 880)
898
985

Segment cluster M78035_node_—40 (SEQ ID NO:912) according to the present invention is supported by 194 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
986
1103

M78035_T3 (SEQ ID NO: 872)
1071
1188

M78035_T4 (SEQ ID NO: 873)
1667
1784

M78035_T7 (SEQ ID NO: 874)
1032
1149

M78035_T9 (SEQ ID NO: 875)
1244
1361

M78035_T11 (SEQ ID NO: 876)
719
836

M78035_T17 (SEQ ID NO: 877)
986
1103

M78035_T18 (SEQ ID NO: 878)
986
1103

M78035_T19 (SEQ ID NO: 879)
986
1103

M78035_T20 (SEQ ID NO: 880)
986
1103

Segment cluster M78035_node_—48 (SEQ ID NO:913) according to the present invention is supported by 180 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1104
1145

M78035_T3 (SEQ ID NO: 872)
1189
1230

M78035_T4 (SEQ ID NO: 873)
1785
1826

M78035_T7 (SEQ ID NO: 874)
1150
1191

M78035_T9 (SEQ ID NO: 875)
1362
1403

M78035_T11 (SEQ ID NO: 876)
837
878

M78035_T17 (SEQ ID NO: 877)
1104
1145

M78035_T18 (SEQ ID NO: 878)
1104
1145

M78035_T19 (SEQ ID NO: 879)
1104
1145

M78035_T20 (SEQ ID NO: 880)
1104
1145

Segment cluster M78035_node_—49 (SEQ ID NO:914) according to the present invention is supported by 190 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1146
1226

M78035_T3 (SEQ ID NO: 872)
1231
1311

M78035_T4 (SEQ ID NO: 873)
1827
1907

M78035_T7 (SEQ ID NO: 874)
1192
1272

M78035_T9 (SEQ ID NO: 875)
1404
1484

M78035_T11 (SEQ ID NO: 876)
879
959

M78035_T17 (SEQ ID NO: 877)
1146
1226

M78035_T18 (SEQ ID NO: 878)
1146
1226

M78035_T19 (SEQ ID NO: 879)
1146
1226

M78035_T20 (SEQ ID NO: 880)
1146
1226

Segment cluster M78035_node_—50 (SEQ ID NO:915) according to the present invention is supported by 190 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1227
1298

M78035_T3 (SEQ ID NO: 872)
1312
1383

M78035_T4 (SEQ ID NO: 873)
1908
1979

M78035_T7 (SEQ ID NO: 874)
1273
1344

M78035_T9 (SEQ ID NO: 875)
1485
1556

M78035_T11 (SEQ ID NO: 876)
960
1031

M78035_T17 (SEQ ID NO: 877)
1227
1298

M78035_T18 (SEQ ID NO: 878)
1227
1298

M78035_T19 (SEQ ID NO: 879)
1227
1298

M78035_T20 (SEQ ID NO: 880)
1227
1298

Segment cluster M78035_node_—52 (SEQ ID NO:916) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1299
1314

M78035_T3 (SEQ ID NO: 872)
1384
1399

M78035_T4 (SEQ ID NO: 873)
1980
1995

M78035_T7 (SEQ ID NO: 874)
1345
1360

M78035_T9 (SEQ ID NO: 875)
1557
1572

M78035_T11 (SEQ ID NO: 876)
1032
1047

M78035_T17 (SEQ ID NO: 877)
1299
1314

M78035_T18 (SEQ ID NO: 878)
1299
1314

M78035_T19 (SEQ ID NO: 879)
1299
1314

M78035_T20 (SEQ ID NO: 880)
1299
1314

Segment cluster M78035_node_—53 (SEQ ID NO:917) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1315
1334

M78035_T3 (SEQ ID NO: 872)
1400
1419

M78035_T4 (SEQ ID NO: 873)
1996
2015

M78035_T7 (SEQ ID NO: 874)
1361
1380

M78035_T9 (SEQ ID NO: 875)
1573
1592

M78035_T11 (SEQ ID NO: 876)
1048
1067

M78035_T17 (SEQ ID NO: 877)
1315
1334

M78035_T18 (SEQ ID NO: 878)
1315
1334

M78035_T19 (SEQ ID NO: 879)
1315
1334

M78035_T20 (SEQ ID NO: 880)
1315
1334

Segment cluster M78035_node_—54 (SEQ ID NO:918) according to the present invention is supported by 213 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875), M78035_T11 (SEQ ID NO:876), M78035_T17 (SEQ ID NO:877), M78035_T18 (SEQ ID NO:878), M78035_T19 (SEQ ID NO:879) and M78035_T20 (SEQ ID NO:880). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1335
1437

M78035_T3 (SEQ ID NO: 872)
1420
1522

M78035_T4 (SEQ ID NO: 873)
2016
2118

M78035_T7 (SEQ ID NO: 874)
1381
1483

M78035_T9 (SEQ ID NO: 875)
1593
1695

M78035_T11 (SEQ ID NO: 876)
1068
1170

M78035_T17 (SEQ ID NO: 877)
1335
1437

M78035_T18 (SEQ ID NO: 878)
1335
1437

M78035_T19 (SEQ ID NO: 879)
1335
1437

M78035_T20 (SEQ ID NO: 880)
1335
1437

Segment cluster M78035_node_—56 (SEQ ID NO:919) according to the present invention can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875) and M78035_T11 (SEQ ID NO:876). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1579
1592

M78035_T3 (SEQ ID NO: 872)
1664
1677

M78035_T4 (SEQ ID NO: 873)
2260
2273

M78035_T7 (SEQ ID NO: 874)
1625
1638

M78035_T9 (SEQ ID NO: 875)
1837
1850

M78035_T11 (SEQ ID NO: 876)
1312
1325

Segment cluster M78035_node_—57 (SEQ ID NO:920) according to the present invention is supported by 225 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875) and M78035_T11 (SEQ ID NO:876). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1593
1662

M78035_T3 (SEQ ID NO: 872)
1678
1747

M78035_T4 (SEQ ID NO: 873)
2274
2343

M78035_T7 (SEQ ID NO: 874)
1639
1708

M78035_T9 (SEQ ID NO: 875)
1851
1920

M78035_T11 (SEQ ID NO: 876)
1326
1395

Segment cluster M78035_node_—59 (SEQ ID NO:921) according to the present invention is supported by 251 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M78035_T0 (SEQ ID NO:871), M78035_T3 (SEQ ID NO:872), M78035_T4 (SEQ ID NO:873), M78035_T7 (SEQ ID NO:874), M78035_T9 (SEQ ID NO:875) and M78035_T11 (SEQ ID NO:876). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

M78035_T0 (SEQ ID NO: 871)
1814
1898

M78035_T3 (SEQ ID NO: 872)
1899
1983

M78035_T4 (SEQ ID NO: 873)
2495
2579

M78035_T7 (SEQ ID NO: 874)
1860
1944

M78035_T9 (SEQ ID NO: 875)
2072
2156

M78035_T11 (SEQ ID NO: 876)
1547
1631

Variant Protein Alignment to the Previously Known Protein:

Sequence name: SAHH_HUMAN (SEQ ID NO:922)

Sequence documentation:

Alignment of: M78035_P4 (SEQ ID NO:924) × SAHH_HUMAN (SEQ ID NO:922) ..

Alignment segment 1/1:

Quality:
3949.00
Escore
0

Matching length:
404
Total length:
404

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: SAHH_HUMAN (SEQ ID NO:922)

Sequence documentation:

Alignment of: M78035_P6 (SEQ ID NO:925) × SAHH_HUMAN (SEQ ID NO:922) ..

Alignment segment 1/1:

Quality:
2982.00
Escore
0

Matching length:
306
Total length:
306

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: SAHH_HUMAN (SEQ ID NO:922)

Sequence documentation:

Alignment of: M78035_P8 (SEQ ID NO:926) × SAHH_HUMAN (SEQ ID NO:922) ..

Alignment segment 1/1:

Quality:
3275.00
Escore
0

Matching length:
334
Total length:
334

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Expression of S-Adenosylhomocysteine Hydrolase (AHCY) M78035 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name M78035Seg42 (SEQ ID NO: 1351) in Normal and Cancerous Colon Tissues

Expression of S-adenosylhomocysteine hydrolase (AHCY) transcripts detectable by or according to seg42, M78035seg42 amplicon (SEQ ID NO: 1351) and M78035seg42F (SEQ ID NO: 1349) and M78035seg42R (SEQ ID NO: 1350) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 55 is a histogram showing over expression of the above-indicated S-adenosylhomocysteine hydrolase (AHCY) transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 55, the expression of S-adenosylhomocysteine hydrolase (AHCY) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 11 out of 37 adenocarcinoma samples, Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of S-adenosylhomocysteine hydrolase (AHCY) transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 1.03E-04. Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 3.76E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: M78035seg42F forward primer (SEQ ID NO: 1349); and M78035seg42R reverse primer (SEQ ID NO: 1350).

Forward primer (SEQ ID NO: 1349):

TGGTCTGGACTCAATCCCG

Reverse primer (SEQ ID NO: 1350):

GGAGTCTGAGTCCAAGCAGCC

Amplicon (SEQ ID NO: 1351):

TGGTCTGGACTCAATCCCGGGACTTTAGGACTTTTGCTAGAAATCTGGTG

TGGTGCAGGAGCGACTCCAGGATTCACTCTGTGGGCTGCTTGGACTCAGA

CTCC

Description for Cluster R30650

Cluster R30650 features 8 transcript(s) and 49 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

R30650_PEA_2_T2
929

R30650_PEA_2_T3
930

R30650_PEA_2_T6
931

R30650_PEA_2_T14
932

R30650_PEA_2_T15
933

R30650_PEA_2_T18
934

R30650_PEA_2_T21
935

R30650_PEA_2_T23
936

TABLE 2

Segments of interest

Segment name
SEQ ID NO:

R30650_PEA_2_node_0
937

R30650_PEA_2_node_1
938

R30650_PEA_2_node_3
939

R30650_PEA_2_node_5
940

R30650_PEA_2_node_9
941

R30650_PEA_2_node_11
942

R30650_PEA_2_node_14
943

R30650_PEA_2_node_20
944

R30650_PEA_2_node_22
945

R30650_PEA_2_node_24
946

R30650_PEA_2_node_26
947

R30650_PEA_2_node_32
948

R30650_PEA_2_node_34
949

R30650_PEA_2_node_36
950

R30650_PEA_2_node_37
951

R30650_PEA_2_node_39
952

R30650_PEA_2_node_41
953

R30650_PEA_2_node_42
954

R30650_PEA_2_node_44
955

R30650_PEA_2_node_46
956

R30650_PEA_2_node_50
957

R30650_PEA_2_node_56
958

R30650_PEA_2_node_60
959

R30650_PEA_2_node_63
960

R30650_PEA_2_node_67
961

R30650_PEA_2_node_70
962

R30650_PEA_2_node_72
963

R30650_PEA_2_node_73
964

R30650_PEA_2_node_75
965

R30650_PEA_2_node_79
966

R30650_PEA_2_node_86
967

R30650_PEA_2_node_87
968

R30650_PEA_2_node_89
969

R30650_PEA_2_node_93
970

R30650_PEA_2_node_8
971

R30650_PEA_2_node_17
972

R30650_PEA_2_node_28
973

R30650_PEA_2_node_31
974

R30650_PEA_2_node_48
975

R30650_PEA_2_node_53
976

R30650_PEA_2_node_58
977

R30650_PEA_2_node_68
978

R30650_PEA_2_node_77
979

R30650_PEA_2_node_82
980

R30650_PEA_2_node_85
981

R30650_PEA_2_node_88
982

R30650_PEA_2_node_90
983

R30650_PEA_2_node_91
984

R30650_PEA_2_node_92
985

TABLE 3

Proteins of interest

SEQ

ID

Protein Name
NO:
Corresponding Transcript(s)

R30650_PEA_2_P4
991
R30650_PEA_2_T2

(SEQ ID NO: 929)

R30650_PEA_2_P5
992
R30650_PEA_2_T3

(SEQ ID NO: 930)

R30650_PEA_2_P8
993
R30650_PEA_2_T6

(SEQ ID NO: 931)

R30650_PEA_2_P12
994
R30650_PEA_2_T14

(SEQ ID NO: 932)

R30650_PEA_2_P13
995
R30650_PEA_2_T15

(SEQ ID NO: 933);

R30650_PEA_2_T21

(SEQ ID NO: 935)

R30650_PEA_2_P15
996
R30650_PEA_2_T18

(SEQ ID NO: 934)

R30650_PEA_2_P17
997
R30650_PEA_2_T23

(SEQ ID NO: 936)

These sequences are variants of the known protein Protein KIAA1199 precursor (SwissProt accession identifier K199_HUMAN), SEQ ID NO: 986, referred to herein as the previously known protein.

Protein Protein KIAA1199 precursor (SEQ ID NO:986) is known or believed to have the following function(s): May be involved in hearing. The sequence for protein Protein KIAA1199 precursor is given at the end of the application, as “Protein KIAA1199 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s)

on amino acid

sequence
Comment

187
R -> C (in nonsyndromic hearing loss; in one

family). /FTId = VAR_018165.

187
R -> H (in nonsyndromic hearing loss;

in two unrelated families). /FTId = VAR_018166.

783
H -> R. /FTId = VAR_018167.

783
H -> Y (in nonsyndromic hearing loss; in one

sporadic case). /FTId = VAR_018168.

1109
V -> I. /FTId = VAR_018169.

1169
P -> A (common polymorphism). /FTId =

VAR_018170.

558-564
HFHLAGD -> TRPPTRP

862
H -> T

Cluster R30650 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 56 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bone
3420

brain
29

colon
63

epithelial
28

general
88

head and neck
0

lung
33

ovary
0

pancreas
0

prostate
2

skin
137

stomach
0

uterus
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bone
6.9e−01
7.8e−01
1
0.0
1
0.0

brain
2.7e−01
5.0e−01
8.8e−02
2.3
3.7e−01
1.3

colon
6.7e−02
4.8e−02
1.6e−01
1.8
1.8e−01
1.8

epithelial
2.7e−03
7.1e−03
8.0e−03
1.6
1.0e−01
1.3

general
7.9e−03
5.0e−02
1
0.6
1
0.4

head and neck
2.1e−01
3.3e−01
0.0e+00
0.0
0.0e+00
0.0

lung
5.7e−01
3.5e−01
8.8e−01
0.8
3.4e−01
1.3

ovary
2.2e−01
2.6e−01
4.7e−01
2.0
5.9e−01
1.7

pancreas
2.2e−02
6.9e−02
3.2e−02
6.5
7.7e−02
4.6

prostate
9.0e−01
9.2e−01
4.5e−01
1.8
5.6e−01
1.5

skin
6.0e−01
5.8e−01
8.1e−01
0.6
1
0.3

stomach
3.0e−01
4.3e−01
4.0e−03
3.0
8.4e−02
2.3

uterus
4.1e−02
1.6e−01
8.5e−02
3.6
2.6e−01
2.3

For this cluster, at least one oligonucleotide was found to demonstrate overexpression of the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously described. The following oligonucleotides were found to hit this cluster but not other segments/transcripts below, shown in Table 7.

TABLE 7

Oligonucleotides related to this cluster

Oligonucleotide name
Overexpressed in cancers
Chip reference

H85953_0_18_0
colorectal cancer
Colon

As noted above, cluster R30650 features 8 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Protein KIAA1199 precursor (SEQ ID NO:986). A description of each variant protein according to the present invention is now provided.

Variant protein R30650_PEA_—2_P4 (SEQ ID NO:991) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T2 (SEQ ID NO:929). An alignment is given to the known protein (Protein KIAA1199 precursor (SEQ ID NO:986)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R30650_PEA_—2_P4 (SEQ ID NO:991) and Q9ULM1 (SEQ ID NO:989):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 90% homologous to MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTEL KHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFF TEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLIN CAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKR PFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVAL EGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEY PGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRST HYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTG VFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCT ATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQV VVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKL KEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 126-1013 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 1-888 of R30650_PEA_—2_P4 (SEQ ID NO:991).

Comparison Report Between R30650_PEA_—2_P4 (SEQ ID NO:991) and Q8WUJ3 (SEQ ID NO: 987):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 90% homologous to MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTEL KHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFF TEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLIN CAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKR PFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVAL EGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEY PGSYLTKND corresponding to amino acids 474-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-504 of R30650_PEA_—2_P4 (SEQ ID NO:991), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTE RAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQG RVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVG FKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 505-888 of R30650_PEA_—2_P4 (SEQ ID NO:991), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTE RAYVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQG RVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVG FKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL in R30650_PEA_—2_P4 (SEQ ID NO:991).

Comparison Report Between R30650_PEA_—2_P4 (SEQ ID NO:991) and Q9NPN9 (SEQ ID NO: 988):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTEL KHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1-91 of R30650_PEA_—2_P4 (SEQ ID NO:991), and a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKS GTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTG PSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPRE PAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGT EMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCP HNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCIN VPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWD QTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSH YYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKK LFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLD TEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 8-804 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 92-888 of R30650_PEA_—2_P4 (SEQ ID NO:991), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between R30650_PEA_—2_P4 (SEQ ID NO:991) and Q9H1K5 (SEQ ID NO:990):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTEL KHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFF TEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLIN CAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKR PFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1-389 of R30650_PEA_—2_P4 (SEQ ID NO:991), and a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSR VFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQ MYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNK GDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKA QNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVK MESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPD NSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPV VKKKKL corresponding to amino acids 2-500 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 390-888 of R30650_PEA_—2_P4 (SEQ ID NO:991), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R30650_PEA_—2_P4 (SEQ ID NO:991), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTEL KHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFF TEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLIN CAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKR PFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_—2_P4 (SEQ ID NO:991).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein R30650_PEA_—2_P4 (SEQ ID NO:991) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P4 (SEQ ID NO:991) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

264
M -> V
Yes

310
H -> R
Yes

Variant protein R30650_PEA_—2_P4 (SEQ ID NO:991) is encoded by the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R30650_PEA_—2_T2 (SEQ ID NO:929) is shown in bold; this coding portion starts at position 1369 and ends at position 4032. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P4 (SEQ ID NO:991) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

464
T -> C
Yes

1833
T -> C
Yes

1920
A -> G
Yes

2158
A -> G
Yes

2297
A -> G
Yes

4180
G -> C
Yes

4396
G -> A
Yes

5457
G -> A
Yes

6505
C -> T
Yes

6644
T -> C
Yes

6736
A -> C
Yes

Variant protein R30650_PEA_—2_P5 (SEQ ID NO:992) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T3 (SEQ ID NO:930). An alignment is given to the known protein (Protein KIAA1199 precursor (SEQ ID NO:986)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R30650_PEA_—2_P5 (SEQ ID NO:992) and Q9ULM1 (SEQ ID NO:989):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 90% homologous to MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWK PGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEM EDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPP TYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSK MCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKN QDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGP GGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFED VPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSG CYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWL INFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLF LKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDH FLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYV ATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQV VPIPVVKKKKL corresponding to amino acids 18-1013 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 1-996 of R30650_PEA_—2_P5 (SEQ ID NO:992).

Comparison Report Between R30650_PEA_—2_P5 (SEQ ID NO:992) and Q8WUJ3 (SEQ ID NO:987):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 90% homologous to MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWK PGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEM EDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPP TYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSK MCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKN QDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGP GGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFED VPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 366-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-612 of R30650_PEA_—2_P5 (SEQ ID NO:992), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTE RAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQG RVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVG FKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 613-996 of R30650_PEA_—2_P5 (SEQ ID NO:992), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTE RAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQG RVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVG FKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL in R30650_PEA_—2_P5 (SEQ ID NO:992).

Comparison Report Between R30650_PEA_—2_P5 (SEQ ID NO:992) and Q9NPN9 (SEQ ID NO:988):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWK PGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEM EDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD (SEQ ID NO:1468) corresponding to amino acids 1-199 of R30650_PEA_—2_P5 (SEQ ID NO:992), and a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKS GTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTG PSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPRE PAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGT EMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCP HNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCIN VPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWD QTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSH YYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKK LFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLD TEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 8-804 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 200-996 of R30650_PEA_—2_P5 (SEQ ID NO:992), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between R30650_PEA_—2_P5 (SEQ ID NO:992) and Q9H1K5 (SEQ ID NO:990):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWK PGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEM EDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPP TYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSK MCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKN QDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGP GGLDH corresponding to amino acids 1-497 of R30650_PEA_—2_P5 (SEQ ID NO:992), and a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSR VFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQ MYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNK GDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKA QNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVK MESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPD NSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPV VKKKKL corresponding to amino acids 2-500 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 498-996 of R30650_PEA_—2_P5 (SEQ ID NO:992), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R30650_PEA_—2_P5 (SEQ ID NO:992), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTILNLEDNVQSWK PGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEM EDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPP TYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSK MCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKN QDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGP GGLDH of R30650_PEA_—2_P5 (SEQ ID NO:992).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein R30650_PEA_—2_P5 (SEQ ID NO:992) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P5 (SEQ ID NO:992) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

372
M -> V
Yes

418
H -> R
Yes

Variant protein R30650_PEA_—2_P5 (SEQ ID NO:992) is encoded by the following transcript(s): R30650_PEA_—2_T3 (SEQ ID NO:930), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R30650_PEA_—2_T3 (SEQ ID NO:930) is shown in bold; this coding portion starts at position 532 and ends at position 3519. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P5 (SEQ ID NO:992) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

15
A -> G
Yes

112
T -> C
Yes

1320
T -> C
Yes

1407
A -> G
Yes

1645
A -> G
Yes

1784
A -> G
Yes

3667
G -> C
Yes

3883
G -> A
Yes

4944
G -> A
Yes

5992
C -> T
Yes

6131
T -> C
Yes

6223
A -> C
Yes

Variant protein R30650_PEA_—2_P8 (SEQ ID NO:993) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T6 (SEQ ID NO:931). An alignment is given to the known protein (Protein KIAA1199 precursor (SEQ ID NO:986)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R30650_PEA_—2_P8 (SEQ ID NO:993) and Q9ULM1 (SEQ ID NO:989):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK corresponding to amino acids 1-348 of R30650_PEA_—2_P8 (SEQ ID NO:993), a second amino acid sequence being at least 90% homologous to AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTN VNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMR AEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIH FHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCL GLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIF HHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDA DPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGE SGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNN AWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLV RHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQK GYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQ SYPGRSHYYWDEDSG corresponding to amino acids 1-788 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 349-1136 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR (SEQ ID NO:1470) corresponding to amino acids 1137-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

3. An isolated polypeptide encoding for a tail of R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KQRTISWR (SEQ ID NO:1470) in R30650_PEA_—2_P8 (SEQ ID NO:993).

Comparison Report Between R30650_PEA_—2_P8 (SEQ ID NO:993) and Q8WUJ3:

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 90% homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLL VKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHV PTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLK PREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNV GTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQS CPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 1-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-977 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGKQRTISWR corresponding to amino acids 978-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSGKQRTISWR in R30650_PEA_—2_P8 (SEQ ID NO:993).

Comparison Report Between R30650_PEA_—2_P8 (SEQ ID NO:993) and Q9NPN9:

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGD corresponding to amino acids 1-564 of R30650_PEA_—2_P8 (SEQ ID NO:993), a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKS GTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTG PSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPRE PAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGT EMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCP HNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCIN VPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWD QTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSH YYWDEDSG corresponding to amino acids 8-579 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 565-1136 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR (SEQ ID NO:1470) corresponding to amino acids 1137-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGD of R30650_PEA_—2_P8 (SEQ ID NO:993).

Comparison Report Between R30650_PEA_—2_P8 (SEQ ID NO:993) and Q9H1K5:

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P8 (SEQ ID NO:993), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLL VKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHV PTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLK PREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNV GTEMMDNRIWGPGGLDH corresponding to amino acids 1-862 of R30650_PEA_—2_P8 (SEQ ID NO:993), a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSR VFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQ MYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNK GDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 2-275 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 863-1136 of R30650_PEA_—2_P8 (SEQ ID NO:993), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR (SEQ ID NO:1470) corresponding to amino acids 1137-1144 of R30650_PEA_—2_P8 (SEQ ID NO:993), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

Variant protein R30650_PEA_—2_P8 (SEQ ID NO:993) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P8 (SEQ ID NO:993) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

737
M -> V
Yes

783
H -> R
Yes

Variant protein R30650_PEA_—2_P8 (SEQ ID NO:993) is encoded by the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R30650_PEA_—2_T6 (SEQ ID NO:931) is shown in bold; this coding portion starts at position 265 and ends at position 3696. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P8 (SEQ ID NO:993) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

9
T -> A
Yes

2148
T -> C
Yes

2235
A -> G
Yes

2473
A -> G
Yes

2612
A -> G
Yes

4290
G -> C
Yes

4506
G -> A
Yes

5567
G -> A
Yes

6615
C -> T
Yes

6754
T -> C
Yes

6846
A -> C
Yes

Variant protein R30650_PEA_—2_P12 (SEQ ID NO:994) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T14 (SEQ ID NO:932). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein R30650_PEA_—2_P12 (SEQ ID NO:994) is encoded by the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R30650_PEA_—2_T14 (SEQ ID NO:932) is shown in bold; this coding portion starts at position 1543 and ends at position 1719. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P12 (SEQ ID NO:994) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

9
T -> A
Yes

381
C -> T
Yes

788
C -> G
Yes

799
A -> G
No

1324
A -> T
Yes

1437
T -> C
Yes

1441
G -> A
Yes

1513
T -> C
Yes

1529
A -> G
Yes

2087
C -> A
Yes

2182
C -> T
Yes

Variant protein R30650_PEA_—2_P13 (SEQ ID NO:995) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T15 (SEQ ID NO:933) and R30650_PEA_—2_T21 (SEQ ID NO:935). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein R30650_PEA_—2_P13 (SEQ ID NO:995) is encoded by the following transcript(s): R30650_PEA_—2_T15 (SEQ ID NO:933) and R30650_PEA_—2_T21 (SEQ ID NO:935), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript R30650_PEA_—2_T15 (SEQ ID NO:933) is shown in bold; this coding portion starts at position 1543 and ends at position 1713. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P13 (SEQ ID NO:995) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

9
T -> A
Yes

381
C -> T
Yes

788
C -> G
Yes

799
A -> G
No

1324
A -> T
Yes

1437
T -> C
Yes

1441
G -> A
Yes

1513
T -> C
Yes

1529
A -> G
Yes

1920
C -> A
Yes

2015
C -> T
Yes

The coding portion of transcript R30650_PEA_—2_T21 (SEQ ID NO:935) is shown in bold; this coding portion starts at position 1543 and ends at position 1713. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P13 (SEQ ID NO:995) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

9
T -> A
Yes

381
C -> T
Yes

788
C -> G
Yes

799
A -> G
No

1324
A -> T
Yes

1437
T -> C
Yes

1441
G -> A
Yes

1513
T -> C
Yes

1529
A -> G
Yes

1956
T -> C
Yes

Variant protein R30650_PEA_—2_P15 (SEQ ID NO:996) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T18 (SEQ ID NO:934). An alignment is given to the known protein (Protein KIAA1199 precursor (SEQ ID NO:986)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R30650_PEA_—2_P15 (SEQ ID NO:996) and Q9ULM1 (SEQ ID NO:989):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK corresponding to amino acids 1-348 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 90% homologous to AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTN VNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMR AEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIH FHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCL GLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIF HHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDA DPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGE SGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNN AWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLV RHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQK GYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQ SYPGRSHYYWDEDSG corresponding to amino acids 1-788 of Q9ULM1 (SEQ ID NO:989), which also corresponds to amino acids 349-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between R30650_PEA_—2_P15 (SEQ ID NO:996) and Q8WUJ3 (SEQ ID NO:987):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 90% homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLL VKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHV PTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLK PREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNV GTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQS CPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 1-977 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-977 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSG corresponding to amino acids 978-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVV TLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMD KVEQSYPGRSHYYWDEDSG in R30650_PEA_—2_P15 (SEQ ID NO:996).

Comparison Report Between R30650_PEA_—2_P15 (SEQ ID NO:996) and Q9NPN9 (SEQ ID NO:988):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGD corresponding to amino acids 1-564 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 90% homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKS GTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTG PSVGMYSPGYSEHIPLGKFYNNPAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPRE PAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGT EMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCP HNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCIN VPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWD QTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSH YYWDEDSG corresponding to amino acids 8-579 of Q9NPN9 (SEQ ID NO:988), which also corresponds to amino acids 565-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGD of R30650_PEA_—2_P15 (SEQ ID NO:996).

Comparison Report Between R30650_PEA_—2_P15 (SEQ ID NO:996) and Q9H1K5 (SEQ ID NO:990):

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P15 (SEQ ID NO:996), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHP GKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNS TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEEIDGVDMRAEV GLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHL AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLL VKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHV PTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLK PREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNV GTEMMDNRIWGPGGLDH corresponding to amino acids 1-862 of R30650_PEA_—2_P15 (SEQ ID NO:996), and a second amino acid sequence being at least 90% homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSR VFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQ MYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNK GDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 2-275 of Q9H1K5 (SEQ ID NO:990), which also corresponds to amino acids 863-1136 of R30650_PEA_—2_P15 (SEQ ID NO:996), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Variant protein R30650_PEA_—2_P15 (SEQ ID NO:996) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P15 (SEQ ID NO:996) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
known SNP?

737
M -> V
Yes

783
H -> R
Yes

Variant protein R30650_PEA_—2_P15 (SEQ ID NO:996) is encoded by the following transcript(s): R30650_PEA_—2_T18 (SEQ ID NO:934), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R30650_PEA_—2_T18 (SEQ ID NO:934) is shown in bold; this coding portion starts at position 265 and ends at position 3672. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P15 (SEQ ID NO:996) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

9
T -> A
Yes

2148
T -> C
Yes

2235
A -> G
Yes

2473
A -> G
Yes

2612
A -> G
Yes

Variant protein R30650_PEA_—2_P17 (SEQ ID NO:997) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R30650_PEA_—2_T23 (SEQ ID NO:936). An alignment is given to the known protein (Protein KIAA1199 precursor (SEQ ID NO:986)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between R30650_PEA_—2_P17 (SEQ ID NO:997) and Q8WUJ3:

1. An isolated chimeric polypeptide encoding for R30650_PEA_—2_P17 (SEQ ID NO:997), comprising a first amino acid sequence being at least 90% homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQGKTLLLTSSA TVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNFTIILYGRADEGIQPDPYYGLKYIG VGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSK KESERLVQYLNAVPDGRILSVAVNDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSV EDHIEYHGHRGSAAARVFKLFQTEHGEYFNVSLSSEWVQ corresponding to amino acids 1-321 of Q8WUJ3 (SEQ ID NO:987), which also corresponds to amino acids 1-321 of R30650_PEA_—2_P17 (SEQ ID NO:997), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEEFQTIW (SEQ ID NO:1473) corresponding to amino acids 322-329 of R30650_PEA_—2_P17 (SEQ ID NO:997), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of R30650_PEA_—2_P17 (SEQ ID NO:997), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEEFQTIW (SEQ ID NO:1473) in R30650_PEA_—2_P17 (SEQ ID NO:997).

Variant protein R30650_PEA_—2_P17 (SEQ ID NO:997) is encoded by the following transcript(s): R30650_PEA_—2_T23 (SEQ ID NO:936), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R30650_PEA_—2_T23 (SEQ ID NO:936) is shown in bold; this coding portion starts at position 265 and ends at position 1251. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R30650_PEA_—2_P17 (SEQ ID NO:997) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

9
T -> A
Yes

1455
T -> C
No

As noted above, cluster R30650 features 49 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster R30650_PEA_—2_node_—0 (SEQ ID NO:937) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T14 (SEQ ID NO:932), R30650_PEA_—2_T15 (SEQ ID NO:933), R30650_PEA_—2_T18 (SEQ ID NO:934), R30650_PEA_—2_T21 (SEQ ID NO:935) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T6 (SEQ ID NO: 931)
1
248

R30650_PEA_2_T14 (SEQ ID NO: 932)
1
248

R30650_PEA_2_T15 (SEQ ID NO: 933)
1
248

R30650_PEA_2_T18 (SEQ ID NO: 934)
1
248

R30650_PEA_2_T21 (SEQ ID NO: 935)
1
248

R30650_PEA_2_T23 (SEQ ID NO: 936)
1
248

Segment cluster R30650_PEA_—2_node_—1 (SEQ ID NO:938) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932), R30650_PEA_—2_T15 (SEQ ID NO:933) and R30650_PEA_—2_T21 (SEQ ID NO:935). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T14 (SEQ ID NO: 932)
249
1237

R30650_PEA_2_T15 (SEQ ID NO: 933)
249
1237

R30650_PEA_2_T21 (SEQ ID NO: 935)
249
1237

Segment cluster R30650_PEA_—2_node_—3 (SEQ ID NO:939) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932), R30650_PEA_—2_T15 (SEQ ID NO:933) and R30650_PEA_—2_T21 (SEQ ID NO:935). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T14 (SEQ ID NO: 932)
1238
1415

R30650_PEA_2_T15 (SEQ ID NO: 933)
1238
1415

R30650_PEA_2_T21 (SEQ ID NO: 935)
1238
1415

Segment cluster R30650_PEA_—2_node_—5 (SEQ ID NO:940) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932), R30650_PEA_—2_T15 (SEQ ID NO:933) and R30650_PEA_—2_T21 (SEQ ID NO:935). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T14 (SEQ ID NO: 932)
1416
1617

R30650_PEA_2_T15 (SEQ ID NO: 933)
1416
1617

R30650_PEA_2_T21 (SEQ ID NO: 935)
1416
1617

Segment cluster R30650_PEA_—2_node_—9 (SEQ ID NO:941) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T21 (SEQ ID NO:935). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T21 (SEQ ID NO: 935)
1713
2152

Segment cluster R30650_PEA_—2_node_—11 (SEQ ID NO:942) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T14 (SEQ ID NO: 932)
1713
1879

Segment cluster R30650_PEA_—2_node_—14 (SEQ ID NO:943) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932) and R30650_PEA_—2_T15 (SEQ ID NO:933). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T14 (SEQ ID NO: 932)
1880
2818

R30650_PEA_2_T15 (SEQ ID NO: 933)
1713
2651

Segment cluster R30650_PEA_—2_node_—20 (SEQ ID NO:944) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T6 (SEQ ID NO: 931)
359
505

R30650_PEA_2_T18 (SEQ ID NO: 934)
359
505

R30650_PEA_2_T23 (SEQ ID NO: 936)
359
505

Segment cluster R30650_PEA_—2_node_—22 (SEQ ID NO:945) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T6 (SEQ ID NO: 931)
506
644

R30650_PEA_2_T18 (SEQ ID NO: 934)
506
644

R30650_PEA_2_T23 (SEQ ID NO: 936)
506
644

Segment cluster R30650_PEA_—2_node_—24 (SEQ ID NO:946) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T6 (SEQ ID NO: 931)
645
881

R30650_PEA_2_T18 (SEQ ID NO: 934)
645
881

R30650_PEA_2_T23 (SEQ ID NO: 936)
645
881

Segment cluster R30650_PEA_—2_node_—26 (SEQ ID NO:947) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T6 (SEQ ID NO: 931)
882
1061

R30650_PEA_2_T18 (SEQ ID NO: 934)
882
1061

R30650_PEA_2_T23 (SEQ ID NO: 936)
882
1061

Segment cluster R30650_PEA_—2_node_—32 (SEQ ID NO:948) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T23 (SEQ ID NO:936). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T23 (SEQ ID NO: 936)
1229
1829

Segment cluster R30650_PEA_—2_node_—34 (SEQ ID NO:949) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T6 (SEQ ID NO: 931)
1229
1350

R30650_PEA_2_T18 (SEQ ID NO: 934)
1229
1350

Segment cluster R30650_PEA_—2_node_—36 (SEQ ID NO:950) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T3 (SEQ ID NO:930). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

R30650_PEA_2_T3 (SEQ ID NO: 930)
1
522

Segment cluster R30650_PEA_—2_node_—37 (SEQ ID NO:951) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T3 (SEQ ID NO: 930)
523
655

R30650_PEA_2_T6 (SEQ ID NO: 931)
1351
1483

R30650_PEA_2_T18
1351
1483

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—39 (SEQ ID NO:952) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T3 (SEQ ID NO: 930)
656
847

R30650_PEA_2_T6 (SEQ ID NO: 931)
1484
1675

R30650_PEA_2_T18
1484
1675

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—41 (SEQ ID NO:953) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
1
1360

Segment cluster R30650_PEA_—2_node_—42 (SEQ ID NO:954) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
1361
1536

R30650_PEA_2_T3 (SEQ ID NO: 930)
848
1023

R30650_PEA_2_T6 (SEQ ID NO: 931)
1676
1851

R30650_PEA_2_T18
1676
1851

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—44 (SEQ ID NO:955) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
1537
1746

R30650_PEA_2_T3 (SEQ ID NO: 930)
1024
1233

R30650_PEA_2_T6 (SEQ ID NO: 931)
1852
2061

R30650_PEA_2_T18
1852
2061

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—46 (SEQ ID NO:956) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
1747
1952

R30650_PEA_2_T3 (SEQ ID NO: 930)
1234
1439

R30650_PEA_2_T6 (SEQ ID NO: 931)
2062
2267

R30650_PEA_2_T18
2062
2267

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—50 (SEQ ID NO:957) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2023
2151

R30650_PEA_2_T3 (SEQ ID NO: 930)
1510
1638

R30650_PEA_2_T6 (SEQ ID NO: 931)
2338
2466

R30650_PEA_2_T18
2338
2466

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—56 (SEQ ID NO:958) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2238
2369

R30650_PEA_2_T3 (SEQ ID NO: 930)
1725
1856

R30650_PEA_2_T6 (SEQ ID NO: 931)
2553
2684

R30650_PEA_2_T18
2553
2684

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—60 (SEQ ID NO:959) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2406
2561

R30650_PEA_2_T3 (SEQ ID NO: 930)
1893
2048

R30650_PEA_2_T6 (SEQ ID NO: 931)
2721
2876

R30650_PEA_2_T18
2721
2876

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—63 (SEQ ID NO:960) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2562
2742

R30650_PEA_2_T3 (SEQ ID NO: 930)
2049
2229

R30650_PEA_2_T6 (SEQ ID NO: 931)
2877
3057

R30650_PEA_2_T18
2877
3057

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—67 (SEQ ID NO:961) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2743
2882

R30650_PEA_2_T3 (SEQ ID NO: 930)
2230
2369

R30650_PEA_2_T6 (SEQ ID NO: 931)
3058
3197

R30650_PEA_2_T18
3058
3197

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—70 (SEQ ID NO:962) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2959
3170

R30650_PEA_2_T3 (SEQ ID NO: 930)
2446
2657

R30650_PEA_2_T6 (SEQ ID NO: 931)
3274
3485

R30650_PEA_2_T18
3274
3485

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—72 (SEQ ID NO:963) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3171
3356

R30650_PEA_2_T3 (SEQ ID NO: 930)
2658
2843

R30650_PEA_2_T6 (SEQ ID NO: 931)
3486
3671

R30650_PEA_2_T18
3486
3671

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—73 (SEQ ID NO:964) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T18 (SEQ ID NO:934). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T18
3672
3886

(SEQ ID NO: 934)

Segment cluster R30650_PEA_—2_node_—75 (SEQ ID NO:965) according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929) and R30650_PEA_—2_T3 (SEQ ID NO:930). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3357
3561

R30650_PEA_2_T3 (SEQ ID NO: 930)
2844
3048

Segment cluster R30650_PEA_—2_node_—79 (SEQ ID NO:966) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment

Segment starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3649
3806

R30650_PEA_2_T3 (SEQ ID NO: 930)
3136
3293

R30650_PEA_2_T6 (SEQ ID NO: 931)
3759
3916

Segment cluster R30650_PEA_—2_node_—86 (SEQ ID NO:967) according to the present invention is supported by 43 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3913
4895

R30650_PEA_2_T3 (SEQ ID NO: 930)
3400
4382

R30650_PEA_2_T6 (SEQ ID NO: 931)
4023
5005

Segment cluster R30650_PEA_—2_node_—87 (SEQ ID NO:968) according to the present invention is supported by 43 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
4896
5316

R30650_PEA_2_T3 (SEQ ID NO: 930)
4383
4803

R30650_PEA_2_T6 (SEQ ID NO: 931)
5006
5426

Segment cluster R30650_PEA_—2_node_—89 (SEQ ID NO:969) according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
5410
5990

R30650_PEA_2_T3 (SEQ ID NO: 930)
4897
5477

R30650_PEA_2_T6 (SEQ ID NO: 931)
5520
6100

Segment cluster R30650_PEA_—2_node_—93 (SEQ ID NO:970) according to the present invention is supported by 108 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
6094
6772

R30650_PEA_2_T3 (SEQ ID NO: 930)
5581
6259

R30650_PEA_2_T6 (SEQ ID NO: 931)
6204
6882

Segment cluster R30650_PEA_—2_node_—8 (SEQ ID NO:971) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T14 (SEQ ID NO:932), R30650_PEA_—2_T15 (SEQ ID NO:933) and R30650_PEA_—2_T21 (SEQ ID NO:935). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T14 (SEQ ID NO: 932)
1618
1712

R30650_PEA_2_T15 (SEQ ID NO: 933)
1618
1712

R30650_PEA_2_T21 (SEQ ID NO: 935)
1618
1712

Segment cluster R30650_PEA_—2_node_—17 (SEQ ID NO:972) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T6 (SEQ ID NO: 931)
249
358

R30650_PEA_2_T18 (SEQ ID NO: 934)
249
358

R30650_PEA_2_T23 (SEQ ID NO: 936)
249
358

Segment cluster R30650_PEA_—2_node_—28 (SEQ ID NO:973) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T6 (SEQ ID NO: 931)
1062
1132

R30650_PEA_2_T18 (SEQ ID NO: 934)
1062
1132

R30650_PEA_2_T23 (SEQ ID NO: 936)
1062
1132

Segment cluster R30650_PEA_—2_node_—31 (SEQ ID NO:974) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T6 (SEQ ID NO:931), R30650_PEA_—2_T18 (SEQ ID NO:934) and R30650_PEA_—2_T23 (SEQ ID NO:936). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T6 (SEQ ID NO: 931)
1133
1228

R30650_PEA_2_T18 (SEQ ID NO: 934)
1133
1228

R30650_PEA_2_T23 (SEQ ID NO: 936)
1133
1228

Segment cluster R30650_PEA_—2_node_—48 (SEQ ID NO:975) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
1953
2022

R30650_PEA_2_T3 (SEQ ID NO: 930)
1440
1509

R30650_PEA_2_T6 (SEQ ID NO: 931)
2268
2337

R30650_PEA_2_T18 (SEQ ID NO: 934)
2268
2337

Segment cluster R30650_PEA_—2_node_—53 (SEQ ID NO:976) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2152
2237

R30650_PEA_2_T3 (SEQ ID NO: 930)
1639
1724

R30650_PEA_2_T6 (SEQ ID NO: 931)
2467
2552

R30650_PEA_2_T18 (SEQ ID NO: 934)
2467
2552

Segment cluster R30650_PEA_—2_node_—58 (SEQ ID NO:977) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2370
2405

R30650_PEA_2_T3 (SEQ ID NO: 930)
1857
1892

R30650_PEA_2_T6 (SEQ ID NO: 931)
2685
2720

R30650_PEA_2_T18 (SEQ ID NO: 934)
2685
2720

Segment cluster R30650_PEA_—2_node_—68 (SEQ ID NO:978) according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930), R30650_PEA_—2_T6 (SEQ ID NO:931) and R30650_PEA_—2_T18 (SEQ ID NO:934). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
2883
2958

R30650_PEA_2_T3 (SEQ ID NO: 930)
2370
2445

R30650_PEA_2_T6 (SEQ ID NO: 931)
3198
3273

R30650_PEA_2_T18 (SEQ ID NO: 934)
3198
3273

Segment cluster R30650_PEA_—2_node_—77 (SEQ ID NO:979) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment

Segment starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3562
3648

R30650_PEA_2_T3 (SEQ ID NO: 930)
3049
3135

R30650_PEA_2_T6 (SEQ ID NO: 931)
3672
3758

Segment cluster R30650_PEA_—2_node_—82 (SEQ ID NO:980) according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment

Segment starting
ending

Transcript name
position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3807
3907

R30650_PEA_2_T3 (SEQ ID NO: 930)
3294
3394

R30650_PEA_2_T6 (SEQ ID NO: 931)
3917
4017

Segment cluster R30650_PEA_—2_node_—85 (SEQ ID NO:981) according to the present invention can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
3908
3912

R30650_PEA_2_T3 (SEQ ID NO: 930)
3395
3399

R30650_PEA_2_T6 (SEQ ID NO: 931)
4018
4022

Segment cluster R30650_PEA_—2_node_—88 (SEQ ID NO:982) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
5317
5409

R30650_PEA_2_T3 (SEQ ID NO: 930)
4804
4896

R30650_PEA_2_T6 (SEQ ID NO: 931)
5427
5519

Segment cluster R30650_PEA_—2_node_—90 (SEQ ID NO:983) according to the present invention can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
5991
5999

R30650_PEA_2_T3 (SEQ ID NO: 930)
5478
5486

R30650_PEA_2_T6 (SEQ ID NO: 931)
6101
6109

Segment cluster R30650_PEA_—2_node_—91 (SEQ ID NO:984) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
6000
6068

R30650_PEA_2_T3 (SEQ ID NO: 930)
5487
5555

R30650_PEA_2_T6 (SEQ ID NO: 931)
6110
6178

Segment cluster R30650_PEA_—2_node_—92 (SEQ ID NO:985) according to the present invention can be found in the following transcript(s): R30650_PEA_—2_T2 (SEQ ID NO:929), R30650_PEA_—2_T3 (SEQ ID NO:930) and R30650_PEA_—2_T6 (SEQ ID NO:931). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68

Segment location on transcripts

Segment

Segment
ending

Transcript name
starting position
position

R30650_PEA_2_T2 (SEQ ID NO: 929)
6069
6093

R30650_PEA_2_T3 (SEQ ID NO: 930)
5556
5580

R30650_PEA_2_T6 (SEQ ID NO: 931)
6179
6203

Variant Protein Alignment to the Previously Known Protein:

Sequence name: Q9ULM1 (SEQ ID NO:989)

Sequence documentation:

Alignment of: R30650_PEA_2_P4 (SEQ ID NO:991) × Q9ULM1 (SEQ ID NO:989)

Alignment segment 1/1:

Quality:
8887.00
Escore
0

Matching length:
888
Total length:
888

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q8WUJ3 (SEQ ID NO:987)

Sequence documentation:

Alignment of: R30650_PEA_2_P4 (SEQ ID NO:991) × Q8WUJ3 (SEQ ID NO:987) ..

Alignment segment 1/1:

Quality:
5070.00
Escore
0

Matching length:
506
Total length:
506

Matching Percent Similarity:
99.80
Matching Percent Identity:
99.80

Total Percent Similarity:
99.80
Total Percent Identity:
99.80

Gaps:
0

Alignment:

Sequence name: Q9NPN9 (SEQ ID NO:988)

Sequence documentation:

Alignment of: R30650_PEA_2_P4 (SEQ ID NO:991) × Q9NPN9 (SEQ ID NO:988) ..

Alignment segment 1/1:

Quality:
7975.00
Escore
0

Matching length:
797
Total length:
797

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9H1K5 (SEQ ID NO:990)

Sequence documentation:

Alignment of: R30650_PEA_2_P4 (SEQ ID NO:991) × Q9HlK5 (SEQ ID NO:990) ..

Alignment segment 1/1:

Quality:
4983.00
Escore
0

Matching length:
499
Total length:
499

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9ULM1 (SEQ ID NO:989)

Sequence documentation:

Alignment of: R30650_PEA_2_P5 (SEQ ID NO:992) × Q9ULM1 (SEQ ID NO:989) ..

Alignment segment 1/1:

Quality:
9960.00
Escore
0

Matching length:
996
Total length:
996

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q8WUJ3 (SEQ ID NO:987)

Sequence documentation:

Alignment of: R30650_PEA_2_P5 (SEQ ID NO:992) × Q8WUJ3 (SEQ ID NO:987) ..

Alignment segment 1/1:

Quality:
6143.00
Escore
0

Matching length:
614
Total length:
614

Matching Percent Similarity:
99.84
Matching Percent Identity:
99.84

Total Percent Similarity:
99.84
Total Percent Identity:
99.84

Gaps:
0

Alignment:

Sequence name: Q9NPN9 (SEQ ID NO:988)

Sequence documentation:

Alignment of: R30650_PEA_2_P5 (SEQ ID NO:992) × Q9NPN9 (SEQ ID NO:988) ..

Alignment segment 1/1:

Quality:
7975.00
Escore
0

Matching length:
797
Total length:
797

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9H1K5 (SEQ ID NO:990)

Sequence documentation:

Alignment of: R30650_PEA_2_P5 (SEQ ID NO:992) × Q9HlK5 (SEQ ID NO:990) ..

Alignment segment 1/1:

Quality:
4983.00
Escore
0

Matching length:
499
Total length:
499

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9ULM1 (SEQ ID NO:989)

Sequence documentation:

Alignment of: R30650_PEA_2_P8 (SEQ ID NO:993) × Q9ULM1 (SEQ ID NO:989) ..

Alignment segment 1/1:

Quality:
7919.00
Escore:
0

Matching length:
788
Total length:
788

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q8WUJ3 (SEQ ID NO:987)

Sequence documentation:

Alignment of: R30650_PEA_2_P8 (SEQ ID NO:993) × Q8WUJ3 (SEQ ID NO:987) ..

Alignment segment 1/1:

Quality:
9764.00
Escore
0

Matching length:
979
Total length:
979

Matching Percent Similarity:
99.90
Matching Percent Identity:
99.90

Total Percent Similarity:
99.90
Total Percent Identity:
99.90

Gaps:
0

Alignment:

Sequence name: Q9NPN9 (SEQ ID NO:988)

Sequence documentation:

Alignment of: R30650_PEA_2_P8 (SEQ ID NO:993) × Q9NPN9 (SEQ ID NO:988) ..

Alignment segment 1/1:

Quality:
5764.00
Escore
0

Matching length:
572
Total length:
572

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9H1K5 (SEQ ID NO:990)

Sequence documentation:

Alignment of: R30650_PEA_2_P15 (SEQ ID NO:993) × Q9H1K5 (SEQ ID NO:990) ..

Alignment segment 1/1:

Quality:
2772.00
Escore
0

Matching length:
274
Total length:
274

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9ULM1 (SEQ ID NO:989)

Sequence documentation:

Alignment of: R30650_PEA_2_P15 (SEQ ID NO:996) × Q9ULM1 (SEQ ID NO:989)

Alignment segment 1/1:

Quality:
7919.00
Escore
0

Matching length:
788
Total length:
788

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q8WUJ3 (SEQ ID NO:987)

Sequence documentation:

Alignment of: R30650_PEA_2_P15 (SEQ ID NO:996) × Q8WUJ3 (SEQ ID NO:987)

Alignment segment 1/1:

Quality:
9764.00
Escore
0

Matching length:
979
Total length:
979

Matching Percent Similarity:
99.90
Matching Percent Identity:
99.90

Total Percent Similarity:
99.90
Total Percent Identity:
99.90

Gaps:
0

Alignment:

Sequence name: Q9NPN9 (SEQ ID NO:988)

Sequence documentation:

Alignment of: R30650_PEA_2_P15 (SEQ ID NO:996) × Q9NPN9 (SEQ ID NO:988)

Alignment segment 1/1:

Quality:
5764.00
Escore
0

Matching length:
572
Total length:
572

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q9H1K5 (SEQ ID NO:990)

Sequence documentation:

Alignment of: R30650_PEA_2_P15 (SEQ ID NO:996) × Q9H1K5 (SEQ ID NO:990)

Alignment segment 1/1:

Quality:
2772.00
Escore
0

Matching length:
324
Total length:
274

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: Q8WUJ3 (SEQ ID NO:987)

Sequence documentation:

Alignment of: R30650_PEA_2_P17 (SEQ ID NO:997) × Q8WUJ3 (SEQ ID NO:987)

Alignment segment 1/1:

Quality:
3170.00
Escore
0

Matching length:
324
Total length:
324

Matching Percent Similarity:
99.38
Matching Percent Identity:
99.38

Total Percent Similarity:
99.38
Total Percent Identity:
99.38

Gaps:
0

Alignment:

Expression of R30650 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name R30650 Seg76 (SEQ ID NO: 1354) in Normal and Cancerous Colon Tissues

Expression of R30650 transcripts detectable by or according to seg76, R30650 amplicon (SEQ ID NO: 1354) and R30650 F (SEQ ID NO: 1352) and R30650 R (SEQ ID NO: 1353) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 57 is a histogram showing over expression of the above-indicated R30650 transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 57, the expression of R30650 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 5 fold was found in 18 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of R30650 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 1.86E-05.

Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 2.42E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: R30650 F forward primer (SEQ ID NO: 1352); and R30650 R reverse primer (SEQ ID NO: 1353).

Forward primer (SEQ ID NO: 1352):

CTTCTTGTCCACGGTTTTGTITG

Reverse primer (SEQ ID NO: 1353):

AACATTCCTGGCCACCTGAA

Amplicon (SEQ ID NO: 1354):

CTTCTTGTCCACGGTTTTGTTGAGTTTTCACTCTTCTAATGCAAGGGTCA

CACTGTGAACCACTTAGGATGTGATCACTTTCAGGTGGCCAGGAATGTT

Description for Cluster T23657

Cluster T23657 features 31 transcript(s) and 33 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

T23657_T0
998

T23657_T1
999

T23657_T2
1000

T23657_T3
1001

T23657_T4
1002

T23657_T5
1003

T23657_T6
1004

T23657_T7
1005

T23657_T8
1006

T23657_T9
1007

T23657_T10
1008

T23657_T11
1009

T23657_T12
1010

T23657_T13
1011

T23657_T14
1012

T23657_T15
1013

T23657_T16
1014

T23657_T17
1015

T23657_T19
1016

T23657_T20
1017

T23657_T21
1018

T23657_T22
1019

T23657_T23
1020

T23657_T24
1021

T23657_T28
1022

T23657_T30
1023

T23657_T31
1024

T23657_T32
1025

T23657_T35
1026

T23657_T37
1027

T23657_T38
1028

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

T23657_node_2
1029

T23657_node_3
1030

T23657_node_8
1031

T23657_node_16
1032

T23657_node_18
1033

T23657_node_23
1034

T23657_node_24
1035

T23657_node_27
1036

T23657_node_29
1037

T23657_node_34
1038

T23657_node_37
1039

T23657_node_38
1040

T23657_node_39
1041

T23657_node_40
1042

T23657_node_45
1043

T23657_node_46
1044

T23657_node_49
1045

T23657_node_0
1046

T23657_node_4
1047

T23657_node_6
1048

T23657_node_11
1049

T23657_node_20
1050

T23657_node_22
1051

T23657_node_25
1052

T23657_node_26
1053

T23657_node_28
1054

T23657_node_30
1055

T23657_node_31
1056

T23657_node_32
1057

T23657_node_41
1058

T23657_node_42
1059

T23657_node_43
1060

T23657_node_44
1061

TABLE 3

Proteins of interest

SEQ

Protein Name
ID NO:
Corresponding Transcript(s)

T23657_P1
1063
T23657_T0 (SEQ ID NO: 998);

T23657_T1 (SEQ ID NO: 999); T23657_T8

(SEQ ID NO: 1006)

T23657_P2
1064
T23657_T2 (SEQ ID NO: 1000);

T23657_T7 (SEQ ID NO: 1005);

T23657_T16

(SEQ ID NO: 1014); T23657_T20

(SEQ ID NO: 1017)

T23657_P3
1065
T23657_T3 (SEQ ID NO: 1001);

T23657_T9 (SEQ ID NO: 1007);

T23657_T21

(SEQ ID NO: 1018)

T23657_P4
1066
T23657_T4 (SEQ ID NO: 1002)

T23657_P5
1067
T23657_T5 (SEQ ID NO: 1003);

T23657_T6 (SEQ ID NO: 1004)

T23657_P6
1068
T23657_T10 (SEQ ID NO: 1008)

T23657_P7
1069
T23657_T12 (SEQ ID NO: 1010);

T23657_T17 (SEQ ID NO: 1015);

T23657_T22 (SEQ ID NO: 1019)

T23657_P8
1070
T23657_T13 (SEQ ID NO: 1011);

T23657_T19 (SEQ ID NO: 1016);

T23657_T28 (SEQ ID NO: 1022)

T23657_P9
1071
T23657_T14 (SEQ ID NO: 1012)

T23657_P10
1072
T23657_T15 (SEQ ID NO: 1013)

T23657_P11
1073
T23657_T23 (SEQ ID NO: 1020)

T23657_P12
1074
T23657_T24 (SEQ ID NO: 1021)

T23657_P16
1075
T23657_T30 (SEQ ID NO: 1023)

T23657_P17
1076
T23657_T31 (SEQ ID NO: 1024);

T23657_T32 (SEQ ID NO: 1025)

T23657_P19
1077
T23657_T35 (SEQ ID NO: 1026)

T23657_P21
1078
T23657_T37 (SEQ ID NO: 1027)

T23657_P22
1079
T23657_T38 (SEQ ID NO: 1028)

T23657_P23
1080
T23657_T11 (SEQ ID NO: 1009)

These sequences are variants of the known protein Solute carrier family 21 member 12 (SwissProt accession identifier S21C_HUMAN; known also according to the synonyms Sodium-independent organic anion transporter E; Organic anion transporting polypeptide E; OATP-E; Colon organic anion transporter; Organic anion transporter polypeptide-related protein 1; OATP-RP1; OATPRP1; POAT), SEQ ID NO:1062, referred to herein as the previously known protein.

Protein Solute carrier family 21 member 12 (SEQ ID NO:1062) is known or believed to have the following function(s): Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate. The sequence for protein Solute carrier family 21 member 12 is given at the end of the application, as “Solute carrier family 21 member 12 amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

78
V -> I

246
T -> M

Protein Solute carrier family 21 member 12 (SEQ ID NO:1062) localization is believed to be Integral membrane protein.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: ion transport, which are annotation(s) related to Biological Process; transporter, which are annotation(s) related to Molecular Function; and integral membrane protein, which are annotation(s) related to Cellular Component.

Cluster T23657 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 58 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

adrenal
0

colon
6

epithelial
14

general
26

kidney
44

lung
30

lymph nodes
39

breast
8

bone marrow
0

ovary
0

pancreas
0

prostate
0

skin
5

stomach
0

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
4.2e−01
4.6e−01
2.1e−01
3.4
2.9e−01
2.7

colon
3.1e−02
2.9e−02
1.2e−01
3.2
1.6e−01
2.8

epithelial
1.8e−02
2.0e−03
1.6e−01
1.6
3.4e−04
2.2

general
2.3e−01
3.3e−02
9.6e−01
0.7
2.1e−01
1.0

kidney
7.0e−01
5.5e−01
9.3e−01
0.7
7.4e−01
1.0

lung
7.7e−01
7.4e−01
1
0.4
6.3e−01
0.8

lymph nodes
6.9e−01
7.5e−01
1
0.5
7.9e−01
0.8

breast
9.5e−01
5.8e−01
1
0.8
3.1e−01
1.7

bone marrow
4.3e−01
4.2e−01
1
2.1
1
1.4

ovary
4.0e−01
2.8e−01
6.8e−01
1.6
5.9e−01
1.7

pancreas
1
4.4e−01
1
1.0
7.7e−02
2.8

prostate
7.3e−01
6.0e−01
4.5e−01
2.0
9.9e−03
2.3

skin
4.0e−01
6.8e−01
1.4e−01
5.0
6.4e−01
1.1

stomach
1
1.3e−01
1
1.0
1.6e−01
2.8

As noted above, cluster T23657 features 31 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Solute carrier family 21 member 12 (SEQ ID NO:1062). A description of each variant protein according to the present invention is now provided.

Variant protein T23657_P1 (SEQ ID NO:1063) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999) and T23657_T8 (SEQ ID NO:1006). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P1 (SEQ ID NO:1063) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P1 (SEQ ID NO:1063) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

Variant protein T23657_P1 (SEQ ID NO:1063) is encoded by the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999) and T23657_T8 (SEQ ID NO:1006), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T0 (SEQ ID NO:998) is shown in bold; this coding portion starts at position 212 and ends at position 2377. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P1 (SEQ ID NO:1063) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2399
C -> T
No

2402
C ->
No

2425
C -> T
Yes

2701
C -> T
Yes

2714
C -> T
Yes

The coding portion of transcript T23657_T1 (SEQ ID NO:999) is shown in bold; this coding portion starts at position 212 and ends at position 2377. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P1 (SEQ ID NO:1063) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2399
C -> T
No

2402
C ->
No

2425
C -> T
Yes

2701
C -> T
Yes

2714
C -> T
Yes

2877
C -> T
Yes

2950
T -> C
Yes

2967
A -> C
Yes

The coding portion of transcript T23657_T8 (SEQ ID NO:1006) is shown in bold; this coding portion starts at position 212 and ends at position 2377. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P1 (SEQ ID NO:1063) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position

on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2399
C -> T
No

2402
C ->
No

2425
C -> T
Yes

Variant protein T23657_P2 (SEQ ID NO:1064) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T2 (SEQ ID NO:1000), T23657_T7 (SEQ ID NO:1005), T23657_T16 (SEQ ID NO:1014) and T23657_T20 (SEQ ID NO:1017). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P2 (SEQ ID NO:1064) and S21C HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P2 (SEQ ID NO:1064), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHA TAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDK ACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-675 of T23657_P2 (SEQ ID NO:1064), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FQLPEVHHSLNVLNRKFQKQTVHNL (SEQ ID NO:1455) corresponding to amino acids 676-700 of T23657_P2 (SEQ ID NO:1064), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P2 (SEQ ID NO:1064), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FQLPEVHHSLNVLNRKFQKQTVHNL (SEQ ID NO:1455) in T23657_P2 (SEQ ID NO:1064).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P2 (SEQ ID NO:1064) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P2 (SEQ ID NO:1064) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s)

on amino acid
Alternative
Previously

sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P2 (SEQ ID NO:1064), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 12

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
yes
557

499
yes
499

Variant protein T23657_P2 (SEQ ID NO:1064) is encoded by the following transcript(s): T23657_T2 (SEQ ID NO:1000), T23657_T7 (SEQ ID NO:1005), T23657_T16 (SEQ ID NO:1014) and T23657_T20 (SEQ ID NO:1017), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T2 (SEQ ID NO:1000) is shown in bold; this coding portion starts at position 212 and ends at position 2311. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P2 (SEQ ID NO:1064) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2503
A -> G
Yes

2789
G -> A
Yes

3444
C -> T
Yes

3936
T -> C
Yes

4196
C -> T
No

4199
C ->
No

4222
C -> T
Yes

4498
C -> T
Yes

4511
C -> T
Yes

The coding portion of transcript T23657_T7 (SEQ ID NO:1005) is shown in bold; this coding portion starts at position 212 and ends at position 2311. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P2 (SEQ ID NO:1064) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on
Alternative
Previously known

nucleotide sequence
nucleic acid
SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2503
A -> G
Yes

2789
G -> A
Yes

3444
C -> T
Yes

3936
T -> C
Yes

4196
C -> T
No

4199
C ->
No

4222
C -> T
Yes

4498
C -> T
Yes

4511
C -> T
Yes

4674
C -> T
Yes

4747
T -> C
Yes

4764
A -> C
Yes

The coding portion of transcript T23657_T16 (SEQ ID NO:1014) is shown in bold; this coding portion starts at position 212 and ends at position 2311. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P2 (SEQ ID NO:1064) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2503
A -> G
Yes

2789
G -> A
Yes

3444
C -> T
Yes

3936
T -> C
Yes

4103
C -> T
No

4106
C ->
No

4129
C -> T
Yes

4405
C -> T
Yes

4418
C -> T
Yes

The coding portion of transcript T23657_T20 (SEQ ID NO:1017) is shown in bold; this coding portion starts at position 212 and ends at position 2311. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P2 (SEQ ID NO:1064) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2569
C -> T
No

2572
C ->
No

2595
C -> T
Yes

2871
C -> T
Yes

2884
C -> T
Yes

Variant protein T23657_P3 (SEQ ID NO:1065) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T3 (SEQ ID NO:1001), T23657_T9 (SEQ ID NO:1007) and T23657_T21 (SEQ ID NO:1018). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P3 (SEQ ID NO:1065) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P3 (SEQ ID NO:1065), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHA TAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDK ACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-675 of T23657_P3 (SEQ ID NO:1065), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TIKHKAF corresponding to amino acids 676-682 of T23657_P3 (SEQ ID NO:1065), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P3 (SEQ ID NO:1065), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TIKHKAF in T23657_P3 (SEQ ID NO:1065).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P3 (SEQ ID NO:1065) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P3 (SEQ ID NO:1065) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P3 (SEQ ID NO:1065), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 18 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 18

Glycosylation site(s)

Position(s) on known
Present in
Position

amino acid sequence
variant protein?
in variant protein?

557
yes
557

499
yes
499

Variant protein T23657_P3 (SEQ ID NO:1065) is encoded by the following transcript(s): T23657_T3 (SEQ ID NO:1001), T23657_T9 (SEQ ID NO:1007) and T23657_T21 (SEQ ID NO:1018), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T3 (SEQ ID NO:1001) is shown in bold; this coding portion starts at position 212 and ends at position 2257. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P3 (SEQ ID NO:1065) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 19

Nucleic acid SNPs

SNP position on
Alternative
Previously known

nucleotide sequence
nucleic acid
SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2270
G -> A
Yes

2801
A -> G
Yes

3087
G -> A
Yes

3742
C -> T
Yes

4234
T -> C
Yes

4494
C -> T
No

4497
C ->
No

4520
C -> T
Yes

4796
C -> T
Yes

4809
C -> T
Yes

The coding portion of transcript T23657_T9 (SEQ ID NO:1007) is shown in bold; this coding portion starts at position 212 and ends at position 2257. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P3 (SEQ ID NO:1065) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2270
G -> A
Yes

2801
A -> G
Yes

3087
G -> A
Yes

3742
C -> T
Yes

4234
T -> C
Yes

4494
C -> T
No

4497
C ->
No

4520
C -> T
Yes

The coding portion of transcript T23657_T21 (SEQ ID NO:1018) is shown in bold; this coding portion starts at position 212 and ends at position 2257. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P3 (SEQ ID NO:1065) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2270
G -> A
Yes

2539
C -> T
No

2542
C ->
No

2565
C -> T
Yes

2841
C -> T
Yes

2854
C -> T
Yes

Variant protein T23657_P4 (SEQ ID NO:1066) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T4 (SEQ ID NO:1002). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P4 (SEQ ID NO:1066) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P4 (SEQ ID NO:1066), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHA TAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1-625 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-625 of T23657_P4 (SEQ ID NO:1066), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTVQCEEAMVSCTVCSLHKGM (SEQ ID NO:1574) corresponding to amino acids 626-646 of T23657_P4 (SEQ ID NO:1066), a third amino acid sequence being at least 90% homologous to GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 626-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 647-696 of T23657_P4 (SEQ ID NO:1066), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TIKHKAF corresponding to amino acids 697-703 of T23657_P4 (SEQ ID NO:1066), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of T23657_P4 (SEQ ID NO:1066), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GTVQCEEAMVSCTVCSLHKGM (SEQ ID NO:1574), corresponding to T23657_P4 (SEQ ID NO:1066).

3. An isolated polypeptide encoding for a tail of T23657_P4 (SEQ ID NO:1066), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TIKHKAF in T23657_P4 (SEQ ID NO:1066).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P4 (SEQ ID NO:1066) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 22, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P4 (SEQ ID NO:1066) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 22

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P4 (SEQ ID NO:1066), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 23 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 23

Glycosylation site(s)

Position(s) on known
Present in
Position

amino acid sequence
variant protein?
in variant protein?

557
yes
557

499
yes
499

Variant protein T23657_P4 (SEQ ID NO:1066) is encoded by the following transcript(s): T23657_T4 (SEQ ID NO:1002), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T4 (SEQ ID NO:1002) is shown in bold; this coding portion starts at position 212 and ends at position 2320. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P4 (SEQ ID NO:1066) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2333
G -> A
Yes

2864
A -> G
Yes

3150
G -> A
Yes

3805
C -> T
Yes

4297
T -> C
Yes

4557
C -> T
No

4560
C ->
No

4583
C -> T
Yes

4859
C -> T
Yes

4872
C -> T
Yes

Variant protein T23657_P5 (SEQ ID NO:1067) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T5 (SEQ ID NO:1003) and T23657_T6 (SEQ ID NO:1004). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P5 (SEQ ID NO:1067) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P5 (SEQ ID NO:1067), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHA TAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLR corresponding to amino acids 1-604 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-604 of T23657_P5 (SEQ ID NO:1067).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P5 (SEQ ID NO:1067) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 25, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P5 (SEQ ID NO:1067) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 25

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P5 (SEQ ID NO:1067), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 26 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 26

Glycosylation site(s)

Position(s) on known
Present in
Position

amino acid sequence
variant protein?
in variant protein?

557
yes
557

499
yes
499

Variant protein T23657_P5 (SEQ ID NO:1067) is encoded by the following transcript(s): T23657_T5 (SEQ ID NO:1003) and T23657_T6 (SEQ ID NO:1004), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T5 (SEQ ID NO:1003) is shown in bold; this coding portion starts at position 212 and ends at position 2023. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P5 (SEQ ID NO:1067) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2156
G -> A
Yes

2795
A -> G
Yes

3081
G -> A
Yes

3736
C -> T
Yes

4228
T -> C
Yes

4488
C -> T
No

4491
C ->
No

4514
C -> T
Yes

4790
C -> T
Yes

4803
C -> T
Yes

The coding portion of transcript T23657_T6 (SEQ ID NO:1004) is shown in bold; this coding portion starts at position 212 and ends at position 2023. The transcript also has the following SNPs as listed in Table 28 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P5 (SEQ ID NO:1067) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 28

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2156
G -> A
Yes

2625
G -> A
Yes

3156
A -> G
Yes

3442
G -> A
Yes

4097
C -> T
Yes

4589
T -> C
Yes

4849
C -> T
No

4852
C ->
No

4875
C -> T
Yes

5151
C -> T
Yes

5164
C -> T
Yes

Variant protein T23657_P6 (SEQ ID NO:1068) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T10 (SEQ ID NO:1008). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P6 (SEQ ID NO:1068) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P6 (SEQ ID NO:1068), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKV corresponding to amino acids 1-547 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-547 of T23657_P6 (SEQ ID NO:1068), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQLVRESPSFWFSYS L (SEQ ID NO:1458) corresponding to amino acids 548-620 of T23657_P6 (SEQ ID NO:1068), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P6 (SEQ ID NO:1068), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQLVRESPSFWFSYS L (SEQ ID NO:1458) in T23657_P6 (SEQ ID NO:1068).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P6 (SEQ ID NO:1068) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 29, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P6 (SEQ ID NO:1068) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29

Amino acid mutations

SNP position on
Alternative
Previously

amino acid sequence
amino acid
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

573
G -> R
Yes

The glycosylation sites of variant protein T23657_P6 (SEQ ID NO:1068), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 30 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 30

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
no

499
yes
499

Variant protein T23657_P6 (SEQ ID NO:1068) is encoded by the following transcript(s): T23657_T10 (SEQ ID NO:1008), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T10 (SEQ ID NO:1008) is shown in bold; this coding portion starts at position 212 and ends at position 2071. The transcript also has the following SNPs as listed in Table 31 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P6 (SEQ ID NO:1068) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 31

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

1928
G -> A
Yes

2257
G -> A
Yes

2896
A -> G
Yes

3182
G -> A
Yes

3837
C -> T
Yes

4329
T -> C
Yes

4589
C -> T
No

4592
C ->
No

4615
C -> T
Yes

4891
C -> T
Yes

4904
C -> T
Yes

Variant protein T23657_P7 (SEQ ID NO:1069) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T12 (SEQ ID NO:1010), T23657_T17 (SEQ ID NO:1015) and T23657_T22 (SEQ ID NO:1019). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P7 (SEQ ID NO:1069) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P7 (SEQ ID NO:1069), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQK corresponding to amino acids 1-546 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-546 of T23657_P7 (SEQ ID NO:1069), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCP corresponding to amino acids 547-549 of T23657_P7 (SEQ ID NO:1069), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P7 (SEQ ID NO:1069) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 32, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P7 (SEQ ID NO:1069) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 32

Amino acid mutations

SNP position on
Alternative
Previously

amino sequence
amino acid
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P7 (SEQ ID NO:1069), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 33 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 33

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
no

499
yes
499

Variant protein T23657_P7 (SEQ ID NO:1069) is encoded by the following transcript(s): T23657_T12 (SEQ ID NO:1010), T23657_T17 (SEQ ID NO:1015) and T23657_T22 (SEQ ID NO:1019), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T12 (SEQ ID NO:1010) is shown in bold; this coding portion starts at position 212 and ends at position 1858. The transcript also has the following SNPs as listed in Table 34 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P7 (SEQ ID NO:1069) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 34

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2330
A -> G
Yes

2616
G -> A
Yes

3271
C -> T
Yes

3763
T -> C
Yes

4023
C -> T
No

4026
C ->
No

4049
C -> T
Yes

4325
C -> T
Yes

4338
C -> T
Yes

The coding portion of transcript T23657_T17 (SEQ ID NO:1015) is shown in bold; this coding portion starts at position 212 and ends at position 1858. The transcript also has the following SNPs as listed in Table 35 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P7 (SEQ ID NO:1069) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 35

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2226
C -> T
No

2229
C ->
No

2252
C -> T
Yes

2528
C -> T
Yes

2541
C -> T
Yes

The coding portion of transcript T23657_T22 (SEQ ID NO:1019) is shown in bold; this coding portion starts at position 212 and ends at position 1858. The transcript also has the following SNPs as listed in Table 36 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P7 (SEQ ID NO:1069) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 36

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2396
C -> T
No

2399
C ->
No

2422
C -> T
Yes

2698
C -> T
Yes

2711
C -> T
Yes

Variant protein T23657_P8 (SEQ ID NO:1070) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T13 (SEQ ID NO:1011), T23657_T19 (SEQ ID NO:1016) and T23657_T28 (SEQ ID NO:1022). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P8 (SEQ ID NO:1070) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P8 (SEQ ID NO:1070), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQK corresponding to amino acids 1-546 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-546 of T23657_P8 (SEQ ID NO:1070), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QHSCTNGNSTMCP (SEQ ID NO:1459) corresponding to amino acids 547-559 of T23657_P8 (SEQ ID NO:1070), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P8 (SEQ ID NO:1070), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence QHSCTNGNSTMCP (SEQ ID NO:1459) in T23657_P8 (SEQ ID NO:1070).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P8 (SEQ ID NO:1070) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 37, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P8 (SEQ ID NO:1070) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 37

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P8 (SEQ ID NO:1070), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 38 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 38

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
no

499
yes
499

Variant protein T23657_P8 (SEQ ID NO:1070) is encoded by the following transcript(s): T23657_T13 (SEQ ID NO:1011), T23657_T19 (SEQ ID NO:1016) and T23657_T28 (SEQ ID NO:1022), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T13 (SEQ ID NO:1011) is shown in bold; this coding portion starts at position 212 and ends at position 1888. The transcript also has the following SNPs as listed in Table 39 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P8 (SEQ ID NO:1070) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 39

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2127
G -> A
Yes

2658
A -> G
Yes

2944
G -> A
Yes

3599
C -> T
Yes

4091
T -> C
Yes

4351
C -> T
No

4354
C ->
No

4377
C -> T
Yes

4653
C -> T
Yes

4666
C -> T
Yes

The coding portion of transcript T23657_T19 (SEQ ID NO:1016) is shown in bold; this coding portion starts at position 212 and ends at position 1888. The transcript also has the following SNPs as listed in Table 40 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P8 (SEQ ID NO:1070) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 40

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2256
C -> T
No

2259
C ->
No

2282
C -> T
Yes

2558
C -> T
Yes

2571
C -> T
Yes

The coding portion of transcript T23657_T28 (SEQ ID NO:1022) is shown in bold; this coding portion starts at position 212 and ends at position 1888. The transcript also has the following SNPs as listed in Table 41 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P8 (SEQ ID NO:1070) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 41

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2308
C -> T
Yes

2442
G -> A
Yes

Variant protein T23657_P9 (SEQ ID NO:1071) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T14 (SEQ ID NO:1012). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.

Variant protein T23657_P9 (SEQ ID NO:1071) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 42, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P9 (SEQ ID NO:1071) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 42

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

63
G -> V
Yes

86
G -> R
Yes

197
G -> R
Yes

345
R ->
No

345
R -> K
No

Variant protein T23657_P9 (SEQ ID NO:1071) is encoded by the following transcript(s): T23657_T14 (SEQ ID NO:1012), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T14 (SEQ ID NO:1012) is shown in bold; this coding portion starts at position 573 and ends at position 1772. The transcript also has the following SNPs as listed in Table 43 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P9 (SEQ ID NO:1071) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 43

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1161
G -> A
Yes

1606
G ->
No

1606
G -> A
No

2308
C -> T
No

2311
C ->
No

2334
C -> T
Yes

2610
C -> T
Yes

2623
C -> T
Yes

Variant protein T23657_P10 (SEQ ID NO:1072) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T15 (SEQ ID NO:1013). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P10 (SEQ ID NO:1072) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P10 (SEQ ID NO:1072), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHA TAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1-625 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-625 of T23657_P10 (SEQ ID NO:1072), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTVQCEEAMVSCTVCSLHKGM (SEQ ID NO:1574) corresponding to amino acids 626-646 of T23657_P10 (SEQ ID NO:1072), and a third amino acid sequence being at least 90% homologous to GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAIACFLYKPLSESS DGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 626-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 647-743 of T23657_P10 (SEQ ID NO:1072), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for an edge portion of T23657_P10 (SEQ ID NO:1072), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GTVQCEEAMVSCTVCSLHKGM (SEQ ID NO:1574), corresponding to T23657_P10 (SEQ ID NO:1072).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P10 (SEQ ID NO:1072) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 44, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P10 (SEQ ID NO:1072) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 44

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P10 (SEQ ID NO:1072), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 45 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 45

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
yes
557

499
yes
499

Variant protein T23657_P10 (SEQ ID NO:1072) is encoded by the following transcript(s): T23657_T15 (SEQ ID NO:1013), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T15 (SEQ ID NO:1013) is shown in bold; this coding portion starts at position 212 and ends at position 2440. The transcript also has the following SNPs as listed in Table 46 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P10 (SEQ ID NO:1072) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 46

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2462
C -> T
No

2465
C ->
No

2488
C -> T
Yes

2764
C -> T
Yes

2777
C -> T
Yes

Variant protein T23657_P11 (SEQ ID NO:1073) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T23 (SEQ ID NO:1020). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P11 (SEQ ID NO:1073) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P11 (SEQ ID NO:1073), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL F corresponding to amino acids 1-425 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-425 of T23657_P11 (SEQ ID NO:1073), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ASCPKAT (SEQ ID NO:1460) corresponding to amino acids 426-432 of T23657_P11 (SEQ ID NO:1073), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P11 (SEQ ID NO:1073), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ASCPKAT (SEQ ID NO:1460) in T23657_P11 (SEQ ID NO:1073).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P11 (SEQ ID NO:1073) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 47, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P11 (SEQ ID NO:1073) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 47

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

430
K ->
No

The glycosylation sites of variant protein T23657_P11 (SEQ ID NO:1073), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 48 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 48

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
no

499
no

Variant protein T23657_P11 (SEQ ID NO:1073) is encoded by the following transcript(s): T23657_T23 (SEQ ID NO:1020), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T23 (SEQ ID NO:1020) is shown in bold; this coding portion starts at position 212 and ends at position 1507. The transcript also has the following SNPs as listed in Table 49 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P11 (SEQ ID NO:1073) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 49

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1501
G ->
No

1501
G -> A
No

2030
C -> T
No

2033
C ->
No

2056
C -> T
Yes

2332
C -> T
Yes

2345
C -> T
Yes

Variant protein T23657_P12 (SEQ ID NO:1074) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T24 (SEQ ID NO:1021). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P12 (SEQ ID NO:1074) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P12 (SEQ ID NO:1074), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHA TAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDK ACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1-675 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-675 of T23657_P12 (SEQ ID NO:1074), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEENEFRRL (SEQ ID NO:1461) corresponding to amino acids 676-684 of T23657_P12 (SEQ ID NO:1074), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P12 (SEQ ID NO:1074), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEENEFRRL (SEQ ID NO:1461) in T23657_P12 (SEQ ID NO:1074).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P12 (SEQ ID NO:1074) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 50, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P12 (SEQ ID NO:1074) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 50

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

The glycosylation sites of variant protein T23657_P12 (SEQ ID NO:1074), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 51 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 51

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
yes
557

499
yes
499

Variant protein T23657_P12 (SEQ ID NO:1074) is encoded by the following transcript(s): T23657_T24 (SEQ ID NO:1021), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T24 (SEQ ID NO:1021) is shown in bold; this coding portion starts at position 212 and ends at position 2263. The transcript also has the following SNPs as listed in Table 52 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P12 (SEQ ID NO:1074) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 52

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

2451
C -> T
Yes

2585
G -> A
Yes

Variant protein T23657_P16 (SEQ ID NO:1075) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T30 (SEQ ID NO:1023). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P16 (SEQ ID NO:1075) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P16 (SEQ ID NO:1075), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGTSPMADPVPAGRQHGSGLDPTTRLSPLC corresponding to amino acids 1-30 of T23657_P16 (SEQ ID NO:1075), and a second amino acid sequence being at least 90% homologous to SLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSS GFGHATAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFG WVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPS QSSAPDSATDSQLQSSV corresponding to amino acids 491-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 31-262 of T23657_P16 (SEQ ID NO:1075), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of T23657_P16 (SEQ ID NO:1075), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGTSPMADPVPAGRQHGSGLDPTTRLSPLC of T23657_P16 (SEQ ID NO:1075).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P16 (SEQ ID NO:1075) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 53, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P16 (SEQ ID NO:1075) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 53

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

36
G ->
No

36
G -> S
No

The glycosylation sites of variant protein T23657_P16 (SEQ ID NO:1075), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 54 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 54

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
yes
97

499
yes
39

Variant protein T23657_P16 (SEQ ID NO:1075) is encoded by the following transcript(s): T23657_T30 (SEQ ID NO:1023), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T30 (SEQ ID NO:1023) is shown in bold; this coding portion starts at position 184 and ends at position 969. The transcript also has the following SNPs as listed in Table 55 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P16 (SEQ ID NO:1075) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 55

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

35
G -> A
Yes

38
G -> A
Yes

145
G -> T
Yes

146
C -> G
Yes

289
G ->
No

289
G -> A
No

991
C -> T
No

994
C ->
No

1017
C -> T
Yes

1293
C -> T
Yes

1306
C -> T
Yes

Variant protein T23657_P17 (SEQ ID NO:1076) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T31 (SEQ ID NO:1024) and T23657_T32 (SEQ ID NO:1025). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P17 (SEQ ID NO:1076) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P17 (SEQ ID NO:1076), comprising a first amino acid sequence being at least 90% homologous to MYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIP ALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYIL IMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 525-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-198 of T23657_P17 (SEQ ID NO:1076).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

The glycosylation sites of variant protein T23657_P17 (SEQ ID NO:1076), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 56 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 56

Glycosylation site(s)

Position(s) on known
Present in
Position in

amino acid sequence
variant protein?
variant protein?

557
yes
33

499
no

Variant protein T23657_P17 (SEQ ID NO:1076) is encoded by the following transcript(s): T23657_T31 (SEQ ID NO:1024) and T23657_T32 (SEQ ID NO:1025), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript T23657_T31 (SEQ ID NO:1024) is shown in bold; this coding portion starts at position 216 and ends at position 809. The transcript also has the following SNPs as listed in Table 57 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P17 (SEQ ID NO:1076) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 57

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

129
G ->
No

129
G -> A
No

831
C -> T
No

834
C ->
No

857
C -> T
Yes

1133
C -> T
Yes

1146
C -> T
Yes

The coding portion of transcript T23657_T32 (SEQ ID NO:1025) is shown in bold; this coding portion starts at position 174 and ends at position 767. The transcript also has the following SNPs as listed in Table 58 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P17 (SEQ ID NO:1076) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 58

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

87
G ->
No

87
G -> A
No

789
C -> T
No

792
C ->
No

815
C -> T
Yes

1091
C -> T
Yes

1104
C -> T
Yes

Variant protein T23657_P19 (SEQ ID NO:1077) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T35 (SEQ ID NO:1026). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein T23657_P19 (SEQ ID NO:1077) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 59, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P19 (SEQ ID NO:1077) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 59

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

36
G ->
No

36
G -> S
No

113
G -> R
Yes

Variant protein T23657_P19 (SEQ ID NO:1077) is encoded by the following transcript(s): T23657_T35 (SEQ ID NO:1026), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T35 (SEQ ID NO:1026) is shown in bold; this coding portion starts at position 184 and ends at position 663. The transcript also has the following SNPs as listed in Table 60 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P19 (SEQ ID NO:1077) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 60

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

35
G -> A
Yes

38
G -> A
Yes

145
G -> T
Yes

146
C -> G
Yes

289
G ->
No

289
G -> A
No

520
G -> A
Yes

849
G -> A
Yes

1488
A -> G
Yes

1774
G -> A
Yes

2429
C -> T
Yes

2921
T -> C
Yes

3181
C -> T
No

3184
C ->
No

3207
C -> T
Yes

3483
C -> T
Yes

3496
C -> T
Yes

Variant protein T23657_P21 (SEQ ID NO:1078) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T37 (SEQ ID NO:1027). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P21 (SEQ ID NO:1078) and S21C_HUMAN:

1. An isolated chimeric polypeptide encoding for T23657_P21 (SEQ ID NO:1078), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWTAR corresponding to amino acids 1-5 of T23657_P21 (SEQ ID NO:1078), and a second amino acid sequence being at least 90% homologous to RCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLY KVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 604-722 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 6-124 of T23657_P21 (SEQ ID NO:1078), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of T23657_P21 (SEQ ID NO:1078), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWTAR of T23657_P21 (SEQ ID NO:1078).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although one of the signal-peptide prediction programs predicts that this protein has a signal peptide (HMM: Signal peptide/NN: NO), both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

The glycosylation sites of variant protein T23657_P21 (SEQ ID NO:1078), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 61 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 61

Glycosylation site(s)

Position(s) on known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

557
no

499
no

Variant protein T23657_P21 (SEQ ID NO:1078) is encoded by the following transcript(s): T23657_T37 (SEQ ID NO:1027), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T37 (SEQ ID NO:1027) is shown in bold; this coding portion starts at position 223 and ends at position 594. The transcript also has the following SNPs as listed in Table 62 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P21 (SEQ ID NO:1078) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 62

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

87
G ->
No

87
G -> A
No

616
C -> T
No

619
C ->
No

642
C -> T
Yes

918
C -> T
Yes

931
C -> T
Yes

Variant protein T23657_P22 (SEQ ID NO:1079) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T38 (SEQ ID NO:1028). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: unknown.

Variant protein T23657_P22 (SEQ ID NO:1079) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 63, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P22 (SEQ ID NO:1079) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 63

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

119
L -> P
Yes

125
T -> P
Yes

Variant protein T23657_P22 (SEQ ID NO:1079) is encoded by the following transcript(s): T23657_T38 (SEQ ID NO:1028), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T38 (SEQ ID NO:1028) is shown in bold; this coding portion starts at position 55 and ends at position 88889. The transcript also has the following SNPs as listed in Table 64 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P22 (SEQ ID NO:1079) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 64

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

35
G -> A
Yes

38
G -> A
Yes

410
T -> C
Yes

427
A -> C
Yes

Variant protein T23657_P23 (SEQ ID NO:1080) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T23657_T11 (SEQ ID NO:1009). An alignment is given to the known protein (Solute carrier family 21 member 12 (SEQ ID NO:1062)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T23657_P23 (SEQ ID NO:1080) and S21C_HUMAN (SEQ ID NO:1062):

1. An isolated chimeric polypeptide encoding for T23657_P23 (SEQ ID NO:1080), comprising a first amino acid sequence being at least 90% homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLCQLWAEKHGARG THEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQGMTVNGFINTVITSLERRYDLHSYQ SGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWGVLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPAN PGAVCADSTSGLSRYQLVFMLGQFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLI GGALLNIYTEMGRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLESQFSLSASEAATL FGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVFSLHCPSVPMAGVTASYGGSLLPE GHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKV corresponding to amino acids 1-547 of S21C_HUMAN (SEQ ID NO:1062), which also corresponds to amino acids 1-547 of T23657_P23 (SEQ ID NO:1080), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNLSEKAPPSGFHIR CNFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS (SEQ ID NO:1464) corresponding to amino acids 548-661 of T23657_P23 (SEQ ID NO:1080), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T23657_P23 (SEQ ID NO:1080), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNLSEKAPPSGFHIR CNFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS (SEQ ID NO:1464) in T23657_P23 (SEQ ID NO:1080).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because both trans-membrane region prediction programs predicted a trans-membrane region for this protein.

Variant protein T23657_P23 (SEQ ID NO:1080) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 65, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P23 (SEQ ID NO:1080) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 65

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

78
V -> I
Yes

206
R -> K
Yes

496
G ->
No

496
G -> S
No

573
G -> R
Yes

The glycosylation sites of variant protein T23657_P23 (SEQ ID NO:1080), as compared to the known protein Solute carrier family 21 member 12 (SEQ ID NO:1062), are described in Table 66 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein).

TABLE 66

Glycosylation site(s)

Position(s) on known amino acid
Present in
Position in

sequence
variant protein?
variant protein?

557
no

499
yes
499

Variant protein T23657_P23 (SEQ ID NO:1080) is encoded by the following transcript(s): T23657_T11 (SEQ ID NO:1009), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T23657_T11 (SEQ ID NO:1009) is shown in bold; this coding portion starts at position 212 and ends at position 2195. The transcript also has the following SNPs as listed in Table 67 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T23657_P23 (SEQ ID NO:1080) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 67

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

132
G -> A
Yes

179
G ->
No

180
A -> T
No

443
G -> A
Yes

760
G -> T
Yes

828
G -> A
Yes

894
-> G
No

894
-> T
No

1252
G -> A
Yes

1697
G ->
No

1697
G -> A
No

1928
G -> A
Yes

2257
G -> A
Yes

2792
C -> T
No

2795
C ->
No

2818
C -> T
Yes

3094
C -> T
Yes

3107
C -> T
Yes

As noted above, cluster T23657 features 33 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T23657_node_—2 (SEQ ID NO:1029) according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1001), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
116
292

T23657_T1 (SEQ ID NO: 999)
116
292

T23657_T2 (SEQ ID NO: 1000)
116
292

T23657_T3 (SEQ ID NO: 1001)
116
292

T23657_T4 (SEQ ID NO: 1002)
116
292

T23657_T5 (SEQ ID NO: 1003)
116
292

T23657_T6 (SEQ ID NO: 1004)
116
292

T23657_T7 (SEQ ID NO: 1005)
116
292

T23657_T8 (SEQ ID NO: 1006)
116
292

T23657_T9 (SEQ ID NO: 1007)
116
292

T23657_T10 (SEQ ID NO: 1008)
116
292

T23657_T11 (SEQ ID NO: 1009)
116
292

T23657_T12 (SEQ ID NO: 1010)
116
292

T23657_T13 (SEQ ID NO: 1011)
116
292

T23657_T14 (SEQ ID NO: 1012)
116
292

T23657_T15 (SEQ ID NO: 1013)
116
292

T23657_T16 (SEQ ID NO: 1014)
116
292

T23657_T17 (SEQ ID NO: 1015)
116
292

T23657_T19 (SEQ ID NO: 1016)
116
292

T23657_T20 (SEQ ID NO: 1017)
116
292

T23657_T21 (SEQ ID NO: 1018)
116
292

T23657_T22 (SEQ ID NO: 1019)
116
292

T23657_T23 (SEQ ID NO: 1020)
116
292

T23657_T24 (SEQ ID NO: 1021)
116
292

T23657_T28 (SEQ ID NO: 1022)
116
292

Segment cluster T23657_node_—3 (SEQ ID NO:1030) according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 69 below describes the starting and ending position of this segment on each transcript.

TABLE 69

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
293
938

T23657_T1 (SEQ ID NO: 999)
293
938

T23657_T2 (SEQ ID NO: 1000)
293
938

T23657_T3 (SEQ ID NO: 1001)
293
938

T23657_T4 (SEQ ID NO: 1002)
293
938

T23657_T5 (SEQ ID NO: 1003)
293
938

T23657_T6 (SEQ ID NO: 1004)
293
938

T23657_T7 (SEQ ID NO: 1005)
293
938

T23657_T8 (SEQ ID NO: 1006)
293
938

T23657_T9 (SEQ ID NO: 1007)
293
938

T23657_T10 (SEQ ID NO: 1008)
293
938

T23657_T11 (SEQ ID NO: 1009)
293
938

T23657_T12 (SEQ ID NO: 1010)
293
938

T23657_T13 (SEQ ID NO: 1011)
293
938

T23657_T14 (SEQ ID NO: 1012)
293
938

T23657_T15 (SEQ ID NO: 1013)
293
938

T23657_T16 (SEQ ID NO: 1014)
293
938

T23657_T17 (SEQ ID NO: 1015)
293
938

T23657_T19 (SEQ ID NO: 1016)
293
938

T23657_T20 (SEQ ID NO: 1017)
293
938

T23657_T21 (SEQ ID NO: 1018)
293
938

T23657_T22 (SEQ ID NO: 1019)
293
938

T23657_T23 (SEQ ID NO: 1020)
293
938

T23657_T24 (SEQ ID NO: 1021)
293
938

T23657_T28 (SEQ ID NO: 1022)
293
938

Segment cluster T23657_node_—8 (SEQ ID NO:1031) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1099
1220

T23657_T1 (SEQ ID NO: 999)
1099
1220

T23657_T2 (SEQ ID NO: 1000)
1099
1220

T23657_T3 (SEQ ID NO: 1001)
1099
1220

T23657_T4 (SEQ ID NO: 1002)
1099
1220

T23657_T5 (SEQ ID NO: 1003)
1099
1220

T23657_T6 (SEQ ID NO: 1004)
1099
1220

T23657_T7 (SEQ ID NO: 1005)
1099
1220

T23657_T8 (SEQ ID NO: 1006)
1099
1220

T23657_T9 (SEQ ID NO: 1007)
1099
1220

T23657_T10 (SEQ ID NO: 1008)
1099
1220

T23657_T11 (SEQ ID NO: 1009)
1099
1220

T23657_T12 (SEQ ID NO: 1010)
1099
1220

T23657_T13 (SEQ ID NO: 1011)
1099
1220

T23657_T14 (SEQ ID NO: 1012)
1008
1129

T23657_T15 (SEQ ID NO: 1013)
1099
1220

T23657_T16 (SEQ ID NO: 1014)
1099
1220

T23657_T17 (SEQ ID NO: 1015)
1099
1220

T23657_T19 (SEQ ID NO: 1016)
1099
1220

T23657_T20 (SEQ ID NO: 1017)
1099
1220

T23657_T21 (SEQ ID NO: 1018)
1099
1220

T23657_T22 (SEQ ID NO: 1019)
1099
1220

T23657_T23 (SEQ ID NO: 1020)
1099
1220

T23657_T24 (SEQ ID NO: 1021)
1099
1220

T23657_T28 (SEQ ID NO: 1022)
1099
1220

Segment cluster T23657_node_—16 (SEQ ID NO:1032) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1333
1487

T23657_T1 (SEQ ID NO: 999)
1333
1487

T23657_T2 (SEQ ID NO: 1000)
1333
1487

T23657_T3 (SEQ ID NO: 1001)
1333
1487

T23657_T4 (SEQ ID NO: 1002)
1333
1487

T23657_T5 (SEQ ID NO: 1003)
1333
1487

T23657_T6 (SEQ ID NO: 1004)
1333
1487

T23657_T7 (SEQ ID NO: 1005)
1333
1487

T23657_T8 (SEQ ID NO: 1006)
1333
1487

T23657_T9 (SEQ ID NO: 1007)
1333
1487

T23657_T10 (SEQ ID NO: 1008)
1333
1487

T23657_T11 (SEQ ID NO: 1009)
1333
1487

T23657_T12 (SEQ ID NO: 1010)
1333
1487

T23657_T13 (SEQ ID NO: 1011)
1333
1487

T23657_T14 (SEQ ID NO: 1012)
1242
1396

T23657_T15 (SEQ ID NO: 1013)
1333
1487

T23657_T16 (SEQ ID NO: 1014)
1333
1487

T23657_T17 (SEQ ID NO: 1015)
1333
1487

T23657_T19 (SEQ ID NO: 1016)
1333
1487

T23657_T20 (SEQ ID NO: 1017)
1333
1487

T23657_T21 (SEQ ID NO: 1018)
1333
1487

T23657_T22 (SEQ ID NO: 1019)
1333
1487

T23657_T23 (SEQ ID NO: 1020)
1333
1487

T23657_T24 (SEQ ID NO: 1021)
1333
1487

T23657_T28 (SEQ ID NO: 1022)
1333
1487

Segment cluster T23657_node_—18 (SEQ ID NO:1033) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1488
1683

T23657_T1 (SEQ ID NO: 999)
1488
1683

T23657_T2 (SEQ ID NO: 1000)
1488
1683

T23657_T3 (SEQ ID NO: 1001)
1488
1683

T23657_T4 (SEQ ID NO: 1002)
1488
1683

T23657_T5 (SEQ ID NO: 1003)
1488
1683

T23657_T6 (SEQ ID NO: 1004)
1488
1683

T23657_T7 (SEQ ID NO: 1005)
1488
1683

T23657_T8 (SEQ ID NO: 1006)
1488
1683

T23657_T9 (SEQ ID NO: 1007)
1488
1683

T23657_T10 (SEQ ID NO: 1008)
1488
1683

T23657_T11 (SEQ ID NO: 1009)
1488
1683

T23657_T12 (SEQ ID NO: 1010)
1488
1683

T23657_T13 (SEQ ID NO: 1011)
1488
1683

T23657_T14 (SEQ ID NO: 1012)
1397
1592

T23657_T15 (SEQ ID NO: 1013)
1488
1683

T23657_T16 (SEQ ID NO: 1014)
1488
1683

T23657_T17 (SEQ ID NO: 1015)
1488
1683

T23657_T19 (SEQ ID NO: 1016)
1488
1683

T23657_T20 (SEQ ID NO: 1017)
1488
1683

T23657_T21 (SEQ ID NO: 1018)
1488
1683

T23657_T22 (SEQ ID NO: 1019)
1488
1683

T23657_T24 (SEQ ID NO: 1021)
1488
1683

T23657_T28 (SEQ ID NO: 1022)
1488
1683

Segment cluster T23657_node_—23 (SEQ ID NO:1034) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T30 (SEQ ID NO:1023) and T23657_T35 (SEQ ID NO:1026). Table 73 below describes the starting and ending position of this segment on each transcript.

TABLE 73

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T30 (SEQ ID NO: 1023)
118
275

T23657_T35 (SEQ ID NO: 1026)
118
275

Segment cluster T23657_node_—24 (SEQ ID NO:1035) according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021), T23657_T28 (SEQ ID NO:1022), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026) and T23657_T37 (SEQ ID NO:1027). Table 74 below describes the starting and ending position of this segment on each transcript.

TABLE 74

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1684
1808

T23657_T1 (SEQ ID NO: 999)
1684
1808

T23657_T2 (SEQ ID NO: 1000)
1684
1808

T23657_T3 (SEQ ID NO: 1001)
1684
1808

T23657_T4 (SEQ ID NO: 1002)
1684
1808

T23657_T5 (SEQ ID NO: 1003)
1684
1808

T23657_T6 (SEQ ID NO: 1004)
1684
1808

T23657_T7 (SEQ ID NO: 1005)
1684
1808

T23657_T8 (SEQ ID NO: 1006)
1684
1808

T23657_T9 (SEQ ID NO: 1007)
1684
1808

T23657_T10 (SEQ ID NO: 1008)
1684
1808

T23657_T11 (SEQ ID NO: 1009)
1684
1808

T23657_T12 (SEQ ID NO: 1010)
1684
1808

T23657_T13 (SEQ ID NO: 1011)
1684
1808

T23657_T14 (SEQ ID NO: 1012)
1593
1717

T23657_T15 (SEQ ID NO: 1013)
1684
1808

T23657_T16 (SEQ ID NO: 1014)
1684
1808

T23657_T17 (SEQ ID NO: 1015)
1684
1808

T23657_T19 (SEQ ID NO: 1016)
1684
1808

T23657_T20 (SEQ ID NO: 1017)
1684
1808

T23657_T21 (SEQ ID NO: 1018)
1684
1808

T23657_T22 (SEQ ID NO: 1019)
1684
1808

T23657_T23 (SEQ ID NO: 1020)
1488
1612

T23657_T24 (SEQ ID NO: 1021)
1684
1808

T23657_T28 (SEQ ID NO: 1022)
1684
1808

T23657_T30 (SEQ ID NO: 1023)
276
400

T23657_T31 (SEQ ID NO: 1024)
116
240

T23657_T32 (SEQ ID NO: 1025)
74
198

T23657_T35 (SEQ ID NO: 1026)
276
400

T23657_T37 (SEQ ID NO: 1027)
74
198

Segment cluster T23657_node_—27 (SEQ ID NO:1036) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T24 (SEQ ID NO:1021), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025) and T23657_T35 (SEQ ID NO:1026). Table 75 below describes the starting and ending position of this segment on each transcript.

TABLE 75

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1850
1992

T23657_T1 (SEQ ID NO: 999)
1850
1992

T23657_T2 (SEQ ID NO: 1000)
1850
1992

T23657_T3 (SEQ ID NO: 1001)
1850
1992

T23657_T4 (SEQ ID NO: 1002)
1850
1992

T23657_T5 (SEQ ID NO: 1003)
1850
1992

T23657_T6 (SEQ ID NO: 1004)
1850
1992

T23657_T7 (SEQ ID NO: 1005)
1850
1992

T23657_T8 (SEQ ID NO: 1006)
1850
1992

T23657_T9 (SEQ ID NO: 1007)
1850
1992

T23657_T10 (SEQ ID NO: 1008)
1951
2093

T23657_T11 (SEQ ID NO: 1009)
1951
2093

T23657_T14 (SEQ ID NO: 1012)
1759
1901

T23657_T15 (SEQ ID NO: 1013)
1850
1992

T23657_T16 (SEQ ID NO: 1014)
1850
1992

T23657_T20 (SEQ ID NO: 1017)
1850
1992

T23657_T21 (SEQ ID NO: 1018)
1850
1992

T23657_T24 (SEQ ID NO: 1021)
1850
1992

T23657_T30 (SEQ ID NO: 1023)
442
584

T23657_T31 (SEQ ID NO: 1024)
282
424

T23657_T32 (SEQ ID NO: 1025)
240
382

T23657_T35 (SEQ ID NO: 1026)
543
685

Segment cluster T23657_node_—29 (SEQ ID NO:1037) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009) and T23657_T35 (SEQ ID NO:1026). Table 76 below describes the starting and ending position of this segment on each transcript.

TABLE 76

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T5 (SEQ ID NO: 1003)
2023
2278

T23657_T6 (SEQ ID NO: 1004)
2023
2278

T23657_T10 (SEQ ID NO: 1008)
2124
2379

T23657_T11 (SEQ ID NO: 1009)
2124
2379

T23657_T35 (SEQ ID NO: 1026)
716
971

Segment cluster T23657_node_—34 (SEQ ID NO:1038) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021), T23657_T28 (SEQ ID NO:1022), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026), T23657_T37 (SEQ ID NO:1027) and T23657_T38 (SEQ ID NO:1028). Table 77 below describes the starting and ending position of this segment on each transcript.

TABLE 77

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
2088
2236

T23657_T1 (SEQ ID NO: 999)
2088
2236

T23657_T2 (SEQ ID NO: 1000)
2088
2236

T23657_T3 (SEQ ID NO: 1001)
2088
2236

T23657_T4 (SEQ ID NO: 1002)
2151
2299

T23657_T5 (SEQ ID NO: 1003)
2380
2528

T23657_T6 (SEQ ID NO: 1004)
2443
2591

T23657_T7 (SEQ ID NO: 1005)
2088
2236

T23657_T8 (SEQ ID NO: 1006)
2088
2236

T23657_T9 (SEQ ID NO: 1007)
2088
2236

T23657_T10 (SEQ ID NO: 1008)
2481
2629

T23657_T11 (SEQ ID NO: 1009)
2481
2629

T23657_T12 (SEQ ID NO: 1010)
1915
2063

T23657_T13 (SEQ ID NO: 1011)
1945
2093

T23657_T14 (SEQ ID NO: 1012)
1997
2145

T23657_T15 (SEQ ID NO: 1013)
2151
2299

T23657_T16 (SEQ ID NO: 1014)
2088
2236

T23657_T17 (SEQ ID NO: 1015)
1915
2063

T23657_T19 (SEQ ID NO: 1016)
1945
2093

T23657_T20 (SEQ ID NO: 1017)
2088
2236

T23657_T21 (SEQ ID NO: 1018)
2088
2236

T23657_T22 (SEQ ID NO: 1019)
1915
2063

T23657_T23 (SEQ ID NO: 1020)
1719
1867

T23657_T24 (SEQ ID NO: 1021)
2088
2236

T23657_T28 (SEQ ID NO: 1022)
1945
2093

T23657_T30 (SEQ ID NO: 1023)
680
828

T23657_T31 (SEQ ID NO: 1024)
520
668

T23657_T32 (SEQ ID NO: 1025)
478
626

T23657_T35 (SEQ ID NO: 1026)
1073
1221

T23657_T37 (SEQ ID NO: 1027)
305
453

T23657_T38 (SEQ ID NO: 1028)
254
402

Segment cluster T23657_node_—37 (SEQ ID NO:1039) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T6 (SEQ ID NO:1004), T23657_T9 (SEQ ID NO:1007), T23657_T13 (SEQ ID NO:1011) and T23657_T21 (SEQ ID NO:1018). Table 78 below describes the starting and ending position of this segment on each transcript.

TABLE 78

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T3 (SEQ ID NO: 1001)
2237
2376

T23657_T4 (SEQ ID NO: 1002)
2300
2439

T23657_T6 (SEQ ID NO: 1004)
2592
2731

T23657_T9 (SEQ ID NO: 1007)
2237
2376

T23657_T13 (SEQ ID NO: 1011)
2094
2233

T23657_T21 (SEQ ID NO: 1018)
2237
2376

Segment cluster T23657_node_—38 (SEQ ID NO:1040) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T6 (SEQ ID NO:1004), T23657_T9 (SEQ ID NO:1007) and T23657_T13 (SEQ ID NO:1011). Table 79 below describes the starting and ending position of this segment on each transcript.

TABLE 79

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T3 (SEQ ID NO: 1001)
2377
2534

T23657_T4 (SEQ ID NO: 1002)
2440
2597

T23657_T6 (SEQ ID NO: 1004)
2732
2889

T23657_T9 (SEQ ID NO: 1007)
2377
2534

T23657_T13 (SEQ ID NO: 1011)
2234
2391

Segment cluster T23657_node_—39 (SEQ ID NO:1041) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T16 (SEQ ID NO:1014), T23657_T20 (SEQ ID NO:1017), T23657_T22 (SEQ ID NO:1019) and T23657_T35 (SEQ ID NO:1026). Table 80 below describes the starting and ending position of this segment on each transcript.

TABLE 80

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T2 (SEQ ID NO: 1000)
2237
2406

T23657_T3 (SEQ ID NO: 1001)
2535
2704

T23657_T4 (SEQ ID NO: 1002)
2598
2767

T23657_T5 (SEQ ID NO: 1003)
2529
2698

T23657_T6 (SEQ ID NO: 1004)
2890
3059

T23657_T7 (SEQ ID NO: 1005)
2237
2406

T23657_T9 (SEQ ID NO: 1007)
2535
2704

T23657_T10 (SEQ ID NO: 1008)
2630
2799

T23657_T12 (SEQ ID NO: 1010)
2064
2233

T23657_T13 (SEQ ID NO: 1011)
2392
2561

T23657_T16 (SEQ ID NO: 1014)
2237
2406

T23657_T20 (SEQ ID NO: 1017)
2237
2406

T23657_T22 (SEQ ID NO: 1019)
2064
2233

T23657_T35 (SEQ ID NO: 1026)
1222
1391

Segment cluster T23657_node_—40 (SEQ ID NO:1042) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T16 (SEQ ID NO:1014) and T23657_T35 (SEQ ID NO:1026). Table 81 below describes the starting and ending position of this segment on each transcript.

TABLE 81

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T2 (SEQ ID NO: 1000)
2407
3973

T23657_T3 (SEQ ID NO: 1001)
2705
4271

T23657_T4 (SEQ ID NO: 1002)
2768
4334

T23657_T5 (SEQ ID NO: 1003)
2699
4265

T23657_T6 (SEQ ID NO: 1004)
3060
4626

T23657_T7 (SEQ ID NO: 1005)
2407
3973

T23657_T9 (SEQ ID NO: 1007)
2705
4271

T23657_T10 (SEQ ID NO: 1008)
2800
4366

T23657_T12 (SEQ ID NO: 1010)
2234
3800

T23657_T13 (SEQ ID NO: 1011)
2562
4128

T23657_T16 (SEQ ID NO: 1014)
2407
3973

T23657_T35 (SEQ ID NO: 1026)
1392
2958

Segment cluster T23657_node_—45 (SEQ ID NO:1043) according to the present invention is supported by 91 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026) and T23657_T37 (SEQ ID NO:1027). Table 82 below describes the starting and ending position of this segment on each transcript.

TABLE 82

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
2363
2789

T23657_T1 (SEQ ID NO: 999)
2363
2942

T23657_T2 (SEQ ID NO: 1000)
4160
4586

T23657_T3 (SEQ ID NO: 1001)
4458
4884

T23657_T4 (SEQ ID NO: 1002)
4521
4947

T23657_T5 (SEQ ID NO: 1003)
4452
4878

T23657_T6 (SEQ ID NO: 1004)
4813
5239

T23657_T7 (SEQ ID NO: 1005)
4160
4739

T23657_T8 (SEQ ID NO: 1006)
2363
2594

T23657_T9 (SEQ ID NO: 1007)
4458
4689

T23657_T10 (SEQ ID NO: 1008)
4553
4979

T23657_T11 (SEQ ID NO: 1009)
2756
3182

T23657_T12 (SEQ ID NO: 1010)
3987
4413

T23657_T13 (SEQ ID NO: 1011)
4315
4741

T23657_T14 (SEQ ID NO: 1012)
2272
2698

T23657_T15 (SEQ ID NO: 1013)
2426
2852

T23657_T16 (SEQ ID NO: 1014)
4067
4493

T23657_T17 (SEQ ID NO: 1015)
2190
2616

T23657_T19 (SEQ ID NO: 1016)
2220
2646

T23657_T20 (SEQ ID NO: 1017)
2533
2959

T23657_T21 (SEQ ID NO: 1018)
2503
2929

T23657_T22 (SEQ ID NO: 1019)
2360
2786

T23657_T23 (SEQ ID NO: 1020)
1994
2420

T23657_T30 (SEQ ID NO: 1023)
955
1381

T23657_T31 (SEQ ID NO: 1024)
795
1221

T23657_T32 (SEQ ID NO: 1025)
753
1179

T23657_T35 (SEQ ID NO: 1026)
3145
3571

T23657_T37 (SEQ ID NO: 1027)
580
1006

Segment cluster T23657_node_—46 (SEQ ID NO:1044) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T1 (SEQ ID NO:999), T23657_T7 (SEQ ID NO:1005) and T23657_T38 (SEQ ID NO:1028). Table 83 below describes the starting and ending position of this segment on each transcript.

TABLE 83

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T1 (SEQ ID NO: 999)
2943
3109

T23657_T7 (SEQ ID NO: 1005)
4740
4906

T23657_T38 (SEQ ID NO: 1028)
403
569

Segment cluster T23657_node_—49 (SEQ ID NO:1045) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 84 below describes the starting and ending position of this segment on each transcript.

TABLE 84

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T24 (SEQ ID NO: 1021)
2237
2587

T23657_T28 (SEQ ID NO: 1022)
2094
2444

Segment cluster T23657_node_—0 (SEQ ID NO:1046) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1000), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021), T23657_T28 (SEQ ID NO:1022) and T23657_T31 (SEQ ID NO:1024). Table 85 below describes the starting and ending position of this segment on each transcript.

TABLE 85

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1
115

T23657_T1 (SEQ ID NO: 999)
1
115

T23657_T2 (SEQ ID NO: 1000)
1
115

T23657_T3 (SEQ ID NO: 1001)
1
115

T23657_T4 (SEQ ID NO: 1002)
1
115

T23657_T5 (SEQ ID NO: 1003)
1
115

T23657_T6 (SEQ ID NO: 1004)
1
115

T23657_T7 (SEQ ID NO: 1005)
1
115

T23657_T8 (SEQ ID NO: 1006)
1
115

T23657_T9 (SEQ ID NO: 1007)
1
115

T23657_T10 (SEQ ID NO: 1008)
1
115

T23657_T11 (SEQ ID NO: 1009)
1
115

T23657_T12 (SEQ ID NO: 1010)
1
115

T23657_T13 (SEQ ID NQ: 1011)
1
115

T23657_T14 (SEQ ID NO: 1012)
1
115

T23657_T15 (SEQ ID NO: 1013)
1
115

T23657_T16 (SEQ ID NO: 1014)
1
115

T23657_T17 (SEQ ID NO: 1015)
1
115

T23657_T19 (SEQ ID NO: 1016)
1
115

T23657_T20 (SEQ ID NO: 1017)
1
115

T23657_T21 (SEQ ID NO: 1018)
1
115

T23657_T22 (SEQ ID NO: 1019)
1
115

T23657_T23 (SEQ ID NO: 1020)
1
115

T23657_T24 (SEQ ID NO: 1021)
1
115

T23657_T28 (SEQ ID NO: 1022)
1
115

T23657_T31 (SEQ ID NO: 1024)
1
115

Segment cluster T23657_node_—4 (SEQ ID NO:1047) according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 86 below describes the starting and ending position of this segment on each transcript.

TABLE 86

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
939
1007

T23657_T1 (SEQ ID NO: 999)
939
1007

T23657_T2 (SEQ ID NO: 1000)
939
1007

T23657_T3 (SEQ ID NO: 1001)
939
1007

T23657_T4 (SEQ ID NO: 1002)
939
1007

T23657_T5 (SEQ ID NO: 1003)
939
1007

T23657_T6 (SEQ ID NO: 1004)
939
1007

T23657_T7 (SEQ ID NO: 1005)
939
1007

T23657_T8 (SEQ ID NO: 1006)
939
1007

T23657_T9 (SEQ ID NO: 1007)
939
1007

T23657_T10 (SEQ ID NO: 1008)
939
1007

T23657_T11 (SEQ ID NO: 1009)
939
1007

T23657_T12 (SEQ ID NO: 1010)
939
1007

T23657_T13 (SEQ ID NO: 1011)
939
1007

T23657_T14 (SEQ ID NO: 1012)
939
1007

T23657_T15 (SEQ ID NO: 1013)
939
1007

T23657_T16 (SEQ ID NO: 1014)
939
1007

T23657_T17 (SEQ ID NO: 1015)
939
1007

T23657_T19 (SEQ ID NO: 1016)
939
1007

T23657_T20 (SEQ ID NO: 1017)
939
1007

T23657_T21 (SEQ ID NO: 1018)
939
1007

T23657_T22 (SEQ ID NO: 1019)
939
1007

T23657_T23 (SEQ ID NO: 1020)
939
1007

T23657_T24 (SEQ ID NO: 1021)
939
1007

T23657_T28 (SEQ ID NO: 1022)
939
1007

Segment cluster T23657_node_—6 (SEQ ID NO:1048) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 87 below describes the starting and ending position of this segment on each transcript.

TABLE 87

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1008
1098

T23657_T1 (SEQ ID NO: 999)
1008
1098

T23657_T2 (SEQ ID NO: 1000)
1008
1098

T23657_T3 (SEQ ID NO: 1001)
1008
1098

T23657_T4 (SEQ ID NO: 1002)
1008
1098

T23657_T5 (SEQ ID NO: 1003)
1008
1098

T23657_T6 (SEQ ID NO: 1004)
1008
1098

T23657_T7 (SEQ ID NO: 1005)
1008
1098

T23657_T8 (SEQ ID NO: 1006)
1008
1098

T23657_T9 (SEQ ID NO: 1007)
1008
1098

T23657_T10 (SEQ ID NO: 1008)
1008
1098

T23657_T11 (SEQ ID NO: 1009)
1008
1098

T23657_T12 (SEQ ID NO: 1010)
1008
1098

T23657_T13 (SEQ ID NO: 1011)
1008
1098

T23657_T15 (SEQ ID NO: 1013)
1008
1098

T23657_T16 (SEQ ID NO: 1014)
1008
1098

T23657_T17 (SEQ ID NO: 1015)
1008
1098

T23657_T19 (SEQ ID NO: 1016)
1008
1098

T23657_T20 (SEQ ID NO: 1017)
1008
1098

T23657_T21 (SEQ ID NO: 1018)
1008
1098

T23657_T22 (SEQ ID NO: 1019)
1008
1098

T23657_T23 (SEQ ID NO: 1020)
1008
1098

T23657_T24 (SEQ ID NO: 1021)
1008
1098

T23657_T28 (SEQ ID NO: 1022)
1008
1098

Segment cluster T23657_node_—11 (SEQ ID NO:1049) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021) and T23657_T28 (SEQ ID NO:1022). Table 88 below describes the starting and ending position of this segment on each transcript.

TABLE 88

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1221
1332

T23657_T1 (SEQ ID NO: 999)
1221
1332

T23657_T2 (SEQ ID NO: 1000)
1221
1332

T23657_T3 (SEQ ID NO: 1001)
1221
1332

T23657_T4 (SEQ ID NO: 1002)
1221
1332

T23657_T5 (SEQ ID NO: 1003)
1221
1332

T23657_T6 (SEQ ID NO: 1004)
1221
1332

T23657_T7 (SEQ ID NO: 1005)
1221
1332

T23657_T8 (SEQ ID NO: 1006)
1221
1332

T23657_T9 (SEQ ID NO: 1007)
1221
1332

T23657_T10 (SEQ ID NO: 1008)
1221
1332

T23657_T11 (SEQ ID NO: 1009)
1221
1332

T23657_T12 (SEQ ID NO: 1010)
1221
1332

T23657_T13 (SEQ ID NO: 1011)
1221
1332

T23657_T14 (SEQ ID NO: 1012)
1130
1241

T23657_T15 (SEQ ID NO: 1013)
1221
1332

T23657_T16 (SEQ ID NO: 1014)
1221
1332

T23657_T17 (SEQ ID NO: 1015)
1221
1332

T23657_T19 (SEQ ID NO: 1016)
1221
1332

T23657_T20 (SEQ ID NO: 1017)
1221
1332

T23657_T21 (SEQ ID NO: 1018)
1221
1332

T23657_T22 (SEQ ID NO: 1019)
1221
1332

T23657_T23 (SEQ ID NO: 1020)
1221
1332

T23657_T24 (SEQ ID NO: 1021)
1221
1332

T23657_T28 (SEQ ID NO: 1022)
1221
1332

Segment cluster T23657_node_—20 (SEQ ID NO:1050) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T32 (SEQ ID NO:1025) and T23657_T37 (SEQ ID NO:1027). Table 89 below describes the starting and ending position of this segment on each transcript.

TABLE 89

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T32 (SEQ ID NO: 1025)
1
73

T23657_T37 (SEQ ID NO: 1027)
1
73

Segment cluster T23657_node_—22 (SEQ ID NO:1051) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T30 (SEQ ID NO:1023), T23657_T35 (SEQ ID NO:1026) and T23657_T38 (SEQ ID NO:1028). Table 90 below describes the starting and ending position of this segment on each transcript.

TABLE 90

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T30 (SEQ ID NO: 1023)
1
117

T23657_T35 (SEQ ID NO: 1026)
1
117

T23657_T38 (SEQ ID NO: 1028)
1
117

Segment cluster T23657_node_—25 (SEQ ID NO:1052) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021), T23657_T28 (SEQ ID NO:1022), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026), T23657_T37 (SEQ ID NO:1027) and T23657_T38 (SEQ ID NO:1028). Table 91 below describes the starting and ending position of this segment on each transcript.

TABLE 91

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1809
1849

T23657_T1 (SEQ ID NO: 999)
1809
1849

T23657_T2 (SEQ ID NO: 1000)
1809
1849

T23657_T3 (SEQ ID NO: 1001)
1809
1849

T23657_T4 (SEQ ID NO: 1002)
1809
1849

T23657_T5 (SEQ ID NO: 1003)
1809
1849

T23657_T6 (SEQ ID NO: 1004)
1809
1849

T23657_T7 (SEQ ID NO: 1005)
1809
1849

T23657_T8 (SEQ ID NO: 1006)
1809
1849

T23657_T9 (SEQ ID NO: 1007)
1809
1849

T23657_T10 (SEQ ID NO: 1008)
1809
1849

T23657_T11 (SEQ ID NO: 1009)
1809
1849

T23657_T12 (SEQ ID NO: 1010)
1809
1849

T23657_T13 (SEQ ID NO: 1011)
1809
1849

T23657_T14 (SEQ ID NO: 1012)
1718
1758

T23657_T15 (SEQ ID NO: 1013)
1809
1849

T23657_T16 (SEQ ID NO: 1014)
1809
1849

T23657_T17 (SEQ ID NO: 1015)
1809
1849

T23657_T19 (SEQ ID NO: 1016)
1809
1849

T23657_T20 (SEQ ID NO: 1017)
1809
1849

T23657_T21 (SEQ ID NO: 1018)
1809
1849

T23657_T22 (SEQ ID NO: 1019)
1809
1849

T23657_T23 (SEQ ID NO: 1020)
1613
1653

T23657_T24 (SEQ ID NO: 1021)
1809
1849

T23657_T28 (SEQ ID NO: 1022)
1809
1849

T23657_T30 (SEQ ID NO: 1023)
401
441

T23657_T31 (SEQ ID NO: 1024)
241
281

T23657_T32 (SEQ ID NO: 1025)
199
239

T23657_T35 (SEQ ID NO: 1026)
401
441

T23657_T37 (SEQ ID NO: 1027)
199
239

T23657_T38 (SEQ ID NO: 1028)
118
158

Segment cluster T23657_node_—26 (SEQ ID NO:1053) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009) and T23657_T35 (SEQ ID NO:1026). Table 92 below describes the starting and ending position of this segment on each transcript.

TABLE 92

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T10 (SEQ ID NO: 1008)
1850
1950

T23657_T11 (SEQ ID NO: 1009)
1850
1950

T23657_T35 (SEQ ID NO: 1026)
442
542

Segment cluster T23657_node_—28 (SEQ ID NO:1054) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T24 (SEQ ID NO:1021), T23657_T28 (SEQ ID NO:1022), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026) and T23657_T38 (SEQ ID NO:1028). Table 93 below describes the starting and ending position of this segment on each transcript.

TABLE 93

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
1993
2022

T23657_T1 (SEQ ID NO: 999)
1993
2022

T23657_T2 (SEQ ID NO: 1000)
1993
2022

T23657_T3 (SEQ ID NO: 1001)
1993
2022

T23657_T4 (SEQ ID NO: 1002)
1993
2022

T23657_T5 (SEQ ID NO: 1003)
1993
2022

T23657_T6 (SEQ ID NO: 1004)
1993
2022

T23657_T7 (SEQ ID NO: 1005)
1993
2022

T23657_T8 (SEQ ID NO: 1006)
1993
2022

T23657_T9 (SEQ ID NO: 1007)
1993
2022

T23657_T10 (SEQ ID NO: 1008)
2094
2123

T23657_T11 (SEQ ID NO: 1009)
2094
2123

T23657_T13 (SEQ ID NO: 1011)
1850
1879

T23657_T14 (SEQ ID NO: 1012)
1902
1931

T23657_T15 (SEQ ID NO: 1013)
1993
2022

T23657_T16 (SEQ ID NO: 1014)
1993
2022

T23657_T19 (SEQ ID NO: 1016)
1850
1879

T23657_T20 (SEQ ID NO: 1017)
1993
2022

T23657_T21 (SEQ ID NO: 1018)
1993
2022

T23657_T24 (SEQ ID NO: 1021)
1993
2022

T23657_T28 (SEQ ID NO: 1022)
1850
1879

T23657_T30 (SEQ ID NO: 1023)
585
614

T23657_T31 (SEQ ID NO: 1024)
425
454

T23657_T32 (SEQ ID NO: 1025)
383
412

T23657_T35 (SEQ ID NO: 1026)
686
715

T23657_T38 (SEQ ID NO: 1028)
159
188

Segment cluster T23657_node_—30 (SEQ ID NO:1055) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009) and T23657_T35 (SEQ ID NO:1026). Table 94 below describes the starting and ending position of this segment on each transcript.

TABLE 94

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T5 (SEQ ID NO: 1003)
2279
2314

T23657_T6 (SEQ ID NO: 1004)
2279
2314

T23657_T10 (SEQ ID NO: 1008)
2380
2415

T23657_T11 (SEQ ID NO: 1009)
2380
2415

T23657_T35 (SEQ ID NO: 1026)
972
1007

Segment cluster T23657_node_—31 (SEQ ID NO:1056) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T24 (SEQ ID NO:1021), T23657_T28 (SEQ ID NO:1022), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026), T23657_T37 (SEQ ID NO:1027) and T23657_T38 (SEQ ID NO:1028). Table 95 below describes the starting and ending position of this segment on each transcript.

TABLE 95

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
2023
2087

T23657_T1 (SEQ ID NO: 999)
2023
2087

T23657_T2 (SEQ ID NO: 1000)
2023
2087

T23657_T3 (SEQ ID NO: 1001)
2023
2087

T23657_T4 (SEQ ID NO: 1002)
2023
2087

T23657_T5 (SEQ ID NO: 1003)
2315
2379

T23657_T6 (SEQ ID NO: 1004)
2315
2379

T23657_T7 (SEQ ID NO: 1005)
2023
2087

T23657_T8 (SEQ ID NO: 1006)
2023
2087

T23657_T9 (SEQ ID NO: 1007)
2023
2087

T23657_T10 (SEQ ID NO: 1008)
2416
2480

T23657_T11 (SEQ ID NO: 1009)
2416
2480

T23657_T12 (SEQ ID NO: 1010)
1850
1914

T23657_T13 (SEQ ID NO: 1011)
1880
1944

T23657_T14 (SEQ ID NO: 1012)
1932
1996

T23657_T15 (SEQ ID NO: 1013)
2023
2087

T23657_T16 (SEQ ID NO: 1014)
2023
2087

T23657_T17 (SEQ ID NO: 1015)
1850
1914

T23657_T19 (SEQ ID NO: 1016)
1880
1944

T23657_T20 (SEQ ID NO: 1017)
2023
2087

T23657_T21 (SEQ ID NO: 1018)
2023
2087

T23657_T22 (SEQ ID NO: 1019)
1850
1914

T23657_T23 (SEQ ID NO: 1020)
1654
1718

T23657_T24 (SEQ ID NO: 1021)
2023
2087

T23657_T28 (SEQ ID NO: 1022)
1880
1944

T23657_T30 (SEQ ID NO: 1023)
615
679

T23657_T31 (SEQ ID NO: 1024)
455
519

T23657_T32 (SEQ ID NO: 1025)
413
477

T23657_T35 (SEQ ID NO: 1026)
1008
1072

T23657_T37 (SEQ ID NO: 1027)
240
304

T23657_T38 (SEQ ID NO: 1028)
189
253

Segment cluster T23657_node_—32 (SEQ ID NO:1057) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T4 (SEQ ID NO:1002), T23657_T6 (SEQ ID NO:1004) and T23657_T15 (SEQ ID NO:1013). Table 96 below describes the starting and ending position of this segment on each transcript.

TABLE 96

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T4 (SEQ ID NO: 1002)
2088
2150

T23657_T6 (SEQ ID NO: 1004)
2380
2442

T23657_T15 (SEQ ID NO: 1013)
2088
2150

Segment cluster T23657_node_—41 (SEQ ID NO:1058) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T16 (SEQ ID NO:1014) and T23657_T35 (SEQ ID NO:1026). Table 97 below describes the starting and ending position of this segment on each transcript.

TABLE 97

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T2 (SEQ ID NO: 1000)
3974
4033

T23657_T3 (SEQ ID NO: 1001)
4272
4331

T23657_T4 (SEQ ID NO: 1002)
4335
4394

T23657_T5 (SEQ ID NO: 1003)
4266
4325

T23657_T6 (SEQ ID NO: 1004)
4627
4686

T23657_T7 (SEQ ID NO: 1005)
3974
4033

T23657_T9 (SEQ ID NO: 1007)
4272
4331

T23657_T10 (SEQ ID NO: 1008)
4367
4426

T23657_T12 (SEQ ID NO: 1010)
3801
3860

T23657_T13 (SEQ ID NO: 1011)
4129
4188

T23657_T16 (SEQ ID NO: 1014)
3974
4033

T23657_T35 (SEQ ID NO: 1026)
2959
3018

Segment cluster T23657_node_—42 (SEQ ID NO:1059) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026) and T23657_T37 (SEQ ID NO:1027). Table 98 below describes the starting and ending position of this segment on each transcript.

TABLE 98

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
2237
2268

T23657_T1 (SEQ ID NO: 999)
2237
2268

T23657_T2 (SEQ ID NO: 1000)
4034
4065

T23657_T3 (SEQ ID NO: 1001)
4332
4363

T23657_T4 (SEQ ID NO: 1002)
4395
4426

T23657_T5 (SEQ ID NO: 1003)
4326
4357

T23657_T6 (SEQ ID NO: 1004)
4687
4718

T23657_T7 (SEQ ID NO: 1005)
4034
4065

T23657_T8 (SEQ ID NO: 1006)
2237
2268

T23657_T9 (SEQ ID NO: 1007)
4332
4363

T23657_T10 (SEQ ID NO: 1008)
4427
4458

T23657_T11 (SEQ ID NO: 1009)
2630
2661

T23657_T12 (SEQ ID NO: 1010)
3861
3892

T23657_T13 (SEQ ID NO: 1011)
4189
4220

T23657_T14 (SEQ ID NO: 1012)
2146
2177

T23657_T15 (SEQ ID NO: 1013)
2300
2331

T23657_T17 (SEQ ID NO: 1015)
2064
2095

T23657_T19 (SEQ ID NO: 1016)
2094
2125

T23657_T20 (SEQ ID NO: 1017)
2407
2438

T23657_T21 (SEQ ID NO: 1018)
2377
2408

T23657_T22 (SEQ ID NO: 1019)
2234
2265

T23657_T23 (SEQ ID NO: 1020)
1868
1899

T23657_T30 (SEQ ID NO: 1023)
829
860

T23657_T31 (SEQ ID NO: 1024)
669
700

T23657_T32 (SEQ ID NO: 1025)
627
658

T23657_T35 (SEQ ID NO: 1026)
3019
3050

T23657_T37 (SEQ ID NO: 1027)
454
485

Segment cluster T23657_node_—43 (SEQ ID NO:1060) according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026) and T23657_T37 (SEQ ID NO:1027). Table 99 below describes the starting and ending position of this segment on each transcript.

TABLE 99

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
2269
2329

T23657_T1 (SEQ ID NO: 999)
2269
2329

T23657_T2 (SEQ ID NO: 1000)
4066
4126

T23657_T3 (SEQ ID NO: 1001)
4364
4424

T23657_T4 (SEQ ID NO: 1002)
4427
4487

T23657_T5 (SEQ ID NO: 1003)
4358
4418

T23657_T6 (SEQ ID NO: 1004)
4719
4779

T23657_T7 (SEQ ID NO: 1005)
4066
4126

T23657_T8 (SEQ ID NO: 1006)
2269
2329

T23657_T9 (SEQ ID NO: 1007)
4364
4424

T23657_T10 (SEQ ID NO: 1008)
4459
4519

T23657_T11 (SEQ ID NO: 1009)
2662
2722

T23657_T12 (SEQ ID NO: 1010)
3893
3953

T23657_T13 (SEQ ID NO: 1011)
4221
4281

T23657_T14 (SEQ ID NO: 1012)
2178
2238

T23657_T15 (SEQ ID NO: 1013)
2332
2392

T23657_T17 (SEQ ID NO: 1015)
2096
2156

T23657_T19 (SEQ ID NO: 1016)
2126
2186

T23657_T20 (SEQ ID NO: 1017)
2439
2499

T23657_T21 (SEQ ID NO: 1018)
2409
2469

T23657_T22 (SEQ ID NO: 1019)
2266
2326

T23657_T23 (SEQ ID NO: 1020)
1900
1960

T23657_T30 (SEQ ID NO: 1023)
861
921

T23657_T31 (SEQ ID NO: 1024)
701
761

T23657_T32 (SEQ ID NO: 1025)
659
719

T23657_T35 (SEQ ID NO: 1026)
3051
3111

T23657_T37 (SEQ ID NO: 1027)
486
546

Segment cluster T23657_node_—44 (SEQ ID NO:1061) according to the present invention is supported by 79 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T23657_T0 (SEQ ID NO:998), T23657_T1 (SEQ ID NO:999), T23657_T2 (SEQ ID NO:1000), T23657_T3 (SEQ ID NO:1001), T23657_T4 (SEQ ID NO:1002), T23657_T5 (SEQ ID NO:1003), T23657_T6 (SEQ ID NO:1004), T23657_T7 (SEQ ID NO:1005), T23657_T8 (SEQ ID NO:1006), T23657_T9 (SEQ ID NO:1007), T23657_T10 (SEQ ID NO:1008), T23657_T11 (SEQ ID NO:1009), T23657_T12 (SEQ ID NO:1010), T23657_T13 (SEQ ID NO:1011), T23657_T14 (SEQ ID NO:1012), T23657_T15 (SEQ ID NO:1013), T23657_T16 (SEQ ID NO:1014), T23657_T17 (SEQ ID NO:1015), T23657_T19 (SEQ ID NO:1016), T23657_T20 (SEQ ID NO:1017), T23657_T21 (SEQ ID NO:1018), T23657_T22 (SEQ ID NO:1019), T23657_T23 (SEQ ID NO:1020), T23657_T30 (SEQ ID NO:1023), T23657_T31 (SEQ ID NO:1024), T23657_T32 (SEQ ID NO:1025), T23657_T35 (SEQ ID NO:1026) and T23657_T37 (SEQ ID NO:1027). Table 100 below describes the starting and ending position of this segment on each transcript.

TABLE 100

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T23657_T0 (SEQ ID NO: 998)
2330
2362

T23657_T1 (SEQ ID NO: 999)
2330
2362

T23657_T2 (SEQ ID NO: 1000)
4127
4159

T23657_T3 (SEQ ID NO: 1001)
4425
4457

T23657_T4 (SEQ ID NO: 1002)
4488
4520

T23657_T5 (SEQ ID NO: 1003)
4419
4451

T23657_T6 (SEQ ID NO: 1004)
4780
4812

T23657_T7 (SEQ ID NO: 1005)
4127
4159

T23657_T8 (SEQ ID NO: 1006)
2330
2362

T23657_T9 (SEQ ID NO: 1007)
4425
4457

T23657_T10 (SEQ ID NO: 1008)
4520
4552

T23657_T11 (SEQ ID NO: 1009)
2723
2755

T23657_T12 (SEQ ID NO: 1010)
3954
3986

T23657_T13 (SEQ ID NO: 1011)
4282
4314

T23657_T14 (SEQ ID NO: 1012)
2239
2271

T23657_T15 (SEQ ID NO: 1013)
2393
2425

T23657_T16 (SEQ ID NO: 1014)
4034
4066

T23657_T17 (SEQ ID NO: 1015)
2157
2189

T23657_T19 (SEQ ID NO: 1016)
2187
2219

T23657_T20 (SEQ ID NO: 1017)
2500
2532

T23657_T21 (SEQ ID NO: 1018)
2470
2502

T23657_T22 (SEQ ID NO: 1019)
2327
2359

T23657_T23 (SEQ ID NO: 1020)
1961
1993

T23657_T30 (SEQ ID NO: 1023)
922
954

T23657_T31 (SEQ ID NO: 1024)
762
794

T23657_T32 (SEQ ID NO: 1025)
720
752

T23657_T35 (SEQ ID NO: 1026)
3112
3144

T23657_T37 (SEQ ID NO: 1027)
547
579

Variant Protein Alignment to the Previously Known Protein:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P2 (SEQ ID NO:1064) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
6620.00
Escore:
0

Matching length:
675
Total length:
675

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P3 (SEQ ID NO:1065) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
6621.00
Escore:
0

Matching length:
677
Total length:
677

Matching Percent Similarity:
99.85
Matching Percent Identity:
99.70

Total Percent Similarity:
99.85
Total Percent Identity:
99.70

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P4 (SEQ ID NO:1066) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
6521.00
Escore:
0

Matching length:
677
Total length:
698

Matching Percent Similarity:
99.85
Matching Percent Identity:
99.70

Total Percent Similarity:
96.85
Total Percent Identity:
96.70

Gaps:
1

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P5 (SEQ ID NO:1067) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
5909.00
Escore:
0

Matching length:
604
Total length:
604

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P6 (SEQ ID NO:1068) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
5354.00
Escore:
0

Matching length:
547
Total length:
547

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P7 (SEQ ID NO:1069) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
5346.00
Escore:
0

Matching length:
546
Total length:
546

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P8 (SEQ ID NO:1070) × S21C_HUMAN (SEQ ID NO:1062) ..

Alignment segment 1/1:

Quality:
5346.00
Escore:
0

Matching length:
546
Total length:
546

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P10 (SEQ ID NO:1072) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
6968.00
Escore:
0

Matching length:
722
Total length:
743

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
97.17
Total Percent Identity:
97.17

Gaps:
1

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P11 (SEQ ID NO:1073) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
4156.00
Escore:
0

Matching length:
425
Total length:
425

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P12 (SEQ ID NO:1074) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
6620.00
Escore:
0

Matching length:
675
Total length:
675

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S2lC_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P16 (SEQ ID NO:1075) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
2296.00
Escore:
0

Matching length:
232
Total length:
232

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P17 (SEQ ID NO:1076) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
1947.00
Escore:
0

Matching length:
198
Total length:
198

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P21 (SEQ ID NO:1078) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
1169.00
Escore:
0

Matching length:
119
Total length:
119

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Sequence name: S21C_HUMAN (SEQ ID NO:1062)

Sequence documentation:

Alignment of: T23657_P23 (SEQ ID NO:1080) × S21C_HUMAN (SEQ ID NO:1062)

Alignment segment 1/1:

Quality:
5354.00
Escore:
0

Matching length:
547
Total length:
547

Matching Percent Similarity:
100.00
Matching Percent Identity:
100.00

Total Percent Similarity:
100.00
Total Percent Identity:
100.00

Gaps:
0

Alignment:

Expression of Solute Carrier Organic Anion Transporter Family, Member 4A1 (SLCO4A1) T23657 Transcripts, which are Detectable by Amplicon as Depicted in Sequence Name T23657 Seg17-18 (SEQ ID NO: 1357), in Normal and Cancerous Colon Tissues

Expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by or according to seg17-18, T23657 amplicon (SEQ ID NO: 1357) and T23657 Seg17-18F (SEQ ID NO: 1355) T23657 Seg17-18 R (SEQ ID NO: 1356) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon —PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 59 is a histogram showing over expression of the above-indicated solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts in cancerous colon samples relative to the normal samples. (Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained). The number and percentage of samples that exhibit at least 4 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 59, the expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 4 fold was found in 28 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 7.22E-04.

Threshold of 4 fold overexpression was found to differentiate between cancer and normal samples with P value of 7.43E-06 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T23657seg17-18F forward primer (SEQ ID NO: 1355); and T23657seg17-18R reverse primer (SEQ ID NO: 1356).

Forward primer (SEQ ID NO: 1355):

CTGCTGGGCATCCTCGTCT

Reverse primer (SEQ ID NO: 1356):

CGTACCCAGGTGCCATCTG

Amplicon (SEQ ID NO: 1357):

CTGGGCATCCTCGTCTTCTCACTGCACTGCCCCAGTGTGCCCATGGCGGG

CGTCACAGCCAGCTACGGCGGGAGGTGAGGGCCAGATGGCACCTGGGTAC

G

Expression of Solute Carrier Organic Anion Transporter Family, Member 4A1 (SLC04A1) T23657 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name T23657 Seg22 (SEQ ID NO: 1360) in Normal and Cancerous Colon Tissues

Expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by or according to seg22, T23657 amplicon (SEQ ID NO: 1360) and T23657 seg22F (SEQ ID NO: 1358) T23657 seg22 R (SEQ ID NO: 1359) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon —HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 60 is a histogram showing over expression of the above-indicated solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts in cancerous colon samples relative to the normal samples (values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained). The number and percentage of samples that exhibit at least 4 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 60, the expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 4 fold was found in 20 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 4 fold overexpression was found to differentiate between cancer and normal samples with P value of 9.50E-04 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T23657seg22F forward primer (SEQ ID NO: 1358); and T23657seg22R reverse primer (SEQ ID NO: 1359).

Forward primer (SEQ ID NO: 1358):

TGGCAAGTTTGTAGACCCGAA

Reverse primer (SEQ ID NO: 1359):

GGTAGGGTCCAGGCCAGAG

Amplicon (SEQ ID NO: 1360):

TGGCAAGTTTGTAGACCCGAAATGCAGGCTGCATGGGGACGAGCCCCATG

GCTGACCCTGTGCCTGCTGGGCGCCAGCATGGCTCTGGCCTGGACCCTAC

C

Expression of Solute Carrier Organic Anion Transporter Family, Member 4A1 (SLC04A1) T23657 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name T23657 Seg29-32 (SEQ ID NO: 1363) in Normal and Cancerous Colon Tissues

Expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by or according to seg29-32, T23657 amplicon (SEQ ID NO: 1363) and T23657 seg29-32F (SEQ ID NO: 1361) T23657 seg29-32 R (SEQ ID NO: 1362) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon —PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 61 is a histogram showing over expression of the above-indicated solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 61, the expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 23 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.97E-04 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T23657seg29-32F forward primer (SEQ ID NO: 1361); and T23657seg29-32R reverse primer (SEQ ID NO: 1362).

Forward primer (SEQ ID NO: 1361):

CCTTTGCCCTGGGAATCC

Reverse primer (SEQ ID NO: 1362):

GCCCTGCTGGCCACAC

Amplicon (SEQ ID NO: 1363):

CCTTTGCCCTGGGAATCCAGTGGATTGTAGTTAGAATACTAGGGGGCATC

CCGGGGCCCATCGCCTTCGGCTGGGTGATCGACAAGGCCTGTCTGCTGTG

GCAGGACCAGTGTGGCCAGCAGGGC

Expression of Solute Carrier Organic Anion Transporter Family, Member 4A1 (SLC04A1) T23657 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name T23657 Seg41 (SEQ ID NO: 1366) in Normal and Cancerous Colon Tissues

Expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by or according to seg41, T23657 amplicon (SEQ ID NO: 1366) and T23657 Seg41F (SEQ ID NO: 1364) T23657 Seg41 R (SEQ ID NO: 1365) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 62 is a histogram showing over expression of the above-indicated solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 4 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 62, the expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 4 fold was found in 6 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 4 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.89E-01 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T23657seg41F forward primer (SEQ ID NO: 1364); and T23657seg41R reverse primer (SEQ ID NO: 1365).

Forward primer (SEQ ID NO: 1364):

CCGTGATGGATGTGGAGTCTC

Reverse primer (SEQ ID NO: 1365):

GCATCGGAAGCAAATGCATT

Amplicon (SEQ ID NO: 1366):

CCGTGATGGATGTGGAGTCTCGGCTTTCTGACAACGTCTTCCAGAGCAGG

CTTTCTCTAGAGGGTGGACTGCCTGTGTTCTCCTGGGAGAGAATGCATTT

GCTTCCGATGC

Description for Cluster T51958

Cluster T51958 features 12 transcript(s) and 48 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

T51958_PEA_1_T4
1081

T51958_PEA_1_T5
1082

T51958_PEA_1_T6
1083

T51958_PEA_1_T8
1084

T51958_PEA_1_T12
1085

T51958_PEA_1_T16
1086

T51958_PEA_1_T33
1087

T51958_PEA_1_T35
1088

T51958_PEA_1_T37
1089

T51958_PEA_1_T39
1090

T51958_PEA_1_T40
1091

T51958_PEA_1_T41
1092

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

T51958_PEA_1_node_0
1093

T51958_PEA_1_node_7
1094

T51958_PEA_1_node_8
1095

T51958_PEA_1_node_9
1096

T51958_PEA_1_node_14
1097

T51958_PEA_1_node_16
1098

T51958_PEA_1_node_18
1099

T51958_PEA_1_node_21
1100

T51958_PEA_1_node_22
1101

T51958_PEA_1_node_24
1102

T51958_PEA_1_node_27
1103

T51958_PEA_1_node_29
1104

T51958_PEA_1_node_33
1105

T51958_PEA_1_node_40
1106

T51958_PEA_1_node_41
1107

T51958_PEA_1_node_46
1108

T51958_PEA_1_node_51
1109

T51958_PEA_1_node_55
1110

T51958_PEA_1_node_67
1111

T51958_PEA_1_node_70
1112

T51958_PEA_1_node_74
1113

T51958_PEA_1_node_78
1114

T51958_PEA_1_node_11
1115

T51958_PEA_1_node_15
1116

T51958_PEA_1_node_20
1117

T51958_PEA_1_node_26
1118

T51958_PEA_1_node_35
1119

T51958_PEA_1_node_36
1120

T51958_PEA_1_node_38
1121

T51958_PEA_1_node_39
1122

T51958_PEA_1_node_42
1123

T51958_PEA_1_node_43
1124

T51958_PEA_1_node_44
1125

T51958_PEA_1_node_45
1126

T51958_PEA_1_node_47
1127

T51958_PEA_1_node_48
1128

T51958_PEA_1_node_49
1129

T51958_PEA_1_node_50
1130

T51958_PEA_1_node_54
1131

T51958_PEA_1_node_61
1132

T51958_PEA_1_node_71
1133

T51958_PEA_1_node_72
1134

T51958_PEA_1_node_75
1135

T51958_PEA_1_node_76
1136

T51958_PEA_1_node_77
1137

T51958_PEA_1_node_80
1138

T51958_PEA_1_node_82
1139

T51958_PEA_1_node_84
1140

TABLE 3

Proteins of interest

SEQ

ID

Protein Name
NO:
Corresponding Transcript(s)

T51958_PEA_1_P5
1151
T51958_PEA_1_T4 (SEQ ID NO:

1081); T51958_PEA_1_T12 (SEQ

ID NO: 1085); T51958_PEA_1_T16

(SEQ ID NO: 1086);

T51958_PEA_1_T33 (SEQ ID NO:

1087); T51958_PEA_1_T35 (SEQ

ID NO: 1088)

T51958_PEA_1_P6
1152
T51958_PEA_1_T5 (SEQ ID NO: 1082)

T51958_PEA_1_P28
1153
T51958_PEA_1_T37 (SEQ ID NO:

1089); T51958_PEA_1_T39 (SEQ

ID NO: 1090)

T51958_PEA_1_P30
1154
T51958_PEA_1_T40 (SEQ ID NO:

1091)

T51958_PEA_1_P34
1155
T51958_PEA_1_T8 (SEQ ID NO: 1084)

T51958_PEA_1_P35
1156
T51958_PEA_1_T6 (SEQ ID NO:

1083); T51958_PEA_1_T41 (SEQ

ID NO: 1092)

These sequences are variants of the known protein Tyrosine-protein kinase-like 7 precursor (SwissProt accession identifier PTK7_HUMAN; known also according to the synonyms Colon carcinoma kinase-4; CCK4), SEQ ID NO:1141, referred to herein as the previously known protein.

Protein Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141) is known or believed to have the following function(s): MAY FUNCTION AS A CELL ADHESION MOLECULE. LACKS PROBABLY THE CATALYTIC ACTIVITY OF TYROSINE KINASE. MAY BE CONNECTED TO THE PATHOPHYSIOLOGY OF COLON CARCINOMAS AND/OR MAY REPRESENT A TUMOR PROGRESSION MARKER. The sequence for protein Tyrosine-protein kinase-like 7 precursor is given at the end of the application, as “Tyrosine-protein kinase-like 7 precursor amino acid sequence”. Known polymorphisms for this sequence are as shown in Table 4.

TABLE 4

Amino acid mutations for Known Protein

SNP position(s) on amino

acid sequence
Comment

92
P -> R

147
K -> T

207
S -> G

495-496
VL -> RV

515
G -> E

881
E -> G

969
A -> P

992
S -> F

Protein Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141) localization is believed to be Type I membrane protein.

The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein amino acid phosphorylation; cell adhesion; signal transduction, which are annotation(s) related to Biological Process; protein tyrosine kinase; transmembrane receptor protein tyrosine kinase; receptor; protein binding; ATP binding; transferase, which are annotation(s) related to Molecular Function; and integral plasma membrane protein, which are annotation(s) related to Cellular Component.

Cluster T51958 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 63 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues.

TABLE 5

Normal tissue distribution

Name of Tissue
Number

bladder
41

bone
97

brain
12

colon
0

epithelial
40

general
24

head and neck
101

kidney
67

liver
0

lung
23

lymph nodes
18

breast
13

muscle
7

ovary
72

pancreas
0

prostate
8

skin
134

stomach
36

uterus
72

TABLE 6

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

bladder
5.4e−01
6.3e−01
6.0e−01
1.3
7.6e−01
1.0

bone
6.6e−01
5.5e−01
8.7e−01
0.6
8.1e−01
0.7

brain
3.1e−02
1.1e−02
2.8e−02
3.8
1.7e−02
3.4

colon
3.0e−02
2.5e−02
2.4e−01
3.1
1.6e−01
3.0

epithelial
6.2e−03
2.0e−02
1.8e−02
1.5
1.9e−01
1.1

general
7.2e−07
2.3e−06
4.4e−07
2.3
1.5e−05
1.9

head and neck
3.4e−01
3.3e−01
7.1e−01
1.3
8.4e−01
0.9

kidney
7.3e−01
5.8e−01
9.7e−01
0.4
9.3e−01
0.6

liver
1
6.8e−01
1
1.0
6.9e−01
1.4

lung
5.9e−01
8.4e−01
5.4e−01
1.5
8.4e−01
0.8

lymph nodes
5.1e−01
6.0e−01
1
1.3
1
0.8

breast
4.0e−01
3.0e−01
1.5e−01
2.5
3.1e−01
1.8

muscle
9.2e−01
4.8e−01
1
0.7
9.1e−03
2.9

ovary
3.7e−01
2.5e−01
7.1e−01
1.0
4.4e−01
1.2

pancreas
1.2e−01
2.1e−01
7.6e−02
5.1
1.5e−01
3.7

prostate
6.5e−01
5.4e−01
1.4e−01
2.5
1.0e−01
2.7

skin
7.7e−01
8.1e−01
1
0.1
1
0.2

stomach
5.8e−01
7.5e−01
1
0.5
9.6e−01
0.6

uterus
2.2e−01
5.6e−01
4.2e−02
1.8
3.7e−01
1.0

As noted above, cluster T51958 features 12 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141). A description of each variant protein according to the present invention is now provided.

Variant protein T51958_PEA_—1_P5 (SEQ ID NO:1151) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T51958_PEA_—1_T4 (SEQ ID NO:1081). An alignment is given to the known protein (Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T51958_PEA_—1_P5 (SEQ ID NO:1151) and PTK7_HUMAN_V4 (SEQ ID NO:1143):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P5 (SEQ ID NO:1151), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVPSWLKKPQDSQLEE GKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLRINSVEVYDGTWYRCMSSTPAGSIEAQAR VQVLEKLKFTPPPQPQQCMEFDKEATVPCSATGREKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDA GNYTCIASNGPQGQIRAHVQLTVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTK LGPRMHIFQNGSLVIHDVAPEDSGRYTCIAGNSCNIKHTEAPLYVV corresponding to amino acids 1-682 of PTK7_HUMAN_V4 (SEQ ID NO:1143), which also corresponds to amino acids 1-682 of T51958_PEA_—1_P5 (SEQ ID NO:1151), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS (SEQ ID NO:1451) corresponding to amino acids 683-733 of T51958_PEA_—1_P5 (SEQ ID NO:1151), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T51958_PEA_—1_P5 (SEQ ID NO:1151), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS (SEQ ID NO:1451) in T51958_PEA_—1_P5 (SEQ ID NO:1151).

It should be noted that the known protein sequence (PTK7_HUMAN (SEQ ID NO:1141)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for PTK7_HUMAN_V4 (SEQ ID NO:1143). These changes were previously known to occur and are listed in the table below.

TABLE 7

Changes to PTK7_HUMAN_V4 (SEQ ID NO: 1143)

SNP position(s) on amino

acid sequence
Type of change

93
conflict

148
conflict

208
conflict

496
conflict

516
conflict

Variant protein T51958_PEA_—1_P5 (SEQ ID NO:1151) is encoded by the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T51958_PEA_—1_T4 (SEQ ID NO:1081) is shown in bold; this coding portion starts at position 209 and ends at position 2407. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T51958_PEA_—1_P5 (SEQ ID NO:1151) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

2059
G -> A
No

3778
T -> A
No

3799
C ->
No

4638
C ->
No

4771
T -> C
No

4979
G -> C
No

Variant protein T51958_PEA_—1_P6 (SEQ ID NO:1152) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T51958_PEA_—1_T5 (SEQ ID NO:1082). An alignment is given to the known protein (Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T51958_PEA_—1_P6 (SEQ ID NO:1152) and PTK7_HUMAN_V4 (SEQ ID NO:1143):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P6 (SEQ ID NO:1152), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVPSWLKKPQDSQLEE GKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLRINSVEVYDGTWYRCMSSTPAGSIEAQAR VQVLEKLKFTPPPQPQQCMEFDKEATVPCSATGREKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDA GNYTCIASNGPQGQIRAHVQLTVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTK LGPRM corresponding to amino acids 1-641 of PTK7_HUMAN_V4 (SEQ ID NO:1143), which also corresponds to amino acids 1-641 of T51958_PEA_—1_P6 (SEQ ID NO:1152), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence APW corresponding to amino acids 642-644 of T51958_PEA_—1_P6 (SEQ ID NO:1152), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

TABLE 9

Changes to PTK7_HUMAN_V4 (SEQ ID NO: 1143)

SNP position(s) on amino

acid sequence
Type of change

93
conflict

148
conflict

208
conflict

496
conflict

516
conflict

Variant protein T51958_PEA_—1_P6 (SEQ ID NO:1152) is encoded by the following transcript(s): T51958_PEA_—1_T5 (SEQ ID NO:1082), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T51958_PEA_—1_T5 (SEQ ID NO:1082) is shown in bold; this coding portion starts at position 209 and ends at position 2140. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T51958_PEA_—1_P6 (SEQ ID NO:1152) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

2059
G -> A
No

3762
T -> A
No

3783
C ->
No

4622
C ->
No

4755
T -> C
No

4963
G -> C
No

Variant protein T51958_PEA_—1_P28 (SEQ ID NO:1153) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T51958_PEA_—1_T37 (SEQ ID NO:1089). An alignment is given to the known protein (Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T51958_PEA_—1_P28 (SEQ ID NO:1153) and PTK7_HUMAN_V11 (SEQ ID NO:1144):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of PTK7_HUMAN_V11 (SEQ ID NO:1144), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in T51958_PEA_—1_P28 (SEQ ID NO:1153).

It should be noted that the known protein sequence (PTK7_HUMAN (SEQ ID NO:1141)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for PTK7_HUMAN_V11 (SEQ ID NO:1144). These changes were previously known to occur and are listed in the table below.

TABLE 11

Changes to PTK7_HUMAN_V11 (SEQ ID NO: 1144)

SNP position(s) on amino

acid sequence
Type of change

93
conflict

148
conflict

208
conflict

Comparison Report Between T51958_PEA_—1_P28 (SEQ ID NO:1153) and Q8NFA5 (SEQ ID NO:1147):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA5 (SEQ ID NO:1147), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between T51958_PEA_—1_P28 (SEQ ID NO:1153) and Q8NFA6 (SEQ ID NO:1149):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA6 (SEQ ID NO:1149), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between T51958_PEA_—1_P28 (SEQ ID NO:1153) and Q8NFA7 (SEQ ID NO:1148):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA7 (SEQ ID NO:1148), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between T51958_PEA_—1_P28 (SEQ ID NO:1153) and Q8NFA8 (SEQ ID NO:1146):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of Q8NFA8 (SEQ ID NO:1146), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Comparison Report Between T51958_PEA_—1_P28 (SEQ ID NO:1153) and AAN04862 (SEQ ID NO:1150) (SEQ ID NO:1150):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P28 (SEQ ID NO:1153), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIADESFARVVLAPQDVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFAN GSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVWW EHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1-409 of AAN04862 (SEQ ID NO:1150), which also corresponds to amino acids 1-409 of T51958_PEA_—1_P28 (SEQ ID NO:1153), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410-459 of T51958_PEA_—1_P28 (SEQ ID NO:1153), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

Variant protein T51958_PEA_—1_P28 (SEQ ID NO:1153) is encoded by the following transcript(s): T51958_PEA_—1_T37 (SEQ ID NO:1089), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T51958_PEA_—1_T37 (SEQ ID NO:1089) is shown in bold; this coding portion starts at position 209 and ends at position 1585.

Variant protein T51958_PEA_—1_P30 (SEQ ID NO:1154) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T51958_PEA_—1_T40 (SEQ ID NO:1091). An alignment is given to the known protein (Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T51958_PEA_—1_P30 (SEQ ID NO:1154) and PTK7_HUMAN_V13 (SEQ ID NO:1145) (SEQ ID NO:1145):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P30 (SEQ ID NO:1154), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIK corresponding to amino acids 1-122 of PTK7_HUMAN_V13 (SEQ ID NO:1145), which also corresponds to amino acids 1-122 of T51958_PEA_—1_P30 (SEQ ID NO:1154), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CESQGGCAQSPCQTLND (SEQ ID NO:1453) corresponding to amino acids 123-139 of T51958_PEA_—1_P30 (SEQ ID NO:1154), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T51958_PEA_—1_P30 (SEQ ID NO:1154), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CESQGGCAQSPCQTLND (SEQ ID NO:1453) in T51958_PEA_—1_P30 (SEQ ID NO:1154).

It should be noted that the known protein sequence (PTK7_HUMAN (SEQ ID NO:1141)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for PTK7_HUMAN_V13 (SEQ ID NO:1145). These changes were previously known to occur and are listed in the table below.

TABLE 12

Changes to PTK7_HUMAN_V13 (SEQ ID NO: 1145)

SNP position(s) on amino

acid sequence
Type of change

93
conflict

Variant protein T51958_PEA_—1_P30 (SEQ ID NO:1154) is encoded by the following transcript(s): T51958_PEA_—1_T40 (SEQ ID NO:1091), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T51958_PEA_—1_T40 (SEQ ID NO:1091) is shown in bold; this coding portion starts at position 209 and ends at position 625.

Variant protein T51958_PEA_—1_P34 (SEQ ID NO:1155) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T51958_PEA_—1_T8 (SEQ ID NO:1084). An alignment is given to the known protein (Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T51958_PEA_—1_P34 (SEQ ID NO:1155) and PTK7_HUMAN_V3 (SEQ ID NO:1142):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P34 (SEQ ID NO:1155), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPR corresponding to amino acids 1-157 of PTK7_HUMAN_V3 (SEQ ID NO:1142), which also corresponds to amino acids 1-157 of T51958_PEA_—1_P34 (SEQ ID NO:1155).

It should be noted that the known protein sequence (PTK7_HUMAN (SEQ ID NO:1141)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for PTK7_HUMAN_V3 (SEQ ID NO:1142). These changes were previously known to occur and are listed in the table below.

TABLE 13

Changes to PTK7_HUMAN_V3 (SEQ ID NO: 1142)

SNP position(s) on amino

acid sequence
Type of change

93
conflict

148
conflict

Variant protein T51958_PEA_—1_P34 (SEQ ID NO:1155) is encoded by the following transcript(s): T51958_PEA_—1_T8 (SEQ ID NO:1084), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T51958_PEA_—1_T8 (SEQ ID NO:1084) is shown in bold; this coding portion starts at position 209 and ends at position 679. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T51958_PEA_—1_P34 (SEQ ID NO:1155) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

1868
G -> A
No

2465
T -> A
No

2486
C ->
No

3325
C ->
No

3458
T -> C
No

3666
G -> C
No

Variant protein T51958_PEA_—1_P35 (SEQ ID NO:1156) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T51958_PEA_—1_T6 (SEQ ID NO:1083). An alignment is given to the known protein (Tyrosine-protein kinase-like 7 precursor (SEQ ID NO:1141)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between T51958_PEA_—1_P35 (SEQ ID NO:1156) and PTK7_HUMAN_V11 (SEQ ID NO:1144):

1. An isolated chimeric polypeptide encoding for T51958_PEA_—1_P35 (SEQ ID NO:1156), comprising a first amino acid sequence being at least 90% homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGPVHVYWLLDGAP VQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANASFNIKWIEAGPVVLKHPASEAEIQP QTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSS QNFTLSIA corresponding to amino acids 1-220 of PTK7_HUMAN_V11 (SEQ ID NO:1144), which also corresponds to amino acids 1-220 of T51958_PEA_—1_P35 (SEQ ID NO:1156), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEPGVGAEGMR (SEQ ID NO:1454) corresponding to amino acids 221-231 of T51958_PEA_—1_P35 (SEQ ID NO:1156), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of T51958_PEA_—1_P35 (SEQ ID NO:1156), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEPGVGAEGMR (SEQ ID NO:1454) in T51958_PEA_—1_P35 (SEQ ID NO:1156).

It should be noted that the known protein sequence (PTK7_HUMAN (SEQ ID NO:1141)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for PTK7_HUMAN_V11 (SEQ ID NO:1144). These changes were previously known to occur and are listed in the table below.

TABLE 15

Changes to PTK7_HUMAN_V11 (SEQ ID NO: 1144)

SNP position(s) on amino

acid sequence
Type of change

93
conflict

148
conflict

208
conflict

Variant protein T51958_PEA_—1_P35 (SEQ ID NO:1156) is encoded by the following transcript(s): T51958_PEA_—1_T6 (SEQ ID NO:1083), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T51958_PEA_—1_T6 (SEQ ID NO:1083) is shown in bold; this coding portion starts at position 209 and ends at position 901. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T51958_PEA_—1_P35 (SEQ ID NO:1156) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 16

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

2149
G -> A
No

2751
T -> A
No

2772
C ->
No

3611
C ->
No

3744
T -> C
No

3952
G -> C
No

As noted above, cluster T51958 features 48 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster T51958_PEA_—1_node_—0 (SEQ ID NO:1093) according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090), T51958_PEA_—1_T40 (SEQ ID NO:1091) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1
287

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1
287

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1
287

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1
287

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1
287

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1
287

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1
287

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1
287

T51958_PEA_1_T37 (SEQ ID NO: 1089)
1
287

T51958_PEA_1_T39 (SEQ ID NO: 1090)
1
287

T51958_PEA_1_T40 (SEQ ID NO: 1091)
1
287

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1
287

Segment cluster T51958_PEA_—1_node_—7 (SEQ ID NO:1094) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090), T51958_PEA_—1_T40 (SEQ ID NO:1091) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
288
451

T51958_PEA_1_T5 (SEQ ID NO: 1082)
288
451

T51958_PEA_1_T6 (SEQ ID NO: 1083)
288
451

T51958_PEA_1_T8 (SEQ ID NO: 1084)
288
451

T51958_PEA_1_T12 (SEQ ID NO: 1085)
288
451

T51958_PEA_1_T16 (SEQ ID NO: 1086)
288
451

T51958_PEA_1_T33 (SEQ ID NO: 1087)
288
451

T51958_PEA_1_T35 (SEQ ID NO: 1088)
288
451

T51958_PEA_1_T37 (SEQ ID NO: 1089)
288
451

T51958_PEA_1_T39 (SEQ ID NO: 1090)
288
451

T51958_PEA_1_T40 (SEQ ID NO: 1091)
288
451

T51958_PEA_1_T41 (SEQ ID NO: 1092)
288
451

Segment cluster T51958_PEA_—1_node_—8 (SEQ ID NO:1095) according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090), T51958_PEA_—1_T40 (SEQ ID NO:1091) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
452
575

T51958_PEA_1_T5 (SEQ ID NO: 1082)
452
575

T51958_PEA_1_T6 (SEQ ID NO: 1083)
452
575

T51958_PEA_1_T8 (SEQ ID NO: 1084)
452
575

T51958_PEA_1_T12 (SEQ ID NO: 1085)
452
575

T51958_PEA_1_T16 (SEQ ID NO: 1086)
452
575

T51958_PEA_1_T33 (SEQ ID NO: 1087)
452
575

T51958_PEA_1_T35 (SEQ ID NO: 1088)
452
575

T51958_PEA_1_T37 (SEQ ID NO: 1089)
452
575

T51958_PEA_1_T39 (SEQ ID NO: 1090)
452
575

T51958_PEA_1_T40 (SEQ ID NO: 1091)
452
575

T51958_PEA_1_T41 (SEQ ID NO: 1092)
452
575

Segment cluster T51958_PEA_—1_node_—9 (SEQ ID NO:1096) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T40 (SEQ ID NO:1091). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T40 (SEQ ID NO: 1091)
576
972

Segment cluster T51958_PEA_—1_node_—14 (SEQ ID NO:1097) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
679
869

T51958_PEA_1_T5 (SEQ ID NO: 1082)
679
869

T51958_PEA_1_T6 (SEQ ID NO: 1083)
679
869

T51958_PEA_1_T12 (SEQ ID NO: 1085)
679
869

T51958_PEA_1_T16 (SEQ ID NO: 1086)
679
869

T51958_PEA_1_T33 (SEQ ID NO: 1087)
679
869

T51958_PEA_1_T35 (SEQ ID NO: 1088)
679
869

T51958_PEA_1_T37 (SEQ ID NO: 1089)
679
869

T51958_PEA_1_T39 (SEQ ID NO: 1090)
679
869

T51958_PEA_1_T41 (SEQ ID NO: 1092)
679
869

Segment cluster T51958_PEA_—1_node_—16 (SEQ ID NO:1098) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
870
1020

T51958_PEA_1_T5 (SEQ ID NO: 1082)
870
1020

T51958_PEA_1_T6 (SEQ ID NO: 1083)
960
1110

T51958_PEA_1_T8 (SEQ ID NO: 1084)
679
829

T51958_PEA_1_T12 (SEQ ID NO: 1085)
870
1020

T51958_PEA_1_T16 (SEQ ID NO: 1086)
870
1020

T51958_PEA_1_T33 (SEQ ID NO: 1087)
870
1020

T51958_PEA_1_T35 (SEQ ID NO: 1088)
870
1020

T51958_PEA_1_T37 (SEQ ID NO: 1089)
870
1020

T51958_PEA_1_T39 (SEQ ID NO: 1090)
870
1020

T51958_PEA_1_T41 (SEQ ID NO: 1092)
960
1110

Segment cluster T51958_PEA_—1_node_—18 (SEQ ID NO:1099) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1021
1169

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1021
1169

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1111
1259

T51958_PEA_1_T8 (SEQ ID NO: 1084)
830
978

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1021
1169

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1021
1169

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1021
1169

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1021
1169

T51958_PEA_1_T37 (SEQ ID NO: 1089)
1021
1169

T51958_PEA_1_T39 (SEQ ID NO: 1090)
1021
1169

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1111
1259

Segment cluster T51958_PEA_—1_node_—21 (SEQ ID NO:1100) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1238
1436

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1238
1436

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1328
1526

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1047
1245

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1238
1436

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1238
1436

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1238
1436

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1238
1436

T51958_PEA_1_T37 (SEQ ID NO: 1089)
1238
1436

T51958_PEA_1_T39 (SEQ ID NO: 1090)
1238
1436

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1328
1526

Segment cluster T51958_PEA_—1_node_—22 (SEQ ID NO:1101) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T37 (SEQ ID NO:1089) and T51958_PEA_—1_T39 (SEQ ID NO:1090). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T37 (SEQ ID NO: 1089)
1437
2469

T51958_PEA_1_T39 (SEQ ID NO: 1090)
1437
2799

Segment cluster T51958_PEA_—1_node_—24 (SEQ ID NO:1102) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1437
1570

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1437
1570

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1527
1660

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1246
1379

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1437
1570

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1437
1570

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1437
1570

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1437
1570

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1527
1660

Segment cluster T51958_PEA_—1_node_—27 (SEQ ID NO:1103) according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1586
1706

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1586
1706

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1676
1796

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1395
1515

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1586
1706

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1586
1706

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1586
1706

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1586
1706

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1676
1796

Segment cluster T51958_PEA_—1_node_—29 (SEQ ID NO:1104) according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T35 (SEQ ID NO:1088). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1707
1826

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1707
1826

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1797
1916

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1516
1635

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1707
1826

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1707
1826

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1707
1826

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1707
1826

Segment cluster T51958_PEA_—1_node_—33 (SEQ ID NO:1105) according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1827
1976

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1827
1976

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1917
2066

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1636
1785

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1827
1976

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1827
1976

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1827
1976

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1827
1976

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1797
1946

Segment cluster T51958_PEA_—1_node_—40 (SEQ ID NO:1106) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T35 (SEQ ID NO:1088). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
2256
2733

T51958_PEA_1_T5 (SEQ ID NO: 1082)
2240
2717

T51958_PEA_1_T12 (SEQ ID NO: 1085)
2256
2733

T51958_PEA_1_T16 (SEQ ID NO: 1086)
2256
2733

T51958_PEA_1_T33 (SEQ ID NO: 1087)
2256
2733

T51958_PEA_1_T35 (SEQ ID NO: 1088)
2256
2733

Segment cluster T51958_PEA_—1_node_—41 (SEQ ID NO:1107) according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T33 (SEQ ID NO:1087). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
2734
3372

T51958_PEA_1_T5 (SEQ ID NO: 1082)
2718
3356

T51958_PEA_1_T12 (SEQ ID NO: 1085)
2734
3372

T51958_PEA_1_T16 (SEQ ID NO: 1086)
2734
3372

T51958_PEA_1_T33 (SEQ ID NO: 1087)
2734
3372

Segment cluster T51958_PEA_—1_node_—46 (SEQ ID NO:1108) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T33 (SEQ ID NO:1087). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

T51958_PEA_1_T12 (SEQ ID NO: 1085)
3577
4406

T51958_PEA_1_T16 (SEQ ID NO: 1086)
3577
4406

T51958_PEA_1_T33 (SEQ ID NO: 1087)
3577
4406

Segment cluster T51958_PEA_—1_node_—51 (SEQ ID NO:1109) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T33 (SEQ ID NO:1087). Table 33 below describes the starting and ending position of this segment on each transcript.

TABLE 33

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T33 (SEQ ID NO: 1087)
4563
4811

Segment cluster T51958_PEA_—1_node_—55 (SEQ ID NO:1110) according to the present invention is supported by 82 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 34 below describes the starting and ending position of this segment on each transcript.

TABLE 34

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3753
3965

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3737
3949

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2726
2938

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2440
2652

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4583
4795

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2606
2818

Segment cluster T51958_PEA_—1_node_—67 (SEQ ID NO:1111) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 35 below describes the starting and ending position of this segment on each transcript.

TABLE 35

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
4047
4198

T51958_PEA_1_T5 (SEQ ID NO: 1082)
4031
4182

T51958_PEA_1_T6 (SEQ ID NO: 1083)
3020
3171

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2734
2885

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4877
5028

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4644
4795

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2900
3051

Segment cluster T51958_PEA_—1_node_—70 (SEQ ID NO:1112) according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 36 below describes the starting and ending position of this segment on each transcript.

TABLE 36

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
4199
4320

T51958_PEA_1_T5 (SEQ ID NO: 1082)
4183
4304

T51958_PEA_1_T6 (SEQ ID NO: 1083)
3172
3293

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2886
3007

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5029
5150

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4796
4917

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3052
3173

Segment cluster T51958_PEA_—1_node_—74 (SEQ ID NO:1113) according to the present invention is supported by 191 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 37 below describes the starting and ending position of this segment on each transcript.

TABLE 37

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
4378
5077

T51958_PEA_1_T5 (SEQ ID NO: 1082)
4362
5061

T51958_PEA_1_T6 (SEQ ID NO: 1083)
3351
4050

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3065
3764

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5208
5907

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4975
5674

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3231
3930

Segment cluster T51958_PEA_—1_node_—78 (SEQ ID NO:1114) according to the present invention is supported by 115 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 38 below describes the starting and ending position of this segment on each transcript.

TABLE 38

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
5124
5376

T51958_PEA_1_T5 (SEQ ID NO: 1082)
5108
5360

T51958_PEA_1_T6 (SEQ ID NO: 1083)
4097
4349

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3811
4063

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5954
6206

T51958_PEA_1_T16 (SEQ ID NO: 1086)
5721
5973

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3977
4229

Segment cluster T51958_PEA_—1_node_—11 (SEQ ID NO:11115) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 39 below describes the starting and ending position of this segment on each transcript.

TABLE 39

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
576
678

T51958_PEA_1_T5 (SEQ ID NO: 1082)
576
678

T51958_PEA_1_T6 (SEQ ID NO: 1083)
576
678

T51958_PEA_1_T8 (SEQ ID NO: 1084)
576
678

T51958_PEA_1_T12 (SEQ ID NO: 1085)
576
678

T51958_PEA_1_T16 (SEQ ID NO: 1086)
576
678

T51958_PEA_1_T33 (SEQ ID NO: 1087)
576
678

T51958_PEA_1_T35 (SEQ ID NO: 1088)
576
678

T51958_PEA_1_T37 (SEQ ID NO: 1089)
576
678

T51958_PEA_1_T39 (SEQ ID NO: 1090)
576
678

T51958_PEA_1_T41 (SEQ ID NO: 1092)
576
678

Segment cluster T51958_PEA_—1_node_—15 (SEQ ID NO:1116) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T6 (SEQ ID NO:1083) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 40 below describes the starting and ending position of this segment on each transcript.

TABLE 40

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T6 (SEQ ID NO: 1083)
870
959

T51958_PEA_1_T41 (SEQ ID NO: 1092)
870
959

Segment cluster T51958_PEA_—1_node_—20 (SEQ ID NO:1117) according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088), T51958_PEA_—1_T37 (SEQ ID NO:1089), T51958_PEA_—1_T39 (SEQ ID NO:1090) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 41 below describes the starting and ending position of this segment on each transcript.

TABLE 41

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1170
1237

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1170
1237

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1260
1327

T51958_PEA_1_T8 (SEQ ID NO: 1084)
979
1046

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1170
1237

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1170
1237

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1170
1237

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1170
1237

T51958_PEA_1_T37 (SEQ ID NO: 1089)
1170
1237

T51958_PEA_1_T39 (SEQ ID NO: 1090)
1170
1237

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1260
1327

Segment cluster T51958_PEA_—1_node_—26 (SEQ ID NO:1118) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 42 below describes the starting and ending position of this segment on each transcript.

TABLE 42

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1571
1585

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1571
1585

T51958_PEA_1_T6 (SEQ ID NO: 1083)
1661
1675

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1380
1394

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1571
1585

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1571
1585

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1571
1585

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1571
1585

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1661
1675

Segment cluster T51958_PEA_—1_node_—35 (SEQ ID NO:1119) according to the present invention is supported by 41 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 43 below describes the starting and ending position of this segment on each transcript.

TABLE 43

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
1977
2087

T51958_PEA_1_T5 (SEQ ID NO: 1082)
1977
2087

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2067
2177

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1786
1896

T51958_PEA_1_T12 (SEQ ID NO: 1085)
1977
2087

T51958_PEA_1_T16 (SEQ ID NO: 1086)
1977
2087

T51958_PEA_1_T33 (SEQ ID NO: 1087)
1977
2087

T51958_PEA_1_T35 (SEQ ID NO: 1088)
1977
2087

T51958_PEA_1_T41 (SEQ ID NO: 1092)
1947
2057

Segment cluster T51958_PEA_—1_node_—36 (SEQ ID NO:1120) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
2088
2127

T51958_PEA_1_T5 (SEQ ID NO: 1082)
2088
2127

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2178
2217

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1897
1936

T51958_PEA_1_T12 (SEQ ID NO: 1085)
2088
2127

T51958_PEA_1_T16 (SEQ ID NO: 1086)
2088
2127

T51958_PEA_1_T33 (SEQ ID NO: 1087)
2088
2127

T51958_PEA_1_T35 (SEQ ID NO: 1088)
2088
2127

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2058
2097

Segment cluster T51958_PEA_—1_node_—38 (SEQ ID NO:1121) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
2128
2143

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2218
2233

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1937
1952

T51958_PEA_1_T12 (SEQ ID NO: 1085)
2128
2143

T51958_PEA_1_T16 (SEQ ID NO: 1086)
2128
2143

T51958_PEA_1_T33 (SEQ ID NO: 1087)
2128
2143

T51958_PEA_1_T35 (SEQ ID NO: 1088)
2128
2143

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2098
2113

Segment cluster T51958_PEA_—1_node_—39 (SEQ ID NO:1122) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087), T51958_PEA_—1_T35 (SEQ ID NO:1088) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
2144
2255

T51958_PEA_1_T5 (SEQ ID NO: 1082)
2128
2239

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2234
2345

T51958_PEA_1_T8 (SEQ ID NO: 1084)
1953
2064

T51958_PEA_1_T12 (SEQ ID NO: 1085)
2144
2255

T51958_PEA_1_T16 (SEQ ID NO: 1086)
2144
2255

T51958_PEA_1_T33 (SEQ ID NO: 1087)
2144
2255

T51958_PEA_1_T35 (SEQ ID NO: 1088)
2144
2255

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2114
2225

Segment cluster T51958_PEA_—1_node_—42 (SEQ ID NO:1123) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3373
3377

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3357
3361

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2346
2350

T51958_PEA_1_T12 (SEQ ID NO: 1085)
3373
3377

T51958_PEA_1_T16 (SEQ ID NO: 1086)
3373
3377

T51958_PEA_1_T33 (SEQ ID NO: 1087)
3373
3377

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2226
2230

Segment cluster T51958_PEA_—1_node_—43 (SEQ ID NO:1124) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3378
3496

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3362
3480

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2351
2469

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2065
2183

T51958_PEA_1_T12 (SEQ ID NO: 1085)
3378
3496

T51958_PEA_1_T16 (SEQ ID NO: 1086)
3378
3496

T51958_PEA_1_T33 (SEQ ID NO: 1087)
3378
3496

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2231
2349

Segment cluster T51958_PEA_—1_node_—44 (SEQ ID NO:1125) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3497
3560

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3481
3544

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2470
2533

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2184
2247

T51958_PEA_1_T12 (SEQ ID NO: 1085)
3497
3560

T51958_PEA_1_T16 (SEQ ID NO: 1086)
3497
3560

T51958_PEA_1_T33 (SEQ ID NO: 1087)
3497
3560

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2350
2413

Segment cluster T51958_PEA_—1_node_—45 (SEQ ID NO:1126) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3561
3576

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3545
3560

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2534
2549

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2248
2263

T51958_PEA_1_T12 (SEQ ID NO: 1085)
3561
3576

T51958_PEA_1_T16 (SEQ ID NO: 1086)
3561
3576

T51958_PEA_1_T33 (SEQ ID NO: 1087)
3561
3576

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2414
2429

Segment cluster T51958_PEA_—1_node_—47 (SEQ ID NO:1127) according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3577
3651

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3561
3635

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2550
2624

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2264
2338

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4407
4481

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4407
4481

T51958_PEA_1_T33 (SEQ ID NO: 1087)
4407
4481

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2430
2504

Segment cluster T51958_PEA_—1_node_—48 (SEQ ID NO:1128) according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3652
3681

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3636
3665

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2625
2654

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2339
2368

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4482
4511

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4482
4511

T51958_PEA_1_T33 (SEQ ID NO: 1087)
4482
4511

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2505
2534

Segment cluster T51958_PEA_—1_node_—49 (SEQ ID NO:1129) according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3682
3717

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3666
3701

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2655
2690

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2369
2404

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4512
4547

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4512
4547

T51958_PEA_1_T33 (SEQ ID NO: 1087)
4512
4547

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2535
2570

Segment cluster T51958_PEA_—1_node_—50 (SEQ ID NO:1130) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086), T51958_PEA_—1_T33 (SEQ ID NO:1087) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3718
3732

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3702
3716

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2691
2705

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2405
2419

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4548
4562

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4548
4562

T51958_PEA_1_T33 (SEQ ID NO: 1087)
4548
4562

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2571
2585

Segment cluster T51958_PEA_—1_node_—54 (SEQ ID NO:1131) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3733
3752

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3717
3736

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2706
2725

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2420
2439

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4563
4582

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2586
2605

Segment cluster T51958_PEA_—1_node_—61 (SEQ ID NO:1132) according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
3966
4046

T51958_PEA_1_T5 (SEQ ID NO: 1082)
3950
4030

T51958_PEA_1_T6 (SEQ ID NO: 1083)
2939
3019

T51958_PEA_1_T8 (SEQ ID NO: 1084)
2653
2733

T51958_PEA_1_T12 (SEQ ID NO: 1085)
4796
4876

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4563
4643

T51958_PEA_1_T41 (SEQ ID NO: 1092)
2819
2899

Segment cluster T51958_PEA_—1_node_—71 (SEQ ID NO:1133) according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
4321
4362

T51958_PEA_1_T5 (SEQ ID NO: 1082)
4305
4346

T51958_PEA_1_T6 (SEQ ID NO: 1083)
3294
3335

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3008
3049

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5151
5192

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4918
4959

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3174
3215

Segment cluster T51958_PEA_—1_node_—72 (SEQ ID NO:1134) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
4363
4377

T51958_PEA_1_T5 (SEQ ID NO: 1082)
4347
4361

T51958_PEA_1_T6 (SEQ ID NO: 1083)
3336
3350

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3050
3064

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5193
5207

T51958_PEA_1_T16 (SEQ ID NO: 1086)
4960
4974

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3216
3230

Segment cluster T51958_PEA_—1_node_—75 (SEQ ID NO:1135) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
5078
5084

T51958_PEA_1_T5 (SEQ ID NO: 1082)
5062
5068

T51958_PEA_1_T6 (SEQ ID NO: 1083)
4051
4057

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3765
3771

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5908
5914

T51958_PEA_1_T16 (SEQ ID NO: 1086)
5675
5681

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3931
3937

Segment cluster T51958_PEA_—1_node_—76 (SEQ ID NO:1136) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084), T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
5085
5107

T51958_PEA_1_T5 (SEQ ID NO: 1082)
5069
5091

T51958_PEA_1_T6 (SEQ ID NO: 1083)
4058
4080

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3772
3794

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5915
5937

T51958_PEA_1_T16 (SEQ ID NO: 1086)
5682
5704

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3938
3960

Segment cluster T51958_PEA_—1_node_—77 (SEQ ID NO:1137) according to the present invention can be found in the following transcript(s): T51958_PEA_—1_T4 (SEQ ID NO:1081), T51958_PEA_—1_T5 (SEQ ID NO:1082), T51958_PEA_—1_T6 (SEQ ID NO:1083), T51958_PEA_—1_T8 (SEQ ID NO:1084),

T51958_PEA_—1_T12 (SEQ ID NO:1085), T51958_PEA_—1_T16 (SEQ ID NO:1086) and T51958_PEA_—1_T41 (SEQ ID NO:1092). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T4 (SEQ ID NO: 1081)
5108
5123

T51958_PEA_1_T5 (SEQ ID NO: 1082)
5092
5107

T51958_PEA_1_T6 (SEQ ID NO: 1083)
4081
4096

T51958_PEA_1_T8 (SEQ ID NO: 1084)
3795
3810

T51958_PEA_1_T12 (SEQ ID NO: 1085)
5938
5953

T51958_PEA_1_T16 (SEQ ID NO: 1086)
5705
5720

T51958_PEA_1_T41 (SEQ ID NO: 1092)
3961
3976

Segment cluster T51958_PEA_—1_node_—80 (SEQ ID NO:1138) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T35 (SEQ ID NO:1088). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

T51958_PEA_1_T35 (SEQ ID NO: 1088)
2734
2788

Segment cluster T51958_PEA_—1_node_—82 (SEQ ID NO:1139) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T35 (SEQ ID NO:1088). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T51958_PEA_1_T35
2789
2877

(SEQ ID NO: 1088)

Segment cluster T51958_PEA_—1_node_—84 (SEQ ID NO:1140) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T51958_PEA_—1_T35 (SEQ ID NO:1088). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment
Segment

Transcript name
starting position
ending position

T51958_PEA_1_T35
2878
2946

(SEQ ID NO: 1088)

Variant Protein Alignment to the Previously Known Protein:

Expression of Homo sapiens PTK7 Protein Tyrosine Kinase 7 (PTK7) T51958 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name T51958Seg38 (SEQ ID NO: 1369) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts detectable by or according to seg38, T51958seg38 amplicon (SEQ ID NO: 1369) and T51958seg38F (SEQ ID NO: 1367) and T51958seg38R (SEQ ID NO: 1368) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 64 is a histogram showing over expression of the above-indicated Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts in cancerous colon samples relative to the normal samples. (Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.) The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 64, the expression of Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 23 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 4.58E-04.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T51958seg38F forward primer (SEQ ID NO: 1367); and T51958seg38R reverse primer (SEQ ID NO: 1368).

Forward primer (SEQ ID NO: 1367):

GCTTGCCCTTTCATGTGGA

Reverse primer (SEQ ID NO: 1368):

TCACGATGAGACCTGACACTCTG

Amplicon (SEQ ID NO: 1369):

GCTTGCCCTTTCATGTGGAGCACTGTGATTGGACCCAAGTTGGCAAGAGT

GGAAGACCAGGGGACAGAACAGAAATCCCCATGGTGGCCAGAGTGTCAGG

TCTCATCGTGA

Expression of Homo sapiens PTK7 Protein Tyrosine Kinase 7 (PTK7) T51958 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name T51958Seg7 (SEQ ID NO: 1372) in Normal and Cancerous Colon Tissues

Expression of Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts detectable by or according to seg7, T51958seg7 amplicon (SEQ ID NO: 1372) and T51958seg7F (SEQ ID NO: 1370) and T51958seg7R (SEQ ID NO: 1371) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 65 is a histogram showing over expression of the above-indicated Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts in cancerous colon samples relative to the normal samples. (Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.) The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 65 the expression of Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 19 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.53E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T51958seg7F forward primer (SEQ ID NO: 1370); and T51958seg7R reverse primer (SEQ ID NO: 1371).

Forward primer (SEQ ID NO: 1370):

GTGCCCAGTCCCCCTGTC

Reverse primer (SEQ ID NO: 1371):

CCTGGCCCGTTTAACTGGA

Amplicon (SEQ ID NO: 1372):

GTGCCCAGTCCCCCTGTCAGACCCTCAATGACTGAGGCCTGGGGGATCCC

TCCCTTACCTCAGCTTCTCCCATTTCCAGTTAAACGGGCCAGG

Description for Cluster Z17877

Cluster Z17877 features 9 transcript(s) and 17 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

Z17877_PEA_1_T0
1157

Z17877_PEA_1_T2
1158

Z17877_PEA_1_T3
1159

Z17877_PEA_1_T4
1160

Z17877_PEA_1_T6
1161

Z17877_PEA_1_T7
1162

Z17877_PEA_1_T8
1163

Z17877_PEA_1_T11
1164

Z17877_PEA_1_T12
1165

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

Z17877_PEA_1_node_0
1166

Z17877_PEA_1_node_3
1167

Z17877_PEA_1_node_8
1168

Z17877_PEA_1_node_9
1169

Z17877_PEA_1_node_10
1170

Z17877_PEA_1_node_11
1171

Z17877_PEA_1_node_13
1172

Z17877_PEA_1_node_15
1173

Z17877_PEA_1_node_16
1174

Z17877_PEA_1_node_18
1175

Z17877_PEA_1_node_1
1176

Z17877_PEA_1_node_2
1177

Z17877_PEA_1_node_4
1178

Z17877_PEA_1_node_5
1179

Z17877_PEA_1_node_6
1180

Z17877_PEA_1_node_14
1181

Z17877_PEA_1_node_17
1182

TABLE 3

Proteins of interest

SEQ

Protein Name
ID NO:
Corresponding Transcript(s)

Z17877_PEA_1_P1
1183
Z17877_PEA_1_T0 (SEQ ID NO:

1157); Z17877_PEA_1_T3 (SEQ ID

NO: 1159); Z17877_PEA_1_T7

(SEQ ID NO: 1162)

Z17877_PEA_1_P2
1184
Z17877_PEA_1_T6 (SEQ ID NO:

1161); Z17877_PEA_1_T11 (SEQ ID

NO: 1164)

Z17877_PEA_1_P3
1185
Z17877_PEA_1_T12 (SEQ ID NO:

1165)

Z17877_PEA_1_P6
1186
Z17877_PEA_1_T2 (SEQ ID NO:

1158); Z17877_PEA_1_T4 (SEQ ID

NO: 1160); Z17877_PEA_1_T8

(SEQ ID NO: 1163)

Cluster Z17877 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term “number” in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as “parts per million” (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

Overall, the following results were obtained as shown with regard to the histograms in FIG. 66 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors and malignant tumors involving the bone marrow.

TABLE 4

Normal tissue distribution

Name of Tissue
Number

adrenal
80

bladder
41

bone
64

brain
5

colon
63

epithelial
73

general
56

head and neck
0

kidney
31

liver
53

lung
44

lymph nodes
98

breast
149

bone marrow
0

muscle
40

ovary
80

pancreas
61

prostate
24

skin
107

stomach
36

Thyroid
0

uterus
186

TABLE 5

P values and ratios for expression in cancerous tissue

Name of Tissue
P1
P2
SP1
R3
SP2
R4

adrenal
5.2e−01
6.0e−01
6.2e−01
1.1
7.4e−01
0.9

bladder
5.4e−01
4.5e−01
2.8e−01
2.0
3.8e−01
1.7

bone
6.5e−02
3.1e−01
1.8e−01
2.3
5.6e−01
1.2

brain
2.5e−01
2.6e−01
1.5e−04
6.7
1.4e−05
6.9

colon
6.7e−02
1.0e−01
2.0e−01
1.9
4.0e−01
1.4

epithelial
3.4e−01
4.0e−01
4.1e−01
1.0
4.7e−01
0.9

general
3.2e−02
4.4e−02
2.8e−04
1.6
1.1e−03
1.4

head and neck
2.1e−01
3.3e−01
0.0e+00
0.0
0.0e+00
0.0

kidney
4.2e−01
5.2e−01
5.7e−02
2.6
1.5e−01
1.9

liver
8.2e−01
6.9e−01
1
0.5
5.1e−01
1.4

lung
3.4e−01
5.2e−01
2.9e−01
1.6
3.3e−01
1.2

lymph nodes
1.6e−01
2.9e−01
6.4e−01
1.1
7.0e−01
0.8

breast
7.2e−01
7.9e−01
8.6e−01
0.7
9.6e−01
0.5

bone marrow
4.3e−01
7.1e−02
1.5e−01
9.0
6.5e−03
7.5

muscle
6.0e−01
6.7e−01
2.6e−02
3.9
3.0e−01
1.3

ovary
5.8e−01
6.4e−01
6.1e−01
0.9
7.9e−01
0.7

pancreas
7.3e−01
7.3e−01
9.2e−01
0.5
8.7e−01
0.7

prostate
7.3e−01
7.6e−01
4.7e−01
1.4
1.0e−01
1.4

skin
5.7e−01
7.1e−01
1
0.1
9.7e−01
0.2

stomach
5.8e−01
5.9e−02
1
0.5
3.2e−01
1.8

Thyroid
2.9e−01
2.9e−01
4.4e−01
2.0
4.4e−01
2.0

uterus
6.9e−01
7.7e−01
1
0.3
9.7e−01
0.4

As noted above, cluster Z17877 features 9 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein Z17877_PEA_—1_P1 (SEQ ID NO:1183) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z17877_PEA_—1_T0 (SEQ ID NO:1157). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because of manual inspection of known protein localization and/or gene structure.

Variant protein Z17877_PEA_—1_P1 (SEQ ID NO:1183) is encoded by the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z17877_PEA_—1_T0 (SEQ ID NO:1157) is shown in bold; this coding portion starts at position 1206 and ends at position 2522. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P1 (SEQ ID NO:1183) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

457
G -> C
Yes

503
A -> C
Yes

628
C -> T
Yes

706
G -> A
Yes

771
T -> C
Yes

819
C -> T
Yes

930
C ->
No

1022
T ->
No

1065
C -> T
Yes

1237
A -> G
Yes

1376
C -> G
No

1379
C -> G
No

1440
C -> G
No

1653
G -> A
No

1683
G -> T
Yes

1713
G -> A
Yes

1898
G -> A
Yes

2123
G -> A
No

2170
C -> T
Yes

2297
C ->
No

2297
C -> T
No

2391
-> T
No

2431
-> G
No

2501
A -> C
No

2522
G -> C
Yes

2575
A -> G
Yes

2634
T -> C
Yes

2654
A -> G
Yes

2750
T -> G
No

2906
T -> A
No

2921
T -> G
No

2948
T -> G
No

Variant protein Z17877_PEA_—1_P2 (SEQ ID NO:1184) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T11 (SEQ ID NO:1164). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because of manual inspection of known protein localization and/or gene structure.

Variant protein Z17877_PEA_—1_P2 (SEQ ID NO:1184) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P2 (SEQ ID NO:1184) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

11
N -> S
Yes

79
P -> A
No

150
A -> T
No

160
G -> C
Yes

170
V -> I
Yes

273
I -> T
Yes

352
P -> L
Yes

Variant protein Z17877_PEA_—1_P2 (SEQ ID NO:1184) is encoded by the following transcript(s): Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T11 (SEQ ID NO:1164), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript Z17877_PEA_—1_T6 (SEQ ID NO:1161) is shown in bold; this coding portion starts at position 1206 and ends at position 2270. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P2 (SEQ ID NO:1184) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 8

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

457
G -> C
Yes

503
A -> C
Yes

628
C -> T
Yes

706
G -> A
Yes

771
T -> C
Yes

819
C -> T
Yes

930
C ->
No

1022
T ->
No

1065
C -> T
Yes

1237
A -> G
Yes

1376
C -> G
No

1379
C -> G
No

1440
C -> G
No

1653
G -> A
No

1683
G -> T
Yes

1713
G -> A
Yes

1898
G -> A
Yes

2023
T -> C
Yes

2260
C -> T
Yes

2453
G -> C
Yes

2482
G -> A
Yes

2553
T ->
Yes

2603
T ->
Yes

2612
T ->
Yes

2875
G -> A
Yes

2938
G -> A
Yes

3295
A -> G
Yes

3499
G -> A
No

3546
C -> T
Yes

3673
C ->
No

3673
C -> T
No

3767
-> T
No

3807
-> G
No

3877
A -> C
No

3898
G -> C
Yes

3951
A -> G
Yes

4010
T -> C
Yes

4030
A -> G
Yes

4126
T -> G
No

4282
T -> A
No

4297
T -> G
No

4324
T -> G
No

The coding portion of transcript Z17877_PEA_—1_T11 (SEQ ID NO:1164) is shown in bold; this coding portion starts at position 602 and ends at position 1666. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P2 (SEQ ID NO:1184) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

418
T ->
No

461
C -> T
Yes

633
A -> G
Yes

772
C -> G
No

775
C -> G
No

836
C -> G
No

1049
G -> A
No

1079
G -> T
Yes

1109
G -> A
Yes

1294
G -> A
Yes

1419
T -> C
Yes

1656
C -> T
Yes

1849
G -> C
Yes

1878
G -> A
Yes

1949
T ->
Yes

1999
T ->
Yes

2008
T ->
Yes

2271
G -> A
Yes

2334
G -> A
Yes

2691
A -> G
Yes

2868
G -> A
No

2915
C -> T
Yes

3042
C ->
No

3042
C -> T
No

3136
-> T
No

3176
-> G
No

3246
A -> C
No

3267
G -> C
Yes

3320
A -> G
Yes

3379
T -> C
Yes

3399
A -> G
Yes

3495
T -> G
No

3651
T -> A
No

3666
T -> G
No

3693
T -> G
No

Variant protein Z17877_PEA_—1_P3 (SEQ ID NO:1185) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z17877_PEA_—1_T12 (SEQ ID NO:1165). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because of manual inspection of known protein localization and/or gene structure.

Variant protein Z17877_PEA_—1_P3 (SEQ ID NO:1185) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P3 (SEQ ID NO:1185) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

11
N -> S
Yes

79
P -> A
No

150
A -> T
No

160
G -> C
Yes

170
V -> I
Yes

331
A -> V
Yes

373
R ->
No

441
E -> D
No

Variant protein Z17877_PEA_—1_P3 (SEQ ID NO:1185) is encoded by the following transcript(s): Z17877_PEA_—1_T12 (SEQ ID NO:1165), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z17877_PEA_—1_T12 (SEQ ID NO:1165) is shown in bold; this coding portion starts at position 602 and ends at position 1945. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P3 (SEQ ID NO:1185) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

418
T ->
No

461
C -> T
Yes

633
A -> G
Yes

772
C -> G
No

775
C -> G
No

836
C -> G
No

1049
G -> A
No

1079
G -> T
Yes

1109
G -> A
Yes

1294
G -> A
Yes

1546
G -> A
No

1593
C -> T
Yes

1720
C ->
No

1720
C -> T
No

1814
-> T
No

1854
-> G
No

1924
A -> C
No

1945
G -> C
Yes

1998
A -> G
Yes

2057
T -> C
Yes

2077
A -> G
Yes

2173
T -> G
No

2329
T -> A
No

2344
T -> G
No

2371
T -> G
No

Variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T4 (SEQ ID NO:1160) and Z17877_PEA_—1_T8 (SEQ ID NO:1163). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: unknown.

Variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Amino acid mutations

SNP position(s) on
Alternative
Previously

amino acid sequence
amino acid(s)
known SNP?

57
A -> G
Yes

79
G -> C
Yes

Variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) is encoded by the following transcript(s): Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T4 (SEQ ID NO:1160) and Z17877_PEA_—1_T8 (SEQ ID NO:1163), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript Z17877_PEA_—1_T2 (SEQ ID NO:1158) is shown in bold; this coding portion starts at position 40 and ends at position 381. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 13

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

457
G -> C
Yes

503
A -> C
Yes

628
C -> T
Yes

706
G -> A
Yes

771
T -> C
Yes

819
C -> T
Yes

930
C ->
No

1022
T ->
No

1065
C -> T
Yes

1344
G -> T
Yes

1361
C -> G
Yes

1413
G -> A
Yes

1418
G -> A
Yes

1790
C -> T
Yes

2059
G -> A
Yes

2244
G -> A
Yes

2451
T -> G
No

2460
T -> A
Yes

2500
G ->
No

2533
C -> T
Yes

2581
C -> T
Yes

2734
C -> G
Yes

2861
A -> G
Yes

3000
C -> G
No

3003
C -> G
No

3064
C -> G
No

3277
G -> A
No

3307
G -> T
Yes

3337
G -> A
Yes

3522
G -> A
Yes

3747
G -> A
No

3794
C -> T
Yes

3921
C ->
No

3921
C -> T
No

4015
-> T
No

4055
-> G
No

4125
A -> C
No

4146
G -> C
Yes

4199
A -> G
Yes

4258
T -> C
Yes

4278
A -> G
Yes

4374
T -> G
No

4530
T -> A
No

4545
T -> G
No

4572
T -> G
No

The coding portion of transcript Z17877_PEA_—1_T4 (SEQ ID NO:1160) is shown in bold; this coding portion starts at position 40 and ends at position 381. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

457
G -> C
Yes

503
A -> C
Yes

628
C -> T
Yes

706
G -> A
Yes

844
C ->
No

936
T ->
No

979
C -> T
Yes

1258
G -> T
Yes

1275
C -> G
Yes

1327
G -> A
Yes

1332
G -> A
Yes

1704
C -> T
Yes

1973
G -> A
Yes

2158
G -> A
Yes

2365
T -> G
No

2374
T -> A
Yes

2414
G ->
No

2447
C -> T
Yes

2495
C -> T
Yes

2648
C -> G
Yes

2775
A -> G
Yes

2914
C -> G
No

2917
C -> G
No

2978
C -> G
No

3191
G -> A
No

3221
G -> T
Yes

3251
G -> A
Yes

3436
G -> A
Yes

3661
G -> A
No

3708
C -> T
Yes

3835
C ->
No

3835
C -> T
No

3929
-> T
No

3969
-> G
No

4039
A -> C
No

4060
G -> C
Yes

4113
A -> G
Yes

4172
T -> C
Yes

4192
A -> G
Yes

4288
T -> G
No

4444
T -> A
No

4459
T -> G
No

4486
T -> G
No

The coding portion of transcript Z17877_PEA_—1_T8 (SEQ ID NO:1163) is shown in bold; this coding portion starts at position 40 and ends at position 381. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z17877_PEA_—1_P6 (SEQ ID NO:1186) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

84
C -> T
Yes

209
C -> G
Yes

274
G -> T
Yes

457
G -> C
Yes

503
A -> C
Yes

628
C -> T
Yes

706
G -> A
Yes

771
T -> C
Yes

819
C -> T
Yes

930
C ->
No

1022
T ->
No

1065
C -> T
Yes

1237
A -> G
Yes

1376
C -> G
No

1379
C -> G
No

1440
C -> G
No

1653
G -> A
No

1683
G -> T
Yes

1713
G -> A
Yes

1898
G -> A
Yes

2150
G -> A
No

2197
C -> T
Yes

2324
C ->
No

2324
C -> T
No

2418
-> T
No

2458
-> G
No

2528
A -> C
No

2549
G -> C
Yes

2602
A -> G
Yes

2661
T -> C
Yes

2681
A -> G
Yes

2777
T -> G
No

2933
T -> A
No

2948
T -> G
No

2975
T -> G
No

As noted above, cluster Z17877 features 17 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster Z17877_PEA_—1_node_—0 (SEQ ID NO:1166) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 16 below describes the starting and ending position of this segment on each transcript.

TABLE 16

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
1
330

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
1
330

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
1
330

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
1
330

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
1
330

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
1
330

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1
330

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
1
330

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
1
330

Segment cluster Z17877_PEA_—1_node_—3 (SEQ ID NO:1167) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T8 (SEQ ID NO:1163). Table 17 below describes the starting and ending position of this segment on each transcript.

TABLE 17

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
404
755

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
404
755

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
404
755

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
404
755

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
404
755

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
404
755

Segment cluster Z17877_PEA_—1_node_—8 (SEQ ID NO:1168) according to the present invention is supported by 100 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T8 (SEQ ID NO:1163). Table 18 below describes the starting and ending position of this segment on each transcript.

TABLE 18

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
862
1007

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
862
1007

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
862
1007

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
776
921

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
862
1007

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
862
1007

Segment cluster Z17877_PEA_—1_node_—9 (SEQ ID NO:1169) according to the present invention is supported by 110 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 19 below describes the starting and ending position of this segment on each transcript.

TABLE 19

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
1008
1190

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
1008
1190

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
1008
1190

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
922
1104

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
1008
1190

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
404
586

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1008
1190

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
404
586

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
404
586

Segment cluster Z17877_PEA_—1_node_—10 (SEQ ID NO:1170) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T2 (SEQ ID NO:1158) and Z17877_PEA_—1_T4 (SEQ ID NO:1160). Table 20 below describes the starting and ending position of this segment on each transcript.

TABLE 20

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
1191
1520

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
1105
1434

Segment cluster Z17877_PEA_—1_node_—11 (SEQ ID NO:1171) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T2 (SEQ ID NO:1158) and Z17877_PEA_—1_T4 (SEQ ID NO:1160). Table 21 below describes the starting and ending position of this segment on each transcript.

TABLE 21

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
1521
2814

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
1435
2728

Segment cluster Z17877_PEA_—1_node_—13 (SEQ ID NO:1172) according to the present invention is supported by 108 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 22 below describes the starting and ending position of this segment on each transcript.

TABLE 22

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
1191
1402

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
2815
3026

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
1191
1402

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
2729
2940

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
1191
1402

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
587
798

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1191
1402

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
587
798

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
587
798

Segment cluster Z17877_PEA_—1_node_—15 (SEQ ID NO:1173) according to the present invention is supported by 139 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 23 below describes the starting and ending position of this segment on each transcript.

TABLE 23

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
1481
1962

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
3105
3586

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
1481
1962

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
3019
3500

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
1481
1962

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
877
1358

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1481
1962

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
877
1358

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
877
1358

Segment cluster Z17877_PEA_—1_node_—16 (SEQ ID NO:1174) according to the present invention is supported by 21 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T11 (SEQ ID NO:1164). Table 24 below describes the starting and ending position of this segment on each transcript.

TABLE 24

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
1963
3311

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
1359
2707

Segment cluster Z17877_PEA_—1_node_—18 (SEQ ID NO:1175) according to the present invention is supported by 263 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 25 below describes the starting and ending position of this segment on each transcript.

TABLE 25

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
1963
3001

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
3587
4625

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
1963
2841

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
3501
4539

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
3339
4377

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
1359
2397

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1990
3028

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
2708
3746

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
1386
2424

Segment cluster Z17877_PEA_—1_node_—1 (SEQ ID NO:1176) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 26 below describes the starting and ending position of this segment on each transcript.

TABLE 26

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
331
378

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
331
378

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
331
378

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
331
378

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
331
378

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
331
378

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
331
378

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
331
378

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
331
378

Segment cluster Z17877_PEA_—1_node_—2 (SEQ ID NO:1177) according to the present invention can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 27 below describes the starting and ending position of this segment on each transcript.

TABLE 27

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
379
403

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
379
403

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
379
403

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
379
403

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
379
403

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
379
403

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
379
403

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
379
403

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
379
403

Segment cluster Z17877_PEA_—1_node_—4 (SEQ ID NO:1178) according to the present invention can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T8 (SEQ ID NO:1163). Table 28 below describes the starting and ending position of this segment on each transcript.

TABLE 28

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
756
763

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
756
763

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
756
763

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
756
763

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
756
763

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
756
763

Segment cluster Z17877_PEA_—1_node_—5 (SEQ ID NO:1179) according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T8 (SEQ ID NO:1163). Table 29 below describes the starting and ending position of this segment on each transcript.

TABLE 29

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
764
849

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
764
849

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
764
849

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
764
849

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
764
849

Segment cluster Z17877_PEA_—1_node_—6 (SEQ ID NO:1180) according to the present invention can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161) and Z17877_PEA_—1_T8 (SEQ ID NO:1163). Table 30 below describes the starting and ending position of this segment on each transcript.

TABLE 30

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
850
861

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
850
861

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
850
861

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
764
775

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
850
861

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
850
861

Segment cluster Z17877_PEA_—1_node_—14 (SEQ ID NO:1181) according to the present invention is supported by 83 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T0 (SEQ ID NO:1157), Z17877_PEA_—1_T2 (SEQ ID NO:1158), Z17877_PEA_—1_T3 (SEQ ID NO:1159), Z17877_PEA_—1_T4 (SEQ ID NO:1160), Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T7 (SEQ ID NO:1162), Z17877_PEA_—1_T8 (SEQ ID NO:1163), Z17877_PEA_—1_T11 (SEQ ID NO:1164) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 31 below describes the starting and ending position of this segment on each transcript.

TABLE 31

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z17877_PEA_1_T0 (SEQ ID NO: 1157)
1403
1480

Z17877_PEA_1_T2 (SEQ ID NO: 1158)
3027
3104

Z17877_PEA_1_T3 (SEQ ID NO: 1159)
1403
1480

Z17877_PEA_1_T4 (SEQ ID NO: 1160)
2941
3018

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
1403
1480

Z17877_PEA_1_T7 (SEQ ID NO: 1162)
799
876

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1403
1480

Z17877_PEA_1_T11 (SEQ ID NO: 1164)
799
876

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
799
876

Segment cluster Z17877_PEA_—1_node_—17 (SEQ ID NO:1182) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z17877_PEA_—1_T6 (SEQ ID NO:1161), Z17877_PEA_—1_T8 (SEQ ID NO:1163) and Z17877_PEA_—1_T12 (SEQ ID NO:1165). Table 32 below describes the starting and ending position of this segment on each transcript.

TABLE 32

Segment location on transcripts

Segment

starting
Segment

Transcript name
position
ending position

Z17877_PEA_1_T6 (SEQ ID NO: 1161)
3312
3338

Z17877_PEA_1_T8 (SEQ ID NO: 1163)
1963
1989

Z17877_PEA_1_T12 (SEQ ID NO: 1165)
1359
1385

Expression of c-myc-P64 mRNA, Initiating from Promoter P0 Z17877 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name Z17877Seg8 (SEQ ID NO: 1375) in Normal and Cancerous Colon Tissues

Expression of c-myc-P64 mRNA, initiating from promoter P0 transcripts detectable by or according to seg8, Z17877seg8 amplicon (SEQ ID NO: 1375) and Z17877seg8 F (SEQ ID NO: 1373) and Z17877seg8 R (SEQ ID NO: 1374) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 67 is a histogram showing over expression of the above-indicated c-myc-P64 mRNA, initiating from promoter P0 transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 67, the expression of c-myc-P64 mRNA, initiating from promoter P0 transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1, “Tissue samples in testing panel”). Notably an over-expression of at least 3 fold was found in 13 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of c-myc-P64 mRNA, initiating from promoter P0 transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 6.27E-05.

Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.85E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z17877seg8F forward primer (SEQ ID NO: 1373); and Z17877seg8R reverse primer (SEQ ID NO: 1374).

Forward primer (SEQ ID NO: 1373):

AGCAAGGACGCGACTCTCC

Reverse primer (SEQ ID NO: 1374):

AATCCAGCGTCTAAGCAGCTG

Amplicon (SEQ ID NO: 1375):

AGCAAGGACGCGACTCTCCCGACGCGGGGAGGCTATTCTGCCCATTTGGG

GACACTTCCCCGCCGCTGCCAGGACCCGCTTCTCTGAAAGGCTCTCCTTG

CAGCTGCTTAGACGCTGGATT

Combined expression of 19 sequences (T23657seg 29-32 (SEQ ID NO: 1363); T23657seg 22 (SEQ ID NO: 1360); T23657seg 41 (SEQ ID NO: 1366); T23657seg17-18 (SEQ ID NO: 1357); AA315457seg8 (SEQ ID NO:1383); R30650seg76 (SEQ ID NO: 1354); HUM-CEASeg33 (SEQ ID NO: 1345); CEA-Seg35 (SEQ ID NO: 1348); CEA-Seg31 (SEQ ID NO: 1342); AA58339seg1 (SEQ ID NO: 1327); AA583399seg17 (SEQ ID NO: 1324); AA583399-seg30-32 (SEQ ID NO: 1321); HUMCACH1A seg101 (SEQ ID NO: 1337); HSHCGIseg20 (SEQ ID NO: 1378); HSHCGIseg35 (SEQ ID NO: 1381); M78035seg 42 (SEQ ID NO: 1351); T51958seg7 (SEQ ID NO: 1372); T51958seg38 (SEQ ID NO: 1369); Z17877seg8 (SEQ ID NO: 1375)) in normal and cancerous colon tissues.

Expression of solute carrier organic anion transporter family, member 4A1 (SLC04A1), Carcinoembryonic antigen-related cell adhesion molecule 5 [Precursor], myeloma overexpressed gene (in a subset of t(11;14) positive multiple myelomas) (MYEOV), Voltage-dependent L-type calcium channel alpha-1D subunit Calcium channel, L type, alpha-1 polypeptide, isoform 2, TRIM31 tripartite motif, S-adenosylhomocysteine hydrolase (AHCY), Homo sapiens PTK7 protein tyrosine kinase 7 (PTK7) and c-myc-P64 mRNA, initiating from promoter PO transcripts detectable by or according to T23657seg 29-32 (SEQ ID NO: 1363); T23657seg 22 (SEQ ID NO: 1360); T23657seg 41 (SEQ ID NO: 1366); T23657seg17-18 (SEQ ID NO: 1357); AA315457seg8 SEQ ID NO: 1383; R30650seg76 (SEQ ID NO: 1354); HUM-CEASeg33 (SEQ ID NO: 1345); CEA-Seg35 (SEQ ID NO: 1348); CEA-Seg31 (SEQ ID NO: 1342); AA58339seg1 (SEQ ID NO: 1327); AA583399seg17 (SEQ ID NO: 1324); AA583399-seg30-32 (SEQ ID NO: 1321); HUMCACH1A seg101 (SEQ ID NO: 1337); HSHCGIseg20 (SEQ ID NO: 1378); HSHCGIseg35 (SEQ ID NO: 1381); M78035seg 42 (SEQ ID NO: 1351); T51958seg7 (SEQ ID NO: 1372); T51958seg38 (SEQ ID NO: 1369); Z17877seg8 (SEQ ID NO: 1375) amplicons was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicons was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample of each amplicon was then divided by the median of the quantities of the normal post-mortem (PM) samples detected for the same amplicon (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing panel”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 68 is a histogram showing over expression of the above-indicated transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 5 fold over-expression of at least one of the sequences, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 68, an over-expression of at least 5 fold in at least one of the sequences was found in 37 out of 37 adenocarcinoma samples.

Statistical analysis was applied to verify the significance of these results, as described below. Threshold of 5 fold overexpression of at least one of the amplicons was found to differentiate between cancer and normal samples with P value of 5.31E-10 as checked by exact fisher test.

The above values demonstrate statistical significance of the results.

The FIG. 68 shows combined results for the colon panel marker, as a non-limiting example of a combination of markers according to the present invention.

Description for Cluster HSHCGI

Cluster HSHCGI features 24 transcript(s) and 29 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

TABLE 1

Transcripts of interest

Transcript Name
SEQ ID NO:

HSHCGI_PEA_3_T0
1187

HSHCGI_PEA_3_T1
1188

HSHCGI_PEA_3_T2
1189

HSHCGI_PEA_3_T3
1190

HSHCGI_PEA_3_T4
1191

HSHCGI_PEA_3_T5
1192

HSHCGI_PEA_3_T6
1193

HSHCGI_PEA_3_T7
1194

HSHCGI_PEA_3_T8
1195

HSHCGI_PEA_3_T9
1196

HSHCGI_PEA_3_T10
1197

HSHCGI_PEA_3_T11
1198

HSHCGI_PEA_3_T12
1199

HSHCGI_PEA_3_T13
1200

HSHCGI_PEA_3_T14
1201

HSHCGI_PEA_3_T15
1202

HSHCGI_PEA_3_T17
1203

HSHCGI_PEA_3_T18
1204

HSHCGI_PEA_3_T19
1205

HSHCGI_PEA_3_T20
1206

HSHCGI_PEA_3_T21
1207

HSHCGI_PEA_3_T22
1208

HSHCGI_PEA_3_T23
1209

HSHCGI_PEA_3_T24
1210

TABLE 2

Segments of interest

Segment Name
SEQ ID NO:

HSHCGI_PEA_3_node_0
1211

HSHCGI_PEA_3_node_2
1212

HSHCGI_PEA_3_node_7
1213

HSHCGI_PEA_3_node_8
1214

HSHCGI_PEA_3_node_14
1215

HSHCGI_PEA_3_node_16
1216

HSHCGI_PEA_3_node_18
1217

HSHCGI_PEA_3_node_20
1218

HSHCGI_PEA_3_node_26
1219

HSHCGI_PEA_3_node_28
1220

HSHCGI_PEA_3_node_30
1221

HSHCGI_PEA_3_node_32
1222

HSHCGI_PEA_3_node_33
1223

HSHCGI_PEA_3_node_34
1224

HSHCGI_PEA_3_node_36
1225

HSHCGI_PEA_3_node_1
1226

HSHCGI_PEA_3_node_4
1227

HSHCGI_PEA_3_node_6
1228

HSHCGI_PEA_3_node_9
1229

HSHCGI_PEA_3_node_11
1230

HSHCGI_PEA_3_node_13
1231

HSHCGI_PEA_3_node_19
1232

HSHCGI_PEA_3_node_21
1233

HSHCGI_PEA_3_node_22
1234

HSHCGI_PEA_3_node_23
1235

HSHCGI_PEA_3_node_24
1236

HSHCGI_PEA_3_node_27
1237

HSHCGI_PEA_3_node_31
1238

HSHCGI_PEA_3_node_35
1239

TABLE 3

Proteins of interest

Protein Name
SEQ ID NO:
Corresponding Transcript(s)

HSHCGI_PEA_3_P17
1243
HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)

HSHCGI_PEA_3_P18
1244
HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)

HSHCGI_PEA_3_P19
1245
HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)

HSHCGI_PEA_3_P1
1246
HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)

HSHCGI_PEA_3_P4
1247
HSHCGI_PEA_3_T5 (SEQ ID NO: 1192); HSHCGI_PEA_3_T12 (SEQ

ID NO: 1199)

HSHCGI_PEA_3_P6
1248
HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)

HSHCGI_PEA_3_P7
1249
HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)

HSHCGI_PEA_3_P8
1250
HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)

HSHCGI_PEA_3_P9
1251
HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)

HSHCGI_PEA_3_P12
1252
HSHCGI_PEA_3_T14 (SEQ ID NO: 1201); HSHCGI_PEA_3_T15

(SEQ ID NO: 1202); HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)

HSHCGI_PEA_3_P13
1253
HSHCGI_PEA_3_T17 (SEQ ID NO: 1203); HSHCGI_PEA_3_T19

(SEQ ID NO: 1205)

HSHCGI_PEA_3_P14
1254
HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)

HSHCGI_PEA_3_P15
1255
HSHCGI_PEA_3_T21 (SEQ ID NO: 1207); HSHCGI_PEA_3_T22

(SEQ ID NO: 1208)

HSHCGI_PEA_3_P16
1256
HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)

HSHCGI_PEA_3_P20
1257
HSHCGI_PEA_3_T1 (SEQ ID NO: 1188); HSHCGI_PEA_3_T2 (SEQ

ID NO: 1189)

HSHCGI_PEA_3_P21
1258
HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)

HSHCGI_PEA_3_P22
1259
HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)

As noted above, cluster HSHCGI features 24 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided.

Variant protein HSHCGI_PEA_—3_P17 (SEQ ID NO:1243) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T13 (SEQ ID NO:1200). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P17 (SEQ ID NO:1243) and TM31_HUMAN (SEQ ID NO: 1242):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCPQCITQIGETSCGFFKCPLCKTSVRRDAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYV corresponding to amino acids 1-218 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 1-218 of HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EIPLMPTVERSQEARCYP (SEQ ID NO:1442) corresponding to amino acids 219-236 of HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P17 (SEQ ID NO:1243), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EIPLMPTVERSQEARCYP (SEQ ID NO:1442) in HSHCGI_PEA_—3_P17 (SEQ ID NO:1243).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P17 (SEQ ID NO:1243) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 4, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P17 (SEQ ID NO:1243) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 4

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

38
Q ->
No

38
Q -> K
No

61
R ->
No

118
R -> C
Yes

233
R -> H
Yes

Variant protein HSHCGI_PEA_—3_P17 (SEQ ID NO:1243) is encoded by the following transcript(s): HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T13 (SEQ ID NO:1200) is shown in bold; this coding portion starts at position 111 and ends at position 814. The transcript also has the following SNPs as listed in Table 5 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P17 (SEQ ID NO:1243) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 5

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

24
-> C
No

60
A ->
No

61
C ->
No

197
C -> T
Yes

222
A ->
No

292
G ->
No

297
-> G
No

419
C -> T
Yes

462
C -> T
Yes

749
G -> A
Yes

804
G -> A
Yes

879
A ->
No

960
C -> T
Yes

981
G -> A
Yes

1274
C -> A
No

1372
G -> A
Yes

1423
A -> C
Yes

1592
G -> A
Yes

1765
G -> A
Yes

1770
G -> C
Yes

1858
T -> C
No

2006
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P18 (SEQ ID NO:1244) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T0 (SEQ ID NO:1187). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P18 (SEQ ID NO:1244) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P18 (SEQ ID NO:1244) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 6

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

256
R ->
No

388
A -> E
No

421
E -> K
Yes

Variant protein HSHCGI_PEA_—3_P18 (SEQ ID NO:1244) is encoded by the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T0 (SEQ ID NO:1187) is shown in bold; this coding portion starts at position 111 and ends at position 1385. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P18 (SEQ ID NO:1244) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 7

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

24
-> C
No

60
A ->
No

61
C ->
No

197
C -> T
Yes

222
A ->
No

292
G ->
No

297
-> G
No

419
C -> T
Yes

462
C -> T
Yes

749
G -> A
Yes

804
G -> A
Yes

878
A ->
No

959
C -> T
Yes

980
G -> A
Yes

1273
C -> A
No

1371
G -> A
Yes

1422
A -> C
Yes

1591
G -> A
Yes

1764
G -> A
Yes

1769
G -> C
Yes

1857
T -> C
No

2005
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P19 (SEQ ID NO:1245) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T11 (SEQ ID NO:1198). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P19 (SEQ ID NO:1245) and TM31_HUMAN_V2 (SEQ ID NO:1241):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRRDAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLE corresponding to amino acids 1-248 of TM31_HUMAN_V2 (SEQ ID NO:1241), which also corresponds to amino acids 1-248 of HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWRKNSVKQNQDTTPSQGA (SEQ ID NO:1443) corresponding to amino acids 249-267 of HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P19 (SEQ ID NO:1245), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWRKNSVKQNQDTTPSQGA (SEQ ID NO:1443) in HSHCGI_PEA_—3_P19 (SEQ ID NO:1245).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V2 (SEQ ID NO:1241). These changes were previously known to occur and are listed in the table below.

TABLE 8

Changes to TM31_HUMAN_V2 (SEQ ID NO: 1241)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P19 (SEQ ID NO:1245) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P19 (SEQ ID NO:1245) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 9

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

261
T -> M
Yes

Variant protein HSHCGI_PEA_—3_P19 (SEQ ID NO:1245) is encoded by the following transcript(s): HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T11 (SEQ ID NO:1198) is shown in bold; this coding portion starts at position 111 and ends at position 911. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P19 (SEQ ID NO:1245) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 10

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

24
-> C
No

60
A ->
No

61
C ->
No

197
C -> T
Yes

222
A ->
No

292
G ->
No

297
-> G
No

419
C -> T
Yes

462
C -> T
Yes

749
G -> A
Yes

804
G -> A
Yes

892
C -> T
Yes

913
G -> A
Yes

1206
C -> A
No

1304
G -> A
Yes

1355
A -> C
Yes

1524
G -> A
Yes

1697
G -> A
Yes

1702
G -> C
Yes

1790
T -> C
No

1938
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P1 (SEQ ID NO:1246) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T3 (SEQ ID NO:1190). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P1 (SEQ ID NO:1246) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P1 (SEQ ID NO:1246) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 11

Amino acid mutations

SNP position(s) on amino
Alternative
Previously

acid sequence
amino acid(s)
known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

256
R ->
No

388
A -> E
No

421
E -> K
Yes

Variant protein HSHCGI_PEA_—3_P1 (SEQ ID NO:1246) is encoded by the following transcript(s): HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T3 (SEQ ID NO:1190) is shown in bold; this coding portion starts at position 139 and ends at position 1413. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P1 (SEQ ID NO:1246) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 12

Nucleic acid SNPs

SNP position on
Alternative
Previously

nucleotide sequence
nucleic acid
known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

906
A ->
No

987
C -> T
Yes

1008
G -> A
Yes

1301
C -> A
No

1399
G -> A
Yes

1450
A -> C
Yes

1566
G -> A
Yes

1571
G -> C
Yes

1659
T -> C
No

1807
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P4 (SEQ ID NO:1247) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T5 (SEQ ID NO:1192). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P4 (SEQ ID NO:1247) and TM31_HUMAN_V1 (SEQ ID NO:1240):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1-256 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-256 of HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YDGPPQMYFAY (SEQ ID NO:1444) corresponding to amino acids 257-267 of HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P4 (SEQ ID NO:1247), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YDGPPQMYFAY (SEQ ID NO:1444) in HSHCGI_PEA_—3_P4 (SEQ ID NO:1247).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 13

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P4 (SEQ ID NO:1247) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P4 (SEQ ID NO:1247) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 14

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

Variant protein HSHCGI_PEA_—3_P4 (SEQ ID NO:1247) is encoded by the following transcript(s): HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T5 (SEQ ID NO:1192) is shown in bold; this coding portion starts at position 139 and ends at position 939. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P4 (SEQ ID NO:1247) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 15

Nucleic acid SNPs

SNP position on nucleotide
Alternative
Previously

sequence
nucleic acid
known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

953
T -> C
Yes

980
A -> G
Yes

1048
T -> C
Yes

1072
T -> C
Yes

1078
C -> A
Yes

1282
T -> C
Yes

1283
G -> T
Yes

1349
C -> T
Yes

1486
G -> A
Yes

1541
G -> A
Yes

1587
G -> A
Yes

1598
G -> A
Yes

1635
G -> T
Yes

1640
C -> T
Yes

1686
C -> G
Yes

1688
A -> G
Yes

1759
A ->
No

1840
C -> T
Yes

1861
G -> A
Yes

2154
C -> A
No

2252
G -> A
Yes

2303
A -> C
Yes

2472
G -> A
Yes

2645
G -> A
Yes

2650
G -> C
Yes

2738
T -> C
No

2886
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P6 (SEQ ID NO:1248) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T7 (SEQ ID NO:1194). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P6 (SEQ ID NO:1248) and TM31_HUMAN_V1 (SEQ ID NO:1240):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1-256 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-256 of HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PTPG (SEQ ID NO:1445) corresponding to amino acids 257-260 of HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P6 (SEQ ID NO:1248), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PTPG (SEQ ID NO:1445) in HSHCGI_PEA_—3_P6 (SEQ ID NO:1248).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 16

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P6 (SEQ ID NO:1248) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P6 (SEQ ID NO:1248) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 17

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

Variant protein HSHCGI_PEA_—3_P6 (SEQ ID NO:1248) is encoded by the following transcript(s): HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T7 (SEQ ID NO:1194) is shown in bold; this coding portion starts at position 139 and ends at position 918. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P6 (SEQ ID NO:1248) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 18

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

1185
C -> A
No

1283
G -> A
Yes

1334
A -> C
Yes

1503
G -> A
Yes

1676
G -> A
Yes

1681
G -> C
Yes

1769
T -> C
No

1917
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P7 (SEQ ID NO:1249) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T8 (SEQ ID NO:1195). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P7 (SEQ ID NO:1249) and TM31_HUMAN_V1 (SEQ ID NO:1240):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCRS corresponding to amino acids 1-257 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-257 of HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA (SEQ ID NO:1446) corresponding to amino acids 258-310 of HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P7 (SEQ ID NO:1249), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA (SEQ ID NO:1446) in HSHCGI_PEA_—3_P7 (SEQ ID NO:1249).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 19

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P7 (SEQ ID NO:1249) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P7 (SEQ ID NO:1249) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 20

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

277
E ->
No

304
T -> M
Yes

Variant protein HSHCGI_PEA_—3_P7 (SEQ ID NO:1249) is encoded by the following transcript(s): HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T8 (SEQ ID NO:1195) is shown in bold; this coding portion starts at position 139 and ends at position 1068. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P7 (SEQ ID NO:1249) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 21

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

968
A ->
No

1049
C -> T
Yes

1070
G -> A
Yes

1363
C -> A
No

1461
G -> A
Yes

1512
A -> C
Yes

1681
G -> A
Yes

1854
G -> A
Yes

1859
G -> C
Yes

1947
T -> C
No

2095
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P8 (SEQ ID NO:1250) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T9 (SEQ ID NO:1196). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P8 (SEQ ID NO:1250) and TM31_HUMAN_V1 (SEQ ID NO:1240):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHD SITGSLKKFKDQLQADRKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAG corresponding to amino acids 1-342 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-342 of HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KSPVSEY corresponding to amino acids 343-349 of HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P8 (SEQ ID NO:1250), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KSPVSEY in HSHCGI_PEA_—3_P8 (SEQ ID NO:1250).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 22

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P8 (SEQ ID NO:1250) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P8 (SEQ ID NO:1250) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 23

Amino acid mutations

SNP position(s) on amino acid
Alternative

sequence
amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

256
R ->
No

Variant protein HSHCGI_PEA_—3_P8 (SEQ ID NO:1250) is encoded by the following transcript(s): HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T9 (SEQ ID NO:1196) is shown in bold; this coding portion starts at position 139 and ends at position 1185. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P8 (SEQ ID NO:1250) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 24

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
know SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

906
A ->
No

987
C -> T
Yes

1008
G -> A
Yes

1281
A -> G
Yes

1613
C -> A
No

1711
G -> A
Yes

1762
A -> C
Yes

1931
G -> A
Yes

2104
G -> A
Yes

2109
G -> C
Yes

2197
T -> C
No

2345
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P9 (SEQ ID NO:1251) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T10 (SEQ ID NO:1197). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P9 (SEQ ID NO:1251) and TM31 HUMAN_V1 (SEQ ID NO:1240):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1-256 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-256 of HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TGEKTQ (SEQ ID NO:1448) corresponding to amino acids 257-262 of HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P9 (SEQ ID NO:1251), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TGEKTQ (SEQ ID NO:1448) in HSHCGI_PEA_—3_P9 (SEQ ID NO:1251).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 25

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P9 (SEQ ID NO:1251) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 26, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P9 (SEQ ID NO:1251) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 26

Amino acid mutations

SNP position(s) on amino acid

Previously

sequence
Alternative amino acid(s)
know SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

Variant protein HSHCGI_PEA_—3_P9 (SEQ ID NO:1251) is encoded by the following transcript(s): HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T10 (SEQ ID NO:1197) is shown in bold; this coding portion starts at position 139 and ends at position 924. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P9 (SEQ ID NO:1251) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 27

Nucleic acid SNPs

SNP position on nucleotide

Previously

sequence
Alternative nucleic acid
known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

943
C -> T
Yes

964
G -> A
Yes

1257
C -> A
No

1355
G -> A
Yes

1406
A -> C
Yes

1575
G -> A
Yes

1748
G -> A
Yes

1753
G -> C
Yes

1841
T -> C
No

1989
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P12 (SEQ ID NO:1252) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T14 (SEQ ID NO:1201). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P12 (SEQ ID NO:1252) and TM31_HUMAN (SEQ ID NO:1242):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P12 (SEQ ID NO:1252), comprising a first amino acid sequence being at least 90% homologous to MNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASY DEISGQGASSQDTKTFDVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 312-425 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 1-114 of HSHCGI_PEA_—3_P12 (SEQ ID NO:1252).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P12 (SEQ ID NO:1252) is encoded by the following transcript(s): HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T14 (SEQ ID NO:1201) is shown in bold; this coding portion starts at position 1795 and ends at position 2136. The transcript also has the following SNPs as listed in Table 28 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P12 (SEQ ID NO:1252) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 28

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

348
C -> T
Yes

442
G -> T
Yes

466
G ->
Yes

468
G ->
Yes

823
T -> C
Yes

850
A -> G
Yes

918
T -> C
Yes

942
T -> C
Yes

948
C -> A
Yes

1152
T -> C
Yes

1153
G -> T
Yes

1219
C -> T
Yes

1356
G -> A
Yes

1411
G -> A
Yes

1457
G -> A
Yes

1468
G -> A
Yes

1505
G -> T
Yes

1510
C -> T
Yes

1556
C -> G
Yes

1558
A -> G
Yes

1629
A ->
No

1710
C -> T
Yes

1731
G -> A
Yes

2024
C -> A
No

2122
G -> A
Yes

2173
A -> C
Yes

2342
G -> A
Yes

2515
G -> A
Yes

2520
G -> C
Yes

2608
T -> C
No

2756
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P13 (SEQ ID NO:1253) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T17 (SEQ ID NO:1203). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P13 (SEQ ID NO:1253) is encoded by the following transcript(s): HSHCGI_PEA_—3_T17 (SEQ ID NO:1203), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T17 (SEQ ID NO:1203) is shown in bold; this coding portion starts at position 585 and ends at position 914. The transcript also has the following SNPs as listed in Table 29 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P13 (SEQ ID NO:1253) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 29

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

606
A -> G
Yes

938
C -> A
No

1036
G -> A
Yes

1087
A -> C
Yes

1256
G -> A
Yes

1429
G -> A
Yes

1434
G -> C
Yes

1522
T -> C
No

1670
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P14 (SEQ ID NO:1254) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T18 (SEQ ID NO:1204). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P14 (SEQ ID NO:1254) and TM31_HUMAN_V1 (SEQ ID NO:1240):

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P14 (SEQ ID NO:1254), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEA GKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHD SITGSLKKFKDQLQADRKKDENRFFKSMNKNDMKS corresponding to amino acids 1-319 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-319 of HSHCGI_PEA_—3_P14 (SEQ ID NO:1254), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CK corresponding to amino acids 320-321 of HSHCGI_PEA_—3_P14 (SEQ ID NO:1254), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 30

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P14 (SEQ ID NO:1254) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 31, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P14 (SEQ ID NO:1254) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 31

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

256
R ->
No

Variant protein HSHCGI_PEA_—3_P14 (SEQ ID NO:1254) is encoded by the following transcript(s): HSHCGI_PEA_—3_T18 (SEQ ID NO:1204), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) is shown in bold; this coding portion starts at position 139 and ends at position 1101. The transcript also has the following SNPs as listed in Table 32 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P14 (SEQ ID NO:1254) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 32

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

906
A ->
No

987
C -> T
Yes

1008
G -> A
Yes

1320
A -> G
Yes

1416
C -> G
Yes

Variant protein HSHCGI_PEA_—3_P15 (SEQ ID NO:1255) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T21 (SEQ ID NO:1207). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P15 (SEQ ID NO:1255) is encoded by the following transcript(s): HSHCGI_PEA_—3_T21 (SEQ ID NO:1207), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T21 (SEQ ID NO:1207) is shown in bold; this coding portion starts at position 338 and ends at position 505. The transcript also has the following SNPs as listed in Table 33 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P15 (SEQ ID NO:1255) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 33

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

15
A -> G
Yes

361
A -> G
Yes

377
C -> T
Yes

429
C -> A
Yes

606
G -> A
Yes

902
T -> C
Yes

1104
G -> C
Yes

1473
T -> C
Yes

1853
A -> G
Yes

2005
C -> A
Yes

2028
C -> T
Yes

2080
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P16 (SEQ ID NO:1256) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P16 (SEQ ID NO:1256) and TM31_HUMAN_V1:

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), comprising a first amino acid sequence being at least 90% homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVRKNAIRFNSLLRN LVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQ EQIQVLQQKEKETVQVKAQGVHRVDVFT corresponding to amino acids 1-171 of TM31_HUMAN_V1 (SEQ ID NO:1240), which also corresponds to amino acids 1-171 of HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRKTPSHDLWKQKHLCQSSWNPLLH (SEQ ID NO:1449) corresponding to amino acids 172-196 of HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a tail of HSHCGI_PEA_—3_P16 (SEQ ID NO:1256), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRKTPSHDLWKQKHLCQSSWNPLLH (SEQ ID NO:1449) in HSHCGI_PEA_—3_P16 (SEQ ID NO:1256).

It should be noted that the known protein sequence (TM31_HUMAN (SEQ ID NO:1242)) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for TM31_HUMAN_V1 (SEQ ID NO:1240). These changes were previously known to occur and are listed in the table below.

TABLE 34

Changes to TM31_HUMAN_V1 (SEQ ID NO: 1240)

SNP position(s) on amino

acid sequence
Type of change

38
conflict

63
conflict

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P16 (SEQ ID NO:1256) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 35, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P16 (SEQ ID NO:1256) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 35

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

Variant protein HSHCGI_PEA_—3_P16 (SEQ ID NO:1256) is encoded by the following transcript(s): HSHCGI_PEA_—3_T23 (SEQ ID NO:1209), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T23 (SEQ ID NO:1209) is shown in bold; this coding portion starts at position 139 and ends at position 726. The transcript also has the following SNPs as listed in Table 36 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P16 (SEQ ID NO:1256) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 36

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

769
T -> G
Yes

947
G -> A
Yes

1000
C -> A
Yes

1061
C -> A
Yes

Variant protein HSHCGI_PEA_—3_P20 (SEQ ID NO:1257) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T1 (SEQ ID NO:1188) and HSHCGI_PEA_—3_T2 (SEQ ID NO:1189). The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P20 (SEQ ID NO:1257) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 37, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P20 (SEQ ID NO:1257) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 37

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

38
K ->
No

61
R ->
No

118
R -> C
Yes

232
V -> I
Yes

256
R ->
No

388
A -> E
No

421
E -> K
Yes

Variant protein HSHCGI_PEA_—3_P20 (SEQ ID NO:1257) is encoded by the following transcript(s): HSHCGI_PEA_—3_T1 (SEQ ID NO:1188) and HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), for which the sequence(s) is/are given at the end of the application.

The coding portion of transcript HSHCGI_PEA_—3_T1 (SEQ ID NO:1188) is shown in bold; this coding portion starts at position 139 and ends at position 1413. The transcript also has the following SNPs as listed in Table 38 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P20 (SEQ ID NO:1257) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 38

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

447
C -> T
Yes

490
C -> T
Yes

777
G -> A
Yes

832
G -> A
Yes

906
A ->
No

987
C -> T
Yes

1008
G -> A
Yes

1301
C -> A
No

1399
G -> A
Yes

1450
A -> C
Yes

1619
G -> A
Yes

1792
G -> A
Yes

1797
G -> C
Yes

1885
T -> C
No

2033
A -> G
Yes

The coding portion of transcript HSHCGI_PEA_—3_T2 (SEQ ID NO:1189) is shown in bold; this coding portion starts at position 112 and ends at position 1386. The transcript also has the following SNPs as listed in Table 39 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P20 (SEQ ID NO:1257) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 39

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

61
A ->
No

62
C ->
No

198
C -> T
Yes

223
A ->
No

293
G ->
No

298
-> G
No

420
C -> T
Yes

463
C -> T
Yes

750
G -> A
Yes

805
G -> A
Yes

879
A ->
No

960
C -> T
Yes

981
G -> A
Yes

1274
C -> A
No

1372
G -> A
Yes

1423
A -> C
Yes

1592
G -> A
Yes

1765
G -> A
Yes

1770
G -> C
Yes

1858
T -> C
No

2006
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P21 (SEQ ID NO:1258) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T4 (SEQ ID NO:1191). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P21 (SEQ ID NO:1258) and TM31_HUMAN:

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ (SEQ ID NO:1450) corresponding to amino acids 1-28 of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), and a second amino acid sequence being at least 90% homologous to FLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHEKQR1 LTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLKTKQNMPPRQLLEDIK VVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQLQADRKKDENRFFKSMNKNDMKSWG LLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASYDEISGQGASSQD TKTFDVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 112-425 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 29-342 of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

2. An isolated polypeptide encoding for a head of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ (SEQ ID NO:1450) of HSHCGI_PEA_—3_P21 (SEQ ID NO:1258).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P21 (SEQ ID NO:1258) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 40, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P21 (SEQ ID NO:1258) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 40

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

23
K ->
No

35
R -> C
Yes

149
V -> I
Yes

173
R ->
No

305
A -> E
No

338
E -> K
Yes

Variant protein HSHCGI_PEA_—3_P21 (SEQ ID NO:1258) is encoded by the following transcript(s): HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T4 (SEQ ID NO:1191) is shown in bold; this coding portion starts at position 252 and ends at position 1277. The transcript also has the following SNPs as listed in Table 41 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P21 (SEQ ID NO:1258) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 41

Nucleic acid SNPs

SNP position on

nucleotide sequence
Alternative nucleic acid
Previously known SNP?

88
A ->
No

89
C ->
No

225
C -> T
Yes

250
A ->
No

320
G ->
No

325
-> G
No

354
C -> T
Yes

641
G -> A
Yes

696
G -> A
Yes

770
A ->
No

851
C -> T
Yes

872
G -> A
Yes

1165
C -> A
No

1263
G -> A
Yes

1314
A -> C
Yes

1483
G -> A
Yes

1656
G -> A
Yes

1661
G -> C
Yes

1749
T -> C
No

1897
A -> G
Yes

Variant protein HSHCGI_PEA_—3_P22 (SEQ ID NO:1259) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSHCGI_PEA_—3_T6 (SEQ ID NO:1193). One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

Comparison Report Between HSHCGI_PEA_—3_P22 (SEQ ID NO:1259) and TM31_HUMAN:

1. An isolated chimeric polypeptide encoding for HSHCGI_PEA_—3_P22 (SEQ ID NO:1259), comprising a first amino acid sequence being at least 90% homologous to MPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQLQADRKKDENRFFKS MNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASY DEISGQGASSQDTKTFDVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 241-425 of TM31_HUMAN (SEQ ID NO:1242), which also corresponds to amino acids 1-185 of HSHCGI_PEA_—3_P22 (SEQ ID NO:1259).

The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellularly because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.

Variant protein HSHCGI_PEA_—3_P22 (SEQ ID NO:1259) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 42, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P22 (SEQ ID NO:1259) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 42

Amino acid mutations

SNP position(s) on

amino acid sequence
Alternative amino acid(s)
Previously known SNP?

16
R ->
No

148
A -> E
No

181
E -> K
Yes

Variant protein HSHCGI_PEA_—3_P22 (SEQ ID NO:1259) is encoded by the following transcript(s): HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSHCGI_PEA_—3_T6 (SEQ ID NO:1193) is shown in bold; this coding portion starts at position 413 and ends at position 967. The transcript also has the following SNPs as listed in Table 43 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSHCGI_PEA_—3_P22 (SEQ ID NO:1259) sequence provides support for the deduced sequence of this variant protein according to the present invention).

TABLE 43

Nucleic acid SNPs

SNP position on nucleotide
Alternative

sequence
nucleic acid
Previously known SNP?

9
A -> T
Yes

73
A -> G
Yes

331
G -> A
Yes

386
G -> A
Yes

460
A ->
No

541
C -> T
Yes

562
G -> A
Yes

855
C -> A
No

953
G -> A
Yes

1004
A -> C
Yes

1173
G -> A
Yes

1346
G -> A
Yes

1351
G -> C
Yes

1439
T -> C
No

1587
A -> G
Yes

As noted above, cluster HSHCGI features 29 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

Segment cluster HSHCGI_PEA_—3_node_—0 (SEQ ID NO:1211) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T21 (SEQ ID NO:1207) and HSHCGI_PEA_—3_T22 (SEQ ID NO:1208). Table 44 below describes the starting and ending position of this segment on each transcript.

TABLE 44

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T21 (SEQ ID NO: 1207)
1
185

HSHCGI_PEA_3_T22 (SEQ ID NO: 1208)
1
185

Segment cluster HSHCGI_PEA_—3_node_—2 (SEQ ID NO:1212) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T21 (SEQ ID NO:1207) and HSHCGI_PEA_—3_T22 (SEQ ID NO:1208). Table 45 below describes the starting and ending position of this segment on each transcript.

TABLE 45

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T21 (SEQ ID NO: 1207)
186
2264

HSHCGI_PEA_3_T22 (SEQ ID NO: 1208)
186
2030

Segment cluster HSHCGI_PEA_—3_node_—7 (SEQ ID NO:1213) according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) and HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). Table 46 below describes the starting and ending position of this segment on each transcript.

TABLE 46

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
28
307

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
56
335

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
29
308

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
56
335

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
56
335

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
56
335

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
56
335

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
56
335

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
56
335

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
56
335

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
28
307

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
56
335

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
28
307

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
56
335

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)
56
335

Segment cluster HSHCGI_PEA_—3_node_—8 (SEQ ID NO:1214) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) and HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). Table 47 below describes the starting and ending position of this segment on each transcript.

TABLE 47

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
308
443

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
336
471

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
309
444

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
336
471

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
336
471

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
336
471

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
336
471

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
336
471

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
336
471

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
308
443

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
336
471

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
308
443

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
336
471

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)
336
471

Segment cluster HSHCGI_PEA_—3_node_—14 (SEQ ID NO:1215) according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). Table 48 below describes the starting and ending position of this segment on each transcript.

TABLE 48

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)
652
1081

Segment cluster HSHCGI_PEA_—3_node_—16 (SEQ ID NO:1216) according to the present invention is supported by 43 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200) and HSHCGI_PEA_—3_T18 (SEQ ID NO:1204). Table 49 below describes the starting and ending position of this segment on each transcript.

TABLE 49

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
624
854

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
652
882

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
625
855

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
652
882

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
516
746

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
652
882

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
206
436

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
652
882

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
652
882

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
652
882

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
652
882

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
624
854

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
652
882

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
624
854

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
652
882

Segment cluster HSHCGI_PEA_—3_node_—18 (SEQ ID NO:1217) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T14 (SEQ ID NO:1201). Table 50 below describes the starting and ending position of this segment on each transcript.

TABLE 50

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1
752

Segment cluster HSHCGI_PEA_—3_node_—20 (SEQ ID NO:1218) according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199) and HSHCGI_PEA_—3_T14 (SEQ ID NO:1201). Table 51 below describes the starting and ending position of this segment on each transcript.

TABLE 51

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
906
1696

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
906
1696

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
776
1566

Segment cluster HSHCGI_PEA_—3_node_—26 (SEQ ID NO:1219) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T19 (SEQ ID NO:1205), HSHCGI_PEA_—3_T20 (SEQ ID NO:1206) and HSHCGI_PEA_—3_T24 (SEQ ID NO:1210). Table 52 below describes the starting and ending position of this segment on each transcript.

TABLE 52

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
1
420

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
1
420

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)
1
420

HSHCGI_PEA_3_T24 (SEQ ID NO: 1210)
1
420

Segment cluster HSHCGI_PEA_—3_node_—28 (SEQ ID NO:1220) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) and HSHCGI_PEA_—3_T24 (SEQ ID NO:1210). Table 53 below describes the starting and ending position of this segment on each transcript.

TABLE 53

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
1097
1473

HSHCGI_PEA_3_T24 (SEQ ID NO: 1210)
496
872

Segment cluster HSHCGI_PEA_—3_node_—30 (SEQ ID NO:1221) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T17 (SEQ ID NO:1203). Table 54 below describes the starting and ending position of this segment on each transcript.

TABLE 54

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
1
421

Segment cluster HSHCGI_PEA_—3_node_—32 (SEQ ID NO:1222) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T17 (SEQ ID NO:1203) and HSHCGI_PEA_—3_T19 (SEQ ID NO:1205). Table 55 below describes the starting and ending position of this segment on each transcript.

TABLE 55

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
1163
1474

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
2016
2327

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
488
799

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
562
873

Segment cluster HSHCGI_PEA_—3_node_—33 (SEQ ID NO:1223) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T17 (SEQ ID NO:1203), HSHCGI_PEA_—3_T19 (SEQ ID NO:1205) and HSHCGI_PEA_—3_T20 (SEQ ID NO:1206). Table 56 below describes the starting and ending position of this segment on each transcript.

TABLE 56

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
1135
1452

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1163
1480

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
1136
1453

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
1163
1480

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
1027
1344

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
2016
2333

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
717
1034

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
1047
1364

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1225
1542

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
1475
1792

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
1119
1436

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
1068
1385

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
2328
2645

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
1136
1453

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1886
2203

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
562
879

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
800
1117

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
874
1191

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)
562
879

Segment cluster HSHCGI_PEA_—3_node_—34 (SEQ ID NO:1224) according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T17 (SEQ ID NO:1203) and HSHCGI_PEA_—3_T19 (SEQ ID NO:1205). Table 57 below describes the starting and ending position of this segment on each transcript.

TABLE 57

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
1453
1678

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1481
1706

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
1454
1679

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
1345
1570

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
2334
2559

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
1035
1260

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
1365
1590

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1543
1768

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
1793
2018

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
1437
1662

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
1386
1611

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
2646
2871

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
1454
1679

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
2204
2429

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
880
1105

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
1118
1343

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
1192
1417

Segment cluster HSHCGI_PEA_—3_node_—36 (SEQ ID NO:1225) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T17 (SEQ ID NO:1203), HSHCGI_PEA_—3_T19 (SEQ ID NO:1205) and HSHCGI_PEA_—3_T20 (SEQ ID NO:1206). Table 58 below describes the starting and ending position of this segment on each transcript.

TABLE 58

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
1792
2038

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1820
2066

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
1793
2039

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
1594
1840

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
1684
1930

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
2673
2919

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
1374
1620

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
1704
1950

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1882
2128

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
2132
2378

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
1776
2022

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
1725
1971

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
2985
3231

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
1793
2039

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
2543
2789

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
1219
1465

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
1457
1703

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
1531
1777

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)
993
1239

Segment cluster HSHCGI_PEA_—3_node_—1 (SEQ ID NO:1226) according to the present invention is supported by 0 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198) and HSHCGI_PEA_—3_T13 (SEQ ID NO:1200). Table 59 below describes the starting and ending position of this segment on each transcript.

TABLE 59

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
1
27

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
1
27

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
1
27

Segment cluster HSHCGI_PEA_—3_node_—4 (SEQ ID NO:1227) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T2 (SEQ ID NO:1189). Table 60 below describes the starting and ending position of this segment on each transcript.

TABLE 60

.Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
1
28

Segment cluster HSHCGI_PEA_—3_node_—6 (SEQ ID NO:1228) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) and HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). Table 61 below describes the starting and ending position of this segment on each transcript.

TABLE 61

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1
55

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
1
55

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
1
55

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
1
55

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
1
55

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1
55

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
1
55

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
1
55

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
1
55

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
1
55

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)
1
55

Segment cluster HSHCGI_PEA_—3_node_—9 (SEQ ID NO:1229) according to the present invention is supported by 32 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) and HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). Table 62 below describes the starting and ending position of this segment on each transcript.

TABLE 62

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
444
527

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
472
555

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
445
528

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
472
555

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
336
419

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
472
555

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
472
555

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
472
555

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
472
555

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
472
555

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
444
527

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
472
555

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
444
527

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
472
555

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)
472
555

Segment cluster HSHCGI_PEA_—3_node_—11 (SEQ ID NO:1230) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T6 (SEQ ID NO:1193). Table 63 below describes the starting and ending position of this segment on each transcript.

TABLE 63

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
1
109

Segment cluster HSHCGI_PEA_—3_node_—13 (SEQ ID NO:1231) according to the present invention is supported by 35 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T18 (SEQ ID NO:1204) and HSHCGI_PEA_—3_T23 (SEQ ID NO:1209). Table 64 below describes the starting and ending position of this segment on each transcript.

TABLE 64

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
528
623

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
556
651

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
529
624

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
556
651

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
420
515

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
556
651

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
110
205

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
556
651

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
556
651

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
556
651

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
556
651

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
528
623

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
556
651

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
528
623

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
556
651

HSHCGI_PEA_3_T23 (SEQ ID NO: 1209)
556
651

Segment cluster HSHCGI_PEA_—3_node_—19 (SEQ ID NO:1232) according to the present invention can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201) and HSHCGI_PEA_—3_T18 (SEQ ID NO:1204). Table 65 below describes the starting and ending position of this segment on each transcript.

TABLE 65

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
855
877

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
883
905

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
856
878

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
883
905

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
747
769

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
883
905

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
437
459

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
883
905

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
883
905

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
883
905

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
883
905

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
883
905

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
753
775

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
883
905

Segment cluster HSHCGI_PEA_—3_node_—21 (SEQ ID NO:1233) according to the present invention can be found in the following transcript(s): HSHCGI_PEA_—3_T13 (SEQ ID NO:1200). Table 66 below describes the starting and ending position of this segment on each transcript.

TABLE 66

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
855
878

Segment cluster HSHCGI_PEA_—3_node_—22 (SEQ ID NO:1234) according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199) and HSHCGI_PEA_—3_T14 (SEQ ID NO:1201). Table 67 below describes the starting and ending position of this segment on each transcript.

TABLE 67

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
1697
1758

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
906
967

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
1697
1758

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1567
1628

Segment cluster HSHCGI_PEA_—3_node_—23 (SEQ ID NO:1235) according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201) and HSHCGI_PEA_—3_T18 (SEQ ID NO:1204). Table 68 below describes the starting and ending position of this segment on each transcript.

TABLE 68

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
878
921

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
906
949

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
879
922

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
906
949

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
770
813

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
1759
1802

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
460
503

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
968
1011

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
906
949

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
1759
1802

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
879
922

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1629
1672

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
906
949

Segment cluster HSHCGI_PEA_—3_node_—24 (SEQ ID NO:1236) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201) and HSHCGI_PEA_—3_T18 (SEQ ID NO:1204). Table 69 below describes the starting and ending position of this segment on each transcript.

TABLE 69

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
922
993

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
950
1021

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
923
994

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
950
1021

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
814
885

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
1803
1874

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
504
575

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1012
1083

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
950
1021

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
906
977

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
855
926

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
1803
1874

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
923
994

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1673
1744

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
950
1021

Segment cluster HSHCGI_PEA_—3_node_—27 (SEQ ID NO:1237) according to the present invention is supported by 43 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T18 (SEQ ID NO:1204), HSHCGI_PEA_—3_T19 (SEQ ID NO:1205), HSHCGI_PEA_—3_T20 (SEQ ID NO:1206) and HSHCGI_PEA_—3_T24 (SEQ ID NO:1210). Table 70 below describes the starting and ending position of this segment on each transcript.

TABLE 70

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
994
1068

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1022
1096

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
995
1069

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
1022
1096

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
886
960

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
1875
1949

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
576
650

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
906
980

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1084
1158

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
1022
1096

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
978
1052

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
927
1001

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
1875
1949

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
995
1069

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1745
1819

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
421
495

HSHCGI_PEA_3_T18 (SEQ ID NO: 1204)
1022
1096

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
421
495

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)
421
495

HSHCGI_PEA_3_T24 (SEQ ID NO: 1210)
421
495

Segment cluster HSHCGI_PEA_—3_node_—31 (SEQ ID NO:1238) according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T17 (SEQ ID NO:1203), HSHCGI_PEA_—3_T19 (SEQ ID NO:1205) and HSHCGI_PEA_—3_T20 (SEQ ID NO:1206). Table 71 below describes the starting and ending position of this segment on each transcript.

TABLE 71

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
1069
1134

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1097
1162

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
1070
1135

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
1097
1162

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
961
1026

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
1950
2015

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
651
716

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
981
1046

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1159
1224

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
1097
1162

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
1053
1118

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
1002
1067

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
1950
2015

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
1070
1135

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
1820
1885

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
496
561

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
422
487

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
496
561

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)
496
561

Segment cluster HSHCGI_PEA_—3_node_—35 (SEQ ID NO:1239) according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSHCGI_PEA_—3_T0 (SEQ ID NO:1187), HSHCGI_PEA_—3_T1 (SEQ ID NO:1188), HSHCGI_PEA_—3_T2 (SEQ ID NO:1189), HSHCGI_PEA_—3_T3 (SEQ ID NO:1190), HSHCGI_PEA_—3_T4 (SEQ ID NO:1191), HSHCGI_PEA_—3_T5 (SEQ ID NO:1192), HSHCGI_PEA_—3_T6 (SEQ ID NO:1193), HSHCGI_PEA_—3_T7 (SEQ ID NO:1194), HSHCGI_PEA_—3_T8 (SEQ ID NO:1195), HSHCGI_PEA_—3_T9 (SEQ ID NO:1196), HSHCGI_PEA_—3_T10 (SEQ ID NO:1197), HSHCGI_PEA_—3_T11 (SEQ ID NO:1198), HSHCGI_PEA_—3_T12 (SEQ ID NO:1199), HSHCGI_PEA_—3_T13 (SEQ ID NO:1200), HSHCGI_PEA_—3_T14 (SEQ ID NO:1201), HSHCGI_PEA_—3_T15 (SEQ ID NO:1202), HSHCGI_PEA_—3_T17 (SEQ ID NO:1203), HSHCGI_PEA_—3_T19 (SEQ ID NO:1205) and HSHCGI_PEA_—3_T20 (SEQ ID NO:1206). Table 72 below describes the starting and ending position of this segment on each transcript.

TABLE 72

Segment location on transcripts

Segment
Segment

starting
ending

Transcript name
position
position

HSHCGI_PEA_3_T0 (SEQ ID NO: 1187)
1679
1791

HSHCGI_PEA_3_T1 (SEQ ID NO: 1188)
1707
1819

HSHCGI_PEA_3_T2 (SEQ ID NO: 1189)
1680
1792

HSHCGI_PEA_3_T3 (SEQ ID NO: 1190)
1481
1593

HSHCGI_PEA_3_T4 (SEQ ID NO: 1191)
1571
1683

HSHCGI_PEA_3_T5 (SEQ ID NO: 1192)
2560
2672

HSHCGI_PEA_3_T6 (SEQ ID NO: 1193)
1261
1373

HSHCGI_PEA_3_T7 (SEQ ID NO: 1194)
1591
1703

HSHCGI_PEA_3_T8 (SEQ ID NO: 1195)
1769
1881

HSHCGI_PEA_3_T9 (SEQ ID NO: 1196)
2019
2131

HSHCGI_PEA_3_T10 (SEQ ID NO: 1197)
1663
1775

HSHCGI_PEA_3_T11 (SEQ ID NO: 1198)
1612
1724

HSHCGI_PEA_3_T12 (SEQ ID NO: 1199)
2872
2984

HSHCGI_PEA_3_T13 (SEQ ID NO: 1200)
1680
1792

HSHCGI_PEA_3_T14 (SEQ ID NO: 1201)
2430
2542

HSHCGI_PEA_3_T15 (SEQ ID NO: 1202)
1106
1218

HSHCGI_PEA_3_T17 (SEQ ID NO: 1203)
1344
1456

HSHCGI_PEA_3_T19 (SEQ ID NO: 1205)
1418
1530

HSHCGI_PEA_3_T20 (SEQ ID NO: 1206)
880
992

Variant Protein Alignment to the Previously Known Protein:

Expression of TRIM31 Tripartite Motif HSHCGI Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HSHCGI Seg20 (SEQ ID NO:1378) in Normal and Cancerous Colon Tissues

Expression of TRIM31 tripartite motif transcripts detectable by or according to seg20, HSHCGIseg20 amplicon (SEQ ID NO: 1378) and HSHCGIseg20F (SEQ ID NO: 1376) HSHCGIseg20R (SEQ ID NO: 1377) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing samples”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

FIG. 69 is a histogram showing over expression of the above-indicated TRIM31 tripartite motif transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

FIG. 70 is a histogram showing over expression of the above-indicated TRIM31 tripartite motif transcripts in cancerous colon samples relative to the normal samples. The number and percentage of samples that exhibit at least 3 fold over-expression, out of the total number of samples tested is indicated in the bottom.

As is evident from FIG. 70, the expression of TRIM31 tripartite motif transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41-45, 49-52, 62-67, 69-71 Table 1, , “Tissue samples in testing samples”). Notably an over-expression of at least 3 fold was found in 8 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

The P value for the difference in the expression levels of TRIM31 tripartite motif transcripts detectable by the above amplicon in colon cancer samples versus the normal tissue samples was determined by T test as 7.56E-03.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSHCGIseg35F forward primer (SEQ ID NO: 1379); and HSHCGIseg35R reverse primer (SEQ ID NO: 1380).

Forward primer (SEQ ID NO: 1379):

TAAGTCTACAGGTGGTCAAAATGCTG

Reverse primer (SEQ ID NO: 1380):

GGAGCGCCCTCTGTTTCC

Amplicon (SEQ ID NO: 1381):

TAAGTCTACAGGTGGTCAAAATGCTGTATCCACCCAATTCCACTAAATGG

AATAAATGAATAAATGAATGAATTCATTTATTCCATTTCCTCAGTTCCTC

CCCAAATTACACCTCTGCCAGGAAACAGAGGGCGCTCC

It should be noted that for R30650_PEA_—2-seg73, no differential expression was observed in one Q-PCR experiment carried out with colon panel. For HUMCEA_PEA_—1 seg 6—no differential expression was observed in one Q-PCR experiment carried out with colon panel.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

As is evident from FIG. 69, the expression of TRIM31 tripartite motif transcripts detectable by the above amplicon in cancer samples was higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, “Tissue samples in testing samples”). Notably an over-expression of at least 3 fold was found in 6 out of 37 adenocarcinoma samples,

Statistical analysis was applied to verify the significance of these results, as described below.

Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: HSHCGIseg20F forward primer (SEQ ID NO: 1376); and HSHCGIseg20R reverse primer (SEQ ID NO: 1377).

Forward primer (SEQ ID NO: 1376):

TGCCTACTGATTCATCCACATACA

Reverse primer (SEQ ID NO: 1377):

GCATTCCCCGGCTGC

Amplicon (SEQ ID NO: 1378):

TGCCTACTGATTCATCCACATACAATTCTCAGCGTATATCCAAATGCAGT

CAACATTCCTCTCTCAGAAATACCCACCCACCTCTAACTCTGCATTCATA

CATTTAGGCTGCAGCCGGGGAATGC

Expression of TRIM31 Tripartite Motif HSHCGI Transcripts which are Detectable by Amplicon as Depicted in Sequence Name HSHCGI Seg35 (SEQ ID NO: 1381) in Normal and Cancerous Colon Tissues

Expression of TRIM31 tripartite motif transcripts detectable by or according to seg35, HSHCGIseg35 amplicon (SEQ ID NO: 1381) and HSHCGIseg35F (SEQ ID NO: 1379) HSHCGIseg35R (SEQ ID NO: 1380) primers was measured by real time PCR. In parallel the expression of four housekeeping genes —PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1576); amplicon—PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_—000194 (SEQ ID NO:1577); amplicon—HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_—000402 (SEQ ID NO:1578); G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_—002954 (SEQ ID NO:1579); RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, “Tissue samples in testing samples”), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

Number	Date	Country
60620916	Oct 2004	US
60628123	Nov 2004	US
60621131	Oct 2004	US
60628145	Nov 2004	US
60620656	Oct 2004	US
60620975	Oct 2004	US
60539129	Jan 2004	US

	Number	Date	Country
Parent	11050875	Jan 2005	US
Child	11976324		US

Novel nucleotide and amino acid sequences, and assays methods of use thereof for diagnosis of colon cancer

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CPC

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Abstract

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Continuation in Parts (1)