Compounds for immunotherapy and diagnosis of colon cancer and methods for their use

Abstract

Compositions and methods for the therapy and diagnosis of cancer, such as colon cancer, are disclosed. Compositions may comprise one or more colon tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a colon tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as colon cancer. Diagnostic methods based on detecting a colon tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Description

TECHNICAL FIELD

The present invention relates generally to therapy and diagnosis of cancer, such as colon cancer. The invention is more specifically related to polypeptides comprising at least a portion of a colon tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides may be used in vaccines and pharmaceutical compositions for prevention and treatment of colon cancer, and for the diagnosis and monitoring of such cancers.

BACKGROUND OF THE INVENTION

Cancer is a significant health problem throughout the world. Although advances have been made in detection and therapy of cancer, no vaccine or other universally successful method for prevention or treatment is currently available. Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients.

Colon cancer is the second most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death. An estimated 95,600 new cases of colon cancer will be diagnosed in 1998, with an estimated 47,700 deaths. The five-year survival rate for patients with colorectal cancer detected in an early localized stage is 92%; unfortunately, only 37% of colorectal cancer is diagnosed at this stage. The survival rate drops to 64% if the cancer is allowed to spread to adjacent organs or lymph nodes, and to 7% in patients with distant metastases.

The prognosis of colon cancer is directly related to the degree of penetration of the tumor through the bowel wall and the presence or absence of nodal involvement, consequently, early detection and treatment are especially important. Currently, diagnosis is aided by the use of screening assays for fecal occult blood, sigmoidoscopy, colonoscopy and double contrast barium enemas. Treatment regimens are determined by the type and stage of the cancer, and include surgery, radiation therapy and/or chemotherapy. Recurrence following surgery (the most common form of therapy) is a major problem and is often the ultimate cause of death. In spite of considerable research into therapies for the disease, colon cancer remains difficult to diagnose and treat. In spite of considerable research into therapies for these and other cancers, colon cancer remains difficult to diagnose and treat effectively. Accordingly, there is a need in the art for improved, methods for detecting and treating such cancers. The present invention fulfills these needs and further provides other related advantages.

SUMMARY OF THE INVENTION

Briefly stated, the present invention provides compositions and methods for the diagnosis and therapy of cancer, such as colon cancer. In one aspect the present invention provides polypeptides comprising at least a portion of a colon tumor protein, or a variant thereof. Certain portions and other variants are immunogenic, such that the ability of the variant to react with antigen-specific antisera is not substantially diminished Within certain embodiments, the polypeptide comprises a sequence that is encoded by a polynucleotide sequence selected from the group consisting of: (a) sequences recited in SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46-49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101, 109-111, 116-119, 123-132, 138-142, 143, 148, 149, 156, 168, 170-182, 184, 189, 191-193, 196, 205, 207, 210-212, 214, 215, 218, 224-226, 228, 233, 234, 236, 238, 241, 242, 245, 246, 248, 250, 253, 254, 256, 259, 260, 262, 263, 266, 267, 270-273, 279 282, 291, 293, 294, 298, 300, 302, 303, 310-313, 315, 317, 320, 322, 324, 332-335, 345, 347, 356, 358, 361, 362, 366, 369 and 371, (b) variants of a sequence recited in SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46-49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101, 109-111, 116-119, 123-132, 138-142, 143, 148, 149, 156, 168, 170-182, 184, 189, 191-193, 196, 205, 207, 210-212, 214, 215, 218, 224-226, 228, 233, 234, 236, 238, 241, 242, 245, 246, 248, 250, 253, 254, 256, 259, 260, 262, 263, 266, 267, 270-273, 279, 282, 291, 293, 294, 298, 300, 302, 303, 310-313, 315, 317, 320, 322, 324, 332-335, 345, 347, 356, 358, 361, 362, 366, 369 and 371; and (c) complements of a sequence of (a) or (b).

The present invention further provides polynucleotides that encode a polypeptide as described above, or a portion thereof (such as a portion encoding at least 15 amino acid residues of a colon tumor protein), expression vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors.

Within other aspects, the present invention provides pharmaceutical compositions comprising a polypeptide or polynucleotide as described above and a physiologically acceptable carrier.

Within a related aspect of the present invention, vaccines are provided. Such vaccines comprise a polypeptide or polynucleotide as described above and a non-specific immune response enhancer.

The present invention further provides pharmaceutical compositions that comprise: (a) an antibody or antigen-binding fragment thereof that specifically binds to a colon tumor protein; and (b) a physiologically acceptable carrier.

Within further aspects, the present invention provides pharmaceutical compositions comprising: (a) an antigen presenting cell that expresses a polypeptide as described above and (b) a pharmaceutically acceptable carrier or excipient. Antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts and B cells.

Within related aspects, vaccines are provided that comprise: (a) an antigen presenting cell that expresses a polypeptide as described above and (b) a non-specific immune response enhancer.

The present invention further provides, in other aspects, fusion proteins that comprise at least one polypeptide as described above, as well as polynucleotides encoding such fusion proteins.

Within related aspects, pharmaceutical compositions comprising a fusion protein, or a polynucleotide encoding a fusion protein, in combination with a physiologically acceptable carrier are provided.

Vaccines are further provided, within other aspects, that comprise a fusion protein, or a polynucleotide encoding a fusion protein, in combination with a non-specific immune response enhancer.

Within further aspects, the present invention provides methods for inhibiting the development of a cancer in a patient, comprising administering to a patient a pharmaceutical composition or vaccine as recited above.

The present invention further provides, within other aspects, methods for removing tumor cells from a biological sample, comprising contacting a biological sample with T cells that specifically react with a colon tumor protein, wherein the step of contacting is performed under conditions and for a time sufficient to permit the removal of cells expressing the protein from the sample.

Within related aspects, methods are provided for inhibiting the development of a cancer in a patient, comprising administering to a patient a biological sample treated as described above.

Methods are further provided, within other aspects, for stimulating and/or expanding T cells specific for a colon tumor protein, comprising contacting T cells with one or more of: (i) a polypeptide as described above, (ii) a polynucleotide encoding such a polypeptide; and/or (iii) an antigen presenting cell that expresses such a polypeptide; under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells. Isolated T cell populations comprising T cells prepared as described above are also provided.

Within further aspects, the present invention provides methods for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a T cell population as described above.

The present invention further provides methods for inhibiting the development of a cancer in a patient, comprising the steps of: (a) incubating CD4 + and/or CD8 + T cells isolated from a patient with one or more of: (i) a polypeptide comprising at least an immunogenic portion of a colon tumor protein; (ii) a polynucleotide encoding such a polypeptide; and (iii) an antigen-presenting cell that expresses such a polypeptide, and (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient. Proliferated cells may, but need not, be cloned prior to administration to the patient.

Within further aspects, the present invention provides methods for determining the presence or absence of a cancer in a patient, comprising: (a) contacting a biological sample obtained from a patient with a binding agent that binds to a polypeptide as recited above; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; and (c) comparing the amount of polypeptide with a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient. Within preferred embodiments, the binding agent is an antibody, more preferably a monoclonal antibody. The cancer may be colon cancer.

The present invention also provides, within other aspects, methods for monitoring the progression of a cancer in a patient. Such methods comprise the steps of: (a) contacting a biological sample obtained from a patient at a first point in time with a binding agent that binds to a polypeptide as recited above; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; (c) repeating, steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polypeptide detected in step (c) with the amount detected step (b) and therefrom monitoring the progression of the cancer in the patient.

The present invention further provides, within other aspects, methods for determining the presence or absence of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a colon tumor protein; (b) detecting in the sample a level of a polynucleotide, preferably mRNA, that hybridizes to the oligonucleotide; and (c) comparing the level of polynucleotide that hybridizes to the oligonucleotide with a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient. Within certain embodiments, the amount of mRNA is detected via polymerase chain reaction using, for example, at least one oligonucleotide primer that hybridizes to a polynucleotide encoding a polypeptide as recited above, or a complement of such a polynucleotide. Within other embodiments, the amount of mRNA is detected using a hybridization technique, employing an oligonucleotide probe that hybridizes to a polynucleotide that encodes a polypeptide as recited above, or a complement of such a polynucleotide.

In related aspects, methods are provided for monitoring the progression of a cancer in a patient, comprising the steps of: (a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a colon tumor protein; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polynucleotide detected in step (c) with the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.

Within further aspects, the present invention provides antibodies, such as monoclonal antibodies, that bind to a polypeptide as described above, as well as diagnostic kits comprising such antibodies. Diagnostic kits comprising one or more oligonucleotide probes or primers as described above are also provided.

These and other aspects of the present invention will become apparent upon reference to the following detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.

BRIEF DESCRIPTION OF THE SEQUENCE IDENTIFIERS

SEQ ID NO: 1 is a first determined cDNA sequence for Contig 1, showing homology to Neutrophil Gelatinase Associated Lipocalin.

SEQ ID NO: 2 is the determined cDNA sequence for Contig 2, showing no significant homology to any known genes.

SEQ ID NO: 3 is the determined cDNA sequence for Contig 4, showing homology to Carcinoembryonic antigen.

SEQ ID NO: 4 is the determined cDNA sequence for Contig 5, showing homology to Carcinoembryonic antigen.

SEQ ID NO: 5 is the determined cDNA sequence for Contig 9, showing homology to Carcinoembryonic antigen.

SEQ ID NO: 6 is the determined cDNA sequence for Contig 52, showing homology to Carcinoembryonic antigen.

SEQ ID NO: 7 is the determined cDNA sequence for Contig 6, showing homology to Villin.

SEQ ID NO: 8 is the determined cDNA sequence for Contig 8, showing no significant homology to any known genes.

SEQ ID NO: 9 is the determined cDNA sequence for Contig 10, showing homology to Transforming Growth Factor (BIGH3).

SEQ ID NO: 10 is the determined cDNA sequence for Contig 19, showing homology to Transforming Growth Factor (BIGH3).

SEQ ID NO: 11 is the determined cDNA sequence for Contig 21, showing homology to Transforming Growth Factor (BIGH3).

SEQ ID NO: 12 is the determined cDNA sequence for Contig 11, showing homology to CO-029.

SEQ ID NO: 13 is the determined cDNA sequence for Contig 55, showing homology to CO-029.

SEQ ID NO: 14 is the determined cDNA sequence for Contig 12, showing homology to Chromosome 17, clone hRPC.1171_I — 10, also referred to as C798P.

SEQ ID NO: 15 is the determined cDNA sequence for Contig 13, showing no significant homology to any known gene.

SEQ ID NO: 16 is the determined cDNA sequence for Contig 14, also referred to as 14261, showing no significant homology to any known gene.

SEQ ID NO: 17 is the determined cDNA sequence for Contig 15, showing homology to Ets-Related Transcription Factor (ERT).

SEQ ID NO: 18 is the determined cDNA sequence for Contig 16, showing homology to Chromosome 5, PAC clone 228g9 (LBNL H142).

SEQ ID NO: 19 is the determined cDNA sequence for Contig 24, showing homology to Chromosome 5, PAC clone 228g9 (LBNL H142).

SEQ ID NO: 20 is the determined cDNA sequence for Contig 17, showing homology to Cytokeratin.

SEQ ID NO; 21 is the determined cDNA sequence for Contig 18, showing homology to L1-Cadherin.

SEQ ID NO: 22 is the determined cDNA sequence for Contig 20, showing no significant homology to any known gene.

SEQ ID NO: 23 is the determined cDNA sequence for Contig 22, showing homology to Bumetanide-sensitive Na-K-Cl cotransporter (NKCCl).

SEQ ID NO: 24 is the determined cDNA sequence for Contig 23, showing no significant homology to any known gene.

SEQ ID NO: 25 is the determined cDNA sequence for Contig 25, showing homology to Macrophage Inflammatory Protein 3 alpha.

SEQ ID NO: 26 is the determined cDNA sequence for Contig 26, showing homology to Laminin.

SEQ ID NO: 27 is the determined cDNA sequence for Contig 48, showing homology to Laminin.

SEQ ID NO: 28 is the determined cDNA sequence for Contig 27, showing homology to Mytobularin (MTM1).

SEQ ID NO: 29 is the determined cDNA sequence for Contig 28, showing homology to Chromosome 16 BAC clone CIT987SK-A-363E6.

SEQ ID NO: 30 is the determined cDNA sequence for Contig 29, also referred to as C751P and 14247, showing no significant homology to any known gene, but partial homology to Rat GSK-3β-interacting protein Axil homolog.

SEQ ID NO: 31 is the determined cDNA sequence for Contig 30, showing homology to Zinc-Finger Transcription Factor (ZNF207).

SEQ ID NO: 32 is the determined cDNA sequence for Contig 31, showing no significant homology to any known gene, but partial homology to Mus musculus GOB-4 homolog.

SEQ ID NO: 33 is the determined cDNA sequence for Contig 35, showing no significant homology to any known gene, but partial homology to Mus musculus GOB-4 homolog.

SEQ ID NO: 34 is the determined cDNA sequence for Contig 32, showing no significant homology to any known gene.

SEQ ID NO: 35 is the determined cDNA sequence for Contig 34, showing homology to Desmoglein 2.

SEQ ID NO: 36 is the determined cDNA sequence for Contig 36, showing no significant homology to any known gene.

SEQ ID NO: 37 is the determined cDNA sequence for Contig 37, showing homology to Putative Transmembrane Protein.

SEQ ID NO: 38 is the determined cDNA sequence for Contig 38, also referred to as C796P and 14219, showing no significant homology to any known gene.

SEQ ID NO: 39 is the determined cDNA sequence for Contig 40, showing homology to Nonspecific Cross-reacting Antigen.

SEQ ID NO: 40 is the determined cDNA sequence for Contig 41, also referred to as C799P and 14308, showing no significant homology to any known gene.

SEQ ID NO: 41 is the determined cDNA sequence for Contig 42, also referred to as C794P and 14309, showing no significant homology to any known gene.

SEQ ID NO: 42 is the determined cDNA sequence for Contig 43, showing homology to Chromosome 1 specific transcript KIAA0487.

SEQ ID NO: 43 is the determined cDNA sequence for Contig 45, showing homology to hMCM2.

SEQ ID NO: 44 is the determined cDNA sequence for Contig 46, showing homology to ETS2.

SEQ ID NO: 45 is the determined cDNA sequence for Contig 49, showing homology to Pump-1.

SEQ ID NO: 46 is the determined cDNA sequence for Contig 50, also referred to as C792P and 18323, showing no significant homology to any known gene.

SEQ ID NO: 47 is the determined cDNA sequence for Contig 51, also referred to as C795P and 14317, showing no significant homology to any known gene.

SEQ ID NO: 48 is the determined cDNA sequence for 11092, showing no significant homology to any known gene.

SEQ ID NO: 49 is the determined cDNA sequence for 11093, showing no significant homology to any known gene.

SEQ ID NO: 50 is the determined cDNA sequence for 11094, showing homology Human Putative Enterocyte Differentiation Protein.

SEQ ID NO: 51 is the determined cDNA sequence for 11095, showing homology to Human Transcriptional Corepressor hKAP1/TIF1B mRNA.

SEQ ID NO: 52 is the determined cDNA sequence for 11096, showing no significant homology to any known gene.

SEQ ID NO: 53 is the determined cDNA sequence for 11097, showing homology to Human Nonspecific Antigen.

SEQ ID NO: 54 is the determined cDNA sequence for 11098, showing no significant homology to any known gene.

SEQ ID NO: 55 is the determined cDNA sequence for 11099, showing homology to Human Pancreatic Secretory Inhibitor (PST) mRNA.

SEQ ID NO: 56 is the determined cDNA sequence for 11186, showing homology to Human Pancreatic Secretory Inhibitor (PST) mRNA.

SEQ ID NO: 57 is the determined cDNA sequence for 11101, showing homology to Human Chromosome X.

SEQ ID NO: 58 is the determined cDNA sequence for 11102, showing homology to Human Chromosome X.

SEQ ID NO: 59 is the determined cDNA sequence for 11103, showing no significant homology to any known gene.

SEQ ID NO: 60 is the determined cDNA sequence for 11174, showing no significant homology to any known gene.

SEQ ID NO: 61 is the determined cDNA sequence for 11104, showing homology to Human mRNA for KIAA0154.

SEQ ID NO: 62 is the determined cDNA sequence for 11105, showing homology toHuman Apurinic/Apyrimidinic Endonuclease (hap 1)mRNA.

SEQ ID NO: 63 is the determined cDNA sequence for 11106, showing homology toHuman Chromosome 12p13.

SEQ ID NO: 64 is the determined cDNA sequence for 11107, showing homology to Human 90 kDa Heat Shock Protein.

SEQ ID NO: 65 is the determined cDNA sequence for 11108, showing no significant homology to any known gene.

SEQ ID NO: 66 is the determined cDNA sequence for 11112, showing no significant homology to any known gene.

SEQ ID NO: 67 is the determined cDNA sequence for 11115, showing no significant homology to any known gene.

SEQ ID NO: 68 is the determined cDNA sequence for 11117, showing no significant homology to any known gene.

SEQ ID NO: 69 is the determined cDNA sequence for 11118, showing no significant homology to any known gene.

SEQ ID NO: 70 is the determined cDNA sequence for 11119, showing homology to Human Elongation Factor 1-alpha.

SEQ ID NO: 71 is the determined cDNA sequence for 11121, showing homology to Human Lamin B Receptor (LBR) mRNA.

SEQ ID NO: 72 is the determined cDNA sequence for 11122, showing homology to H. sapiens mRNA for Novel Glucocorticoid.

SEQ ID NO: 73 is the determined cDNA sequence for 11123, showing homology to H. sapiens mRNA for snRNA protein B.

SEQ ID NO: 74 is the determined cDNA sequence for 11124, showing homology to Human Cisplatin Resistance Associated Beta-protein.

SEQ ID NO: 75 is the determined cDNA sequence for 11127, showing homology to M. musculus Calumenin mRNA.

SEQ ID NO: 76 is the determined cDNA sequence for 11128, showing homology to Human ras-related small GTP binding protein.

SEQ ID NO: 77 is the determined cDNA sequence for 11130, showing homology to Human Cosmid U169d2.

SEQ ID NO: 78 is the determined cDNA sequence for 11131, showing homology to H. sapiens mRNA for protein homologous to Elongation 1-g.

SEQ ID NO: 79 is the determined cDNA sequence for 11134, showing no significant homology to any known gene.

SEQ ID NO: 80 is the determined cDNA sequence for 11135, showing homology to H. sapiens Nieman-Pick (NPC1) mRNA.

SEQ ID NO: 81 is the determined cDNA sequence for 11137, showing homology to H. sapiens mRNA for Niecin b-chain.

SEQ ID NO: 82 is the determined cDNA sequence for 11138, showing homology to Human Endogenous Retroviral Protease mRNA.

SEQ ID NO: 83 is the determined cDNA sequence for 11139, showing homology to H. sapiens mRNA for DMBT1 protein.

SEQ ID NO: 84 is the determined cDNA sequence for 11140, showing homology to H. sapiens ras GTPase activating-like protein.

SEQ ID NO: 85 is the determined cDNA sequence for 11143, showing homology to Human Acidic Ribosomal Phosphoprotein PO mRNA.

SEQ ID NO: 86 is the determined cDNA sequence for 11144, showing homology to H. sapiens U21 mRNA.

SEQ ID NO: 87 is the determined cDNA sequence for 11145, showing homology to Human GTP-binding protein.

SEQ ID NO: 88 is the determined cDNA sequence for 11148, showing homology to H. sapiens U21 mRNA.

SEQ ID NO: 89 is the determined cDNA sequence for 11151, showing no significant homology to any known gene.

SEQ ID NO: 90 is the determined cDNA sequence for 11154, showing no significant homology to any known gene.

SEQ ID NO: 91 is the determined cDNA sequence for 11156, showing homology to H. sapiens Ribosomal Protein L27.

SEQ ID NO: 92 is the determined cDNA sequence for 11157, showing homology to H. sapiens Ribosomal Protein L27.

SEQ ID NO: 93 is the determined cDNA sequence for 11158, showing no significant homology to any known gene.

SEQ ID NO: 94 is the determined cDNA sequence for 11162, showing homology to Ag-X antigen.

SEQ ID NO: 95 is the determined cDNA sequence for 11164, showing homology to H. sapiens mRNA for Signal Recognition Protein sub14.

SEQ ID NO: 96 is the determined cDNA sequence for 11165, showing homology to Human PAC 204e5/127h14.

SEQ ID NO: 97 is the determined cDNA sequence for 11166, showing homology to Human mRNA for KIAA0108.

SEQ ID NO: 98 is the determined cDNA sequence for 11167, showing homology to H. sapiens mRNA for Neutrophil Gelatinase asset. Lipocalin.

SEQ ID NO: 99 is the determined cDNA sequence for 11168, showing no significant homology to any known gene.

SEQ ID NO: 100 is the determined cDNA sequence for 11172, showing no significant homology to any known gene.

SEQ ID NO: 101 is the determined cDNA sequence for 11175, showing no significant homology to any known gene.

SEQ ID NO: 102 is the determined cDNA sequence for 11176, showing homology to Human maspin mRNA.

SEQ ID NO: 103 is the determined cDNA sequence for 11177, showing homology to Human Carcinoembryonic Antigen.

SEQ ID NO: 104 is the determined cDNA sequence for 11178, showing homology to Human A-Tubulin mRNA.

SEQ ID NO: 105 is the determined cDNA sequence for 11179, showing homology to Human mRNA for proton-ATPase-like protein.

SEQ ID NO: 106 is the determined cDNA sequence for 11180, showing homology to Human HepG2 3′ region cDNA clone hmd.

SEQ ID NO: 107 is the determined cDNA sequence for 11182, showing homology to Human MHC homologous to Chicken B-Complex Protein.

SEQ ID NO: 108 is the determined cDNA sequence for 11183, showing homology to Human High Mobility Group Box (SSRP1) mRNA.

SEQ ID NO: 109 is the determined cDNA sequence for 11184, showing no significant homology to any known gene.

SEQ ID NO: 110 is the determined cDNA sequence for 11185, showing no significant homology to any known gene.

SEQ ID NO: 111 is the determined cDNA sequence for 11187, showing no significant homology to any known gene.

SEQ ID NO: 112 is the determined cDNA sequence for 11190, showing homology to Human Replication Protein A 70 kDa.

SEQ ID NO: 113 is the determined cDNA sequence for Contig 47, also referred to as C797P, showing homology to Human Chromosome X clone bWXD342.

SEQ ID NO: 114 is the determined cDNA sequence for Contig 7, showing homology to Equilibrative Nucleoside Transporter 2 (ent2).

SEQ ID NO: 115 is the determined cDNA sequence for 14235.1, also referred to as C791P, showing homology to H. sapiens chromosome 21 derived BAC containing ets-2 gene.

SEQ ID NO: 116 is the determined cDNA sequence for 14287.2, showing no significant homology to any known gene, but some degree of homology to Putative Transmembrane Protein.

SEQ ID NO: 117 is the determined cDNA sequence for 14233.1, also referred to as Contig 48, showing no significant homology to any known gene.

SEQ ID NO: 118 is the determined cDNA sequence for 14298.2, also referred to as C793P, showing no significant homology to any known gene.

SEQ ID NO: 119 is the determined cDNA sequence for 14372, also referred to as Contig 44, showing no significant homology to any known gene.

SEQ ID NO: 120 is the determined cDNA sequence for 14295, showing homology to secreted cement gland protein XAG-2 homolog.

SEQ ID NO: 121 is the determined full-length cDNA sequence for a clone showing homology to Beta 1G-H3.

SEQ ID NO: 122 is the predicted amino acid sequence for the clone of SEQ ID NO: 121.

SEQ ID NO: 123 is a longer determined cDNA sequence for C751P.

SEQ ID NO: 124 is a longer determined cDNA sequence for C791P.

SEQ ID NO: 125 is a longer determined cDNA sequence for C792P.

SEQ ID NO: 126 is a longer determined cDNA sequence for C793P.

SEQ ID NO: 127 is a longer determined cDNA sequence for C794P.

SEQ ID NO: 128 is a longer determined cDNA sequence for C795P.

SEQ ID NO: 129 is a longer determined cDNA sequence for C796P.

SEQ ID NO: 130 is a longer determined cDNA sequence for C797P.

SEQ ID NO: 131 is a longer determined cDNA sequence for C798P.

SEQ ID NO: 132 is a longer determined cDNA sequence for C799P.

SEQ ID NO: 133 is a first partial determined cDNA sequence for CoSub-3 (also known as 23569).

SEQ ID NO: 134 is a second partial determined cDNA sequence for CoSub-3 (also known as 23569).

SEQ ID NO: 135 is a first partial determined cDNA sequence for CoSub-13 (also known as 23579).

SEQ ID NO: 136 is a second partial determined cDNA sequence for CoSub-13 (also known as 23579).

SEQ ID NO: 137 is the determined cDNA sequence for CoSub-17 (also known as 23583).

SEQ ID NO: 138 is the determined cDNA sequence for CoSub-19 (also known as 23585).

SEQ ID NO: 139 is the determined cDNA sequence for CoSub-22 (also known as 23714).

SEQ ID NO: 140 is the determined cDNA sequence for CoSub-23 (also known as 23715).

SEQ ID NO: 141 is the determined cDNA sequence for CoSub-26 (also known as 23717).

SEQ ID NO: 142 is the determined cDNA sequence for CoSub-33 (also known as 23724).

SEQ ID NO: 143 is the determined cDNA sequence for CoSub-34 (also known as 23725).

SEQ ID NO: 144 is the determined cDNA sequence for CoSub-35 (also known as 23726).

SEQ ID NO: 145 is the determined cDNA sequence for CoSub-37 (also known as 23728).

SEQ ID NO: 146 is the determined cDNA sequence for CoSub-39 (also known as 23730).

SEQ ID NO: 147 is the determined cDNA sequence for CoSub-42 (also known as 23766).

SEQ ID NO: 148 is the determined cDNA sequence for CoSub-44 (also known as 23768).

SEQ ID NO: 149 is the determined cDNA sequence for CoSub-47 (also known as 23771).

SEQ ID NO: 150 is the determined cDNA sequence for CoSub-54 (also known as 23778).

SEQ ID NO: 151 is the determined cDNA sequence for CoSub-55 (also known as 23779).

SEQ ID NO: 152 is the determined cDNA sequence for CT1 (also known as 24099).

SEQ ID NO: 153 is the determined cDNA sequence for CT2 (also known as 24100).

SEQ ID NO: 154 is the determined cDNA sequence for CF3 (also known as 24101).

SEQ ID NO: 155 is the determined cDNA sequence for CT6 (also known as 24104).

SEQ ID NO: 156 is the determined cDNA sequence for CT7 (also known as 24105).

SEQ ID NO: 157 is the determined cDNA sequence for CT2 (also known as 24110).

SEQ ID NO: 158 is the determined cDNA sequence for CT3 (also known as 24111).

SEQ ID NO: 159 is the determined cDNA sequence for CT14 (also known as 24112).

SEQ ID NO: 160 is the determined cDNA sequence for CT15 (also known as 24113).

SEQ ID NO: 161 is the determined cDNA sequence for CT17 (also known as 24115).

SEQ ID NO: 162 is the determined cDNA sequence for CT18 (also known as 24116).

SEQ ID NO: 163 is the determined cDNA sequence for CT22 (also known as 23848).

SEQ ID NO: 164 is the determined cDNA sequence for CT24 (also known as 23849).

SEQ ID NO: 165 is the determined cDNA sequence for CT31 (also known as 23854).

SEQ ID NO: 166 is the determined cDNA sequence for CT34 (also known as 23856).

SEQ ID NO: 167 is the determined cDNA sequence for CT37 (also known as 23859).

SEQ ID NO: 168 is the determined cDNA sequence for CT39 (also known as 23860).

SEQ ID NO: 169 is the determined cDNA sequence for CT40 (also known as 23861).

SEQ ID NO: 170 is the determined cDNA sequence for CT51 (also known as 24130).

SEQ ID NO: 171 is the determined cDNA sequence for CT53 (also known as 24132).

SEQ ID NO: 172 is the determined cDNA sequence for CT63 (also known as 24595).

SEQ ID NO: 173 is the determined cDNA sequence for CT88 (also known as 24608).

SEQ ID NO: 174 is the determined cDNA sequence for CT92 (also known as 24800).

SEQ ID NO: 175 is the determined cDNA sequence for CT94 (also known as 24802).

SEQ ID NO. 176 is the determined cDNA sequence for CT102 (also known as 24805).

SEQ ID NO: 177 is the determined cDNA sequence for CT103 (also known as 24806).

SEQ ID NO: 178 is the determined cDNA sequence for CT111 (also known as 25520).

SEQ ID NO: 179 is the determined cDNA sequence for CT118 (also known as 25522).

SEQ ID NO: 180 is the determined cDNA sequence for CT121 (also known as 25523).

SEQ ID NO: 181 is the determined cDNA sequence for CT126 (also known as 25527).

SEQ ID NO: 182 is the determined cDNA sequence for CT135 (also known as 25534).

SEQ ID NO: 183 is the determined cDNA sequence for CT140 (also known as 25537).

SEQ ID NO: 184 is the determined cDNA sequence for CT 145 (also known as 25542).

SEQ ID NO: 185 is the determined cDNA sequence for CT147 (also known as 25543).

SEQ ID NO: 186 is the determined cDNA sequence for CT148 (also known as 25544).

SEQ ID NO: 187 is the determined cDNA sequence for CT502 (also known as 26420).

SEQ ID NO: 188 is the determined cDNA sequence for CT507 (also known as 26425).

SEQ ID NO: 189 is the determined cDNA sequence for CT521 (also known as 27366).

SEQ ID NO: 190 is the determined cDNA sequence for CT544 (also known as 27375).

SEQ ID NO: 191 is the determined cDNA sequence for CT577 (also known as 27385).

SEQ ID NO: 192 is the determined cDNA sequence for CT580 (also known as 27387).

SEQ ID NO: 193 is the determined cDNA sequence for CT594 (also known as 27540).

SEQ ID NO: 194 is the determined cDNA sequence for CT606 (also known as 27547).

SEQ ID NO: 195 is the determined cDNA sequence for CT607 (also known as 27548).

SEQ ID NO: 196 is the determined cDNA sequence for CT599 (also known as 27903).

SEQ ID NO: 197 is the determined cDNA sequence for CT632 (also known as 27922).

SEQ ID NO: 198 is the predicted amino acid sequence for CT502 (SEQ ID NO: 187).

SEQ ID NO: 199 is the predicted amino acid sequence for CT507 (SEQ ID NO: 188).

SEQ ID NO: 200 is the predicted amino acid sequence for CT521 (SEQ ID NO: 189).

SEQ ID NO: 201 is the predicted amino acid sequence for CT544 (SEQ ID NO: 190).

SEQ ID NO: 202 is the predicted amino acid sequence for CT606 (SEQ ID NO: 194).

SEQ ID NO: 203 is the predicted amino acid sequence for CT607 (SEQ ID NO: 195).

SEQ ID NO: 204 is the predicted amino acid sequence for CT632 (SEQ ID NO: 197).

SEQ ID NO: 205 is the determined cDNA sequence for clone 25244.

SEQ ID NO: 206 is the determined cDNA sequence for clone 25245.

SEQ ID NO: 207 is the determined cDNA sequence for clone 25246.

SEQ ID NO: 208 is the determined cDNA sequence for clone 25248.

SEQ ID NO: 209 is the determined cDNA sequence for clone 25249.

SEQ ID NO: 210 is the determined cDNA sequence for clone 25250.

SEQ ID NO: 211 is the determined cDNA sequence for clone 25251.

SEQ ID NO: 212 is the determined cDNA sequence for clone 25252.

SEQ ID NO. 213 is the determined cDNA sequence for clone 25253.

SEQ ID NO: 214 is the determined cDNA sequence for clone 25254.

SEQ ID NO: 215 is the determined cDNA sequence for clone 25255.

SEQ ID NO: 216 is the determined cDNA sequence for clone 25256.

SEQ ID NO: 217 is the determined cDNA sequence for clone 25257.

SEQ ID NO: 218 is the determined cDNA sequence for clone 25259.

SEQ ID NO: 219 is the determined cDNA sequence for clone 25260.

SEQ ID NO: 220 is the determined cDNA sequence for clone 25261.

SEQ ID NO: 221 is the determined cDNA sequence for clone 25262.

SEQ ID NO: 222 is the determined cDNA sequence for clone 25263.

SEQ ID NO: 223 is the determined cDNA sequence for clone 25264.

SEQ ID NO: 224 is the determined cDNA sequence for clone 25265.

SEQ ID NO: 225 is the determined cDNA sequence for clone 25266.

SEQ ID NO: 226 is the determined cDNA sequence for clone 25267.

SEQ ID NO: 227 is the determined cDNA sequence for clone 25268.

SEQ ID NO: 228 is the determined cDNA sequence for clone 25269.

SEQ ID NO: 229 is the determined cDNA sequence for clone 25271.

SEQ ID NO: 230 is the determined cDNA sequence for clone 25272.

SEQ ID NO: 231 is the determined cDNA sequence for clone 25273.

SEQ ID NO: 232 is the determined cDNA sequence for clone 25274.

SEQ ID NO: 233 is the determined cDNA sequence for clone 25275.

SEQ ID NO: 234 is the determined cDNA sequence for clone 25276.

SEQ ID NO: 235 is the determined cDNA sequence for clone 25277.

SEQ ID NO: 236 is the determined cDNA sequence for clone 25278.

SEQ ID NO: 237 is the determined cDNA sequence for clone 25280.

SEQ ID NO: 238 is the determined cDNA sequence for clone 25281.

SEQ ID NO: 239 is the determined cDNA sequence for clone 25282.

SEQ ID NO: 240 is the determined cDNA sequence for clone 25283.

SEQ ID NO: 241 is the determined cDNA sequence for clone 25284.

SEQ ID NO: 242 is the determined cDNA sequence for clone 25285.

SEQ ID NO: 243 is the determined cDNA sequence for clone 25286.

SEQ ID NO: 244 is the determined cDNA sequence for clone 25287.

SEQ ID NO: 245 is the determined cDNA sequence for clone 25288.

SEQ ID NO: 246 is the determined cDNA sequence for clone 25289.

SEQ ID NO: 247 is the determined cDNA sequence for clone 25290.

SEQ ID NO: 248 is the determined cDNA sequence for clone 25291.

SEQ ID NO: 249 is the determined cDNA sequence for clone 25292.

SEQ ID NO: 250 is the determined cDNA sequence for clone 25293.

SEQ ID NO: 251 is the determined cDNA sequence for clone 25294.

SEQ ID NO: 252 is the determined cDNA sequence for clone 25295.

SEQ ID NO: 253 is the determined cDNA sequence for clone 25296.

SEQ ID NO: 254 is the determined cDNA sequence for clone 25297.

SEQ ID NO: 255 is the determined cDNA sequence for clone 25418.

SEQ ID NO: 256 is the determined cDNA sequence for clone 25419.

SEQ ID NO: 257 is the determined cDNA sequence for clone 25420.

SEQ ID NO: 258 is the determined cDNA sequence for clone 25421.

SEQ ID NO: 259 is the determined cDNA sequence for clone 25422.

SEQ ID NO: 260 is the determined cDNA sequence for clone 25423.

SEQ ID NO: 261 is the determined cDNA sequence for clone 25424.

SEQ ID NO: 262 is the determined cDNA sequence for clone 25426.

SEQ ID NO: 263 is the determined cDNA sequence for clone 25427.

SEQ ID NO: 264 is the determined cDNA sequence for clone 25428.

SEQ ID NO: 265 is the determined cDNA sequence for clone 25429.

SEQ ID NO: 266 is the determined cDNA sequence for clone 25430.

SEQ ID NO: 267 is the determined cDNA sequence for clone 25431.

SEQ ID NO: 268 is the determined cDNA sequence for clone 25432.

SEQ ID NO: 269 is the determined cDNA sequence for clone 25433.

SEQ ID NO: 270 is the determined cDNA sequence for clone 25434.

SEQ ID NO: 271 is the determined cDNA sequence for clone 25435.

SEQ ID NO: 272 is the determined cDNA sequence for clone 25436.

SEQ ID NO: 273 is the determined cDNA sequence for clone 25437.

SEQ ID NO: 274 is the determined cDNA sequence for clone 25438.

SEQ ID NO: 275 is the determined cDNA sequence for clone 25439.

SEQ ID NO: 276 is the determined cDNA sequence for clone 25440.

SEQ ID NO: 277 is the determined cDNA sequence for clone 25441.

SEQ ID NO: 278 is the determined cDNA sequence for clone 25442.

SEQ ID NO: 279 is the determined cDNA sequence for clone 25443.

SEQ ID NO: 280 is the determined cDNA sequence for clone 25444.

SEQ ID NO: 281 is the determined cDNA sequence for clone 25445.

SEQ ID NO: 282 is the determined cDNA sequence for clone 25446.

SEQ ID NO: 283 is the determined cDNA sequence for clone 25447.

SEQ ID NO: 284 is the determined cDNA sequence for clone 25448.

SEQ ID NO: 285 is the determined cDNA sequence for clone 25844.

SEQ ID NO: 286 is the determined cDNA sequence for clone 25845.

SEQ ID NO: 287 is the determined cDNA sequence for clone 25846.

SEQ ID NO: 288 is the determined cDNA sequence for clone 25847.

SEQ ID NO: 289 is the determined cDNA sequence for clone 25848.

SEQ ID NO: 290 is the determined cDNA sequence for clone 25850.

SEQ ID NO: 291 is the determined cDNA sequence for clone 25851.

SEQ ID NO: 292 is the determined cDNA sequence for clone 25852.

SEQ ID NO: 293 is the determined cDNA sequence for clone 25853.

SEQ ID NO: 294 is the determined cDNA sequence for clone 25854.

SEQ ID NO: 295 is the determined cDNA sequence for clone 25855.

SEQ ID NO: 296 is the determined cDNA sequence for clone 25856.

SEQ ID NO: 297 is the determined cDNA sequence for clone 25857.

SEQ ID NO: 298 is the determined cDNA sequence for clone 25858.

SEQ ID NO: 299 is the determined cDNA sequence for clone 25859.

SEQ ID NO: 300 is the determined cDNA sequence for clone 25860.

SEQ ID NO: 301 is the determined cDNA sequence for clone 25861.

SEQ ID NO: 302 is the determined cDNA sequence for clone 25862.

SEQ ID NO: 303 is the determined cDNA sequence for clone 25863.

SEQ ID NO: 304 is the determined cDNA sequence for clone 25864.

SEQ ID NO: 305 is the determined cDNA sequence for clone 25865.

SEQ ID NO: 306 is the determined cDNA sequence for clone 25866.

SEQ ID NO: 307 is the determined cDNA sequence for clone 25867.

SEQ ID NO: 308 is the determined cDNA sequence for clone 25868.

SEQ ID NO: 309 is the determined cDNA sequence for clone 25869.

SEQ ID NO: 310 is the determined cDNA sequence for clone 25870.

SEQ ID NO: 311 is the determined cDNA sequence for clone 25871.

SEQ ID NO: 312 is the determined cDNA sequence for clone 25872.

SEQ ID NO: 313 is the determined cDNA sequence for clone 25873.

SEQ ID NO: 314 is the determined cDNA sequence for clone 25875.

SEQ ID NO: 315 is the determined cDNA sequence for clone 25876.

SEQ ID NO: 316 is the determined cDNA sequence for clone 25877.

SEQ ID NO: 317 is the determined cDNA sequence for clone 25878.

SEQ ID NO: 318 is the determined cDNA sequence for clone 25879.

SEQ ID NO: 319 is the determined cDNA sequence.for clone 25880.

SEQ ID NO: 320 is the determined cDNA sequence for clone 25881.

SEQ ID NO: 321 is the determined cDNA sequence for clone 25882.

SEQ ID NO: 322 is the determined cDNA sequence for clone 25883.

SEQ ID NO: 323 is the determined cDNA sequence for clone 25884.

SEQ ID NO: 324 is the determined cDNA sequence for clone 25885.

SEQ ID NO: 325 is the determined cDNA sequence for clone 25886.

SEQ ID NO: 326 is the determined cDNA sequence for clone 25887.

SEQ ID NO: 327 is the determined cDNA sequence for clone 25888.

SEQ ID NO: 328 is the determined cDNA sequence for clone 25889.

SEQ ID NO: 329 is the determined cDNA sequence for clone 25890.

SEQ ID NO: 330 is the determined cDNA sequence for clone 25892.

SEQ ID NO: 331 is the determined cDNA sequence for clone 25894.

SEQ ID NO: 332 is the determined cDNA sequence for clone 25895.

SEQ ID NO: 333 is the determined cDNA sequence for clone 25896.

SEQ ID NO: 334 is the determined cDNA sequence for clone 25897.

SEQ ID NO: 335 is the determined cDNA sequence for clone 25899.

SEQ ID NO: 336 is the determined cDNA sequence for clone 25900.

SEQ ID NO: 337 is the determined cDNA sequence for clone 25901.

SEQ ID NO: 338 is the determined cDNA sequence for clone 25902.

SEQ ID NO: 339 is the determined cDNA sequence for clone 25903.

SEQ ID NO: 340 is the determined cDNA sequence for clone 25904.

SEQ ID NO: 341 is the determined cDNA sequence for clone 25906.

SEQ ID NO: 342 is the determined cDNA sequence for clone 25907.

SEQ ID NO: 343 is the determined cDNA sequence for clone 25908.

SEQ ID NO: 344 is the determined cDNA sequence for clone 25909.

SEQ ID NO: 345 is the determined cDNA sequence for clone 25910.

SEQ ID NO: 346 is the determined cDNA sequence for clone 25911.

SEQ ID NO: 347 is the determined cDNA sequence for clone 25912.

SEQ ID NO: 348 is the determined cDNA sequence for clone 25913.

SEQ ID NO: 349 is the determined cDNA sequence for clone 25914.

SEQ ID NO: 350 is the determined cDNA sequence for clone 25915.

SEQ ID NO: 351 is the determined cDNA sequence for clone 25916.

SEQ ID NO: 352 is the determined cDNA sequence for clone 25917.

SEQ ID NO: 353 is the determined cDNA sequence for clone 25918.

SEQ ID NO: 354 is the determined cDNA sequence for clone 25919.

SEQ ID NO: 355 is the determined cDNA sequence for clone 25920.

SEQ ID NO: 356 is the determined cDNA sequence for clone 25921.

SEQ ID NO: 357 is the determined cDNA sequence for clone 25922.

SEQ ID NO: 358 is the determined cDNA sequence for clone 25924.

SEQ ID NO: 359 is the determined cDNA sequence for clone 25925.

SEQ ID NO: 360 is the determined cDNA sequence for clone 25926.

SEQ ID NO: 356 is the determined cDNA sequence for clone 25927.

SEQ ID NO: 362 is the determined cDNA sequence for clone 25928.

SEQ ID NO: 363 is the determined cDNA sequence for clone 25929.

SEQ ID NO: 364 is the determined cDNA sequence for clone 25930.

SEQ ID NO: 365 is the determined cDNA sequence for clone 25931.

SEQ ID NO: 366 is the determined cDNA sequence for clone 25932.

SEQ ID NO: 367 is the determined cDNA sequence for clone 25933.

SEQ ID NO: 368 is the determined cDNA sequence for clone 25934.

SEQ ID NO: 369 is the determined cDNA sequence for clone 25935.

SEQ ID NO: 370 is the determined cDNA sequence for clone 25936.

SEQ ID NO: 371 is the determined cDNA sequence for clone 25939.

DETAILED DESCRIPTION OF THE INVENTION

As noted above, the present invention is generally directed to compositions and methods for the therapy and diagnosis of cancer, such as colon cancer. The compositions described herein may include colon tumor polypeptides, polynucleotides encoding such polypeptides, binding agents such as antibodies, antigen presenting cells (APCs) and/or immune system cells (e.g., T cells). Polypeptides of the present invention generally comprise at least a portion (such as an immunogenic portion) of a colon tumor protein or a variant thereof. A “colon tumor protein” is a protein that is expressed in colon tumor cells at a level that is at least two fold, and preferably at least five fold, greater than the level of expression in a normal tissue, as determined using a representative assay provided herein. Certain colon tumor proteins are tumor proteins that react detectably (within an immunoassay, such as an ELISA or Western blot) with antisera of a patient afflicted with colon cancer. Polynucleotides of the subject invention generally comprise a DNA or RNA sequence that encodes all or a portion of such a polypeptide, or that is complementary to such a sequence. Antibodies are generally immune system proteins, or antigen-binding fragments thereof, that are capable of binding to a polypeptide as described above. Antigen presenting cells include dendritic cells, macrophages, monocytes, fibroblasts and B-cells that express a polypeptide as described above. T cells that may be employed within such compositions are generally T cells that are specific for a polypeptide as described above.

The present invention is based on the discovery of human colon tumor proteins. Partial sequences of polynucleotides encoding specific tumor proteins are provided in SEQ ID NO: 1-120 and 123-371.

COLON TUMOR PROTEIN POLYNUCLEOTIDES

Any polynucleotide that encodes a colon tumor protein or a portion or other variant thereof as described herein is encompassed by the present invention. Preferred polynucleotides comprise at least 15 consecutive nucleotides, preferably at least 30 consecutive nucleotides and more preferably at least 45 consecutive nucleotides, that encode a portion of a colon tumor protein. More preferably, a polynucleotide encodes an immunogenic portion of a colon tumor protein. Polynucleotides complementary to any such sequences are also encompassed by the present invention. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA or synthetic) or RNA molecules. RNA molecules include HnRNA molecules, which contain introns and correspond to a DNA molecule in a one-to-one manner, and mRNA molecules, which do not contain introns. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide of the present invention, and a polynucleotide may, but need not, be linked to other molecules and/or support materials.

Polynucleotides may comprise a native sequence (i.e. an endogenous sequence that encodes a colon tumor protein or a portion thereof) or may comprise a variant of such a sequence. Polynucleotide variants may contain one or more substitutions, additions, deletions and/or insertions such that the immunogenicity of the encoded polypeptide is not diminished, relative to a native tumor protein. The effect on the immunogenicity of the encoded polypeptide may generally be assessed as described herein. Variants preferably exhibit at least about 70% identity, more preferably at least about 80% identity and most preferably at least about 90% identity to a polynucleotide sequence that encodes a native colon tumor protein or a portion thereof.

Two polynucleotide or polypeptide sequences are said to be “identical” if the sequence of nucleotides or amino acids in the two sequences is the same when aligned for maximum correspondence as described below. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A “comparison window” as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned

Optimal alignment of sequences for comparison may be conducted using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, Wis.), using default parameters. This program embodies several alignment schemes described in the following references: Dayhoff, M. O. (1978) A model of evolutionary change in proteins—Matrices for detecting distant relationships. In Dayhoff., M. O. (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington D.C. Vol. 5, Suppl. 3, pp. 345-358; Hemi J. (1990) Unified Approach to Alignment and Phylogenes pp. 626-645 Methods in Enzymology vol. 183, Academic Press. Inc., San Diego, Calif.; Higgins, D. G. and Sharp, P. M. (1989) CABIOS 5:151-153; Myers, E. W. and Muller W. (1988) CABIOS 4:11-17; Robinson, E. D. (1971) Comb. Theor 11:105; Santou, N. Nes, M. (1987) Mol. Biol. Evol . 4:406-425; Sneath, P. H. A. and Sokal, R. R. (1973) Numerical Taxonomy—the Principles and Practice of Numerical Taxoniomy , Freeman Press, San Francisco, Calif.; Wilbur, W. J. and Lipman, D. J. (1983) Proc. Natl. Acad., Sci. USA 80:726-730.

Preferably, the “percentage of sequence identity” is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e. gaps) of 20 percent or less, usually 5 to 15 percent, or 10 to 12 percent, as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid bases or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e. the window size) and multiplying the results by 100 to yield the percentage of sequence identity.

Variants may also, or alternatively, be substantially homologous to a native gene, or a portion or complement thereof. Such polynucleotide variants are capable of hybridizing under moderately stringent conditions to a naturally occurring DNA sequence encoding a native colon tumor protein (or a complementary sequence). Suitable moderately stringent conditions include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50° C.-65° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5× and 0.2×SSC containing 0.1% SDS.

It will be appreciated by those of ordinary skill in the art that, as a result of the degeneracy of the genetic code, there are many nucleotide sequences that encode a polypeptide as described herein. Some of these polynucleotides bear minimal homology to the nucleotide sequence of any native gene. Nonetheless, polynucleotides that vary due to differences in codon usage are specifically contemplated by the present invention. Further, alleles of the genes comprising the polynucleotide sequences provided herein are within the scope of the present invention. Alleles are endogenous genes that are altered as a result of one or more mutations, such as deletions, additions and/or substitutions of nucleotides. The resulting mRNA and protein may, but need not, have an altered structure or function. Alleles may be identified using standard techniques (such as hybridization, amplification and/or database sequence comparison).

Polynucleotides may be prepared using any of a variety of techniques. For example, a polynucleotide may be identified, as described in more detail below, by screening a microarray of cDNAs for tumor-associated expression (i.e., expression that is at least two fold greater in a colon tumor than in normal tissue, as determined using a representative assay provided herein). Such screens may be performed using a Synteni microarray (Palo Alto, Calif.) according to the manufacturer's instructions (and essentially as described by Schena et al., Proc. Natl. Acad. Sci. USA 93:10614-10619, 1996 and Heller et al., Proc. Natl. Acad. Sci. USA 94:2150-2155, 1997). Alternatively, polypeptides may be amplified from cDNA prepared from cells expressing the proteins described herein, such as colon tumor cells. Such polynucleotides may be amplified via polymerase chain reaction (PCR). For this approach, sequence-specific primers may be designed based on the sequences provided herein, and may be purchased or synthesized.

An amplified portion may be used to isolate a full length gene from a suitable library (e.g., a colon tumor cDNA library) using well known techniques. Within such techniques, a library (cDNA or genomic) is screened using one or more polynucleotide probes or primers suitable for amplification. Preferably, a library is size-selected to include larger molecules. Random primed libraries may also be preferred for identifying 5′ and upstream regions of genes. Genomic libraries are preferred for obtaining introns and extending 5′ sequences.

For hybridization techniques, a partial sequence may be labeled (e.g., by nick-translation or end-labeling with 32 P) using well known techniques. A bacterial or bacteriophage library is then screened by hybridizing filters containing denatured bacterial colonies (or lawns containing phage plaques) with the labeled probe (see Sambrook et al., Molecular Cloning: A Laboratory Manual , Cold Spring Harbor Laboratories, Cold Spring Harbor, N.Y., 1989). Hybridizing colonies or plaques are selected and expanded, and the DNA is isolated for further analysis. cDNA clones may be analyzed to determine the amount of additional sequence by, for example, PCR using a primer from the partial sequence and a primer from the vector. Restriction maps and partial sequences may be generated to identify one or more overlapping clones. The complete sequence may then be determined using standard techniques, which may involve generating a series of deletion clones. The resulting overlapping sequences are then assembled into a single contiguous sequence. A full length cDNA molecule can be generated by ligating suitable fragments, using well known techniques.

Alternatively, there are numerous amplification techniques for obtaining a full length coding sequence from a partial cDNA sequence. Within such techniques, amplification is generally performed via PCR. Any of a variety of commercially available kits may be used to perform the amplification step. Primers may be designed using, for example, software well known in the art. Primers are preferably 22-30 nucleotides in length, have a GC content of at least 50% and anneal to the target sequence at temperatures of about 68° C. to 72° C. The amplified region may be sequenced as described above, and overlapping sequences assembled into a contiguous sequence.

One such amplification technique is inverse PCR (see Triglia et al., Nucl. Acids Res . 16:8186, 1988), which uses restriction enzymes to generate a fragment in the known region of the gene. The fragment is then circularized by intramolecular ligation and used as a template for PCR with divergent primers derived from the known region. Within an alternative approach, sequences adjacent to a partial sequence may be retrieved by amplification with a primer to a linker sequence and a primer specific to a known region. The amplified sequences are typically subjected to a second round of amplification with the same linker primer and a second primer specific to the known region. A variation on this procedure, which employs two primers that initiate extension in opposite directions from the known sequence, is described in WO 96/38591. Another such technique is known as “rapid amplification of cDNA ends” or RACE This technique involves the use of an internal primer and an external primer, which hybridizes to a polyA region or vector sequence, to identify sequences that are 5′ and 3′ of a known sequence. Additional techniques include capture PCR (Lagerstrom et al., PCR Methods Applic . 1:111-19, 1991) and walking PCR (Parker et al., Nucl. Acids Res . 19:3055-60, 1991). Other methods employing amplification may also be employed to obtain a full length cDNA sequence.

In certain instances, it is possible to obtain a full length cDNA sequence by analysis of sequences provided in an expressed sequence tag (EST) database, such as that available from GenBank. Searches for overlapping ESTs may generally be performed using well known programs (e.g., NCBI BLAST searches), and such ESTs may be used to generate a contiguous full length sequence.

Certain nucleic acid sequences of cDNA molecules encoding portions of colon tumor proteins are provided in SEQ ID NO: 1-120 and 123-371. These polynucleotides were isolated from colon tumor cDNA libraries using conventional and/or PCR-based subtraction techniques, as described below.

Polynucleotide variants may generally be prepared by any method known in the art, including chemical synthesis by, for example, solid phase phosphoramidite chemical synthesis. Modifications in a polynucleotide sequence may also be introduced using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis (see Adelman et al., DNA 2:183, 1983). Alternatively, RNA molecules may be generated by in vitro or in vivo transcription of DNA sequences encoding a colon tumor protein, or portion thereof, provided that the DNA is incorporated into a vector with a suitable RNA polymerase promoter (such as T7 or SP6). Certain portions may be used to prepare an encoded polypeptide, as described herein. In addition, or alternatively, a portion may be administered to a patient such that the encoded polypeptide is generated in vivo (e.g., by transfecting antigen-presenting cells, such as dendritic cells, with a cDNA construct encoding a colon tumor polypeptide, and administering the transfected cells to the patient).

A portion of a sequence complementary to a coding sequence (i.e., an antisense polynucleotide) may also be used as a probe or to modulate gene expression. cDNA constructs that can be transcribed into antisense RNA may also be introduced into cells of tissues to facilitate the production of antisense RNA. An antisense polynucleotide may be used, as described herein, to inhibit expression of a tumor protein. Antisense technology can be used to control gene expression through triple-helix formation, which compromises the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors or regulatory molecules (see Gee et al., In Huber and Carr, Molecular and Immunologic Approaches , Futura Publishing Co. (Mt. Kisco, N.Y.; 1994)). Alternatively, an antisense molecule may be designed to hybridize with a control region of a gene (e.g., promoter, enhancer or transcription initiation site), and block transcription of the gene; or to block translation by inhibiting binding of a transcript to ribosomes.

A portion of a coding sequence, or of a complementary sequence, may also be designed as a probe or primer to detect gene expression. Probes may be labeled with a variety of reporter groups, such as radionuclides and enzymes, and are preferably at least 10 nucleotides in length, more preferably at least 20 nucleotides in length and still more preferably at least 30 nucleotides in length. Primers, as noted above, are preferably 22-30 nucleotides in length.

Any polynucleotide may be further modified to increase stability in vivo. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5′ and/or 3′ ends; the use of phosphorothioate or 2′ O-methyl rather than phosphodiesterase linkages in the backbone; and/or the inclusion of nontraditional bases such as inosine, queosine and wybutosine, as well as acetyl- methyl-, thio- and other modified forms of adenine, cytidine, guanine, thymine and uridine.

Nucleotide sequences as described herein may be joined to a variety of other nucleotide sequences using established recombinant DNA techniques. For example, a polynucleotide may be cloned into any of a variety of cloning vectors, including plasmids, phagemids, lambda phage derivatives and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors and sequencing vectors. In general, a vector will contain an origin of replication functional in at least one organism, convenient restriction endonuclease sites and one or more selectable markers. Other elements will depend upon the desired use, and will be apparent to those of ordinary skill in the art.

Within certain embodiments, polynucleotides may be formulated so as to permit entry into a cell of a mammal, and expression therein. Such formulations are particularly useful for therapeutic purposes, as described below. Those of ordinary skill in the art will appreciate that there are many ways to achieve expression of a polynucleotide in a target cell, and any suitable method may be employed. For example, a polynucleotide may be incorporated into a viral vector such as, but not limited to, adenovirus, adeno-associated virus, retrovirus, or vaccinia or other pox virus (e.g., avian pox virus). Techniques for incorporating DNA into such vectors are well known to those of ordinary skill in the art. A retroviral vector may additionally transfer or incorporate a gene for a selectable marker (to aid in the identification or selection of transduced cells) and/or a targeting moiety, such as a gene that encodes a ligand for a receptor on a specific target cell, to render the vector target specific. Targeting may also be accomplished using an antibody, by methods known to those of ordinary skill in the art.

Other formulations for therapeutic purposes include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. A preferred colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (i.e., an artificial membrane vesicle). The preparation and use of such systems is well known in the art.

COLON TUMOR POLYPEPTIDES

Within the context of the present invention, polypeptides may comprise at least an immunogenic portion of a colon tumor protein or a variant thereof, as described herein. As noted above, a “colon tumor protein” is a protein that is expressed by colon tumor cells. Proteins that are colon tumor proteins also react detectably within an immunoassay (such as an ELISA) with antisera from a patient with colon cancer. Polypeptides as described herein may be of any length. Additional sequences derived from the native protein and/or heterologous sequences may be present, and such sequences may (but need not) possess further immunogenic or antigenic properties.

An “immunogenic portion,” as used herein is a portion of a protein that is recognized (i.e., specifically bound) by a B-cell and/or T-cell surface antigen receptor. Such immunogenic portions generally comprise at least 5 amino acid residues, more preferably at least 10, and still more preferably at least 20 amino acid residues of a colon tumor protein or a variant thereof. Certain preferred immunogenic portions include peptides in which an N-terminal leader sequence and/or transmembrane domain have been deleted. Other preferred immunogenic portions may contain a small N- and/or C-terminal deletion (e.g., 1-30 amino acids, preferably 5-15 amino acids), relative to the mature protein.

Immunogenic portions may generally be identified using well known techniques, such as those summarized in Paul, Fundamental Immunology, 3rd ed., 243-247 (Raven Press, 1993) and references cited therein. Such techniques include screening polypeptides for the ability to react with antigen-specific antibodies, antisera and/or T-cell lines or clones. As used herein, antisera and antibodies are “antigten-specific” if they specifically bind to an antigen (i.e., they react with the protein in an ELISA or other immunoassay, and do not react detectably with unrelated proteins). Such antisera and antibodies may be prepared as described herein, and using well known techniques. An immunogenic portion of a native colon tumor protein is a portion that reacts with such antisera and/or T-cells at a level that is not substantially less than the reactivity of the full length polypeptide (e.g., in an ELISA and/or T-cell reactivity assay). Such immunogenic portions may react within such assays at a level that is similar to or greater than the reactivity of the full length polypeptide. Such screens may generally be performed using methods well known to those of ordinary skill in the art, such as those described in Harlow and Lane, Antibodies: A Laboratory Manual , Cold Spring Harbor Laboratory, 1988. For example, a polypeptide may be immobilized on a solid support and contacted with patient sera to allow binding of antibodies within the sera to the immobilized polypeptide. Unbound sera may then be removed and bound antibodies detected using, for example, 125 I-labeled Protein A.

As noted above, a composition may comprise a variant of a native colon tumor protein. A polypeptide “variant,” as used herein, is a polypeptide that differs from a native colon tumor protein in one or more substitutions, deletions, additions and/or insertions, such that the immunogenicity of the polypeptide is not substantially diminished. In other words, the ability of a variant to react with antigen-specific antisera may be enhanced or unchanged, relative to the native protein, or may be diminished by less than 50%, and preferably less than 20%, relative to the native protein. Such variants may generally be identified by modifying one of the above polypeptide sequences and evaluating the reactivity of the modified polypeptide with antigen-specific antibodies or antisera as described herein. Preferred variants include those in which one or more portions, such as an N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include variants in which a small portion (e.g., 1-30 amino acids, preferably 5-15 amino acids) has been removed from the N- and/or C-terminal of the mature protein.

Polypeptide variants preferably exhibit at least about 70%, more preferably at least about 90% and most preferably at least about 95% identity (determined as described above) to the identified polypeptides.

Preferably, a variant contains conservative substitutions. A “conservative substitution” is one in which an amino acid is substituted for another amino acid that has similar properties such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. Amino acid substitutions may generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the residues. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophilicity values include leucine, isoleucine and valine; glycine and alanine; asparagine and glutamine, and serine, threonine, phenylalanine and tyrosine. Other groups of amino acids that may represent conservative changes include: (1) ala, pro, gly, glu, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his. A variant may also, or alternatively, contain non-conservative changes. In a preferred embodiment, variant polypeptides differ from a native sequence by substitution, deletion or addition of five amino acids or fewer. Variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the immunogenicity, secondary structure and hydropathic nature of the polypeptide.

As noted above, polypeptides may comprise a signal (or leader) sequence at the N-terminal end of the protein which co-translationally or post-translationally directs transfer of the protein. The polypeptide may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region.

Polypeptides may be prepared using any of a variety of well known techniques. Recombinant polypeptides encoded by DNA sequences as described above may be readily prepared from the DNA sequences using any of a variety of expression vectors known to those of ordinary skill in the art. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a DNA molecule that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are E. coli , yeast or a mammalian cell line such as COS or CHO. Supernatants from suitable host/vector systems which secrete recombinant protein or polypeptide into culture media may be first concentrated using a commercially available filter. Following concentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombinant polypeptide.

Portions and other variants having fewer than about 100 amino acids, and generally fewer than about 50 amino acids, may also be generated by synthetic means, using techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Merrifield solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain. See Merrifield, J. Am. Chem. Soc . 85:2149-2146, 1963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Perkin Elmer/Applied BioSystems Division (Foster City, Calif.), and may be operated according to the manufacturer's instructions.

Within certain specific embodiments, a polypeptide may be a fusion protein that comprises multiple polypeptides as described herein, or that comprises at least one polypeptide as described herein and an unrelated sequence, such as a known tumor protein. A fusion partner may, for example, assist in providing T helper epitopes (an immunological fusion partner), preferably T helper epitopes recognized by humans, or may assist in expressing the protein (an expression enhancer) at higher yields than the native recombinant protein. Certain preferred fusion partners are both immunological and expression enhancing fusion partners. Other fusion partners may be selected so as to increase the solubility of the protein or to enable the protein to be targeted to desired intracellular compartments. Still further fusion partners include affinity tags, which facilitate purification of the protein.

Fusion proteins may generally be prepared using standard techniques, including chemical conjugation. Preferably, a fusion protein is expressed as a recombinant protein, allowing the production of increased levels relative to a non-fused protein, in an expression system. Briefly, DNA sequences encoding the polypeptide components may be assembled separately, and ligated into an appropriate expression vector. The 3′ end of the DNA sequence encoding one polypeptide component is ligated, with or without a peptide linker, to the 5′ end of a DNA sequence encoding the second polypeptide component so that the reading frames of the sequences are in phase. This permits translation into a single fusion protein that retains the biological activity of both component polypeptides.

A peptide linker sequence may be employed to separate the first and the second polypeptide components by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. Such a peptide linker sequence is incorporated into the fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be chosen based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) their inability to adopt a secondary structure that could interact with functional epitopes on the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes. Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used in the linker sequence. Amino acid sequences which may be usefully employed as linkers include those disclosed in Maratea et al., Gene 40:39-46, 1985, Murphy et al., Proc. Natl Acad. Sci. USA 83:8258-8262, 1986; U.S. Pat. No. 4,935,233 and U.S. Pat. No. 4,751,180. The linker sequence may generally be from 1 to about 50 amino acids in length. Linker sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate the functional domains and prevent steric interference.

The ligated DNA sequences are operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for expression of DNA are located only 5′ to the DNA sequence encoding the first polypeptides. Similarly, stop codons required to end translation and transcription termination signals are only present 3′ to the DNA sequence encoding the second polypeptide.

Fusion proteins are also provided that comprise a polypeptide of the present invention together with an unrelated immunogenic protein. Preferably the immunogenic protein is capable of eliciting a recall response. Examples of such proteins include tetanus, tuberculosis and hepatitis proteins (see, for example, Stoute et al. New Engl. J. Med ., 336:86-91, 1997).

Within preferred embodiments, an immunological fusion partner is derived from protein D, a surface protein of the gram-negative bacterium Haemophilus influenza B (WO 91/18926). Preferably, a protein D derivative comprises approximately the first third of the protein (e.g., the first N-terminal 100-110 amino acids), and a protein D derivative may be lipidated. Within certain preferred embodiments, the first 109 residues of a Lipoprotein D fusion partner is included on the N-terminus to provide the polypeptide with additional exogenous T-cell epitopes and to increase the expression level in E. coli (thus functioning as an expression enhancer). The lipid tail ensures optimal presentation of the antigen to antigen presenting cells. Other fusion partners include the non-structural protein from influenzae virus, NS1 (hemaglutinin). Typically, the N-terminal 81 amino acids are used, although different fragments that include T-helper epitopes may be used.

In another embodiment, the immunological fusion partner is the protein known as LYTA, or a portion thereof (preferably a C-terminal portion). LYTA is derived from Streptococcus pneumoniae , which synthesizes an N-acetyl-L-alanine amidase known as amidase LYTA (encoded by the LytA gene; Gene 43:265-292, 1986). LYTA is an autolysin that specifically degrades certain bonds in the peptidoglycan backbone. The C-terminal domain of the LYTA protein is responsible for the affinity to the choline or to some choline analogues such as DEAE. This property has been exploited for the development of E coli C-LYTA expressing plasmids useful for expression of fusion proteins. Purification of hybrid proteins containing the C-LYTA fragment at the amino terminus has been described (see Biotechnology 10:795-798, 1992). Within a preferred embodiment, a repeat portion of LYTA may be incorporated into a fusion protein. A repeat portion is found in the C-terminal region starting at residue 178. A particularly preferred repeat portion incorporates residues 188-305.

In general, polypeptides (including fusion proteins) and polynucleotides as described herein are isolated. An “isolated” polypeptide or polynucleotide is one that is removed from its original environment. For example, a naturally-occurring protein is isolated if it is separated from some or all of the coexisting materials in the natural system. Preferably, such polypeptides are at least about 90% pure, more preferably at least about 95% pure and most preferably at least about 99% pure. A polynucleotide is considered to be isolated if, for example, it is cloned into a vector that is not a part of the natural environment.

BINDING AGENTS

The present invention further provides agents, such as antibodies and antigen-binding fragments thereof, that specifically bind to a colon tumor protein. As used herein, an antibody, or antigen-binding fragment thereof, is said to “specifically bind” to a colon tumor protein if it reacts at a detectable level (within, for example, an ELISA) with a colon tumor protein, and does not react detectably with unrelated proteins under similar conditions. As used herein, “binding” refers to a noncovalent association between two separate molecules such that a complex is formed. The ability to bind may be evaluated by, for example, determining a binding constant for the formation of the complex. The binding constant is the value obtained when the concentration of the complex is divided by the product of the component concentrations. In general, two compounds are said to “bind,” in the context of the present invention, when the binding constant for complex formation exceeds about 10 3 L/mol. The binding constant may be determined using methods well known in the art.

Binding agents may be further capable of differentiating between patients with and without a cancer, such as colon cancer, using the representative assays provided herein. In other words, antibodies or other binding agents that bind to a colon tumor protein will generate a signal indicating the presence of a cancer in at least about 20% of patients with the disease, and will generate a negative signal indicating the absence of the disease in at least about 90% of individuals without the cancer. To determine whether a binding agent satisfies this requirement, biological samples (e.g., blood, sera, sputum, urine and/or tumor biopsies) from patients with and without a cancer (as determined using standard clinical tests) may be assayed as described herein for the presence of polypeptides that bind to the binding agent. It will be apparent that a statistically significant number of samples with and without the disease should be assayed. Each binding agent should satisfy the above criteria; however, those of ordinary skill in the art will recognize that binding agents may be used in combination to improve sensitivity.

Any agent that satisfies the above requirements may be a binding agent. For example, a binding agent may be a ribosome, with or without a peptide component, an RNA molecule or a polypeptide. In a preferred embodiment, a binding agent is an antibody or an antigen-binding fragment thereof Antibodies may be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, e.g. Harlow and Lane, Antibodies: A Laboratory Manual , Cold Spring Harbor Laboratory, 1988. In general, antibodies can be produced by cell culture techniques, including the generation of monoclonal antibodies as described herein, or via transfection of antibody genes into suitable bacterial or mammalian cell hosts, in order to allow for the production of recombinant antibodies. In one technique, an immunogen comprising the polypeptide is initially injected into any of a wide variety of mammals (e.g., mice, rats, rabbits, sheep or goats). In this step, the polypeptides of this invention may serve as the immunogen without modification. Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably according to a predetermined schedule incorporating one or more booster immunizations, and the animals are bled periodically. Polyclonal antibodies specific for the polypeptide may then be purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support.

Monoclonal antibodies specific for an antigenic polypeptide of interest may be prepared, for example, using the technique of Kohler and Milstein, Eur. J. Immunol. 6:511-519, 1976, and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (i.e., reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and their culture supernatants tested for binding activity against the polypeptide. Hybridomas having high reactivity and specificity are preferred.

Monoclonal antibodies may be isolated from the supernatants of growing hybridoma colonies. In addition, various techniques may be employed to enhance the yield, such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the blood. Contaminants may be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography step.

Within certain embodiments, the use of antigen-binding fragments of antibodies may be preferred. Such fragments include Fab fragments, which may be prepared using standard techniques. Briefly, immunoglobulins may be purified from rabbit serum by affinity chromatography on Protein A bead columns (Harlow and Lane, Antibodies: A Laboratory Manual , Cold Spring Harbor Laboratory, 1988) and digested by papain to yield Fab and Fc fragments. The Fab and Fc fragments may be separated by affinity chromatography on protein A bead columns.

Monoclonal antibodies of the present invention may be coupled to one or more therapeutic agents. Suitable agents in this regard include radionuclides, differentiation inducers, drugs, toxins, and derivatives thereof. Preferred radionuclides include 90 Y, 123 I, 125 I, 131 I, 186 Re, 188 Re, 221 At, and 212 Bi. Preferred drugs include methotrexate, and pyrimidine and purine analogs. Preferred differentiation inducers include phorbol esters and butyric acid. Preferred toxins include ricin, abrin, diptheria toxin, cholera toxin, gelonin, Pseudomonas exotoxin, Shigella toxin, and pokeweed antiviral protein.

A therapeutic agent may be coupled (e.g., covalently bonded) to a suitable monoclonal antibody either directly or indirectly (e.g., via a linker group). A direct reaction between an agent and an antibody is possible when each possesses a substituent capable of reacting with the other. For example, a nucleophilic group, such as an amino or sulfhydryl group, on one may be capable of reacting with a carbonyl-containing group, such as an anhydride or an acid halide, or with an alkyl group containing a good leaving group (e.g., a halide) on the other.

Alternatively, it may be desirable to couple a therapeutic agent and an antibody via a linker group. A linker group can function as a spacer to distance an antibody from an agent in order to avoid interference with binding capabilities. A linker group can also serve to increase the chemical reactivity of a substituent on an agent or an antibody, and thus increase the coupling efficiency. An increase in chemical reactivity may also facilitate the use of agents, or functional groups on agents, which otherwise would not be possible.

It will be evident to those skilled in the art that a variety of bifunctional or polyfunctional reagents, both homo- and hetero-functional (such as those described in the catalog of the Pierce Chemical Co., Rockford, Ill.), may be employed as the linker group. Coupling may be effected, for example, through amino groups, carboxyl groups, sulfhydryl groups or oxidized carbohydrate residues. There are numerous references describing such methodology, e.g., U.S. Pat. No. 4,671,958, to Rodwell et al.

Where a therapeutic agent is more potent when free from the antibody portion of the immunoconjugates of the present invention, it may be desirable to use a linker group which is cleavable during or upon internalization into a cell. A number of different cleavable linker groups have been described. The mechanisms for the intracellular release of an agent from these linker groups include cleavage by reduction of a disulfide bond (e.g., U.S. Pat. No. 4,489,710, to Spitler), by irradiation of a photolabile bond (e.g., U.S. Pat. No. 4,625,014, to Senter et al.), by hydrolysis of derivatized amino acid side chains (e.g., U.S. Pat. No. 4,638,045, to Kohn et al.), by serum complement-mediated hydrolysis (e.g., U.S. Pat. No. 4,671,958, to Rodwell et al.), and acid-catalyzed hydrolysis (e.g., U.S. Pat. No. 4,569,789, to Blattler et al.).

It may be desirable to couple more than one agent to an antibody. In one embodiment, multiple molecules of an agent are coupled to one antibody molecule. In another embodiment, more than one type of agent may be coupled to one antibody. Regardless of the particular embodiment, immunoconjugates with more than one agent may be prepared in a variety of ways. For example, more than one agent may be coupled directly to an antibody molecule, or linkers which provide multiple sites for attachment can be used. Alternatively, a carrier can be used.

A carrier may bear the agents in a variety of ways, including covalent bonding either directly or via a linker group. Suitable carriers include proteins such as albumins (e.g., U.S. Pat. No. 4,507,234, to Kato et al.), peptides and polysaccharides such as aminodextran (e.g., U.S. Pat. No. 4,699,784, to Shih et al.). A carrier may also bear an agent by noncovalent bonding or by encapsulation, such as within a liposome vesicle (e.g., U.S. Pat. Nos. 4,429,008 and 4,873,088). Carriers specific for radionuclide agents include radiohalogenated small molecules and chelating compounds. For example, U.S. Pat. No. 4,735,792 discloses representative radiohalogenated small molecules and their synthesis. A radionuclide chelate may be formed from chelating compounds that include those containing nitrogen and sulfur atoms as the donor atoms for binding the metal, or metal oxide, radionuclide. For example, U.S. Pat. No. 4,673,562, to Davison et al discloses representative chelating compounds and their synthesis.

A variety of routes of administration for the antibodies and immunoconjugates may be used. Typically, administration will be intravenous, intramuscular, subcutaneous or in the bed of a resected tumor. It will be evident that the precise dose of the antibody/immunoconjugate will vary depending upon the antibody used, the antigen density on the tumor, and the rate of clearance of the antibody.

T CELLS

Immunotherapeutic compositions may also, or alternatively, comprise T cells specific for a colon tumor protein. Such cells may generally be prepared in vitro or ex vivo, using standard procedures. For example, T cells may be isolated from bone marrow, peripheral blood, or a fraction of bone marrow or peripheral blood of a patient, using a commercially available cell separation system, such as the ISOLEX™ system, available from Nexell Therapeutics Inc., Irvine, Calif. Alternatively, T cells may be derived from related or unrelated humans, non-human mammals, cell lines or cultures.

T cells may be stimulated with a colon tumor polypeptide, polynucleotide encoding a colon tumor polypeptide and/or an antigen presenting cell (APC) that expresses such a polypeptide. Such stimulation is performed under conditions and for a time sufficient to permit the generation of T cells that are specific for the polypeptide. Preferably, a colon tumor polypeptide or polynucleotide is present within a delivery vehicle, such as a microsphere, to facilitate the generation of specific T cells.

T cells are considered to be specific for a colon tumor polypeptide if the T cells kill target cells coated with the polypeptide or expressing a gene encoding the polypeptide. T cell specificity may be evaluated using any of a variety of standard techniques. For example, within a chromium release assay or proliferation assay, a stimulation index of more than two fold increase in lysis and/or proliferation, compared to negative controls, indicates T cell specificity. Such assays may be performed, for example, as described in Chen et al., Cancer Res .. 54:1065-1070, 1994. Alternatively, detection of the proliferation of T cells may be accomplished by a variety of known techniques. For example, T cell proliferation can be detected by measuring an increased rate of DNA synthesis (e.g., by pulse-labeling cultures of T cells with tritiated thymidine and measuring the amount of tritiated thymidine incorporated into DNA). Contact with a colon tumor polypeptide (100 ng/ml-100 μg/ml, preferably 200 ng/ml-25 μg/ml) for 3-7 days should result in at least a two fold increase in proliferation of the T cells. Contact as described above for 2-3 hours should result in activation of the T cells, as measured using standard cytokine assays in which a two fold increase in the level of cytokine release (e.g., TNF or IFN-γ) is indicative of T cell activation (see Coligan et al., Current Protocols in Immunology, vol. 1, Wiley Interscience (Greene 1998)). T cells that have been activated in response to a colon tumor polypeptide, polynucleotide or polypeptide-expressing APC may be CD4 + and/or CD8 + . Colon tumor protein-specific T cells may be expanded using standard techniques. Within preferred embodiments, the T cells are derived from either a patient or a related, or unrelated, donor and are administered to the patient following stimulation and expansion.

For therapeutic purposes, CD4 + or CD8 + T cells that proliferate in response to a colon tumor polypeptide, polynucleotide or APC can be expanded in number either in vitro or in vivo. Proliferation of such T cells in vitro may be accomplished in a variety of ways. For example, the T cells can be re-exposed to a colon tumor polypeptide, or a short peptide corresponding to an immunogenic portion of such a polypeptide, with or without the addition of T cell growth factors, such as interleukin-2, and/or stimulator cells that synthesize a colon tumor polypeptide. Alternatively, one or more T cells that proliferate in the presence of a colon tumor protein can be expanded in number by cloning. Methods for cloning cells are well known in the art, and include limiting dilution.

PHARMACEUTICAL COMPOSITIONS AND VACCINES

Within certain aspects, polypeptides, polynucleotides, T cells and/or binding agents disclosed herein may be incorporated into pharmaceutical compositions or immunogenic compositions (i.e., vaccines). Pharmaceutical compositions comprise one or more such compounds and a physiologically acceptable carrier. Vaccines may comprise one or more such compounds and a non-specific immune response enhancer. A ion-specific immune response enhancer may be any substance that enhances an immune response to an exogenous antigen. Examples of non-specific immune response enhancers include adjuvants, biodegradable microspheres (e.g., polylactic galactide) and liposomes (into which the compound is incorporated, see e.g. Fullerton, U.S. Pat. No. 4,235,877). Vaccine preparation is generally described in, for example, M. F. Powell and M. J. Newman, eds., “Vaccine Design (the subunit and adjuvant approach),” Plenum Press (NY, 1995). Pharmaceutical compositions and vaccines within the scope of the present invention may also contain other compounds, which may be biologically active or inactive. For example, one or more immunogenic portions of other tumor antigens may be present, either incorporated into a fusion polypeptide or as a separate compound, within the composition or vaccine.

A pharmaceutical composition or vaccine may contain DNA encoding one or more of the polypeptides as described above, such that the polypeptide is generated in situ. As noted above, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Numerous gene delivery techniques are well known in the art, such as those described by Rolland, Crit. Rev. Therap. Drug Carrier Systems 15:143-198, 1998, and references cited therein. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface or secretes such an epitope. In a preferred embodiment, the DNA may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective), replication competent virus. Suitable systems are disclosed, for example, in Fisher-Hoch et al., Proc. Natl. Acad. Sci. USA 86:317-321, 1989; Flexner et al., Ann. N.Y. Acad. Sci . 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990; U.S. Pat. Nos. 4,603,112, 4,769,330, and 5,017,487, WO 89/01973; U.S. Pat. No. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805, Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls et al., Proc. Natl. Acad. Sci. USA 91:215-219, 1994; Kass-Eisler et al., Proc. Natl. Acad. Sci. USA 90:11498-11502, 1993; Guzman et al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res . 73:1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA may also be “naked,” as described, for example, in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.

While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. Compositions of the present invention may be formulated for any appropriate manner of administration, including for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous or intramuscular administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres (e.g., polylactate polyglycolate) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. Nos. 4,897,268 and 5,075,109.

Such compositions may also comprise buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, chelating agents such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide) and/or preservatives. Alternatively, compositions of the present invention may be formulated as a lyophilizate. Compounds may also be encapsulated within liposomes using well known technology.

Any of a variety of non-specific immune response enhancers may be employed in the vaccines of this invention. For example, an adjuvant may be included. Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, Mich.); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, N.J.); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2, -7, or -12, may also be used as adjuvants.

Within the vaccines provided herein, the adjuvant composition is preferably designed to induce an immune response predominantly of the Th1 type. High levels of Th1-type-cytokines (e.g., IFN-γ, IL-2 and IL-12) tend to favor the induction of cell mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines (e.g., IL-4, IL-5, IL-6, IL-10 and TNF-β) tend to favor the induction of humoral immune responses. Following application of a vaccine as provided herein, a patient will support an immune response that includes Th1- and Th2-type responses. Within a preferred embodiment, in which a response is predominantly Th1-type, the level of Th1-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines may be readily assessed using standard assays. For a review of the families of cytokines, see Mosmann and Coffman, Ann. Rev. Immunol . 7:145-173, 1989.

Preferred adjuvants for use in eliciting a predominantly Th1-type response include, for example, a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A (3D-MPL), together with an aluminum salt. MPL adjuvants are available from Ribi ImmunoChem Research Inc. (Hamilton, Mont.) (see U.S. Pat. Nos. 4,436,727; 4,877,611; 4,866,034 and 4,912,094). CpG-containing oligonucleotides (in which the CpG dinucleotide is unmethylated) also induce a predominantly Th1 response. Such oligonucleotides are well known and are described, for example, in WO 96/02555. Another preferred adjuvant is a saponin, preferably QS21, which may be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the combination of QS21 and 3D-MPL as described in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol, as described in WO 96/3373.9. Other preferred formulations comprises an oil-in-water emulsion and tocopherol. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil-in-water emulsion is described in WO 95/17210. Any vaccine provided herein may be prepared using well known methods that result in a combination of antigen, immune response enhancer and a suitable carrier or excipient.

The compositions described herein may be administered as part of a sustained release formulation (i.e., a formulation such as a capsule or sponge that effects a slow release of compound following administration). Such formulations may generally be prepared using well known technology and administered by, for example, oral, rectal or subcutaneous implantation, or by implantation at the desired target site. Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling membrane. Carriers for use within such formulations are biocompatible, and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release. The amount of active compound contained within a sustained release formulation depends upon the site of implantation, the rate and expected duration of release and the nature of the condition to be treated or prevented.

Any of a variety of delivery vehicles may be employed within pharmaceutical compositions and vaccines to facilitate production of an antigen-specific immune response that targets tumor cells. Delivery vehicles include antigen presenting cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells that may be engineered to be efficient APCs. Such cells may, but need not, be genetically modified to increase the capacity for presenting the antigen, to improve activation and/or maintenance of the T cell response, to have anti-tumor effects per se and/or to be immunologically compatible with the receiver (i.e., matched HLA haplotype). APCs may generally be isolated from any of a variety of biological fluids and organs, including tumor and peritumoral tissues, and may be autologous, allogeneic, syngeneic or xenogeneic cells.

Certain preferred embodiments of the present invention use dendritic cells or progenitors thereof as antigen-presenting cells. Dendritic cells are highly potent APCs (Banchereau and Steinman, Nature 392:245-251 1998) and have been shown to be effective as a physiological adjuvant for eliciting prophylactic or therapeutic antitumor immunity (see Timmerman and Levy, Ann. Rev. Med . 50:507-529, 1999). In general, dendritic cells may be identified based on their typical shape (stellate in situ, with marked cytoplasmic processes (dendrites) visible in vitro) and based on the lack of differentiation markers of B cells (CD19 and CD20), T cells (CD3), monocytes (CD14) and natural-killer cells (CD56), as determined using standard assays. Dendritic cells may, of course, be engineered to express specific cell-surface receptors or ligands that are not commonly found on dendritic cells in vivo or ex vivo, and such modified dendritic cells are contemplated by the present invention. As an alternative to dendritic cells, secreted vesicles antigen-loaded dendritic cells (called exosomes) may be used within a vaccine (see Zitvogel et al., Nature Med . 4:594-600, 1998).

Dendritic cells and progenitors may be obtained from peripheral blood, bone marrow, tumor-infiltrating cells, peritumoral tissues-infiltrating cells, lymph nodes, spleen, skin, umbilical cord blood or any other suitable tissue or fluid. For example, dendritic cells may be differentiated ex vivo by adding a combination of cytokines such as GM-CSF, IL-4, IL-13 and/or TNFα to cultures of monocytes harvested from peripheral blood. Alternatively, CD34 positive cells harvested from peripheral blood, umbilical cord blood or bone marrow may be differentiated into dendritic cells by adding to the culture medium combinations of GM-CSF, IL-3, TNFα, CD40 ligand, LPS, flt3 ligand and/or other compound(s) that induce maturation and proliferation of dendritic cells.

Dendritic cells are conveniently categorized as “immature” and “mature” cells, which allows a simple way to discriminate between two well characterized phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as APC with a high capacity for antigen uptake and processing, which correlates with the high expression of Fcγ receptor, mannose receptor and DEC-205 marker. The mature phenotype is typically characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules (e.g., CD54 and CD11) and costimulatory molecules (e.g., CD40, CD80 and CD86).

APCs may generally be transfected with a polynucleotide encoding a colon tumor protein (or portion or other variant thereof) such that the colon tumor polypeptide, or an immunogenic portion thereof, is expressed on the cell surface. Such transfection may take place ex vivo, and a composition or vaccine comprising-such transfected cells may then be is used for therapeutic purposes, as described herein. Alternatively, a gene delivery vehicle that targets a dendritic or other antigen presenting cell may be administered to a patient, resulting in transfection that occurs in vivo. In vivo and ex vivo transfection of dendritic cells, for example, may generally be performed using any methods known in the art, such as those described in WO 97/24447, or the gene gun approach described by Mahvi et al., Immunology and cell Biology 75:456-460, 1997. Antigen loading of dendritic cells may be achieved by incubating dendritic cells or progenitor cells with the colon tumor polypeptide, DNA (naked or within a plasmid vector) or RNA, or with antigen-expressing recombinant bacterium or viruses (e.g., vaccinia, fowlpox, adenovirus or lentivirus vectors). Prior to loading, the polypeptide may be covalently conjugated to an immunological partner that provides T cell help (e.g., a carrier molecule). Alternatively, a dendritic cell may be pulsed with a non-conjugated immunological partner, separately or in the presence of the polypeptide.

CANCER THERAPY

In further aspects of the present invention, the compositions described herein may be used for immunotherapy of cancer, such as colon cancer. Within such methods, pharmaceutical compositions and vaccines are typically administered to a patient. As used herein, a “patient” refers to any warm-blooded animal, preferably a human. A patient may or may not be afflicted with cancer. Accordingly, the above pharmaceutical compositions and vaccines may be used to prevent the development of a cancer or to treat a patient afflicted with a cancer. A cancer may be diagnosed using criteria generally accepted in the art, including the presence of a malignant tumor. Pharmaceutical compositions and vaccines may be administered either prior to or following surgical removal of primary tumors and/or treatment such as administration of radiotherapy or conventional chemotherapeutic drugs.

Within certain embodiments, immunotherapy may be active immunotherapy, in which treatment relies on the in vivo stimulation of the endogenous host immune system to react against tumors with the administration of immune response-modifying agents (such as polypeptides and polynucleotides disclosed herein).

Within other embodiments, immunotherapy may be passive immunotherapy, in which treatment involves the delivery of agents with established tumor-immune reactivity (such as effector cells or antibodies) that can directly or indirectly mediate antitumor effects and does not necessarily depend on an intact host immune-system. Examples of effector cells include T cells as discussed above, T lymphocytes (such as CD8 − cytotoxic T lymphocytes and CD4 + T-helper tumor-infiltrating lymphocytes), killer cells (such as Natural Killer cells and lymphokine-activated killer cells), B cells and antigen-presenting cells (such as dendritic cells and macrophages) expressing a polypeptide provided herein. T cell receptors and antibody receptors specific for the polypeptides recited herein may be cloned, expressed and transferred into other vectors or effector cells for adoptive immunotherapy. The polypeptides provided herein may also be used to generate antibodies or anti-idiotypic antibodies (as described above and in U.S. Pat. No. 4,918,164) for passive immunotherapy.

Effector cells may generally be obtained in sufficient quantities for adoptive immunotherapy by growth in vitro, as described herein. Culture conditions for expanding single antigen-specific effector cells to several billion in number with retention of antigen recognition in vivo are well known in the art. Such in vitro culture conditions typically use intermittent stimulation with antigen, often in the presence of cytokines (such as IL-2) and non-dividing feeder cells. As noted above, immunoreactive polypeptides as provided herein may be used to rapidly expand antigen-specific T cell cultures in order to generate a sufficient number of cells for immunotherapy. In particular, antigen-presenting cells, such as dendritic, macrophage, monocyte, fibroblast or B cells, may be pulsed with immunoreactive polypeptides or transfected with one or more polynucleotides using standard techniques well known in the art. For example, antigen-presenting cells can be transfected with a polynucleotide having a promoter appropriate for increasing expression in a recombinant virus or other expression system. Cultured effector cells for use in therapy must be able to grow and distribute widely, and to survive long term in vivo. Studies have shown that cultured effector cells can be induced to grow in vivo and to survive long term in substantial numbers by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever et al., Immunological Reviews 15:177, 1997).

Alternatively, a vector expressing a polypeptide recited herein may be introduced into antigen presenting cells taken from a patient and clonally propagated ex vivo for transplant back into the same patient. Transfected cells may be reintroduced into the patient using any means known in the art, preferably in sterile form by intravenous, intracavitary, intraperitoneal or intratumor administration.

Routes and frequency of administration of the therapeutic compositions disclosed herein, as well as dosage, will vary from individual to individual, and may be readily established using standard techniques. In general, the pharmaceutical compositions and vaccines may be administered by injection (e.g., intracutaneous, intramuscular, intravenous or subcutaneous), intranasally (e.g., by aspiration) or orally. Preferably, between 1 and 10 doses may be administered over a 52 week period. Preferably, 6 doses are administered, at intervals of 1 month, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of a compound that, when administered as described above, is capable of promoting an anti-tumor immune response, and is at least 10-50% above the basal (i.e., untreated) level. Such response can be monitored by measuring the anti-tumor antibodies in a patient or by vaccine-dependent generation of cytolytic effector cells capable of killing the patient's tumor cells in vitro. Such vaccines should also be capable of causing an immune response that leads to an improved clinical outcome (e.g., more frequent remissions, complete or partial or longer disease-free survival) in vaccinated patients as compared to non-vaccinated patients. In general, for pharmaceutical compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide present in a dose ranges from about 100 μg to 5 mg per kg of host. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.1 mL to about 5 mL.

In general, an appropriate dosage and treatment regimen provides the active compound(s) in an amount sufficient to provide therapeutic and/or prophylactic benefit. Such a response can be monitored by establishing an improved clinical outcome (e.g., more frequent remissions, complete or partial, or longer disease-free survival) in treated patients as compared to non-treated patients. Increases in preexisting immune responses to a colon tumor protein generally correlate with an improved clinical outcome. Such immune responses may generally be evaluated using standard proliferation, cytotoxicity or cytokine assays, which may be performed using samples obtained from a patient before and after treatment.

METHODS FOR DETECTING CANCER

In general, a cancer may be detected in a patient based on the presence of one or more colon tumor proteins and/or polynucleotides encoding such proteins in a biological sample (for example, blood, sera, sputum, urine and/or tumor biopsies) obtained from the patient. In other words, such proteins may be used as markers to indicate the presence or absence of a cancer such as colon cancer. In addition, such proteins may be useful for the detection of other cancers. The binding agents provided herein generally permit detection of the level of antigen that binds to the agent in the biological sample. Polynucleotide primers and probes may be used to detect the level of mRNA encoding a tumor protein, which is also indicative of the presence or absence of a cancer. In general, a colon tumor sequence should be present at a level that is at least three fold higher in tumor tissue than in normal tissue There are a variety of assay formats known to those of ordinary skill in the art for using a binding agent to detect polypeptide markers in a sample. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual , Cold Spring Harbor Laboratory, 1988. In general, the presence or absence of a cancer in a patient may be determined by (a) contacting a biological sample obtained from a patient with a binding agent; (b) detecting in the sample a level of polypeptide that binds to the binding agent; and (c) comparing the level of polypeptide with a predetermined cut-off value.

In a preferred embodiment, the assay involves the use of binding agent immobilized on a solid support to bind to and remove the polypeptide from the remainder of the sample. The bound polypeptide may then be detected using a detection reagent that contains a reporter group and specifically binds to the binding agent/polypeptide complex. Such detection reagents may comprise, for example, a binding agent that specifically binds to the polypeptide or an antibody or other agent that specifically binds to the binding agent, such as an anti-immunoglobulin, protein G, protein A or a lectin. Alternatively, a competitive assay may be utilized, in which a polypeptide is labeled with a reporter group and allowed to bind to the immobilized binding agent after incubation of the binding agent with the sample. The extent to which components of the sample inhibit the binding of the labeled polypeptide to the binding agent is indicative of the reactivity of the sample with the immobilized binding agent. Suitable polypeptides for use within such assays include full length colon tumor proteins and portions thereof to which the binding agent binds, as described above.

The solid support may be any material known to those of ordinary skill in the art to which the tumor protein may be attached. For example, the solid support may be a test well in a microtiter plate or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S. Pat. No. 5,359,681. The binding agent may be immobilized on the solid support using a variety of techniques known to those of skill in the art, which are amply described in the patent and scientific literature. In the context of the present invention, the term “immobilization” refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the agent and functional groups on the support or may be a linkage by way of a cross-linking agent). Immobilization by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the binding agent, in a suitable buffer, with the solid support for a suitable amount of time. The contact time varies with temperature, but is typically between about 1 hour and about 1 day. In general, contacting a well of a plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of binding agent ranging from about 10 ng to about 10 μg, and preferably about 100 ng to about 1 μg, is sufficient to immobilize an adequate amount of binding agent.

Covalent attachment of binding agent to a solid support may generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the binding agent. For example, the binding agent may be covalently attached to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the binding partner (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at A12-A13).

In certain embodiments, the assay is a two-antibody sandwich assay. This assay may be performed by first contacting an antibody that has been immobilized on a solid support, commonly the well of a microtiter plate, with the sample, such that polypeptides within the sample are allowed to bind to the immobilized antibody. Unbound sample is then removed from the immobilized polypeptide-antibody complexes and a detection reagent (preferably a second antibody capable of binding to a.different site on the polypeptide) containing a reporter.group is added. The amount of detection reagent that remains bound to the solid support is then determined using a method appropriate for the specific reporter group.

More specifically, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked. Any suitable blocking agent known to those of ordinary skill in the art, such as bovine serum albumin or Tween 20™ (Sigma Chemical Co., St. Louis, Mo.). The immobilized antibody is then incubated with the sample, and polypeptide is allowed to bind to the antibody. The sample may be diluted with a suitable diluent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time (i.e., incubation time) is a period of time that is sufficient to detect the presence of polypeptide within a sample obtained from an individual with colon cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least about 95% of that achieved at equilibrium between bound and unbound polypeptide. Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.

Unbound sample may then be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1% Tween 20™. The second antibody, which contains a reporter group, may then be added to the solid support. Preferred reporter groups include those groups recited above.

The detection reagent is then incubated with the immobilized antibody-polypeptide complex for an amount of time sufficient to detect the bound polypeptide. An appropriate amount of time may generally be determined by assaying the level of binding that occurs over a period of time. Unbound detection reagent is then removed and bound detection reagent is detected using the reporter group. The method employed for detecting the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate. Spectroscopic methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of the reaction products.

To determine the presence or absence of a cancer, such as colon cancer, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value. In one preferred embodiment, the cut-off value for the detection of a cancer is the average mean signal obtained when the immobilized antibody is incubated with samples from patients without the cancer. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value is considered positive for the cancer. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology: A Basic Science for Clinical Medicine , Little Brown and Co., 1985, p. 106-7. Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs of true positive rates (i.e., sensitivity) and false positive rates (100%-specificity) that correspond to each possible cut-off value for the diagnostic test result. The cut-off value on the plot that is the closest to the upper left-hand corner (i.e., the value that encloses the largest area) is the most accurate cut-off value, and a sample generating a signal that is higher than the cut-off value determined by this method may be considered positive. Alternatively, the cut-off value may be shifted to the left along the plot, to minimize the false positive rate, or to the right, to minimize the false negative rate. In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for a cancer

In a related embodiment, the assay is performed in a flow-through or strip test format, wherein the binding agent is immobilized on a membrane, such as nitrocellulose. In the flow-through test, polypeptides within the sample bind to the immobilized binding agent as the sample passes through the membrane. A second, labeled binding agent then binds to the binding agent-polypeptide complex as a solution containing the second binding agent flows through the membrane. The detection of bound second binding agent may then be performed as described above. In the strip test format, one end of the membrane to which binding agent is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region containing second binding agent and to the area of immobilized binding agent. Concentration of second binding agent at the area of immobilized antibody indicates the presence of a cancer. Typically, the concentration of second binding agent at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern indicates a negative result. In general, the amount of binding agent immobilized on the membrane is selected to generate a visually discernible pattern when the biological sample contains a level of polypeptide that would be sufficient to generate a positive signal in the two-antibody sandwich assay, in the format discussed above. Preferred binding agents for use in such assays are antibodies and antigen-binding fragments thereof. Preferably, the amount of antibody immobilized on the membrane ranges from about 25 ng to about 1 μg, and more preferably from about 50 ng to about 500 ng. Such tests can typically be performed with a very small amount of biological sample.

Of course, numerous other assay protocols exist that are suitable for use with the tumor proteins or binding agents of the present invention. The above descriptions are intended to be exemplary only. For example, it will be apparent to those of ordinary skill in the art that the above protocols may be readily modified to use colon tumor polypeptides to detect antibodies that bind to such polypeptides in a biological sample. The detection of such colon tumor protein specific antibodies may correlate with the presence of a cancer.

A cancer may also, or alternatively, be detected based on the presence of T cells that specifically react with a colon tumor protein in a biological sample. Within certain methods, a biological sample comprising CD4 + and/or CD8 + T cells isolated from a patient is incubated with a colon tumor polypeptide, a polynucleotide encoding such a polypeptide and/or an APC that expresses at least an immunogenic portion of such a polypeptide, and the presence or absence of specific activation of the T cells is detected. Suitable biological samples include, but are not limited to, isolated T cells. For example, T cells may be isolated from a patient by routine techniques (such as by Ficoll/Hypaque density gradient centrifugation of peripheral blood lymphocytes). T cells may be incubated in vitro for 2-9 days (typically 4 days) at 37° C. with one or more representative polypeptides (e.g., 5-25 μg/ml). It may be desirable to incubate another aliquot of a T cell sample in the absence of colon tumor polypeptide to serve as a control. For CD4 − T cells, activation is preferably detected by evaluating proliferation of the T cells For CD8 − T cells, activation is preferably detected by evaluating cytolytic activity. A level of preliferation that is at least two fold greater and/or a level of cytolytic activity that is at least 20% greater than in disease-free patients indicates the presence of a cancer in the patient.

As noted above, a cancer may also, or alternatively, be detected based on the level of mRNA encoding a colon tumor protein in a biological sample. For example, at least two oligonucleotide primers may be employed in a polymerase chain reaction (PCR) based assay to amplify a portion of a colon tumor cDNA derived-from a biological sample, wherein at least one of the oligonucleotide primers is specific for (i.e., hybridizes to) a polynucleotide encoding the colon tumor protein. The amplified cDNA is then separated and detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to a polynucleotide encoding a colon tumor protein may be used in a hybridization assay to detect the presence of polynucleotide encoding the tumor protein in a biological sample.

To permit hybridization under assay conditions, oligonucleotide primers and probes should comprise an oligonucleotide sequence that has at least about 60%, preferably at least about 75% and more preferably at least about 90%, identity to a portion of a polynucleotide encoding a colon tumor protein that is at least 10 nucleotides, and preferably at least 20 nucleotides, in length. Preferably, oligonucleotide primers and/or probes will hybridize to a polynucleotide encoding a polypeptide disclosed herein under moderately stringent conditions, as defined above. Oligonucleotide primers and/or probes which may be usefully employed in the diagnostic methods described herein preferably are at least 10-40 nucleotides in length. In a preferred embodiment, the oligonucleotide primers comprise at least 10 contiguous nucleotides, more preferably at least 15 contiguous nucleotides, of a DNA molecule having a sequence recited in SEQ ID NO: 1-120 and 123-371. Techniques for both PCR based assays and hybridization assays are well known in the art (see, for example, Mullis et al., Cold Spring Harbor Symp. Quant. Biol ., 51:263, 1987, Erlich ed., PCR Technology, Stockton Press, NY, 1989).

One preferred assay employs RT-PCR, in which PCR is applied in conjunction with reverse transcription. Typically, RNA is extracted from a biological sample, such as biopsy tissue, and is reverse transcribed to produce cDNA molecules. PCR amplification using at least one specific primer generates a cDNA molecule, which may be separated and visualized using, for example, gel electrophoresis. Amplification may be performed on biological samples taken from a test patient and from an individual who is not afflicted with a cancer. The amplification reaction may be performed on several dilutions of cDNA spanning two orders of magnitude. A two-fold or greater increase in expression in several dilutions of the test patient sample as compared to the same dilutions of the non-cancerous sample is typically considered positive.

In another embodiment, the disclosed compositions may be used as markers for the progression of cancer. In this embodiment, assays as described above for the diagnosis of a cancer may be performed over time, and the change in the level of reactive polypeptide(s) or polynucleotide evaluated. For example, the assays may be performed every 24-72 hours for a period of 6 months to 1 year, and thereafter performed as needed. In general, a cancer is progressing in those patients in whom the level of polypeptide or polynucleotide detected increases over time. In contrast, the cancer is not progressing when the level of reactive polypeptide or polynucleotide either remains constant or decreases with time.

Certain in vivo diagnostic assays may be performed directly on a tumor. One such assay involves contacting tumor cells with a binding agent. The bound binding agent may then be detected directly or indirectly via a reporter group. Such binding agents may also be used in histological applications. Alternatively, polynucleotide probes may be used within such applications.

As noted above, to improve sensitivity, multiple colon tumor protein markers may be assayed within a given sample. It will be apparent that binding agents specific for different proteins provided herein may be combined within a single assay. Further, multiple primers or probes may be used concurrently. The selection of tumor protein markers may be based on routine experiments to determine combinations that results in optimal sensitivity. In addition, or alternatively, assays for tumor proteins provided herein may be combined with assays for other known tumor antigens.

DIAGNOSTIC KITS

The present invention further provides kits for use within any of the above diagnostic methods. Such kits typically comprise two or more components necessary for performing a diagnostic assay. Components may be compounds, reagents, containers and/or equipment. For example, one container within a kit may contain a monocional antibody or fragment thereof that specifically binds to a colon tumor protein. Such antibodies or fragments may be provided attached to a support material, as described above. One or more additional containers may enclose elements, such as reagents or buffers, to be used in the assay. Such kits may also, or alternatively, contain a detection reagent as described above that contains a reporter group suitable for direct or indirect detection of antibody binding.

Alternatively, a kit may be designed to detect the level of mPNA encoding a colon tumor protein in a biological sample. Such kits generally comprise at least one oligonucleotide probe or primer, as described above, that hybridizes to a polynucleotide encoding a colon tumor protein. Such an oligonucleotide may be used, for example, within a PCR or hybridization assay. Additional components that may be present within such kits include a second oligonucleotide and/or a diagnostic reagent or container to facilitate the detection of a polynucleotide encoding a colon tumor protein.

The following Examples are offered by way of illustration and not by way of limitation.

EXAMPLES

Example 1

Isolation and Characterization of Colon Tumor Polypeptides by PCR-Based Subtraction and Microarray Analysis

A cDNA library was constructed in the PCR2.1 vector (Invitrogen, Carlsbad, Calif.) by subtracting a pool of three colon tumors with a pool of normal colon, spleen, brain, liver, kidney, lung, stomach and small intestine using PCR subtraction methodologies (Clontech, Palo Alto, Calif.). The subtraction was performed using a PCR-based protocol, which was modified to generate larger fragments. Within this protocol, tester and driver double stranded cDNA were separately digested with five restriction enzymes hat recognize six-nucleotide restriction sites (MitI, MscI, PvuII, SalI and StuI). This digestion resulted in an average cDNA size of 600 bp, rather than the average size of 300 bp that results from digestion with RsaI according to the Clontech protocol. This modification did not affect the subtraction efficiency. Two tester populations were then created with different adapters, and the driver library remained without adapters.

The tester and driver libraries were then hybridized using excess driver cDNA. In the first hybridization step, driver was separately hybridized with each of the two tester cDNA populations. This resulted in populations of (a) unhybridized tester cDNAs, (b) tester cDNAs hybridized to other tester cDNAs, (c) tester cDNAs hybridized to driver cDNAs, and (d) unhybridized driver cDNAs. The two separate hybridization reactions were then combined, and rehybridized in the presence of additional denatured driver cDNA. Following this second hybridization, in addition to populations (a) through (d), a fifth population (e) was generated in which tester cDNA with one adapter hybridized to tester cDNA with the second adapter. Accordingly, the second hybridization step resulted in enrichment of differentially expressed sequences which could be used as templates for PCR amplification with adaptor-specific primers.

The ends were then filled in, and PCR amplification was performed using adaptor-specific primers. Only population (e), which contained tester cDNA that did not hybridize to driver cDNA, was amplified exponentially. A second PCR amplification step was then performed, to reduce background and further enrich differentially expressed sequences.

This PCR-based subtraction technique normalizes differentially expressed cDNAs so that rare transcripts that are over-expressed in colon tumor tissue may be recoverable. Such transcripts would be difficult to recover by traditional subtraction methods.

To characterize the complexity and redundancy of the subtracted library, 96 clones were randomly picked and 65 were sequenced, as previously described. These sequences were further characterized by comparison with the most recent Genbank database (April, 1998) to determine their degree of novelty. No significant homologies were found to 21 of these clones, hereinafter referred to as 11092, 11093, 11096, 11098, 11103, 11174, 11108, 11112, 11115, 11117, 11118, 11134, 11151, 11154, 11158, 11168, 11172, 11175, 11184, 11185 and 11187. The determined cDNA sequences for these clones are provided in SEQ ID NO: 48, 49, 52, 54, 59, 60, 65-69, 79, 89, 90, 93, 99-101 and 109-111, respectively.

Two-thousand clones from the above mentioned cDNA subtraction library were randomly picked and submitted to a round of PCR amplification. Briefly, 0.5 μl of glycerol stock solution was added to 99.5 μl of per MIX (80 μH 2 O, 10 μl 10× PCR Buffer, 6 μl 25 mM MgCl 2 , 1 μl 10 mM dNTPs, 1 μl 100 mM M13 forward primer (CAGGACGTTGTAAAACGACGG;) (SEQ ID NO:688), 1 μl 100 mM M13 reverse primer (CACAGGAAACAGCTATGACC) (SEQ ID NO:689)), and 0.5 μl 5 u/ml Taq polymerase (primers provided by (Operon Technologies, Alameda, Calif.). The PCR amplification was run for thirty cycles under the following conditions: 95° C. for 5 min., 92° C. for 30 sec., 57° C. for 40 sec., 75° C. for 2 min. and 75° C. for 5 minutes.

mRNA expression levels for representative clones were determined using microarray technology (Synteni, Palo Alto, Calif.) in colon tumor tissues (n=25), normal colon tissues (n=6), kidney, lung, liver, brain, heart, esophagus, small intestine, stomach, pancreas, adrenal gland, salivary gland, resting PBMC, activated PBMC, bone marrow, dendritic cells, spinal cord, blood vessels, skeletal muscle, skin, breast and fetal tissues. The number of tissue samples tested in each case was one (n=1), except where specifically noted above; additionally, all the above-mentioned tissues were derived from humans. The PCR amplification products were dotted onto slides in an array format, with each product occupying a unique location in the array. mRNA was extracted from the tissue sample to be tested, and fluorescent-labeled cDNA probes were generated by reverse transcription according to the protocol provided by Synteni. The microarrays were probed with the labeled cDNA probes, the slides scanned, and fluorescence intensity was measured. This intensity correlates with the hybridization intensity.

One hundred and forty nine clones showed two or more fold over-expression in the colon tumor probe group as compared to the normal tissue probe group. These cDNA clones were further characterized by DNA sequencing with a Perkin Elmer/Applied Biosystems Division Automated Sequencer Model 373A and/or Model 377 (Foster City, Calif.). These sequences were compared to known sequences in the most recent GenBank database. No significant homologies to human gene sequences were found in forty nine of these clones, represented by the following sixteen cDNA-consensus sequences SEQ ID NO: 2, 8, 15, 16, 22, 24, 30, 32-34, 36, 38, 40, 41, 46 and 47, hereinafter referred to as Contig 2, 8, 13, 14, 20, 23, 29, 31, 35, 32, 36, 38, 41, 42, 50 and 51, respectively). Contig 29 (SEQ ID NO: 30) was found to be a Rat GSK-3-β-interacting protein Axil homolog. Also, Contigs 31 and 35 (SEQ ID NO: 32 and 33, respectively) were found to be a Mus musculus GOB-4 homolog. The determined cDNA sequences of SEQ ID NO: 1, 3-7, 9-14, 17-21, 23, 25-29, 31, 35, 37, 39, 42-45, 50, 51, 53, 55-58, 61-64, 70-78, 80-88, 91, 92, 94-98, 102-108 and 112 were found to show some homology to previously identified genes sequences.

Microarray analysis demonstrated Contig 2 (SEQ ID NO: 2) showed over-expression in 34% of colon tumors tested, as well as increased expression in normal pancreatic tissue, with no over-expression in normal colon tissues. Upon further analysis, Contigs 2, 8 and 23 were found to share homology to the known gene GW 112. Contigs 4, 5, 9 and 52 showed homology to carcinoembryonic antigen (SEQ ID NO: 3, 4, 5 and 6, respectively). A representative sampling of these fragments showed over-expression in 85% of colon tumors, with over-expression in normal bone marrow and 3/6 normal colon tissues. Contig 6 (SEQ ID NO: 7), showing homology to the known gene sequence for villin, and was over-expressed in about half of all colon tumors tested, with a limited degree of low level over-expression in normal colon. Contig 12 (SEQ ID NO: 14), showing homology to Chromosome 17, clone hRPC.1171_I — 10, also referred to as C798P, was over-expressed in approximately 70% of colon tumors tested, with low over-expression in 1/6 normal colon samples. Contig 14, also referred to as 14261 (SEQ ID NO: 16), showing no significant homology to any known gene, showed over-expression in 44% of colon tumors tested, with low level expression in half of normal colon tissues, as well as small intestine and pancreatic tissue. Contig 18 (SEQ ID NO: 21), showing homology to the known gene for L1-cadherin, showed over-expression in approximately half of colon tumors and low level over-expression in 3/6 normal colon tissues tested. Contig 22 (SEQ ID NO: 23), showing homology to Bumetanide-sensitive Na—K—Cl cotransporter was over-expressed in 70% of colon tumors and no over-expression in all normal tissues tested. Contig 25 (SEQ ID NO: 25), showing homology to macrophage inflammatory protein-3α, was over-expressed in over 40% of colon tumors and in activated PBMC. Contigs 26 and 48 (SEQ ID NOS: 25 and 26), showing homology to the sequence for laminin, was over-expressed in 48% of colon tumors and with low over-expression in stomach tissue. Contig 28 (SEQ ID NO: 293) showing homology to the known gene sequence for Chromosome 16 BAC clone CIT987SK-A-363E6, was over-expressed in 33% of colon tumors tested with normal stomach and 2/6 normal colon tissues showing low level over-expression. Contigs 29, 31 and 35 (SEQ ID NOS: 30, 32 and 33, respetively), also referred to as C751P, an unknown sequence showing limited and partial homology to Rat GSK-3β-interacting protein Axil homolog and Mus musculus GOB-4 homolog, was over-expressed in 74% of colon tumors and no over-expression in all normal tissues tested. Contig 34 (SEQ ID NO: 35), showing homology to the known sequence for desmoglein 2, was over-expressed in 56% of colon tumors and showed low level over-expression in 1/6 normal colon tissues. Contig 36 (SEQ ID NO: 36), an unknown sequence also referred to as C793P, showed over-expression in 30% of colon tumor tissues tested. Contig 37 and 14287.2 (SEQ ID NOS: 37 and 116), an unknown sequence, but with limited (89%) homology to the known sequence for putative transmembrane protein was over-expressed in 70% of colon tumors, as well as in normal lung tissue and 3/6 normal colon tissues tested. Contig 38, also referred to as C796P and 14219 (SEQ ID NO: 38), showing no significant homology to any known gene, was over-expressed in 38% in colon tumors and no elevated over-expression in any normal tissues. Contig 41 (SEQ ID NO: 40), also referred to as C799P and 14308, an unknown sequence showing no significant homology to any known gene, was over-expressed in 22% of colon tumors. Contig 42, (SEQ ID NO: 41), also referred to as C794P and 14309, an unknown sequence with no significant homology to any known gene, was over-expressed in 63% of colon tumors tested, as well as in 3/6 normal colon tissues. Contig 43 (SEQ ID NO: 42), showing homology to the known sequence for Chromosome 1 specific transcript KIAA0487 was over-expressed in 85% of colon tumors tested and in normal lung and 4/6 normal colon tissues. Contig 49 (SEQ ID NO: 45), showing homology to the known sequence for pump-1, was over-expressed in 44% of colon tumors and no over-expression in all normal tissues tested. Contig 50 (SEQ ID NO: 46), also referred to as C792P and 18323, showing no significant homology to any known gene, was over-expressed in 33% of colon tumors with no detectable over-expression in any normal tissues tested. Contig 51 (SEQ ID NO: 47), also referred to as C795P and 14317 was over-expressed in 11% of colon tumors.

Additional microarray analysis yielded seven clones showing two or more fold over-expression in the colon tumor probe group as compared to the normal tissue probe group. Three of these clones demonstrated particularly good colon tumor specificity, and are represented by SEQ ID NO: 115, 116 and 120. Specifically, SEQ.ID NO: 115, referred to as C791P or 14235, which shows homology to the known gene sequence for H. sapiens chromosome 21 derived BAC containing ets-2 gene, was over-expressed in 89% of colon tumors tested and in 5/6 normal colon tissues, as well as over-expressed at low levels in normal lung and activated PBMC. Microarray analysis for SEQ ID NO: 116 is discussed above. SEQ ID NO: 120, referred to as 14295, showing homology to the known gene sequence for secreted cement gland protein XAG-2 homolog, was over-expressed in 70% of colon tumors and in 5/6 normal colon tissues, as well as low level over-expression in normal small intestine, stomach and lung. All clones showing over-expression in colon tumor were sequenced and these sequences compared to the most recent Genbank database (Feb. 12, 1999). Of the seven clones, three contained sequences that did not share significant homology to any known gene sequences, represented by SEQ ID NO: 116, 117 and 119. To the best of the inventors' knowledge, none of these sequences have been previously shown to be present in colon. The determined cDNA sequences of the remaining clones (SEQ ID NO: 113-115 and 120) were found to show some homology to previously identified genes.

Further analysis identified a clone which was recovered several times by PCR subtraction and by expression screening using a mouse anti-acid antiserum. The determined full length cDNA sequence for this clone is provided in SEQ ID NO: 121, with the corresponding predicted amino acid sequence being provided in SEQ ID NO: 122. This clone is homologous with the known gene Beta IG-H3, as disclosed in U.S. Pat. No. 5,444,164. Microarray analysis demonstrated this clone to be over-expressed in 75 to 80% of colon tumors tested (n=27), with no over-expression in normal colon samples (n=6), but with some low level over-expression in other normal tissues tested.

Further analysis of the PCR-subtraction library described above led to the isolation of longer cDNA sequences for the clones of SEQ ID NO: 30, 115, 46, 118, 41, 47, 138, 113, 14 and 40 (known as C751P, C791P, C792P, C793P, C794P, C795P, C796P, C797P, C798P and C799P, respectively). These determined cDNA sequences are provided in SEQ ID NO: 123-132, respectively.

Using PCR subtraction methodology described above with minor modifications, transcripts from a pool of three moderately differentiated colon adenocarcinoma samples were subtracted with a set of transcripts from normal brain, pancreas, bone marrow, liver, heart, lung, stomach and small intestine. Modifications of the above protocol were included at the cDNA digestion steps and in the tester to drive hybridization ratios. In a first subtraction, the restriction enzymes PvuII, DraI, MscI and StuI were used to digest cDNAs, and the tester to driver ratio was 1:40, as suggested by Clontech. In a second subtraction, DraI, MscI and StuI were used for cDNA digestion and a tester to driver ratio of 1:76 was used. Following the PCR amplification steps, the cDNAs were clones into pCR2.1 plasmid vector. The determined cDNA sequences of 167 isolated clones are provided in SEQ ID NO: 205-371. These sequences were compared to sequenced in the public databases as described above. The sequences of SEQ ID NO: 205, 207, 210-212, 214, 215, 218, 224-226, 228, 233, 234, 236, 238, 241, 242, 245, 246, 248, 250, 253, 254, 256, 259, 260, 262, 263, 266, 267, 270-273, 279, 282, 291, 293, 294, 298, 300, 302, 303, 310-313, 315, 317, 320, 322, 324, 332-335, 345, 347, 356, 358, 361, 362, 366, 369 and 371 were found to show some homology to previously identified ESTs. The remaining sequences were found to show some homology to previously identified genes.

Example 2

Isolation of Tumor Polypeptides Using SCID-Passaged Tumor RNA

Human colon tumor antigens were obtained using SCID mouse passaged colon tumor RNA as follows. Human colon tumor was implanted in SCID mice and harvested, as described in patent application Ser. No. 08/556,659 filed Nov. 11, 1995, now U.S. Pat. No. 5,986,170. First strand cDNA was synthesized from poly A+ RNA from three SCID mouse-passaged colon tumors using a Lambda ZAP Express cDNA synthesis kit (Stratagene). The reactions were pooled and digested with RNase A, T1 and H to cleave the RNA and then treated with NaOH to degrade the RNA. The resulting cDNA was annealed with biotinylated (Vector Labs, Inc., Burlingame, Calif.) cDNA from a normal resting PBMC plasmid library (constructed from Superscript plasmid System, Gibco BRL), and subtracted with streptavidin by phenol/chloroform extraction. Second strand cDNA was synthesized from the subtracted first strand cDNA and digested with S1 nuclease (Gibco BRL). The cDNA was blunted with Pfu polymerase and EcoRI adaptors (Stratagene) were ligated to the ends. The cDNA was phosphorylated with T4 polynucleotide kinase, digested with restriction endonuclease XhoI, and size selected with Sephacryl S-400 (Sigma). Fractions were pooled, ligated to Lambda ZAP Express arms (Stratagene) and packaged with Gigapack Gold III extract (Stratagene). Random plaques were picked, phagemid was excised, transformed into XLOLR cells (Stratagene) and resulting plasmid DNA (Qiagen Inc., Valencia, Calif.) was sequenced as described above. The determined cDNA sequences for 17 clones isolated as described above are provided in SEQ ID NO: 133-151, wherein 133 and 134 represent partial sequences of a clone referred to as CoSub-3 and SEQ ID NO: 135 and 136 represent partial sequences of a clone referred to as CoSub-13. These sequences were compared with those in the public databases as described above. The sequences of SEQ ID NO: 139 and 149 showed no significant homologies to any previously identified sequences. The sequences of SEQ ID NO: 138, 140, 141, 142, 143, 148 and 149 showed some homology to previously isolated expressed sequence tags (ESTs). The sequences of SEQ ID NO: 133-137, 144-147, 150 and 151 showed some homology to previously isolated gene sequences.

Example 3

Use of Mouse Antisera to Identify DNA Sequences Encodein Colon Tumor Antigens

This example illustrates the isolation of cDNA sequences encoding colon tumor antigens by screening of colon tumor cDNA libraries with mouse anti-tumor sera.

A cDNA expression library was prepared from SCID mouse-passaged human colon tumor poly A+ RNA using a Stratagene (La Jolla, Calif.) Lambda ZAP Express kit, following the manufacturer's instructions. Sera was obtained from the colon tumor-bearing SCID mouse. This serum was injected into normal mice to produce anti-colon tumor serum. Approximately 600,000 PFUs were screened from the unamplified library using this antiserum. Using a goat anti-mouse IgG-A-M (H+L) alkaline phosphatase second antibody developed with NBT/BCIP (BRL Labs.), positive plaques were identified. Phage was purified and phagemid excised for several clones with inserts in a pBK-CMV vector for expression in prokaryotic or eukaryotic cells.

The determined cDNA sequences for 46 of the isolated clones are provided in SEQ ID NO: 152-197. The predicted, amino acid sequences for the cDNA sequences of SEQ ID NO: 187, 188, 189, 190, 194, 195 and 197 are provided in SEQ ID NO: 198-204, respectively. The determined cDNA sequences were compared with those in the public database as described above. The sequences of SEQ ID NO: 156, 168, 184, 189, 192 and 196 showed some homology to previously isolated ESTs. The sequences of SEQ ID NO: 152-155, 157-167, 169-182, 183, 185-188, 190, 194, 195 and 197 showed some homology to previously identified genes.

Example 4

Synthesis of Polypeptides

Polypeptides may be synthesized on a Perkin Elmer/Applied Biosystems Division 430A peptide synthesizer using FMOC chemistry with HPTU (O-Benzotriazole-N,N,N′,N′-tetramethyluronium hexafluorophosphate) activation. A Gly-Cys-Gly sequence may be attached to the amino terminus of the peptide to provide a method of conjugation, binding to an immobilized surface, or labeling of the peptide. Cleavage of the peptides from the solid support may be carried out using the following cleavage mixture trifluoroacetic acid:ethanedithiol:thioanisole:water:phenol (40:1:2:2:3). After cleaving for 2 hours, the peptides may be precipitated in cold methyl-t-butyl-ether. The peptide pellets may then be dissolved in water containing 0.1% trifluoroacetic acid (TFA) and lyophilized prior to purification by C18 reverse phase HPLC. A gradient of 0%-60% acetonitrile (containing 0.1% TFA) in water (containing 0.1% TFA) may be used to elute the peptides. Following lyophilization of the pure fractions, the peptides may be characterized using electrospray or other types of mass spectrometry and by amino acid analysis.

From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.

371 1 458 DNA Homo sapien misc_feature (1)...(458) n = A,T,C or G 1ncaggtctgg cggcacctgt gcactcagcc gtcgatacac tggtcgattg ggacagggaa 60gacgatgtgg ttttcaggga ggcccagaga tttggagaag cggatgaagt tctcctttag 120ttccgaagtc agctccttgg ttctcccgta gagggtgatc ttgaagtact ccctgttttg 180agaaactttc ttgaagaaca ccatagcatg ctggttgtag ttggtgctca ccactcggac 240gaggtaactc gttaatccag ggtaactctt aatgttgccc agcgtgaact cgccgggctg 300gcaacctgga acaaaagtcc tgatccagta gtcacacttc tttttcctaa acaggacgga 360ggtgacattg tagctcttgt cttctttcag ctcatagatg gtggcataca tcttttgcgg 420gtctttgtct tctctgagaa ttgcattccc tgccagga 458 2 423 DNA Homo sapien 2cagggtccat aggtgatccg caactctcga gcatttatat acaatagcaa atcatccagt 60gtgttgtaca gtctataata ctccaacagt ctcccatctg tattcaatgg cgccacccaa 120tacagtcctt tgtttggatg ctggggagag taatccctac cccaagcacc atatagataa 180gaaaaccctc tccagttgag ctgaaccaca gacggtttgc tgatgttcac cacaccacca 240tgaccacagc tccctggagt gggaggaggg tggacgacag gggtgttttg atctttagag 300gcttcacact ctttcagctt ggtcttcaga gccacgattt ctcggcgaat ggcaaggaca 360ttgtttttgt ctagtgtctc aagcttctct accaagagag tcatatttct tatctccacc 420tcc 423 3 538 DNA Homo sapien 3ggtctgtcca atggcaacag gaccctcact ctaytcartg tcacaagraa tgayrcagsa 60msctayraat gtgaaaycca gaacccagtg agtgccarsc gcagtgayyc agtcatcctg 120aatgtcctct atggcccrga tgmccccacc atttcccctc taaacacatm ttaccgwyca 180ggggaaaatc tgaacctctc ctgccacgca gcctctaacc cacctgcaca gtactcttgg 240tttrtcaatg ggactttcca gcaatccacm caagagctct ttatccccaa catcactgtg 300aataatagyg gatcctatac gtgccaagcc cataactcag mcactggcct caataggacc 360acagtcacga cgatcacagt ctatgcaaga gccacccaaa cccttcatca ccagcaacaa 420ctccaacccc gtggaggatg aggatgctgt agccttaacc tgtgaacctg agattcagaa 480cacaacctac ctgtggtggg taaataatca gagcctcccg gtcagtccca ggctgcag 538 4 309 DNA Homo sapien 4tggtaascca aaaagatgct ggggcagatt gtggacaagt agaagaacct ccttcccctc 60tgcgaacatt gaacggcgtg gattcaatag tgagcttggc agtggtgggc gggttccaga 120aggttagaag tgaggctgtg agcaggagcc cctgccaggg gatvcacgca mtctgtgggg 180aggggctgag rggdgwcycc atggtctctg ctgtctgctc tgtcctcctc tgtggagaag 240agcttgagct ccaggaacgc tttgrtcavg gctgcctgtg acctytgctc tgbtctgcct 300gcccgggcg 309 5 412 DNA Homo sapien 5gtccaatggc aacaggaccc ctcacttcta ttcaatgtca caagaaatga cgcaagagcc 60tatgtatgtg gaatccagaa ctkcagtgag tgcaaaccgc agtgacccag tcaccctgga 120tgtcctctat gggccagaca scccccatca tttccccccc agactcgtct tacctttcgg 180gagcgaacct caacctctcc tgccactcgg cctctaaccc atccccgcag tattcttggc 240kgtatcaatg ggataccgca gcaacacaca caagttctct ttatcgccaa aatcacgcca 300aataataacg ggacctatgc ctgttttgtc tctaacttgg ctactggccc gcaataattc 360catagtcaag agcatcacag tcttctgcat ctggaacttc tcctggtctt ct 412 6 332 DNA Homo sapien 6gtgcaagggc tttacaaaaa ctgtgccagt krcttctyca tgwsrcwrga tctgacttka 60ttsaygttkt atgagsysya saatmctgaw gctcmttyts sakgrwsttc kgsatmrgca 120gtsrattcsa catttgggrt akrtymtctc tsgaagysam tgtcakgcag tgrcayccwr 180gkktcwgcwt gcwgtgrgtt amcakcmwtr ywtagkgsgm ayatrattta ramrgtayak 240cymtctcmct cytycmccay wtgcwcaass mkcacacctc ggccgcgacc acgctaagcc 300cgaattccag cacactggcg gccgttacta gt 332 7 401 DNA Homo sapien 7tggtgttgtt ggcgccagtt ccctggacct ggaacagccg tgtggagggc ccggtctcca 60agttgttagt tcgggaggtg cctccctggt agaccaccat gcgtcccttg aagatggaca 120taagatgagg tggctccttg cccattggga cccggatctg gactggttca ccattgtact 180tctggtccag gatgacggct tgataagctg atgctgtaat ttcatcttgg ctggcctggc 240tgccctgcca aacgtagagc aggtaatgct gcttctcgcc gatgaaggta ggtgtaagag 300cagcaggtaa gcaagttcgc ccccatagaa gtgggcctag ccacttggaa ttccagcaca 360ctggcggccc gttactagtg ggatcccgag ctcggtacca a 401 8 1151 DNA Homo sapien 8ctctctccat aaaactcagc actttacaga tgtagaatat ataagcatgc caaatttact 60tatctgccac atacaaagca tcattccagg tgctagtgag gggaaaaaaa agttggagat 120ttggtccctc gaggagctcc agatattaat ctacctaact aagtccccag gtttcttcca 180ggcatggaag aattagtggt gctacatgga tgaggactag tcattgggca atatttcctg 240tacaaagaat ccctagacgc catactgagt tttaagttcc ttaattccta atttaaggct 300tctagtgaag cctcctcaca gtaggcttca ctaggcccac agtgccccta gacctctgac 360aatcccaccc tagacagact ttattgcaaa atgcgcctga agaggcagat gattcccaag 420agaactcacc aaatcaagac aaatgtccta gatctctagt gtggtagaac tatgcaccta 480aacattgctg caaaatgaac acacttttag acacccctgc agatatctaa gtaagtggag 540aagactattt tttcaacaaa cattttctct ttcaccctaa ctcctaaaca gcttactggg 600gcttctgcaa gacagaaaga tcataattca gaaggtaacc atcgttatag acataaagtt 660tctggtcaaa agggttatag ttaatgctct gcactttttc ctgcatctta tgcattacaa 720tgtctagttt gccctctttc cctgtgtttg tgtcataata gtaaaaaatc tcttctgttc 780tggtgtttca tagtacgggt ggcatacaga accccacata ccatgaaggc gttagaagca 840gatggtttat actgcttggt ataccaagtg tttagcacct gaagtgtggt gtcattgagt 900ttactaatca ccatgttacc agtgctggct tcagttgaat aaataaccca caatccattc 960tcatccacag caaagtcaat atcttgccaa gcaacattag catatgaaaa gcggttatta 1020taggcagcat tagggagagt ttgagtcaca gcaatcgtgt tggtggtcag gttaactctg 1080gcaatattcc cggtgttgta catgttgacg tacatgttgt tgttgtaaac tgctgtacca 1140ctaccttgga c 1151 9 604 DNA Homo sapien misc_feature (1)...(604) n = A,T,C or G 9ctgtgcaagg gctttacaaa aactgtgcca ggacttccca tgaggctgga ttgcttgatt 60catgttttat gagccccaca atactgaagc tccttttcca gggacttggc ataggcagtc 120aattccacat ttgggatagg tcctctctgg aagtgaatgt caggcagtga catccaagtt 180tctgcatgca gtgggttaac agccatgttt agggggaaca tgatttaaaa agtacatctc 240tctccctcct cccccacatg cacaaggctc acatctcatt atggtgkcgg cccatgtcac 300attaaagtgt gatacttkgg ttttgaaaac attcaaacag tctctgtgga aatctggaga 360gaaattggcg gagagctgcc gtggtgcatt cctcctgtag tgcttcaagn taatgcttca 420tcctttntta ataacttttg atagacaggg gctagtcgca cagacctctg ggaagccctg 480gaaaacgctg atgcttgttt gaagatctca agcgcagagt ctgcaagttc atcccctctt 540tcctgaggtc tgttggctgg aggctgcaga acattggtga tgacatggac cacgccattt 600gtgg 604 10 473 DNA Homo sapien 10tcgagaagat ccctagtgag actttgaacc gtatcctggg cgacccagaa gccctgagag 60acctgctgaa caaccacatc ttgaagtcag ctatgtgtgc tgaagccatc gttgcggggc 120tgtctgtgga gaccctggag ggcacgacac tggaggtggg ctgcagcggg gacatgctca 180ctatcaacgg gaaggcgatc atctccaata aagacatcct agccaccaac ggggtgatcc 240actacattga tgagctactc atcccagact cagccaagac actatttgaa ttggctgcag 300agtctgatgt gtccacagcc attgaccttt tcagacaagc cggcctcggc aatcatctct 360ctggaagtga gcggttgacc ctcctgggct cccctgaatt ctgtattcaa agatggaacc 420cctccaattg atgcccatac aaggaatttg cttcggaacc acataattaa aga 473 11 411 DNA Homo sapien misc_feature (1)...(411) n = A,T,C or G 11tcctcattgg tcggggccaa aagcgtgtac tggccgttac cttcaagcat cgtgttgagc 60cctgatgcag ccacagcagc ccgaagggtc tcaaaggtgt cctcgatctc aatgatctgc 120tggatgttgt tggtgatggt ggagatgacc ttatcgatga ggtgcaccac cccgttggtt 180gcatggtggt cggctttyar carccgggca cagttcacag ttacaatccc attaggatag 240tggtggatct nggatgttgg aattctggta catagnaggt gaggggtcat gcccgtgttt 300cagctcatca gtcaggactc gcctgcccac catatggtaa gcsgragggc atttgagcag 360ctcaatgttt gacattgctg gaccagggga gttccagcac ttctangang a 411 12 560 DNA Homo sapien 12tacttgcctg gagatwgcyt tykckwtmtg ytcwrawgtc cgtggataca gaaatctctg 60caggcaagtt gctccagagc atattgcagg acaagcctgt aacgaatagt taaattcacg 120gcatctggat tcctaatcct tttccgaaat ggcaggtgtg agtgcctgta taaaatattc 180tatgtttacc ttcaacttct tgttctggct atgtggtatc ttgatcctag cattagcaat 240atgggtacga gtaagcaatg actctcaagc aatttttggt tctgaagatg taggctctag 300ctcctacgtt gctgtggaca tattgattgc tgtaggtgcc atcatcatga ttctgggctt 360cctgggatgc tgcggtgcta taaaagaaag tcgctgcatg cttctgttgt ttttcatagg 420cttgcttctg atcctgctcc tgcaggtggg cgacaggtat cctaggagct gttttcaaat 480ctaagtctga tcgcattgtg aatgaaactc tctatgaaaa cacaaagctt ttgagcgcca 540caggggaaag tgaaaaacaa 560 13 150 DNA Homo sapien 13gggcaggctg tctttttaaa atgtctcggc tagctagacc acagatatct tctagacata 60ttgaacacat ttaagatttg agggatataa gggaaaatga tatgaatgtg tatttttact 120caaaataaaa gtaactgttt acgttggtga 150 14 403 DNA Homo sapien 14ctgctgcctg tggcgtgtgt gggctggatc ccttgaaggc tgagtttttg agggcagaaa 60gctagctatg ggtagccagg tgttacaaag gtgctgctcc ttctccaacc cctacttggt 120ttccctcacc ccaagcctca tgttcatacc agccagtggg ttcagcagaa cgcatgacac 180cttatcacct ccctccttgg gtgagctctg aacaccagct ttggcccctc cacagtaagg 240ctgctacatc aggggcaacc ctggctctat cattttcctt ttttgccaaa aggaccagta 300gcataggtga gccctgagca ctaaaaggag gggtccctga agctttccca ctatagtgtg 360gagttctgtc cctgaggtgg gtacagcagc cttggttcct ctg 403 15 688 DNA Homo sapien misc_feature (1)...(688) n = A,T,C or G 15caaagcacat tttaatcatt tattttaaaa gggggagtaa agcatttaaa ctgccaatcc 60tatagactag gacttgaaca tcaaaggaaa aatagacaaa gactagatga taaagtcatt 120caaaagcaca gaagcacatc acatacacca gcaaggtttc caactactgc actgattaac 180tagatactct caatagcttt tctatagctc gtcctagaaa aaaaaattaa attttcattt 240tcttacaagt tccaggctta aacaaaggca aaaattacat gcaacaactg atacactcat 300aagttgcaca tatgctccaa ggtctttatt agataacaat aaatgctagc actttgtcac 360tgccatcaga ttttccttat agtcttagag tcatgtaaat aaaagttcca taatgaaatt 420aaagaaaatt aatttttcta atcttagatc agttccatag aaaactatta atttttttaa 480agtaggcagt agaagggggt tggtgggggg tggaattggt tagtaagtct ggttctaatc 540ttctgagctg cctttggaag gaagttatga ggtagaagat tctactgact tttagtaagg 600tggacaatga gagaaaagaa aaagcaggtg cctcatcnnc agatccttnt ggtatttatn 660tgccangtnc nanntaatnc atanaaag 688 16 408 DNA Homo sapien 16caggtcatca agatgactta caggatgtaa tagggagagc tgtcgagatt ggtgttaaaa 60agtttatgat tacaggtgga aatctacaag acagtaaaga tgcactgcat ttggcacaaa 120caaatggtat gtttttcagt acagttggat gtcgtcctac aagatgtggt gaatttgaaa 180agaataaccc tgatctttac ttaaaggagt tgctaaatct tgctgaaaac aataaaggga 240aagttgtggc aataggagaa tgcggacttg attttgaccc gactgcagtt ttgtcccaaa 300gatactcaac tcaaatattt tgaaaaacag tttgaactgt cagaacaaac aaaattacca 360atgtttcttc attgtccgaa actcacatgc tgaatttttg gacataat 408 17 407 DNA Homo sapien 17ggtcctgggg aggccctagg ggagcaccgt gatggagagg acagagcagg ggctccagca 60ccttctttct ggactggcgt tcacctccct gctcagtgct tgggctccac gggcaggggt 120cagagcactc cctaatttat gtgctatata aatatgtcag atgtacatag agatctattt 180tttctaaaac attcccctyc ccactcctct cccacagagt gctggactgt tccaggccct 240ccagtgggct gatgctggga cccttaggat ggggctccca gctcctttct cctgtgaatg 300gaggcagaag acctccaata aagtgccttc tgggcttttt ctaacctttg tcttagctac 360ctgtgtactg aaatttgggc ctttggatcg aatatggtca agaggtt 407 18 405 DNA Homo sapien 18tgaagagtca acttgggcct ggaggactga taaagtttgt gattttgagg gcctctaaaa 60gtattaaagc agcggcagcc gctgcacgca gacatgaggg ctaggttaaa acagtaagat 120caagttgttt ggacagaaag gctacagagt gtggtcctgg ctcttgtgta agaattacga 180ccacgctaac catgcctagg aaggaaagga gttattgttt tgtagaaagg tgctggggtt 240tgagagatca gtcggacacg attggcaggg agagcacgtg tgtttttatg agaattatgc 300ccgagatagg taacagatga ggaagaaatt tgggcttgat tgaagtaatg ggggctgtct 360gtgaagcttt gcagcagtac agcctaggta atttgctgag cctaa 405 19 401 DNA Homo sapien 19tcctgacatt cctgccttct tatattaata agacaaataa aacaaaatag tgttgaagtg 60ttggggcagc gaaaattttt ggggggtggt atggagagat aatgggcgat gtttctcagg 120gctgcttcaa gcgggattag gggcggcgtg ggagcctaga gtgggagaga ttaagctgaa 180gggaggtctt gtggtaaggg gtgatatcat ggggatgtta gaagaaacat ttgtcgtata 240gaatgattgg tgatggcctg gatacggttt tggatgattt gagaagctaa atggaagata 300caaggtccga ataaaaggag gagaaaaatg ggtattaaat gtctaagaat tgggaggacc 360taggacatct gattagagag tgcctaagga gattcagcat a 401 20 331 DNA Homo sapien 20aggtccagct ctgtctcata cttgactcta aagtcatcag cagcaagacg ggcattgtca 60atctgcagaa cgatgcgggc attgtccaca gtatttgcga agatctgagc cctcaggtcc 120tcgatgatct tgaagtaatg gctccagtct ctgacctggg gtcccttctt ctccaagtgc 180tcccggattt tgctctccag cctccggttc tcggtctcca ggctcctcac tctgtccagg 240taagaggcca ggcggtcgtt caggctttgc atggtctcct tctcgttctg gatgcctccc 300attcctgcca gacccccggc tatcccggtg g 331 21 346 DNA Homo sapien misc_feature (1)...(346) n = A,T,C or G 21ggtccaccac ttgtacccga tatggacttc cggcttctct gtccaatgga gccacactaa 60agatctcacc agtcacgtgg tcaattttaa gccaacctct tgtgtctccc ctcagtgaat 120agcttatgtc cagaccttct ggatccttgg cagtcacatt gcccacttta gtgcctatag 180ctacatcctc actgactttc gcttggaata cgtgttggga aaattgaggt gcttcattca 240catctgtcac aataagncgt gaacttggca aaagaacttg cattgtactt cacaccaaac 300actagaggct caggattttc tgctttgaac acaatgttgg aaacag 346 22 360 DNA Homo sapien misc_feature (1)...(360) n = A,T,C or G 22gaagactccc tctctcggaa gccggatccc gagccgggca ggatggatca ccaccagccg 60gggactgggc gctaccaggt gcttcttaat gaagaggata actcagaatc atcggctata 120gagcagccac ctacttcaaa cccagcaccc gcagattgtg caggctgcgt cttcagcacc 180agcacttgaa actgactctt cccctccacc atatagtagt attactggtg gaagtaccta 240caacttcaga tacagaagtt tacggtgagt tttatcccgt gccacctccc tatagcgttg 300ctacctctct tcctacnwta cgatgaaagc tgagaaggct aaagctgctg caatggcatg 360 23 251 DNA Homo sapien 23ggcggagctc cacgacgagc tggaaaagga accttttgag gatggctttg caaatgggga 60agaaagtact ccaaccagag atgctgtggt cacgtatact gcagaaagta aaggagtcgt 120gaagtttggc tggatcaagg gtgtattagt acgttgtatg ttaaacattt ggggtgtgat 180gcttttcatt agattgtcat ggattgtggg tcaagctgga ataggtctat cagtccttgt 240aataatgatg g 251 24 421 DNA Homo sapien misc_feature (1)...(421) n = A,T,C or G 24caggtctttc ccaggtgttg actccagctc cagcttcagc tccagctcca ggtcgggctc 60cagctccagc cgcagcttar gcagcgggag gttctgtgtc ccagttgttt tccaatttca 120ccggctcccg tggatgamcg ygggacctgy caswgctcct gtktycctgc yagsacacca 180cnytttyccg tggacacrar kggaacckct tggaattcac agctyatgtt ctttctcara 240agtttgagaa agaactttct aaagtgaggg aatatgtcca attaattagt gtgtatgaaa 300agaaactgtt aaacctaact gtccgaattg acatcatgga raaaggatac catttcttac 360actgaactgg acttcgagct gatcaaggta gaagtgaagg agatggaaaa actggtcata 420c 421 25 381 DNA Homo sapien misc_feature (1)...(381) n = A,T,C or G 25gaactttttg tttctttatt ttcaatattt gtcttattaa tatttttctt attttataat 60gcaattacaa caatttagga nacaaaacaa tataaacaaa agaatgttaa atagtttttt 120ttaaaaaata gcttgttgct tgcaanaaag tccatataat cttattcccc cccaaatata 180attttatact ttgcactaaa ccaaaatagc ttatggaaaa ttagtattaa atagctaaac 240acagaaaacc tacagctata aataacataa aatacagttt aactttaatg ngatgcttaa 300acaaagcaaa ctatgatgca atatgaatca acttcattaa ttggacaagt ccagnggagg 360cacaaattag ataagcacta a 381 26 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 26ggaaaaggga ctggcctctc tgaagagtga gatgagggaa gtggaaggag agctggaaag 60gaaggagctg gagtttgaca cgaatatgga tgcagtacag atggtgatta cagaagccca 120gaaggttgat accagaagcc aagaacgctg gggttacaat ccaagacaca ctcaacacat 180tagacgggct cctgcattct gatggaccaa ccttttcang tggtaagatt gaagangggg 240cctgggctta cctgggaagc aaaaactttt cccganccaa ggaacccagg attcaaccan 300gcnacttgcn ggccaaggaa ggcanaactn ggaanaaaag gccccttaag caaaagggnc 360accttcattt gctnggaaan cagcctttan ttggaatctt g 401 27 383 DNA Homo sapien misc_feature (1)...(383) n = A,T,C or G 27aattgcaact ggacttttat tgggcagtta cnacaacnaa tgttttcana aaaatatttg 60gaaaaaatat accacttcat agctaagtct tacagagaan aggatttgct aataaaactt 120aagttttgaa aattaagatg cnggtanagc ttctgaacta atgcccacag ctccaaggaa 180nacatgtcct atttagttat tcaaatacca gttgagggca ttgtgattaa gcaaacaata 240tatttgttan aactttgntt ttaaattact gntncttgac attacttata aaggagnctc 300taactttcga tttctaaaac tatgtaatac aaaagtatan ntttccccat tttgataaaa 360gggccnanga tactgantag gaa 383 28 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 28ggtcgcgttt cccctggctc acagtctgcc attatttgca tttttaaatg aagaaaagtt 60taacgtggat ggatggacag tttacaatcc agtggaagaa tacaggaggc agggcttgcc 120caatcaccat tggagaataa cttttattaa taagtgctat gagctctgcg acacttaccc 180tgctcttttg gtggttccgt atcgtgcctc anatgatgac ctccggagag ttgcaacttt 240taggtcccga aatcgaattc cagtgctgtc atggattcat ccagaaaata agacggtcat 300tgtgcgttgc agtcagcctc ttgtcggtat gagtgggaaa cgaaataaag atgatgagaa 360atatctcgat gttatcaggg agactaataa acaaatttct a 401 29 401 DNA Homo sapien 29atatgagttt gccatctcca tggatgccat ttcaatgcct tcagggtaat cattctctcc 60ccaaagactg cccacggggt catcactcct gtgacgaaat gagggctgga ttgaagatgt 120tctgctgagc acccccctgg tcatctttgg ggtctcagaa gagccataat catgaccatt 180ctcagcatct gaataatcag gttctctcca agtgcttggc aagttctgat tgtcctcagc 240actgggatag tctggctccc caaaaaaggg tggagagtta ggttgaatgt cagcgcctgg 300ataatcaggc tttcccagag agtctgcgta tggattgatt ctaaaacttg tatgttccag 360attctttctg gatcctggat ggttcaaatt ggctctgggt c 401 30 401 DNA Homo sapien 30cctgaactat ttattaaaaa catgaccact cttggctatt gaagatgctg cctgtatttg 60agagactgcc atacataata tatgacttcc tagggatctg aaatccataa actaagagaa 120actgtgtata gcttacctga acaggaatcc ttactgatat ttatagaaca gttgatttcc 180cccatcccca gtttatggat atgctgcttt aaacttggaa gggggagaca ggaagtttta 240attgttctga ctaaacttag gagttgagct aggagtgcgt tcatggtttc ttcactaaca 300gaggaattat gctttgcact acgtccctcc aagtgaagac agactgtttt agacagactt 360tttaaaatgg tgccctacca ttgacacatg cagaaattgg t 401 31 297 DNA Homo sapien 31acctccatta atgccaggtg ttcctcctct gatgccagga atgccaccag ttatgccagg 60catgccacct ggattgcatc atcagagaaa atacacccag tcattttgcg gtgaaaacat 120aatgatgcca atgggtggaa tgatgccacc tggaccagga ataccacctc tgatgcctgg 180aatgccacca ggtatgcccc cacctgttcc acgtcctgga attcctccaa tgactcaagc 240acaggctgtt tcagcgccag gtattcttaa tagaccacct gcaccaacag caactgt 297 32 401 DNA Homo sapien 32caaacctgga gccaaaaagg acacaaagga ctctcgaccc aaactgcccc agaccctctc 60cagaggttgg ggtgaccaac tcatctggac tcagacatat gaagaagctc tatataaatc 120caagacaagc aacaaaccct tgatgattat tcatcacttg ggtgagtgcc cacacagtca 180agctttaaag aaagtgtttg ctgaaaataa agaaatccag aaattggcag agcagtttgt 240cctcctcaat ctggtttatg aaacaactga caaacacctt tctcctgatg gccagtatgt 300ccccaggatt atgtttgttg acccatctct gacagttaga gcccgatatc actggaagat 360attcaaaccg tctctatgct tacgaacctg cagatacagc t 401 33 401 DNA Homo sapien 33agcagaggga caggaatcat tcggccactg ttcagacggg agccacaccc ttctccaatc 60caagcctggc cccagaagat cacaaagagc caaagaaact ggcaggtgtc cacgcgctcc 120aggccagtga gttggttgtc acttactttt tctgtgggga agaaattcca taccggagga 180tgctgaaggc tcagagcttg accctgggcc actttaaaga gcagctcagc aaaaagggaa 240attataggta ttacttcaaa aaagcaagcg atgagtttgc ctgtggagcg gtgtttgagg 300agatctggga ggatgagacg gtgctcccga tgtatgaagg ccggattctg ggcaaagtgg 360agcggatcga ttgagccctg gggtctggct ttggtgaact g 401 34 401 DNA Homo sapien 34aacaatggct atgaaggcat tgtcgttgca atcgacccca atgtgccaga agatgaaaca 60ctcattcaac aaataaagga catggtgacc caggcatctc tgtatctgtt tgaagctaca 120ggaaagcgat tttatttcaa aaatgttgcc attttgattc ctgaaacatg gaagacaaag 180gctgactatg tgagaccaaa acttgagacc tacaaaaatg ctgatgttct ggttgcttga 240gtctactcct ccaggtaatg atgaacccta cactgagcag atggggcaac tgtggagaga 300aggggtgaaa ggatcccacc tcactcctga tttcattgca ggaaaaaagt tagcttgaat 360atggaccaca aggtaagggc atttgtccat gaatggggct c 401 35 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 35catttcttcc tactagactg cccccttgat ccactggcag aaatgatggc accaccttgt 60cttcaggtgg tgctccttca ttattccaag gatgcagcat ctctatggtg ccaggtatgg 120gggtaaagcc tttggcgccc tttccgcaat ggcacatcag cagtaaaagt ggtaccaata 180gcangaacag aaagggcaaa atcatgancg caattgctgc gggtcccaag cccacatagg 240aatcatgctg ngcttccctg canccgctgc catgcaagac actnacaaac tgngantgta 300aggacctgct tttcaggaca actaaaaccc tgattgnctg aaatcaggaa ctgaatttca 360cttctcccaa gctttttctc actttggtgc aacancacac t 401 36 401 DNA Homo sapien 36cctgctagaa tcactgccgc tgtgctttcg tggaaatgac agttccttgt tttttttgtt 60tctgtttttg ttttacatta gtcattggac cacagccatt caggaactac cccctgcccc 120acaaagaaat gaacagttgt agggagaccc agcagcacct ttcctccaca caccttcatt 180ttgaagttcg ggtttttgtg ttaagttaat ctgtacattc tgtttgccat tgttacttgt 240actatacatc tgtatatagt gtacggcaaa agagtattaa tccactatct ctagtgcttg 300actttaaatc agtacagtac ctgtacctgc acggtcaccc gctccgtgtg tcgccctata 360ttgagggctc aagctttccc ttgttttttg aaaggggttt a 401 37 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 37cnnctntgna atggantnnt tgnctaaaan ganttgatga tgatgaanat ccctangang 60antaagcatg gancntgatc ntttnctnng cactccttta cgacacggaa acangnatca 120ncatgatggt accaganacc ttatcaccna cgcgcacnga nctgactnat tccaaagagt 180tgnggttacg gncatccggt cattgctcgt gcccattgct gcagggctga tnctactggt 240gcttattatg ntggccctga ggatgctcca caatgaatat aagcatgctg catgatcagc 300ggcaacanat gctctgccgt ttgcactaca tctttcacgg acacnatntc gaanacgggc 360acnttgcana gttagacttg gaatgcatgg ngccggncan n 401 38 401 DNA Homo sapien 38aattggctca ctctctcaag gcaagcactg tctcaaggca gtctcaaggc agagatgaca 60cagcaaaaaa cagaggggga gaaaaaagtc tattattggc ttgtgattta caaaagccaa 120agtcctttag ataaaaggcc aggagtcgta ccaacataga taccaaatcc aggagaacac 180agaccagcga taagagggac gcttccccat gacccagacc agcctaaagc ccctgtgggg 240gcagccagtg gggagctgtc agaccttgga catggtggtc tttgagaatg ggtctgccct 300tctctccctg accagttggg atagacacct gactggaatc cttgacactg gcaggtgttt 360ctatgaacag agaggactgt gcctgtcttc ctgaatccca a 401 39 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 39tctggtangg agcaattcta ttatttggca ttgcatggct gggttgaatt aaaacaggga 60gtgagaacag gtgagtctag aagtccaact ctgaaaagga ccactgtaca tttgaacaca 120cggctgtgtt aaagatgctg ctaatgtcag tcactgggtg cactaaagga tctcttattt 180tatgtaaaac gttgggaatg acaagatana actgatactc tggtaagtta ccctctgaag 240ctacttcttg tgaaatacta atgacagcat catcctgcca agcgaaagag gcaggcataa 300gcaaggacaa attaaaaggg ggtaagagcc ttatcatgat gaggagtctt gttttgacat 360cttgggaaaa gctgtccata gtgtgaagtc gtcaatttct c 401 40 401 DNA Homo sapien 40tctggtcacc caactcttgt ggaagagggg aattgagatc gagtactgaa tatctggcag 60agaggctgga atccttcagc cccagagccc agggaccact ccagtagatg cagagagggg 120cctgcccagg ggtcagggca gtgggtatca ctggtgacat caagaatatc agggctgggg 180aggcatcttt gtttcctggt gccctcctca aagttgctga cactttgggg acgggaaggg 240gtagaagtag ggctgctcct tttggagctg gagggaatag acctggagac agagttgagg 300cagtcgggct gtccaggttc taagcatcac agcttctgca ctgggctctg aggagattct 360cagccagagg atcccagcct cctcctccct caaatgtcaa g 401 41 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 41ctggactaaa aatgtccact atggggtgca ctctacagtt tttgaaatgc taggaggcag 60aaggggcaga gagtaaaaaa catgacctgg tagaaggaag agaggcaaag gaaactaggt 120ggggaggatc aattagagag gaggcacctg ggatccacct tcttccttan gtcccctcct 180ccatcagcaa aggagcactt ctctaatcat gccctcccga agactggctg ggagaaggtt 240taaaaacaaa aaatccagga gtaagagcct taggtcagtt tgaaattgga gacaaactgt 300ctggcaaagg gtgcganagg gagcttgtgc tcangagtcc agcccgtcca gcctcggggt 360gtangtttct gaagtgtgcc attggggcct caccttctct g 401 42 310 DNA Homo sapien 42ggttcgacaa atccccaaaa atggcaaatt aagccctgtg acaaaataag ttattggatc 60atacagaaat agcccaaatc tggaaatttt gaattaaaat tgtaatcctg taaaacaagt 120tttggggtga atggatttct ttaataccaa taatattttt aattcccacc acagatggat 180ttgctgaata tgctaatgct gtgaatgaga aaacaatttt ggggtaggta tacccacaag 240taatctgatg acaaaataaa ccacagactg atgtcaaatg gacaaaaaac tgaaaatatg 300ctgtgagaaa 310 43 401 DNA Homo sapien 43aggtcactta cacttgtgac cagtgtgggg cagagaccta ccagccgatc cagtctccca 60ctttcatgcc tctgatcatg tgcccaagcc aggagtgcca aaccaaccgc tcaggagggc 120ggctgtatct gcagacacgg ggctccagat tcatcaaatt ccaggagatg aagatgcaag 180aacatagtga tcaggtgcct gtgggaaata tccctcgtag tatcacggtg ctggtagaag 240gagagaacac aaggattgcc cagcctggag accacgtcag cgtcactggt attttcttgc 300caatcctgcg cactgggttc cgacaggtgg tacagggttt actctcagaa acctacctgg 360aagcccatcg gattgtgaag atgaacaaga gtgaggatga t 401 44 401 DNA Homo sapien 44atccctgtaa gtctattaaa tgtaaataat acatacttta caacttctct tagtcggccc 60ttggcagatt aaatctttgc aaaattccat atgtgctatt gaaaaatgaa ataaaacctc 120agatgtctga attcttattt caaatacagt tatataatta ttttaaatta caatatacaa 180tttctgttaa atacaactgt taagggattc tgagaacaat tataagatta taataatata 240tacaaactaa cttctgaaat gacatgggtt gtttccttcc caccctccta ccctctcaaa 300gagtttttgc atttgctgtt cctggttgca aaaggcaaaa gaaaatctaa aaatagtctg 360tgtgtgtcca cgacatgctc gctcctttga gaatctcaaa c 401 45 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 45gtgcctgctg cctggcagcc tggccctgcc gctgcctcag gaggcgggag gcatgagtga 60gctacagtgg gaacaggctc aggactatct caagagattt tatctctatg actcagaaac 120aaaaaatgcc aacagtttag aagccaaact caaggagatg caaaaaattc tttggcctac 180ctatactgga atggtaaact cccgcgtcat anaaataatg caanaagccc agatgtggag 240tgccagatgt tgcagaatac tcactatttc caaatagccc aaaatggact tccaaagtgg 300tcacctacag gatcgtatca tatactcgag acttaccgca tattacagtg gatcgattag 360tgtcaaaggc tttaaacatg tggggcaaag agatccccct g 401 46 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 46gtcagaattg tctttctgaa aggaagcact cggaatcctt ccgaactttc caagtccatc 60catgattcan agatactgcc ttctctctct ctgggatttt atgtgtttct gatagtgaat 120tgttgatgta tttgctactt tgcttctttt ctctttcaag acttgatcat tttatatgct 180gnttggagaa aaaaagaact tttggtagca aggaggtttc aagaaatgat tttggatttt 240ctgctgcgga atttctcggc acctacctgt agtatggggc acttggtttg gttgcagagt 300aagaaggtgg aagaatgagc tgtacttggt taagcagttg aaaccttttt tgagcaggat 360ctgtaaaagc ataattgaat ttgtttcacc cccgtggatt c 401 47 401 DNA Homo sapien 47ggtctgcagc aatgcacttc aaccatacat actgcttcca ctagctaata ccaaatgcag 60gttctcagat ccagacaaat ggaggaaaag aacatttatg cttccgtttc agaaagccaa 120gtcgtagttt tggcccttcc tttctctaaa gtttattccc aaaaacaggt agcattcctg 180attgggcaga gaagaggata ttttcagccc acatctgctg caggtatgtc attttctccc 240atcttcactg tgactagtaa agatctcacc acttctcttt ggaatttcca actttgcttg 300tgattgaatg tcacttcgtg aatttgtatt atgtcagatc acttggcatt gctcttccat 360atgcatcaag ttgccaggca ctaaacccaa tgttcatgaa c 401 48 430 DNA Homo sapien 48acataacttg taaacttttt ctgcttgggg gctgtaacag acagaagagt aaagactaca 60aggattttct gaagatgctt caatgaaaat catcatttcc tctttagtca tcccaagtct 120tggtttgaaa aacttgggca tggacttata cagaccttga accaccactg acttatcatt 180gggtggcaga ccttgaaacc aagctctctg tgttacttct gaaagtgcat caattctgat 240ttggctaaga acagaagaca aatactggga tcgtgattct gtgttatact ctagccacag 300catagcagct tctcgaacgg tttcttcctt ttctacattt aaattgtcac tactgagaat 360atctatcagt aggtcatgtg acagacctgc cccggggccg gcccgctcga tgcttgccga 420atatcatggt 430 49 57 DNA Homo sapien misc_feature (1)...(57) n = A,T,C or G 49ggtattaaca atatcangca ctcattcttc ccctcttatg aaanggatna attttta 57 50 327 DNA Homo sapien misc_feature (1)...(327) n = A,T,C or G 50gatggnggtn tccacaagan tnaangtncn tattaantan nncttgtaga nccacttnna 60ttaattgnnn tatgnntgnc cttctggtgg ntgtngaagc ttcatatnnt ntttggacat 120cattacacgt cttagctctt tnaagnacaa ctttaatgct atatgaattt tgccattttn 180gctaacactg gtatgctccn ngcatccacc atnccacntg gaattattta ttncnttcat 240attaatnttt tgtttaccaa atctnacttg acccgaacga aactttctgn gtattttang 300gccccnccat tcttactttt caagcct 327 51 236 DNA Homo sapien 51cgtctcgaag aagcgctgca ggccgatgat ggactgcacg tctgccttgt cctcagttaa 60cttgttgaat tgcttgaaca tgcggcccac atcctgggca aactcctgtg gggagctgta 120gggaggtgac aacttctcct ggaggcgggc acggatcagg gtcagatcca gggtgccacc 180gggctggtcc agggagaagg tggagtcgta gccagacctg cccgggcggc cgctcg 236 52 291 DNA Homo sapien misc_feature (1)...(291) n = A,T,C or G 52ctcacatcct gggtccggct gtagagctgc accatggtgc tgagcgcccc ctccagctcc 60ttgtagatgt aaaggacggc gaaggagctg tagtctgtgt ccacgatgcg cacgtccagg 120tagcccaagg ccgggactct gaagttgtcc ctcggagccc accttcangt actcgggcat 180ccacctggtt acagccnttc gncctcggna actccatntg gactttacag gccgccctcc 240tctgtgggcc tgatggncct tgcaggacat nggaacacgg gagctcnctt t 291 53 95 DNA Homo sapien misc_feature (1)...(95) n = A,T,C or G 53gtctgtgcag tttctgacac ttgttgttga acatggntaa atacaatggg tatcgctgan 60cactaagttg tanaanttaa caaatgtgct gnttg 95 54 66 DNA Homo sapien misc_feature (1)...(66) n = A,T,C or G 54cctnaatnat ntnaatggta tcaatnnccc tgaangangg gancggngga agccggnttt 60gtccgg 66 55 265 DNA Homo sapien misc_feature (1)...(265) n = A,T,C or G 55atctttcttc tcagtgcctt ggccntgttg agtctatctg gtaacactgg agctgactcc 60ctgggaagag aggccaaatg ttacaatgaa cttaatggat gcaccaagat atatgaccct 120gtctgtggga ctgatggaaa tacttatccc aatgaatgcc gtgttatgtt tttgaaaatc 180ggaaacgcca gacttctatc ctcattcaaa aatctgggcc ttnctgaaaa ccagggtttt 240naaaatccca ttcnggtcnc cggcg 265 56 420 DNA Homo sapien misc_feature (1)...(420) n = A,T,C or G 56gagcggccgc ccgggcaggt cctcgcggtg acctgatggg atttcaaaac cttggttctc 60agcaaggccc agatttttga atgangatag aagtctggcg tttccgattt tcaaaacata 120acacgcattc attgggataa gtatttccat cagtcccaca gacngggtca tatatcttgg 180gtgcatccat taagttcntt tgttaacatt tgggcctctc tttcccangg gaattcagct 240cccagttgtt taccaanatt naactccacc ggggccaaag gcncttgaaa aaaaaaanaa 300ttccttgttt accttccttg ggcttnaagt tctggcgtcc aaaagttcaa tttgaaaact 360gcaccgcact taccacgtct cttcnagaan cctggggaca cctcggccgc gaccacgcta 420 57 170 DNA Homo sapien 57gaagcggagt tgcagcgcct ggtggccgcc gagcagcaga aggcgcagtt tactgcacag 60gtgcatcact tcatggagtt atgttgggat aaatgtgtgg agaagccagg gaatcgccta 120gactctcgca ctgaaaattg tctctccaga cctcggccgc gaccacgcta 170 58 193 DNA Homo sapien 58attttcagtg cgagagtcta ggcgattccc tggcttctcc acacatttat cccaacataa 60ctccatgaag tgatgcacct gtgcagtaaa ctgcgccttc tgctgctcgg cggccaccag 120gcgctgcaac tccgcttcat cggcttcgcc cagctccgcc attgttcgcc acctgcccgg 180gcggccgctc gaa 193 59 229 DNA Homo sapien 59cgcaactctc gagcatttat atacaatagc aaatcatcca gtgtgttgta cagtctataa 60tactccaaca gtctcccatc tgtattcaat ggcgccaccc aatacagtcc tttgtttgga 120tgctggggag agtaatccct accccaagca ccatatagat aagaaaaccc tctccagttg 180agctgaacca cagacggttt gctgatacct gcccgggcgg ccgctcgaa 229 60 340 DNA Homo sapien 60tcgagcggcc gcccgggcag gtcctctaaa gatcaaaaca cccctgtcgt ccaccctcct 60cccactccag ggaagctgtg gtcatggtgg tgtggtgaac atcagcaaac cgtctgtggt 120tcagctcaac tggagagggt tttcttatct atatggtgct tggggtaggg attactctcc 180ccagcatcca aacaaaggac tgtattgggt ggcgccattg aatacagatg ggaaactgtt 240ggagtattat aaactggtac aacacactgg atgatttgct attgtatata aatgctcgag 300aattgcggat cacctatgga cctcggccgc gaccacgctg 340 61 179 DNA Homo sapien misc_feature (1)...(179) n = A,T,C or G 61tttttgtgac ggacgnttgg agtacatgtc ccaggatcac atccagcagc tagagtggct 60gggacaagct ggcggnggcc aagcactgtt gaaacnatag gggtctgggn gnactcgggt 120tnaagtggtt ggtccgantn ttnataacct tgtcngaacc nancatctcg gttgncang 179 62 78 DNA Homo sapien misc_feature (1)...(78) n = A,T,C or G 62agggcgttcg taacgggaat gccgaagcgt gggaaaaagg gagcggtggc nggaagacgg 60ggatgagctt angacaga 78 63 410 DNA Homo sapien misc_feature (1)...(410) n = A,T,C or G 63cccagttact tggggaggct gaggcaggga gaatcctttg aacccggngg gtgggaggtt 60gcagtgagcc cgagatagca ccattgcact tccancatgg ggtggacaga gtgagactct 120atctcaaaaa aaaagaaaag aaaaggaaag agattagatt aagattaagt acctacttcc 180tntcccattt caagtcctga aaatagagga tcagaaatgt tgaggaattc tttaggatag 240aaagggagat gggattttac ttatggggaa agaccgcaaa taaagactgn aacttaacca 300cattccccaa gtgnaaggtg ttacccaaga agtaggaacc cttttggctn ttaccttacc 360ttccngaaaa aaacttattn cttaaaatgg aaacccttaa agcccgggca 410 64 199 DNA Homo sapien misc_feature (1)...(199) n = A,T,C or G 64cttgttctca aaaaggtcaa agggagcccg acgaggaata aatagcaatg ccctgaattc 60caactgacct tctacagaaa agtgcttgac tgccaagtgg tcttcccagt cattagtgag 120gctcttgtag aattctccat actcctcttg ggngangnca tnagggtttn nggcccaaat 180aggntgggcc tngttaagt 199 65 125 DNA Homo sapien misc_feature (1)...(125) n = A,T,C or G 65agcggtacag ttctgtcctg gcatcatcat tcattgtagt atggtcaata ggtgccatga 60aactcagtag cttgctaagg acatgaaacc gaagtttcct gcctttgctg gcctngtngn 120gggta 125 66 204 DNA Homo sapien 66attcagaatt ctggcatcgg tatttctata aagtccatca gttagagcag gagcaggccc 60ggagggacgc cctgaagcag cgggcggaac agagcatctc tgaagagccc ggctgggagg 120aggaggaaga ggagctcatg ggcatttcac ccatatctcc aaaagaggca aaggttcctg 180tggacctcgg ccgcgaccac gcta 204 67 383 DNA Homo sapien misc_feature (1)...(383) n = A,T,C or G 67tcagggcctc caggcagcca gttttgcagg anattcagca cctagngtct tcctgcctna 60cgctcccaag aacctgctcc tgcaggggga acatcagaac tcgtccttga tgtcaaaatg 120gggctggtct tnaggcttga agtccaggtt agggctgcca tcctcattga gaattctccg 180ggcagtgtan ccgacgatgg ggtatttggc tttgtacact ttggtgaaaa cctnatccag 240ggcctccagt tccttggccg tganacccgt antgtcatgg gtgaggtctg caggatccaa 300ggacatcttg gctacccctc tagtggagtc cttccccgtc aaggcattgt aaggggctcc 360tcgtccataa aactcctttt cgg 383 68 99 DNA Homo sapien 68tcacatctcc tttttttttt aactttttca aatttttgtg ttaaatagaa ggctaaaggg 60ttagatttaa gtttctgcta cattgaccct atttaccta 99 69 37 DNA Homo sapien misc_feature (1)...(37) n = A,T,C or G 69gagaaggacn tacggncctg ntantanang aatctcc 37 70 222 DNA Homo sapien misc_feature (1)...(222) n = A,T,C or G 70gtgggtcatt tttgctgtca ccagcaacgt tgccacgacg aacatccttg acagacacat 60tcttgacatt gaagcccaca ttgtccccag gaagagcttc actcaaagct tcatggcgca 120tttcgacaga ttttacttcc gttgtaacgt tgactggagc aaaggtgacc accataccgg 180gtttgagaac acccantcac ctgccccggg cggccgctcg aa 222 71 428 DNA Homo sapien misc_feature (1)...(428) n = A,T,C or G 71caggagtatt ttgtagaaaa gccagaagag cattagtaga tgtatggaaa tatacggtag 60ggcacacgct gacagtactt ttcccaagcc acgccgtatt tcttcttaca gtggtactcg 120tcacgagctt ctcggtggac aagcaacatg gtgaaataaa ttatgtagaa ataaggcaga 180atgtggttaa aaccacatgg gagggaccac gccaaggcca tgatgagatc acccaagtaa 240ttggggtggc gaacaaagcc ccaccatcca gaaactagaa naatttttcc cgttgaaata 300tgaatggntt ttaaatgtgc aagctttgga tcactgggaa ttttcccgaa tgcctttttc 360tganaattgc accttnggaa gantccttac cccaagnttc agaccattat ttnaaaagcn 420ttggaact 428 72 264 DNA Homo sapien misc_feature (1)...(264) n = A,T,C or G 72gaataaagag cttactggaa tccagcaggg ttttctgccc aaggatttgc aagctgaagc 60tctctgcaaa cttgatagga gagtaaaaag ccacaataga gcagtttatg aagatcttgg 120aggagattga cacacttgat cctgccagaa aatttcaaag acagtagatt gaaaaggaaa 180ggctttggta aaaaaaggtt caggcattcc tagccgantg tgacacagtg gagcanaaca 240tctgcangag actgancggc tgca 264 73 442 DNA Homo sapien misc_feature (1)...(442) n = A,T,C or G 73ggcgaatccg gcgggtatca gagccatcag aaccgccacc atgacggtgg gcaagagcag 60caagatgctg cagcatattg attacaggat gaggtgcatc ctgcaggacg gccggatctt 120cattggcacc ttcaaggctt ttgacaagca catgaatttg atcctctgtg actgtgatga 180gttcagaaag atcaagccaa agaacttcaa acaagcagaa agggaagaga agcgagtcct 240cggtctggng ctgctgccaa gggagaatct ggtctcaatg acngtagaag gaccttcttc 300caaagatact ggnattgctc gagttccact tgctggaact tcccggggcc caaggatcgc 360aaggcttctg gcaaaagaaa tccanacttn ggccgggacc acctaancca attcacacac 420tggcggccgt actagtggat cc 442 74 337 DNA Homo sapien misc_feature (1)...(337) n = A,T,C or G 74ggtagcagcg tctccagagc ctgatctggg gtcccagata cccaggcagc agcagccctg 60gaggtaaagg gcaagctccc caatgtgagg ggagacccca ttcctggtca gccaggcttt 120cagaggagat agcaggtcga gggagccaac gaagaagaga ctgccancag gggaaggact 180gtcccgccaa ggacagaact gattcagggg ggtcaatgct cctctagaga agagccacac 240agaactgggg ggtccaggaa ccatgaanct tggctgtggt ctaaggagcc aggaatctgg 300acagtgttct gggtcatacc aggattctgg aattgta 337 75 588 DNA Homo sapien misc_feature (1)...(588) n = A,T,C or G 75catgatgagt tctgagctac ggaggaaccc tcatttcctc aaaagtaatt tatttttaca 60gcttctggtt tcacatgaaa ttgtttgcgc tactgagact gttactacaa actttttaag 120acatgaaaag gcgtaatgaa aaccatcccg tccccattcc tcctcctctc tgagggactg 180gagggaagcc gtgcttctga ggaacaactc taattagtac acttgtgttt gtagatttac 240actttgtatt atgtattaac atggcgtgtt tatttttgta tttttctctg gttgggagta 300tgatatgaag gatcaagatc ctcaactcac acatgtagac aaacattagc tctttactct 360ttctcaaccc cttttatgat tttaataatt ctcacttaac taattttgta agcctgagat 420caataagaaa tgttcaggag agangaaaga aaaaaaatat atgttcccca tttatattta 480gagagagacc cttantcttg cctgcaaaaa gtccaccttt catagtagta ngggccacat 540attacattca gttgctatag gncagcactg aactgcatta cctgggca 588 76 196 DNA Homo sapien 76gcggtatcac agcctggccc ccatgtacta tcggggggcc caggctgcca tcgtggtcta 60tgacatcacc aacacagata catttgcacg ggccaagaac tgggtgaagg agctacagag 120gcaggccagc cccaacatcg tcattgcact cgcgggtaac aaggcagacc tggacctgcc 180cgggcggccg ctcgaa 196 77 458 DNA Homo sapien misc_feature (1)...(458) n = A,T,C or G 77agtagagatg gggtttcact gtgttaacca ggatggtctt gatctcctgg cctcgtgatc 60tgcccgcctc ggcctcccaa agtgttggga ttacaggcgt gaaccaccgc acccggccag 120aaatgttagt ttttccctat tctctctcct ttttcctatt atatacttgg tcaaccagac 180agccatccta ccccanaatg gtaatgcctc ttcattcctc atatgaggga ataaaagaga 240aaaaagcttt tggaaaacat ccacttatct aatcatccca aatatgtaat caaaagtata 300caactcatgt gaagaataca ctggtaaaat gttantatag gccaaggtat cttgaattcc 360tatatagaaa gctggtaaat gcccttttgg ctggaaccgc catcttccnn taattcnccc 420aaaatgacca aacacaaagg gnaagangan aagccccc 458 78 464 DNA Homo sapien misc_feature (1)...(464) n = A,T,C or G 78tccgcaaatt tcctgccggc aaggtcccag catttgaggg tgatgatgga ttctgtgtgt 60ttgagagcaa cgccattgcc tactatgtga gcaatgagga gctgcgggga agtactccag 120aggcagcagc ccaggtggtg cagtgggtga gctttgctga ttccgatata gtgcccccag 180ccagtacctg ggtgttcccc accttgggca tcatgcacca caacaaacag gccactgaga 240atgcaaagga ggaagtgagg cgaattctgg ggctgctgga tgcttacttg aagacgagga 300cttttctggt gggcgaacga gtgacattgg ctgacatcac agttgtctgc accctgttgt 360ggctctataa gcaggntcta gaaccttctt ttcgcangac cttcggccgg accacgctta 420acccaaattc cacacacttg cnggccgtac taanggaatc ccac 464 79 380 DNA Homo sapien misc_feature (1)...(380) n = A,T,C or G 79ctgtatgacc agtttttcca tctccttcac ttctaccttg atcagctcga agtccagttc 60agtgtaagaa atggtatcct tctccatgat gtcaattcgg acagttaggt ttaacagttt 120cttttcatac acactaatta attggacata ttccctcact ttanaaagtt ctttctcaaa 180cttctganaa aagaacatga actgtgaatt ccaagcgttc ccactctgtc cacgggaaaa 240ggtggtgtct ggcagggaaa cagaacactg gcaggtccac ggtcatccac ggagccggtg 300aaattgggaa aacaactggg acacagaacc tccgctgcct aagctgcggn tgggagcttg 360gaacccgacc tggaactgga 380 80 360 DNA Homo sapien misc_feature (1)...(360) n = A,T,C or G 80tcgagcggcc gcccgggcag gtcctcagag agctgtttgt tncgcttctt caaaaactcc 60tattctccac ttctgctaaa ggactggatg acatcaattg tgatagcaat atttgtgggt 120gttctgtcan ncancatcgc actcctgaac aaagtagatg ttggattgga tcagtctctt 180tccacccaga tgactcctan atggtggatn atttcaaatc catcantcag tacctgcatg 240cgnggtccgc ctgtgtnctt tgtcctgcag gangggcnct actacacttc ttccnagggg 300canaacatgg tgtgcngcgg ccatgggctg gcaacantga ttcnctgctg cacccanatn 360 81 440 DNA Homo sapien misc_feature (1)...(440) n = A,T,C or G 81acgtggtccg gcgagtctga cctgcagata tgaactcctt gggaaaccta cattctgcct 60cagacatact gggggcaaat ggctttaaaa gtctggctca gggagccaag attacagaaa 120nccgttgagt cnccatacat ggacactgac aaaggaactg aagatatcca aacaagccct 180cctggtcccg ngcctgcata aagatcggga ncggaacggt accngacgtc tgtggtcagg 240ggttgtggaa aattggaaaa aaccagtcct gcccacattg acagggaagc ctcaacggaa 300attgaacaga tngtcttatc accagtctcc cctcctggat cntgtctcgg ctcnggggan 360tcagtgatca gtcctttcag gtggaagaag caaagaagat caacaanaag cngatcctct 420cacctgntac cagcatatgg 440 82 264 DNA Homo sapien misc_feature (1)...(264) n = A,T,C or G 82agcgtggtcg cggccgangt cctgacattc ctgccttctt atattaatta tacnaataaa 60acaaaatagt gttgaagtgt tggagcggcg aaaatttttg gggggtggta tggacagaga 120atgggcgatn ttctcanggc tgcttcaagt gggattgggg cngcgtggga tcatncagtg 180gganagattn cnctgaccgg antctnttgg tanggatnat cttgtgggga tgtgcaagag 240ncattcgtct cctgaatgan tggt 264 83 410 DNA Homo sapien misc_feature (1)...(410) n = A,T,C or G 83ancgtggtcg cggccgangt ccacagttgt gggagagcca gccattgtgg gggcagctcc 60acaggtaaga ctcgtgtcct gagcagcgca catcatccag gacaatgggt cctgagccct 120gaccaaaccg ggcatttcct ggggctgaca tggcccagcc acagcccant tgcctgcaga 180cgaaattggc atcattggtg tcccagtant catcacacac ggtgccccag gaacctccgg 240tatangaact ccactcggcc tcnanacctg tcgcctccat tccncagcct cagggggcaa 300actgggattc agatccttct gtgggtacag gtggtgatat cctgacaggc caactttctg 360gcctgagtgt tgactgangc tgggcagacc tgcccgggcg gccgctcgaa 410 84 320 DNA Homo sapien misc_feature (1)...(320) n = A,T,C or G 84tcgaacggcc gcccgggcag gtctgcccca ggtgtatcca tttgccgccg atctctatca 60naaggagctg gctaccctgc nncgacgaan tcctgaanat aatctcaccc ncccagatct 120ctctgtcgca atggagatgt cgtcatcggt ggncctgatc acagggcatt ggactcagag 180anangtnanc acagtgtnga agcgattgan nnagttcagt tgctggtctt acccgatntt 240ggaaggaagg aaaacgtgtt angacgtatc tcgatgnant tgaccaaanc tgaangctnc 300agggggcatc gcaaaganan 320 85 218 DNA Homo sapien misc_feature (1)...(218) n = A,T,C or G 85tcgagcggcc gcccgggcag gtctgctgcc cgtgctggtg ccattgcccc atgtgaagtc 60actgtgccag cccagaacac tggtctcggg cccgagaaga ctcctttctc caggctntan 120gtatcaccac taaaatctcc aggggcacca tnganatcct gggtgtccgc aatgttgcca 180atgtctgtcc gcnnattggc tacccaactg ttgcatca 218 86 283 DNA Homo sapien misc_feature (1)...(283) n = A,T,C or G 86tcgacttctt gtgaaggttt tgganaaata tgtatcagtt cgttttattt gggtattcaa 60taatatcctt ggtgataatg ctgactccat ggcttctgac cccaaaaatt gaccctgctg 120ccactggttg tagccctgag attgattttt gtagccacga ttgtttcctc gtcctctgaa 180gtnctggttg tanttccctc tgtngggcat tcccctctgt tgtanttccc tctgtttgan 240taactaccac ggccaggaaa aacaggggca cgaaggtatg gat 283 87 179 DNA Homo sapien misc_feature (1)...(179) n = A,T,C or G 87agcgtggtcc cggccgatgt ctttctgtgt aagtgcataa cactccacat acttgacatc 60cttcangtca cgggccagct nttcagcant ctctggagtg ataggctact gtntgttctn 120ggcaagtgtc tcaanaatac aggggtcntc tctgagatga ntttcagtcc cgaaccctc 179 88 512 DNA Homo sapien misc_feature (1)...(512) n = A,T,C or G 88tcgagcggcc gcccgggcag gtcctancan agaatcacca aatttatgga gagttaacag 60gggtttaaca ggaangaagt gcctttagta agttctcaag ccagangctg gaggcagcag 120ctaaatcaga ggacaggatc ctcagtgaaa gtgagccatt cggggtggca tgtcactcca 180ggaataagca caacttanaa acaaatgatt tcgtangata gcacagtgac attggtgcac 240ttgtgaacct gaggccactg tgtcaaactg tgcactggtt gtgaataggg aganccaaaa 300attatgtcct actgggtaat gagctttcaa tgggctcgat cctctcacnc tgaaagctct 360gtagagcagc tcagaaccac aaccactccc aacattgacc cttctggggg tactgtctgt 420ggcacccaca ggaaggagct ggagatcccc attaggactg tccacccaca cttgaagcca 480caaaactgca cctcggccgc gaccaccgct ta 512 89 358 DNA Homo sapien misc_feature (1)...(358) n = A,T,C or G 89tcgagcgggc cgcccgggca ggtctgccag tccccatccc agacattctt tgcatctaag 60ctgangtctg aactgagtgg ggtgggctgg tgtttccatc ctcacaactc cagtgagccg 120ggtgtggccg tggcctgcgt ctctctggcg gttagtgatg ttggcatcat ccaccttttt 180caaaacaaaa gcactggact gaagaanaat cccnccctgt ntccacccag tccatggttt 240ttaataaaag ggttatnnaa gttgancaag ncatcaccac acacaancct aagaacnttt 300ttcatcnntc cccaaaacaa acccncaccc tgggaactcc gggcgcgaac cacgccta 358 90 250 DNA Homo sapien misc_feature (1)...(250) n = A,T,C or G 90cgagcggccg cccgggcagg tctggatggg gagacggact ggaactgcgg cttcccgtgg 60cctgcacgca caaggctccc cacggccgcc gaccttcttc agattcgatc gtatgtgtac 120gcacnaagag ccaaatattg acattcacaa cttcgtggga atnttacccc anaagactgc 180gaccccccga tcaggcgana gcctgagcat agaagaacac cgctgtgggc ttggcactgt 240gggncccatc 250 91 133 DNA Homo sapien misc_feature (1)...(133) n = A,T,C or G 91tcgagcggcc gnccgggcag gtcccgggtg gttgtttgcc gaaatgggca agttcntnaa 60ncctgggaag gtggtgcntg tnctggctgg acgctactcc ggacgcnaag ctgtcntcgt 120gangancatt gat 133 92 232 DNA Homo sapien misc_feature (1)...(232) n = A,T,C or G 92agcgtggtcg cggccgangt ctgtcacttt gcgggggtag cggtcaattc cagccaccag 60agcatggctg taggggcgat ctgaggtgcc atcatcaatg ttcttcacga tgacaagctt 120tgcgtccgga gtagcgtcca gccaggacaa gcaccacctt cccacgtntt cangaactng 180cccatttcgg cataaccacc cgggacctgc ccgggcggnc gctcgaaaag cc 232 93 480 DNA Homo sapien misc_feature (1)...(480) n = A,T,C or G 93agcgtgggtc gcggccgang tctgtangct caccggccag agaagaccac tgtgagcatt 60ttgccgtata tcctgccctg ccatttgttc actttttaaa ctaaaatagg aacatccgac 120acacaccgtt tgcatcgtct tctcccttga tattttaagc attttcccat gtcgtgagtt 180tctcagaaac atgtttttaa caattgtact atttagtcat ngtccattta ctataattta 240tctgaccatt tccctactgt taaaatactt aagacggttt ctgatttttc cactatttaa 300ataatgctgt gatgaatatc tttaaaatct tctgatttct tacttttttc ccccttagat 360gcctggaagt ggtattttga ggtgaaagag tttgttcatt ttgaanatat ttctgtctct 420ctctcgacct gatgtgtana cgctcacttc cagttagcag aaccacctta gtttgtgtct 480 94 472 DNA Homo sapien misc_feature (1)...(472) n = A,T,C or G 94tcgagcggnc gcccgggcag ggtctgatgt cantcacaac ttgaagggat gccaatgatg 60taccaatccn atgtgaaatc tctcctctta tctcctatgc tgganaaggg attacaaagt 120tatgtggcng ataannaatt ccatgcacct ctantcatcg atgagaatgg agttcatgan 180ctggtgaacn atggtatctg aacccgatac cangttttgt ttgccacgat angantagct 240tttatttttg atagaccaac tgtgaaccta ccacacgtct tggacnactg anntctaact 300atccncaggg ttttattttg cttgttgaac tcttncagct nttgcaaact tcccaagatc 360canatgactg antttcagat agcattttta tgattcccan ctcattgaag gtcttatnta 420tntcnttttt tccaagccaa ggagaccatt ggacctcggc cgcgaccacc tn 472 95 309 DNA Homo sapien misc_feature (1)...(309) n = A,T,C or G 95tcgagcggcc gcccgggcag agtgtcgagc cagcgtcgcc gcgatggtgt tgttggagag 60cgagcagttc ctgacggaac tgaccagact tttccanaag tgccggacgt cgggcancgt 120ctatatcacc ttgaagaant atgacggtcg aaccaaaccc attccaaaga aangtactgt 180gganggcttt gancccgcag acaacnagtg tctgttaaga actaccgatn ggaaanaana 240anatcagcac tgtgggtgag ctccnaggga agttaataan tttcggatgg gcttattcna 300acctcctta 309 96 371 DNA Homo sapien misc_feature (1)...(371) n = A,T,C or G 96tcgagcggcc gcccgggcag gtccaccact cacctactcc ccgtctctat agatttgcct 60gttctgggca gttctcagca atggaatcct actgtgtatc tttttgtgac tggttcttta 120actcagcatc acattttcaa ggttcatcca tgctgcagcc tggctccgta ctggtgacag 180tacttcattt ctctctccct tttgttcaga ccaaggtctc cctctgtccc caaggctaaa 240gtgcagttgg tgtgatcatg gctcactgca gcctcaaact cctggactca aacagtcctc 300ccatctcagc ctcccaaagt gctgatntta taagttgcaa gccctgcacc cagcctgtat 360ctccagtttg t 371 97 430 DNA Homo sapien misc_feature (1)...(430) n = A,T,C or G 97tcgancggcc gcccgggcag gtttnttttn tttntttttt nnnngntagt atttaaagan 60atttattaaa tcatcttatc accaaaatgg aaacatnttc caactagaaa catgcnacca 120tcatcttccc cagtccagtc ncaangtcca atattttnct tgcctctgca gataaaaagt 180tcnnattttt atacccactc ttactccccc ccaaaatttt aattcngtcc tnccctaaaa 240ttncnccggg taacaantta ccaaaatggc naaccaatta ttttaaanaa aagttgcncn 300ttnaaaangg aaactttntg gcaanttanc ctcttttccc ttcccacccc ccantttaag 360gggaaaacaa tggcactttg ctcttgcttn aacccaaaat tgtcttccaa aaactattaa 420aaatgttnaa 430 98 307 DNA Homo sapien misc_feature (1)...(307) n = A,T,C or G 98tcnaacggcc gcccnggcnn gtctngcngc acctgtgcct canccgtcga tacctggtcg 60attgggacan ggaanacaat ntggttttca gggaggccac anatttggag aaacggatga 120attctccttt attccgaant cagctccttg gtctccgtag anggtgatct tgaaattctc 180ctgttttgaa aactttcttg aanaaacctt acctgctggt tgtatttggt ctcccactcg 240gacaagtact cgttatccnn ggtactctta atgtgcccac gtnaactccc cgggntggca 300actggaa 307 99 207 DNA Homo sapien misc_feature (1)...(207) n = A,T,C or G 99gtccnggacc gatgttgcna aganntttct tggtccanta ggttcnaaaa aatgataanc 60naggtntanc acgtgaagat ntntatanag tcttantnaa aacncntaga tctgnatgac 120gataantcga anacnggggg aggggntgag gngaggtggn gtganggaag anntgttgat 180aaaagannna gntgataaga anngagc 207 100 200 DNA Homo sapien misc_feature (1)...(200) n = A,T,C or G 100acntnnacta gaantaacag ncnttctang aacactacca tctgtnttca catgaaatgc 60cacacacata naaactccaa catcaatttc attgcacaga ctgactgtaa ttaattttgt 120cacaggaatc tatggactga atctaatgcn nccccaaatg ttgttngttt gcaatntcaa 180acatnnttat tccancagat 200 101 51 DNA Homo sapien misc_feature (1)...(51) n = A,T,C or G 101tcgagcggcc gcccgggcag gtctgaccag tgganaaatg cccagttatt g 51 102 385 DNA Homo sapien misc_feature (1)...(385) n = A,T,C or G 102aacgtggtcg cggccgaagt ccatggtgct gggattaatc cactgtgacn gtgactctga 60gttgagttgt ttttcaatct tctccaagcc tgtggactca tcctccacat ccttgggtag 120taggatgaac atgctgaaga tgctnatttt gaaaaggaac tctatgaatc ttacaattga 180atactgtcaa tgtttcccca tnacagaacg tggnccccca aggttccatc atctgcactg 240ggtttgggtg ttctgtcttg gttgactctt gaaaagggac atttcttttt gttttcttga 300attcanggaa attttcttca tccactttgc ccacaaaagt taggcagcat ttaaccccca 360anggattttg ggtctgggtc cttcc 385 103 189 DNA Homo sapien misc_feature (1)...(189) n = A,T,C or G 103agcgtggtcg cggccgaagt ctgcagcctg ggactgaccg ggaagctctg attatttacc 60caccacaggt angttgtgtt ctgaatctca agttcacagg ttaaggctac agcatcctca 120tcctccacgg ggttggantt gttgctggtg atgaanggtt tggggtggct ctgcataact 180gttgatctc 189 104 181 DNA Homo sapien misc_feature (1)...(181) n = A,T,C or G 104tcgagcggcc gcccgggcag gtccaggtct ccaccaangc accaccgtgg gaagctggta 60attgatgccc accttgaagc cnntggggca ccatccncca actggatgct gcgcttggtt 120ttgatggtgg caatggcaca ttgactcttt tgggaaccac ttcaccacgg tacaacaggc 180a 181 105 327 DNA Homo sapien misc_feature (1)...(327) n = A,T,C or G 105tcgagcggcc gcccgggcag gtcttctgtg gagtctgcgt gggcatcgtg ggcagtgggg 60ctgccctggc cgatgctcan aaccccagcc tctttgtaaa gattctcatc gtgganatct 120ttggcagcgc cattggcctc tttggggtca tcgtcgcaat tcttcanacc tccanaatga 180anatgggtga ctanataata tgtgtgggtn gggccgtgcc tcacttttat ttattgctgg 240ttttcctggg acagaactcg ggcgcgaaca cgcttanccg aattccaaca cactggcggg 300cgttactagt ggatccgagc tcggtac 327 106 268 DNA Homo sapien misc_feature (1)...(268) n = A,T,C or G 106agcgtggtcg cggccgangt ctggcgtgtg ccacatcggt cccacctcgc tttacaaaac 60agtcctgaac ttnatctaat aaaattattg tacacnacat ttacattaga aaaaganagc 120tgggtgtang aaaccgggcc tggtgttccc tttaagcgaa ngtggctcca cagttggggc 180atcgtcgctt cctcnaagca aaaacgccaa tgaaccccna agggggaaaa aggaatgaag 240gaactgnccn gggangnccg ctccgaaa 268 107 353 DNA Homo sapien misc_feature (1)...(353) n = A,T,C or G 107tcgagcggcc gcccgggcag gtggccaggc catgttatgg gatctcaacg aaggcaaaca 60cctttacacn ctagatggtg gggacatcat caacgccctg tgcttcagcc ctaaccgcta 120ctggctgtgt gctgccgcag gccccagcat caagatctgg gatttanagg gaaagatcnt 180tgtnnatgaa ctgaancnta aattatcagt tccannacca ngcaaaaacc acccngtgca 240ctccctggcc tggtctgctg atgggacctc gggcgcgaac acgctnancc caattccanc 300acactgggcg gncgttacta ntggatccga actcnggtac caancttggc gtt 353 108 360 DNA Homo sapien misc_feature (1)...(360) n = A,T,C or G 108agcgtggtcg cggccgaagt cctggcctca catgaccctg ctccagcaac ttgaacagga 60naagcagcag ctacatcctt aaggtccgga aagttagatg aagatttgga tcctgcattg 120ncctgcctcc cacctatctc tcccnaatta taaacagcct ccttgggaag cagcagaatt 180taaaaactct cccnctgccc tnttgaacta cacaccnacc gggaaaacct ttttcanaat 240ggcacaaaaa tncnagggaa tgcatttcca tgaangaana aactgggtta cccaaaatta 300ttgggttggg gaaatccngg gggggttttn aaaaaagggc aanccnccaa anaaaaaaac 360 109 101 DNA Homo sapien misc_feature (1)...(101) n = A,T,C or G 109atcgtggtcn cggccgaagt cctgtgtcct ggatgggccg tgtgcancga atccgttggc 60gactcctaac taccaanaaa angactctcg gaagaaattt c 101 110 300 DNA Homo sapien misc_feature (1)...(300) n = A,T,C or G 110ccanggaaac ccagagtcac atgagatagg gtggctttcg ggacaggggg tcagangaat 60ggtacatgga tctcagcccc tgatggacac ggaacaggtg tggtcagaac tcccangatt 120ctgcatccan gatccagtct ctatagaagt tatggatcat tccttcattt cattcccccc 180ttcatgaaaa aacttctgaa caagcctttt ttctcacttt ggggccctgt ttggcncaag 240gtnttnantt ggggaaaaaa aaacaaatcc nttccnttan ccctccgtgg ggaatgacct 300 111 366 DNA Homo sapien misc_feature (1)...(366) n = A,T,C or G 111cgagcggccg cccgggcagg tccttgtgtt gccatctgtt ancattgatt tctggaatgg 60aacanctttc tcaaagtttg gtcttgctan tcatgaagtc atgtcagtgt cttaagtcac 120tgctgctcac ttccttaccc agggaatata ctgcataagt ttctgaacac ctgttttcan 180tattcactgt tcctctcctg cccaaaattg gaagggacct catttaaaaa tcaaatttga 240atcctgaaan aaaaacngga aatntttctc ttggaatttg gaatagaatt attcanttga 300ataacatgtt ttttcccctt gccttgctct tcncaanaac atctggacct cggccgcgac 360acctta 366 112 405 DNA Homo sapien misc_feature (1)...(405) n = A,T,C or G 112ctgactncta aacttctaat tcnatcaana taactactct ccttccgtct tncagagtgt 60tcacaataaa tctgtgaatc tggcatacac agttgctgga aaattgttct tcctccacna 120aaaggtcaat tgttcnccnc atgaaanaag ataaattgtt catccatcac tnctgaacca 180tccaaaacgc cggcggaatt attnccccgt tattatgggg aacggaattt tnaataaatt 240tgggaangaa tggggctttt attgttttgt tttccccctt tcttggcatt gattgggccg 300caatgggccc cctcgctcan aanntgcccc ggggccggcc gctccaaaac cgaaattccc 360anccacactt ggcgggccgt tactanttgg atccgaactc ggtta 405 113 401 DNA Homo sapien 113ggatagaaga gtatatgggt ttggcaccac ggggtggata ggcaaaacat ttggttgata 60aggcgcagat tctgaactaa cttgtaaggc ttgtctggtt ttaggacagg taaaatgggg 120gaatggtaag gagagtttat aggttttagg agcccatgct gtagcaggca agtgataaca 180ggctttaatc ctttcaaagc atgctgtggg atgagatatt ggcatttgag cggggtaagg 240gtgattaggt tttaatgaga tggtaagggg tgcatgatcc ggtccgccaa ggaagggaag 300tagaggtatc ttatacttgt ggggttaagg tgggggggat ataagaggga ggacgccaaa 360ggaggctttg gattaggaat aaggggcggc aatgagatgc a 401 114 401 DNA Homo sapien misc_feature (1)...(401) n = A,T,C or G 114angtccacag gangcangag gccaggctcc gtcccancca gtccatgatg ttgaagagga 60ggaagcagca catggggttg aagaactgac tccacttccc aggactggtg gagctggtca 120ccatggctgt ggtggcgggg aagacggaca gggtgacttc tggaagacag tgaagactga 180aggttttcct ggcttctggg gctcatctgg ctctgattcc ggctccttct ccaggtcaag 240atccagggtt cagagctact ttcttggggg actactnggg aatcccgttc tcatctgggg 300gtngaggggg gacggggnaa gggncatgct tgtgacccag gtttcccacc tcggcccgcg 360accacgctaa ggcccgaatt ncagcacact tggcggcccg t 401 115 401 DNA Homo sapien 115atccctgtaa gtctattaaa tgtaaataat acatacttta caacttctct tagtcggccc 60ttggcagatt aaatctttgc aaaattccat atgtgctatt gaaaaatgaa ataaaacctc 120agatgtctga attcttattt caaatacagt tatataatta ttttaaatta caatatacaa 180tttctgttaa atacaactgt taagggattc tgagaacaat tataagatta taataatata 240tacaaactaa cttctgaaat gacatgggtt gtttccttcc caccctccta ccctctcaaa 300gagtttttgc atttgctgtt cctggttgca aaaggcaaaa gaaaatctaa aaatagtctg 360tgtgtgtcca cgacatgctc gctcctttga gaatctcaaa c 401 116 301 DNA Homo sapien misc_feature (1)...(301) n = A,T,C or G 116ngatttaatt gnnagcttct ttttaatgga atnnttggct aaaatgaatt gatgattatg 60aatatcccta ggaggagtta gcatggannn tgatcatttt cttngnactc ctttangaca 120nggaaacagg natcagcatg anggtancan aaaccttatn accnangcgc acganctgac 180ttcttccaaa gagttgnggt tccgggcagc ggtcattgcc gtgcccattg ctggagggct 240gattctagtg ntgcttatta tgctggccct gaggatgctt ccaanatgaa aataagangc 300t 301 117 383 DNA Homo sapien misc_feature (1)...(383) n = A,T,C or G 117aattgcaact ggacttttat tgggcagtta cnacaacnaa tgttttcana aaaatatttg 60gaaaaaatat accacttcat agctaagtct tacagagaan aggatttgct aataaaactt 120aagttttgaa aattaagatg cnggtanagc ttctgaacta atgcccacag ctccaaggaa 180nacatgtcct atttagttat tcaaatacca gttgagggca ttgtgattaa gcaaacaata 240tatttgttan aactttgntt ttaaattact gntncttgac attacttata aaggagnctc 300taactttcga tttctaaaac tatgtaatac aaaagtatan ntttccccat tttgataaaa 360gggccnanga tactgantag gaa 383 118 301 DNA Homo sapien 118ctgctagaat cactgccgct gtgctttcgt ggaaatgaca gttccttgtt ttttttgttt 60ctgtttttgt tttacattag tcattggacc acagccattc aggaactacc ccctgcccca 120caaagaaatg aacagttgta gggagaccca gcagcacctt tcctccacac accttcattt 180tgaagttcgg gtttttgtgt taagttaatc tgtacattct gtttgccatt gttacttgta 240ctatacatct gtatatagtg tacggcaaaa gagtattaat ccactatctc tagtgcttga 300c 301 119 401 DNA Homo sapien 119taaggacatg gacccccggc tgattgcatg gaaaggaggg gcagtgttgg cttgtttgga 60tacaacacag gaactgtgga tttatcagcg agagtggcag cgctttggtg tccgcatgtt 120acgagagcgg gctgcgtttg tgtggtgaat ggggaggaaa tgtcactgcc gaagaccaaa 180aacaagcttc ttggtataaa agactcttac agaatatgtg tattgtaatt tattgatctg 240gatgcttaag tgtcatggac agtaaatgaa tttgaacttt atgtttgagg acatgacatt 300gggtttgaaa atataaactg cttttgagca gtttaagtca gggcatttga gaataaaata 360ggaactttct cttcagtttg taaaactctc ttgccctctc t 401 120 301 DNA Homo sapien 120tccagagata ccacagtcaa acctggagcc aaaaaggaca caaaggactc tcgacccaaa 60ctgccccaga ccctctccag aggttggggt gaccaactca tctggactca gacatatgaa 120gaagctctat ataaatccaa gacaagcaac aaacccttga tgattattca tcacttgggt 180gagtgcccac acagtcaagc tttaaagaaa gtgtttgctg aaaataaaga aatccagaaa 240ttggcagagc agtttgtcct cctcaatctg gtttatgaaa caactgacaa acacctttct 300c 301 121 2691 DNA Homo sapien 121gcttgcccgt cggtcgctag ctcgctcggt gcgcgtcgtc ccgctccatg gcgctcttcg 60tgcggctgct ggctctcgcc ctggctctgg ccctgggccc cgccgcgacc ctggcgggtc 120ccgccaagtc gccctaccag ctggtgctgc agcacagcag gctccggggc cgccagcacg 180gccccaacgt gtgtgctgtg cagaaggtta ttggcactaa taggaagtac ttcaccaact 240gcaagcagtg gtaccaaagg aaaatctgtg gcaaatcaac agtcatcagc tacgagtgct 300gtcctggata tgaaaaggtc cctggggaga agggctgtcc agcagcccta ccactctcaa 360acctttacga gaccctggga gtcgttggat ccaccaccac tcagctgtac acggaccgca 420cggagaagct gaggcctgag atggaggggc ccggcagctt caccatcttc gcccctagca 480acgaggcctg ggcctccttg ccagctgaag tgctggactc cctggtcagc aatgtcaaca 540ttgagctgct caatgccctc cgctaccata tggtgggcag gcgagtcctg actgatgagc 600tgaaacacgg catgaccctc acctctatgt accagaattc caacatccag atccaccact 660atcctaatgg gattgtaact gtgaactgtg cccggctcct gaaagccgac caccatgcaa 720ccaacggggt ggtgcacctc atcgataagg tcatctccac catcaccaac aacatccagc 780agatcattga gatcgaggac acctttgaga cccttcgggc tgctgtggct gcatcagggc 840tcaacacgat gcttgaaggt aacggccagt acacgctttt ggccccgacc aatgaggcct 900tcgagaagat ccctagtgag actttgaacc gtatcctggg cgacccagaa gccctgagag 960acctgctgaa caaccacatc ttgaagtcag ctatgtgtgc tgaagccatc gttgcggggc 1020tgtctgtaga gaccctggag ggcacgacac tggaggtggg ctgcagcggg gacatgctca 1080ctatcaacgg gaaggcgatc atctccaata aagacatcct agccaccaac ggggtgatcc 1140actacattga tgagctactc atcccagact cagccaagac actatttgaa ttggctgcag 1200agtctgatgt gtccacagcc attgaccttt tcagacaagc cggcctcggc aatcatctct 1260ctggaagtga gcggttgacc ctcctggctc ccctgaattc tgtattcaaa gatggaaccc 1320ctccaattga tgcccataca aggaatttgc ttcggaacca cataattaaa gaccagctgg 1380cctctaagta tctgtaccat ggacagaccc tggaaactct gggcggcaaa aaactgagag 1440tttttgttta tcgtaatagc ctctgcattg agaacagctg catcgcggcc cacgacaaga 1500gggggaggta cgggaccctg ttcacgatgg accgggtgct gaccccccca atggggactg 1560tcatggatgt cctgaaggga gacaatcgct ttagcatgct ggtagctgcc atccagtctg 1620caggactgac ggagaccctc aaccgggaag gagtctacac agtctttgct cccacaaatg 1680aagccttccg agccctgcca ccaagagaac ggagcagact cttgggagat gccaaggaac 1740ttgccaacat cctgaaatac cacattggtg atgaaatcct ggttagcgga ggcatcgggg 1800ccctggtgcg gctaaagtct ctccaaggtg acaagctgga agtcagcttg aaaaacaatg 1860tggtgagtgt caacaaggag cctgttgccg agcctgacat catggccaca aatggcgtgg 1920tccatgtcat caccaatgtt ctgcagcctc cagccaacag acctcaggaa agaggggatg 1980aacttgcaga ctctgcgctt gagatcttca aacaagcatc agcgttttcc agggcttccc 2040agaggtctgt gcgactagcc cctgtctatc aaaagttatt agagaggatg aagcattagc 2100ttgaagcact acaggaggaa tgcaccacgg cagctctccg ccaatttctc tcagatttcc 2160acagagactg tttgaatgtt ttcaaaacca agtatcacac tttaatgtac atgggccgca 2220ccataatgag atgtgagcct tgtgcatgtg ggggaggagg gagagagatg tactttttaa 2280atcatgttcc ccctaaacat ggctgttaac ccactgcatg cagaaacttg gatgtcactg 2340cctgacattc acttccagag aggacctatc ccaaatgtgg aattgactgc ctatgccaag 2400tccctggaaa aggagcttca gtattgtggg gctcataaaa catgaatcaa gcaatccagc 2460ctcatgggaa gtcctggcac agtttttgta aagcccttgc acagctggag aaatggcatc 2520attataagct atgagttgaa atgttctgtc aaatgtgtct cacatctaca cgtggcttgg 2580aggcttttat ggggccctgt ccaggtagaa aagaaatggt atgtagagct tagatttccc 2640tattgtgaca gagccatggt gtgtttgtaa taataaaacc aaagaaacat a 2691 122 683 PRT Homo sapien 122Met Ala Leu Phe Val Arg Leu Leu Ala Leu Ala Leu Ala Leu Ala Leu 1 5 10 15Gly Pro Ala Ala Thr Leu Ala Gly Pro Ala Lys Ser Pro Tyr Gln Leu 20 25 30Val Leu Gln His Ser Arg Leu Arg Gly Arg Gln His Gly Pro Asn Val 35 40 45Cys Ala Val Gln Lys Val Ile Gly Thr Asn Arg Lys Tyr Phe Thr Asn 50 55 60Cys Lys Gln Trp Tyr Gln Arg Lys Ile Cys Gly Lys Ser Thr Val Ile65 70 75 80Ser Tyr Glu Cys Cys Pro Gly Tyr Glu Lys Val Pro Gly Glu Lys Gly 85 90 95Cys Pro Ala Ala Leu Pro Leu Ser Asn Leu Tyr Glu Thr Leu Gly Val 100 105 110Val Gly Ser Thr Thr Thr Gln Leu Tyr Thr Asp Arg Thr Glu Lys Leu 115 120 125Arg Pro Glu Met Glu Gly Pro Gly Ser Phe Thr Ile Phe Ala Pro Ser 130 135 140Asn Glu Ala Trp Ala Ser Leu Pro Ala Glu Val Leu Asp Ser Leu Val145 150 155 160Ser Asn Val Asn Ile Glu Leu Leu Asn Ala Leu Arg Tyr His Met Val 165 170 175Gly Arg Arg Val Leu Thr Asp Glu Leu Lys His Gly Met Thr Leu Thr 180 185 190Ser Met Tyr Gln Asn Ser Asn Ile Gln Ile His His Tyr Pro Asn Gly 195 200 205Ile Val Thr Val Asn Cys Ala Arg Leu Leu Lys Ala Asp His His Ala 210 215 220Thr Asn Gly Val Val His Leu Ile Asp Lys Val Ile Ser Thr Ile Thr225 230 235 240Asn Asn Ile Gln Gln Ile Ile Glu Ile Glu Asp Thr Phe Glu Thr Leu 245 250 255Arg Ala Ala Val Ala Ala Ser Gly Leu Asn Thr Met Leu Glu Gly Asn 260 265 270Gly Gln Tyr Thr Leu Leu Ala Pro Thr Asn Glu Ala Phe Glu Lys Ile 275 280 285Pro Ser Glu Thr Leu Asn Arg Ile Leu Gly Asp Pro Glu Ala Leu Arg 290 295 300Asp Leu Leu Asn Asn His Ile Leu Lys Ser Ala Met Cys Ala Glu Ala305 310 315 320Ile Val Ala Gly Leu Ser Val Glu Thr Leu Glu Gly Thr Thr Leu Glu 325 330 335Val Gly Cys Ser Gly Asp Met Leu Thr Ile Asn Gly Lys Ala Ile Ile 340 345 350Ser Asn Lys Asp Ile Leu Ala Thr Asn Gly Val Ile His Tyr Ile Asp 355 360 365Glu Leu Leu Ile Pro Asp Ser Ala Lys Thr Leu Phe Glu Leu Ala Ala 370 375 380Glu Ser Asp Val Ser Thr Ala Ile Asp Leu Phe Arg Gln Ala Gly Leu385 390 395 400Gly Asn His Leu Ser Gly Ser Glu Arg Leu Thr Leu Leu Ala Pro Leu 405 410 415Asn Ser Val Phe Lys Asp Gly Thr Pro Pro Ile Asp Ala His Thr Arg 420 425 430Asn Leu Leu Arg Asn His Ile Ile Lys Asp Gln Leu Ala Ser Lys Tyr 435 440 445Leu Tyr His Gly Gln Thr Leu Glu Thr Leu Gly Gly Lys Lys Leu Arg 450 455 460Val Phe Val Tyr Arg Asn Ser Leu Cys Ile Glu Asn Ser Cys Ile Ala465 470 475 480Ala His Asp Lys Arg Gly Arg Tyr Gly Thr Leu Phe Thr Met Asp Arg 485 490 495Val Leu Thr Pro Pro Met Gly Thr Val Met Asp Val Leu Lys Gly Asp 500 505 510Asn Arg Phe Ser Met Leu Val Ala Ala Ile Gln Ser Ala Gly Leu Thr 515 520 525Glu Thr Leu Asn Arg Glu Gly Val Tyr Thr Val Phe Ala Pro Thr Asn 530 535 540Glu Ala Phe Arg Ala Leu Pro Pro Arg Glu Arg Ser Arg Leu Leu Gly545 550 555 560Asp Ala Lys Glu Leu Ala Asn Ile Leu Lys Tyr His Ile Gly Asp Glu 565 570 575Ile Leu Val Ser Gly Gly Ile Gly Ala Leu Val Arg Leu Lys Ser Leu 580 585 590Gln Gly Asp Lys Leu Glu Val Ser Leu Lys Asn Asn Val Val Ser Val 595 600 605Asn Lys Glu Pro Val Ala Glu Pro Asp Ile Met Ala Thr Asn Gly Val 610 615 620Val His Val Ile Thr Asn Val Leu Gln Pro Pro Ala Asn Arg Pro Gln625 630 635 640Glu Arg Gly Asp Glu Leu Ala Asp Ser Ala Leu Glu Ile Phe Lys Gln 645 650 655Ala Ser Ala Phe Ser Arg Ala Ser Gln Arg Ser Val Arg Leu Ala Pro 660 665 670Val Tyr Gln Lys Leu Leu Glu Arg Met Lys His 675 680 123 1205 DNA Homo sapien 123ccagtcagca gagggacagg aatcattcgg ccactgttca gacgggagcc acacccttct 60ccaatccaag cctggcccca gaagatcaca aagagccaaa gaaactggca ggtgtccacg 120cgctccaggc cagtgagttg gttgtcactt actttttctg tggggaagaa attccatacc 180ggaggatgct gaaggctcag agcttgaccc tgggccactt taaagagcag ctcagcaaaa 240agggaaatta taggtattac ttcaaaaaag caagcgatga gtttgcctgt ggagcggtgt 300ttgaggagat ctgggaggat gagacggtgc tcccgatgta tgaaggccgg attctgggca 360aagtggagcg gatcgattga gccctgcggt ctggctttgg tgaactgttg gagcccgaag 420ctcttgtgaa ctgtcttggc tgtgagcaac tgcgacaaaa cattttgaag gaaaattaaa 480ccaatgaaga agacaaagtc taaggaagaa tcggccagtg ggccttcggg agggcggggg 540gaggttgatt ttcatgattc atgagctggg tactgactga gataagaaaa gcctgaacta 600tttattaaaa acatgaccac tcttggctat tgaagatgct gcctgtattt gagagactgc 660catacataat atatgacttc ctagggatct gaaatccata aactaagaga aactgtgtat 720agcttacctg aacaggaatc cttactgata tttatagaac agttgatttc ccccatcccc 780agtttatgga tatgctgctt taaacttgga agggggagac aggaagtttt aattgttctg 840actaaactta ggagttgagc taggagtgcg ttcatggttt cttcactaac agaggaatta 900tgctttgcac tacgtccctc caagtgaaga cagactgttt tagacagact ttttaaaatg 960gtgccctacc attgacacat gcagaaattg gtgcgttttg tttttttttc ctatgctgct 020ctgttttgtc ttaaaggtct tgaggattga ccatgttgcg tcatcatcaa cattttgggg 080gttgtgttgg atgggatgat ctgttgcaga gggagaggca gggaaccctg ctccttcggg 1140ccccaggttg atcctgtgac tgaggctccc cctcatgtag cctccccagg cccagggccc 1200tgagg 1205 124 583 DNA Homo sapien 124ccaagaagca gtggccttat tgcatcccaa accacgcctc ttgaccaggc tgcctccctt 60gtggcagcaa cggcacagct aattctactc acagtgcttt taagtgaaaa tggtcgagaa 120agaggcacca ggaagccgtc ctggcgcctg gcagtccgtg ggacgggatg gttctggctg 180tttgagattc tcaaaggagc gagcatgtcg tggacacaca cagactattt ttagattttc 240ttttgccttt tgcaaccagg aacagcaaat gcaaaaactc tttgagaggg taggagggtg 300ggaaggaaac aaccatgtca tttcagaagt tagtttgtat atattattat aatcttataa 360ttgttctcag aatcccttaa cagttgtatt taacagaaat tgtatattgt aatttaaaat 420aattatataa ctgtatttga aataagaatt cagacatctg aggttttatt tcatttttca 480atagcacata tggaattttg caaagattta atctgccaag ggccgactaa gagaagttgt 540aaagtatgta ttatttacat ttaatagact tacagggata agg 583 125 783 DNA Homo sapien 125tcaaccatac atactgcttc cactagctaa taccaaatgc aggttctcag atccagacaa 60atggaggaaa agaacattta tgcttccgtt tcagaaagcc aagtcgtagt tttggccctt 120cctttctcta aagtttattc ccaaaaacag gtagcattcc tgattgggca gagaagagga 180tattttcagc ccacatctgc tgcaggtatg tcattttctc ccatcttcac tgtgactagt 240aaagatctca ccacttctct ttggaatttc caactttgct tgtgattgaa tgtcacttcg 300tgaatttgta ttatgtcaga tcacttggca ttgctcttcc atatgcatca agttgccagg 360cactgttgcg ctgtcgggcc cactggaatc cacgggggtg aaacaaattc aattatgctt 420ttacagatcc tgctcaaaaa aggtttcaac tgcttaacca agtacagctc attcttccac 480cttcttactc tgcaaccaaa ccaagtgccc catactacag gtaggtgccg agaaattccg 540cagcagaaaa tccaaaatca tttctgaaac ctccttgcta acaaaagttc tttttttctc 600caaacagcat ataaaatgat caagtcttga aagagaaaag aagcaaagta gcaaatacat 660caacaattca ctatcagaaa cacataaaat cccagagaga gagaaggcag tatctctgaa 720tcatggatgg acttggaaag ttcggaagga ttccgagtgc ttcctttcag aaagacaatt 780ctg 783 126 604 DNA Homo sapien 126cctgctagaa tcactgccgc tgtgctttcg tggaaatgac agttccttgt tttttttgtt 60tctgtttttg ttttacatta gtcattggac cacagccatt caggaactac cccctgcccc 120acaaagaaat gaacagttgt agggagaccc agcagcacct ttcctccaca caccttcatt 180ttgaagttcg ggtttttgtg ttaaagttaa tctgtacatt ctgtttgcca ttgttacttg 240tactatacat ctgtatatag tgtacggcaa aagagtatta atccactatc tctagtgctt 300gactttaaat cagtacagta cctgtacctg cacggtcacc cgctccgtgt gtcgccctat 360attgagggct caagctttcc cttgtttttt gaaaggggtt tatgtataaa tatattttat 420gcctttttat tacaagtctt gtactcaatg acttttgtca tgacattttg ttctacttat 480actgtaaatt atgcattata aagagttcat ttaaggaaaa ttacttggta caataattat 540tgtaattaav agatgtagcc tttattaaaa ttttatattt ttcaaaaaaa aaaaaaaaaa 600aaaa 604 127 417 DNA Homo sapien 127ctgagcctct gtcaccagag aaggctgagg ccccaatggc acacctcaga aacctacacc 60ccgaggctgg acggctggac tcctgagcac aagctccctc tcgcaccctt tgccagacag 120tttgtctcca atttcaaact gacctaaggc tcttactcct ggattttttg tttttaaacc 180ttctcccagc cagtcttcgg gagggcatga ttagagaagt gctcctttgc tgatggagga 240ggggacctaa ggaagaaggt ggatcccagg tgcctcctct ctaattgatc ctccccacct 300agtttccttt gcctctcttc cttctaccag gtcatgtttt ttactctctg ccccttctgc 360ctcctagcat ttcaaaaact gtagagtgca ccccatagtg gacattttta gtccagg 417 128 657 DNA Homo sapien 128ccacactgaa atgcagttta atgtggaaac ttttctaaat acatattgta gcatctttgg 60acatcaacgt gtggcctgaa atttttatta ttgttccctc ttctcctcca ttaaaaaaaa 120aatctccttg tggtatttag tcatttacca ttaacacata ttatggctta aaaagggcca 180tcccttcctt ttctgagctg gagttcttca cgctcacctt tgatgcatgg ccttagctgg 240ttactttgcc ttggtttggt catgaacatt ggggttagtg gcctggcaac ttgaatgcat 300atggaaagaa caatgccaag tgatctgaca taatacaaat tccgaagtga cattcaatca 360caagcaaagt tggaaattcc aaagagaagt ggtgagatct ttactagtca cagtgaagat 420gggagaaaat gacatacctg cagcagatgt gggctgaaaa tatcctcttc tctgcccaat 480caggaatgct acctgttttt gggaataaac tttagagaaa ggaagggcca aaactacgac 540ttggctttct gaaacggaag cataaatgtt cttttcctcc atttgtctgg atctgagaac 600ctgcatttgg tattagctag tggaagcagt atgtatggtt gaagtgcatt gctgcag 657 129 1220 DNA Homo sapien 129cgcgtgctcg gctcacacca acaaggcaag ccaaaggcgc ccctccccag agggatccct 60aacgtgccca gcatgtagat tctggactaa cagacaacat acattcaccg ctggtcaccc 120agatcctcat tcaaacccac tgctggcaca tccctttcct tactttgccc tgtgctacca 180gccacggaag gagcctctct tgttttttct ataaaatggg taggcaggag aaaagcaggt 240gccctaagat tgctctaagg cccagcatgt ggttacagtt ctctgacttg cagaacctgc 300caggtgtatg gctacaagtt atcctcgtgc tgatctgtct cattactaag ttaatggaga 360agacagaaag gtaaaaatca cgtgtagcaa gaacaactct tatttcacaa actcaggtat 420gaaacgaaac gcctgtcctt catggaactg cttttagctc ctgtcttttc aaaatggcag 480agggagttcc tacacacact ttttccctgg aggccaaggt ctaggggtag aaaggggagg 540ggtggggcta ccaggtagca gttgacaacc caaggtcaga ggagtggccc tcagtgtcat 600ctgtccacag tgatacctgc caagatgacc actgacccac atctggtctt agtcattggt 660ctcctcagat ttctggggcc acctgcaagc cccattccat tcctacagat ctctcagcca 720cctgtaagtc ctttgtgaag atgtgggtga cacaggggga caggaaaacc catttctcaa 780cccagatcca tgtctccact gcttctactc tgggttggga ttcaggaaga caggcacagt 840cctctctgtt catagaaaca cctgccagtg tcaaggattc cagtcaggtg tctatcccaa 900ctggtcaggg agagaagggc agacccattc tcaaagacca ccatgtccaa ggtctgacag 960ctccccactg gctgccccca caggggcttt aggctggtct gggtcatggg gaagcgtccc 020tcttatcgct ggtctgtgtt ctcctggatt tggtatctat gttggtacga ctcctggcct 080tttatctaaa ggactttggc ttttgtaaat cacaagccaa taatagactt ttttctcccc 1140ctctgttttt tgctgtgtca tctctgcctt gagactgcct tgagacagtg cttgccttga 1200gagagtgagc caattaacag 1220 130 1274 DNA Homo sapien 130ccatatgagt ttgccatctc catggatgcc atttcaatgc cttcagggta atcattctct 60ccccaaagac tgcccacggg gtcatcactc ctgtgacgaa atgagggctg gattgaagat 120gttctgctga gcacccccct ggtcatcttt ggggtctcag aagagccata atcatgacca 180ttctcagcat ctgaataatc aggttctctc caagtgcttg gcaagttctg attgtcctca 240gcactgggat agtctggctc cccaaaaaag ggtggagagt taggttgaat gtcagcgcct 300ggataatcag gctttcccag agagtctgcg tatggattga ttctaaaact tgtatgttcc 360agattctttc tggatcctgg atggttcaaa ttggctctgg gtccaggatg atcagagttg 420ctctgagctc cagggtagtc cggttctaag gagccaaaat gatctggatg tgttctggag 480cctgcatagt ttccactgct gctggagcct gcaaaatcag gatttcgttg agatccaggg 540tagtctggtt gtctggatga tgctcggtgg tagggatgac tctgaaattc actataatct 600ggctctggta gagaggtagg atggtctggg cttgttctag aggctgcaga gtatgcattg 660cttctggtgc cagaatagtc tggattactc agagatctag gataatttgg ttctgccaga 720gacccaggat agtctggacg tgttctggag gctacagagt atggattgct cctggtgccg 780gggtaatctg gattgttcag aggacctgga acatctggat aaccttgagt tttcaaatac 840ccctgcgtac ggttctgaga ccctgaatag tcagggtaat ctgggtcttc ctcagaccag 900ttattcctgt agtaggcaga catgttggta tggactcttc accctggagt ggtaaactgt 960cccagcattt gcaattactc agggatcttt tttttttcac ttttttgccc ttattgttct 1020tgctttgtcc caagtagatg caaatgttgt gcaaaccaac ttgatcttaa gatgttgtta 1080agaacactgg agtcacgtgt ccatgggtcc ttcaggctgg cttttgatgg gagctgggat 1140gcagatgatt tacggagggt tataatctgt gatgctggtc tgaagtctga atattccaag 1200ttgctgactg caggcagagc ctcatgtcct cctggcgctc ctgttgccgc tgcttgcgct 1260ggccctcggg tcga 1274 131 554 DNA Homo sapien misc_feature (1)...(554) n = A,T,C or G 131ctgtaattct gccttttcta ccttcattcc atccttcctc tgcccagata aagkccagca 60gaaattcctc ctttctacct ctctgggact ctgagacagg aaatcttcaa ggaggagttt 120ttccctcccc actattctta ttctcaaccc ccagaggaac caaggctgct gtacccacct 180cagggacaga actccacact atagtgggaa agcttcaggg acccctcctt ttagtgctca 240gggctcacct atgctactgg tccttttggc aaaaaaggaa aatgatagag ccagggttgc 300ccctgatgta gcagccttac tgtggagggg ccaaagctgg tgttcagagc tcacccaagg 360agggaggtga taaggtgtca tgcgttctgc tgaacccact ggntggtatg aacatgaggc 420ttggggtgag ggaaaccaag taggggttgg agaaggagca gcacctttgt macacctggc 480tacccatagc tagctttctg ccctcaaaaa ctcagccttc aagggatcca gcccacacac 540gccacaggca gcag 554 132 787 DNA Homo sapien 132ctggtcaccc aactcttgtg gaagagggga attgagatcg agtactgaat atctggcaga 60gaggctggaa tccttcagcc ccagagccca gggaccactc cagtagatgc agagaggggc 120ctgcccaggg gtcagggcag tgggtatcac tggtgacatc aagaatatca gggctgggga 180ggcatctttg tttcctggtg ccctcctcaa agttgctgac actttgggga cgggaagggg 240tagaagtagg gctgctcctt ttggagctgg agggaataga cctggagaca gagttgaggc 300agtcgggctg tccaggttct aagcatcaca gcttctgcac tgggctctga ggagattctc 360agccagagga tcccagcctc ctcctccctc aaatgtcagt ccaagcaaat accaaagcaa 420cgcatcgatt ttgtggaagt caattagaga tgtggggagc tatcggagac aagcactatt 480gtaccttttc acctccacac ttgtcacaag cagggactgt ctcctcccca ctttgcttgc 540cacgcctgcc atggcttgag ctggggtgag gagtggtctt tatcttcttt gggagatcct 600gactggttgc gcacttgcta agggcaggaa gtctggaggg ctgcaggaat ggtgccgttg 660ataaacaggt ggacttataa tcatcatgca ctgcaattgt agaacatagt ctcctgcctt 720ttctcatttg tataattgtc tgggtcaata ttctcccaat attgggaggg gctctgcagc 780cctccag 787 133 219 DNA Homo sapien misc_feature (1)...(219) n = A,T,C or G 133tactgctcta agttttgtna aatttttcat attttaattt caagcttatt ttggagagat 60aggaaggtca tttccatgta tgcataataa tcctgcaaag tacaggtact ttgtctaaga 120aacattggaa gcaggttaaa tgttttgtaa actttgaaat atatggtcta atgtttaagc 180agaattggaa nagactaata tcggttaaca aataacaac 219 134 234 DNA Homo sapien 134 135 414 DNA Homo sapien 135ctccagcctg gctatatccg gtcccgctat aacctgggca tcagctgcat caacctcggg 60gctcaccggg aggctgtgga gcactttctg gaggccctga acatgcagag gaaaagccgg 120ggcccccggg gtgaaggagg tgccatgtcg gagaacatct ggagcaccct gcgtttggca 180ttgtctatgt taggccagag cgatgcctat ggggcagccg acgcgcggga tctgtccacc 240ctcctaacta tgtttggcct gccccagtga cagtgggacg ggctgccctg tgagtgtcca 300cctggggatt aaatatgtct tcaacaaggg aggcctggct tctacaatgg tttaggtaaa 360ggggcctttg aagtagttct ggccaggctt gcaatacaca caacacaaga gcca 414 136 461 DNA Homo sapien 136gaagtgatta ataggtttat ttgcatatac acagagaaga gtcagcattg ttgggtgaga 60agaggcaggc tgtgaggagg taaggcttca gcagaggaag gcaccttgac agacaacacg 120agactcctat taaatcagca cagttgcaaa cttcacctgc ctcaagccaa cagctcattg 180aactcatatg tcgattgaga atcatttaca aaaccaggag agaaacaatg ggaagagcaa 240cggtctctca tccctggacc tgacactcaa aacattatgt acaggatgca ggaacaaaat 300ctgtctgatc agtgccctct cctgctggga aaaacaccca tcacggaaga atttggggat 360taaatatgtc ttcaacaagg gaggcctggc ttctacaatg gtttaggtaa aggggccttt 420gaagtagttc tggccaggct tgcaatacac acaacacaag a 461 137 269 DNA Homo sapien 137atagcaaatg gacacaaatt acaaatgtgt gtgcgtggga cgaagacatc tttgaaggtc 60atgagtttgt tagtttaaca tcatatattt gtaatagtga aacctgtact caaaatataa 120gcagcttgaa actggcttta ccaatcttga aatttgacca caagtgtctt atatatgcag 180atctaatgta aaatccagaa cttggactcc atcgttaaaa ttatttatgt gtaacattca 240aatgtgtgca ttaaatatgc ttccacagt 269 138 452 DNA Homo sapien misc_feature (1)...(452) n = A,T,C or G 138ctccatggga ggcaaaatat agagaattta tggtgcccaa ctcttatgta atcactggac 60taatcttccc tggtaactat gcaacatttg gacagaaagg cacacaaaaa agtttaaata 120tttcatgtgc caatctggaa aaaaataatt taaatcaaca gaacagacag tacatctaca 180caaatgagga aagcagaaaa gatacctcac attcatttat ctcaggtttc aaagtggctt 240caatgctaaa gtaaatgtat taacatttgg aaaatacaag acaatttttt tgtttgtttt 300caattttttt agctctatac aatgattaca acataagaca aaaaaaaaaa aaaaacacaa 360aaaacaaaac aaaaaaggag ttcaggactt gttatcagtg tccaagtggc taanaactgg 420ttcccataac aagcattgaa agttaaggcc cc 452 139 474 DNA Homo sapien 139tgtgcctcat tgaggttaca attgaaacag atgtgagcac ctgagagact ttccctgatt 60atattcctcc acaaaccact gtaccatatt accttatttt atcttcttga aattcttatt 120cattggcttg tttgttgtct ctttgcatta gatatatgta agctccttgg cataaatttg 180acattggtag gggactgaca ttctaacctg gcccaggccc taggagagag ataactccac 240aaagcagcac atactatctt aggttagcag ggagctaact caccatgtag cagatgaaaa 300aaaccaaacc cagcactgtg cataaatacc acttgccaag aagtcaggtc ctcggcaacc 360gagaatcaac ctcagcacaa acgcaggtgg ctgggctctg ttccccctta gccaccacct 420cagcctctcc cctcccctgc cccaagtgcc caagagcttg gctctctgtg cttt 474 140 487 DNA Homo sapien 140cttccctgcc tcgtgttcct gagaaacgga ttaatagccc tttatccccc tgcaccctcc 60tgcaggggat ggcactttga gccctctgga gccctcccct tgctgagcct tactctcttc 120agactttctg aatgtacagt gccgttggtt gggatttggg gactggaagg gaccaaggac 180actgacccca agctgtcctg cctagcgtcc agcgtcttct aggagggtgg ggtctgcctg 240tcctggtgtg gttggtttgg ccctgtttgc tgtgactacc cccccccctc cccgaaccga 300gggacggctg cctttgtctc tgcctcagat gccacctgcc ccgcccatgc tccccatcag 360cagcatccag actttcagga agggcagggc cagccagtcc agaaccgcat ccctcagcag 420ggactgataa gccatctctc ggagggcccc ctaataccca agtggagtct ggttcacacc 480ctggggg 487 141 248 DNA Homo sapien misc_feature (1)...(248) n = A,T,C or G 141 142 173 DNA Homo sapien 142tactaagatt gtccaagcct ccctcttaaa actttctttc cctttagagg aatcattact 60tcgtattaaa agtttctact tccttgtaga atatctacat ccaatgggcc atggcacaaa 120atttaagtct agaaagaatc ttaaaggctc atcttatagt aaccagaggc agg 173 143 511 DNA Homo sapien misc_feature (1)...(511) n = A,T,C or G 143cctcgtcaga ggggtggttc ctggtnacct gtactccacg gacctcggtg aagcaaaagc 60ttcagggcag agggaatgag gcaacccagt ggcagccccg ctgggccccg tggctcctgc 120tctcctattg gacgtagagg caggggagag acttctctat acaaatattc tcatcacaga 180agggatgatc cttgctgctc tgccgtaggg tttttgatgc tgagctatgc tgcacatgac 240gttaacctaa agaacttgga ctgagctttt aaaaaaggac agcaaacaat tttataatcc 300ttaaagtgta atagacggtt acactagtgc agggtattgg ggaggctctt tgggtgtgga 360ggctgtcact tgtatttatt gtgactctaa atctttgata gtaaaacaaa tgtaaaaaga 420aatgtttgcc accagatggg aatagaagtt ccaataagca ggctggaatg ggtggctata 480cgttgtatca cgaggaagtt ttagactctg a 511 144 190 DNA Homo sapien 144cattcttctg tcacatgcca attcagttgt caatcccatt gtctatgctt accggaaccg 60agacttccgc tacacttttc acaaaattat ctccaggtat cttctctgcc aagcagatgt 120caagagtggg aatggtcagg ctggggtaca gcctgctctc ggtgtgggcc tatgatctag 180gctctcgcct 190 145 169 DNA Homo sapien 145gatgtggtta tctcctcaga tggccagttt gccctctcag gctcctggga tggaaccctg 60cgcctctggg atctcacaac gggcaccacc acgaggcgat ttgtgggcca taccaaggat 120gtgctgagtg tggccttctc ctctgacaac cggcagattg tctctggat 169 146 511 DNA Homo sapien 146atctagagaa gatttgggaa acacatgata gctatggtta aatacttaac agggcaatca 60cagggaagat gactagattt cctaacatcc atgagtgaaa tttatagaag tatactctct 120gacttgatat aaaggaagat tttaaaaaac atgactgttc aggagtgttc aagtagggtc 180agatgaccag tgattgggaa tacttcgtaa gcaggagcaa gtaagatctg agccactgtt 240ctatcggtag ggtgtctgtg gtattccttg gtcaaagaag tactctaagc aacttcagtc 300tcacgaatta ctatcaccct cgtgggcata catgatggtt accctaaaga ggaagtttca 360gaaggcagta atattggatc ctggaatagt cagacaggag ccttcatgca gatacccttt 420tcagttctcc atacacccat tcacaagtgg tcacaaaaac acccagtacc tttacttggc 480tttacccact taacaatatg ctcaatatga g 511 147 421 DNA Homo sapien misc_feature (1)...(421) n = A,T,C or G 147gaccagttga gttcttcctg gctattgtat aatccacagc cacactgtga aagcaaatct 60ggccagttag caacacaggg agaatctgcc tgaactgacc aaaggtgtcc atacttcatg 120tcagtgagaa tttcacctcc atcatgttct aaagagccaa caacagattc tagggcactg 180caaaatgctt cagcaattaa ttgaagttct gtttgagtac attcatcatc tttgagaatg 240ctttctgggt cgttgtgagt cttgtgtctg atatatgcag ccaaatgagt ttcagtacag 300ccacctccca acaaagccca tggttccttg agtgttaact gcaggacatg cagtgccgtc 360tgacacgtga gcttcagctc atcccangca gtgtcatttc tgttgcagag aagccaagct 420g 421 148 237 DNA Homo sapien 148acacaccact gttggccttc catctgggtt aagtcaactg tgagtagaaa ccgaagataa 60cagttttgta ttcataatgg ccttttcata ctccaagtac ttttgagcac agagcctctt 120gcttctgacc tggcacttgg aacacagata tatatatctt ttgttctgtc cctgggaaac 180tgatatttgt gtaagacaac caccagatat tttctctaat aaaatcttct aaaatta 237 149 168 DNA Homo sapien 149agagaaagtt aaagtgcaat aatgtttgaa gacaataagt ggtggtgtat cttgtttcta 60ataagataaa cttttttgtc tttgctttat cttattaggg agttgtatgt cagtgtataa 120aacatactgt gtggtataac aggcttaata aattctttaa aaggagag 168 150 68 DNA Homo sapien misc_feature (1)...(68) n = A,T,C or G 150ggtggggttt ggcagagatg antttaagtg ctgtggccag aagcgggggg ggggtttggt 60ggaaattt 68 151 421 DNA Homo sapien 151aggtgacacg tattcgggat gaaagtataa tagtcattcc ttcaaccctt gcatttatgg 60actctggaaa tcgaagatcc acagtgagta aagatgttcg tccaaagaca aaaaatagaa 120acagctcaac aaagcgagag acaaaaaaac aaaatggcac tgtggctctg cctttgaagt 180ctgggctcca gcagagggct gatcttccca caggagacga gacggcctat gacactctcc 240agaactgttg tcagtgccga attttacttc ccttgcccat tctaaatgag caccaggaga 300agtgccagag gttagctcac caaaagaaac tccagtgggg ctggtgagat ggctcagcgg 360gtaagagcac ccgactgctc ttccgaaggt ccggagttca aatcccagca accacatggt 420g 421 152 507 DNA Homo sapien misc_feature (1)...(507) n = A,T,C or G 152gaattcggca cnagctcgtg ccgccagggt nggtccnttt tttgctccgc ctcgccanga 60cttcctacag ctatcgccag tcgtcggcca cgtcntcctt cngaggcctg ggcggcggct 120ccgtgcgttn tgggccgggg gtcgcctttc nctcncccag cattcacggg ggctccggcg 180gccgcggcgt atccgtgtcc tccgcccgct ntgtgtcctc gtcctcctcn ggggcctacg 240gctngctgct acngcggctt cctgaccgct tccnacgggc tgctggcngg caacgagaag 300ctaaccatgc agaacctnaa cnaccgcctg gcctcctacc tgnacaaggt gcgcnccctg 360taggcggcca acggcnagct agaggtgaag atccnctact gggtaccaga agcaggggcc 420tgggccctgc ccgactacag ccactnctnc acnaccatgc agtacctgcn ggganaagat 480tntngggngc caccatngag aactgca 507 153 513 DNA Homo sapien 153gaattcggca cgaggtggct cagatgtcca ctactgggag tatggtcgaa ttgggaattt 60tattgtgaaa aagcccatgg tgctgggaca tgaagcttcg ggaacagtcg aaaaagtggg 120atcatcggta aagcacctaa aaccaggtga tcgtgttgcc atcgagcctg gtgctccccg 180agaaaatgat gaattctgca agatgggccg atacaatctg tcaccttcca tcttcttctg 240tgccgcgccc cccgatgacg ggaacctctg ccggttctat aagcacaatg cagccttttg 300ttacaagctt cctgacaatg tcacctttga ggaaggcgcc ctgatcgagc cactttctgt 360ggggatccat gcctgcagga gaggcggagt taccctggga cacaaggtcc ttgtgtgtgg 420agctgggcca atcgggatgg tcactttgct cgtggccaaa gcaatgggag cagctcaagt 480agtggtgact gatctgtctg ctacccgatt gtc 513 154 507 DNA Homo sapien misc_feature (1)...(507) n = A,T,C or G 154ggcacgagct cgtgccgaat tcggcncgag cagacacaat ggtaagaatg gtgcctgtcc 60tgctgtctct gctgctgctt ctgggtcctg ctgtccccca ggagaaccaa gatggtcgtt 120actctctgac ctatatctac actgggctgt ccaagcatgt tgaagacgtc cccgcgtttc 180aggcccttgg ctcactcaat gacctccagt tctttagata caacagtaaa gacaggaagt 240ctcagcccat gggactctgg agacaggtgg aaggaatgga ggattggaag caggacagcc 300aacttcagaa ggccagggag gacatcttta tggagaccct gaaagacatc gtggagtatt 360acaacgacag taacgggtct cacgtattgc agggaaggtt tggttgtgag atcgagaata 420acagaagcag cggagcattc tggaaatatt actatgatgg aaaggactac attgaattca 480acaaagaaat cccagcctgg gtcccct 507 155 507 DNA Homo sapien misc_feature (1)...(507) n = A,T,C or G 155ggcacgagga gacctaaggg ctgagtntcg ggaacaggag aaagctctgt tggccctcca 60gcagcagtgt gctgagcagg cacaggagca tgaggtggag accagggccc tgcaggacag 120ctggctgcag gcccaggcag tgctcaagga acgggaccag gagctggaag ctctgcgggc 180agaaagtcag tcctcccggc atcaggagga ggctgcccgg gcccgggctg aggctctgca 240ggaggccctt ggcaaggctc atgctgccct gcaggggaaa gagcagcatc tcctcgagca 300ggcagaattg agccgcagtc tggaggccag cactgcaacc ctgcaagcct ccctggatgc 360ctgccaggca cacagtcggc agctggagga ggctctgagg atacaagaag gtgagatcca 420ggaccaggat ctccgatacc aggaggatgt gcagcagctg cagcaggcac ttgcccagag 480ggatgaagag ctgagacatc agcagga 507 156 509 DNA Homo sapien misc_feature (1)...(509) n = A,T,C or G 156ggcacgagga cagagagaac cctgtngaaa gagcgttacc aggaggtcct ggacaaacag 60aggcaagtgg agaatcagct ccaagtgcaa ttaaagcagc ttcagcaaag gagagaagag 120gaaatgaaga atcaccagga gatattaaag gctattcagg atgtgacaat aaagcgggaa 180gaaacaaaga agaagataga gaaagagaag aaggagtttt tgcagaagga gcaggatctg 240aaagctgaaa ttgagaagct ttgtgagaag ggcagaagag aggtgtggga aatggaactg 300gatagactca agaatcagga tggcgaaata aataggaaca ttatggaaga gactgaacgg 360gcctggaagg cagagatctt atcactagag agccggaaag agttactggt actgaaacta 420gaagaagcag aaaaagaggc agaattgcac cttacttacc tcaagtcaac tcccccaaca 480ctggagacag ttcgttccaa acaggagtg 509 157 507 DNA Homo sapien 157ggcacgaggg cagccctcct accggcgcac gtggtgccgc cgctgctgcc tcccgctcgc 60cctgaaccca gtgcctgcag ccatggctcc cggccagctc gccttattta gtgtctctga 120caaaaccggc cttgtggaat ttgcaagaaa cctgaccgct cttggtttga atctggtcgc 180ttccggaggg actgcaaaag ctctcaggga tgctggtctg gcagtcagag atgtctctga 240gttgacggga tttcctgaaa tgttgggggg acgtgtgaaa actttgcatc ctgcagtcca 300tgctggaatc ctagctcgta atattccaga agataatgct gacatggcca gacttgattt 360caatcttata agagttgttg cctgcaatct ctatcccttt gtaaagacag tggcttctcc 420aggtgtaagt gttgaggagg ctgtggagca aattgacatt ggtggagtaa ccttactgag 480agctgcagcc aaaaaccacg ctcgagt 507 158 507 DNA Homo sapien misc_feature (1)...(507) n = A,T,C or G 158ggcacgagtc gagctgtgcc tattcgngtc aatccaagag tgagtaatgt gaagtctgtc 60tacaaaaccc acattgatgt cattcattat cggaaaacgg atgcaaaacg tctgcatggc 120cttgatgaag aagcagaaca gaaacttttt tcagagaaac gtgtggaatt gcttaaggaa 180ctttccagga aaccagacat ttatgagagg cttgcttcag ccttggctcc aagcatttat 240gaacatgaag atataaagaa gggaattttg cttcagctct ttggcgggac aaggaaggat 300tttagtcaca ctggaagggg caaatttcgg gctgagatca acatcttgct gtgtggcgac 360cctggtacca gcaagtccca gctgctgcag tacgtgtaca acctcgtccc caggggccag 420tacacgtntg ggaagggctc cagtgcannt ggcctnactg cntacgtaat gaaagaccct 480gagacaaggn anctggnnct gnnacag 507 159 508 DNA Homo sapien misc_feature (1)...(508) n = A,T,C or G 159ggcacnanaa accaggatta tggtnnggat ccaaagattg ctaatgcaat aatgaaggca 60gcagatgagg tagctgaagg taaattaaat gatcattttc ctctcgtggt atggcagact 120ggatcaggaa ctcagacaaa tatgaatgta aatgaagtca ttagcaatag agcaattgaa 180atgttaggag gtgaacttgg cagcaagata cctgtgcatc ccaacgatca tgttaataaa 240agccagagct caaatgatac ttttcccaca gcaatgcaca ttgctgctgc aatagaagtt 300catgaagtac tgttaccagg actacagaag ttacatgatg ctcttgatgc aaaatccaaa 360gagtttgcac agatcatcaa gattggacgt actcatactc aggatgctgt tccacttact 420cttgggcagg aatttagtgg ttatgttcaa caagtaaaat atgcaatgac aagaataaaa 480gctgccatgc caagaatcta tgagctcg 508 160 508 DNA Homo sapien misc_feature (1)...(508) n = A,T,C or G 160ggcacgagct tggagcaaag tcatctnaag gaattagagg acacacttca ggttaggcac 60atacaagagt ttgagaaggt tatgacagac cacagagttt ctttggagga attaaaaaag 120gaaaaccaac aaataattaa tcaaatacaa gaatctcatg ctgaaattat ccaggaaaaa 180gaaaaacagt tacaggaatt aaaactcaag gtttctgatt tgtcagacac gagatgcaag 240ttagaggttg aacttgcgtt gaaggaagca gaaactgatg aaataaaaat tttgctggaa 300gaaagcagag cccagcagaa ggagaccttg aaatctcttc ttgaacaaga gacagaaaat 360ttgagaacag aaattagtaa actcaaccaa aagattcagg ataataatga aaattatcag 420gtgggcttag cagagctaag aactttaatg acaattgaaa aagatcagtg tatttccgag 480ttaattagta gacatgaaga agaatcta 508 161 507 DNA Homo sapien 161ggcacgagcg ctaccggcgc ctcctctgcg gccactgagc cggagccggc ctgagcagcg 60ctctcggttg cagtacccac tggaaggact taggcgctcg cgtggacacc gcaagcccct 120cagtagcctc ggcccaagag gcctgctttc cactcgctag ccccgccggg ggtccgtgtc 180ctgtctcggt ggccggaccc gggcccgagc ccgagcagta gccggcgcca tgtcggtggt 240gggcatagac ctgggcttcc agagctgcta cgtcgctgtg gcccgcgccg gcggcatcga 300gactatcgct aatgagtata gcgaccgctg cacgccggct tgcatttctt ttggtcctaa 360gaatcgttca attggagcag cagctaaaag ccaggtaatt tctaatgcaa agaacacagt 420ccaaggattt aaaagattcc atggccgagc attctctgat ccatttgtgg aggcagaaaa 480atctaacctt gcatatgata ttgtgca 507 162 507 DNA Homo sapien misc_feature (1)...(507) n = A,T,C or G 162ggcacgagca gctgtgcacc gacatgntct cagtgtcctg agtaagacca aagaagctgg 60caagatcctc tctaataatc ccagcaaggg actggccctg ggaattgcca aagcctggga 120gctctacggc tcacccaatg ctctggtgct actgattgct caagagaagg aaagaaacat 180atttgaccag cgtgccatag agaatgagct actggccagg aacatccatg tgatccgacg 240aacatttgaa gatatctctg aaaaggggtc tctggaccaa gaccgaaggc tgtttgtgga 300tggccaggaa attgctgtgg tttacttccg ggatggctac atgcctcgtc agtacagtct 360acagaattgg gaagcacgtc tactgctgga gaggtcacat gctgccaagt gcccagacat 420tgccacccag ctggctggga ctaagaaggt gcagcaggag ctaagcaggc cgggcatgct 480ggagatgttg ctccctggcc agcctga 507 163 460 DNA Homo sapien 163ggcacgagaa ataactttat ttcattgtgg gtcgcggttc ttgtttgtgg atcgctgtga 60tcgtcacttg acaatgcaga tcttcgtgaa gactctgact ggtaagacca tcaccctcga 120ggttgagccc agtgacacca tcgagaatgt caaggcaaag atccaagata aggaaggcat 180ccctcctgac cagcagaggc tgatctttgc tggaaaacag ctggaagatg ggcgcaccct 240gtctgactac aacatccaga aagagtccac cctgcacctg gtgctccgtc tcagaggtgg 300gatgcaaatc ttcgtgaaga cactcactgg caagaccatc acccttgagg tggagcccag 360tgacaccatc gagaacgtca aagcaaagat ccaggacaag gaaggcattc ctcctgacca 420gcagaggttg atctttgccg gaaagcagct ggaagatggg 460 164 462 DNA Homo sapien 164ggcacgagcc ggatctcatt gccacgcgcc cccgacgacc gcccgacgtg cattcccgat 60tccttttggt tccaagtcca atatggcaac tctaaaggat cagctgattt ataatcttct 120aaaggaagaa cagacccccc agaataagat tacagttgtt ggggttggtg ctgttggcat 180ggcctgtgcc atcagtatct taatgaagga cttggcagat gaacttgctc ttgttgatgt 240catcgaagac aaattgaagg gagagatgat ggatctccaa catggcagcc ttttccttag 300aacaccaaag attgtctctg gcaaagacta taatgtaact gcaaactcca agctggtcat 360tatcacggct ggggcacgtc agcaagaggg agaaagccgt cttaatttgg tccagcgtaa 420cgtgaacatc tttaaattca tcattcctaa tgttgtaaaa ta 462 165 462 DNA Homo sapien 165ggcacgagga agccatgagc agcaaagtct ctcgcgacac cctgtacgag gcggtgcggg 60aagtcctgca cgggaaccag cgcaagcgcc gcaagttcct ggagacggtg gagttgcaga 120tcagcttgaa gaactatgat ccccagaagg acaagcgctt ctcgggcacc gtcaggctta 180agtccactcc ccgccctaag ttctctgtgt gtgtcctggg ggaccagcag cactgtgacg 240aggctaaggc cgtggatatc ccccacatgg acatcgaggc gctgaaaaaa ctcaacaaga 300ataaaaaact ggtcaagaag ctggccaaga agtatgatgc gtttttggcc tcagagtctc 360tgatcaagca gattccacga atcctcggcc caggtttaaa taaggcagga aagttccctt 420ccctgctcac acacaacgaa aacatggtgg ccaaagtgga tg 462 166 459 DNA Homo sapien misc_feature (1)...(459) n = A,T,C or G 166 167 464 DNA Homo sapien misc_feature (1)...(464) n = A,T,C or G 167gaattgggac caacganaan cntgcggntc ttnttttgcn tccanngccc agctnattgc 60tcagacacac atggggaagg tnaaggtcgg gagtcaacng atttggtngt attgnagcgt 120ttggtcacca gngctgcttt taactctggn aaagtggata ttgttgtcat naatgacccc 180tncattgacc tnaactacat ggtttacatg ttccaatatg attccaccca tggcaaattc 240catngcaccg tnaaggctga gaacgggaag cttgtnatca atggaaatcc catcaccatc 300tttcangaac ganatccntn caaaaatcaa anttgggggc gatgcttggc cncttgaagt 360accgttcaan gggaannncc ccactttggc cgntntttnc aancccaccc caatttgggn 420aaaaaaaaag gggnntttgg gggggggcct tttanntttt tttt 464 168 462 DNA Homo sapien misc_feature (1)...(462) n = A,T,C or G 168ggcacgaggn nnaacctncg gggctggggc agcacgcctt gngcaancct gcactgcact 60gaagacccgg tgccggaagc cgnnggcngc nacatgcagn aactgaacca gctgggcgcg 120cancagttct cagacctgac agaggtgctt ttacacttcc taactgatcc anantangtg 180gaaatattnt tngttnatnt catntgaatn atccancncc aatcatanca nntttnattn 240cctcataanc nttgagaana gcnnccttnt gnttncanan ggtgctntga anangagtct 300cacangcaan caggtccaag cggatttnnt aactntgggt cttantgang agaaagncac 360ttacttttct gaaancngga agcagaatgc tcccaccctt gctcgatggg ccatacgtca 420agactctgat gattaaccag ctttanatat ggacnggaaa tt 462 169 460 DNA Homo sapien misc_feature (1)...(460) n = A,T,C or G 169ggcacgaggg acagcagacn agacagtcac agcagccttg acaaaacgtt cctggaactc 60aagntcttnt ncncaaagga ggacagagca nacagcagag accatggant ctncctcggc 120ccctccccac agatggtgca tcccctggca naggctcctg ctcacagcct cacttctaac 180cttctggaac ccgcccacca ctgccaagct cactattgaa tccacgccgt tcaatgnntc 240ntaggggaag gaggngcttt ctactnttnc acaatctgan ccccttcttn tttggttact 300ancatggctc tncatgtnaa aatactggna tggntaacct gtcaaattta taggnantnt 360gctaattggg aaactnccnn tngtctaccc caggggnccc agattcctnn gttcncataa 420cnattaattt aacccctaat gncaanccct tngttaaaga 460 170 508 DNA Homo sapien misc_feature (1)...(508) n = A,T,C or G 170ggcacgaggg ggatttttag gtggtcnggt gtggtatcag gaataatgtg ggaggccaga 60ttgaagtcca ggccaggaac aatggtaatt gtgggactta agaaagtgtg agtacagctg 120aatgagccgg ggagcagaaa gtatatgcgt caggtatgag gaagaaaata gattttggaa 180gttatgagaa atgtagagag tgagttgagc atagtttgtg attttgaggg cctctaacag 240tattaaagca gcggcagcgg ctgcacacag acatgatggc taggctaaaa caggaaggtc 300aagttgtttg gacagaaagg ctacagggtg cagtcctggc tcttgtgtaa gaattctgac 360cacactaacc atgcctagga aggaaaggag ttgttctttt gtaagggatt gaggtttggg 420agattaatcg gacacgatca gcagggagag cacctgtgtt tttatgagaa ttatgctgag 480ataggtaaca gatgaggatg aaatttgg 508 171 507 DNA Homo sapien misc_feature (1)...(507) n = A,T,C or G 171ggcacgagac cagccactag cgcagnctcg agcgatggcc tatgtccccg caccgggcta 60ccagcccacc tacaacccga cgctgcctta ctaccagccc atcccgggcg ggctcaacgt 120gggaatgtct gtttacatcc aaggagtggc cagcgagcac atgaagcggt tcttcgtgaa 180ctttgtggtt gggcaggatc cgggctcaga cgtcgccttc cacttcaatc cgcggtttga 240cggctgggac aaggtggtct tcaacacgtt gcagggcggg aagtggggca gcgaggagag 300gaagaggagc atgcccttca aaaagggtgc cgcctttgag ctggtcttca tagtcctggc 360tgagcactac aaggtggtgg taaatggaaa tcccttctat gagtacgggc accggcttcc 420cctacagatg gtcacccacc tgcaagtgga tggggatctg caacttcaat caatcaactt 480catcggaggc cagcccctcc ggcccca 507 172 409 DNA Homo sapien 172ggcacgagct ggagtgtctg ctgccacccc ctcgtcctct gcagaaatgt ctgtcaccta 60cgatgactct gtgggagtgg aagtgtccag cgacagcttc tgggaggttg ggaactacaa 120acggactgtg aagcggattg acgatggcca ccgcctgtgt ggtgacctca tgaactgtct 180gcatgagcgg gcacgcatcg agaaggcgta tgcacagcag ctcactgagt gggcccgacg 240ctggaggcag ctggtagaga agggaccaca gtatgggacc gtggagaagg cctggatagc 300tgtcatgtct gaagcagaga gggtgagtga actgcacctg gaagtgaagg catcactgat 360gaatgaagac tttgagaaga tcaagaactg gcagaaggaa gcctttcac 409 173 409 DNA Homo sapien 173ggcacgaggg cagctagagg aagagtccaa ggccaagaac gcactggccc acgccctgca 60gtcagctcgc catgactgtg acctgctgcg ggaacagtat gaagaggagc aggaagccaa 120ggctgagctg cagagggcca tgtccaaggc caacagcgag gtagcccagt ggaggacgaa 180atatgagacg gatgccatcc agcgcacaga ggagctggaa gaggccaaga agaagctggc 240tcagcgtctg caggatgctg aggaacatgt agaagctgtg aattccaaat gcgcttctct 300tgaaaagacg aagcagcgac ttcagaatga agtggaggac ctcatgattg acgtggagag 360gtctaatgct gcctgcgctg cgcttgataa gaagcagagg aactttgac 409 174 407 DNA Homo sapien 174ggcacgagcc ggggcggggc gcggcgctcc ggctcgaggc attcggagct gcgggagccg 60ggctggcagg agcaggatgg cggcggcggc ggctgcaggc gaggcgcgcc gggtgctggt 120gtacggcggc aggggcgctc tgggttctcg atgcgtgcag gcttttcggg cccgcaactg 180gtgggttgcc agcgttgatg tggtggagaa tgaagaggcc agcgctagca tcattgttaa 240aatgacagac tcgttcactg agcaggctga ccaggtgact gctgaggttg gaaagctctt 300gggtgaagag aaggtggatg caattctttg cgttgctgga ggatgggccg ggggcaatgc 360caaatccaag tctctcttta agaactgtga cctgatgtgg aagcaga 407 175 407 DNA Homo sapien 175ggcacgagct tgcccgtcgg tcgctagctc gctcggtgcg cgtcgtcccg ctccatggcg 60ctcttcgtgc ggctgctggc tctcgccctg gctctggccc tgggccccgc cgcgaccctg 120gcgggtcccg ccaagtcgcc ctaccagctg gtgctgcagc acagcaggct ccggggccgc 180cagcacggcc ccaacgtgtg tgctgtgcag aaggttattg gcactaatag gaagtacttc 240accaactgca agcagtggta ccaaaggaaa atctgtggca aatcaacagt catcagctac 300gagtgctgtc ctggatatga aaaggtccct ggggagaagg gctgtccagc agccctacca 360ctctcaaacc tttacgagac cctgggagtc gttggatcca ccaccac 407 176 409 DNA Homo sapien 176ggcacgagtg gtgccaaaac gggaccatgc cctcctggag gagcagagca agcagcagtc 60caacgagcac ctgcgccgcc agttcgccag ccaggccaat gttgtggggc cctggatcca 120gaccaagatg gaggagatcg ggcgcatctc cattgagatg aacgggaccc tggaggacca 180gctgagccac ctgaagcagt atgaacgcag catcgtggac tacaagccca acctggacct 240gctggagcag cagcaccagc tcatccagga ggccctcatc ttcgacaaca agcacaccaa 300ctataccatg gagcacatcc gcgtgggctg ggagcagctg ctcaccacca ttgcccgcac 360catcaacgag gtggagaacc agatcctcac ccgcgacgcc aagggcatc 409 177 408 DNA Homo sapien 177ggcacgaggt ccaggtaact gcaaaaacaa tggctcagca tgaagaactg atgaagaaaa 60ctgaaacaat gaatgtagtt atggagacca ataaaatgct aagagaagag aaggagcagg 120tttcaaaaat ggcatcagtc cgtcagcatt tggaagaaac aacacagaaa gcagaatcac 180agttgttgga gtgtaaagca tcttgggagg aaagagagag aatgttaaag gatgaagttt 240ccaaatgtgt atgtcgctgt gaagatctgg agaaacaaaa cagattactt catgatcaga 300tcgaaaaatt aagtgacaag gtcgttgcct ctgtgaagga aggtgtacaa ggtccactga 360atgtatctct cagtgaagaa ggaaaatctc aagaacaaat tttggaaa 408 178 92 DNA Homo sapien 178ggcacgagaa gaaattaaga gctaaagaca aggagaatga aaatatggtt gcaaagctga 60acaaaaaagt taaagagcta gaagaggaga tg 92 179 411 DNA Homo sapien 179ggcacgagga gacacgccac ctataccaca gttctcagaa tgaattagct aagttggaat 60cagaacttaa gagtctcaaa gaccagttga ctgatttaag taactcttta gaaaaatgta 120aggaacaaaa aggaaacttg gaagggatca taaggcagca agaggctgat attcaaaatt 180ctaagttcag ttatgaacaa ctggagactg atcttcaggc ctccagagaa ctgaccagta 240ggctgcatga agaaataaat atgaaagagc aaaagattat aagcctgctt tctggcaagg 300aagaggcaat ccaagtagct attgctgaac tgcgtcagca acatgataaa gaaattaaag 360agctggaaaa cctgctgtcc caggaggaag aggagaatat tgttttagaa g 411 180 411 DNA Homo sapien 180ggcacgaggt tgttcggagc gggcgagcgg agttagcagg gctttactgc agagcgcgcc 60gggcactcca gcgaccgtgg ggatcagcgt aggtgagctg tggccttttg cgaggtgctg 120cagccatagc tacgtgcgtt cgctacgagg attgagcgtc tccacccatc ttctgtgctt 180caccatctac ataatgaatc ccagtatgaa gcagaaacaa gaagaaatca aagagaatat 240aaagactagt tctgtcccaa gaagaactct gaagatgatt cagccttctg catctggatc 300tcttgttgga agagaaaatg agctgtccgc aggcttgtcc aaaaggaaac atcggaatga 360ccacttaaca tctacaactt ccagccctgg ggttattgtc ccagaatcta g 411 181 411 DNA Homo sapien 181ggcacgaggc gggacagggc gaagcggcct gcgcccacgg agcgcgcgac actgcccgga 60agggaccgcc acccttgccc cctcagctgc ccactcgtga tttccagcgg cctccgcgcg 120cgcacgatgc cctcggccac cagccacagc gggagcggca gcaagtcgtc cggaccgcca 180ccgccgtcgg gttcctccgg gagtgaggcg gccgcgggag ccggggccgc cgcgccggct 240tctcagcacc ccgcaaccgg caccggcgct gtccagaccg aggccatgaa gcagattctc 300ggggtgatcg acaagaaact tcggaacctg gagaagaaaa agggtaagct tgatgattac 360caggaacgaa tgaacaaagg ggaaaggctt aatcaagatc agctggatgc c 411 182 411 DNA Homo sapien 182ggcacgagcc gacatggagc tgttcctcgc gggccgccgg gtgctggtca ccggggcagg 60caaaggtata gggcgcggca cggtccaggc gctgcacgcg acgggcgcgc gggtggtggc 120tgtgagccgg actcaggcgg atcttgacag ccttgtccgc gagtgcccgg ggatagaacc 180cgtgtgcgtg gacctgggtg actgggaggc caccgagcgg gcgctgggca gcgtgggccc 240cgtggacctg ctggtgaaca acgccgctgt cgccctgctg cagcccttcc tggaggtcac 300caaggaggcc tttgacagat cctttgaggt gaacctgcgt gcggtcatcc aggtgtcgca 360gattgtggcc aggggcttaa tagcccgggg agtcccaggg gccatcgtga a 411 183 409 DNA Homo sapien 183ggcacgagcc tacactctgg ccagagatac cacagtcaaa cctggagcca aaaaggacac 60aaaggactct cgacccaaac tgccccagac cctctccaga ggttggggtg accaactcat 120ctggactcag acatatgaag aagctctata taaatccaag acaagcaaca aacccttgat 180gattattcat cacttggatg agtgcccaca cagtcaagct ttaaagaaag tgtttgctga 240aaataaagaa atccagaaat tggcagagca gtttgtcctc ctcaatctgg tttatgaaac 300aactgacaaa cacctttctc ctgatggcca gtatgtcccc aggattatgt ttgttgaccc 360atctctgaca gttagagccg atatcactgg aagatattca aatcgtctc 409 184 410 DNA Homo sapien 184ggcacgaggt cattccagca ccaacaggat ccaagccaga ttgattgggc tgcattggcc 60caagcttgga ttgcccaaag agaagcttca ggacagcaaa gcatggtaga acaaccacca 120ggaatgatgc caaatggaca agatatgtct acaatggaat ctggtccaaa caatcatggg 180aatttccaag gggattcaaa cttcaacaga atgtggcaac cagaatgggg aatgcatcag 240caacccccac acccccctcc agatcagcca tggatgccac caacaccagg cccaatggac 300attgttcctc cttctgaaga cagcaacagt caggacagtg gggaatttgc ccctgacaac 360aggcatatat ttaaccagaa caatcacaac tttggtggac cacccgataa 410 185 411 DNA Homo sapien misc_feature (1)...(411) n = A,T,C or G 185ggcacgagca cagatgtagt tttctctgcg cgtgtgcgtt ttccctcctc ccccgccctc 60agggtccacg gccaccatgg cgtattaggg gcagcagtgc ctgcggcagc attggccttt 120gcagcggcgg cagcagcacc aggctctgca gcggcaaccc ccagcggctt aagccatggc 180gcttctcacg gcattcagca gcagcgttgc tgtaaccgac aaagacacct tcgaattaag 240cacattcctc gattccagca aagcaccgca acatgaccga aatgagcttc ctgagcagcg 300aggtgttggt gggggacttg atgtccccct tcgacccgtc gggtttgggg gctgaagaaa 360gcctangtct cttagatgat tacctggagg tggccaagca cttcaaacct c 411 186 410 DNA Homo sapien 186ggcacgagct tctagtcccg ccatggccgc tctcacccgg gacccccagt tccagaagct 60gcagcaatgg taccgcgagc accgctccga gctgaacctg cgccgcctct tcgatgccaa 120caaggaccgc ttcaaccact tcagcttgac cctcaacacc aaccatgggc atatcctggt 180ggattactcc aagaacctgg tgacggagga cgtgatgcgg atgctggtgg acttggccaa 240gtccaggggc gtggaggccg cccgggagcg gatgttcaat ggtgagaaga tcaactacac 300cgagggtcga gccgtgctgc acgtggctct gcggaaccgg tcaaacacac ccatcctggt 360agacggcaag gatgtgatgc cagaggtcaa caaggttctg gacaagatga 410 187 506 DNA Homo sapien 187ctttcgtggc tcactccctt tcctctgctg ccgctcggtc acgcttgtgc ccgaaggagg 60aaacagtgac agacctggag actgcagttc tctatccttc acacagctct ttcaccatgc 120ctggatcact tcctttgaat gcagaagctt gctggccaaa agatgtggga attgttgccc 180ttgagatcta ttttccttct caatatgttg atcaagcaga gttggaaaaa tatgatggtg 240tagatgctgg aaagtatacc attggcttgg gccaggccaa gatgggcttc tgcacagata 300gagaagatat taactctctt tgcatgactg tggttcagaa tcttatggag agaaataacc 360tttcctatga ttgcattggg cggctggaag ttggaacaga gacaatcatc gacaaatcaa 420agtctgtgaa gactaatttg atgcagctgt ttgaagagtc tgggaataca gatatagaag 480gaatcgacac aactaatgca tgctat 506 188 506 DNA Homo sapien 188gccacagagg cggcggagag atggccttca gcggttccca ggctccctac ctgagtccag 60ctgtcccctt ttctgggact attcaaggag gtctccagga cggacttcag atcactgtca 120atgggaccgt tctcagctcc agtggaacca ggtttgctgt gaactttcag actggcttca 180gtggaaatga cattgccttc cacttcaacc ctcggtttga agatggaggg tacgtggtgt 240gcaacacgag gcagaacgga agctgggggc ccgaggagag gaagacacac atgcctttcc 300agaaggggat gccctttgac ctctgcttcc tggtgcagag ctcagatttc aaggtgatgg 360tgaacgggat cctcttcgtg cagtacttcc accgcgtgcc cttccaccgt gtggacacca 420tctccgtcaa tggctctgtg cagctgtcct acatcagctt ccagcctccc ggcgtgtggc 480ctgccaaccc ggctcccatt acccag 506 189 399 DNA Homo sapien 189ctggacagga gaagagcctg gctgctgaag gcagggctga cacgaccacg ggcagcattg 60ctggagcccc agaggatgaa agatcgcaga gcacagcccc ccaggcacca gagtgcttcg 120accctgccgg accggctggg ctcgtgaggc cgacatctgg cctttcccag ggcccaggaa 180aggaaacctt ggaaagtgct ctaatcgctc tagactctga aaaacccaag aaacttcgct 240tccacccaaa gcagctgtac ttctctgcca ggcagggtga gctgcagaag gtgcttctca 300tgctggttga tggaattgat cccaacttca aaatggagca ccaaagtaag cgttccccat 360tacatgctgc tgcggaggct ggccacgtgg acatctgcc 399 190 401 DNA Homo sapien 190cggcgacggt ggtggtgact gagcggagcc cggtgacagg atgttggtgt tggtattagg 60agatctgcac atcccacacc ggtgcaacag tttgccagct aaattcaaaa aactcctggt 120gccaggaaaa attcagcaca ttctctgcac aggaaacctt tgcaccaaag agagttatga 180ctatctcaag actctggctg gtgatgttca tattgtgaga ggagacttcg atgagaatct 240gaattatcca gaacagaaag ttgtgactgt tggacagttc aaaattggtc tgatccatgg 300acatcaagtt attccatggg gagatatggc cagcttagcc ctgttgcaga ggcaatttga 360tgtggacatt cttatctcgg gacacacaca caaatttgaa g 401 191 406 DNA Homo sapien 191tggcagccta agccgtggga gggttccagt cgagaatggg aagatgaaag acttcagatg 60gaacagaaat aaatgccttt tttgacaaac gcagcagtgc gtgcctctag cttgcaagag 120cgttactccc cttcatagct ttaaaaggtt ttcgcactgc gtgcagttag agtagctaaa 180tcttgtgtga cgctccacaa acacttgtaa gaattttgca gagaaagata accgttgcca 240cccaatgccc cccacaggca ttctactccc cagtacctct tagggtggga gaaatggtga 300agagttgttc ctacaacttg ctaacctagt ggacagggta gtagattagc atcatccgga 360tagatgtgaa gaggacggct gtttggataa taattaagga taaaat 406 192 316 DNA Homo sapien 192ccggggagg ccctggtcat aaaactttaa attttactag tgttacttaa tgtatattct 60aaaagagaa tgcagtaact aatgccctaa atgtttgatc tctgtttgtc attacttttt 120aaaattatt tttttctgta aagtataata tataaaactt cttgcttaaa ttgaatttct 180tattagtgg ttaattgcag tttattaaag ggatcattat cagtaatttc atagcaactg 240tctagtgtt ttgtgttttt aaaacagaat taggaatttg agatatctga ttatattttt 300atatgaatc acagac 316 193 146 DNA Homo sapien 193gaaacatgga ctgcccctta aattttgact gtcctaaaaa cctatttctg atttataata 60tgctgcctga taaagtgaca ctagatgtac cagctgagtg tttaatcttc ccatcacaga 120tcagatttga gcattaacag gtattt 146 194 405 DNA Homo sapien 194cggatgtgct cactgacatt ctactccaag tcggagatgc agatccactc caagtcacac 60accgagacca agccccacaa gtgcccacat tgctccaaga ccttcgccaa cagctcctac 120ctggcccagc acatccgtat acactcaggg gctaagccct acagttgtaa cttctgtgag 180aaatccttcc gccagctctc ccaccttcag cagcacaccc gaatccacac tggtgataga 240ccatacaaat gtgcacaccc aggctgtgag aaagccttca cacaactctc caatctgcag 300tcccacagac ggcaacacaa caaagataaa cccttcaagt gccacaactg tcatcgggcg 360tacacggatg cagcctcact agaggtgcac ctgtctacgc acaca 405 195 421 DNA Homo sapien 195agaattcggc acgagctact ccttgcgcgc tggcactccg cagcctttaa ggttcgcgcg 60ggggccaggc aagagttagc catgaagagc ctcaagtccc gcctgaggag gcaggacgtg 120cccggccccg cgtcgtctgg cgccgccgcc gccagcgcgc atgcagcaga ttggaataaa 180tatgatgacc gattgatgaa agcagcagaa aggggggatg tagaaaaagt gacgtcaatc 240cttgctaaaa agggggtcaa tccaggcaaa ctagatgtgg aaggcagatc tgtcttccat 300gttgtgacct caaaggggaa tcttgagtgt ttgaatgcca tccttataca tggagttgat 360attacaacca gtgacactgc agggagaaat gctcttcacc tggctgctaa gtatggacat 420g 421 196 476 DNA Homo sapien 196agaattgatc tatagattta atgcaatgcc tactaaaatc ccagtacgat tttttacagg 60catagacaat agacatagcc aaaacttatt ctaaaataca tatgaagatg cacaggccct 120agttatacaa tcttgacaaa gaagaataaa gtgggaagaa tctatttgat tttaaggctt 180accatgtaac tacagtcatc aagagagtgt ggtatcggca gacggtcaga catacagatc 240aatggaatgt aacagaggac ccagaaatag gcccacacag atatgctcaa tggatatttg 300acaagcgtgc aaaacaattc aatggaagaa taagctttca aaaaaatggc gttggagcaa 360ccggacatcc ataggaaaaa atgaacccat acctaaacca taaaccttat ataaaaataa 420acacaaaatg aatcataggc ttaaatgtaa gctataaaac ttttagagaa aaacac 476 197 503 DNA Homo sapien 197tagccctcgg tgaagcccca gaccacagct atgagtccct tcgtgtgacg tctgcgcaga 60aacatgttct gcatgtccag ctcaaccggc ccaacaagag gaatgccatg aacaaggtct 120tctggagaga gatggtagag tgcttcaaca agatttcgag agacgctgac tgtcgggcgg 180tggtgatctc tggtgcagga aaaatgttca ctgcaggtat tgacctgatg gacatggctt 240cggacatcct gcagcccaaa ggagatgatg tggcccggat cagctggtac ctccgtgaca 300tcatcactcg ataccaggag accttcaacg tcatcgagag gtgccccaag cccgtgattg 360ctgccgtcca tgggggctgc attggcggag gtgtggacct tgtcaccgcc tgtgacatcc 420ggtactgtgc ccaggatgct ttcttccagg tgaaggaggt ggacgtgggt ttggctgccc 480atgtaggaac actgcagcgc ctg 503 198 168 PRT Homo sapien 198Phe Val Ala His Ser Leu Ser Ser Ala Ala Ala Arg Ser Arg Leu Cys 1 5 10 15Pro Lys Glu Glu Thr Val Thr Asp Leu Glu Thr Ala Val Leu Tyr Pro 20 25 30Ser His Ser Ser Phe Thr Met Pro Gly Ser Leu Pro Leu Asn Ala Glu 35 40 45Ala Cys Trp Pro Lys Asp Val Gly Ile Val Ala Leu Glu Ile Tyr Phe 50 55 60Pro Ser Gln Tyr Val Asp Gln Ala Glu Leu Glu Lys Tyr Asp Gly Val65 70 75 80Asp Ala Gly Lys Tyr Thr Ile Gly Leu Gly Gln Ala Lys Met Gly Phe 85 90 95Cys Thr Asp Arg Glu Asp Ile Asn Ser Leu Cys Met Thr Val Val Gln 100 105 110Asn Leu Met Glu Arg Asn Asn Leu Ser Tyr Asp Cys Ile Gly Arg Leu 115 120 125Glu Val Gly Thr Glu Thr Ile Ile Asp Lys Ser Lys Ser Val Lys Thr 130 135 140Asn Leu Met Gln Leu Phe Glu Glu Ser Gly Asn Thr Asp Ile Glu Gly145 150 155 160Ile Asp Thr Thr Asn Ala Cys Tyr 165 199 168 PRT Homo sapien 199His Arg Gly Gly Gly Glu Met Ala Phe Ser Gly Ser Gln Ala Pro Tyr 1 5 10 15Leu Ser Pro Ala Val Pro Phe Ser Gly Thr Ile Gln Gly Gly Leu Gln 20 25 30Asp Gly Leu Gln Ile Thr Val Asn Gly Thr Val Leu Ser Ser Ser Gly 35 40 45Thr Arg Phe Ala Val Asn Phe Gln Thr Gly Phe Ser Gly Asn Asp Ile 50 55 60Ala Phe His Phe Asn Pro Arg Phe Glu Asp Gly Gly Tyr Val Val Cys65 70 75 80Asn Thr Arg Gln Asn Gly Ser Trp Gly Pro Glu Glu Arg Lys Thr His 85 90 95Met Pro Phe Gln Lys Gly Met Pro Phe Asp Leu Cys Phe Leu Val Gln 100 105 110Ser Ser Asp Phe Lys Val Met Val Asn Gly Ile Leu Phe Val Gln Tyr 115 120 125Phe His Arg Val Pro Phe His Arg Val Asp Thr Ile Ser Val Asn Gly 130 135 140Ser Val Gln Leu Ser Tyr Ile Ser Phe Gln Pro Pro Gly Val Trp Pro145 150 155 160Ala Asn Pro Ala Pro Ile Thr Gln 165 200 132 PRT Homo sapien 200Gly Gln Glu Lys Ser Leu Ala Ala Glu Gly Arg Ala Asp Thr Thr Thr 1 5 10 15Gly Ser Ile Ala Gly Ala Pro Glu Asp Glu Arg Ser Gln Ser Thr Ala 20 25 30Pro Gln Ala Pro Glu Cys Phe Asp Pro Ala Gly Pro Ala Gly Leu Val 35 40 45Arg Pro Thr Ser Gly Leu Ser Gln Gly Pro Gly Lys Glu Thr Leu Glu 50 55 60Ser Ala Leu Ile Ala Leu Asp Ser Glu Lys Pro Lys Lys Leu Arg Phe65 70 75 80His Pro Lys Gln Leu Tyr Phe Ser Ala Arg Gln Gly Glu Leu Gln Lys 85 90 95Val Leu Leu Met Leu Val Asp Gly Ile Asp Pro Asn Phe Lys Met Glu 100 105 110His Gln Ser Lys Arg Ser Pro Leu His Ala Ala Ala Glu Ala Gly His 115 120 125Val Asp Ile Cys 130 201 120 PRT Homo sapien 201Met Leu Val Leu Val Leu Gly Asp Leu His Ile Pro His Arg Cys Asn 1 5 10 15Ser Leu Pro Ala Lys Phe Lys Lys Leu Leu Val Pro Gly Lys Ile Gln 20 25 30His Ile Leu Cys Thr Gly Asn Leu Cys Thr Lys Glu Ser Tyr Asp Tyr 35 40 45Leu Lys Thr Leu Ala Gly Asp Val His Ile Val Arg Gly Asp Phe Asp 50 55 60Glu Asn Leu Asn Tyr Pro Glu Gln Lys Val Val Thr Val Gly Gln Phe65 70 75 80Lys Ile Gly Leu Ile His Gly His Gln Val Ile Pro Trp Gly Asp Met 85 90 95Ala Ser Leu Ala Leu Leu Gln Arg Gln Phe Asp Val Asp Ile Leu Ile 100 105 110Ser Gly His Thr His Lys Phe Glu 115 120 202 135 PRT Homo sapien 202Arg Met Cys Ser Leu Thr Phe Tyr Ser Lys Ser Glu Met Gln Ile His 1 5 10 15Ser Lys Ser His Thr Glu Thr Lys Pro His Lys Cys Pro His Cys Ser 20 25 30Lys Thr Phe Ala Asn Ser Ser Tyr Leu Ala Gln His Ile Arg Ile His 35 40 45Ser Gly Ala Lys Pro Tyr Ser Cys Asn Phe Cys Glu Lys Ser Phe Arg 50 55 60Gln Leu Ser His Leu Gln Gln His Thr Arg Ile His Thr Gly Asp Arg65 70 75 80Pro Tyr Lys Cys Ala His Pro Gly Cys Glu Lys Ala Phe Thr Gln Leu 85 90 95Ser Asn Leu Gln Ser His Arg Arg Gln His Asn Lys Asp Lys Pro Phe 100 105 110Lys Cys His Asn Cys His Arg Ala Tyr Thr Asp Ala Ala Ser Leu Glu 115 120 125Val His Leu Ser Thr His Thr 130 135 203 135 PRT Homo sapien 203Leu Leu Leu Ala Arg Trp His Ser Ala Ala Phe Lys Val Arg Ala Gly 1 5 10 15Ala Arg Gln Glu Leu Ala Met Lys Ser Leu Lys Ser Arg Leu Arg Arg 20 25 30Gln Asp Val Pro Gly Pro Ala Ser Ser Gly Ala Ala Ala Ala Ser Ala 35 40 45His Ala Ala Asp Trp Asn Lys Tyr Asp Asp Arg Leu Met Lys Ala Ala 50 55 60Glu Arg Gly Asp Val Glu Lys Val Thr Ser Ile Leu Ala Lys Lys Gly65 70 75 80Val Asn Pro Gly Lys Leu Asp Val Glu Gly Arg Ser Val Phe His Val 85 90 95Val Thr Ser Lys Gly Asn Leu Glu Cys Leu Asn Ala Ile Leu Ile His 100 105 110Gly Val Asp Ile Thr Thr Ser Asp Thr Ala Gly Arg Asn Ala Leu His 115 120 125Leu Ala Ala Lys Tyr Gly His 130 135 204 167 PRT Homo sapien 204Ala Leu Gly Glu Ala Pro Asp His Ser Tyr Glu Ser Leu Arg Val Thr 1 5 10 15Ser Ala Gln Lys His Val Leu His Val Gln Leu Asn Arg Pro Asn Lys 20 25 30Arg Asn Ala Met Asn Lys Val Phe Trp Arg Glu Met Val Glu Cys Phe 35 40 45Asn Lys Ile Ser Arg Asp Ala Asp Cys Arg Ala Val Val Ile Ser Gly 50 55 60Ala Gly Lys Met Phe Thr Ala Gly Ile Asp Leu Met Asp Met Ala Ser65 70 75 80Asp Ile Leu Gln Pro Lys Gly Asp Asp Val Ala Arg Ile Ser Trp Tyr 85 90 95Leu Arg Asp Ile Ile Thr Arg Tyr Gln Glu Thr Phe Asn Val Ile Glu 100 105 110Arg Cys Pro Lys Pro Val Ile Ala Ala Val His Gly Gly Cys Ile Gly 115 120 125Gly Gly Val Asp Leu Val Thr Ala Cys Asp Ile Arg Tyr Cys Ala Gln 130 135 140Asp Ala Phe Phe Gln Val Lys Glu Val Asp Val Gly Leu Ala Ala His145 150 155 160Val Gly Thr Leu Gln Arg Leu 165 205 381 DNA Homo sapien 205aaatttggga tcatcgcctg ttctgaaaac tagatgcacc aaccgtatca ttatttgttt 60gaggaaaaaa agaaatctgc attttaattc atgttggtca aagtcgaatt actatctatt 120tatcttatat cgtagatctg ataaccctat ctaaaagaaa gtcacacgct aaatgtattc 180ttacatagtg cttgtatcgt tgcatttgtt ttaatttgtg gaaaagtatt gtatctaact 240tgtattactt tggtagtttc atctttatgt attattgata tttgtaattt tctcaactat 300aacaatgtag ttacgctaca acttgcctaa aacattcaaa cttgttttct tttttctgtt 360gttttctttg ttaattcatt t 381 206 514 DNA Homo sapien 206aaaagtaaat tgcataaaat tacatccaat ttctttctct aaaccaacat attcttcacc 60ttcacaaagc aaacacatgg tgcactgaaa ccgaggtgtt accagcttta catactgttc 120tgccatttgt ggggggtgca accacaacat aagtcagaaa aaaagctatc cagcttttcg 180tggaatctgg tgaagtttac acttagcgat aagcctctaa gcctgaactt agcagggcta 240gcaaaacttt atttatttcc taactcctat tattttagaa tggttttcaa aataatactg 300caagttccta attgaaatac aaaacagaac aaaaagctgt gagaaatctt tttttttctt 360tggctcctta aagacttgga ataatttata ttagtgttgc atacatttta ccttctacat 420tttgatgtac ttgctcttga aagcactaga acaaattaat tgaaataaaa cctctctgaa 480accatttgaa tctttgatcc taccatagag tttt 514 207 522 DNA Homo sapien misc_feature (1)...(522) n = A,T,C or G 207caagcttttg gtgcatagca gccngcctgg aagcattctg agtgctctgt ctgccctggt 60gggtttcatt atcctgtctg tcaaacaggc caccttaaat cctgcctcac tgcagtgtga 120gttggacaaa aataatatac caacaagaag ttatgtttct tacttttatc atgattcact 180ttataccacg gactgctata cagccaaagc cagtctggct ggaactctct ctctgatgct 240gatttgcact ctgctggaat tctgcctagc tgtgctcact gctgtgctgc ggtggaaaca 300ggcttactct gacttccctg ggagtgtact tttcctgcct cacagttaca ttggtaattc 360tggcatgtcc tcaaaaatga ctcatgactg tggatatgaa gaactattga cttcttaaga 420aaaaagggag aaatattaat cagaaagttg attcttatga taatatggaa aagttaacca 480ttatagaaaa gcaaagcttg agtttcctaa atgtaagctt tt 522 208 278 DNA Homo sapien 208aaatgcact accccttttt tccaacacgg agcttaaaac aaattaatga aagagtggaa 60attcaaaat aagggcaaga gataaggttt tttttttttt tcctttaaga tagactcagg 120taggtagat agctttcact gatgtagatg tggaataaat tattacttca ggaaaaaaat 180cccaaacat cttatgaaaa agtatacaac tctacttcaa aatatgctat ttactcactg 240caaagacag ttttatttga aatcttgttt ctgtattt 278 209 234 DNA Homo sapien misc_feature (1)...(234) n = A,T,C or G 209cctcccaaat ttagcaggtg ctgggnagga ccctagggag tggtttatgg gggctagctg 60gtgaaactgc cctttccttt ctgttctatg agtgtgatgg tgtttgagaa aatgtggggc 120tatggttcag gcgcacttca catgtgcaaa gatggagaaa gcactcacct acacgtttag 180gctcagaatg ttgattgaaa cattttgaat gatcaaaaat aaaatgttat tttt 234 210 186 DNA Homo sapien misc_feature (1)...(186) n = A,T,C or G 210aaaataactg atggcaaaat aaaanattta catcacatca tactgtgtaa acatgtaagg 60tctctgtaca aagaaatata catgcaaaat aatgtaaaaa tttaactgaa ataataaaag 120aaacaataca caaataaaaa ttatgaggtt acgaatacac atccagtttc gaatccaatt 180tctttt 186 211 403 DNA Homo sapien 211aaaaattggt aaaatattta agtacaaaat aagtagcttc cagcgaggtt tttataccat 60agtaagagca cacaatagat attactagca cacatgggtt atctgggagc gctatagcta 120caataaacct aattatggaa cagaaatttg cattctgttt ccagtgctac tacactccta 180ctttctcaaa agtctgctct attaatatca gctcagtgca gtttactatg aatagtttat 240gtctgtgatg caaagcatta attgttctct ttttacaaac atacattttt ttcataagga 300agactggggg aaaacccaga aacatacaga gaaaaggaaa gcatcatcaa atatatgtta 360aaaattaaga tgatgtttac tactagtcat cctacaacaa ttt 403 212 345 DNA Homo sapien 212ctctttatg agttcattac tgctgttcag tctcggcaca cagacacccc tgtgcaccgg 60gtgtacttt ctactctgat cgctgggcct gtggttgaga taagtcacca gctacggaag 120tttctgacg tagaagagct tacccctcca gagcatcttt ctgatcttcc accattttca 180ggtgtttaa taggaataat aataaagtct tcgaatgtgg tcaggtcatt tttggatgaa 240taaaggcat gtgtggcttc taatgatatt gaaggcattg tgtgcctcac ggctgctgtg 300atattatcc tggttattaa tgcaggtaaa cataaaagct caaaa 345 213 318 DNA Homo sapien 213aaatgtttt attattttga aaataatgtt gtaattcatg ccagggactg acaaaagact 60gagacagga tggttattct tgtcagctaa ggtcacattg tgcctttttg accttttctt 120ctggactat tgaaatcaag cttattggat taagtgatat ttctatagcg attgaaaggg 180aatagttaa agtaatgagc atgatgagag tttctgttaa tcatgtatta aaactgattt 240tagctttac aaatatgtca gtttgcagtt atgcagaatc caaagtaaat gtcctgctag 300tagttaagg attgtttt 318 214 462 DNA Homo sapien 214aaacacatct ggttctggca gcaagttata ttatgcattt agagcaatag gtgccctgaa 60agttattgtt gctttttttg tttttttttt cagtttgtgc gtgtcacttg aatcagaaac 120caaacacatg taaaaaaata tcatcctcaa tgccccccat taactctctc tccagaaggt 180gacaatgtta gtgaactcaa gactctcact gatgatggta ttttacaatg aaaacacaag 240gaaacccttt gaggtccaat tttcacatca tattctccaa atagtaaaat agcagctcta 300catgttgatg aaaagaaatt tcaatttctt cctatttgtt tttactcata tcaacattaa 360tatgtatctg gatttattaa tttccaaaaa gaaaatttta gttaccaaat atttcagaaa 420tttaataaag cattatatat atgtaattag cacttatcta cc 462 215 280 DNA Homo sapien 215 216 210 DNA Homo sapien 216aaaatctctg gcttcaaagt ttcttgggga aaggtcggtt tacctcacat tttttgtttc 60cattagtaat attctaggta cctcacaaaa tgtattatgg tgccatggct gttagttttt 120agtgagtgct gtaggattaa ttcgaaaata ggcagaattc cattcctccc aaggtggcaa 180aaattagcta tactgatgta attgtcattt 210 217 398 DNA Homo sapien 217ctggagctgc tagaacttga gatgagggca agagcgatta aagccctaat gaaagctggt 60gatataaaaa agccagccta ggtatttaac ttgattttga attttaggta tgtttgaaca 120aagccacatc atttaatttt gtatctaaaa tttatttggg gtcttatatg ttatttctca 180tgtaaccctt attaggactc attttagccc taaattacct gtggctgttt ctttttattt 240ttttgactac ttttatatta taaatgtgtg ttactgtctt atgaattcat ggcaatatag 300ttggatagcc tggatacttt gttagatgag tatttagctg tgtctgcaaa tcttaaaagc 360cattagcaaa gagtcgtggt atttttttct ttattttt 398 218 487 DNA Homo sapien 218ctgccgccgg tcaggctggt taaagatcag gtcccccagg accttgcgat ttatgtcgcc 60attctccagc aagacctcag tgccgaagac ctctacgatg cgccggtggg cagggtatcc 120tggctgcacg acgtgccggg ccatcacgtc cacgtcaatc accgcacagc ccagtttcag 180tgtttttaca cattatattg ttataatctc acaataacta taaattaggt agaacaggaa 240atgaggtttg gagaagatac ttgacttatc cgaccatctg tacttgtccc atagtaagga 300gcctcaagca gagacaaagg aggaagttgc ctatgttgta tggtttacag gccataaatg 360aatgtcatct ttttcctccc ctggggaaaa atgtctcaaa aatcccacca taggacatga 420catctccaga acctctatta caaaatacac atttcctgta gaggggtaac aaatttgggt 480taacctg 487 219 390 DNA Homo sapien 219aaaaaataca ccacacgata caactcaata caggagtatt tcttctcaaa ttcttctagc 60accatcaaca ttcttcaagt atctgaaata ctattaatta gcacctttgt attatgaaca 120aaacaaaaca aggacctcag ttcatctctg tctaggtcag cacctaacaa tgtggatcac 180actcatggga aagtgttttg aggtagttta aacctttgga agtttgggtt ttaaacttcc 240ctctgtggaa gatattcaaa agccacaagt ggtgcaaatg tttatggttt ttatttttca 300atttttattt tggttttctt acaaaggttg acattttcca taacaggtgt aagagtgttg 360aaaaaaaagt tcaaattttt gggggagcgg 390 220 341 DNA Homo sapien misc_feature (1)...(341) n = A,T,C or G 220aaacaggca aagttttaca gagaggatac atttaataaa actgcgagga catcaaagtg 60taaatactg tgaaatacct tttctnnnca aaaggcaaat attgaagttg tttatcaact 120cgctagaaa aaaaaaaaca cttggcatac aaaatattta agtgaaggag aagtctaacg 180tgaactnnn aatgaaggga aattgtttat gtgttatgaa catccaagtc tttcttcttt 240ttaagttgt caaagaagct tccacaaaat tagaaaggac aacagttctg agctgtaatt 300cgccttaaa ctctggacac tctatatgta gtgcattttt a 341 221 234 DNA Homo sapien 221ccagggggaa ttgagggagg ctctaagcta ggggcactgc atggtgggac aggatggccc 60cttgaggact gaaccctggg gagaagacaa acagtaataa taaaaacaaa taacaagtac 120tttaagaatg gattgtatga cctatagtga cagatgacat cactaatact gaaagcttct 180tatattaata attttggcaa aatgtcattt tgtaatatag tatatgcttt ccag 234 222 186 DNA Homo sapien 222aaattttcat tgagttgtcc atctccagca tatagggctt caggagcaga gcagaccttg 60tttttagtgg ttccatggga taaaatggga ttggaggagc tagaagaatt cagggtctgg 120tccaatctgc cagtcttcct gaaatatcga aaatacacca gggctgctat atcagagcca 180ccctgg 186 223 486 DNA Homo sapien 223ccataagcag ataagtagca gttcaactgg atgtctctct tctccaaatg ctacagtaca 60aagccctaag catgagtgga aaatcgttgc ttcagaaaag acttcaaata acacttactt 120gtgcctggct gtgctggatg gtatattctg tgtcattttt cttcatggga gaaacagccc 180acagagctca ccaacaagta ctccaaaact aagtaagagt ttaagctttg agatgcaaca 240agatgagcta atcgaaaagc ccatgtctcc tatgcagtac gcacgatctg gtctgggaac 300agcagagatg aatggcaaac tcatagctgc aggtggctat aacagagagg aatgtcttcg 360aacagtcgaa tgctataatc cacatacaga tcactggtcc tttcttgctc ccatgagaac 420accaagagcc cgatttcaaa tggctgtact catgggccag ctctatgtgg taggtggatc 480aaatgg 486 224 322 DNA Homo sapien 224aatgttcac tatgtcattt agtgtccaac tttacggata ggttgactat ctaaataggc 60tttttagtc attaaaaaaa aatctagtca ccaggaggat ccctataact caaaataact 120gtttgtaaa agaaaatttg tttacttacc cattagtaag ttcctgcata ttcattataa 180atggcaaat caaacttttc taggatgaag acagcttatt tttaagttgt atagtcttag 240tggtttagg gtctcaattt taattaataa aatacttggt ttttatttgc ttgtcctttt 300aattcctgt tttaataatt tt 322 225 489 DNA Homo sapien 225aaatgtagga ataaaatggc tggcatctaa gcactttagt aaaagaggtt tttacaaata 60actaaggatt gtagagcttc cttctctttt tttttctttt tctttctttt gttttacatg 120aactcaactt attcctaaca tttgtctacc tcaaagaaat ttcaagatta tttagataac 180atggatatgt gccaaatcct ttgagctgtt aagatgataa tttcctgctt tcctcctaca 240tcttctcctc ccactccctc ctttggtgtg aatattggct tcccaattaa gacctttttt 300ttttttttcc agtttgtttt agcttattat aggttttgga ggaactttgc cattttgtaa 360tctttcaaat cattcttcac ccttcctcac atcagcttcc tgcttttccc agtgttttac 420tgtaaattgt gtagcatatg acaaatcttg agctgacttt cctcttcact gatgtcatct 480tgagctctt 489 226 398 DNA Homo sapien 226caagggccca ccgcagagca cacctatgct atggggagcc ctgctggcag ccccgagagc 60catgccatgg cctgcaggag ccaggctcct gtgtggatga agtccctctt cctctgtgcc 120ttgatccctt gggggtgcct ttggtcatct cttctgtcct ttcctgtctc tgaaatagtc 180atcactcccc ttgactctct ctgttcacgt cttctcagtc tgcagagtta acttctgtaa 240ggagtttaat ctggggttcc aagaaaacaa gttccttgtt aacatagcac tgactttgca 300acaatagaaa actaacaaat gagcaacaat ataaagagta gaggtagttc tcattgggtg 360taacttcaac ccattctgct tgtggttaga atttataa 398 227 535 DNA Homo sapien 227ctgctgcata gaaaatatgc taacatacaa cagtcaagtt taagcctgtg catagagaag 60ataaagcact tatggtaact gcaaatggta acgagtcctt aaggtttgta caacctagta 120tgggtccata aggaaaaact gtagtagaaa tggttaggac aaacaataaa gtagaaacag 180gggggaaact tgagaagaga agaaagaagc aagaaaaaaa gactttcaat tgtataaaat 240tcacaaacca gtaaagtata aagacaccat ggagaaatgg ttaactctgc cccaaacacc 300caacagcaaa caaaaccaga atgaataagc ctttggcaga caattttaga aatttgaatg 360ttacatttct caataattca caaacaatat attatatggt atatttatat taaatattgg 420gaaaccaatg ttgtaaattt gatgcttata atgctttagc caatgagagc acaatgatat 480caatcaagct aaatgaatgc tggtgttatc acaacagtgc tcatttatga aacaa 535 228 301 DNA Homo sapien 228aaacaataaa caccatcaac cttattgact ttattgtccc ttaaattata ttgactgttg 60tgattccatc aagtttgtac actcttttct ctccctgttt tgcagcaaca aattgcgaag 120tgcttttgtt tgtttgtttt cgtttggtta aagcttattg ccatgctggt gcggctatgg 180agactgtctg gaaggcttgg aatggtttat tgcttatggt aaaatttgcc tgatttctta 240caggcagcgt ttggaaacct tttattatat agttgtttac atacttataa gtctatcatt 300t 301 229 420 DNA Homo sapien 229aaagttgctt tgctggaagt ttttataagg aatctcagat taaaccttta gaagtttaat 60tgacactagg aagccaaacc aaggctgact tcagactttg tttgtagtac ctgtgggttt 120attacctatg ggtttatatc ctcaaatacg acattctagt caaagtcttg gtaatataac 180caatgttttc aaatgtattc tgtcatacaa agagcagatt tttattgaac ttgtgcaata 240actatattac catacaatat aaatattcat gaatagtttc ccaagtctgg agcgaccaca 300tagggagaaa atgcaaatgt ctcaattttt gttcacaaaa gtatatttta tcaaattgct 360gtaagctgtg gatagcttaa aagaaaaaaa gtttcctgaa atctgggaaa caagacattt 420 230 419 DNA Homo sapien 230gtgaagtcct aaagcttgca ttccaccagc ttctacaata gccggcttat tactagagca 60gacagatagc accttcagca ctctgcttgt ggtccacagt agtttttcgt aagtataggt 120cctcattata tttactaaag cttggggtcc accactagcc agtatgatga gcttgctttc 180ttggttgcca taagctaaaa tttgaaggca gtctgtcgta atagccaaga atttaacatt 240tgttttgttg agcaaggcaa ccattttctg cagcccacca gctaaacgca ctgccatttt 300agctccttct tgatgtaata aaaggttgtg gagagttgta atggcataaa acaacacaga 360atccactggt gaaccaagca ttttcaccag ggcaggaatg cctccagact taaagatgg 419 231 389 DNA Homo sapien 231ttgttcagag ccctggtgga tcttgcaatc cagtgcccta caaaggctag aacactacag 60gggatgaatt cttcaaatag gagccgatgg atctgtggtc ctttgggact catcaaagcc 120ttggtttagc attttgtcag ttttatcttc agaaattctc tgcgattaag aagataattt 180attaaaggtg gtccttccta cctctgtggt gtgtgtcgcg cacacagctt agaagtgcta 240taaaaaagga aagagctcca aattgaatca cctttataat ttacccattt ctatacaaca 300ggcagtggaa gcagtttcag agaacttttt gcatgcttat ggttgatcag ttaaaaaaga 360atgttacagt aacaaataaa gtgcagttt 389 232 397 DNA Homo sapien 232ccaggataat atacacaggt ttgcagctaa aactgtgcac agtgggtcat tgatgctagt 60cacagtggaa ctgaaggaag gctctacagc ccagcttatc ataaacactg agaaaactgt 120gattggctct gttctgctgc gggaactgaa gcctgtcctg tctcaggggt aacctgctta 180catctggact ttagaatctg gcacacaaca aaagtgcctg gcatccacta ctgctgcctt 240tcatttataa taatagccct tccatctggc agtgggggaa gaatacactc ttgacattct 300tgtctcctgc tttagaatgc tagtgtgtat ctatcatgta tgcaatactt tccccctttt 360tgctttgcta accaaagagc atatatttta ctgtcag 397 233 508 DNA Homo sapien 233cgaggagtcg cttaagtgcg aggacctcaa agtgggacaa tatatttgta aagatccaaa 60aataaatgac gctacgcaag aaccagttaa ctgtacaaac tacacagctc atgtttcctg 120ttttccagca cccaacataa cttgtaagga ttccagtggc aatgaaacac attttactgg 180gaacgaagtt ggttttttca agcccatatc ttgccgaaat gtaaatggct attcctacaa 240agtggcagtc gcattgtctc tttttcttgg atggttggga gcagatcgat tttaccttgg 300ataccctgct ttgggtttgt taaagttttg cactgtaggg ttttgtggaa ttgggagcct 360aattgatttc attcttattt caatgcagat tgttggacct tcagatggaa gtagttacat 420tatagattac tatggaacca gacttacaag actgagtatt actaatgaaa catttagaaa 480aacgcaatta tatccataaa tatttttt 508 234 358 DNA Homo sapien 234aaatgttggt attcaaaacc aaagatataa ccgaaaggaa aaacagatga gacataaaat 60gatttgcaag atgggaaata tagtagttta tgaatgtaaa ttaaattcca gttataatag 120tggctacaca ctctcactac acacacagac cccacagtcc tatatgccac aaacacattt 180ccataacttg aaaatgagta ttttgcatat ctcagttcag gatatgtttt ttacaagtta 240atcctaaagt cataaagcaa gaagctattc atagtacaag attttatttg ctaagcttta 300caaattaaac tctaaaaaat tattacaatg atactgaaag atattttatt ggcctttt 358 235 482 DNA Homo sapien 235gaagaaagtt agatttacgc cgatgaatat gatagtgaaa tggattttgg cgtaggtttg 60gtctagggtg tagcctgaga ataggggaaa tcagtgaatg aagcctccta tgatggcaaa 120tacagctcct attgatagga catagtggaa gtgagctaca acgtagtacg tgtcgtgtag 180tacgatgtct agtgatgagt ttgctaatac aatgccagtc aggccaccta cggtgaaaag 240aaagatgaat cctagggctc agagcactgc agcagatcat ttcatattgc ttccgtggag 300tgtggcgagt cagctaaata ctttgacgcc ggtggggata gcgatgatta tggtagcgga 360ggtgaaatat gctcgtgtgt ctacgtctat tcctactgta aatatatggt gtgctcacac 420gataaaccct aggaagccaa ttgatatcat agctcagacc atacctatgt atccaaatgg 480tt 482 236 149 DNA Homo sapien 236cctcttcatt gttcacatgt cacaggagga ggctctgagc aaaggccact ggcaagttag 60ggcaacacca agaaggctct gcggagagac tccctgtggg ttggggcctg gcaggaacgg 120tgcctgtgga ctgtttatgg tctgtccag 149 237 391 DNA Homo sapien 237gaagctaaat ccaaagaaat atgaaggtgg ccgtgaatta agtgatttta ttagctatct 60acaaagagaa gctacaaacc cccctgtaat tcaagaagaa aaacccaaga agaagaagaa 120ggcacaggag gatctctaaa gcagtagcca aacaccactt tgtaaaagga ctcttccatc 180agagatggga aaaccattgg ggaggactag gacccatatg ggaattatta cctctcaggg 240ccgagaggac agaatggata taatctgaat cctgttaaat tttctctaaa ctgtttctta 300gctgcactgt ttatggaaat accaggacca gtttatgttt gtggttttgg gaaaaattat 360ttgtgttggg ggaaatgttg tgggggtggg g 391 238 374 DNA Homo sapien 238aaaaaacaaa acaatgtaag taaaggatat ttctgaatct taaaattcat cccatgtgtg 60atcataaact cataaaaata attttaagat gccggaaaag gatactttga ttaaataaaa 120acactcatgg atatgtaaaa actgtcaaga ttaaaattta atagtttcat ttatttgtta 180ttttatttgt aagaaatagt gatgaacaaa gatccttttt catactgata cctggttgta 240tattatttga tgcaacagtt ttctgaaatg atatttcaaa ttgcatcaag aaattaaaat 300catctatctg agtagtcaaa atacaagtaa aggagagcaa ataaacaaca tttggaaaaa 360aaaaaaaaaa aaaa 374 239 200 DNA Homo sapien 239aaagatgtct ttgaccgcat atgtactgga aatttcaaac gtggatcttc ccaggttgta 60gtctttgtgt tatgatcaat gaagaagggc cggccgtttg gcgctatcct catttcccag 120ccgggtggca agaagctctg tgtgactttg tgttgtggtt tgggggagtt gtaaggtgat 180ggctgtgggg actgtgggtt 200 240 314 DNA Homo sapien misc_feature (1)...(314) n = A,T,C or G 240ctggtaaact gtccaaaaca aggttccaaa taacacctct tactgattta ccctacccat 60acatatncca natagntttt gatcaaaaac atgaaatana tccacctgct tattttaagc 120atattaaaaa ggaaactaat tggaccattt tctatttgtc tattttatac aaaaaggcta 180cacaattgat acactctatt cagataacaa tcaattagag tgantatgaa ttactggcga 240caccatcact caattcttaa aaattagaaa ttgctgtagc agtattcact ataacttaac 300actaccgaga gact 314 241 375 DNA Homo sapien misc_feature (1)...(375) n = A,T,C or G 241ccaagtcctt ggagttatag gatattcatt acttcctctc attgtaatag cccctgtact 60tttggtggtt ggatcatttg aagtggtgtc tacacttata aaactgtttg gtgtgttttg 120ggctgcctac agtgctgctt cattgttagt gggtgaagaa ttcaagacca aaaagcctct 180tctgatttat ccaatctttt tattatacat ttatcttttg tcgttatata ctggtgtgtg 240atccaagtta tacatgaata gaaaaagatg gtgttaaatt tgtgtgtagg ctgggaattc 300tngctaaagg aatggnaaaa aacctgtnnt tgnaaaattn acntgtccca aagnnaagga 360anctaaacgc ttttt 375 242 387 DNA Homo sapien 242aaaggcattc tctgatttac atgagaattg agaaactgag atgtatgatt tgtctgttag 60tcaatttcac accctttcat tctcataagc cccaaatttt gctcagttaa ggagcttgct 120ttaggcccac ctatgtaagt ctgttatact agctaatgtg cccatttgaa tagttcaagg 180gtcagctaat gctctgagct tcatggctcc agtataaaga acaaatttaa caaaattaag 240ctgttactgt agccgagtta cccttctgct ccacacatat gtagtgggat cttgcaggat 300ttccatagtg ccaattatca aaggccttga ctacttagca ttgctgtatt acagatgtgc 360aaactgaggc actgaaaagt caaattt 387 243 536 DNA Homo sapien misc_feature (1)...(536) n = A,T,C or G 243aaaccaaaag gacgaagaaa aaacactttn aaaaaaaaaa aaaaaaaaga aaaaccaaac 60catattttgc cacatgtgag agtacggtca agcagtattt acaaaaaggt taacggaaca 120acactctgac acatgctctg agaatactgg gactgctgtt tcaaaaaaaa aggttcaaac 180ttattgtcac agcatcatca caaaatagag gatcaccatt ggtttgcttg gcttttcttt 240ttttttttcc cccaagtgag gacctaactc caaataatac aatagaatat gcaaattatc 300ttcacatcaa gagtacccca agaaaaacga aatccatggc acanacactg tacaagggtg 360cagggcaggg ctctgagggg cccaaacccc attttgccaa ctcgattttc tagcattgaa 420gggagcaagg ggtcaggcat atgatggaga tgatactgaa atgatttatc caaaatccat 480gcaaatcaag ttctttggat agaggtgaan aacttggaca tggctgtttc aggcag 536 244 397 DNA Homo sapien 244ccaggataat atacacaggt ttgcagctaa aactgtgcac agtgggtcat tgatgctagt 60cacagtggaa ctgaaggaag gctctacagc ccagcttatc ataaacactg agaaaactgt 120gattggctct gttctgctgc gggaactgaa gcctgtcctg tctcaggggt aacctgctta 180catctggact ttagaatctg gcacacaaca aaagtgcctg gcatccacta ctgctgcctt 240tcatttataa taatagccct tccatctggc agtgggggaa gaatacactc ttgacattct 300tgtctcctgc tttagaatgc tagtgtgtat ctatcatgta tgcaatactt tccccctttt 360tgctttgcta accaaagagc atatatttta ctgtcag 397 245 508 DNA Homo sapien 245cgaggagtcg cttaagtgcg aggacctcaa agtgggacaa tatatttgta aagatccaaa 60aataaatgac gctacgcaag aaccagttaa ctgtacaaac tacacagctc atgtttcctg 120ttttccagca cccaacataa cttgtaagga ttccagtggc aatgaaacac attttactgg 180gaacgaagtt ggttttttca agcccatatc ttgccgaaat gtaaatggct attcctacaa 240agtggcagtc gcattgtctc tttttcttgg atggttggga gcagatcgat tttaccttgg 300ataccctgct ttgggtttgt taaagttttg cactgtaggg ttttgtggaa ttgggagcct 360aattgatttc attcttattt caatgcagat tgttggacct tcagatggaa gtagttacat 420tatagattac tatggaacca gacttacaag actgagtatt actaatgaaa catttagaaa 480aacgcaatta tatccataaa tatttttt 508 246 358 DNA Homo sapien 246aaatgttggt attcaaaacc aaagatataa ccgaaaggaa aaacagatga gacataaaat 60gatttgcaag atgggaaata tagtagttta tgaatgtaaa ttaaattcca gttataatag 120tggctacaca ctctcactac acacacagac cccacagtcc tatatgccac aaacacattt 180ccataacttg aaaatgagta ttttgcatat ctcagttcag gatatgtttt ttacaagtta 240atcctaaagt cataaagcaa gaagctattc atagtacaag attttatttg ctaagcttta 300caaattaaac tctaaaaaat tattacaatg atactgaaag atattttatt ggcctttt 358 247 673 DNA Homo sapen misc_feaure (1)...(673) n = A,T,C or G 247gaagaaagtt agatttacgc cgatgaatat gatagtgaaa tggattttgg cgtaggtttg 60gtctagggtg tagcctgaga ataggggaaa tcagtgaatg aagcctccta tgatggcaaa 120tacagctcct attgatagga catagtggaa gtgagctaca acgtagtacg tgtcgtgtag 180tacgatgtct agtgatgagt ttgctaatac aatgccagtc aggccaccta cggtgaaaag 240aaagatgaat cctagggctc agagcactgc agcagatcat ttcatattgc ttccgtggag 300tgtggcgagt cagctaaata ctttgacgcc ggtggggata gcgatgatta tggtagcgga 360ggtgaaatat gctcgtgtgt ctacgtctat tcctactgta aatatatggt gtgctcacac 420gataaaccct aggaagccaa ttgatatcat agctcagacc atacctatgt atccaaatgg 480ttcttttttt ccggagtagt aagttacaat atgggagatt attccgaagc ctggtaggat 540aagaatataa acttcagggt gaccgaaaaa tcagaatagg tgttggtata gaatggggtc 600tcctnctccg cggggtcnaa gaaggtggtg ttgangttgc cggnctgtta ntagtatagn 660gatgccanca gct 673 248 149 DNA Homo sapien 248cctcttcatt gttcacatgt cacaggagga ggctctgagc aaaggccact ggcaagttag 60ggcaacacca agaaggctct gcggagagac tccctgtggg ttggggcctg gcaggaacgg 120tgcctgtgga ctgtttatgg tctgtccag 149 249 458 DNA Homo sapien misc_feature (1)...(458) n = A,T,C or G 249gaagctaaat ccaaagaaat atgaaggtgg ccgtgaatta agtgatttta ttagctatct 60acaaagagaa gctacaaacc cccctgtaat tcaagaagaa aaacccaaga agaagaagaa 120ggcacaggag gatctctaaa gcagtagcca aacaccactt tgtaaaagga ctcttccatc 180agagatggga aaaccattgg ggaggactag gacccatatg ggaattatta cctctcaggg 240ccgagaggac agaatggata taatctgaat cctgttaaat tttctctaaa ctgtttctta 300gctgcactgt ttatggaaat accaggacca gtttatgttt gtggttttgg gaaaaattat 360ttgtgttggg ggaaatgttg tgggggtggg gttgagttgg gggtattttc taattttttt 420tgtacatttg gaacagtgac aataaatgan accccttt 458 250 374 DNA Homo sapien 250aaaaaacaaa acaatgtaag taaaggatat ttctgaatct taaaattcat cccatgtgtg 60atcataaact cataaaaata attttaagat gccggaaaag gatactttga ttaaataaaa 120acactcatgg atatgtaaaa actgtcaaga ttaaaattta atagtttcat ttatttgtta 180ttttatttgt aagaaatagt gatgaacaaa gatccttttt catactgata cctggttgta 240tattatttga tgcaacagtt ttctgaaatg atatttcaaa ttgcatcaag aaattaaaat 300catctatctg agtagtcaaa atacaagtaa aggagagcaa ataaacaaca tttggaaaaa 360aaaaaaaaaa aaaa 374 251 356 DNA Homo sapien 251aaagatcttc tctaacaagc tatgggaatt tggcttcata ctctttcttt gcaacagcag 60tgttctgggt gataattttg aattgatacc tgttcctttt tctgggtttt gttggctttt 120tgaaaaattg tctttcctta tcattggtgg gaggcttggt agcaaagtaa cattttttgg 180aaaagaggac agaaaaattg aactacagct tgagaacgta ttcttttttt cctactttgt 240tattgcaaat tgaggaatca cttttaactg ttttaggtgt gtgtgtccag agtgagcaag 300gattatgttt ttggattgtc aaagaggatg cttagtctta aaataaaaat aaattt 356 252 484 DNA Homo sapien 252ctggtaaact gtccaaaaca aggttccaaa taacacctct tactgattta ccctacccat 60acatatccca aatagttttt gatcaaaaac atgaaataga tccacctgct tattttaagc 120atattaaaaa ggaaactaat tggaccattt tctatttgtc tattttatac aaaaaggcta 180cacaattgtt acactttatt cagattacaa ttaattagag tgattatgaa ttagtgttct 240acaccattac tcaattctta aaaattagaa attgctgtag cagtattcac tataacttaa 300cactacgaga gacttaaaaa acagttactg caaaaaaaaa aaagagctac ttcaaagcaa 360gcaaagtcag taccattaca gatattctta aaaaaaaaaa aaaatttaac aagcaaggct 420agggtttgat aaattccatc ttgtgatcca ttcttgtgca ttcttcactt cttgagtcac 480tccc 484 253 379 DNA Homo sapien 253aaaaagcgct tagacttccc tttccatctg gaacatgtaa aattttgcag caacaggttt 60tctccaattc cttcagcaag aattcccagc ctacacacaa atttaacacc atctttttct 120attcatgtat aacttggatc acacaccagt atataacgac aaaagataaa tgtataataa 180aaagattgga taaatcagaa gaggcttttt ggtcttgaat tcttcaccca ctaacaatga 240agcagcactg taggcagccc aaaacacacc aaacagtttt ataagtgtag acaccacttc 300aaatgatcca accaccaaaa gtacaggggc tattacaatg agaggaagta atgaatatcc 360tataactcca aggacttgg 379 254 387 DNA Homo sapien misc_feature (1)...(387) n = A,T,C or G 254aaatttgact tttcagtgcc tcagtttgca catctgtaat acagcaatgc taagtagtca 60aggccnttga taattggcac tatggaaatc ctgcaagatc ccactacata tgtgtggagc 120agaagggtaa ctcggctaca gtaacagctt aattttgtta aatttgttct ttatactgga 180gccatgaagc tcagagcatt agctgaccct tgaactattc aaatgggcac attagctagt 240ataacagact tacataggtg ggcctaaagc aagctcctta actgagcaaa atttggggct 300tatgagaatg aaagggtgtg aaattgacta acagacaaat catacatctc agtttctcaa 360ttctcatgta aatcagagaa tgccttt 387 255 225 DNA Homo sapien misc_feature (1)...(225) n = A,T,C or G 255aaatgtcttg tttcccagat ttcaggaaan tttttttctt ttaagctatc cacagcttac 60agcacctttg ataaaatata cttttgtgaa caaaaattga gacatttaca ttttctccct 120atgtggtcgc tccagacttg ggaaactatt catgaatatt tatattgtat ggtaatatag 180ttattgcaca agttcaataa aaatctgctc tttgtatgac agaat 225 256 544 DNA Homo sapien misc_feature (1)...(544) n = A,T,C or G 256ccttgcttaa agcccagaag tggtttaggc ntttggaaaa tctggttcac atcataaaga 60acttgatttg aaatgttttc tatagaaaca agtgctaagt gtaccgtatt atacttgatg 120ttggtcattt ctcagtccta tttctcagtt ctattatttt agaacctagt cagttcttta 180agattataac tggtcctaca ttaaaataat gcttctcgat gtcagatttt acctgtttgc 240tgctgagaac atctctgcct aatttaccaa agccagacct tcagttcaac atgcttcctt 300agcttttcat agttgtctga catttccatg aaaacaaagg aaccaacttt gttttaacca 360aactttgttt ggttacagtt ttcaggggag cgtttcttcc atgacacaca gcaacatccc 420aaagaaataa acaagtgtga caaanaaaaa aacaaaccta aatgctactg ttccaaagag 480caacttgatg gtttttttta atactgagtg caaaaggnca cccaaattcc tatgatgaaa 540tttt 544 257 420 DNA Homo sapien 257aaatgtcttg tttcccagat ttcaggaaac tttttttctt ttaagctatc cacagcttac 60agcaatttga taaaatatac ttttgtgaac aaaaattgag acatttacat tttctcccta 120tgtggtcgct ccagacttgg gaaactattc atgaatattt atattgtatg gtaatatagt 180tattgcacaa gttcaataaa aatctgctct ttgtatgaca gaatacattt gaaaacattg 240gttatattac caagactttg actagaatgt cgtatttgag gatataaacc cataggtaat 300aaacccacag gtactacaaa caaagtctga agtcagcctt ggtttggctt cctagtgtca 360attaaacttc taaaagttta atctgagatt ccttataaaa acttccagca aagcaacttt 420 258 736 DNA Homo sapien 258aaacaaaatg ctaaacctaa aaacattgtt ctgtcagttc ccaaattaaa tctacttaga 60acaaaaacaa aaatttatag ctcggtcaca tactacttaa ataatattgt tcaggcatct 120ctaaaatcct ccatgttttc aagtatggaa atagaactca aatattccac aatacagtac 180taaacagatg gagtatttag gaaagacttt gttgtcatat ggcacaatat taatattttg 240ttgcttcaat acgttttgaa ataaatatca gatttttgtt tttttttcct aaaagaccaa 300aattataatc tacattaaga taattctgac tgtggttaag acttaagagt gtaaaataca 360acatcaatat tttatcacaa aagtaaagct ggtaacaaat tataaaagga gccagtactc 420tactgagaca ggctcggaga ttaaagctca tcatgataga aatagtcatc atggagctgt 480ctgccataat ctgtggcttc actggtgaga aacaagtccg ggttttccag aatctcttct 540tcagagagct ttttgtcacc attcaaatcc atttcatcaa ttagatgaag cgcctcctct 600tgtgcaatgc cctgattatt aggtctaccc aaggtaacag ctcttgggga tcaagcctgc 660catcgttatc tttgtcataa tcattcaccg aatctgtctt tctcacaagt atcccattct 720ggatcttcat ttgcag 736 259 437 DNA Homo sapien misc_feature (1)...(437) n = A,T,C or G 259aaaaccatac tgaaatcatt taccaaataa cnaagatctt aatctaaaag atagtgaata 60catcatcatc atgaaatctg gttttatgtg ctctatgaag tacttggaga attgcttttt 120tatttttctt ttgctttatt aggtcacaca aaacagaatg aattagcaga aaaatgtatg 180ttataaaaca gcatttacta cttcaattta atttttttta ctaacaattg tggacctttt 240tgatgacact tatgtatgtt tttaataaat tatgtactta ttagtactta atgagccctt 300cctgcctcaa tataaaatta ctaaacttgg agaattacag attttattgt aggccctgat 360gttagtcact ttggagaagc taaaaatttg gaaatgatgt aattcccact gtaatagcat 420agggattttg gaagcag 437 260 592 DNA Homo sapien 260tttttttttt gaaaaatata aaattttaat aaaggctaca tctcttaatt acaataatta 60ttgtaccaag taattttcct taaatgaact ctttataatg cataatttac agtataagta 120gaacaaaatg tcatgacaaa agtcattgag tacaagactt gtaataaaaa ggcataaaat 180atatttatac ataaacccct ttcaaaaaac aagggaaagc ttgagccctc aatatagggc 240gacacacgga gcgggtgacc gtgcaggtac aggtactgta ctgatttaaa gtcaagcact 300agagatagtg gattaatact cttttgccgt acactatata cagatgtata gtacaagtaa 360caatggcaaa cagaatgtac agattaactt aacacaaaaa cccgaacatc aaaatgaagg 420tgtgtggagg aaaggtgctg ctgggtctcc ctacaactgt tcatttcttt gtggggcagg 480gggtagttcc tgaatggctg tggtccaatg actaatgtaa aacaaaaaca gaaacaaaaa 540aaacaaggaa ctgtcatttc cacgaaagca cagcggcagt gattctagca gg 592 261 450 DNA Homo sapien 261gtggcagggc ccagccccga accagacaag ggacccctca aggagcttca ttctagcatg 60agaaaattga gaagtaaacc agaaagttac agaatgtctg aaggggacag tgtgggagaa 120tccgtccatg ggaaaccttc ggtggtgtac agatttttca caagacttgg acagatttat 180cagtcctggc tagacaagtc cacaccctac acggctgtgc gatgggtcgt gacactgggc 240ctgagctttg tctacatgat tcgagtttac ctgctgcagg gttggtacat tgtgacctat 300gccttgggga tctaccatct aaatcttttc atagcttttc tttctcccaa agtggatcct 360tccttaatgg aagactcaga tgacggtcct tcgctaccca ccaaacagaa cgaggaattc 420cgccccttca ttcgaaggct cccagagttt 450 262 239 DNA Homo sapien misc_feature (1)...(239) n = A,T,C or G 262taactttgat gacaaaatct aaaattaaag anttagtctt aaaagcctat agtgacttgt 60ttacttgcat aaataatatt ttcacttagt acaggctatt aatataagta atgagaattt 120aagtattaac tcaaaaaaag atagaggctc caaacttttc taagaaatta atgcattttc 180aaagtaataa tataatcaat ctgtaagtca aaagtaattt catattcatt gccaaattt 239 263 376 DNA Homo sapien misc_feature (1)...(376) n = A,T,C or G 263aaaaaaaaaa aaaaaaaatt ccttgtngtt tnttagagga aaaaaagaaa aaccccaact 60tttancactg atactacata ttgctctgtt aaagaatttt ctctgccaaa aaaaagaaaa 120aacaaaaaaa cgcttaaagc tggagtttga cattctgctt tcagatgctg tctttttatt 180agtgagtgat gatggtttgc taataatcaa taggtaataa ttttttgtaa tcccatcaag 240tggctccata tgtttctgct ctctcgtgac tgtgttaatg tttaactgtt gtaccttaaa 300gccgaaatca gtaactatgc atactgtaac caaggtattg ggcttacaga gttgtttgtt 360gnataaagaa aatttt 376 264 207 DNA Homo sapien 264aaattagcat tccacaaata tacaggtaat ttaataatta ttgtgcatga atacatacac 60aatgcttata tatacaaatt ccagtttgtt ttcatgtgct ggcaagggat ttgtatacaa 120tcataagctg tgttcatatt ggtcccattg aatattcaca atacaaaagc acaaaagaac 180cattgattta caaaaggaaa tctattt 207 265 388 DNA Homo sapien misc_feature (1)...(388) n = A,T,C or G 265naactgcact ttatttgtta ctgtaacatt nttttttaac tgatcaacca taagcatgca 60aaagnccnct gaaactgctt ccactgcctg ttgtatagaa atgggtaaat tataaaggtg 120attcaatttg gagctccttc cttttttata gcacttctaa gctgtgtgcg cgacacacac 180cacagaggta ggaaggacca cctttaataa attatcttct taatcgcaga gaatttctga 240agataaaact gacaaaatgc taaaccaagg ctttgatgag tcccaaagga ccacagatcc 300atcggctcct atttgaagaa ttcatcccct gtagtgttct agcctttgta gggcactgga 360ttacaagatc caccagggct ctgaacaa 388 266 616 DNA Homo sapien misc_feature (1)...(616) n = A,T,C or G 266aaatacagag tcaaaagatg atttataaaa tntaaaacat tttctgcttg gccgtatttg 60aagacaagct gaatacatat ctatgttctg aataagtcca ctatggatat atataggaag 120agatatacat atatccatcc acagatacac acacacatat atatttctgc atgtatatat 180acataattct ttctatagtt acaggaaata cttcttctat aattctgatt ttgactccca 240tcctccacca tttactcatc cactcattac ctaaatcttg gctttctttc ctatattgta 300aataatccat ccaaacttct agccagtact gtcaggaggg ttcttgctcg agtgagctgt 360taatactatt ttccactgac aacttctgca catcgaggac acagtgtatc tgaagactcc 420gctgtatact tccaacaacg ggggcatttt tctttcgtag tcggcatgac aattacttta 480taggaagact cttcacgaat atcaccacct tctaagttga tgaggaattt ccctttaagc 540tcgattacat ctgcagtcat ctctcgtggt tcctgaccag taaagttgac tcagaagcca 600tcattaattc attcaa 616 267 341 DNA Homo sapien 267cattatgta tgtattttct tgaaaaatac ttatttcagc tacttatttt taatagttac 60tattcttgt tgtattgtca tttgagtttt gtatatattt ttgatattaa ccccttgtca 120atgtataat ttgcaaatat tttctccctt tttttagttg tcacattctg ttcattgtat 180agattctgt gcagcagctt tttaatttga agtgatctga ctgacttgtt cttccttttg 240gtcctggga tatttaggtt aaatcaaaaa acttgctgcc cagaccaatg ttatggggct 300tcactctat tttttggtag tagtagttta agagttttag g 341 268 367 DNA Homo sapien misc_feature (1)...(367) n = A,T,C or G 268ttgtagattg gaatagcaaa agtgaatgct ntgaccaaaa tttttgccct cctaaataaa 60gacgtntcct tctagagagc aaatctatca taaaatgtca aaactagaag agaataaaat 120gaaaggaaaa aacctagaaa aatatcctaa aatatcaaat gcagtcattt ctaaatataa 180gccataatta tagctttacc tattgttctt attgttccta tgctgcttct acaatgttac 240atcaactata cttagcttta ctctcccaaa atcttggtga tgaagccttc tgagtgtgct 300ttccaatgtg ccagaaccag aagggcattc caaggcttcc ccacatttcc tccatttacg 360gagacag 367 269 270 DNA Homo sapien misc_feature (1)...(270) n = A,T,C or G 269caaatctctc cctcactaga cgtaagccnt ttnctcactc tctcaatctt atgcatcata 60gnaangcngn tgaggtggat taaaccaaac ccagctacgc aaaatcttag catactcctc 120aattacccac ataggatgaa taatagcagt tctaccgtac aaccctaaca taaccattct 180taatttaact atttatatta tcctaactac taccgcatcc ctactactca acttaaactc 240cagcaccacg accctactac tatntcgcac 270 270 368 DNA Homo sapien misc_feature (1)...(368) n = A,T,C or G 270ctgaatcatg aataacacta tataatagag tntaaggaac acaagcatta gatgtgatcc 60ttgccccata cccttagatt atgtcagact aaagctgaca attctgccag gctctgaacc 120cctagtgccc ccaacccaaa tcttggaagc aaagaatatg ccctgtcata caactttgta 180caagttgtag taaaacaaag cttaagtttt ctcatctttc tacagcaaat ggtcagttat 240ttaataaaca ctaaaatgct cctaagaatc cattttgagt ttgtttacca aacacattgt 300gcaagaactg actacacaaa aagttccttt gaaatttggt ccacaaattc acttaaggtt 360ggaaattt 368 271 313 DNA Homo sapien misc_feature (1)...(313) n = A,T,C or G 271aaatttatat aaaactctgt acatgttcac tttattattg cataaacagc ataatcttca 60agacaanngt ttgcaaacac atgtccaatt caggaaaaaa aatttcacgt ttctcgtctg 120gcttttttct tcttttttat ttgtttggga gattcccagc tagtttcaga cttggtctgt 180gaaggaggca cactattttg cttggtattt gacttggatt tatctgtctc ttgtagtatt 240ggcggcactt gggaagagct cttgtcagaa tcactttttg ataagattac agatggctcg 300gtagaagtag cag 313 272 462 DNA Homo sapien misc_feature (1)...(462) n = A,T,C or G 272aaaaaacatt tattttaata agactattgc naacacatta aaaaaactaa atagtaatat 60tacaaaatct atatacttgc acatttagta tttgtcaatg tgccagaggt tttcttcatg 120aaatttgact tctttgaagt gaaggctttt ttctatcatc tcttatagct ctgactgaat 180aagtcttaat gctttcttca tgttttctat caataggggt aaatcccgag gctcatatgt 240gtacaatctg ttagagtatc ttccagctat gtcagctcta actgttaaag aagggtctac 300aaacatgatt ctaggcacat attgcccatc aggtgataaa ttcttatcag tggtttcatg 360cataaggttt agcatgatga acttattctg agccatttct tgtatttctt cattttgggc 420aaatactttc tttagtgctt gagagtattg acaatcctcc ag 462 273 282 DNA Homo sapien misc_feature (1)...(282) n = A,T,C or G 273ctgatcaaag catgggatat tttaatagtn ttatacataa tatttttaca tagaaaactt 60tacatnncat ttcatattat ataattctgc ttattctttc aaaaatttat acatccattg 120ggcaaggaat ggttttcatt aaattaccaa tattaaatgc acttaatcat tgtgtatagg 180ttaaaccaaa gtaactatta actaactttt aggcatttta aggaggtaaa acatacattt 240tacacataag tatttgatgc aaatatgcag ataaaatttt tt 282 274 125 DNA Homo sapien misc_feature (1)...(125) n = A,T,C or G 274cagccctaga cctcaactac ctaaccaacn ttncttaaaa taaaatcccc actatgcaca 60ttnaatcnct ccaacatact cggattctac cctagcatca cacaccgcac aatcccctat 120ctagg 125 275 528 DNA Homo sapien misc_feature (1)...(528) n = A,T,C or G 275aaagctgtgg aaaagcttta ttatagattt ttntacagaa ttaaaaaagt tcaaacaata 60ataagccngg aaccacaaat aattaaaagg aaacacagca atcccataaa caagcattct 120ggcatctgtt agaaattttc cctcaaatta tgaaatgtag ctctccatgc tttccaatga 180ttgttataat acccacaaat atctgtgatt tcagtggaat actttaacaa aagttttctt 240tttaaggcat gatcctgatt cattttttct tcaatatctc agtcatttca ggaactacct 300taaataaatc tgcaactatt ccataatctg ccacttggaa aattggagct tctgggtctt 360tattaattgc cacaattgtc ttgctgtctt tcatcccagc taaatgttgg atggctccag 420atattccaac agcaatataa agttctggtg ctactatttt tcccgtctgn ccaacttgca 480tgtcattggg aacaaagcca gcatcaacag cagcacggga agcaccaa 528 276 420 DNA Homo sapien misc_feature (1)...(420) n = A,T,C or G 276aaatgtcttg tttcccagat ttcaggaaan tttttttctt ttaagctatc cacagcttac 60agaaacctga taaaatatac ttttgtgaac aaaaattgag acatttacat tttctcccta 120tgtggtcgct ccagacttgg gaaactattc atgaatattt atattgtatg gtaatatagt 180tattgcacaa gttcaataaa aatctgctct ttgtatgaca gaatacattt gaaaacattg 240gttatattac caagactttg actagaatgt cgtatttgag gatataaacc cataggtaat 300aaacccacag gtactacaaa caaagtctga agtcagcctt ggtttggctt cctagtgtca 360attaaacttc taaaagttta atctgagatt ccttataaaa acttccagca aagcaacttt 420 277 668 DNA Homo sapien misc_feature (1)...(668) n = A,T,C or G 277ccagggtggc tctgatatag cagccctggt ntattttcga tatttcagga agactggcag 60atngcaccag accctgaatt cttctagctc ctccaatccc attttatccc atggaaccac 120taaaaacaag gtctgctctg ctcctgaagc cctatatgct ggagatggac aactcaatga 180aaatttaaag ggaaaaccct caggcctgag gtgtgtgcca ctcagagact tcacctaact 240agagacaggc aaactgcaaa ccatggtgag aaattgacga cttcacacta tggacagctt 300ttcccaagat gtcaaaacaa gactcctcat catgataagg ctcttacccc cttttaattt 360gtccttgctt atgcctgcct ctttcgcttg gcaggatgat gctgtcatta gtatttcaca 420agaagtagct tcagagggta acttaacaga gtatcagatc tatcttgtca atcccaacgt 480tttacataaa ataagagatc ctttagtgca cccagtgact gacattagca gcatctttaa 540cacagccgtg tgttcaaatg tacagnggtc cttttcagag ttggacttct agactcacct 600gttctcactc cctgttttaa ttcaacccag ccatgcaatg ccaaataata gaaattgctc 660cctaccag 668 278 202 DNA Homo sapien misc_feature (1)...(202) n = A,T,C or G 278aaattggtat cgacggcaac caggggaagn tnctaaactc ctaatctatt ctggatccaa 60ttngcnaagt ggggtcccat caaggttcag tggcagtgga tctgggacag atttcactct 120cacgatcagc agtctgcaac ccgaagattt tgcaacttac tactgtcaac agagttacat 180gtccccgtac acttttggac cc 202 279 694 DNA Homo sapien misc_feature (1)...(694) n = A,T,C or G 279ctgtacttgg acaaaataag ttaattctat ttggttgtcc attaaagttt tatgtggcta 60tgnacccact ggagctaaaa attggctttt aactgtttcc aaatcagaac tagcagagga 120gagaagtaaa taaagccaat ggcactccct tcagaggctc aaaatggtta gattttgatg 180cagatttaac cttagcgagt ttcagtcagt ccatttagat gatcctgtag gttcatacaa 240atacactgaa ccgttggttt aacttctctt ccttcctcaa agtttatgat aaagagactc 300atccctgtat tgggagtgac tgacataagt tcagatctgc tcagagtggc tggtaaggaa 360cacttaaggt cagtcagaaa ataatcaaac agacttctca tgtaagcacc gtgactcaca 420actaagacac tggctgctaa tcctggaata ccgctgtctg aattaacttt agagctgtga 480ttttttccta aaggaaatat ctctgccaaa gaagtttcca gacagntgct tgggagatcc 540ttggggaaaa ctggtctttt tgatccggtt ctttcangan taggtngaca aaagaaatnc 600aaaaaagnct atcccacgcn tttntcacct gggcccagcg gnnctcctcc nggggggggn 660aaacacangg gactcttccc ngggctngct tnng 694 280 441 DNA Homo sapien 280aaaaaacttc catgcaactt ctggtttatt gtttggcaac tccacatgat aaaaaaataa 60aaacagccca accgagtttc ggaattaagt attcttctag taagtgattc aaacttgtaa 120tatttgccac aggactgact tatttattta ctagctagaa gctcttaagt tcacttgttt 180atcagggcat atacagaagg gtttgttaaa actcgatgtt aactttacaa ctttctgacc 240tggtgcatga attctcaagt actgtatttc actgtgttgg tgtgtctgat ggaaatttcg 300aggtggtccc acaaaaatat tttatgtagt gtgccttcaa agagaaccat ttatttctct 360tcacttatcg tcccacaaag tcacatttgg tggtggtcag ccaagtcgca tctggtctag 420ttttactctt gtcccaattt t 441 281 398 DNA Homo sapien 281aaatttgtta ggtctgaaga atctaaaact gttaatttaa cccttaactt gtgcctagaa 60actacagcac atataaaata tgtaaacacc agcctgttgc tgtacttttc tgcttatttt 120acagcctcaa atatttctca ttatcttgtc acttagttct tcatgtttct ccttctgact 180tttaataatg gtaataggaa aacaaaaccc aaagcttttc agaacttcag tgtgaggttt 240cctattttga caagttaact tgtaaatact caggttttac gatgtataat ttacctaata 300gaccaaacta actcatggag atattttgaa ctattattta ggtacaaact ttataaagaa 360tgttagtatg tcataaaata taacattaca gcttattt 398 282 226 DNA Homo sapien misc_feature (1)...(226) n = A,T,C or G 282aaaacaatat tctctttttg aaaatagtat naacaggcca tgcatataat gtacagtgta 60ttacnccaat atgtaaagat tcttcaaggt aacaagggtt tgggttttga aataaacatc 120tggatcttat agaccgttca tacaatggtt ttagcaagtt catagtaaga caaacaagtc 180ctatcttttt ttttggctgg ggtgggggcg cccaggccga ggctgg 226 283 358 DNA Homo sapien 283aacaaaaat actcaagatc atttatattt ttttggagag aaaactgtcc taatttagaa 60ttccctcaa atctgaggga cttttaagaa atgctaacag atttttctgg aggaaattta 120acaaaacaa tgtcatttag tagaatattt cagtatttaa gtggaatttc agtatactgt 180ctatccttt ataagtcatt aaaataatgt ttcatcaaat ggttaaatgg accactggtt 240cttagagaa atgtttttag gcttaattca ttcaattgtc aagtacactt agtcttaata 300actcaggtt tgaacagatt attctgaata ttaaaattta atccattctt aatatttt 358 284 288 DNA Homo sapien 284aaaacttttg ttaagaaaaa ctgccagttt gtgcttttga aatgtctgtt ttgacatcat 60agtctagtaa aattttgaca gtgcatatgt actgttacta aaagctttat atgaaattat 120taatgtgaag tttttcattt ataattcaag gaaggatttc ctgaaaacat ttcaagggat 180ttatgtctac atatttgtgt gtgtgtgtgt gtatatatat gtaatatgca tacacagatg 240catatgtgta tatataatga aatttatgtt gctggtattt tgcatttt 288 285 629 DNA Homo sapien misc_feature (1)...(629) n = A,T,C or G 285cctaaaagca gccaccaatt aacaaagcgt ncannctcaa cacccactac ctaaaaaatc 60ccaaacatat aactgaactc ctcacaccca attggaccaa tctatcaccc tatanaagaa 120ctaatgttag tataagtaac atgaaaacat tctcctctgc ataagcctgc gtcagattaa 180aacactgaac tgacaattaa cagcccaata tctacaatca accaacaagt cattattacc 240ctcactgtca acccaacaca ggcatgctca taaggaaagg ttaaaaaaag taaaaggaac 300tcggcaaatc ttaccccgcc tgtttaccaa aaacatcacc tctagcatca ccagtattag 360aggcaccgcc tgcccagtga cacatgttta acggccgcgg taccctaacc gtgcaaaggt 420agcataatca cttgntcctt aattagggac ctgtatgaat ggcttcacga gggttcagct 480gtctcttact tttaaccagt gaaattgacc tgcccgtgaa gaggcnggca tgacacagca 540agacgagaag accctatgga gctttaattt attaatgcaa acagnaccta acaaacccca 600caggtcctaa acttacccaa accctggca 629 286 485 DNA Homo sapien 286aaatgtactt gctcagctca actgcatttc agttgtatta tagtccagtt cttatcaaca 60ttaaaaccta tagcaatcat ttcaaatcta ttctgcaaat tgtataagaa taaagttaga 120attaacaatt ttattttgta caacagtgga attttctgtc atggataatg tgcttgagtc 180cctataatct atagacatgt gatagcaaaa gaaacaaaca aaagccagga aaacactcat 240tttcgccttg aatatgtaaa tgggattaat tttgtcctgt gccttatgtg gaaaggaact 300tctttggttt tccttttttg ttctggtgga agcatgtgca ggagacatat catccaaaca 360taaaccatta aaatgtttgt ggtttgcttg gctgtaattt tcaaagtagt taattgagga 420caaagggtaa tgcagaagtg atagctttgg tttgctgagt cttgttttaa gtggccttga 480tattt 485 287 340 DNA Homo sapien 287cctggagtcc aataaccacc ccctcatacc acaccctgtg catacaccag ccaagccttt 60cctggtctgg gaagggaaga gaaaaaagac gcaggccacc tgggggttct gcagtctttg 120gtcagtccag ccttctatct tagctgcctt tggcttccgc agtgtaaacc ttgcctgccc 180ggaggcagga ggcccagctg gacctccgag ggccatgagc aggcagcagc catcttggcc 240tcaagcttgc ctttcccttg agtccctctc tcccctcggc tctagccaga ggtgtagcct 300gcagatctag gaagagaaga gctggggagg aggatgaagg 340 288 290 DNA Homo sapien 288aaacagtctc tcctcggtgt tctccttgtc aaactgttca tcccagtttc ctctgaaata 60gacagcattc accagaacca gccttgtcaa tggatccact gagcccggag agagcaactc 120cgcaatttta ccttctgtct tttcagctac ccaggtgttt atgtgttttc tggacttctc 180tacggcgctg ataaagtcaa gctcctccat ctctgcttgg tagaattttt ggcaggaatc 240tctaaaagat gagaggaaat cacaagactt ttccccaaag agcctgttgg 290 289 404 DNA Homo sapien 289ccacccacgc ttaggttccc atcacactga tgactccggg tttggcgagc acaggagcgc 60aaaccttttc acattctttc tgtgatccaa atttgttttc gtttccacca caacctccat 120accagaatct tgcacagctt ttggtgtttg gatcatagta ccattttaat atgaaatccc 180tgcaagttcc ttcgtctttc ggcaacttgc atatatctgt ttcagtgaga gccaatggtt 240ctgtgctcac cattagattg atggttgaac tagaagctga ccttgctggc tgtggaggtg 300ggggctgaga tttctttgta ctgaaacttc cgtggtaggt ggctctgacc tgagacctca 360ggtagcagac cacagccaca tggtatgtct gcccagcgag cagg 404 290 384 DNA Homo sapien misc_feature (1)...(384) n = A,T,C or G 290ccaggcgctc cttgtcggca tcagggaggg tggccttgaa ctgctcatgg gctgtggtca 60gtccctggat ctcctcaatg gtgtgcacaa tgaaggtgtc ctgcaggtcc tccatggccc 120cctccatcca gttgttgaag ggtgcagccc gcttggcata ctccaagtac agctggtcaa 180tggtctccag cagtttctcg gtccgctcca gagcttccct tcgcttctga gttagggccc 240ccagattgtc ccactggtca cagatctttt ggcaacgggc gttgacactg ggtgagtcat 300aatantccag ctcattgagc tcctgtgcga tggcggcaat ctgctccaca cggtcctggt 360gggcagccag gccactctcg aagg 384 291 278 DNA Homo sapien 291aaagtttatt tttactattt ctttatcact ttattgtatc atcaccattg gtttcataat 60gtaaatacta tatgttgaac aaattaaatg tcaaaatttt ttattaccat agtccatgtt 120aatagtgggg ctttcaggtg tttagagatt ttttttgttg ttgttaacat tcattgcaaa 180agtactagat ggtgtataac tctagagttg aattttaagg gattccctaa tatgtatact 240atctttttat ctgaagtaat aaataaacaa tgatcttg 278 292 177 DNA Homo sapien 292ccttggcccg gtcattcttg tccagtttga taggttcagg aaattcgttg tacagctcca 60cctccgtttc ctgcttaagt gcattccgtg caatcgtctg gaacgcctgc tccacgttga 120tggcctcctt ggcactggtc tcaaagtagg gaatgttgtt tttgctgtag caccagg 177 293 403 DNA Homo sapien 293aaaaagaagg acttagggtg tcgttttcac atatgacaat gttgcattta tgatgcagtt 60tcaagtacca aaacgttgaa ttgatgatgc agttttcata tatcgagatg ttcgctcgtg 120cagtactgtt ggttaaatga caatttatgt ggattttgca tgtaatacac agtgagacac 180agtaatttta tctaaattac agtgcagttt agttaatcta ttaatactga ctcagtgtct 240gcctttaaat ataaatgata tgttgaaaac ttaaggaagc aaatgctaca tatatgcaat 300ataaaatagt aatgtgatgc tgatgctgtt aaccaaaggg cagaataaat aagcaaaatg 360ccaaaagggg tcttaattga aatgaaaatt taattttgtt ttt 403 294 305 DNA Homo sapien misc_feature (1)...(305) n = A,T,C or G 294aaagcaatct ggcatggtgt cctgtagtga agcagaggat cataacataa gtaaactctc 60tatgggtgga agttggagag aaggacattt tggctttgta catgaaaaga ctctccagat 120agaaacagat tctgcccata agtgaaataa aatgctttgt gggggtaatg agtgacttat 180agtattcagg cagatgttac ataactgcta attaagtttc cctggattga ntttanncaa 240anaattgaaa gtngattttg gtcangtgtc agnaaactac tgcctataaa cccatatcnt 300accca 305 295 397 DNA Homo sapien misc_feature (1)...(397) n = A,T,C or G 295cctatctggt tggccttttt gaagacacca acctgtgtgc tatccatgcc aaacgtgtaa 60caattatgcc aaaagacatc cagctagcac gccgcatacg tggagaacgt gcttaagaat 120ccactatgat gggaaacatt tcattcccaa aaaaaaaaaa aaaaaaaaat ttctcttctt 180cctgttattg gtagttctga acgttagata ttttttttcc atggggtcaa aaggtaccta 240agtatatgat tgccgagtgg aaaaataggg gacagaaatc aggtattggc agtttttcca 300tttncatttg tgggngaatt tttaatataa atgcggagac gtaaagcatt aatgcnagtt 360aaaatgtttc agtgaacaag tttcagcggt tcaactt 397 296 447 DNA Homo sapien 296ccatcctcga tgttgaagtt gtcgtggggc ccgaagacgt tggtggggat gacagcggtg 60aaggtgcagc cgtactgctg gaagtaggcc ctgttctgca cgtcgatcat cctcttggca 120tacgagtacc caaaattgct gttgtgggga ggcccattgt ggatcatggt ctcatctatc 180gggtaggtcg tcttgtcagg gaagatacag gtggacaggc aggacaccac cttgcgggcg 240cccacctcga aggccgagtg caggacgttg tcgttcatgt gcacgttttt cctccagaag 300tccaaattgt atttgatatt ccggaacagg ccccccacca ttgcagcaag atggatgacg 360tgtgtgagtt ggaccttctc aaacagggcg cgggtctgtg ctgtatccgt gagatcggcg 420tctttagagg agacaaacac ccagtcc 447 297 681 DNA Homo sapien misc_feature (1)...(681) n = A,T,C or G 297aaataacagc atgtaaaata ttaaaataca agctttcaaa aataaataca taaataagta 60gaaccctcgt aagaaatagt caaacacatt aagtcctttc cagctgtccc tagaaagctg 120ctgttctctt tttcattttc agctctggta agggcaggga ccaccctgca ggaagtgtca 180atgatacgct gataagcttc ttacttctct cctgtcagtt ggtgctcccc ctgtgatgag 240aaaagggtta ctgttgcagg tgctaaggaa ggctgctctt ctgtcactct gaagttgctt 300ggagggatgt ccccatgcag actctctccc agccctccac tcagggaagg tctgtctgta 360cccactgcct tctatagcag aaaacttgca ctcctgaatg cttttttttt ttttcaagaa 420agaagnggct gnggactcaa ctagattctt ggtttgaaaa agccaaaaca tattggtcac 480tgattgtcac attgggttag aaatgtccat tcatgatctc ccttaagctg cacacaaccc 540tatgaaataa ctaccattat ctaccctatt ttgctaaagc tcaaagagat taaataatgt 600tgacagggat cttagccttg aactcactga aggngttact gcaaagttct gctcttcacc 660aagaaggntt acaggccaaa g 681 298 353 DNA Homo sapien misc_feature (1)...(353) n = A,T,C or G 298cctggcttaa gaccagacat ttgaagaagg ctccaggcag ggaaaggaaa ggagaggcca 60gccccacnct gncccctccc tgcccccacg tctccagcaa cacaaggcgg ccagtggacc 120gtgaaccatt tatttccaaa ctataaagaa acctgctctc tgagaaaana cactgcccag 180gngatgaagc tccagcccct ggaggtccaa aacccagtcc aaactcagtc cctttagaaa 240gctgctgtgc cttggaaatg annntcggnt gtcanagcct gggaagtggt gggaagaacc 300agcccactcc cctctcctgc tgcgattcca gcgcncgttg ggnccagatc tgg 353 299 560 DNA Homo sapien 299aaagttcaag gactaacctt atttatttgg gaaaggggag gaggaaggaa atgatatggt 60acccagacac tgggctaggc tgcaacttta tctcatttaa tactcccagc tgtcatgtga 120gaaagaaagc aggctaggca tgtgaaatca ctttcatgga ttattaatgg atttaagagg 180gcatcaatca gctcaactca agatttcata atcattttta gtatttagat tgtgcctcaa 240agttgtagta cctcacaata cctccactgg tttcctgttg taaaaacctt cagtgagttt 300gaccattgtg ctcttggctc ttgggctgga gtaccgtggt gagggagtaa acactagaag 360tctttagtac aaaactgctc tagggacacc tggtgattcc tacacaagtg atgtttatat 420ttctcataaa gagtcttccc tatcccaagg tcttcatgat gccagtagcc atatatgata 480aattatgttc agtgataact tagttatcag aaatcagctc agtggtcttc cccgccatga 540ttcacatttg atgagttttt 560 300 165 DNA Homo sapien misc_feature (1)...(165) n = A,T,C or G 300aaaaactaca taggggtgtg tgtgtgtgtg tatgtttatt ttatacacac atatttgtat 60attctaatat attactaagg caattttaat gaattaccat gtatataaaa aaatatctgn 120cacttggcac acaggtttgt atgtatgtgt atatatatat gtatg 165 301 438 DNA Homo sapien 301aaaatatatg tatttaaaaa caaaaagcaa cagtaatcta tgtgtttctg taacaaattg 60ggatctgtct tggcattaaa ccacatcatg gaccaaatgt gccatactaa tgatgagcat 120ttagcacaat ttgagactga aatttagtac actatgttct aggtcagtct aacagtttgc 180ctgctgtatt tatagtaacc attttccttt ggactgttca agcaaaaaag gtaactaact 240gcttcatctc cttttgcgct tatttggaaa ttttagttat agtgtttaac tggcatggat 300taatagagtt ggagttttat ttttaagaaa aattcacaag ctaacttcca ctaatccatt 360atcctttatt ttattgaaat gtataattaa cttaactgaa gaaaaggttc ttcttgggag 420tatgttgtca taacattt 438 302 172 DNA Homo sapien 302ccaaaacagg agtcctgggt gatatcatca tgagacccag ctgtgctcct ggatggtttt 60accacaagtc caattgctat ggttacttca ggaagctgag gaactggtct gatgccgagc 120tcgagtgtca gtcttacgga aacggagccc acctggcatc tatcctgagt tt 172 303 552 DNA Homo sapien 303ccagcctgtt gcaggctgct tcgtagcggg cgtcggctgc ggacttccct tcccgggtct 60ggatcttttc atcctaccag atgagaaagg gaatgagtga atggagtgac cccgcaccct 120gtcactttcc tgagacatga ctgccaggaa gaagagctgc tctggtctcc atcagggctg 180gcaggacaaa ctgaccagtg agtcagtagg cagagttcac actgaaaaag ggcacaaggg 240ctgtcccaca atgggaggaa atggggtctc agaacttcta cttctctgaa aactaagaca 300caattgggac aaccaccacc cccgtgtgag atttctcacc tcgagacagg acaagatgaa 360gttcacggct tcttctgggg taaagacctt gaagagccca tcacaggcca acaaaatgaa 420cctacaacac cagggagaaa tataaacggg ttttaggccc aaccaaaaaa taaaaaataa 480aaaaagggcc tggagatgga gataaaataa atatttgtcc aactattcaa aggctaaggt 540ttttttttct tt 552 304 601 DNA Homo sapien 304cctttgattc ttggtagtac attgcatgta aaatgtttat aagaagctac ttttccttca 60tgggaagaaa ttcccacatg agattcataa attcttagac tccgtggctt ctttggtccg 120gaatgcttaa actcatatga gtgttctgga tcccagtgta tccaatcata attcacatta 180tcaccttcac gaaccacata ctttgcccac ggtgaaatac gatacaagat ctctccgctt 240ttactagtaa taactacctt taatttggat ccatgaggca cgagtacaga tttattctgc 300tttggtggga tatacagctc ccattttcca taatccagtt ttttgtatgg gtacgaaaat 360ggattccaac cattaaaatc tccagtaaga aaaactcctt ctgctcccgg ggcccattct 420ttgcagtata aaccaccatc agcacatctg tggacgccaa atgattcata gcctctggaa 480aacttatcaa taccaccttc attttctcca atgttcttca aaatttggct aaactgctta 540tacctgcgct ggaagtccac ggcgtagggc ttcaagtacc ggtcgatctc caggagtctg 600g 601 305 401 DNA Homo sapien 305aaataacagc atgtaaaata ttaaaataca agctttcaaa aataaataca taaataagta 60gaaccctcgt aagaaatagt caaacacatt aagtcctttc cagctgtccc tagaaagctg 120ctgttctctt tttcattttc agctctggta agggcaggga ccaccctgca ggaagtgtca 180atgatacgct gataagcttc ttacttctct cctgtcagtt ggtgctcccc ctgtgatgag 240aaaagggtta ctgttgcagg tgctaaggaa ggctgctctt ctgtcactct gaagttgctt 300ggagggatgt ccccatgcag actctctccc agccctccac tcagggaagg tctgtctgta 360cccactgcct tctatagcag aaaacttgca ctcctgaatg c 401 306 313 DNA Homo sapien 306aaactgacta tggattcctt gaaggtctgg cagttgttga tgatggcgat catgtactga 60acgtagcagt gagggtgctg ccgattcctc aggtgctctt ctttatacag ctgcgcttca 120tctttatatc tgaggacaga caggcttcgg tcagacagca ctaagggcaa catggagctg 180tttcaaatgc cacgctgacg tcacgcctgg cctgaaattt cacatcacta acatctgacc 240ggatgagcct ctaaaaataa aacaatcttt agacgatcca gactaatgga aggacagaga 300ggttgattac ttt 313 307 366 DNA Homo sapien misc_feature (1)...(366) n = A,T,C or G 307aaagatgctg ntaatgaaca ttacggacaa ttcatggtgt ggctagttgg taacacttca 60gctgattttt cttatgagat ggaaaaaaaa aatcagccaa gtaagggcac atcttcactt 120catttataag tcagcatcca aggtaaaaga attctctgtt ggacttgaca tcactcccat 180cctctgatac tcgcctactc tcttctcaaa gaagttagnt ctttccttcc antgaaatat 240tctcataaaa gtcaaatggg ttctctactc tgaaaacctt gctaaaaccc aattccagca 300taagtttgtc tgncacaaac ncaatgnatt gcttcattaa antgcaattc atcccaatga 360gcttcc 366 308 534 DNA Homo sapien misc_feature (1)...(534) n = A,T,C or G 308ccagctatca gctgatcgtc ttctgtctgg acgctcgtcc tgcttctgac atcaaaatct 60tctgtctcaa agtcagagtc atccaactcc tcaggggtcc ttatcatcag cactgctttc 120ctgatgtccc ggatgccatc atataccagg cgggaagcat cgataaactc attctcatcc 180atgggctggg cagggtccga gctgagggct tccacggctg cttctacttg ctcagtaaaa 240cgtggcatga ctgtgttgga gagcagctta gtggcttcca gaaccttctc tgtgtagact 300cctggctcat agtcgtccat ctctgaggtg actacgtgaa tgacccgggc tgcccggcct 360cgaattgcac cagctgtgcg gccaggccat ccacatcctt ctcttggaga gcaatgacac 420atttggtcac atcttccaaa atgtgattct ctgagacagc caagaagtca tcaatggaag 480taatgncatc gacagcatct gtgagaacac cgacttgttt ttccattgnt cttt 534 309 164 DNA Homo sapien 309catactcctt acactattcc tcatcaccca actaaaaata ttaaacacaa actaccacct 60acctccctca ccaaagccca taaaaataaa aaattataac aaaccctgag aaccaaaatg 120aacgaaaatc tgttcgcttc attcattgcc cccacaatcc tagg 164 310 131 DNA Homo sapien 310aaaaatcatt tatctttcgg tgcttcaaca tgatgccaaa caaaaatcta ctgaataaaa 60atagcaagga agggaatcaa acatttataa gatatattta ttatttttct gaccaaagtg 120caatgatttt t 131 311 626 DNA Homo sapien 311cctatgtgcg ccagtttcag gtcatcgaca accagaacct cctcttcgag ctctcctaca 60agctggaggc aaacagtcag tgagagtgga ggctccagtc agacccgcca gatccttggg 120cacctggcac tcaagcactt tgcacgatgt ctcaaccaac atctgacatc tttcccgtgg 180agcaacttcc tgctccacgg gaaagaggtc gatggattta cccctggacc cataagtctg 240ttcatcctgc tgaagtcccc tccccattgc tccttcaagc caaaactaca ctttgctggt 300tcctgtcccc tctgagaaag gggatagaaa gctccttcct ctatgtcctc ccatcgagat 360ctgttctggg gatggagctt ccaacttcct cttgcagcag gaaagaatgc tgctcaccct 420tctgtcttgc agagtgggat tgtgggaggg attggcagcc ttcttctcca ccacctgtcc 480agcttcctcc tggtcagggc tgggaccccc aggaatatta tgttgccgtg tgtgtgtgtg 540tgtgtgtgtg tcttctttta gggagcagga gtgcatctgg taattgaggg tagatgttgt 600gtgtgctggg gaggggtcct tctgtt 626 312 616 DNA Homo sapien 312aaaccaaaga aattaagaaa aaagacttca ttgcttgaat gacgcgaaca gctgtctgag 60tcacctagac tttaacacca cctggggccc tgggaatgac gctgacgaga gatctgcaca 120tagtaggcgt gggctccaaa tgtgctcatc agctgacttc acatcctcac aagtcagcct 180cagatatgac ccaagggata cgtaccatct cttcttgaaa cagcgtgtca aattatatat 240atgtatgcaa aaaagagtaa tgtactaagc aaaccaagtt tcgtcttttt cttctgaatc 300tggttttaat gtgacctgtc atccccatct ttcgaattta tgagctccat cttctctaga 360ctgttaactt cttgaggaaa acatgctatt ttaccacctt tcactgctga atccctagcc 420cttaagcaca gtctctggca cagaataaat acgaaatgaa tgagtgaatg aatggatgga 480tgggtgaaga gaaaaggcaa tgcacaagat ttacctatca aaatccacca atggtcctta 540aaaatggttt tgtcagtaga gatgctgaat atattcatat aatacattta tttcaatact 600attaagaatt ctagtg 616 313 553 DNA Homo sapien 313aaaaaatggc agcattgtac ttgaatcaga aagcttactg ggatttcctc atcgaaagta 60gagattgcag ctaatcctag taccttttgt tagtaattac ttaaggcaca gtgcaaagtt 120gaaggactgt tttggtacaa actcaagcca gctacatgta tgcttgcctt ggtatccttg 180ctagagcaca tgcgggtata ataccgtatt atacacaaca aggccaccct gttgtatctg 240tgttacaatt aaacatcagt cccagaaagt gaaccctagt catttattat aggtgcccac 300ctctgacttg gaacaaaatg ccactccatt catgttcatt tttgtcctgg agaggattta 360tttcctaaaa gattctgaaa gccaacaaat caatgtagtt cttcatagag aacttaagag 420taaggctcaa aatggcctca aaatgggctt cttggatgac ttccaacagt gactggcctt 480ctcaacactg cagatgtctg agcactacca taacctaacg aagtgaggaa ggaggaggca 540aattggtatt ttt 553 314 330 DNA Homo sapien 314ccagcgactc cagcggtggc agcaggcagt gcacgtactc tgggcctccc accagggtag 60tgaaggttcc cagctgttct gccagggcca ggaggacctc atcttcatca tagatggtat 120ctgtaaggaa aggcagaagc tcacttcggg tcctttcaac cccaagggcc aaggcgatgg 180tggacagctt cttgatgctg ttgaggcgaa gctgaacgtc ctcattgcgg agttcgtcta 240tgagcaccgc gatggggtac agcgagtcgt cgccgtcggc cgccgccatc ttggctccgt 300ccctttcctg tcagactgcg gccagcgctg 330 315 380 DNA Homo sapien 315aaaaatgaca ttgcgtttag cttattgtaa gaggttgaac ttttgtattt tgtaactatc 60tttaagccct tcagtttata attcatataa aatgcctttt gtatttaaaa taatcctatt 120ttaatcagtg catgaaattt gcttttttaa agttcatttg aatgattatt ccttccctct 180aaagaaatga ttttggtaat gttgagaggt accttaccac aaatcctaac tgtaagtgta 240ttcatggtta ttttcaaaag aattatgact cttccccaaa agaatcctaa aaaacttgta 300ataaacctat aaagctgatt tgcatattta caaaattttg aatagcaaat ataggcaact 360catatatgta tataattttt 380 316 222 DNA Homo sapien 316aaactacaga gggttttcca gctattattt cctttagttt ctaaaagtaa cgacttatat 60taatgtttta taaaagatag tgatgaaaaa aaggtaatgc tgaaataaag gcgcttttag 120aaatatttaa ggacaacata aggtattaat attggaaaaa aactgtacat attttcaagc 180acaacactga aatattgcag cagtgtttaa ctgaattgtt tt 222 317 490 DNA Homo sapien 317ccttgaatga gcgtggagag cgattaggcc gagcagagga gaagacagaa gacctgaaga 60acagcgccca gcagtttgca gaaactgcgc acaagcttgc catgaagcac aaatgttgag 120aaactgccta tcctggtgac tcttcttaag agaaactgaa gagtttgttc agcagttttt 180acaagaattc gggacctccg cttgcttctt tttttccaat atttggacac ttagagtggt 240ttttgttttt tcttttcaga tgttaatgtg aaagaaaggg tgttgcattt ttacatttcc 300ctaatgatct tgctaataaa tgctacaata gcatcggctt cattttgggt ttttgcctcc 360tcccactgtg tgtatgtgtg tatatgtatg ttttgaatat gttttcttta ttaaaaaata 420ttttttgtag tttgaatatg aaatttggac caaatgataa actgcgctga gtctaaactg 480gcaacatgta 490 318 340 DNA Homo sapien 318cctggagtcc aataaccacc ccctcatacc acaccctgtg catacaccag ccaagccttt 60cctggtctgg gaagggaaga gaaaaaagac gcaggccacc tgggggttct gcagtctttg 120gtcagtccag ctttctatct tagctgcctt tggcttccgc agtgtaaacc ttgcctgccc 180ggaggcagga ggcccagctg gacctccgag ggccatgagc aggcagcagc catcttggcc 240tcaagcttgc ctttcccttg agtccctctc tcccctcggc tctagccaga ggtgtagcct 300gcagatctag gaagagaaga gctggggagg aggatgaagg 340 319 373 DNA Homo sapien 319aaagatgctg ttaatgaaca ttacggacaa ttcatggtgt ggctagttgg taacacttca 60gctgattttt cttatgagat ggaaaaaaaa atcagccaag taagggcaca tcttcagttc 120atttagaagt cagcatccaa ggtaaaagaa ttctctgttg gacttgacat cactcccatc 180ctctgatact cgcctactct cttctcaaag aagttagtct ttccttccag tgaaatattc 240tccataaagt caaatgggtt ctctactctg aaaaccttgc taaaacccag ttccagcata 300agtctgtctg ccacaaactc aatgtattgc ttcattagag tgcaattcat gccaatgagc 360ttcacaggca agg 373 320 509 DNA Homo sapien 320aaaaacaaaa ttaaattttc atttcaatta agaccccttt tggcattttg cttacttatt 60ctgccctttg gttaacagca tcagcatcac attactattt tatattgcat atatgtagca 120tttgcttcct taagttttca acatatcatt tatatttaaa ggcagacact gagtcagtat 180taatagatta actaaactgc actgtaattt agataaaatt actgtgtctc actgtgtatt 240acatgcaaaa tccacataaa ttgtcattta accaacagta ctgcacgagc gaacatctcg 300atatatgaaa actgcatcat caattcaacg ttttggtact tgaaactgca tcataaatgc 360aacattgtca tatgtgaaaa cgacacccta agtccttctt tttaaaaatg acattgcgtt 420tagcttattg taagaggttg aacttttgta ttttgtaact atctttaagc tcttcagttt 480ataattcata taaaatgcct tttgtattt 509 321 617 DNA Homo sapien 321ccaaggcccc ttttgcagcc cacggctatg gtgccttcct gactctcagt atcctcgacc 60gatactacac accgactatc tcacgtgaga gggcagtgga actccttagg aaatgtctgg 120aggagctcca gaaacgcttc atcctgaatc tgccaacctt cagtgttcga atcattgaca 180aaaatggcat ccatgacctg gataacattt ccttccccaa acagggctcc taacatcatg 240tcctccctcc cacttgccag ggaacttttt tttgatgggc tcctttattt ttttctactc 300ttttcaggcg cactcttgat aaatggttaa ttcagaataa aggtgactat ggatataatt 360gagccctctg gtccaggtct cagtttacct aatattacct cagaaaggat atggagggaa 420gatgatcttt ttgccaggtc tgacttttct tcctgctccg ccctccatta acgctcagta 480ccctttagca gctgacggcc ccacgttcta ctccatgctt ggcttccttt ccaactagct 540ctttcatata ttttacttgc tagtatctcc attctctcta aagtagtggt tctttttgcc 600cttaaactta aattttt 617 322 403 DNA Homo sapien 322aaaaagaagg acttagggtg tcgttttcac atatgacaat gttgcattta tgatgcagtt 60tcaagtacca aaacgttgaa ttgatgatgc agttttcata tatcgagatg ttcgctcgtg 120cagtactgtt ggttaaatga caatttatgt ggattttgca tgtaatacac agtgagacac 180agtaatttta tctaaattac agtgcagttt agttaatcta ttaatactga ctcagtgtct 240gcctttaaat ataaatgata tgttgaaaac ttaaggaagc aaatgctaca tatatgcaat 300ataaaatagt aatgtgatgc tgatgctgtt aaccaaaggg cagaataaat aagcaaaatg 360ccaaaagggg tcttaattga aatgaaaatt taattttgtt ttt 403 323 298 DNA Homo sapien 323ccagaattag ggaatcagaa tcaaaccagt gtaaggcagt gctggctgcc attgcctggt 60cacattgaaa ttggtggctt cattctagat gtagcttgtg cagatgtagc aggaaaatag 120gaaaacctac catctcagtg agcaccagct gcctcccaaa ggaggggcag ccgtgcttat 180atttttatgg ttacaatggc acaaaattat tatcaaccta actaaaacat tccttttctc 240ttttttcctg aattatcatg gagttttcta attctctctt ttggaatgta gatttttt 298 324 78 DNA Homo sapien 324ccatgggaag gtttaccagt agaatccttg ctaggttgat gtgggccata cattccttta 60ataaaccatt gtgtacat 78 325 174 DNA Homo sapien 325ccatcatggt caggaactcc gggaagtcaa tggtcccgtt cccatctgca tccacctcat 60tgatcatatc ctgcagctct gcttcagtgg ggttctgtcc cagggatctc atcactgtcc 120ccaactcctt ggtggtgata gtgccatctc catccttgtc aaagagggag aagg 174 326 679 DNA Homo sapien misc_feature (1)...(679) n = A,T,C or G 326aaaactgaaa tacctcttaa aataatttga tccccagcgt ttgctctttt tgaagtaacc 60aacttactct taaaaaggat ggntgccaag atggaaagtc ttactgggtt ttcatgttaa 120cctattcttt ggacataact atgaattttg tatacaatgc acttcatgaa aagttgtggc 180tcccccagat tgcccacaag tgtgatcttg aagtcctaaa catttgtcca tgtaagcttc 240aaaacagcgt taactgagtt attcaagtag cagtacttaa agatacaatt cttgaagcag 300tttcaatggt ttctgatcca aataatcagt ttctgaacat tactacttca cataatagag 360tccatcttca gtttcttctc actttctctt tcccttttgg gtttcctttt tgtggcctga 420ggccaccagt tctttgggta ctatcaagat acttccatca tgggtacact ggagagcata 480gtggttggga ttgactggcc taccttggtc atctcttaat ctactaaaaa tatcatgata 540aaggtcatgc agtttctgtt tcattatgtt aatagctttg gtacattgtg cttgctctct 600cttaanagtt tccttctttg cttgcaagtt acatacatca tcttctaaat tcaaaattat 660gtccattttg gcgtttacc 679 327 619 DNA Homo sapien misc_feature (1)...(619) n = A,T,C or G 327aaaataagtt actggtaaat ggagttgcat tctatagtca cttaataaat attaacaaaa 60tatttataac tggaacctta atgaaatgta tcatcaaatc aggtaaaagc aacttgtccg 120cagttaccaa agcctanata cgcgttagat gcgccttttc cggcctgtgc gtctgctctg 180gttcctctca ggcagcaaag ctggggaagg aagctcaggc aggagcctcc ccgacgccac 240aacggcacaa gcagcagcta aagcaccgca ctttgctcta ctaacctttt acttaaatga 300ggttttgcca aatccacatc tggaaccgcg tcacacccat ttgcaaggat gtttgttctt 360tgatgaaact gcatctctac tgcacatgag ggctttcatt gtaggacaag aggagagttc 420gtttattttt gtaactgttt tacatgttcc gattagttaa tcggtagctt atgtcatttg 480ctatgcctgn agncttctaa tctctcctta ctaaaacatt acttcaaatt tgaattgacc 540cttggttata atttatttag ccgggatttg tgtgtcattg tagagcaact ctaattcaag 600aatagtgaca acttttaag 619 328 132 DNA Homo sapien 328aaatccaaat acaaaagcat agtctctgca agattttgtt ctttgaattt cttgatattg 60taattgatta ttgataactg tcatcatgaa attatctctc aataataaga taaataaact 120agcatatgaa tc 132 329 854 DNA Homo sapien misc_feature (1)...(854) n = A,T,C or G 329ccttgaggta actattgcaa aatatacagt gtaagttcag tctgatggaa accccagatt 60catcaaggat acaaatctac agtagcccaa tggcggtttc atagtgtata atttattatc 120aataaaatta actccgttac aatcagcatt catttcctcc aattaaaatt aagcataaac 180cctaggtagt aaccttctgc acatatgtat agctccgaat ttcctcactg ttcgtctggt 240gcaaaaacaa tattcaagct tgtctgatta tgcatatttt ctttaatcat atagattata 300tatacaatag acaagacagg actatataga taatggacag acttaaatgc ccgcattttt 360aaggtggaga aaatgatgaa tctatgcatc cccgagaaca cttaaaattt ttttttattt 420cactgggaaa ttcttacagc tactttacaa tcataggtta acagcctagt tatacagaag 480acatattcca ctacagagct atactctatg caactgtttt ttcccctcat aaacaacctg 540agttcaaatt gaattctatc ttccacaatc acaatgggtg catcacccag tacacagaag 600tttgaatcac aaaacataat taccacaata aaacacagtg ttcaagtatc ttggcagagc 660aatctgccgc acaaactgca aattaaatta actacacaga ctaaaaacta tacagcctac 720catcacagtt gtgcattata aaaaagggag tttctttcct ttggttttaa gtcaggaaca 780gggtaggatt ttttaccctc nggccgggga ccacgctaaa ggggcgaaat ttcttgccan 840natattccnt tcac 854 330 299 DNA Homo sapien 330ccaatgaata actgacttta taatcctggg caatcagctt ttggcgggtt gtaagtgctt 60ctcgacactt ttcactcatg gattcttcaa atttatggtt aaagaggcac ttatacactc 120tgccctcacc agcttgtgta ttttcacaaa aacgctcccg atcatctcgg caagcaaaat 180ataaatgccg gtctaagtga aagtcatccg atgacagctc agccacccgg agaatggctt 240tcttgcagag ttcagaaact tgaatcttgg gttctctttc ttctgcttct ttcaccagg 299 331 573 DNA Homo sapien 331aaagatatga acagcttaat tttccgtgtg attatctaat taaaaaagaa aaacaaaaca 60agcaaaatgt tcaagttaaa aaaaaaacat accgggtgag caatgcacta aaattatcca 120catgaaaaca aatggtctgt aatcttataa accaacatag catttcactg tcaacaatgt 180gaaaatttaa tatcttctca aacaggcata agatgaagaa gtgctatttt ttaattgtaa 240aaggaactta tgtaatgtaa aattacatta taatttttca ttccgaattg acaaatgatt 300tcaaaaacaa ggatcaaagt ttgactgcaa atagtaatgc aatataattt cataaaaatc 360cttcaatttc tatttttttc cttttctgta gttgacatat gaagaccact tcaatttcta 420aaaaagggaa ccattccaat tttccctccc caagaaaatg tctcacaatt acaaagtaga 480aaaacagccg ttcataaatg caaaaaaatt ctgatttata tatgaaataa tttctagatc 540aattcaacat atttgatgac atttgttgag ttt 573 332 555 DNA Homo sapien 332aaatttgaaa gttgtaagca ctgatgttaa tgtgattgat cagcatgggc atatgtaaaa 60tgtccttttc tggttgcctc tctatgctat tgtgttcaga tacttacacc ataattaaac 120agtaagttat agacttgctg agtttggcat agatagtgcg ctcatttaat ctgtgcctct 180caaaacttca gaatattagc atattaccac aaataatttt tggtgaaact attgagatat 240taaaattttt gaaatcacta ctgttacctg ttatagaaaa tagtgttggc ttagtctagt 300ctctgtgtaa ctggttacat tttgatggtt gtctatactc aactggatat gtgtatgtaa 360attagaaaat acatacctat ccagacataa atgctaagta acattttttt cttcctccaa 420ctacataatt tgtagctcat catttttcct taatcctttc ctaacttgtc gcagcagttt 480gaatttccca gatatttatg tttgaacata atggctcaga atacatattt gaacatcata 540gttgtatata ttttt 555 333 460 DNA Homo sapien 333aatttcttt caacagtcta ttggggtcca aaaagcatat atcaaaacaa aaataacaaa 60gcaaaacaa aatgctacat gtaaaagcta aagaaagaaa atgcagcata ttcaggttct 120tttcttgag gtacctatat aaatttaatc acctgcccca aagtcctctc gttaggttaa 180aacacaatg cgtcctgggg agccaattgc ccggcacgtc ttattactga gaaagtgcaa 240aatgctgat catcttatgc agcatactaa aggatgattt actctttaca aaatagagct 300aagtatcaa cctgatggaa gttagaaaat taaaaacatt taagtagaat catctctctc 360ctatttttg agatcctgca gcaaaaagcc tcccaaatca actttcaaag ttctgccatt 420aggaatgtt ggttctcttg taaaattcag agatctcttt 460 334 190 DNA Homo sapien 334ccaaggaagg ctgtgctcta gcccatctga ccctgtctgc aaaccacctg ggggacaagg 60ctgatagaga cctgtgcaga tgtctctctc tgtgcccctc actcatctca ctggatctgt 120ctgccaaccc tgagatcagc tgtgccagct tggaagagct cctgtccacc ctccaaaagc 180ggccccaagg 190 335 394 DNA Homo sapien 335aaatttggac agactctag cggacagtta cttctcaaga attttctata caaaagctgt 60gccaggcata tatttctca ccaggacaca tggggcagcg gacccctggt gtcagtaaga 120acacacccag aatgtataa ccagatattt ttcagtttct aaattaaggc atattcaaaa 180aattccatgt acaatttac accacttttc taagttactc accaggtaat taaagcagat 240tcacagatga attatctca gtttaactat atgcaacaac catgccaata acttttcttc 300taaattttgc ataaaatgg ttaaaaaaag tggtagttta actatcatgt tcacaattgt 360catttttcaa ggcatagaa gaccaagaca tttt 394 336 429 DNA Homo sapien 336aaagctatc accattgtag tagaatcatc cttctttttt gaaatttgaa gcatcccagg 60ttaaaatct tgtgtttcag aaagacagtt tataccatga ctgcttaatt atccccccaa 120gaccttctg attgaagtca tgtacagttc agtggcctaa attctctgcc tttttaactt 180ctttgcaag cctactctga aaataagtta tttagtcaag ttattctcaa agatgtccca 240ttgcctaga aaggatcaaa tggaacattt gacacacata ctcaaaaaaa tgtaactgac 300ataaacact ttaacctaat catctgtatc aaactttcta aaaatcaaat ctcaggattg 360tccacttta gagattctat gtaaagttta tataactata cttgtcaaat agcacctatc 420atgcattt 429 337 373 DNA Homo sapien 337aaagatgctg ttaagaaca ttacggacaa ttcatggtgt ggctagttgg taacacttca 60gctgattttt cttagagat ggaaaaaaaa atcagccaag taagggcaca tcttcagttc 120atttagaagt cagctccaa ggtaaaagaa ttctctgttg gacttgacat cactcccatc 180ctctgatact cgccactct cttctcaaag aagttagtct ttccttccag tgaaatattc 240tccataaagt caaagggtt ctctactctg aaaaccttgc taaaacccag ttccagcata 300agtctgtctg ccacaactc aatgtattgc ttcatcagag tgcaattcat cccaatgagt 360ttcacaggca agg 373 338 366 DNA Homo sapien 338ccatcccctt atgacgggc gcagtgatta taggctttcg ctctaagatt aaaaatgccc 60tagcccactt cttacacaa ggcacaccta caccccttat ccccatacta gttattatcg 120aaaccatcag cctatcatt caaccaatag ccctggccgt acgcctaacc gctaacatta 180ctgcaggcca cctatcatg cacctaattg gaagcgccac cctagcaata tcaaccatta 240accttccctc tacattatc atcttcacaa ttctaattct actgactatc ctagaaatcg 300ctgtcgcctt aatcaagcc tacgttttca cacttctagt aagcctctac ctgcacgaca 360acacat 366 339 319 DNA Homo sapien 339ccttccctcc ccaccaccat caacctcttc aaaacctact ccctccctct aagtatctct 60caacacagta tgtctggggc tagatttcaa aacccacgta atgaaaaagt cagttttaca 120agcctaattt tgttgttttt ttttttatat caattaacgt taaaaattgc atcaactatt 180taattcatga ggatctttca tattaaaatt taaccttaag attcaaccgc catgtgcttt 240tataaaggaa acatttttta gagacgtctg agctcacttt tacatggtgg tgcctactgc 300cgttaatgtt tgtgatttt 319 340 278 DNA Homo sapien misc_feature (1)...(278) n = A,T,C or G 340ctaataaaat gaattaacca ctcattcatn natctaccca cccnatccaa catctccnca 60tgatgaaacn ncggctcact ccttggcgcc tgcctgatcc tccaantcac cacaggacta 120ttcctagcca tgcactactn accagacncc tcaacngcct tttnatcaat nggncacatn 180actcganacn taaatnatgg ctgaatcatc cgctacctnc acgccaatgg cagcctcaat 240attctttatg ctgcctcttc ctacacatgc gggcgagg 278 341 400 DNA Homo sapien 341ccagcatggg gctgagctg aacctcacct atgagaggaa ggacaacacg acggtgacaa 60ggcttctcaa catcacccc aacaagacct cggccagcgg gagctgcggc gcccacctgg 120tgactctgga gctgacagc gagggcacca ccgtcctgct cttccagttc gggatgaatg 180caagttctag ccggttttc ctacaaggaa ttcagttgaa tacaattctt cctgacgcca 240gagaccctgc ctttaagct gccaacggct ccctgcgagc gctgcaggcc acagtcggca 300attcctacaa gtgcacgcg gaggagcacg tccgtgtcac gaaggcgttt tcagtcaata 360tattcaaagt gtggtccag gctttcaagg tggaaggtgg 400 342 536 DNA Homo sapien 342aagaacaat gggaaaaaca agtccgtgtt ctcacagatg ctgtcgatga cattacttcc 60ttgatgact tcttggctgt ctcagagaat cacattttgg aagatgtgaa caaatgtgtc 120ttgctctcc aagagaagga tgtggatggc ctggaccgca cagctggtgc aattcgaggc 180gggcagccc gggtcattca cgtagtcacc tcagagatgg acaactatga gccaggagtc 240acacagaga aggttctgga agccactaag ctgctctcca acacagtcat gccacgtttt 300ctgagcaag tagaagcagc cgtggaagcc ctcagctcgg accctgccca gcccatggat 360agaatgagt ttatcgatgc ttcccgcctg gtatatgatg gcatccggga catcaggaaa 420cagtgctga tgataaggac ccctgaggag ttggatgact ctgactttga gacagaagat 480ttgatgtca gaagcaggac gagcgtccag acagaagacg atcagctgat agctgg 536 343 646 DNA Homo sapien 343aaaacttcta ttcatcaaaa gacataaaga aaacagtcaa gccacagact aggtgtaata 60tctcaataca tatatccgac aagagaattg catctagaat gtataaagaa tttctatgac 120ccaattatag ctatcaggga tatacaaatt aaaaccaaaa tgaaacatca ctacacaccg 180attggaatgg ttaaaaagga aaaatactga caacaccaat atttgtaaag acaggaggta 240ccagaactct cattcattat attcataaat tgacaaatat aaaaactgct atagtagggc 300agtcttcctt agaaagggat tgtgggcatg acagagaaca atattaatct gtccattata 360ttccttaact gtaaaatgga gaccatatgt tccaccagct tcacttggta attatgatac 420atggctatta agagactcaa atgactccat ttcatcaact aatatgccct gtcaattcta 480cttctaaagt atcccatgtt ctatccaatg tcataccact atcataattt aagtgttcat 540aactctctat aatatttcaa taatctaact ggtctcaatg cctgtagtag aaattgcaga 600ttgggctccc caatttctgt tccctaggaa ggctgagaaa gctttt 646 344 383 DNA Homo sapien 344cctgcacccc agtataaggg cctccccagc tgagtaagaa gctgcttccc ctcctctcat 60aggccaagcc tattgtgtga aaccatctca tggtcttggt gacgtagacc atttttgaaa 120ccgtctcatg gtcttggtga cgtagaccgt ttgcttcttt aactccagcc gcggaatgac 180attagtggaa ccgggctagg gaactgctgg aagttcagga tgccaccacc ttgaacacct 240aggccaggga tccccaccat gtcccgggtt tctttcttcg agagtataga accgttcatt 300cttgctttgt gtcccattcc atctcttgaa aaaatgtagt ctttgaatgt gtgaaaatct 360agggacattc aatctagtct ttt 383 345 263 DNA Homo sapien 345cctccccttc ccctttgctg gtgggaggag ctcgtgtgct ccttggccgc ttactggaag 60ggcgtttttc agagctgcag ggacagggtg agcagctgaa gggctaggag ggaagccggc 120ccccgctctg cagaagctgc atttcagctg aatctgtgtt tcagcctcag ttggttgcac 180cgttagcccc tctcctcccg gatggtcatg tttttgtcac attagagaat aaacagccac 240acacacattt ttttttttcc ttt 263 346 132 DNA Homo sapien 346aaatccaaat acaaaagcat agtctctgca agattttgtt ctttgaattt cttgatattg 60taattgatta ttgataactg tcatcatgaa attatctctc aataataaga taaataaact 120agcatatgaa tc 132 347 564 DNA Homo sapien misc_feature (1)...(564) n = A,T,C or G 347cctgggtatc cagggaggct ctgcagccct gctgaagggc cctaactaga gttctagagt 60ttctgattct gtttctcagt agtcctttta gaggcttgct atacttggtc tgcttcaagg 120aggtcgacct tctaatgtat gaagaatggg atgcatttga tctcaagacc aaagacagat 180gtcagtgggc tgctctggcc ctggtgtgca cggctgtggc agctgttgat gccagtgtcc 240tctaactcat gctgtccttg tgattaaaca cctctatctc ccttgggaat aagcacatac 300aggcttaagc tctaagatag ataggtgttt gtccttttac catcgagcta cttcccataa 360taaccacttt gcatccaaca ctcttcaccc acctcccata cgcaagggga tgtggatact 420tggcccaaag taactggtgg taggaatctt agaaacaaga ccacttatac tgtctgtctg 480aggnagaaga taacagcagc atctcgacca gcctctgcct taaaggaaat ctttattaat 540cacgtatggt tcacaagata attc 564 348 321 DNA Homo sapien misc_feature (1)...(321) n = A,T,C or G 348gcncatgaac anggagcaac ganaagagat gtcgggctaa gggcccggga cgggcggcac 60ccatcctgcn acggaacacn ttcgggttnt ggttttgatt ngttcacctc tgtttatatg 120canctatttg ntcctcctcc cccaccccag nccccaactt catgcttntc ttccgcnctc 180agccnccctg ccctgtcctc gcggtgagtc antgaccacn gnttcccctg cangagccgc 240cgggcgtgag acncngaccc tcnntgcata caccaggccg ggcccnngct ggctcccccn 300gnggccctgt gaaanagctg g 321 349 255 DNA Homo sapien 349ccatgacagt gaaggggctg ttaggaatat caacaccacc gaagcgcaca tagatcacat 60atgtgcccgg cttggcagct gtgtagaaga tgtcataggt tccatcttca ttctcaatga 120catcggcctc ggcctcagtg ccatctgggg tcagaaccgt gcaggtcact ttacccttcc 180cggcagtctt ggcatcaacc acaaagccta cttcttcgcc agttttcaca gtggaggcga 240ttccaggacc cgtag 255 350 496 DNA Homo sapien misc_feature (1)...(496) n = A,T,C or G 350ggcttattn gctcacaaaa tcattcnctt ttggaactat ggccaattga agctacacac 60gaatttatt aatacagcat taagtttctt tgtgtnaaaa aatctttgtn cncagtaata 120aaaaagata aggcaagatg cattaaacat gaaaccttct ggctcttttc ctctgcgttt 180tacagagcc actgatgact atctgcaaca aaagagttaa gtttctgatt ttccgtatca 240gcatcttat gcctttgctg tggtaagaat tctggccaag caccctgaag gacagatgct 300gtgatggnc tttggcactt atgctggcaa actgagcttc tttcccttga gtacttttgn 360atgtacaag tagaagaagt cacaagtata ggatggtctg gactacgccg gccaccacag 420aatgaggtc aaagaagccc tcaaagnaga agcgnccaga tccagttgac aagatacaaa 480cacgataga ggccca 496 351 109 DNA Homo sapien misc_feature (1)...(109) n = A,T,C or G 351ccatagtgaa gcctgggaat gagtgttact gcagcatctg ggctgccanc cacagggaag 60ggccaagccc catgtagccc cagtcatcct gcccagcccc gcctcctgg 109 352 384 DNA Homo sapien 352ccttcgagag tgacctggct gcccaccagg accgtgtgga gcagattgcc gccatcgcac 60aggagctcaa tgagctggac tattatgact cacccagtgt caacgcccgt tgccaaaaga 120tctgtgacca gtgggacaat ctgggggccc taactcagaa gcgaagggaa gctctggagc 180ggaccgagaa actgctggag accattgacc agctgtactt ggagtatgcc aagcgggctg 240cacccttcaa caactggatg gagggggcca tggaggacct gcaggacacc ttcattgtgc 300acaccattga ggagatccag ggactgacca cagcccatga gcagttcaag gccaccctcc 360ctgatgccga caaggagcgc ctgg 384 353 345 DNA Homo sapien misc_feature (1)...(345) n = A,T,C or G 353ccttggtcag gatgaagtng gctgacacac cttagcttgg ntttgcttat tcaaaagana 60aaataactac acatggaaat gaaactagct gaagcctttt cttgttttan caactgaaaa 120ttgnacttgg ncacttttgt gcttgaggag gcccattttc tgcctggcag ggggcaggta 180tgtgccctcc cgctgactcc tgctgtgtcc tgaggtgcat ttcctgttgn ncacacaang 240gccangntcc attctccctc ccttttcacc agngccacan cctnntctgg aaaaangacc 300agnggtcccg gaggaaccca tttgngctct gcttggacag canag 345 354 712 DNA Homo sapien 354ccatctacaa tagcatcaat ggtgccatca cccagttctc ttgcaacatc tcccacctca 60gcagcctgat cgctcagcta gaagagaagc agcagcagcc caccagggag ctcctgcagg 120acattgggga cacattgagc agggctgaaa gaatcaggat tcctgaacct tggatcacac 180ctccagattt gcaagagaaa atccacattt ttgcccaaaa atgtctattt ttgacggaga 240gtctaaagca gttcacagaa aaaatgcagt cagatatgga gaaaatccaa gaattaagag 300aggctcagtt atactcagtg gacgtgactc tggacccaga cacggcctac cccagcctga 360tcctctctga taatctgcgg caagtgcggt acagttacct ccaacaggac ctgcctgaca 420accccgagag gttcaatctg tttccctgtg tcttgggctc tccatgcttc atcgccggga 480gacattattg ggaggtagag gtgggagata aagccaagtg gaccataggt gtctgtgaag 540actcagtgtg cagaaaaggt ggagtaacct cagcccccca gaatggattc tgggcagtgt 600ctttgtggta tgggaaagaa tattgggctc ttacctccca atgactgccc tacccctgcg 660gaccccgctc cagcgggtgg gggattttct tggactatga tgctggggga gg 712 355 385 DNA Homo sapien 355cctcatagcc gcttagcaca gttacagaat gtctgaaggg gacagtgtgg gagaatccgt 60ccatgggaaa ccttcggtgg tgtacagatt tttcacaaga cttggacaga tttatcagtc 120ctggctagac aagtccacac cctacacggc tgtgcgatgg gtcgtgacac tgggcctgag 180ctttgtctac atgattcgag tttacctgct gcagggttgg tacattgtga cctatgcctt 240ggggatctac catctaaatc ttttcatagc ttttctttct cccaaagtgg atccttcctt 300aatggaagac tcagatgacg gtccttcgct acccaccaaa cagaacgagg aattccgccc 360cttcattcga aggctcccag agttt 385 356 347 DNA Homo sapien 356aaatgagata aagaaagtct ccttttgttt ttagatggaa aagaaagcac aagttttttc 60tacctgtgaa tgaactttgg tgacctatat gtgccattca tgcagcattt ttgttcatat 120tggcttagaa ttcagtgcat gaatatcatt acattcttat atctaacatt cctagttagc 180tttgattcaa aatatacaaa atctgataca tgaatacttt gctagattaa tgacttgatc 240atctttggaa tgagtaggca agacgatttt tacctattat ttctatgttg tgggtaatgt 300taaaactaaa tacagatgat aataattgct atttcacagt gatgttt 347 357 313 DNA Homo sapien 357aaagtaatca acctctctgt ccttccatta gtctggatcg tctaaagatt gttttatttt 60tagaggctca tccggtcaga tgttagtgat gtgaaatttc aggccaggcg tgacgtcagc 120gtggcatttg aaacagctcc atgttgccct tagtgctgtc tgaccgaagc ctgtctgtcc 180tcagatataa agatgaagcg cagctgtata aagaagagca cctgaggaat cggcagcacc 240ctcactgcta cgttcagtac atgatcgcca tcatcaacaa ctgccagacc ttcaaggaat 300ccatagtcag ttt 313 358 403 DNA Homo sapien 358aaaaagaagg acttagggtg tcgttttcac atatgacaat gttgcattta tgatgcagtt 60tcaagtacca aaacgttgaa ttgatgatgc agttttcata tatcgagatg ttcgctcgtg 120cagtactgtt ggttaaatga caatttatgt ggattttgca tgtaatacac agtgagacac 180agtaatttta tctaaattac agtgcagttt agttaatcta ttaatactga ctcagtgtct 240gcctttaaat ataaatgata tgttgaaaac ttaaggaagc aaatgctaca tatatgcaat 300ataaaatagt aatgtgatgc tgatgctgtt aaccaaaggg cagaataaat aagcaaaatg 360ccaaaagggg tcttaattga aatgaaaatt taattttgtt ttt 403 359 411 DNA Homo sapien 359aaataaatac ttagaacacg acttggctcc tacaagcatc tggactctag gtctcagtac 60tggagtgtct cacccatggg ccccacgcag ggacgccacg gttccctccc accccgtgat 120caagacacgg aatcggctgc cgatggttgg atcgcaatgc gccccttttc tagagccttc 180cccggccatc tacaggcagg atgcggctgg gaaaaagaca actggaattt ctcgaaggtt 240gatggtccgc acggttgagg attctacgtg gttctcttgg ttcccctggt gtgtgtgtgt 300gtggaggagg ccgcggccct tagatcacct tcttgagctc gtcgtacagg accagcacga 360aggcgccccc catgccccgc aggacgttgg accacgcacc cttgaagaag g 411 360 378 DNA Homo sapien misc_feature (1)...(378) n = A,T,C or G 360cctcttcagg ggcccgagcc agggacaggg ccttggtttc cttctccctg gcttctgcct 60cagctctgtc cctctcatcc gcgtatttgg aagagatgtt tttctcctcg gctaacaact 120gatcaaattt cctctgcttc ttttccaggt tggacacgag ttgccgctgg ttgtccaaat 180caacaaccag gtcgtccagc tcctgctgaa gcctgttctt ggtcttttcc agtttatcat 240aagcggccgc cttctcctcg tactgctggg tgaggntctc gatctccttc tggaacctct 300tcttcccctc ttccagagct tccacggngc tggcaaagtc ctgcagcttc ttcttcgagt 360cggagagctg gatgttga 378 361 372 DNA Homo sapien 361aaatactggg ggccattaag agtggatgta gctaagagct tagctaacat tgccttttca 60ctctattttt ctcagatatt gtaagcattc tgtttttcaa tattgtagtt aattttttgg 120ctttcaacag cagccctagt aatggtggag ttgttaatta atgtgtatat tgtactgaat 180ttctgtcagt taaggggttc actgctttgg tggaaattgg tggaaattgc tagcaggttc 240cacgatgttt atttttttct ccatgttgta tatcattacc atttcacata cgcgtttcta 300tttttcttcc tctcctcctg atctccttaa aaatgaatct agagttggtg gctttttccc 360cctcctcttt gg 372 362 544 DNA Homo sapien 362cctgagtcac ctagcatagg gttgcagcaa gccctggatt cagagtgtta aacagaggct 60tgccctcttc aggacaacag ttccaattcc aaggagccta cctgaggtcc ctactctcac 120tggggtcccc aggatgaaaa cgacaatgtg cctttttatt attatttatt tggtggtcct 180gtgttattta agagatcaaa tgtataacca cctagctctt ttcacctgac ttagtaataa 240ctcatactaa ctggtttgga tgcctgggtt gtgacttcta ctgaccgcta gataaacgtg 300tgcctgtccc ccaggtggtg ggaataattt acaatctgtc caaccagaaa agaatgtgtg 360tgtttgagca gcattgacac atatctactt tgataagaga cttcctgatt ctctaggtcg 420gttcgtggtt atcccattgt ggaaattcat cttgaatccc attgtcctat agtcctagca 480ataagagaaa tttcctcaag tttccatgtg cggttctcct agctgcagca atactttgac 540attt 544 363 328 DNA Homo sapien 363aaactggtta tgacaaaagc ctttagttgt gtttcttgaa ctataaagaa aacaaatttt 60ggcagtcttt aagtatatat agcttaaaat ataattttta gcatttggca ccatatgtat 120gccattatat ttgattttgc attactgttt cacaatgaag ctttctttaa ggctttgatt 180tttatgatta tgaaagaaat aaggcacaac cacagttttt ctttcttaaa tttcatcact 240gttgatgtgg ttcttttgtg ttaaaaaaaa aaagtgcaac tatcaaaact aaaaaattat 300agagtaatat tgccgttctg ctgatttt 328 364 569 DNA Homo sapien 364cctgggcacc tctttgcttg aaatatggca agacttggaa aaatgtttgc ccttagaatc 60tatctcacta ctttagttag ttgtctcctt tgggcctggg cacagttctg gccctgatct 120ggaacagact cccttttcta aaactgaact tgaccacatc aaaagtttgt aaaacaatct 180ccatggtaat taaacttgca ttcaacacca tatggtaaca gaagatggca aaggataaga 240ttcagatctt agatctttcc aagtagggca tgttagatga tagaaggatt agttgcaagc 300tggatctgag ctcaggcttg ggcatgaagg aaactgtctc ccatgtggtt tggaagagtt 360aggggctccc tgagctctat tgtgaactat acgggtttca tccaaggaat ggtatgatgt 420gggcataaaa ccattcttca gacaactgaa gatggtcccc ttctgtagcc agaaacacta 480gctgtcctgc attgtccatt tcctttagcc ccaggcggtc ctgtgtgtac agggaggtct 540cctgtaaggg aatggtttcc ttggcttgg 569 365 151 DNA Homo sapien 365aaaaaaaaaa atccttttat tatggaattt gtcaaacaca cacacaagca taacaaaccc 60ctaggtaccc atctccaagt tttgacccct attataattt catcttcagt gttttattat 120ccacttcctc tctctctatc tttagtattt t 151 366 508 DNA Homo sapien misc_feature (1)...(508) n = A,T,C or G 366agtataaaga tatattccat aaaagagttt ggcagtcaaa ganaagcatc gcacttccga 60aaaacacaag cattcttctc ctagtctaca gagaattgng taaaaaaaaa aaaaaatcat 120catcaacagc cnccantnta cnccacacta gaatgtacac tccggcaagt aaattaaggn 180tgcagtccat ccctgaacga tganaagngg tctgagctat ggcaaagngt tanaaagtag 240cccagctana caaatgcccc agctatcccc aggggagtta ttcagtactt aanacttcat 300ttccaananc agccccggaa aagccctgac aggaaggggg gaccagngat caccgatntc 360ccattagggg cggncaccaa aaacaaaatg cctggagctt ntgagcagct gcagcctggg 420gttgtggcta ggcncngggn gnggttgcaa aaaaacggct gtntccgggg agaggcaaat 480ggcaggccag ccagccctgg gtacatgg 508 367 382 DNA Homo sapien 367cctgagcggc tagtctttaa gatgcgcttc tatcgtttgc tgcaaatccg agcagaagcc 60ctcctggcgg caggcagcca tgtgatcatt ctgggtgacc tgaatacagc ccaccgcccc 120attgaccact gggatgcagt caacctggaa tgctttgaag aggacccagg gcgcaagtgg 180atggacagct tgctcagtaa cttggggtgc cagtctgcct ctcatgtagg gcccttcatc 240gatagctacc gctgcttcca accaaagcag gagggggcct tcacctgctg gtcagcagtc 300actggcgccc gccatctcaa ctatggctcc cggcttgact atgtgctggg ggacaggacc 360ctggtcatag acacctttca gg 382 368 174 DNA Homo sapien 368ccttctccct ctttgacaag gatggagatg gcactatcac caccaaggag ttggggacag 60tgatgagatc cctgggacag aaccccactg aagcagagct gcaggatatg atcaatgagg 120tggatgcaga tgggaacggg accattgact tcccggagtt cctgaccatg atgg 174 369 216 DNA Homo sapien 369aaatctcatg ggttctatta aaaaaatata tatatagggc cccaatccat tgccatcaaa 60ttgcccttgg acttttccaa ggtatattat ggggttttat gcaaaattcc aagctaccat 120gtaacttttt ttaaccattt aacaaggagg gggaactgtt tcctaccttc tttacatgtt 180gtgcattgtt gtggtccaga aatgccaaac cttttt 216 370 344 DNA Homo sapien 370ccttggtcag gatgaagttg gctgacacag cttagcttgg ttttgcttat tcaaaagaga 60aaataactac acatggaaat gaaactagct gaagcctttt cttgttttag caactgaaaa 120ttgtacttgg tcacttttgt gcttgaggag gcccattttc tgcctggcag ggggcaggtc 180tgtgccctcc cgctgactcc tgctgtgtcc tgaggtgcat ttcctgttgt acacacaagg 240gccaggctcc attctccctc cctttccacc agtgccacag cctcgtctgg aaaaaggacc 300aggggtcccg gaggaaccca tttgtgctct gcttggacag cagg 344 371 741 DNA Homo sapien misc_feature (1)...(741) n = A,T,C or G 371aaattacata tctaattgtg tgatttgtta aatgcccatt tcttcatcta agtgctaagt 60gctaagtgta gcagtttgtt ccctgctaca ctccaaggca caaaggagtt caaggaatgt 120gcaatggaaa tcagttagat gaatgtgtta ggaaccttcc ctttaataaa gctggatccc 180acactagccc ctacaccctc tcatcaccaa atattcctgc ttcctctcac ctgcacttgc 240tgttctctcc tctgccacac aaatctacct ctcaagccta ggtcccacct gcttcatgac 300aactttccag actattccag aacctttaac catctctgac ctctcatcag atctatgttg 360tacataacac caattaatga gatcattact gctttatgct ctaattgctt cctgtattca 420aaatcttctc tccaaccaca taatgactcc ctaaacttct cttgtatttt ccaatgcctt 480gtacaagcac agaactggtc aatcaataaa tactcactgg ttatttgagg aaaaaatgtt 540gccaagcacc atctttatca gaaaataaat caattcttct aaacttggag aaatcaccct 600attcctagta tgtgatctta attagaacaa ttcagattga gaangngaca gcatgctggc 660agtcctcaga gccctcgctt gctctcggna cctccctgcc tgggctccca ctttggtggc 720atttgaggag cccttcagcc t 741

Claims

1. A method for determining the presence of colon cancer in a patient, comprising the steps of:(a) obtaining a biological sample from the patient; (b) contacting the biological sample with an oligonucleotide, wherein said oligonucleotide is capable of hybridizing under moderately stringent conditions to a polynucleotide sequence selected from the group consisting of: (i) SEQ ID NO:12; and (ii) SEQ ID NO:13;  wherein said moderately stringent conditions include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50° C.-65° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5× and 0.2×SSC containing 0.1% SDS; (c) detecting in the sample an amount of oligonucleotide that hybridizes to the polynucleotide; and (d) comparing the amount of oligonucleotide that hybridizes to the polynucleotide TO a predetermined cut-off value, wherein an increase in the amount of oligonucleotide that hybridizes to the polynucleotide as compared to the predetermined cut-off value indicates the presence of cancer in the patient.

2. A method for monitoring the progression of colon cancer in a patient, comprising:(a) obtaining a biological sample from the patient; (b) contacting the biological sample with an oligonucleotide, wherein said oligonucleotide is capable of hybridizing under moderately stringent conditions to a polynucleotide sequence selected from the group consisting of: (i) SEQ ID NO:12; and (ii) SEQ ID NO:13  wherein said moderately stringent conditions include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50° C.-65° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5× and 0.2×SSC containing 0.1% SDS; (c) detecting in the sample an amount of oligonucleotide that hybridizes to the polynucleotide; (d) repeating steps (a)-(c) wherein the biological sample is obtained from the patient at a subsequent point in time; and (e) comparing the amount of oligonucleotide detected in (d) to the amount detected in (c) wherein an increase in the amount of oligonucleotide in step (d) as compared to the amount of oligonucleotide in step (c) indicates progression of said colon cancer and wherein a decrease in the amount of oligonucleotide in step (d) as compared to the amount of oligonucleotide in step (c) indicates a remission of said colon cancer.

3. A method for determining the presence or absence of a colon cancer in a patient, comprising the steps of:(a) contacting a biological sample obtained from the patient with at least two oligonucleotide primers specific for a polynucleotide sequence selected from the group consisting of: (i) SEQ ID NO:12; (ii) SEQ ID NO:13; and (iii) The complement of any of the sequences of (i)-(ii); under conditions effective for amplifying an expressed product in an reversed transcription-polymerase chain reaction (RT-PCR) reaction; (b) detecting in the sample an amount of said product; and (c) comparing the amount of said product to a predetermined cut-off value and therefrom determining the presence of colon cancer in a patient.

4. A method for monitoring the progression of a colon cancer in a patient, comprising the steps of:(a) contacting a biological sample obtained from the patient with at least two oligonucleotide primers specific for a polynucleotide sequence selected from the group consisting of: (i) SEQ ID NO:12; (ii) SEQ ID NO:13; and (iii) The complement of any of The sequences of (i)-(ii); under conditions effective for amplifying an expressed product in an reverse transcription-polymerase chain reaction (RT-PCR) reaction; (b) detecting in the sample an amount of said product; and (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and thereby monitoring the progression of colon cancer in the patient.