Method of determining epidermal growth factor receptor and HER2-neu gene expression and correlation of levels thereof with survival rates

Information

  • Patent Grant
  • 6582919
  • Patent Number
    6,582,919
  • Date Filed
    Monday, June 11, 2001
    23 years ago
  • Date Issued
    Tuesday, June 24, 2003
    21 years ago
Abstract
The present invention relates to prognostic methods which are useful in medicine, particularly cancer chemotherapy. The object of the invention to provide a method for assessing HER2-neu and/or EGFR expression levels in fixed or fixed and paraffin embedded tissues and prognosticate the probable sensitivity of a patient's tumor to treatment with receptor tyrosine kinase targeted chemotherapy by examination of the amount of HER2-neu and/or EGFR mRNA in a patient's tumor cells and comparing it to a predetermined threshold expression level for those genes. More specifically, the invention provides to oligonucleotide primer pairs EGFR and HER2-neu and methods comprising their use for detecting levels of EGFR and HER2-neu mRNA, respectively.
Description




FIELD OF THE INVENTION




The present invention relates to prognostic methods which are useful in medicine, particularly cancer chemotherapy. More particularly, the invention relates to assessment of surviviability of a patient whose tumor cell gene expression is analyzed. Additionally, the sensitivity of tumor cells to receptor tyrosine kinase targeted chemotherapeutic regimen is assayed by examining the mRNA expression of the EGFR and Her2-neu genes in humans.




BACKGROUND OF THE INVENTION




Lung cancer is the leading cause of cancer-related deaths among both males and females in western countries. In the United States, approximately 171,000 new cases of lung cancer are diagnosed and 160,000 individuals die from this disease each year. Despite improvements in the detection and treatment of lung cancer in the past two decades, the overall 5-year survival remains less than 15%. Ginsberg, et al., In: DeVita, et al.,


Cancer: Principles in Practice of Oncology


, Ed. 5, pp. 858-910. Philadelphia Lipincott-Raven Publishers, 1997. To further improve the survival rate in patients with Non-Small Cell Lung Carcinoma (NSCLC), their prognostic classification based on molecular alterations is crucial. Such classification will provide more accurate and useful diagnostic tools and, eventually, more effective therapeutic options.




Cancer arises when a normal cell undergoes neoplastic transformation and becomes a malignant cell. Transformed (malignant) cells escape normal physiologic controls specifying cell phenotype and restraining cell proliferation. Transformed cells in an individual's body thus proliferate, forming a tumor. When a tumor is found, the clinical objective is to destroy malignant cells selectively while mitigating any harm caused to normal cells in the individual undergoing treatment.




Chemotherapy is based on the use of drugs that are selectively toxic (cytotoxic) to cancer cells. Several general classes of chemotherapeutic drugs have been developed, including drugs that interfere with nucleic acid synthesis, protein synthesis, and other vital metabolic processes. These generally are referred to as anti-metabolite drugs. Other classes of chemotherapeutic drugs inflict damage on cellular DNA. Drugs of these classes generally are referred to as genotoxic. Additionally, a class of chemotherapeutic agents specifically inhibit mitogenic signaling through receptor tyrosine kinases (RTKs), in cells where RTKs are over active. (Drugs of the Future, 1992, 17, 119).




Susceptibility of an individual neoplasm to a desired chemotherapeutic drug or combination of drugs often, however, can be accurately assessed only after a trial period of treatment. The time invested in an unsuccessful trial period poses a significant risk in the clinical management of aggressive malignancies. Therefore, it is of importance to assess the expression status of genetic determinants targeted by specific chemotherapeutic agents. For example, if a tumor expresses high levels of DNA repair genes, it is likely that the tumor will not respond well to low doses of DNA-damaging genotoxic agents. Thus, the expression status of genetic determinants of a tumor will help the clinician develop an appropriate chemotherapeutic regimen specific to the genetic repertoire of the tumor.




Receptor tyrosine kinases (RTKs) are important in the transduction of mitogenic signals. RTKs are large membrane spanning proteins which possess an extracellular ligand binding domain for growth factors such as epidermal growth factor (EGF) and an intracellular portion which functions as a kinase to phosphorylate tyrosine amino acid residues on cytosol proteins thereby mediating cell proliferation. Various classes of receptor tyrosine kinases are known based on families of growth factors which bind to different receptor tyrosine kinases. (Wilks, Advances in Cancer Research, 1993, 60, 43-73)




Class I kinases such as the EGF-R family of receptor tyrosine kinases include the EGF, HER2-neu, erbB, Xmrk, DER and let23 receptors. These receptors are frequently present in common human cancers such as breast cancer (Sainsbury et al., Brit. J. Cancer, 1988, 58, 458; Guerin et al., Oncogene Res., 1988, 3, 21), squamous cell cancer of the lung (Hendler et al., Cancer Cells, 1989, 7, 347), bladder cancer (Neal et al., Lancet, 1985, 366), oesophageal cancer (Mukaida et al, Cancer, 1991, 68, 142), gastrointestinal cancer such as colon, rectal or stomach cancer (Bolen et al., Oncogene Res., 1987, 1, 149), leukaemia (Konaka et al., Cell, 1984, 37, 1035) and ovarian, bronchial or pancreatic cancer (European Patent Specification No. 0400586). As further human tumor tissues are tested for the EGF family of receptor tyrosine kinases it is expected that its widespread prevalence will be established in other cancers such as thyroid and uterine cancer.




Specifically, EGFR tyrosine kinase activity is rarely detected in normal cells whereas it is more frequently detectable in malignant cells (Hunter, Cell, 1987, 50, 823). It has been more recently shown that EGFR is overexpressed in many human cancers such as brain, lung squamous cell, bladder, gastric, breast, head and neck, oesophageal, gynaecological and thyroid tumours. (W J Gullick, Brit. Med. Bull., 1991, 47, 87). Receptor tyrosine kinases are also important in other cell-proliferation diseases such as psoriasis. EGFR disorders are those characterized by EGFR expression by cells normally not expressing EGFR, or increased EGFR activation leading to unwanted cell proliferation, and/or the existence of inappropriate EGFR levels. The EGFR is known to be activated by its ligand EGF as well as transforming growth factor-alpha (TGF-α).




The Her2-neu protein is also a member of the class I receptor tyrosine kinase (RTK) family. Yarden and Ullrich, Annu. Rev. Biochem. 57:443, 1988; Ullrich and Schlessinger, Cell 61:203, 1990. Her2-neu protein is structurally related to EGFR. Carraway, et al., Cell 78:5, 1994; Carraway, et al., J. Biol. Chem. 269:14303, 1994. These receptors share a common molecular architecture and contain two cysteine-rich regions within their cytoplasmic domains and structurally related enzymatic regions within their cytoplasmic domains.




Ligand-dependent activation of Her2-neu protein is thought to be mediated by neuactivating factor (NAF) which can directly bind to p165(Her2-neu) and stimulate enzymatic activity. Dougall et al., Oncogene 9:2109, 1994; Samata et al., Proc. Natl. Acad. Sci. USA 91:1711, 1994. Ligand-independent homodimerization of Her2-neu protein and resulting receptor activation is facilitated by over-expression of Her2-neu protein. An activated Her2-neu complex acts as a phosphokinase and phosphorylates different cytoplasmic proteins. HER2-neu disorders are characterized by inappropriate activity or over-activity of HER2-neu have increased HER2-neu expression leading to unwanted cell proliferation such as cancer.




Inhibitors of receptor tyrosine kinases EGFR and HER2-neu are employed as selective inhibitors of the growth of mammalian cancer cells (Yaish et al. Science, 1988, 242, 933). For example, erbstatin, an EGF receptor tyrosine kinase inhibitor, reduced the growth of EGFR expressing human mammary carcinoma cells injected into athymic nude mice, yet had no effect on the growth of tumors not expressing EGFR. (Toi et al., Eur. J. Cancer Clin. Oncol., 1990, 26, 722.) Various derivatives of styrene are also stated to possess tyrosine kinase inhibitory properties (European Patent Application Nos. 0211363, 0304493 and 0322738) and to be of use as anti-tumour agents. Two such styrene derivatives are Class I RTK inhibitors whose effectiveness has been demonstrated by attenuating the growth of human squamous cell carcinoma injected into nude mice (Yoneda et al., Cancer Research, 1991, 51, 4430). It is also known from European Patent Applications Nos. 0520722 and 0566226 that certain 4-anilinoquinazoline derivatives are useful as inhibitors of receptor tyrosine kinases. The very tight structure-activity relationships shown by these compounds suggests a clearly-defined binding mode, where the quinazoline ring binds in the adenine pocket and the anilino ring binds in an adjacent, unique lipophilic pocket. Three 4-anilinoquinazoline analogues (two reversible and one irreversible inhibitor) have been evaluated clinically as anticancer drugs. Denny, Farmaco January-February 2001;56(1-2):51-6. Recently, the U.S. FDA approved the use of the monoclonal antibody trastazumab (Herceptin®) for the treatment of HER2-neu overexpressing metastatic breast cancers. Scheurle, et al., Anticancer Res 20:2091-2096, 2000.




Because effective chemotherapy against tumors often requires a combination of agents, the identification and quantification of determinants of resistance or sensitivity to each single drug has become an important tool to design individual combination chemotherapy. Studies have unsuccessfully attempted to reliably correlate the relative levels of expression of EGFR and/or HER2-neu in malignant cells from cancer patients with survivability.




The prognostic importance of EGFR and in NSCLC has heretofore remained controversial. Studies using binding assays correlated increased EGFR expression with advanced stage NSCLC and shortened overall survival, whereas studies using semi-quantitative techniques for measuring EGFR mRNA or protein expression failed to show a consistent correlation with clinical outcome. Veale et al., Br. J. Caner 68:162-165, 1993; Fujino et al., Eur. Cancer 32:2070-2074, 1996; Rusch, et al., Cancer Res 53:2379-2385, 1993; Pfeiffer, et al., Br J Cancer 74:86-91, 1996; Pastorino, et al.,. J Clin Oncol 15:2858-2865, 1997. Studies of EGFR expression in NSCLC tumors using immunohistochemical methods have shown frequencies for EGFR overexpression between 32% and 47% in NSCLC tumors. Veale et al., Br. J. Caner 55:513-516, 1987; Veale et al., Br. J. Caner 68:162-165, 1993; Fujino et al., Eur. Cancer 32:2070-2074, 1996; Rusch, et al., Cancer Res 53:2379-2385, 1993; Pastorino et al., J. Clin. Onc. 15:2858-2865, 1997; Tateishi, et al., Eur J Cancer 27:1372-75, 1991; Rachwal, et al., Br J Cancer 72:56-64,1995; Rusch, et al., Cancer Res 15:2379-85,1993; Pfeiffer, et al., Br J Cancer 78:96-9, 1998; Ohsaki, et al., Oncol Rep 7:603-7,2000. Moreover, significant differences in EGFR expression has been reported among histological subtypes, generally with higher EGFR expression in SCC compared to AC and LC. Fujino et al., Eur. Cancer 32:2070-2074, 1996; Veale et al., Br. J. Caner 55:513-516, 1987; Pastorino et al., J. Clin. Onc. 15:2858-2865, 1997; Pfeiffer, et al., Br J Cancer 78:96-9, 1998; Ohsaki et al., Oncol. Rep. &:603-7, 2000. However, these studies reported no consistent correlation of EGFR overexpression with lung cancer patient survival.




Observations of a purported correlation of EGFR overexpression with a decrease in patient survival were made in some inconclusive studies. Veale et al., 1987; Ohsaki et al., 2000. However, Veale et al., analyzed a population of only nineteen NSCLC patients. Ohsaki et al., correlated EGFR protein expression with poor prognosis in NSCLC patients with p53 overexpression (P=0.024).




As with EGFR, the prognostic importance of HER2-neu and in NSCLC has heretofore remained controversial. HER2-neu protein overexpression has been demonstrated in NSCLC, including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Veale et al., 1987; Schneider, et al., Cancer Res 49:4968-4971, 1989; Kern et al., Cancer Res. 50:5184-5191, 1990; Weiner, et al., Cancer Res 50:421425, 1990; Scheurle, et al., Anticancer Res. 20:2091-2096, 2000. Earlier studies, using protein assays, reported an association of HER2-neu protein overexpression and inferior overall survival in pulmonary adenocarcinomas (AC). Kern, et al., Cancer Res 50:5184-5191, 1990; Kern et al., J Clin Invest 93:516-20, 1994. However, contradictory studies reported no correlation of HER2-neu protein overexpression with inferior overall survival in pulmonary adenocarcinomas (AC). Pfeiffer et al., Br. J. Cancer 74:86-91, 1996.




Another critical question is the evaluation of interrelationships between HER2-neu and EGFR co-overexpression as prognosticators of cancer. Tateishi et al., (Eur. J. Cancer 27:1372-75, 1991), measured EGFR and HER2-neu protein co-expression, in 13% of AC analysed, and found that co-overexpression of these two genes correlated with inferior 5-year survival. However, as with HER2-neu overexpression alone, association between HER2-neu and EGFR co-expression and survival in squamous cell carcinoma (SCC) and large cell carcinoma (LCC) of the lung has not been reported.




Inconsistent methodologies for the determination of EGFR and HER2-neu expression levels has been at the root of the problem in determining to what extent expression of these genes may be used to prognosticate cancer patient survivability. Heretofore investigations of HER2-neu and EGFR expression in NSCLC has resulted in enormous variations in frequencies of NSCLC tumors scored positive for both EGFR and HER2-neu expression. Overexpression of HER2-neu, defined as positive protein staining in adenocarcinomas (AC), was reported in 13-80%, in 2-45% in squamous cell carcinomas (SCC), and in 0-20% in large cell carcinomas (LC) by using paraffin embedded tissue on light microscope slides and HER2-neu antisera. Pfeiffer et at., 1996; Kern et al., 1990; Kern et al., 1994; Tateishi et al., 1991; Shi, et al., Mol Carcing 5:213-8, 1992; Bongiorno, et al., J Thorac Cardiovasc Surg 107:590-5,1994; Harpole, et al., Clin Cancer Res 1:659-64, 1995; Volm et al., Anticancer Res 12:11-20,1992. Moroever, a recent report illustrates the non-specificity of current protocols designed to assess HER2-neu expression levels. The HercepTest® for measurement of HER2-neu expression in invasive breast cancers was shown to have very high false positivity. Jacobs et al., J Clin Oncol 17:1983-1987, 1999.




If a precise, accurate, and consistent method for determining the expression levels of EGFR and HER2-neu existed, one could ascertain what expression levels correlate to patient survivability and whether or not a receptor tyrosine kinase targeted chemotherapy is appropriate. Consistent demonstration of EGFR and/or HER2-neu overexpression in NSCLC, using a standardized method, is desirable in establishing clinical trials for current and future receptor tyrosine kinase targeted chemotherapies, e.g., chemotherapeutic agents, antibody-based drugs, to treat cancers overexpressing these receptors.




The current protocols for measuring EGFR and/or HER2-neu gene expression, aside from being insufficiently accurate for tumor prognostication, suffer from a second limitation in that they require a significant amount of fresh tissue that contains non-degraded mRNA. Most patient derived pathological samples are routinely fixed and paraffin-embedded (FPE) to allow for histological analysis and subsequent archival storage. Thus, most biopsy tissue samples are not useful for analysis of gene expression because such studies require a high integrity of RNA so that an accurate measure of gene expression can be made. Currently, gene expression levels can be only qualitatively monitored in such fixed and embedded samples by using immunohistochemical staining to monitor protein expression levels.




The use of frozen tissue by health care professionals poses substantial inconveniences. Rapid biopsy delivery to avoid tissue and subsequent mRNA degradation is the primary concern when planning any RNA-based quantitative genetic marker assay. The health care professional performing the biopsy, must hastily deliver the tissue sample to a facility equipped to perform an RNA extraction protocol immediately upon tissue sample receipt. If no such facility is available, the clinician must promptly freeze the sample in order to prevent mRNA degradation. In order for the diagnostic facility to perform a useful RNA extraction protocol prior to tissue and RNA degradation, the tissue sample must remain frozen until it reaches the diagnostic facility, however far away that may be. Maintaining frozen tissue integrity during transport using specialized couriers equipped with liquid nitrogen and dry ice, comes only at a great expense.




Routine biopsies generally comprise a heterogenous mix of stromal and tumorous tissue. Unlike with fresh or frozen tissue, FPE biopsy tissue samples are readily microdissected and separated into stromal and tumor tissue and therefore, offer andvantage over the use of fresh or frozen tissue. However, isolation of RNA from fixed tissue, and especially fixed and paraffin embedded tissue, results in highly degraded RNA, which is generally not thought to be applicable to gene expression studies.




A number of techniques exist for the purification of RNA from biological samples, but none is reliable for isolation of RNA from FPE samples. For example, Chomczynski (U.S. Pat. No. 5,346,994) describes a method for purifying RNA from tissues based on a liquid phase separation using phenol and guanidine isothiocyanate. A biological sample is homogenized in an aqueous solution of phenol and guanidine isothiocyanate and the homogenate thereafter mixed with chloroform. Following centrifugation, the homogenate separates into an organic phase, an interphase and an aqueous phase. Proteins are sequestered in the organic phase, DNA in the interphase, and RNA in the aqueous phase. RNA can be precipitated from the aqueous phase. Unfortunately, this method is not applicable to fixed and paraffin-embedded (FPE) tissue samples.




Other known techniques for isolating RNA typically utilize either guanidine salts or phenol extraction, as described for example in Sambrook, J. et al., (1989) at pp. 7.3-7.24, and in Ausubel, F. M. et al., (1994) at pp. 4.0.3-4.4.7. Again, none of the known methods provides reproducible quantitative results in the isolation of RNA from paraffin-embedded tissue samples.




Techniques for the isolation of RNA from paraffin-embedded tissues are thus particularly needed for the study of gene expression in tumor tissues, since expression levels of certain receptors or enzymes can then be used to determine the likelihood of success or appropriateness of a particular treatment.




We report here a significant association between high levels of the intratumoral EGFR mRNA and high levels of intratumoral HER2-neu mRNA with an inferior survivability. Accordingly, it is the object of the invention to provide a method of quantifying EGFR and/or HER2-neu mRNA from tumor tissue in order to provide an early prognosis for receptor tyrosine kinase targeted chemotherapies. It is also the object of the invention to provide a method for assessing EGFR and/or HER2-neu levels in tissues fixed and paraffin-embedded (FPE) and predicting the probable sensitivity of a patient's tumor to treatment with receptor tyrosine kinase targeted chemotherapy by examining the amount EGFR and/or HER2-neu mRNA in a patient's tumor cells and comparing it to a predetermined threshold expression level.




SUMMARY OF THE INVENTION




In one aspect of the invention there is provided a method for assessing levels of expression of EGFR mRNA obtained from fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor cells.




In another aspect of the invention there is provided a method for assessing levels of expression of HER2-neu mRNA obtained from fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor cells.




In another aspect of the invention there is provided a method of quantifying the amount of EGFR mRNA expression relative to an internal control from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tissue sample. This method includes isolation of total mRNA from said sample and determining the quantity of EGFR mRNA relative to the quantity of an internal control gene's mRNA.




In another aspect of the invention there is provided a method of quantifying the amount of HER2-neu mRNA expression relative to an internal control from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tissue sample. This method includes isolation of total mRNA from said sample and determining the quantity of HER2-neu mRNA relative to the quantity of an internal control gene's mRNA.




In an embodiment of this aspect of the invention, there are provided oligonucleotide primers having the sequence of EGFR-1753F (SEQ ID NO: 1) or EGFR-1823R (SEQ ID NO:2) and sequences substantially identical thereto. The invention also provides for oligonucleotide primers having a sequence that hybridizes to SEQ ID NO: 1 or SEQ ID NO:2 or their complements under stringent conditions.




In another embodiment of this aspect of the invention, there are provided oligonucleotide primers having the sequence of HER2-neu 267 IF (SEQ ID NO: 4) or HER2-neu 2699R (SEQ ID NO: 5) and sequences substantially identical thereto. The invention also provides for oligonucleotide primers having a sequence that hybridizes to SEQ ID NO: 4 or SEQ ID NO: 5 or their complements under stringent conditions.




In yet another aspect of the invention there is provided a method for determining a receptor tyrosine kinase targeted chemotherapeutic regimen for a patient, comprising isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor sample; isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) matching non-malignant tissue sample; determining a gene expression level of EGFR in both samples; dividing the level of EGFR expression in the tumor sample with the EGFR expression level in the matching non-malignant tissue sample to determine a differential expression level; comparing the differential EGFR gene expression level with a predeterimined threshold level for the EGFR gene; and determining a chemotherapeutic regimen based on results of the comparison of the differential EGFR gene expression level with the predetermined threshold level.




In yet another aspect of the invention there is provided a method for determining a receptor tyrosine kinase targeted chemotherapeutic regimen for a patient, comprising isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor sample; isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) matching non-malignant tissue sample; determining a gene expression level of HER2-neu in both samples; dividing the level of HER2-neu expression in the tumor sample with the HER2-neu expression level in the matching non-malignant tissue sample to determine a differential expression level; comparing the differential HER2-neu gene expression levels with a predeterimined threshold level for the HER2-neu gene; and determining a chemotherapeutic regimen based on results of the comparison of the differential HER2-neu gene expression level with the predetermined threshold level.




In yet another aspect of the invention there is provided a method for determining a receptor tyrosine kinase targeted chemotherapeutic regimen for a patient, comprising isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor sample; isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) matching non-malignant tissue sample; determining gene expression levels of HER2-neu and EGFR in both of the samples; dividing the level of EGFR expression in the tumor sample with the EGFR expression level in the matching non-malignant tissue sample to determine a EGFR differential expression level; dividing the level of HER2-neu expression in the tumor sample with the HER2-neu expression level in the matching non-malignant tissue sample to determine a differential HER2-neu expression level; comparing the differential HER2-neu and EGFR gene expression levels with a predeterimined threshold level for each of the HER2-neu and EGFR genes; and determining a chemotherapeutic regimen based on results of the comparison of the differential HER2-neu and EGFR gene expression levels with the predetermined threshold levels.




In yet another aspect of the invention there is provided a method for determining the survivability of a patient, comprising isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor sample; isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) matching non-malignant tissue sample; determining a gene expression level of EGFR in both samples; dividing the level of EGFR expression in the tumor sample with the EGFR expression level in the matching non-malignant tissue sample to determine a differential expression level; comparing the differential EGFR gene expression level with a predeterimined threshold level for the EGFR gene; and determining the survivability of a patient based on results of the comparison of the differential EGFR gene expression levels with the predetermined threshold level.




In yet another aspect of the invention there is provided a method for determining the survivability of a patient, comprising isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor sample; isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) matching non-malignant tissue sample; determining a gene expression level of HER2-neu in both samples; dividing the level of HER2-neu expression in the tumor sample with the EGFR expression level in the matching non-malignant tissue sample to determine a differential expression level; comparing the differential HER2-neu gene expression levels with a predeterimined threshold level for the HER2-neu gene; and determining the survivability of a patient based on results of the comparison of the differential HER2-neu gene expression levels with the predetermined threshold level.




In yet another aspect of the invention there is provided a method for determining the survivability of a patient, comprising isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tumor sample; isolating RNA from a fresh, frozen, fixed or fixed and paraffin-embedded (FPE) matching non-malignant tissue sample; determining gene expression levels of HER2-neu and EGFR in both of the samples; dividing the level of EGFR expression in the tumor sample with the EGFR expression level in the matching non-malignant tissue sample to determine a EGFR differential expression level; dividing the level of HER2-neu expression in the tumor sample with the HER2-neu expression level in the matching non-malignant tissue sample to determine a HER2-neu differential expression level; comparing the differential HER2-neu and EGFR gene expression levels with a predetermined threshold level for each of the HER2-neu and EGFR genes; and determining the survivability of a patient based on results of the comparison of the EGFR and HER2-neu gene expression levels with the predetermined threshold levels.




The invention further relates to a method of normalizing the uncorrected gene expression (UGE) of EGFR and HER2-neu relative to an internal control gene in a tissue sample analyzed using TaqMan® technology to known EGFR and HER2-neu expression levels relative to an internal control from samples analyzed by pre-TaqMan® technology.











BRIEF DESCRIPTION OF THE DRAWINGS




FIG.


1


. Estimated probability of survival of curatively resected non-small cell lung cancer patients versus the HER2-neu mRNA expression status. The median survival was not reached in the low HER2-neu expression group compared to 31.1 months (95% C.I: 21.96-40.24) in the high HER2-neu expression group (P=0.004).




FIG.


2


. Estimated probability of survival of curatively resected non-small cell lung cancer patients versus the EGFR mRNA expression status. A trend towards inferior overall survival was observable for the high EGFR expression group, but did not reach statistical significance. The median survival was not reached in the low EGFR expression group compared to 32.37 months (95% C.I: 8.43-56.31) in the high EGFR expresser group (P=0.176).




FIG.


3


. Estimated probability of survival of curatively resected non-small cell lung cancer patients versus combined patterns of EGFR and HER2-neu co-expression in NSCLC. The median survival was not reached in the group that showed low HER2-neu and EGFR expression, compared to 45.47 months in the high EGFR expression group, 31.10 months (95% C.I.: 14.77-47.43) in the high HER2-neu expression group, and 22.03 months (95% C.I: 2.30-41.76; P=0.003) in the high HER2-neu and EGFR expression group.




FIG.


4


. Table showing high and low EGFR and HER2-neu expression in patients and tumors.




FIG.


5


. Table showing the survival of patients based on clinical and molecular parameters.




FIG.


6


. Table showing Cox-proportional hazard regression models. Double marker refers to both EGFR and HER2-neu expression.





FIG. 7

is a chart illustrating how to calculate EGFR expression relative to an internal control gene. The chart contains data obtained with two test samples, (unknowns 1 and 2), and illustrates how to determine the uncorrected gene expression data (UGE). The chart also illustrates how to normalize UGE generated by the TaqMan® instrument with known relative EGFR values determined by pre-TaqMan® technology. This is accomplished by multiplying UGE to a correction factor K


EGFR


. The internal control gene in the figure is β-actin and the calibrator RNA is Human Liver Total RNA (Stratagene, Cat #735017).





FIG. 8

is a chart illustrating how to calculate HER2-neu expression relative to an internal control gene. The chart contains data obtained with two test samples, (unknowns 1 and 2), and illustrates how to determine the uncorrected gene expression data (UGE). The chart also illustrates how to normalize UGE generated by the TaqMan® instrument with previously published HER2-neu values. This is accomplished by multiplying UGE to a correction factor K


HER2-neu


. The internal control gene in the figure is β-actin and the calibrator RNA is Human Liver Total RNA (Stratagene, Cat #735017).





FIG. 9

is a graph showing the corrected EGFR expression values of 5 different colon cancer patients' tumors. The patients were on a CPT-11/C225 receptor tyrosine kinase targeted treatment regimen. Patient 1 was determined to have a corrected EGFR expression level of 2.08×10


−3


and had a completed response (CR). Patient 2 had a corrected EGFR expression level of 8.04×10


−3


and had a partial response (PR). Patient 3 had a corrected EGFR expression level of 1.47×10


−3


and also showed a partial response (PR). Patient 4 had a corrected EGFR expression level of 0.16×10


−3


and had stable disease (SD) showing no response. Patient 5 had a no EGFR expression (0.0×10


−3


) and had progressive disease (PR).











DETAILED DESCRIPTION OF THE INVENTION




Tumors expressing high levels of HER2-neu and/or EGFR mRNA are considered likely to be sensitive to receptor tyrosine kinase targeted chemotherapy. Conversely, those tumors expressing low amounts of HER2-neu and EGFR mRNA are not likely to be sensitive to receptor tyrosine kinase targeted chemotherapy. A patient's differential HER2-neu and EGFR mRNA expression status is judged by comparing it to a predetermined threshold expression level.




The invention provides a method of quantifying the amount of HER2-neu and/or EGFR mRNA expression in fresh, frozen, fixed or fixed and paraffin-embedded (FPE) tissue relative to gene expression of an internal control. The present inventors have developed oligonucleotide primers that allow accurate assessment of HER2-neu and EGFR gene expression in fresh, frozen, fixed or fixed and embedded tissues. The oligonucleotide primers, EGFR-1753F (SEQ ID NO: 1), EGFR-1823R (SEQ ID NO: 2), or oligonucleotide primers substantially identical thereto, preferably are used together with RNA extracted from fresh, frozen, fixed or fixed and paraffin embedded (FPE) tumor samples. The invention also provides oligonucleotide primers, HER2-neu 2671F (SEQ ID NO: 4), HER2-neu 2699R (SEQ ID NO: 5), or oligonucleotide primers substantially identical thereto, preferably are used together with RNA extracted from fresh, frozen, fixed or fixed and paraffin embedded (FPE) tumor samples. This measurement of HER2-neu and/or EGFR gene expression may then be used for prognosis of receptor tyrosine kinase targeted chemotherapy




This embodiment of the invention involves, a method for reliable extraction of RNA from fresh, frozen, fixed or FPE samples, determination of the content of EGFR mRNA in the sample by using a pair of oligonucleotide primers, preferably oligionucleotide primer pair EGFR-1753F (SEQ ID NO: 1) and EGFR-1823R (SEQ ID NO: 2), or oligonucleotides substantially identical thereto, for carrying out reverse transcriptase polymerase chain reaction.




Another embodiment of the invention involves a method for reliable extraction of RNA from fresh, frozen, fixed or FPE samples, and determination of the content of HER2-neu mRNA in the sample by using a pair of oligonucleotide primers oligonucleotide primers, HER2-neu 2671F (SEQ ID NO: 4), HER2-neu 2699R (SEQ ID NO: 5), or oligonucleotide primers substantially identical thereto.




“Substantially identical” in the nucleic acid context as used herein, means hybridization to a target under stringent conditions, and also that the nucleic acid segments, or their complementary strands, when compared, are the same when properly aligned, with the appropriate nucleotide insertions and deletions, in at least about 60% of the nucleotides, typically, at least about 70%, more typically, at least about 80%, usually, at least about 90%, and more usually, at least, about 95-98% of the nucleotides. Selective hybridization exists when the hybridization is more selective than total lack of specificity. See, Kanehisa, Nucleic Acids Res., 12:203-213 (1984).




The methods of the present invention can be applied over a wide range of tumor types. This allows for the preparation of individual “tumor expression profiles” whereby expression levels of HER2-neu and/or EGFR are determined in individual patient samples and response to various chemotherapeutics is predicted. Preferably, the methods of the invention are applied to solid tumors, most preferably NSCLC tumors.




A “differential expression level” as defined herein refers to the difference in the level of expression of either EGFR or HER2-neu in a tumor with respect to the level of expression of either EGFR or HER2-neu in a matching non-malignant tissue sample, respectively. The differential expression level is determined by dividing the UGE of a particular gene from the tumor sample with the UGE of the same gene from a matching non-malignant tissue sample.




A “predetermined threshold level”, as defined herein relating to EGFR expression, is a level of differential EGFR expression above which (i.e., high), tumors are likely to be sensitive to a receptor tyrosine kinase targeted chemotherapeutic regimen. A high differential EGFR expression level is prognostic of lower patient survivability. Tumors with expression levels below this threshold level are not likely to be affected by a receptor tyrosine kinase targeted chemotherapeutic regimen. A low differential EGFR expression level is prognostic of higher patient survivability. Whether or not differential expression is above or below a “predetermined threshold level” is determined by the method used by Mafune et al., who calculated individual differential tumor/normal (T/N) expression ratios in matching non-malignant tissues obtained from patients with squamous cell carcinoma of the esophagus. Mafune et al., Clin Cancer Res 5:4073-4078, 1999. This method of analysis leads to a precise expression value for each patient, being based on the individual background expression obtained from matching non-malignant tissue. The differential expression of EGFR is considered “high” and indicative of low survivability if the UGE of EGFR: β-actin in a tumor sample divided by the UGE of EGFR: β-actin in a matching non-malignant tissue sample, is above the predetermined threshold value of about 1.8. The differential expression of EGFR is considered “low” and indicative of high survivability if the UGE of EGFR: β-actin in a tumor sample divided by the UGE of EGFR: β-actin in a matching n+on-malignant tissue sample, is below the predetermined threshold value of about 1.8.




A “predetermined threshold level”, as defined herein relating to differential HER2-neu expression, is a level of HER2-neu expression above which (i.e., high), tumors are likely to be sensitive to a receptor tyrosine kinase targeted chemotherapeutic regimen. A high differential HER2-neu expression level is prognostic of lower patient survivability. Tumors with expression levels below this threshold level are not likely to be affected by a receptor tyrosine kinase targeted chemotherapeutic regimen. A low differential HER2-neu expression level is prognostic of higher patient survivability. The differential expression of HER2-neu is considered “high” and indicative of low survivability if the UGE of HER2-neu: β-actin in a tumor sample divided by the UGE of HER2-neu: β-actin in a matching non-malignant tissue sample, is above the predetermined threshold value of about 1.8. The differential expression of HER2-neu is considered “low” and indicative of high survivability if the UGE of HER2-neu: β-actin in a tumor sample divided by the UGE of HER2-neu: β-actin in a matching non-malignant tissue sample, is below the predetermined threshold value of about 1.8.




A “threshold level” for HER2-neu was determined using the following results and method. The corrected HER2-neu mRNA expression, expressed as the ratio between HER2-neu and β-Actin PCR product, was 4.17×10


−3


(range 0.28-23.86×10


3


) in normal lung and 4.35×10


−3


(range: 0.21-68.11×10


−3


) in tumor tissue (P=0.019 Wilcoxon test). The maximal chi-square method by Miller and Siegmund (Miller et al., Biometrics 38:1011-1016, 1982) and Halpern (Biometrics 38:1017-1023, 1982) determined a threshold value of 1.8 to segregate patients into low and high differential HER2-neu expressors. By this criterion, 29 (34.9%) patients had a high differential HER2-neu expression and 54 (65.1%) had a low differential HER2-neu expression.




A “threshold level” for EGFR was determined using the following results and method. The median corrected EGFR mRNA expression was 8.17×10


−3


(range: 0.31-46.26×10


−3


) in normal lung and 7.22×10


−3


(range: 0.27-97.49×10


−3


) in tumor tissue (P=n.s.). The maximal chi-square method (Miller (1982); Halpern (1982)) determined a threshold value of 1.8 to segregate patients into low and high differential EGFR expressors. By this criterion, 28 (33.7%) patients had a high differential EGFR expression and 55 (66.3%) had a low differential EGFR expression status.




In performing the method of the present invention either differential EGFR expression levels or differential HER2-neu expression levels are assayed in a patient to prognosticate the efficacy of a receptor tyrosine kinase targeted chemotherapeutic regimen. Moreover, in the method of the present invention differential HER2-neu expression levels are assayed in a patient prognosticate the efficacy of a receptor tyrosine kinase targeted chemotherapeutic regimen. Additionally, in the method of the present invention differential EGFR expression levels are assayed in a patient to prognosticate the efficacy of a receptor tyrosine kinase targeted chemotherapeutic regimen. Alternatively, both differential EGFR expression levels and differential HER2-neu expression levels are assayed in a patient to prognosticate the efficacy of a receptor tyrosine kinase targeted chemotherapeutic regimen.




“Matching non-malignant sample” as defined herein refers to a sample of non-cancerous tissue derived from the same individual as the tumor sample to be analyzed for differential EGFR and/or differential HER2-neu expression. Preferably a matching non-malignant sample is derived from the same organ as the organ from which the tumor sample is derived. Most preferably, the matching non-malignant tumor sample is derived from the same organ tissue layer from which the tumor sample is derived. Also, it is preferable to take a matching non-malignant tissue sample at the same time a tumor sample is biopsied. In a preferred embodiment tissues from the following two locations are analyzed: lung tumor and non-malignant lung tissue taken from the greatest distance form the tumor or colon tumor and non-malignant colon tissue taken from the greatest distance form the tumor as possible under the circumstances.




In performing the method of this embodiment of the present invention, tumor cells are preferably isolated from the patient. Solid or lymphoid tumors or portions thereof are surgically resected from the patient or obtained by routine biopsy. RNA isolated from frozen or fresh tumor samples is extracted from the cells by any of the methods typical in the art, for example, Sambrook, Fischer and Maniatis, Molecular Cloning, a laboratory manual, (2nd ed.), Cold Spring Harbor Laboratory Press, New York, (1989). Preferably, care is taken to avoid degradation of the RNA during the extraction process.




However, tissue obtained from the patient after biopsy is often fixed, usually by formalin (formaldehyde) or gluteraldehyde, for example, or by alcohol immersion. Fixed biological samples are often dehydrated and embedded in paraffin or other solid supports known to those of skill in the art. See Plenat et al., Ann Pathol January 2001 ;21(1):29-47. Non-embedded, fixed tissue as well as fixed and embedded tissue may also be used in the present methods. Solid supports for embedding fixed tissue are envisioned to be removable with organic solvents for example, allowing for subsequent rehydration of preserved tissue.




RNA is extracted from paraffin-embedded (FPE) tissue cells by any of the methods as described in U.S. patent application Ser. No. 09/469,338, filed Dec. 20, 1999, now U.S. Pat. No. 6,248,535, which is hereby incorporated by reference in its entirety. As used herein, FPE tissue means tissue that has been fixed and embedded in a solid removable support, such as storable or archival tissue samples. RNA may be isolated from an archival pathological sample or biopsy sample which is first deparaffinized. An exemplary deparaffinization method involves washing the paraffinized sample with an organic solvent, such as xylene, for example. Deparaffinized samples can be rehydrated with an aqueous solution of lower alcohol. Suitable lower alcohols, for example include, methanol, ethanol, propanols and butanols. Deparaffinized samples may be rehydrated with successive washes with lower alcoholic solutions of decreasing concentration, for example. Alternatively, the sample is simulatneously deparaffinized and rehydrated. RNA is then extracted from the sample.




For RNA extraction, the fixed or fixed and deparaffinized samples can be homogenized using mechanical, sonic or other means of homogenization. Rehydrated samples may be homogenized in a solution comprising a chaotropic agent, such as guanidinium thiocyanate (also sold as guanidinium isothiocyanate). Homogenized samples are heated to a temperature in the range of about 50 to about 100° C. in a chaotropic solution, which contains an effective amount of a chaotropic agent, such as a guanidinium compound. A preferred chaotropic agent is guanidinium thiocyanate.




An “effective concentration of chaotropic agent” is chosen such that RNA is purified from a paraffin-embedded sample in an amount of greater than about 10-fold that isolated in the absence of a chaotropic agent. Chaotropic agents include, for example: guanidinium compounds, urea, formamide, potassium iodiode, potassium thiocyantate and similar compounds. The preferred chaotropic agent for the methods of the invention is a guanidinium compound, such as guanidinium isothiocyanate (also sold as guanidinium thiocyanate) and guanidinium hydrochloride. Many anionic counterions are useful, and one of skill in the art can prepare many guanidinium salts with such appropriate anions. The effective concentration of guanidinium solution used in the invention generally has a concentration in the range of about 1 to about 5M with a preferred value of about 4M. If RNA is already in solution, the guanidinium solution may be of higher concentration such that the final concentration achieved in the sample is in the range of about 1 to about 5M. The guanidinium solution also is preferably buffered to a pH of about 3 to about 6, more preferably about 4, with a suitable biochemical buffer such as Tris-Cl. The chaotropic solution may also contain reducing agents, such as dithiothreitol (DTT) and β-mercaptoethanol (BME). The chaotropic solution may also contain RNAse inhibitors.




RNA is then recovered from the chaotropic solution by, for example, phenol chloroform extraction, ion exchange chromatography or size-exclusion chromatography. RNA may then be further purified using the techniques of extraction, electrophoresis, chromatography, precipitation or other suitable techniques.




The quantification of HER2-neu or EGFR mRNA from purified total mRNA from fresh, frozen or fixed is preferably carried out using reverse-transcriptase polymerase chain reaction (RT-PCR) methods common in the art, for example. Other methods of quantifying of HER2-neu or EGFR mRNA include for example, the use of molecular beacons and other labeled probes useful in multiplex PCR. Additionally, the present invention envisages the quantification of HER2-neu and/or EGFR mRNA via use of a PCR-free systems employing, for example fluorescent labeled probes similar to those of the Invader® Assay (Third Wave Technologies, Inc.). Most preferably, quantification of HER2-neu and/or EGFR cDNA and an internal control or house keeping gene (e.g. β-actin) is done using a fluorescence based real-time detection method (ABI PRISM 7700 or 7900 Sequence Detection System [TaqMan®], Applied Biosystems, Foster City, Calif.) or similar system as described by Heid et al., (Genome Res 1996;6:986-994) and Gibson et al.(Genome Res 1996;6:995-1001). The output of the ABI 7700 (TaqMan® Instrument) is expressed in Ct's or “cycle thresholds”. With the TaqMan® system, a highly expressed gene having a higher number of target molecules in a sample generates a signal with fewer PCR cycles (lower Ct) than a gene of lower relative expression with fewer target molecules (higher Ct).




As used herein, a “house keeping” gene or “internal control” is any constitutively or globally expressed gene whose presence enables an assessment of HER2-neu and/or EGFR mRNA levels. Such an assessment comprises a determination of the overall constitutive level of gene transcription and a control for variations in RNA recovery. “House-keeping” genes or “internal controls” can include, but are not limited to the cyclophilin gene, β-actin gene, the transferrin receptor gene, GAPDH gene, and the like. Most preferably, the internal control gene is β-actin gene as described by Eads et al., Cancer Research 1999; 59:2302-2306.




A control for variations in RNA recovery requires the use of “calibrator RNA.” The “calibrator RNA” is intended to be any available source of accurately pre-quantified control RNA. Preferably, Human Liver Total RNA (Stratagene, Cat #735017) is used.




“Uncorrected Gene Expression (UGE)” as used herein refers to the numeric output of HER2-neu and/or EGFR expression relative to an internal control gene generated by the TaqMan® instrument. The equation used to determine UGE is shown in Examples 3 and 4, and illustrated with sample calculations in

FIGS. 7 and 8

.




These numerical values allow the determination of whether or not the differential gene expression (i.e., “UGE” or of a particular tumor sample divided by the “UGE” of a matching non-tumor sample) falls above or below the “predetermined threshold” level. The predetermined threshold level for EGFR and HER2-neu is about 1.8.




A further aspect of this invention provides a method to normalize uncorrected gene expression (UGE) values acquired from the TaqMan® instrument with “known relative gene expression” values derived from non-TaqMan® technology. Preferably, TaqMan® derived HER2-neu and/or EGFR UGE values from a tissue sample are normalized to samples with known non-TaqMan® derived relative HER2-neu and/or EGFR: β-actin expression values.




“Corrected Relative EGFR Expression” as used herein refers to normalized EGFR expression whereby UGE is multiplied with a EGFR specific correction factor (K


EGFR


), resulting in a value that can be compared to a known range of EGFR expression levels relative to an internal control gene. Example 3 and

FIG. 7

illustrate these calculations in detail. K


EGFR


specific for EGFR, the internal control β-actin and calibrator Human Liver Total RNA (Stratagene, Cat #735017), is 26.95×10


−3


. These numerical values also allow the determination of whether or not the “Corrected Relative Expression” of a particular tumor sample divided by the “Corrected Relative Expression” of a matching non-tumor sample (i.e., differential expression) falls above or below the “predetermined threshold” level. The predetermined threshold level for HER2-neu or EGFR is about 1.8. In determining whether the differential expression of either EGFR or HER2-neu in a tumor sample is 1.8 times greater than in a matching non-tumor sample, one will readily recognize that either UGE values or Corrected Relative Expression values can be used. For example, if one divides the Corrected Relative Expression level of the tumor with that of the matching non-tumor sample, the K-factor cancels out and one is left with same ratio as if one had used UGE values.




“Known relative gene expression” values are derived from previously analyzed tissue samples and are based on the ratio of the RT-PCR signal of a target gene to a constitutively expressed internal control gene (e.g. β-Actin, GAPDH, etc.). Preferably such tissue samples are formalin fixed and paraffin-embedded (FPE) samples and RNA is extracted from them according to the protocol described in Example 1. To quantify gene expression relative to an internal control standard quantitative RT-PCR technology known in the art is used. Pre-TaqMan® technology PCR reactions are run for a fixed number of cycles (i.e., 30) and endpoint values are reported for each sample. These values are then reported as a ratio of EGFR expression to β-actin expression.




K


EGFR


may be determined for an internal control gene other than β-actin and/or a calibrator RNA different than Human Liver Total RNA (Stratagene, Cat #735017). To do so, one must calibrate both the internal control gene and the calibrator RNA to tissue samples for which EGFR expression levels relative to that particular internal control gene have already been determined (i.e., “known relative gene expression”). Preferably such tissue samples are formalin fixed and paraffin-embedded (FPE) samples and RNA is extracted from them according to the protocol described in Example 1. Such a determination can be made using standard pre-TaqMan®, quantitative RT-PCR techniques well known in the art. Upon such a determination, such samples have “known relative gene expression” levels of EGFR useful in the determining a new K


EGFR


specific for the new internal control and/or calibrator RNA as described in Example 3.




“Corrected Relative HER2-neu Expression” as used herein refers to normalized HER2-neu expression whereby UGE is multiplied with a HER2-neu specific correction factor (K


HER2-neu


), resulting in a value that can be compared to a known range of HER2-neu expression levels relative to an internal control gene. Example 4 and

FIG. 8

illustrate these calculations in detail. K


HER2-neu


specific for HER2-neu, the internal control β-actin and calibrator Human Liver Total RNA (Stratagene, Cat #735017), is 13.3×10


−3


.




K


HER2-neu


may be determined for an internal control gene other than β-actin and/or a calibrator RNA different than Human Liver Total RNA (Stratagene, Cat #735017). To do so, one must calibrate both the internal control gene and the calibrator RNA to tissue samples for which HER2-neu expression levels relative to that particular internal control gene have already been determined (i.e., “known relative gene expression”). Preferably such tissue samples are formalin fixed and paraffin-embedded (FPE) samples and RNA is extracted from them according to the protocol described in herein. Such a determination can be made using standard pre-TaqMan®, quantitative RT-PCR techniques well known in the art, for example. Upon such a determination, such samples have “known relative gene expression” levels of HER2-neu useful in the determining a new K


HER2-neu


specific for the new internal control and/or calibrator RNA as described in Example 4.




The methods of the invention are applicable to a wide range of tissue and tumor types and so can be used for assessment of clinical treatment of a patient and as a diagnostic or prognostic tool for a range of cancers including breast, head and neck, lung, esophageal, colorectal, and others. In a preferred embodiment, the present methods are applied to prognosis of NSCLC tumors.




Pre-chemotherapy treatment tumor biopsies are usually available only as fixed paraffin embedded (FPE) tissues, generally containing only a very small amount of heterogeneous tissue. Such FPE samples are readily amenable to microdissection, so that HER2-neu and/or EGFR gene expression may be determined in tumor tissue uncontaminated with non-malignant stromal tissue. Additionally, comparisons can be made between non-malignant stromal and tumor tissue within a biopsy tissue sample, since such samples often contain both types of tissues.




Generally, any oligonucleotide pairs that flank a region of EGFR gene, as shown in SEQ ID NO: 10, may be used to carry out the methods of the invention. Primers hybridizing under stringent conditions to a region of the EGFR gene for use in the present invention will amplify a product between 20-1000 base pairs, preferably 50-100 base pairs, most preferably less than 100 base pairs.




The invention provides specific oligonucleotide primer pairs and oligonucleotide primers substantially identical thereto, that allow particularly accurate assessment of EGFR expression using fresh, frozen, fixed or FPE tissues. Preferable are oligonucleotide primers, EGFR-1753F (SEQ ID NO: 1) and EGFR-1823R (SEQ ID NO: 2), (also referred to herein as the oligonucleotide primer pair EGFR) and oligonucleotide primers substantially identical thereto. The oliogonucleotide primers EGFR-1753F (SEQ ID NO: 1) and EGFR-1823R, (SEQ ID NO: 2) have been shown to be particularly effective for measuring EGFR mRNA levels using RNA extracted from fresh, frozen, fixed or FPE cells by any of the methods for mRNA isolation, for example as described Example 1.




Furthermore, any oligonucleotide pairs that flank a region of HER2-neu gene, as shown in SEQ ID NO: 11, may be used to carry out the methods of the invention. Primers hybridizing under stringent conditions to a region of the HER2-neu gene for use in the present invention will amplify a product between about 20-1000 base pairs, preferably about 50-100 base pairs, most preferably less than about 100 base pairs.




The invention provides specific oligonucleotide primers pairs and oligonucleotide primers substantially identical thereto, that allow particularly accurate assessment of HER2-neu expression in fresh, frozen, fixed or FPE tissues. Preferable are oligonucleotide primers, HER2-neu 2671F (SEQ ID NO: 4) and HER2-neu 2699R (SEQ ID NO: 5), (also referred to herein as the oligonucleotide primer pair HER2-neu) and oligonucleotide primers substantially identical thereto. The oliogonucleotide primers HER2-neu 2671F (SEQ ID NO: 4) and HER2-neu 2699R (SEQ ID NO: 5) have been shown to be particularly effective for measuring HER2-neu mRNA levels using RNA extracted from fresh, frozen, fixed or FPE cells by any of the methods for mRNA isolation, for example as described herein.




This invention includes substantially identical oligonucleotides that hybridize under stringent conditions (as defined herein) to all or a portion of the oligonucleotide primer sequence of EGFR-1753F (SEQ ID NO: 1), its complement or EGFR-1823R (SEQ ID NO: 2), or its complement or oligonucleotide primer sequence of HER2-neu 2671F (SEQ ID NO: 4), its complement or HER2-neu 2699R (SEQ ID NO: 5), or its complement.




Under stringent hybridization conditions, only highly complementary, i.e., substantially similar nucleic acid sequences as defined herein hybridize. Preferably, such conditions prevent hybridization of nucleic acids having 4 or more mismatches out of 20 contiguous nucleotides, more preferably 2 or more mismatches out of 20 contiguous nucleotides, most preferably one or more mismatch out of 20 contiguous nucleotides.




The hybridizing portion of the nucleic acids is typically at least about 10 (e.g., 15) nucleotides in length. The hybridizing portion of the hybridizing nucleic acid is at least about 80%, preferably at least about 95%, or most preferably about at least 98%, identical to the sequence of a portion or all of oligonucleotide primer EGFR-1753F (SEQ ID NO: 1), its complement or EGFR-1823R (SEQ ID NO: 2), or its complement or oligonucleotide primer HER2-neu 267 IF (SEQ ID NO: 4), its complement or HER2-neu 2699R (SEQ ID NO: 5), or its complement.




Hybridization of the oligonucleotide primer to a nucleic acid sample under stringent conditions is defined below. Nucleic acid duplex or hybrid stability is expressed as a melting temperature (T


m


), which is the temperture at which the probe dissociates from the target DNA. This melting temperature is used to define the required stringency conditions. If sequences are to be identified that are substantially identical to the probe, rather than identical, then it is useful to first establish the lowest temperature at which only holmologous hybridization occurs with a particular concentration of salt (e.g. SSC or SSPE). Then assuming that 1% mismatching results in a 1° C. decrease in T


m


, the temperatre of the final wash in the hybridization reaction is reduced accordingly (for example, if sequences having >95% identity with the probe are sought, the final wash temperature is decrease by 5° C.). In practice, the change in T


m


can be between 0.5° C. and 1.5° C. per 1% mismatch.




Stringent conditions involve hybridizing at about 68° C. in 5× SSC/5× Denhart's solution/1.0% SDS, and washing in 0.2× SSC/0.1% SDS at room temperature. Moderately stringent conditions include washing in 3× SSC at about 42° C. The parameters of salt concentration and temperature be varied to achieve optimal level of identity between the primer and the target nucleic acid. Additional guidance regarding such conditions is readily available in the art, for example, Sambrook, Fischer and Maniatis, Molecular Cloning, a laboratory manual, (2nd ed.), Cold Spring Harbor Laboratory Press, New York, (1989) and F. M. Ausubel et al eds., Current Protocols in Molecular Biology, John Wiley and Sons (1994).




Oligonucleotide primers disclosed herein are capable of allowing accurate assessment of HER2-neu and/or EGFR gene expression in a fixed or fixed and paraffin embedded tissue, as well as frozen or fresh tissue. This is despite the fact that RNA derived from FPE samples is more fragmented relative to that of fresh or frozen tissue. Thus, the methods of the invention are suitable for use in assaying HER2-neu and/or EGFR gene expression levels in all tissues where previously there existed no accurate and consistent way to assay HER2-neu and/or EGFR gene in fresh and frozen tissues and no way at all to assay HER2-neu and/or EGFR gene expression using fixed tissues.




Over-activity of HER2-neu refers to either an amplification of the gene encoding HER2-neu or the production of a level of HER2-neu activity which can be correlated with a cell proliferative disorder (i.e., as the level of HER2-neu increases the severity of one or more of the symptoms of the cell proliferative disorder increases).




A “receptor tyrosine kinase targeted” chemotherapy or chemotherapeutic regimen in the context of the present invention refers a chemotherapy comprising agents that specifically interfere with Class I receptor tyrosine kinase function. Preferably, such agents will inhibit EGFR and/or HER2-neu receptor tyrosine kinase signaling activity. Such agents include 4-anilinoquinazolines such as 6-acrylamido-4-anilinoquinazoline Bonvini et al., Cancer Res. Feb. 15, 2001 ;61(4):1671-7 and derivatives, erbstatin (Toi et al., Eur. J. Cancer Clin. Oncol., 1990, 26, 722.), Geldanamycin, bis monocyclic, bicyclic or heterocyclic aryl compounds (PCT WO 92/20642), vinylene-azaindole derivatives (PCT WO 94/14808) and 1-cycloproppyl-4-pyridyl-quinolones (U.S. Pat. No. 5,330,992) which have been described generally as tyrosine kinase inhibitors. Also, Styryl compounds (U.S. Pat. No. 5,217,999), styryl-substituted pyridyl compounds (U.S. Pat. No. 5,302,606), certain quinazoline derivatives (EP Application No. 0 566 266 Al), seleoindoles and selenides (PCT WO 94/03427), tricyclic polyhydroxylic compounds (PCT WO 92/21660) and benzylphosphonic acid compounds (PCT WO 91/15495) have been described as compounds for use as tyrosine kinase inhibitors for use in the treatment of cancer.




Other agents targeting EGFR and/or HER2-neu receptor tyrosine kinase signaling activity include antibodies that inhibit growth factor receptor biological function indirectly by mediating cytotoxicity via a targeting function




Antibodies complexing with the receptor activates serum complement and/or mediate antibody-dependent cellular cytotoxicity. The antibodies which bind the receptor can also be conjugated to a toxin (immunotoxins). Advantageously antibodies are selected which greatly inhibit the receptor function by binding the steric vicinity of the ligand binding site of the receptor (blocking the receptor), and/or which bind the growth factor in such a way as to prevent (block) the ligand from binding to the receptor. These antibodies are selected using conventional in vitro assays for selecting antibodies which neutralize receptor function. Antibodies that act as ligand agonists by mimicking the ligand are discarded by conducting suitable assays as will be apparent to those skilled in the art. For certain tumor cells, the antibodies inhibit an autocrine growth cycle (i.e. where a cell secretes a growth factor which then binds to a receptor of the same cell). Since some ligands, e.g. TGF-α, are found lodged in cell membranes, the antibodies serving a targeting function are directed against the ligand and/or the receptor




The cytotoxic moiety of the immunotoxin may be a cytotoxic drug or an enzymatically active toxin of bacterial or plant origin, or an enzymatically active fragment of such a toxin. Enzymatically active toxins and fragments thereof used are diphtheria, nonbinding active fragments of diphtheria toxin, exotoxin (from


Pseudomonas aeruginosa


), ricin, abrin, modeccin, alpha-sarcin,


Aleurites fordii


proteins, dianthin proteins,


Phytolacca americana


proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, and enomycin. In another embodiment, the antibodies are conjugated to small molecule anticancer drugs. Conjugates of the monoclonal antibody and such cytotoxic moieties are made using a variety of bifunctional protein coupling agents. Examples of such reagents are SPDP, IT, bifunctional derivatives of imidoesters such a dimethyl adipimidate HCl, active esters such as disuccinimidyl suberate, aldehydes such as glutaraldehyde, bis-azido compounds such as bis (p-azidobenzoyl) hexanediamine, bis-diazonium derivatives such as bis-(p-diazoniumbenzoyl)-ethylenediamine, diisocyanates such as tolylene 2,6-diisocyanate, and bis-active fluorine compounds such as 1,5-difluoro-2,4-dinitrobenzene. The lysing portion of a toxin may be joined to the Fab fragment of the antibodies.




Cytotoxic radiopharmaceuticals for treating cancer may be made by conjugating radioactive isotopes to the antibodies. The term “cytotoxic moiety” as used herein is intended to include such isotopes.




In another embodiment, liposomes are filled with a cytotoxic drug and the liposomes are coated with antibodies specifically binding a growth factor receptor. Since there are many receptor sites, this method permits delivery of large amounts of drug to the appropriate cell type. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See e.g. Fingl et al., in The Pharmacological Basis of Therapeutics, 1975, Ch. 1 p. 1). It should be noted that the attending physician would know how and when to terminate, interrupt, or adjust administration due to toxicity, or organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the oncogenic disorder of interest will vary with the severity of the condition to be treated and to the route of administration. The severity of the condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency, will also vary according to the age, body weight, and response of the individual patient.




Depending on the specific conditions being treated, such agents may be formulated and administered systemically or locally. Techniques for formulation and




administration may be found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Co., Easton, Pa. (1990). Suitable routes may include oral, rectal, transdermal, vaginal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections, just to name a few. For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. For such transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.




The invention being thus described, practice of the invention is illustrated by the experimental examples provided below. The skilled practitioner will realize that the materials and methods used in the illustrative examples can be modified in various ways. Such modifications are considered to fall within the scope of the present invention.




EXAMPLES




Example 1




RNA Isolation from FPE Tissue




RNA is extracted from paraffin-embedded tissue by the following general procedure.




A. Deparaffinization and Hydration of Sections:




(1) A portion of an approximately 10 μM section is placed in a 1.5 mL plastic centrifuge tube.




(2) 600 μL, of xylene are added and the mixture is shaken vigorously for about 10 minutes at room temperature (roughly 20 to 25° C.).




(3) The sample is centrifuged for about 7 minutes at room temperature at the maximum speed of the bench top centrifuge (about 10-20,000× g).




(4) Steps 2 and 3 are repeated until the majority of paraffin has been dissolved. Two or more times are normally required depending on the amount of paraffin included in the original sample portion.




(5) The xylene solution is removed by vigorously shaking with a lower alcohol, preferably with 100% ethanol (about 600 PL) for about 3 minutes.




(6) The tube is centrifuged for about 7 minutes as in step (3). The supernatant is decanted and discarded. The pellet becomes white.




(7) Steps 5 and 6 are repeated with successively more dilute ethanol solutions: first with about 95% ethanol, then with about 80% and finally with about 70% ethanol.




(8) The sample is centrifuged for 7 minutes at room temperature as in step.




(9) The supernatant is discarded and the pellet is allowed to dry at room temperature for about 5 minutes.




B. RNA Isolation with Phenol-Chloroform




(1) 400 μL guanidine isothiocyanate solution including 0.5% sarcosine and 8 μL dithiothreitol is added.




(2) The sample is then homogenized with a tissue homogenizer (Ultra-Turrax, IKA-Works, Inc., Wilmington, N.C.) for about 2 to 3 minutes while gradually increasing the speed from low speed (speed 1) to high speed (speed 5).




(3) The sample is then heated at about 95° C. for about 5-20 minutes. It is preferable to pierce the cap of the tube containing the sample with a fine gauge needle before heating to 95° C. Alternatively, the cap may be affixed with a plastic clamp or with laboratory film.




(4) The sample is then extracted with 50 μL 2M sodium acetate at pH 4.0 and 600 μL of phenol/chloroform/isoamyl alcohol (10:1.93:0.036), prepared fresh by mixing 18 mL phenol with 3.6 mL of a 1:49 isoamyl alcohol:chloroform solution. The solution is shaken vigorously for about 10 seconds then cooled on ice for about 15 minutes.




(5) The solution is centrifuged for about 7 minutes at maximum speed. The upper (aqueous) phase is transferred to a new tube.




(6) The RNA is precipitated with about 10 μL glycogen and with 400 μL isopropanol for 30 minutes at −20° C.




(7) The RNA is pelleted by centrifugation for about 7 minutes in a benchtop centrifuge at maximum speed; the supernatant is decanted and discarded; and the pellet washed with approximately 500 μL of about 70 to 75% ethanol.




(8) The sample is centrifuged again for 7 minutes at maximum speed. The supernatant is decanted and the pellet air dried. The pellet is then dissolved in an appropriate buffer for further experiments (e.g., 50 pI. 5 mM Tris chloride, pH 8.0).




Example 2




mRNA Reverse Transcription and PCR




Reverse Transcription: RNA was isolated from microdissected or non-microdissected formalin fixed paraffin embedded (FPE) tissue as illustrated in Example 1, or from fresh or frozen tissue by a single step guanidinium isocyanate method using the QuickPrep™ Micro mRNA purification kit (Amersham Pharmacia Biotech Inc., Piscataway, N.J.) according to the manufacturer's instructions. After precipitation with ethanol and centrifugation, the RNA pellet was dissolved in 50 ul of 5 mM Tris/Cl at pH 8.0. M-MLV Reverse Transcriptase will extend an oligonucleotide primer hybridized to a single-stranded RNA or DNA template in the presence of deoxynucleotides, producing a complementary strand. The resulting RNA was reverse transcribed with random hexamers and M-MLV Reverse Transcriptase from Life Technologies. The reverse transcription was accomplished by mixing 25 μl of the RNA solution with 25.5 μl of “reverse transcription mix” (see below). The reaction was placed in a thermocycler for 8 min at 26° C. (for binding the random hexamers to RNA), 45 min at 42° C. (for the M-MLV reverse transcription enzymatic reaction) and 5 min at 95° C. (for heat inactivation of DNAse).




“Reverse transcription mix” consists of 10 ul 5× buffer (250 mM Tris-HCl, pH 8.3, 375 mM KCl, 15 mM MgCl2), 0.5 ul random hexamers (50 O.D. dissolved in 550 ul of 10 mM Tris-HCl pH 7.5) 5 ul 10 mM dNTPs (dATP, dGTP, dCTP and dTTP), 5 ul 0.1 M DTT, 1.25 ul BSA (3 mg/ml in 10 mM Tris-HCL, pH 7.5), 1.25 ul RNA Guard 24,800U/ml (RNAse inhibitor) (Porcine #27-0816, Amersham Pharmacia) and 2.5 ul MMLV 200U/ul (Life Tech Cat #28025-02).




Final concentrations of reaction components are: 50 mM Tris-HCl, pH 8.3, 75 mM KCl, 3 mM MgCl2, 1.0 mM dNTP, 1.0 mM DTT, 0.00375. mg/ml BSA, 0.62 U/ul RNA Guard and 10 U/ul MMLV.




PCR Quantification of mRNA expression. Quantification of EGFR cDNA and an internal control or house keeping gene (e.g., β-actin) cDNA was done using a fluorescence based real-time detection method (ABI PRISM 7700 or 7900 Sequence Detection System [TaqMan®], Applied Biosystems, Foster City, Calif.) as described by Heid et al., (Genome Res 1996;6:986-994); Gibson et al., (Genome Res 1996;6:995-1001). In brief, this method uses a dual labelled fluorogenic TaqMan® oligonucleotide probe, (EGFR-1773 (SEQ ID NO: 3), T


m


=70° C.; HER2-neu 2657 (SEQ ID NO: 6), β-actin-611 (SEQ ID NO: 7) that anneals specifically within the forward and reverse primers. Laser stimulation within the capped wells containing the reaction mixture causes emission of a 3′ quencher dye (TAMARA) until the probe is cleaved by the 5′ to 3′ nuclease activity of the DNA polymerase during PCR extension, causing release of a 5′ reporter dye (6FAM). Production of an amplicon thus causes emission of a fluorescent signal that is detected by the TaqMan®'s CCD (charge-coupled device) detection camera, and the amount of signal produced at a threshold cycle within the purely exponential phase of the PCR reaction reflects the starting copy number of the sequence of interest. Comparison of the starting copy number of the sequence of interest with the starting copy number of theinternal control gene provides a relative gene expression level. TaqMan® analyses yield levels that are expressed as ratios between two absolute measurements (gene of interest/internal control gene).




The PCR reaction mixture consisted 0.5 μl of the reverse transcription reaction containing the cDNA prepared as described above 600 nM of each oligonucleoride primers EGFR-1753F (SEQ ID NO: 1, T


m


=59° C.) and EGFR-1823R (SEQ ID NO: 2, T


m


=58° C.) or oligonucleotide primers HER2-neu 2671F (SEQ ID NO:4) and HER2-neu 2699R (SEQ ID NO: 5) 200 nM TaqMan® probe (SEQ ID NO:3 or SEQ ID NO: 6), 5 U AmpliTaq Gold Polymerase, 200 μM each dATP, dCTP, dGTP, 400 μM dTTP, 5.5 mM MgCl


2


, and 1× TaqMan® Buffer A containing a reference dye, to a final volume of less than or equal to 25 μl (all reagents Applied Biosystems, Foster City, Calif.). Cycling conditions were, 95° C. for 10 min, followed by 45 cycles at 95° C. for 15s and 60° C. for 1 min. Oligonucleotides used to quantify internal control gene β-Actin were β-Actin-592F (SEQ ID NO: 8) and β-Actin-651R (SEQ ID NO: 9).




Example 3




Determining the Uncorrected Gene Expression (UGE) for EGFR




Two pairs of parallel reactions are carried out. The “test” reactions and the “calibration” reactions. FIG.


7


. The EGFR amplification reaction and the β-actin internal control amplification reaction are the test reactions. Separate EGFR and β-actin amplification reactions are performed on the calibrator RNA template and are referred to as the calibration reactions. The TaqMan® instrument will yield four different cycle threshold (Ct) values: Ct


EGFR


and Ct


β-actin


from the test reactions and Ct


EGFR


and Ct


β-actin


from the calibration reactions. The differences in Ct values for the two reactions are determined according to the following equation:






Δ


Ct




test




=Ct




EGFR




−Ct




β-actin


(From the “test” reaction)








Δ


Ct




calibrator




=Ct




EGFR




−Ct




β-actin


(From the “calibration” reaction)






Next the step involves raising the number 2 to the negative ΔCt, according to the following equations.






2


−ΔCt




test


(From the “test” reaction)








2


−ΔCt




calibrator


(From the “calibration” reaction)






In order to then obtain an uncorrected gene expression for EGFR from the TaqMan® instrument the following calculation is carried out:






Uncorrected gene expression (


UGE


) for


EGFR


=2


−ΔCt




test


/2


−ΔCt




calibrator








Normalizing UGE with Known Relative EGFR Expression Levels




The normalization calculation entails a multiplication of the UGE with a correction factor (K


EGFR


) specific to EGFR and a particular calibrator RNA. A correction factor K


EGFR


can also be determined for any internal control gene and any accurately pre-quantified calibrator RNA. Preferably, the internal control gene β-actin and the accurately pre-quantified calibrator RNA, Human Liver Total RNA (Stratagene, Cat #735017), are used. Given these reagents correction factor K


EGFR


equals 1.54.




Normalization is accomplished using a modification of the ΔCt method described by Applied Biosystems, the TaqMan® manufacturer, in User Bulletin #2 and described above. To carry out this procedure, the UGE of 6 different FPE test tissues were analyzed for EGFR expression using the TaqMan® methodology described above. The internal control gene β-actin and the calibrator RNA, Human Liver Total RNA (Stratagene, Cat #735017) was used.




The already known relative EGFR expression level of each sample AG22 1, AG222, AG252, Adult Lung, PC3, AdCol was divided by its corresponding TaqMan® derived UGE to yield an unaveraged correction factor K.








K




unaveraged


=Known Values/


UGE








Next, all of the K values are averaged to determine a single K


EGFR


correction factor specific for EGFR, Stratgene Human Liver Total RNA (Stratagene, Cat #735017) from calibrator RNA and β-actin.




Therefore, to determine the Corrected Relative EGFR Expression in an unknown tissue sample on a scale that is consistent with pre-TaqMan® EGFR expression studies, one merely multiplies the uncorrected gene expression data (UGE) derived from the TaqMan® apparatus with the K


EGFR


specific correction factor, given the use of the same internal control gene and calibrator RNA.






Corrected Relative


EGFR


Expression=


UGE×K




EGFR








A K


EGFR


may be determined using any accurately pre-quantified calibrator RNA or internal control gene. Future sources of accurately pre-quantified RNA can be calibrated to samples with known relative EGFR expression levels as described in the method above or may now be calibrated against a previously calibrated calibrator RNA such as Human Liver Total RNA (Stratagene, Cat #735017) described above.




For example, if a subsequent K


EGFR


is determined for a different internal control gene and/or a different calibrator RNA, one must calibrate both the internal control gene and the calibrator RNA to tissue samples for which EGFR expression levels relative to that particular internal control gene have already been determined. Such a determination can be made using standard pre-TaqMan®, quantitative RT-PCR techniques well known in the art. The known expression levels for these samples will be divided by their corresponding UGE levels to determine a K for that sample. K values are then averaged depending on the number of known samples to determine a new K


EGFR


specific to the different internal control gene and/or calibrator RNA.




Example 4




Determining the Uncorrected Gene Expression (UGE) for HER2-neu




Two pairs of parallel reactions are carried out. The “test” reactions and the “calibration” reactions. FIG.


8


. The HER2-neu amplification reaction and the β-actin internal control amplification reaction are the test reactions. Separate HER2-neu and β-actin amplification reactions are performed on the calibrator RNA template and are referred to as the calibration reactions. The TaqMan® instrument will yield four different cycle threshold (Ct) values: Ct


HER2-neu


and Ct


β-actin


from the test reactions and Ct


Her2-neu


and Ct


β-actin


from the calibration reactions. The differences in Ct values for the two reactions are determined according to the following equation:






Δ


Ct




test




=Ct




HER2-neu




−Ct




β-actin


(From the “test” reaction)








Δ


Ct




calibrator




=Ct




Her2-neu




−Ct




β-actin


(From the “calibration” reaction)






Next the step involves raising the number 2 to the negative ΔCt, according to the following equations.






2


−ΔCt




test


(From the “test” reaction)








2


−ΔCt




calibrator


(From the “calibration” reaction)






In order to then obtain an uncorrected gene expression for HER2-neu from the TaqMan® instrument the following calculation is carried out:






Uncorrected gene expression (


UGE


) for


HER


2-


neu


=2


−ΔCt




test


/2


−ΔCt




calibrator








Normalizing UGE with Known Relative HER2-neu Expression Levels




The normalization calculation entails a multiplication of the UGE with a correction factor (K


HER2-neu


) specific to HER2-neu and a particular calibrator RNA. A correction factor K


HER2-neu


can also be determined for any internal control gene and any accurately pre-quantified calibrator RNA. Preferably, the internal control gene β-actin and the accurately pre-quantified calibrator RNA, Human Liver Total RNA (Stratagene, Cat #735017) are used. Using β-actin and the accurately pre-quantified calibrator RNA, Human Liver Total RNA (Stratagene, Cat #735017) the correction factor K


HER2-neu


equals 12.6×10


−3


.




Normalization is accomplished using a modification of the ΔCt method described by Applied Biosystems, the TaqMan® manufacturer, in User Bulletin #2 and described above. To carry out this procedure, the UGE of 6 different FPE test tissues were analyzed for HER2-neu expression using the TaqMan® methodology described above. The internal control gene β-actin and the calibrator RNA, Human Liver Total RNA (Stratagene, Cat #735017) was used.




The already known relative HER2-neu expression level of each sample AG221, AG222, AG252, Adult Lung, PC3, AdCol is divided by its corresponding TaqMan® derived UGE to yield an unaveraged correction factor K.








K




unaveraged


=Known Values/


UGE








Next, all of the K values are averaged to determine a single K


EGFR


correction factor specific for HER2-neu, Human Liver Total RNA (Stratagene, Cat #735017) calibrator, and β-actin.




Therefore, to determine the Corrected Relative HER2-neu Expression in an unknown tissue sample on a scale that is consistent with pre-TaqMan® HER2-neu expression studies, one merely multiplies the uncorrected gene expression data (UGE) derived from the TaqMan® apparatus with the K


HER2-neu


specific correction factor, given the use of the same internal control gene and calibrator RNA.






Corrected Relative


HER


2-


neu


Expression=


UGE×K




HER2-neu








A K


HER2-neu


may be determined using any accurately pre-quantified calibrator RNA or internal control gene. Future sources of accurately pre-quantified RNA can be calibrated to samples with known relative EGFR expression levels as described in the method above or may now be calibrated against a previously calibrated calibrator RNA such as Human Liver Total RNA (Stratagene, Cat #735017) described above.




For example, if a subsequent K


HER2-neu


is determined for a different internal control gene and/or a different calibrator RNA, one should calibrate both the internal control gene and the calibrator RNA to tissue samples for which HER2-neu expression levels relative to that particular internal control gene have already been determined or published. Such a determination can be made using standard pre-TaqMan®, quantitative RT-PCR techniques well known in the art. The known expression levels for these samples will be divided by their corresponding UGE levels to determine a K for that sample. K values are then averaged depending on the number of known samples to determine a new K


HER2-neu


specific to the different internal control gene and/or calibrator RNA.




Example 5




Patient Population and Tissue Acquisition




Patients. Eighty-three patients suffering from NSCLC consisting of sixty-five (78.3%) men and 18 (21.7%) women, with a median age of 63.5 years (range, 34-82) were studied. Thirty-nine (47%) patients had squamous cell carcinomas, 32 (38.6%) had adenocarcinoma, and 12 (14.5%) had large cell carcinomas. The primary tumors were graded histopathologically as well-differentiated (G1, one patient), moderately-differentiated (G2, 18 patients), and poorly-differentiated (G3, 64 patients). Tumor staging was performed according to the International Union Against Cancer (UICC) TNM classification: Forty-one (49.4%) had stage I tumors, 16 (19.3%) had stage II tumors, and 26 (31.3%) had stage IIIa tumors. All tumors were completely resected (R0 category), by at least a lobectomy as quality control. Patients with histopathological stage IIIa tumors received postoperative radiotherapy. The median follow-up was 85.9 months (min. 63.3; mar. 105.2 months) and no patient was lost to follow-up




Tissue Acquisition. Tissue for gene expression analysis was obtained immediately after lung resection before starting mediastinal lymphadenectomy and was immediately frozen in liquid nitrogen. Tissues were analyzed from the following 2 locations: tumor and uninvolved lung tissue taken from the greatest distance to the tumor. 6 μm frozen sections were taken from blocks of tumor tissue and starting with the first section every fifth was routinely stained with HE and histopathologically evaluated. Sections were pooled for analysis from areas of estimated 75% malignant cells. RNA was isolated from tissue samples according to the methods in Example 2.




Example 6




Statistical Analysis




TaqMan® analyses yield values that are expressed as UGE. The ratio between UGE in tumor tissue and UGE in matching non-malignant lung tissue was used to determine differential gene expression. Associations between the two UGE variables were tested by using Wilcox on signed rank test. The Chi-Square test was used to analyze the associations between categorial clinicopathological variables. Hazards ratios were used to calculate the relative risks of death. These calculations were based on the Pike estimate, with the use of the observed and expected number of events as calculated in the log-rank test statistic. Pike, J R Stat Soc Series A 135:201-203; 1972. The maximal chi-square method of Miller and Sigmund (Miller et al., Biometrics 38:1011-1016, 1982) and Halpern (Biometrics 38:1017-1023, 1982) was adapted to determine which expression value best segregated patients into poor- and good prognosis subgroups (in terms of likelihood of surviving), with the log-rank test as the statistics used to measure the strength of the grouping. To determine a P value that would be interpreted as a measure of the strength of the association based on the maximal chi-square analysis, 1000 boot-strap-like simulations were used to estimate the distribution of the maximal chi-square statistics under the hypothesis of no association. Halpern, Biometrics 38:1017-1023, 1982. Cox's proportional hazards modeling of factors that were significant in anivariate analysis was performed to identify which factors might have a significant influence on survival. The level of significance was set to p<0.05.




HER2-neu mRNA expression was detectable by quantitative real-time RT-PCR in 83 of 83 (100%) normal lung and 83 of 83 (100%) tumor samples. The corrected HER2-neu mRNA expression, expressed as the ratio between HER2-neu and P-Actin PCR product, was 4.17×10


−3


(range 0.28-23.86×10


−3


) in normal lung and 4.35×


10




−3


(range: 0.21-68.11×10


−3


) in tumor tissue (P=0.019 Wilcoxon test). The maximal chi-square method by Miller and Siegmund (Miller et al., Biometrics 38:1011-1016, 1982) and Halpern (Biometrics 38:1017-1023, 1982) determined a threshold value of 1.8 to segregate patients into low and high differential HER2-neu expressors. By this criterion, 29 (34.9%) patients had a high differential HER2-neu expression and 54 (65.1%) had a low differential HER2-neu expression.

FIG. 4

shows associations between clinicopathological data and differential HER2-neu gene expression status. There were no statistically significant differences detectable.

FIG. 1

displays a Kaplan Meier plot of the estimated probability of survival versus the differential HER2-neu mRNA expression status. The median survival was not reached in the low differential HER2-neu expression group compared to 31.1 months (95% C.I.: 21.96-40.24) in the high differential HER2-neu expression group. To determine a P value, bootstrap-like simulations were used to estimate the distribution of a maximal chi-square statistic, since the threshold value of 1.8 had been chosen after examining the data. The resulting adjusted P value was 0.004 (Log-rank test).




The accuracy of HER2-neu as a prognostic factor was next determined by the Cox's proportional hazards model analysis. In univariate analysis of potential prognostic factors, high differential HER2-neu expression as well as advanced pT (tumor stage) classification, pN (lymph node stage) classification, and tumor stage were significant unfavorable prognostic factors (FIG.


5


). In a multivariate analysis of prognostic factors (FIG.


6


), high differential HER2-neu expression was a significant and independent unfavorable prognostic factor, as well as advanced pN classification and tumor stage.




EGFR mRNA expression was detectable by quantitative real-time RT-PCR in 83 of 83 (100%) normal lung and 83 of 83 (100%) tumor samples. The median corrected EGFR mRNA expression was 8.17×10


−3


(range: 0.31-46.26×10


−3


) in normal lung and 7.22×10


−3


(range: 0.27-97.49×10


−1


) in tumor tissue (P=n.s.). The maximal chi-square method (Miller (1982); Halpern (1982)) determined a threshold value of 1.8 to segregate patients into low and high differential EGFR expressors. By this criterion, 28 (33.7%) patients had a high differential EGFR expression and 55 (66.3%) had a low differential EGFR expression status. There were no statistical significant differences between clinicopathological variables and differential EGFR mRNA expression status detectable (FIG.


4


). A trend towards inferior overall survival was observable for the high differential EGFR expression group, but did not reach statistical significance (FIG.


2


). The median survival was not reached in the low differential EGFR expression group compared to 32.37 months (95% C.I.: 8.43-56.31) in the high differential EGFR expressor group (P=0.176).




High expression levels (above 1.8) of differential HER2-neu and EGFR were found in 14 of 83 (16.9%) patients. Forty of 83 (48.2%) patients showed a low differential expression status (below 1.8) for HER2-neu and EGFR, whereas 14 of 83 (16.9%) showed a high differential expression for EGFR only, and 15 of 83 (18.1%) patients displayed a high differential expression for HER2-neu. The median survival was not reached in the group that showed low differential HER2-neu and EGFR expression, compared to 45.47 months in the high differential EGFR expression group, 31.10 months (95% C.I.: 14.77-47.43) in the high differential HER2-neu expression group, and 22.03 months (95% C.I: 2.30; 41.76; P=0.003; log-rank test;

FIGS. 3 and 5

) in the high differential HER2-neu and EGFR expression group. Univariate analysis displayed high differential HER2-neu and EGFR coexpression as a significant unfavorable prognostic factor (FIG.


5


). In a multivariate analysis of prognostic factors (FIG.


6


), high differential HER2-neu and high differential EGFR coexpression was a significant and independent unfavorable prognostic factor, as was advanced pN classification and tumor stage.




Example 7




Tumor Response to a Receptor Tyrosine Kinase Targeted Chemotherapy




Five colon cancer patients' tumors were initially identified as expressing EGFR by immunohistochemistry. Patients were treated with Imclone IMC-C225, 400 mg/m


2


loading dose followed by 250 mg/m


2


weekly, plus CPT-11 at the same dose and schedule that the patient had previously progressed on. Previous CPT-11 dose attenuations were maintained.




Using the methodology described in Examples 1-4, Patient 1 was determined to have a corrected EGFR expression level of 2.08×10


−3


and had a completed response (CR) to a a receptor tyrosine kinase targeted chemotherapy comprising CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carboxycamptothecin)/C225 (an anti-EGFR monoclonal antibody effective in anti-cancer therapy; Mendelsohn, Endocr Relat Cancer March 2001 ;8(1):3-9). Patient 2 had a corrected EGFR expression level of 8.04×10


−3


and had a partial response (PR) to the receptor tyrosine kinase targeted chemotherapy. Patient 3 had a corrected EGFR expression level of 1.47×10


−3


and also showed a partial response (PR) to the receptor tyrosine kinase targeted chemotherapy. Patient 4 had a corrected EGFR expression level of 0.16×10


−3


and had stable disease (SD) showing no response to the receptor tyrosine kinase targeted chemotherapy. Patient 5 had a no EGFR expression (0.0×10


−3


) and had progressive disease (PR) showing no response to the receptor tyrosine kinase targeted chemotherapy. See FIG.


9


.

















                  






#             SEQUENCE LISTING




















<160> NUMBER OF SEQ ID NOS: 11













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ggctcaccct ccagaagctt            






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acgcattccc tgcctcggct g           






#                  






#                  






#21




















<210> SEQ ID NO 4






<211> LENGTH: 23






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<213> ORGANISM: Artificial Sequence






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ctgaactggt gtatgcagat tgc           






#                  






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<210> SEQ ID NO 5






<211> LENGTH: 17






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<213> ORGANISM: Artificial Sequence






<220> FEATURE:






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ttccgagcgg ccaagtc             






#                  






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<210> SEQ ID NO 6






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tgtgtacgag ccgcacatcc tcca          






#                  






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accaccacgg ccgagcgg             






#                  






#                  






#  18




















<210> SEQ ID NO 8






<211> LENGTH: 18






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<213> ORGANISM: Artificial Sequence






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tgagcgcggc tacagctt             






#                  






#                  






#  18




















<210> SEQ ID NO 9






<211> LENGTH: 22






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<213> ORGANISM: Artificial Sequence






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tccttaatgt cacgcacgat tt           






#                  






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<210> SEQ ID NO 10






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<400> SEQUENCE: 10













ttctttttag cacagaataa caatccattg tccacatgta ccatggttta tt






#tatccact     60













catccacatg aagacatctt agttgattct aagttaggga agttatgaat aa






#agctgtta    120













taaatattca tgagcagatt tatgtggaca acagtgttca actcatttgg gt






#aagtatca    180













aggagagaaa tcattggatc atatggtaag agtatgtaca cttttatagg aa






#actgctaa    240













gctgcattcc taagtggctg taccattgtg ccttcccatc agcaatgaat ga






#gacttcct    300













attgttccac atcctcatca gaatttggtg ttgtcactga tctgaatttt tt






#ccattgta    360













acagatgtgt agtggtatct cactgttgtt ttaatttgca atttcctaat ga






#catatgat    420













gttgaacatc tttttatatg cttacttgcc atcagtgtat cctctgatga gg






#tgtttgtg    480













tagggctttg gcccattttt aaatcaggtt atttatcctc ttattattaa ct






#tttaagag    540













tttagttctt tgcatatttt ggataacaat cctttatcac atatttcttt tg






#caaatttt    600













tctccagtat atggcttgtc ttcttctcct ggcattgtcc ttctcagagc ag






#aagttttt    660













aattttaata aactccagct tataaattat ttatttcatg gattgtgcct tt






#ggttttgt    720













acttaaaaag tcattgtcat acctaaggtc atctaggttt tctcctacgt ta






#tctcctag    780













gtgttttata gttttgcatt ttacatttat atgtatgatc agttttgagt ta






#atttttat    840













gaagtgtgta aggtttgtat ctacattcat tttttgcatg tggatgtcca tt






#tgttccag    900













caatatttgt tgaaaagact atacttgctc tattgtattg tgtttctttt tt






#gtcaaaga    960













tcaattgact aaatttatgt gcgtcagttt ctgatctctc tggtccattg at






#atatttgt   1020













ctattctttc accaatacca catagtctag actactgtag ttgtatatgt ct






#tgaagtca   1080













ggtagtgttg atcctccaat tttgttctcc aatattgagt tggctattgt gg






#gtcttttg   1140













cttgcccata gaatcaatta gtcaatattt acaaaataac ttgctcgaac tt






#tgactggg   1200













attaatctat aaatcaagtt gggaataagt gacattttga cattatggag tc






#tttctgac   1260













catgaacaca aactattgat ccatttattt agttatttga tatctttcac ca






#gagttttt   1320













ttgttttttt cttatagatc ttatacatat tttcttatat tcatacctca gt






#attccatt   1380













tcagggtgtt aatgtaaatg gtaatgtgtt tttaatttca aattccctta gt






#tctttgct   1440













ggtatatagg aaagtgattg gcttttgtat gttaacgttg tatcctgctc ac






#ttgctata   1500













actgcttatt agttccagga gcttttttat tgtttctttt ggattttcta ag






#agacaatt   1560













acattatcag tgaacaaaca cgatttattt cttccctccc aatcagtatt ca






#ttttattt   1620













atttattgtg tgttattgca ttagctagga cttctaatac aatgttgaaa ag






#cattggtg   1680













aaaggaaaca tccttgcttt gttcctgatt ttagctatag gtttttgtag ct






#gttcttta   1740













ttaagttgag gatatccttc tctattctta gtttgctgag aatttttatc at






#gaataggt   1800













gtaggatttt gcctaatgtt ttcttctgta tctattgata tgatcatgta at






#ttttcttt   1860













atctattgat atgatctgtt gatgtgatga actacattaa ttgagttttc aa






#atgttgaa   1920













ccagtcttgc atatctggaa taaatcggag ttggtcatca tgtataactt tg






#ttacactt   1980













tgttgcattt gattttgtaa tattttcttg agaattttta catctatgtt ca






#taaaagat   2040













atcggtctac agttttcttt cctttcttgt aatatctctg tctggttttg ct






#attaaggt   2100













aattctggct tcacaaaatt aattatggag tcttccctct acttctagtt tc






#tggaagag   2160













attgtagaga atggatgtaa tttctttctt aaatgtttga cgaaaatcag ca






#ctgatctc   2220













atctgggctt ggtgctttct gttttggaag gttattaatt atttattcaa tt






#tctatagt   2280













ggatataggc ctatattgat tggcaatttc ttcttgtatg acttttggta ca






#ttctattt   2340













caaggaattg gttcatttca tgtaggttgt taaattcgtg ggtatagctg tt






#cataatat   2400













tcatttatta tcctttcaat gttcatgaga tcagtagtga tgttccttct tt






#catttctg   2460













atattcataa tttgtgtatt ctctctttgt ttcttagcct ggtgagaggc tt






#ataaattt   2520













tattgatttt ttgaagaatc actttttggt tttgctgatt ttcttgctgg ga






#ttataggc   2580













gtgagccacc acactcttgc tcattttttc tatttttgtt ttccacactt tt






#tctgcctc   2640













tgtggatttt acacagcatt ttgtataatt cgatttcctc tttttagcat ag






#caattatt   2700













ttagtcttta actttttaaa atcagttgcc ctagattttt ttctcccaac at






#tttgggag   2760













gccaagggga gaggatcact tcaagccagg agtttgagac cagcctgagc aa






#catagcaa   2820













ggcactatct atacaaacat aattttaaaa agtccaggca ttagctagga ct






#gtgcctgt   2880













agtcccagct actcaggagg ctgagatgag aagatcaccg gagcctagaa at






#ttgaggct   2940













gcagtgggct gtgatcatgt cacttcactc ctgcctagaa gacagttaga cc






#ctgcctct   3000













aaaataaaca agcaaataaa taaaaagaaa ggaagaaaag aagagcaagg gc






#agcaaata   3060













gaaaatagta ataaatatgg tagctattaa tccaactatg tcaataatta cc






#ttaaatgt   3120













tagtggtcta aatatactgc aatggactga atgtttatgt ctcctcaaaa tg






#tatatgat   3180













gaaatgtaag ctcccaaaat gatgttatca ggggagagtg tttttgggag gg






#gattatgt   3240













catgagggtg gaggccttac aaatggggtt agtgctataa aagagaccac ag






#agagctgc   3300













cttggtcctt ctgccatgtg agggcactgt gaaattatgg ccatctatga ag






#aagtgggc   3360













ccttattaga catcaaatct gcaaatacct tgatcttgaa tttcccagcc tc






#cagaacta   3420













tgggaaataa atttctgttg tttacaagta aatcatttta tgttattttg tt






#acagaagc   3480













ccaaaaagat gaagacatac accagatcac tccattctct tcttgcttgc at






#ggtttctg   3540













aggatacgtt ggatgtaatt ctaatattct ctataggtat tttctttatg gc






#tcctctac   3600













aggtaaggtg ttttttccct ttggcttcat ttaagaattt ttcgttaacc tt






#tgattttc   3660













tgaagtgtga atatgttatg cctaggtatc atttgtttgt ttgggttttc tt






#ggcatata   3720













tcttcctgat gttctctgaa cttccagaat ctgtgatttg ttgtctgaca tt






#aatttgga   3780













ggaatttttg gtattattgc tttaaatatt gcttctgctc ctttttctct tt






#ctttgact   3840













tacagtattc ccattacatg taattatctc acagttcttg aaagttttgt tt






#tgttcttt   3900













ttgttagtcg tttttctttc tgtttttcag ttttggcagt ttctgtttac gt






#atcttcaa   3960













tctcagaaat tctttcctca agcatgttca gcccactaat gtgtacttca aa






#agtattct   4020













acatttcttt tacagtgttt ttgatctcta gaatttttaa attctttctt aa






#aactttca   4080













tctctcagga attcaagact agcctgggca acatagtgaa actctatctc ta






#caaaacat   4140













tagccaggta tggtgatgca tgcctgtagt cagagctact caggaggcta ag






#gtgggagg   4200













atcacctgag cctgggaagt tgaggttgca gtgagccaag gtcacgccac tg






#cactctgg   4260













attgggcaac agagccagac cctgtctcaa aaaaaagaaa aattccatgg ct






#ctgcttac   4320













attatccatc tgatcttaca tgttgcctat tttttccatt aaaactccta gc






#ctattaat   4380













catagttttt ttataattaa tactccgatg tgataatgtc ttagtccaat ta






#ctgtggtt   4440













ataacagaat gccacaaact gggtgattta taaacaaaag aagctgattt ag






#gctgattt   4500













agaggctggg gagtccaaga gcttggtgct agcatctgat gagtgtcttc tt






#gcttcatc   4560













ataacatggg agagggcatc acgtgtgaag agagcttact cttataacat ag






#ccactccc   4620













acaagaatta acccaccgcc atgagagcca tgtgaattca ttcatgagga ca






#gcgggtta   4680













agtttccaat atatggactt ttcggggaca cattcaaacc acagcagtta gt






#tgtaacgt   4740













tcgtgtcatg tctcattctg gttctgatgc ttgtgcagtc tcttcaaact gc






#gtctttgc   4800













cttttagtgt gccttgcaat gtggaaatga tatactgggt aagaggagct gt






#agtaaaga   4860













ggcttctagt gacgtagtga caagctgtgg ggagagggag tgttgcacag tc






#ctgccgca   4920













tgtcacagtc ttccagtgag cctgtgtccc tggactgtga acttcatgct tg






#cttctcag   4980













cttccccagc cccttagatg gtacagaact gttggagggg ggtggagttg ta






#tatttccc   5040













ttgctctggg taggtcaccc tctgataaaa caccaggtta ggcctctggt ga






#aataattt   5100













ctcctgaggg cagaccttct attaataata gaatgttcca acctatttca aa






#atggttcc   5160













tcttctcctt ccactgccag aagcataatg agattttccc cctaatattc gt






#ggtaagga   5220













cctagcagag ctccaggagg taacactctc aagtgtctca tactaccctg ca






#ccatgact   5280













gggctctgct ggagttctta atttgcagaa ctgcccacac tgagcctccc gc






#aatttctc   5340













aattacaggg caaactttcc cagccggcac tgggtccttg gaggtttctg tc






#tgctggtt   5400













tcttcctctg gaggttgtgc ttctgtgttt gcctgtctct ccaatttggg gg






#gcagtggt   5460













ttgcccaatg acctcaattc tctgaaagag ctaagaagag gtgttaattt tt






#cggtttgc   5520













tcagctttct acttgttgct agaatggagc gccaatagtg cctcctatag tg






#acatgtaa   5580













ccctcaactc tagagatgat gaagcatact aatgacaaag gagaaatgct tc






#agcagttt   5640













tctgtcagca cattacccct tgaaaaagct gcttcttcca cattctgcaa ga






#gatgggtc   5700













tcaactcaga gctcaaggca aatgacttcc ttcaaggaga aggaataaac ag






#tctcagaa   5760













accatgaaag cctgccccca ggagtgtccc tgaacctcag caggggccac ac






#ttaccttg   5820













cagaaatagg tgaggcatgc tcctggtaca aaatcccaat ggtacagaag ga






#caaattga   5880













aaaacaagtc tccctctaaa cccctgaccc cgagctacct agttctcctc cc






#tagaggca   5940













aagctgttac cagattcttg tatctcctta acatatatcc ttagaagagc tg






#tcaagtga   6000













acacatgttt aagtgaaaac ctattttaga agtgcatttt cttaaggaac tt






#tagggttg   6060













gaaggaacct gtgtcagtcc ttaattcaca acctccatta gtacttattg tt






#cttgcaca   6120













aaaatctttc tcaaaaaagc cctttccact ctgacatagc ttattctact tt






#tacttagc   6180













tccaataact tataaaacat atttttgaaa gtctaaaatc tgccactatg tt






#tttttttc   6240













ctaatcaatc tttactttga cctctaagcc agagaaaaca ggtggtcaaa tg






#ccttttgc   6300













ctaagatgga acttagaata tttgaagacc tcagatcttc accctgccaa at






#aacgtgtt   6360













tctcctcccc tttcacagag catttggttt taggaaattc agagccacat tc






#cttataga   6420













caagactaaa ctcttattca acatactcag aaacttcttc taagaggata ac






#cactcatc   6480













agaggaaaaa agtttctcat gtacagctgg caaagggatg gaaccatctg tg






#ttattaaa   6540













attgacagac gcttatgaga tttattaagg gaaatactag agtcttagta ca






#tacttgct   6600













aatatagcat acatgaaggc tttatctata atttttttgg ccaagcagaa at






#tttggtat   6660













tactcaccct aacaaatttc caagacatta tgaaatagaa ttttaggtcc tg






#acatcacc   6720













atttgtctca ggttttgaag cgttgctgga caagaggggt aaaacacggc tc






#tgccttgg   6780













attcaaagtt ggcctctcat actagcaagt ataccttggt atcctggtca ct






#tctcccgg   6840













ccacagcatc acattgctat aaaaggcaga tacaagtatt aaccagctca ca






#ggttatca   6900













gataagctta gtctgaccaa tgcttaacac agcaactggg ccactattgt ca






#ttcctgtg   6960













gtggtggcac acacacccag cctctgtccg ggccatggtc taggaccacc ct






#ccacagag   7020













gctgtgagct agagccctaa ctgtgcaggg ccctaactat gccaggctac tt






#atctctct   7080













taagaggact tcattagtgc ctgctcggcc atacagtttt ttacttacca ag






#taacacag   7140













ttatcagcac actccaggta ctagccaagg actacaaaat caacgtgaat gt






#cagctttt   7200













gtatcaaaag ctcaaaggag aaactcaaac tttacataga tgtcccatga ag






#atgttcag   7260













caaacccatt cttctctgtt ccctggaatc catcccagta ttgtgctatg tg






#tgtgtcta   7320













gtaattcttt acaaaaagct ctgtttcttg tgatgctatc agatcacatt ga






#agaatata   7380













caagccgtac tatgaaggct gttgtctcat atagtcctaa cgtagtgaga ac






#tgatgttc   7440













ttacatgctg tctttttggg cactcaaaga aattcctgta cagtcttaca aa






#tcagttgt   7500













agcttaaatt gatttgtgtt gtgacttgta cacacaggtc acattccctt ga






#cagaaaat   7560













atagtttaaa accaaatttg cagcccttgt taagtgaatg cacaggactt ta






#ttgtattc   7620













aggtctttta ttgtaagact cactcctgtc ttcattttat gttccactgt tg






#tgcttccc   7680













atttgccttt ctctagtttt gttttctgtg tttctacgga ctgctctcag cc






#caggtgtg   7740













caggaagcac acacatgcct gcagagcctt catggcctct gcattcaggg ca






#tgacttca   7800













acgcacagtg gctgtactga tttgttaaaa caaaggaaca gattacttct cc






#taattcac   7860













agggaagttc caggttgtgc gggcagtgag cagacctgtg tctgtctgcg ct






#tgccctgg   7920













tgaaaaaccc caccgttcag gctgcagggt gcgagaccca ggcacaaaca tt






#ttgctgga   7980













tgaggaggaa agatgtaagg ttgctcccct tcagagacag caaagggcag gt






#ctgtagct   8040













tcacttactt caggattgtg atttttgaca gagccgagag atcagggttg tt






#gaaccagg   8100













cctgaaggtc ctagtgaatc tcgtgaagag aggaggggtc tggctgtaac at






#ggacctag   8160













aggacatttt tactgcagga gaaggaacag tggggatggg gtggacttgc ca






#aaggaata   8220













tagctcaagt tcctgcagcc caaaaaagct cagtttcttt tggccaaagc tt






#ccgcgagt   8280













ttccctggca tttctcctgc gggagctaca ggggcagtgg gacacttagc ct






#ctctaaaa   8340













gcacctccac ggctgtttgt gtcaagcctt tattccaaga gcttcacttt tg






#cgaagtaa   8400













tgtgcttcac acattggctt caaagtaccc atggctggtt gcaataaaca tt






#aaggaggc   8460













ctgtctctgc acccggagtt gggtgccctc atttcagatg atttcgaggg tg






#cttgacaa   8520













gatctgaagg accctcggac tttagagcac cacctcggac gcctggcacc cc






#tgccgcgc   8580













gggcacggcg acctcctcag ctgccaggcc agcctctgat ccccgagagg gt






#cccgtagt   8640













gctgcagggg aggtggggac ccgaataaag gagcagtttc cccgtcggtg cc






#attatccg   8700













acgctggctc taaggctcgg ccagtctgtc taaagctggt acaagtttgc tt






#tgtaaaac   8760













aaaagaaggg aaagggggaa ggggaccctg gcacagattt ggctcgacct gg






#acataggc   8820













tgggcctgca agtccgcggg gaccgggtcc agaggggcag tgctgggaac gc






#ccctctcg   8880













gaaattaact cctcagggca cccgctcccc tcccatgcgc cgccccactc cc






#gccggaga   8940













ctaggtcccg cgggggccac cgctgtccac cgcctccggc ggccgctggc ct






#tgggtccc   9000













cgctgctggt tctcctccct cctcctcgca ttctcctcct cctctgctcc tc






#ccgatccc   9060













tcctccgccg cctggtccct cctcctcccg ccctgcctcc ccgcgcctcg gc






#ccgcgcga   9120













gctagacgtc cgggcagccc ccggcgcagc gcggccgcag cagcctccgc cc






#cccgcacg   9180













gtgtgagcgc ccgacgcggc cgaggcggcc ggagtcccga gctagccccg gc






#ggccgccg   9240













ccgcccagac cggacgacag gccacctcgt cggcgtccgc ccgagtcccc gc






#ctcgccgc   9300













caacgccaca accaccgcgc acggccccct gactccgtcc agtattgatc gg






#gagagccg   9360













gagcgagctc ttcggggagc agcgatgcga ccctccggga cggccggggc ag






#cgctcctg   9420













gcgctgctgg ctgcgctctg cccggcgagt cgggctctgg aggaaaagaa ag






#gtaagggc   9480













gtgtctcgcc ggctcccgcg ccgcccccgg atcgcgcccc ggaccccgca gc






#ccgcccaa   9540













ccgcgcaccg gcgcaccggc tcggcgcccg cgcccccgcc cgtcctttcc tg






#tttccttg   9600













agatcagctg cgccgccgac cgggaccgcg ggaggaacgg gacgtttcgt tc






#ttcggccg   9660













ggagagtctg gggcgggcgg aggaggagac gcgtgggaca ccgggctgca gg






#ccaggcgg   9720













ggaacggccg ccgggacctc cggcgccccg aaccgctccc aactttcttc cc






#tcactttc   9780













cccgcccagc tgcgcaggat cggcgtcagt gggcgaaagc cgggtgctgg tg






#ggcgcctg   9840













gggccggggt cccgcacgtg cgccccgcgc tgtcttccca gggcgcgacg gg






#gtcctggc   9900













gcgcacccga ggggcgggcg ctgcccaccc gccgagactg cactgtttag gg






#aagctgag   9960













gaaggaaccc aaaaatacag cctcccctcg gaccccgcgg gacaggcggc tt






#tctgagag  10020













gacctccccg cctccgccct ccgcgcaggt ctcaaactga agccggcgcc cg






#ccagcctg  10080













gccccggccc ctctccaggt ccccgcgatc ctcgttcccc agtgtggagt cg






#cagcctcg  10140













acctgggagc tgggagaact cgtctaccac cacctgcggc tcccggggag gg






#gtggtgct  10200













ggcggcggtt agtttcctcg ttggcaaaag gcaggtgggg tccgacccgc cc






#cttgggcg  10260













cagaccccgg ccgctcgcct cgcccggtgc gccctcgtct tgcctatcca ag






#agtgcccc  10320













ccacctcccg gggaccccag ctccctcctg ggcgcccgcg ccgaaagccc ca






#ggctctcc  10380













ttcgatggcc gcctcgcgga gacgtccggg tctgctccac ctgcagccct tc






#ggtcgcgc  10440













ctgggcttcg cggtggagcg ggacgcggct gtccggccac tgcagggggg ga






#tcgcggga  10500













ctcttgagcg gaagccccgg aagcagagct catcctggcc aacaccatgg tg






#tttcaaaa  10560













tggggctcac agcaaacttc tcctcaaaac ccggagactt tctttcttgg at






#gtctcttt  10620













ttgctgtttg aagaatttga gccaaccaaa atattaaacc tgtcttacac ac






#acacacac  10680













acacacacac acacacacac cggattgctg tccctggttc aagtgtgcca ag






#tgtgcaga  10740













cagaacatga gcgagtctgg cttcgtgact accgaccata aacccacttg ac






#aggggaaa  10800













catgccttgg aaggtttaat tgcacaattc caaccttgag ctgcgcgggt tc






#caagagcc  10860













aggcccgtac ttgctgttga tgtcattggc ttggggagtt ggggtttggt gc






#ccagcgcg  10920













gtcgttgggg gaggggcaag gcatagaaca gtggttccca gaccttgctg ca






#cattggaa  10980













ttacctggga ttaaaaaaaa aaaaatcaaa acaaaaacca gtgtctggct cc






#cgccccca  11040













gacattctga tttaattggc atggggcaag acctggactt gggatttttt tt






#aatgctct  11100













tcatgtgatc tgttgggcag ccagatttgg ggatcactag acggaagaag ga






#ttgttaaa  11160













gtctccggag atgttacttg ccaatgctaa gagctctttg aggacatctg ga






#attgttac  11220













aatattgcca aatataggaa agagggaaaa ggtagagtgt gattccaata at






#aaaggatt  11280













ccgcttttca ttgaaggaac tggtggaaag gtttcttctc tgctgagcct gc






#aggcccgt  11340













cctgcctgcc tggggtgccc gggagacgcg ggcctgctcc ggagactgct ga






#ctgccggt  11400













cctgttagtc aggtgtcagc cctgtctctg ccgaagagac tcttctcttt at






#tttaaatt  11460













aaaccctcag agcaccacca aagcatcact tttctccctc cattggtgtt ct






#cattcttt  11520













gatgttactt gtttgaacac cactattagt agttggagat ttgttcctga ga






#aaaatata  11580













aataccactt aatttgcctg tttgtcccgc attcactcaa aacagaatgc tc






#ctgaagac  11640













aagagagaga gtaggagaac agacgctatt ccattacagt aacataaaag ac






#tggatttt  11700













caggggcaaa ttattaaaat aggagatgag ctcttttaac agaaatttgt tt






#aaggcctg  11760













tgtctatcaa attcagtgga ttttattcaa gatgcacttt gtttagtggg ag






#ttttgttt  11820













ggttctggga catgctaact tctagacttg ctgctcttag aggtaatgac tg






#ccagacac  11880













catttcatga gtcctaatcc ccacattaag cataagaggt gcacactctc ct






#cctatggg  11940













ggaaactgag gtacgaagaa ctaaagtgac tttcccacag ctggtgggag gc






#agacggga  12000













aattcacacc aggggcttcc aactccagat ccctctctca acttccaaac tc






#cactgcct  12060













tgtccgagtt ctggtttcag gagatccaaa tcaggtgtgt gcaaatgtct aa






#tgtcagag  12120













ctggcaaggg gaaagggccc agggagccgg ctcatgacga tgagcctgtc tg






#aagcttca  12180













acgcgggctg tccggcagtc tgcattcctg ccgagttcct cagccctctg tt






#gggtcacc  12240













ttccatagag gcagcttagt cctcagttca gtgagcatgg agtggagact gc






#ttgagggg  12300













tgctgagcaa agccctgcct cttacaggat gaaggtgctc tccagaaggg ac






#actggaaa  12360













gtattccaag gcgagtcgaa ttcccaactg agggagcttt gtggaaataa gc






#ccgcccag  12420













ccccacttct ggagacgttc ccattcagta ggtccgagct gtcttaaaga ga






#aaccaaag  12480













tggggatatt aatggtatcc aaagtgagat ctaccccacc ctccctcctc aa






#aggaggtc  12540













agatcaagaa agcccaagcc cggcctggca attgggacct ttcttctcac tc






#cagcccag  12600













ggtgaaggtg gacaagtcac tttgaccctt caggcttctg agctgttgtt tc






#tgaattca  12660













gtgaatattt actgagtgca tagaatatgc tagatattct gggctaaagg tt






#gaaggggg  12720













ggtgagtttt aagggtttct gctcttgctt ccagattgct ttcaaatctg ga






#aaggacac  12780













cagtggtttg tgtgttagac ccacactgcc gtagcacaga atacaagaaa ct






#ggctgaga  12840













gctccaatag gcttttaaca gtaatttctg gcttcacgta tttagtttca ta






#actcatga  12900













tttttcaaaa acttctggtt tgaagacacc gattgccgaa agtccattgt gc






#tgcataat  12960













tacacttggt ccacgtgaca gcactaacat gttctgaaat gtttttagaa gt






#agtctcag  13020













caaagatgaa ggattcctcc ctgtttgaaa agaaaatatt ctttgttttt tc






#tttgatct  13080













aagctctaag actagcagct agcatctgaa acttttttga cgagagtgac aa






#accaactc  13140













taatattaaa ggcaattgat gattatgggc actgaaggga aggtaacccc ag






#gctggtgc  13200













cccggaatag ggatgggtca caatgttgag gacatttcgc ctgttgcaga ac






#ccacctgc  13260













aacacagtgt ggcccttgcc atgtgacttg tgtgtgtgcc tgtgtgtctg tg






#tgtgcgtg  13320













ttttaatttt gacttcataa gtactctagt tatgagctta tttaacattg gg






#ttttacta  13380













ataggggtat gtgttgagaa aatttcaaag ttttagaata tggttcaccc ac






#atgttgct  13440













tccctgtaaa tataattttt aaaaccagat tctgggccgg gcatggtggc tc






#acctctat  13500













aatcccaaaa cgttgggagg ccgaggcagg cgaatcatga agccaggagt tt






#gagaccag  13560













gctgaccaac acggtgaaac ccagtctcta ctaaaaatac aaaaaaaatt ag






#ctgggcgt  13620













ggtggcaggt gcctgtaatc ccagctactc aggaggctga ggcaggagaa tt






#gcttgaac  13680













ccaggaggca gaggttgcag tgagccaaga tcgcaccatt gcactccagc cc






#gcgcgaca  13740













gtgtgagact ccatctcaaa aaaaaaaaaa aaaaaacaga ttctgttcct ca






#gatccatt  13800













ccatttttgt tttcctttat cacttatgga catttgaaat tatggtaata aa






#cattgtta  13860













gtctcagtta attattactg gtttattctt gaaccactaa tccatagaga at






#agagtgta  13920













aatcttaact tgttcctgta ggccatcccc attaaacatc atagtgtttt ct






#cattcgtt  13980













ctttttcgtt ttcctcctac aggaatgaat tttctaagaa aattccagca gt






#tggctctt  14040













tggacgacat ctctagattg tcctccattg ggcccatagg cacaagctgg cc






#agtttgaa  14100













tttgggcaag aatccaggca ttggaactta ttcaaataac tagtttgcct gt






#aattttca  14160













ctttttcaga gtcatctgat aaagctttct tgctacacat ttagatagat ac






#actcaatc  14220













cagttgtcta gaaagttccc tgagccagct gggagcagga ggggtagttg gg






#gccaggaa  14280













tattgggggt gtgtttactg agcccctaga aagtaagtgc tagatttgac at






#ttcaatcc  14340













ctgaaggccc tgaagttcag tatcaaatga ctggtcctgt ggactgagca tc






#tgtgaatt  14400













gcatatgctt agagtaaatt ttactcctac cagtttcagc agcttgcttt ag






#caagcagt  14460













atggaaacac taacatgggg gagtagaatt tctctctctg atccaagttt ta






#tctcattc  14520













tggtgggttt tcaaggagag actcggagtc caagtgtcct ttctgaatat at






#ctggaact  14580













tctcattaac aaaagactca agttataatt taggggacaa ggcacccaat ga






#gaatgcct  14640













tgcaggcagc cctaagtaca cctgcaatta caccattact agcgcggcag ca






#cacatggc  14700













cctgacttag tttaaataat tacgtaagtc aaccatgatt gtttgccctt tg






#catagaag  14760













ggcaagtatt ggtacctgtt acaacttagg cttttttttc tttatgtttg ag






#ccatgatg  14820













agtgatttac actgttgcat ccatatgttg agatgtaaga ataaattaga ct






#tggtaatt  14880













gcccttaagt gtctggaagt caactgggga aagagagcta gagataataa gt






#gtgaaaca  14940













atgtcacaga atcaatgacg gaactcttcc caggacaaag gatgactttt ga






#gttcagtc  15000













tttgccttta attctacatg gggaggagag cacgtttagc cacaaatgga ag






#ggattact  15060













catttgagct atttggttat atgattattt ccccagagaa taggatgtgc ag






#ggcattac  15120













acaagcagtg ccaatagcag caaagttctt gagagtgcta gtaattcaaa tg






#gcaggaag  15180













agaaggaata aatggtaagg ctacctacag ttcacagaga gctccatcct ca






#ctgtggct  15240













ttggattttg tcctgtgtga aagagaagtg actgtgaact gacatgctgt gt






#ttggtgtt  15300













ttagaaagat ggctgcagca gcggtttggg gaatggactg caggagtggc at






#tggaaaca  15360













ggaaggttca tgactattgc cagagacaga ggatgaagca ggagcaagga ag






#attcagga  15420













caggggactc cggggctgat caggaggcag aactggttga taagtatatg ta






#gcagcata  15480













agaaagaaag aatcccagat tgacacccag gcttctcact tggaagcctg ga






#tagatact  15540













gaatgcaatc acaaaggctg ggaagtcaat gggactgcag ggaagggaag gg






#aagggagg  15600













agaagaggaa gggcaggagg gtccaatatc aatattcagc ttttagatgt gt






#tgagcttg  15660













aagtgctcag atggagaagt ccaggaggca gtagaatacg gtggtccaga gc






#acaggaga  15720













gcaatgtggc ttgagttgtc atttgctcac atatttccgt gtcagttact tg






#tcttagat  15780













cacagaacaa gttctcctct cacagtttcc tggctccacc tgtctcatgc tc






#accgtcag  15840













catcgaaatt gagccacacc aggggttctg gataccagct tctctctagg tg






#aggctgct  15900













atagtcagca gctgattagt tgcagttatc agcaactggt aatataatat at






#tgtgcata  15960













taagtgtacc agaagtcatg tttatatatt gctgcaaata ctcggaatgg gg






#atctcttg  16020













ttccctgctt aagaccacat cacattactt ggttttgtac gctagtggct ga






#accaaaaa  16080













aagtaggaga tgattttttt tcttttttct taaagcagta gcttttgaac ct






#tgaccatg  16140













ctttctaacc agctgagggg cttttgaaaa agagggtgcc ttactgtgcc cc






#agaccagg  16200













acaatcagta tttctgggga atggagcctg gcacacacac atttcttaaa gc






#tcccttgg  16260













caattctgag gagtggatta catgttgtat gtagctcgta acgaaagaaa tc






#ttgtcttt  16320













gctctcagac ccccatttct tactcatctc atgagctcct tcgagatcca ga






#aacagttg  16380













catatttcat tagtaaatca gttccagagt cacattttat ttcacaagtt ag






#tccattaa  16440













aagtttcctg cagtgaggaa atagccagaa agaacactcc acccctcctc ct






#ttttataa  16500













ctatagggtc tggctcgaca gagcaggagc atcgccatct tggacaagcc cc






#tcattcta  16560













aagttcacct taataaaaaa ctgcctaaat tcaaactgca tcagcctaat gg






#ctaaggtc  16620













agcatgacca taaaccacaa ataacatctc caaccggaaa cattcgaaac tc






#ctcctcga  16680













ccagagacat gctagtcccg agataacccc cctccagcag ggaagatgcc ag






#tctcggga  16740













taacctctct ctggccggaa agatgcctgc cccaagataa acttgcctcc tc






#ccagagat  16800













attccaaccc tgccataaaa cttctccctc aaacaggaac attccaaaat tc






#tgataatc  16860













tccctcaccc taaaaccaat atatactcct agtctgtaag agaaagcgct ct






#tgaccaaa  16920













attcaccagg agtgcctccc aggttttaac taaagaaaac ctctctttaa ct






#gccaaaaa  16980













aaaaaaggga aaaaaaaaag ctttctgcag tggctttcag cgggcccagc at






#ggcagcag  17040













cacctgagaa cctgttggag atgcacactc ttggacccca ccctggcctc tg






#agtaagac  17100













actggaaggg caggccccgg tctgtgcaca caagtcctca gggagattct ga






#ctgatgca  17160













tgccagattt tgagaactgc tgatatactc caggcacatc gcatgctggg at






#ctagatac  17220













accaagggaa caaaataact gcacttgtcc tctgaggacc gacttacctt tt






#ggaagggc  17280













tgagaaagag agacacatac aagatcactc cctgtaatgc aatgttttat aa






#cagatgtg  17340













atttgggatt tcagtgggag cccaaaagag ggactgacta attcagcctc tg






#tgacaagg  17400













ggagtttctc agaaacagaa tgcttagctg ggcctccagg cacagggaca gg






#aatgagga  17460













aatacttgta ggccctgtgc tccttcagca aaaccctcag tttcttgtta tt






#tttataaa  17520













tgcaaacatc ttattaaagt agatgctaag gcattagaat ttcctgcttt at






#ttttctaa  17580













atgaccatga ggaaacctgg aatgtcaaag ataaagtgca acacattctg ca






#tttaaaaa  17640













ttaaaatgat cctttttaaa agtagcaacc agatgtgaaa aattggactg ga






#gtccaggt  17700













tatagttgat agctttaact ttctccccaa cagcaacagc acaattttcc ct






#aaaatgtg  17760













ttatgaataa gtaaaatgac tacttcacat cctttaactc ttcctacaga aa






#tctaagag  17820













agaaatgaaa caaaagtttg cacagttcta gacacgataa atacatgtga aa






#tcacacaa  17880













ctcagaaaat gtcccttaaa ttaattgagc cattggtact tgtgaattag aa






#gagacatc  17940













tatgttctga tccactgttg aaagctgtac aatgttacct atttatttgc ag






#acatcctt  18000













tggaaacaaa taggtagatt tgcaacaaat aaagagtgga gtacagctgc tg






#acattacc  18060













ttgtatattc atgcctttat gtaaaaaaaa aaaaaaaaat atatatatat at






#atatatat  18120













atatatatat atacacacac acacacatat ggaggtaaag accactgctt gc






#tttgcagt  18180













tgttttaaga gcattcatga aggattttat tttataagca gaaatgtgat at






#ctgacgat  18240













tttaccacta catgcttgca ggccagtgca cagcagatga cgtcatgatt gt






#tttagcag  18300













tcctatcgtt ttacttatga tgtcattaca accctttgct aaaatttctt tc






#ctttactc  18360













caggttttgg ataaaattga tgcattgcac atagtctctc tgataagaca aa






#ctggcatt  18420













tgtatgtgaa aaactgtgca tgttttagtg tctctgctga tactcaaatt at






#ccattatt  18480













ttagtgctgg aataaaaaca aaccacttag tgaatttgtg caggtcctta ag






#gacaggca  18540













aaggtgtcct gagattttct gatcattgta taccaaattt tagaaacttt tt






#caaaaaca  18600













tttttttaat ttcaaaaacc tggttttgtt tatttaccag caatcattga at






#acctgaaa  18660













gctttcagga gattttatta caatggtttc tattcactta caaaattatc tc






#ctagttca  18720













ttctcataca ctgtaagcca ttgtaaatgc ttcaaattgt gccgaacaag at






#aaactaga  18780













caaactattt taagtttgtt ctagtgctaa cttgcaagat ctaatggctc ca






#actagatt  18840













tttaaaataa agtatatttt aatatattat tagaaagtta agcaattatc tg






#tttatagg  18900













taacaaaaac cctggaaccc caatgtcaga tgtcatccac ttttgattaa gt






#ccaaacat  18960













atgacagata aacaaaagat ggttggctgg gctcagtggc tcatgcctgt aa






#tctcagca  19020













ctttcagagg ccgaggcggg cggatcacaa ggtcaggagt ttgagacttg cc






#tgaccaac  19080













atggtgaaac ccgcctctac taaaaataca aaaaaaacag ctgggtgcgg tg






#gcacgtgc  19140













ctgtagtccc agctactcag gaggctgagg caggagaatc acttaaacct gg






#aaggcagg  19200













ggttgcagtg agctgagatc acaccactac actccagcct aggcgacaga gc






#aagactca  19260













gtcaaaaaac aaaaaaaaag tggtcattgg agaattattg tgtcacctgt tg






#ttttttaa  19320













tgtactaatt ttgagaggct tttaaataga gtgcactata gaactttttc tt






#ggcttcaa  19380













tttgctacaa tgttaataga gaatcagaaa ccttatcctt atagatgttt ct






#tgattttt  19440













ttaatttctg gtgacattta tgagtgagaa tagtgtattg ccctgttttc tt






#tcttactc  19500













ccctttcttc ttccttcctt gctttctttc ttcttccctt ccttctttct ct






#tcctcgct  19560













ccttcttttt tacaagctgt tatgaattag ccttcacaga gaaagaaaaa tt






#tttataaa  19620













taactggaaa tgaaactttg caaaggactg cagatgaaaa actttgtcaa at






#gactgtaa  19680













aaatatacta tataattttc aaaagttaga aagtaccaaa cacactcagt at






#tcatggtt  19740













atacaagtat gcatacacat gtattgctcc ctgaaaagtg gtgttgttaa gg






#gagttttt  19800













cttagtacgc ggcttaacat atttttttct gtaatttgtt gttagttata at






#ggggagag  19860













aaaacaggtt agagtctccc ctctcagttt caccttccat aaaacagcta aa






#ctagacga  19920













tcgtcagact ccttccagct gaaaacatct gtaaaattaa aaacaaatct aa






#atgtatgc  19980













aagatatgta tttaaacatg ctggtaataa gtgtgctgtc cctataattt ag






#atgctaaa  20040













acattgatgt cataataata acaacacctc gcatttgtac agcacctcat ag






#tttacaca  20100













atgccttaac attcttctct ctcagcctcc tacaacccca caggattggg at






#agctttcc  20160













agattgggag gtgagggacc caggctcaga gcgattctgc tgttgtccgt aa






#tcaccagg  20220













ctggtgatca gtgggcactg ggtgctctcc tgctacacag cactgtctct ca






#acatgcag  20280













gtcaaggtta cttattcctc cttcaagacg tcattgggtt ttttagctat gg






#atgcccca  20340













tcacttttag ttctatttgt gaatcaaagg ctaaataaag tattcctcaa aa






#tttgttat  20400













acttctgtta ctaatgctta atgtccctca caatttctgt atatttctgt gt






#atttctgc  20460













tctgttttgg ttcctttccc aggtttcttt tttgttatga agtagttttt ag






#actcaagt  20520













ctcttctgta tgtgttataa ctgcccattc cataagatac agggcagtga at






#ttgtgagc  20580













cttgaaaata tttactttag aaatgagaag tatgactttt caacgttgtg tc






#atcaactt  20640













ctgtaaattt tccagaccta taaatacttg cagaaaaaaa atgaaaggag aa






#ggcaactt  20700













gatttagcag ttgggtcagt tagcaatgcc tatggcaagc tgtagtaatt cc






#cttacata  20760













gatttgtaag actcatttct atgatttaaa tgaaggcata cacttaacct ct






#ttagggtg  20820













tgaaacagct tttacaaaaa gagacaaact taagaaacag tgtggccctc ca






#agagtgtt  20880













cattttccat atcataccat ttgtaataag ctattctggc tgggatttac tt






#gcaagcat  20940













tggcttttaa gaagagatgg tttcacacat caaattattc acttggaggc ac






#tttctggg  21000













ttgaaggaat ggaatggaga gtgcggcagt gagtagatct ctcagtgacg gt






#gatgtgcc  21060













tctcccagaa gaaatttcaa aatgcagtgt tcattttcct ccacaagaaa gg






#aagaaact  21120













gttttgttat tgtttattcc taacatagtg gaaacttttc agtactctgg ca






#gaaatttc  21180













ccaaaagcaa ttttctattt catgattata aagtagcaaa ggaaaaagtc ct






#gcactcca  21240













gctgagcaat ggatctccag ttgttatcta ggtgctgcag gtttagagag ga






#ttgccagg  21300













agaacacatc gatttttcag gcctgtgatg acgtatctct tgttgaataa gt






#aaaccctt  21360













ccagtaaaca gacagttagt atattgattt cagggtggct ttagccactg aa






#cctgtaag  21420













tcttgcaaag gttacttggg caaaagcatc attattttac cttcagtcaa ca






#aaaatcta  21480













cctggccaag gcagaacaga aagttcagca atttgatgaa gtgggacaac at






#gaagaatc  21540













aggtgagttg cctacttttt cacttcactt tccaccttta gagattcttg tt






#tagatgca  21600













gagtagtgac gtgcctggtg tcagggagag agttgaatga gaaaagtccc ag






#aagggcag  21660













aagacttggg tgattatctg agtccatctt tccttatcac atgacagagt tc






#ttgaagtc  21720













ttggctagga attctaggct tttagattct ttgggcaatg gctactaaat gt






#tcataatg  21780













ttgctcagtt gcaaaaacaa gacattcaaa ctatagccag ggagataagt ag






#tcacgaac  21840













tcaaggccta aattctgctg atggagccga tgagaattgg gtgctaaggc aa






#agagagtt  21900













gccaatatta tattcttcgg ggttttttgt ttttattcgc attttggaaa ag






#gaaaatat  21960













tagcattcct ctgacttaat attgagaaga cattgggcac tctttttcct cc






#cacacttg  22020













tcttctttca ctaggtgaca agggaagagg tagcatgagg tggtggtcac ag






#gtgagagg  22080













ggctgttgtg agcacaggca tgttgactgc acattggtca cctagtagaa gt






#tttgcagg  22140













cttggtgact tctgaacact gttttcaagg ttgattttta gttgagagaa cc






#tctaggta  22200













ccacgtaatg ttattaacag tagtactgat ctcacaatcg ccctatgtcc ca






#ttcacaag  22260













atgttctgcc aagccataaa aggcccagtt aagtttaaga gaagtctcaa aa






#gtaacaga  22320













tgataactaa ttaataccca gtgattttga aatgtagaca tcaaacatac ca






#attcagtg  22380













gtatcatcct tagaggcaga cagaggatga ttaaatcatt cagcccatct ct






#gtctgagg  22440













acgcagctta gcacagcatg gtggaggcta aatgggcctt aagggaaaaa at






#gatatctg  22500













aagatgcaat ttatttcaaa aagagtttgc tcccgtgaat tttcactctc ta






#tgtagaac  22560













ggcaccagca cacacttttc ctgagccttt gcatgtgtgg caggcagcgg cc






#tggcatcc  22620













tggggaactg aatgaggacg cagatgaccc ggacgtgttc acagtttgac ac






#atctgact  22680













cccagatcag ggacagctag ctttgctggc tggttaagtt gatgattcca tc






#tttgcctg  22740













gttctctgac tgtctcatgc tttctgttat tactattttg cagcagatat tt






#ctgctcat  22800













ttttcaatca tatatgcatc ctggatggca tagagttgat tctcctaaca aa






#tcagtgtc  22860













cctttgtatt tttttctggc cataagatag aatatatatg tcatttatta aa






#aatggaga  22920













aaatgttcag gagtttcttg actcagagag ggaaaaggga tactcagggc ac






#tttttcag  22980













ccaggaattt actacctttg cagggtaaag gggactcacc acgctggaag tc






#aaaataag  23040













ccaccagtgc caagtgttca aagcccttag aatcacaatg ctcttaaagc aa






#agtcttca  23100













acaatgcttg aaaacttcca ctggttctca gtatgtccaa aattgtcatg tc






#tatgaatg  23160













attttctcaa tctgaaaatt tttatagcag gctaaagaat gagataggtc ag






#tgtgattc  23220













tagaactaat cattaacatt caatagatga ctattttatt ctagaaaaag ca






#gcaacttt  23280













ctatttactc tctattttga gggtaaattc tctgtaagta gaaaaagcaa aa






#tgtggaca  23340













tgggactaac atatgaatat acaaagcaaa tgtaccgaaa aaatcttaag ac






#ctgccttg  23400













tggtgttttt tgttttgttt tgttttcatt aaagtgactt gttagcctct tg






#ctccctgt  23460













gaagcacagg gaggtgacgt gatgtgcaca gggcagactc tgccatatgc cc






#tggccttg  23520













aactcagggc cccctgggga ctgcagggga tgctggccat gctgagcaat gc






#ctgtgggt  23580













gtcagtttcc tcatctgcag aatgagggta ggcctggtgc ttatttcata gg






#gtcgcaga  23640













ggggattcag tgacagggtg gtgtagaggc tggagcgtgc cccatgtgtg ca






#cgacagcc  23700













ttccaactag gggaggcggg cctgggctct caccagagag cctgtgttct cc






#atggctac  23760













atgactttgc cccagacgtc cttcccgtgg tctggaccct gggaagtcgc ca






#agagccag  23820













acaggagaaa ggctccactt ggctctcctc tttggtgacc atcccttgcc tc






#catggcgg  23880













gactctcagg tgacatccca ccaaccctca ctttgcttcc ctggtgggtc tc






#actttccc  23940













tcaagagtgt tgcttttttg tttcctgcat agtcctgggc cagttttgat aa






#ccctcttc  24000













atttcacttc agaaaccctg atgatttctt cctgtgctct ttttacctta gg






#acttttac  24060













tatgacgact gtgactggcc catttcttgt tttttttctc ttgctctgct tt






#ctccccca  24120













tcatcactaa agcagacatg gcaatgatgg ccatgcacac tttccaaggg tc






#cagctgta  24180













gatcttcatg gttccccagg tgcctggacc atcttgtgag gagggaggca aa






#cacaccct  24240













gcctggagca cttggccctt tcggcaatgt tttggcttcc tcaagtgaga aa






#agaatgga  24300













tttgtattcc ccctctgcat tattgttttt gttttgtttg tttgttttgt tt






#tgtattga  24360













gacagagtct cacttttttc cccaggctgg agtgcagtgg cccgacctcg gc






#tcactgca  24420













acctccacct tccgggttca agtgattctc ctgtctcagc cccctgagta gc






#tgggacta  24480













caggtgcccg ccaccacacc tgactaattt ttgtatgttt tgtagagaca gg






#gtttcacc  24540













atgttggcca ggtgcccatt attatttgat ctggaattaa ctgagctact gc






#aggaattg  24600













cttgattcac tgatgactgg tgttgagcca gtacacaccc acacccaagg ac






#tgtgactg  24660













tcttctgagg tccatcctca gaaattcctg tctcttcacc tagtgtgtaa ta






#aggcctgc  24720













gcgtgttata tggaactgta aaaaatgcgc caaccatctg tccttcctct tt






#atctgatt  24780













acttatcatt gttctctaag ttgcaagtta atagactgat cataaattaa tg






#catgctgg  24840













agacttgctg tttcctacta gcagcatata aaagttattt ttaaagttgt tt






#taaatctg  24900













tgagtaaaaa taaattgctt tgctgcaaga aacaccaaac atggaaaagc ta






#acggttca  24960













aagttaataa tttatcttat ggacatcact agtggcatag ttgctttaaa ca






#gtgagagg  25020













atttaataga tatttgattt gcaagtggga tgaagggtgg tctaaccttt gt






#cctgtgtt  25080













taccttccat gagatcctag aggttgtaca gcacagtagt ggcatgtgac ac






#acttgaga  25140













gtgcctgttc tgtttggaaa cctggaaact atgaagggaa gtggccttcg ag






#cttaacac  25200













ataagacttg ggaggcaaaa ccttttattc tctttaaata ttcactttag ga






#taagcatt  25260













tttttaggtg ttaggaacag ggaaaactgt gtggttagga aggaagaaag aa






#gaaagtta  25320













actgttgtac attccctagg taatgttttt aagcattgtt attcactttc aa






#aacacatt  25380













ttatttattt ggacttaata ttttgatctt attttttcaa tttcttttaa tt






#taacagac  25440













aggatgagtt tttttatagt tgtattactt agaaattata ctaaaaatgg cc






#gagtgtgg  25500













tggctcacac ctgtaatccc agcactttgg gaggccaagg caggtggatc ac






#ttggatca  25560













cttgaggttg ggagttcaag accagcctgg ccaacatagc aaaaccccgt ct






#tcactaaa  25620













aaaaaaaaac aaaaaaaaaa ctagccacgc atggtggcag gtgtgcctgt aa






#ccctatct  25680













actagggaga ctgagacata agaatcactt gaatccagga agcagaggtt gc






#agtgagca  25740













gagattgcac cactgcactt cagcctgggt gacagagcaa gactctgtct cg






#gaaaaaaa  25800













aaaaaaaaag gataaagaaa tcatactaaa aacaaaacag aatgctgacc ac






#cttataga  25860













aatagaaata gtggtttgct gtgatagcaa attttcttgt taacttttta tt






#tttaaaga  25920













attgcacatt cacaggaagt tgcaaaaaat ctactgggag gtcctatccc cc






#ttccccca  25980













acctcctcca gtagtaacat cttagtagca aagttttgta tatttatttt ga






#tatcatta  26040













tctaagtttg acatcattat ctaatattaa cctaagccaa aagcccacta tt






#ttaattat  26100













ctagtgatgc agtgttatag aactcatagc ctttcacagc attatttgga ag






#ttaatttt  26160













cttaagtgaa atgtttttgg tctttaaggt ttggaggcca tggaggcatg ag






#gagaaatg  26220













ggatgaggga gagagagcta agatagataa agacagagat ggggagatcc ac






#tgattcgt  26280













tgaacaaacc agatacttcc ttatagtttt tggattaact tacatgagct aa






#gtttatat  26340













tctgttcaga tcacaagtgg tcaagtttgt gtgtgtgtgg gggggggggg gt






#gggtgtgt  26400













gtgtgtacca ctctacccat cctatattta ttgtcctgta tttggtctgt tc






#tgccttct  26460













ttattttcag gataggtgtc ctaaatgagg gtctttggaa agctggtgag gc






#catgttgc  26520













ccgtttcagg tgttccgtgc tcaaatgtat tcatttcttg aaaaattcag gg






#agtgcaca  26580













cttttgtaca ttttcctatg tgtatatgat accattatat aaatcttaaa aa






#tatatatg  26640













gttcacctga atccccagcc atttggtaga gaagatagaa aacctacaga gg






#aggctaag  26700













attttattag aaaattcagc ttctcgacgg aggtattggc tttaaagtca ag






#gcaatgca  26760













tctattcttt cttttgatat aactagctaa aagatctctt aaattcaaag tg






#gccctcat  26820













cttactgtta ctgcaattta ctcttaatta caaattatat aaaaataggt tt






#tgaaatac  26880













tgtagcgaca aagtaacata cctctgctcc attacacaga taaaacctct aa






#ggaacacc  26940













tcctctctta acaggcatta accaactgca gaaactgcag aaggacaggg ct






#atttggga  27000













ataacacagc tcccttcctt gtctgttccc tcccattgtc aggcttctgt gg






#agccatat  27060













tcagagcaac atagggaggg ggaagagaaa atcaacccct tggtgaagga aa






#gctcccaa  27120













ttcacagagc aaacatgggt actcttgttt gtgggagctc ccagggcctc cc






#agctcacc  27180













gagcattctg agccctgatc cttacactaa ttgtattatg caaccataaa tg






#atgtctgc  27240













tgtaccagcg gggacagttt attttaatag attggtataa cttggcagaa tc






#ttatctgc  27300













atgtttcatc ttggattttt agctcaattc aactcaatag gcatgtgtca aa






#tgtctact  27360













gcagactgag cactgaaaag ctgctgggta cagggttaca tggatagaaa ac






#gtagcctc  27420













tgacccctaa ggagcctgta atccagatcc ccattctttc catcccattc tc






#ccaagcaa  27480













gaatttacct aatgtggttt gcgagaattt aagagctgga aaggtggtca cg






#agaagccg  27540













gaatgggttc gctaaaatgt gtctatatga ttaagcataa cgtagctttg ca






#gcactctt  27600













cacagcttcc tcagagcctt ccgcacgcgg tgtctcattt gaatacttgt gt






#gaggatag  27660













cctcataccc ctcagtgagc tcttcatgga gtgatgcagt agacagcaag cc






#tcacactt  27720













ctatgctcac ggaagaccaa atttgccttg aaaaatcttt atagtctctt ca






#catttcta  27780













agttgacatc aaaaatcggt taccataaaa tcctaatagt tgaagagatg ta






#atttcaat  27840













tatttggtaa acctgacctt cattgtcaaa gcaattagtc aactcagatt ta






#ctttctcc  27900













cagataatag attctgactt ctttttttct gattaaaaaa cttaacacct tc






#ctcaggag  27960













atctatctca gttctgaatg ctgattctaa ctaagaagga tatttggcta ca






#tgctggga  28020













agaggggtac tgaggcacgc cgcgattcca ctccagcatt tccagttagt cg






#ggtgcctc  28080













tgcactcccg gtgttccggc gcccagttag ttgtgtactc tgggctgtcc ct






#atactgga  28140













gtcctaaaac acttacgact gcagataggg ggaggttttt caaaaccttg gt






#ctgaaaag  28200













ccatagaagg gagataggaa agcggggggg tggagccaca gtacattcag gt






#ggatccgt  28260













ttttggaaat agtacaaact ggaggtgaaa ccctggaaat tgatctgtcg tt






#cacatgct  28320













tcatgccgag tccttgtgga cccacagaga cacactcgcc ccagtttgaa gg






#ctgctaac  28380













ttgattctga ggacaccagt gaggtggtag tgtgcaaatg atgtgtgagg aa






#actttgga  28440













ggagtctcac cctgcctgga gcacgtggcc cctaaaacag cgcagcctcc ca






#aagacaga  28500













agatgtggac tagtgagaag ccaggtatgg tgactgctgc tggatgaagc tt






#gtcccacc  28560













agaggctcgc ttgtttcatt gagcacctac tgtgtgcttg tgggatgcaa ac






#acacgtgt  28620













ggtccctgcc ctcaggttaa taggcagggg tggaacagtt atgaaactgc tc






#taaagtca  28680













ttttctcaaa ctgggagtga caaatgtatc cacttggaaa agattgagaa tt






#ttataaga  28740













tttttaaatt tttgtttatt cacattgagg agaatctaaa ttcttttgaa ct






#tatgtata  28800













gatttcacca ttttatagta ataaatcagt cctcctgtgt gtgtgtgtgt at






#gtgtgtgt  28860













gtgtgtatgt aaacctcacc ttgcaatatt attattttaa atagccactt gc






#atcttaag  28920













gaaattaaga ggacaaaaga aaagctgctg ttttgtatgt atccacatat tt






#accagctg  28980













cttccctgcc ggcaggtgct ctggttctgc actgcctgtt gtcccttgcc tg






#aaaatggt  29040













tgcctccaat attttgctca gttttctgat tgtttacagt ggcagaggag gg






#tagatctg  29100













gtaccagtta gtaattgcca gaggtggaag tctgtggatg aaatttgtat aa






#catggaac  29160













gttagttcca cagttaatgc tactcaattg gaacccatgg aaattatttt tt






#ggtgaaaa  29220













gggcccatgc gttatgaaat ttgagatcca tcactttaag tgaatgtagg cc






#ctggatac  29280













agtgggagct cagaagagca aatcagttgg tcaccttgct caacgtattt ta






#ctaagggc  29340













atcagtaagg ctttctatga cctgctcctt caatgcttgg ttgacatttg gg






#gagcaaag  29400













ataaactaag gattctaagt tctgtcctgt gatgctgtaa ggggaatctc aa






#acctctag  29460













gtggaggagt gcagagatga ccaggatggt ggaagcctgc aggagagctg aa






#cacctgaa  29520













gacacccagt gggaagacca ggacctttaa cgcccatatc tgctgctcaa ga






#ctggcaga  29580













gagaagaggg tttgtgatga gaaaaggtgg tgaaaggcac aaggaggcac ag






#agcatgtc  29640













aggtcccata tcccaaaagg aatgtgcttg ggtgagggag agctcctcca tg






#gctggagg  29700













cattcagaga ccaggcagtc gcttgtgggt ttgtgattag agtgaggttc tt






#ttataaag  29760













ggagtgagaa gagaaggtct gtggatactt gagtgtatcg gtaattaaga aa






#taaattgt  29820













gtacatccca tttctttcca cattttcctg ggctgtcaca gtggctgcaa ag






#aaagcagt  29880













ccgtgaactg aactgtgatc ccagacaggc aagcacacca ggaatctctt ct






#cagctgtt  29940













gataatgagg gagcgctggg gagagaaatg gggtcctctt tgagtttcct ct






#gtgccgat  30000













acctttctct ttgttaaaac agctaattaa acactgaagc agtatagctc tc






#ttactata  30060













cactggtagt catagttctc ttactgttct cttcactgac agttctctta ct






#atacactg  30120













atggtgacgc agaaattcag aattccccgc atgtgtcccg gtttgaaagc ca






#ctgtgctt  30180













tgctgtggat taggatcaga cagttgagtc ttgttccaac aaggaaagtt gc






#ttattgga  30240













aagttttgct gcagggagcc ttgagttctg catcaggctt ggaagtgggc tc






#tgtggagg  30300













tcagaaggag gatcccccac ccgcagcctc aagaaaaata tgaaaagtgg at






#tatgcctc  30360













tgtagctata ttgcctataa actttctgca gaatgacagt attcatatcc ta






#catttttt  30420













caaagcgata ttaatcctga gacctgcagc taaagtcaag tagaatttag gg






#ataattaa  30480













taggaggaag gtggggttgg aagatctgca tgattatagt cctctgatat aa






#ctggaaaa  30540













ttctttccat tagcaaggag ctttggttaa tataaaatgg acagattaaa cc






#taggcaat  30600













ttattttact cattgctgta tttttatttc agagctggtt gaaaatatta ca






#aagtaata  30660













ttttaaagtg cttatctaaa ctcttactct gcattttatc attgggttat ga






#aatgactg  30720













gggaaagact tttcttgctt ttatttctca gtgtctactt ataaacatgt tt






#tttgaact  30780













actgtttttg tgacaacatg cctttttccc agaaaatctc aggttaacat ta






#aataggca  30840













ctggatgttt atctgatctt gtttatagaa acacaagaaa attttaacct tg






#tatatact  30900













ttactcaatt aactaggtaa gaggtcattg aaacatttag aattccactc ta






#catttcaa  30960













taattatcag gtgaaagcta ctgcatctac atcagaagat gtttgtaatt ta






#tttaagaa  31020













taaaattagc tatgcaagaa atagtatgtg gagtcctatg tggaaatcac ag






#aaaccctg  31080













acaacttgat gatctttccg caagctaaaa atatcactct ggatcacagc ag






#tagaggac  31140













tctgtaaatt taatctgtgt gtctcctgta aataagtgca ttagcagtac ac






#aggtggtg  31200













tcagagtcag tgatgatgga tagaaattct acataaaatc caggctcagt gg






#ctcatgcc  31260













tttaatccca gcactttggg agtctgaggc gggtggatca cctgaggtca gg






#agttcgag  31320













accagcctgg ccaacatggc aaaacctcgt ctctactaaa aatacaaaaa tt






#agctggat  31380













gatggcacat gcctgtaatc ccagctattc gggaggcgga ggcaggagaa tc






#tcttgaac  31440













ctgggaggta gaggttgcag tgagccgaga tcacgccatt gcactccagc ct






#gggcaaaa  31500













gagcgacact ccatcgcaaa aaaaaaagaa gtaagaagtt ttacataaaa ac






#gtggagtg  31560













agcccaaggt gccatttatc cagcccatac acatcgtacc atgtacagag tg






#gacaccag  31620













ataaatacat tgactgcatg ccacaaacat atatatgtag gcaccgttgc at






#tcaaatac  31680













acatctgcag ccctaacaca tctttatttg ctaacgagca tcaatgtatt ta






#aaaacaaa  31740













catgtttaaa ctagtgaatg attagattat aatgatctta attcataagt tt






#tctcattg  31800













gccttttgta tacttcaatt gtaataccta gaaaaacagt tatgtccaaa gg






#agtgaata  31860













ggccttatct gaaacaggtg agcgtgacaa gtgttttctt acttatttta ct






#tttcagat  31920













aattcatcct taaagtacat tagtttaaaa gtactgttta aggaaacagt ac






#ttggatta  31980













aaacttgaat cattgttaag gaaaactata ccttaacttc atgtaatcac aa






#ttaaacct  32040













cttcatatag aaggatctaa gaattttctg cagcattcac cagcaccaaa aa






#gctcagag  32100













acatatattt ctttctctgt atatgtattt taaattcaag ttagtataaa tt






#gacaggca  32160













ggtcagagta atatatgatc ttctgagtcc ccttagtaat taaaagaaat ga






#ttattttt  32220













gcatgaaata tgataaagtg attttaagtg cctgataaaa agtcttaacc at






#gacaacca  32280













ttaaagatta catcaaagaa aaataagttt gactttcatt taccttggaa ac






#agctatta  32340













actggtaacc tcaagaaaca ccatgaagag tcagtttgct ccacacatgt ct






#tgtaaaag  32400













tcaaataact ggtggttatc cagtaatgac aagaggtaga agttacatcc tt






#gctgtctg  32460













attgaacctt cccagagctg gcacaaggct gggaagacca taggtgctaa at






#gaggaact  32520













acttaaagaa agaaaatgga atttcacgga caagaaaatc catgtccatt tg






#gttctgtg  32580













acccacatcc tttgtatcct atgctttttt acacttggta catggttgca ag






#attgcccc  32640













tgttttctac ttatagttcc atgcagcatg gatgtgggaa aaagtctcct ct






#gcaaaggg  32700













ggttaatgca ggtcactcta cgtatgtgca cgaggtcgtt ataaagctcg aa






#aatatggg  32760













ctcaccaacc aggtgatttt tttaattatc caaccagaag acataacata ta






#ggggaatc  32820













aaaagaaatc tctgagtaaa ataatgataa caggtcaaac tttgcggtcc ca






#cgtgaggc  32880













tggagatgcg tattgtcttg actttgcatc tacaagttta acaaatgatg ct






#ttctcagt  32940













ttacctctgg aaatggaaat tagcattgca aatgacttca tgaggaggta ga






#agctatct  33000













gtgaatttcc tttcgctgtg tttacgatag actctcacgt ctagatgtgt ca






#tgtattat  33060













gttaaattgg tatgtcttga agttataaag cacagccctc tataagtata ta






#tattccac  33120













ctctttcaaa tcggatggta cctatccttc aaactgctat ttaatgactg tc






#tgctatgt  33180













tcaaggcact gctctcaatg ttaatacttg atgagatcgg gcgcgttcaa gg






#tggcatgg  33240













ccgtagactc aatgttagta tctgaaatat ggcctacgag ctgagttgtg aa






#tcaagtta  33300













atagattttc ggaatgttaa ggtctaaacc agtagctctt aactgagaca at






#cctgtcct  33360













catctcacct gggagacatc tggcaatgtt tggagaacct tttggttgtc ac






#actggggc  33420













atctagtgag tagaggtcag ggatggtggt aaacaagttt ttttgtttgt tt






#gttttgtt  33480













tttgagacag agtctcactt tgtcacccag gctggagtgc agtggtgtga tc






#tcagctca  33540













ctgcaacctc tgcctcctag gttcaagcaa ttcttatgcc tcagcctccc aa






#gtagtagc  33600













tgggattaca ggtgtgcacc actacactca gctaattttt gcatttttag ta






#gagacggg  33660













gttttgccat gttggctagg ttggtctcga actcctggcc tcaagagaac cg






#cccccttc  33720













ttggcctccc aatatgccgg gattacaggt gtgagccacc gtgcccaggc ta






#acattctt  33780













taatgcatag gacagccccc accatacaga ggaatcccca gcccagaatg tt






#aatagttc  33840













taaggttgag aaacccaagg ttaagccaag tcaacttatc tatcttcttt aa






#aattgcat  33900













aagaatgcag tcctgttctt cattcctctt gctttgcagt taatgatcct tt






#gcctggac  33960













tttctaagtg cccagaagag caacagccag catgcaggat ggcattcctg ac






#cagttgca  34020













cttggcctag cattccaacc tcacctgcct cagcttgttc aacctgaaaa cc






#taccaagt  34080













gaaagcaaga gccacgtgaa gacgccttag ttatatgcac ccacccagac ac






#ttgctcag  34140













aaaggaatca gtggggccct ggccttagaa actggctcct tcactgctgt ag






#aaacaaca  34200













taaatttaac ataaaacacg tgcttttctt ttttcttctt actttttcct gt






#cttggcaa  34260













tgcaaggatg ccattaggta aagaaatcct tcaccacact aatcctgcag ag






#ccagaaga  34320













gaaaccagct tgttctaacc cagctttgtc atggagagaa ggcagctgct cc






#agtctgaa  34380













ctattctttc ttttggtagc agcctgccca agggtgaaag tgtgtttaat ag






#tttgaatt  34440













acacaagtga acagtaaatg tatgcctgtt tctgctttat gggactttga aa






#taatgttg  34500













tttgtgccaa ggttttagat tactatacct aacaacctag aaaaagaaat ga






#aaaggaag  34560













ccttctgcca ggcagaggtc actacgggcc tggagctggg cacctgactc ag






#cagctgcc  34620













cagatcccca gagctgagaa gtcaccatgc atttgtggtg cttcgagcga gt






#taccagag  34680













tcctggaaca gagcagcaca cctgcggggt gtccccttgg catttgggca gg






#gcaggtga  34740













ccaagggtct tgttggaact gaagtccagc ttgaaaagca aatctggttg tg






#agctagag  34800













tccagtaaca cttgtttccc gccgcccccc gcataactcg tgtgtcctaa aa






#tacaataa  34860













tttcttgaac ttcagtcact tatgcctata agcgggcata caacaggggc ac






#aataaatg  34920













tttgttaagt gaatgaattc tttcagaact agatgggatc ttagtccaac tc






#tcttattt  34980













aacgaggtcc acagaggttc tgcgattgtc taagaaagaa ggctgtgttc at






#ggcctttg  35040













ttgtttacgt ggccctgtga ttctcttggc tccgtgaaag tcctgatgca ga






#cattccgg  35100













ccatctagaa aggcatgcag acaagccatc cagctggcat gatcctgagt cc






#agctttct  35160













ttaaaagagc ttccaaaact gcttaagctt tgactgcaca aaacctgcat ca






#cctccagt  35220













tgagaaactc aagagaataa gtaagttatg gagttggaga ccccagctta ac






#tactagtt  35280













ttaaaatagt gaaatcaaca ttttcaaatc tttgacttca ctaagattta at






#aaagttta  35340













ttaatcatat attatgagtt attgctctct ctttatgtct gtaatgcagt tg






#ctcctctc  35400













tgtataaatt aataagtttt agagatccaa aatgagaatt ttaaaataaa tt






#acgtatat  35460













tttaatcaag tttaatttga ctatatccag ctaaacaatt gattgaactt ca






#cttgcttt  35520













tctatgacag gttttttgtt cttagtaaaa gaccccagtt ttctcacttg tg






#aacagaag  35580













gggttagact tcatgacagc taaggttcct tccgtctcta acaaaagtgg cc






#tgaagaga  35640













ggcttctaga ctatactcac ggtgggttct tgggacctca gagtcagctc ca






#tcacttaa  35700













gtggctgtgt gattgagtgg agacacctca atctctttgt gcctcagttt cc






#tcacctgt  35760













cgagtgtcaa catgatggca cctaaagctg ttgagacttc agaaaggtaa tg






#tgtgaaaa  35820













gtgaaaagtg cctggcatcc aggaagtact caataaatac caactatttt at






#tgctgcag  35880













ctgttcttat agatgtgatt tctagaacat tgccttctaa tagggtagcc at






#gggccaca  35940













attgttggct gttcggtgtt tcacatatgg ttagtccaaa ctaagatgtg tt






#gtgagtct  36000













caaatacaca ctggattgtg aagacttagg acaaggaaaa caatgttaat aa






#aatctcat  36060













tgataacttt taaattaatt acatgttgaa atgaaaatat ttgggacata tt






#gagttaaa  36120













taaaacagga gattaatttc ttctgtttct ttctactttt tttattagtg tg






#gctactca  36180













aaaatgtgac attatgtatg catctcgtat tacatttcta ttggacagca gc






#gctctaga  36240













cagtactatg ggtagtatct gtggggaggt tctcagaaac atgtcgcatg ct






#cttttaga  36300













accttaaagt attcctagtc tcctctactt ccagcccttg gctcttgggc ct






#cagtcttt  36360













ttacttttgc ggctgtgttt ctctgaaggc ttggcattag tagattgaaa ag






#aataacca  36420













tctagggaaa tgtgaattca gtttctttct gacattctgc tctctacaag gg






#gatattat  36480













gtacacataa acctacttcc aaaataatga agtgaggcct aattccttac tc






#ttcagaga  36540













gcccactgtg gaagtgtcac tgaccttgtg tatgggctgc ccttcatggc tc






#tgggagtc  36600













attataaagg gcagcatttg gcgtggtgcg tcctaagcca gtgtttctcg gc






#tctgttcc  36660













ttagacatgt gttagtgtta atagatgttc ttggaaaaaa aaaaaaaaaa ca






#gcattctg  36720













aggtcaaaca tgctcagaaa gcttggaatc tgcactacgc ttctcgtaca ca






#tttcatat  36780













taaagatttt ggaaagtcct gcaatacaga gccctgtcta atattgccac aa






#cccacaat  36840













tgctcaaatg taaatagatt tgagtttatt cacattcaga tcacctctta ag






#gccccacc  36900













tcccaatgct gtcacaatgg caattagatt tccacatgag ttttggaagg ga






#cattcaga  36960













ccacagcagg ggaaagcagg gtacttgctg ctttgcaagt gtgtccacat ct






#aattaata  37020













gtacagttct tactcttggt gtgtccggtg atattaaaaa ttaatgtgcc tt






#atttagat  37080













aagtaacata aaaatcacaa aatgtatgcc ttagatttat atgtatttat aa






#ctagtcta  37140













tttcctgaaa acagttgaga caccttgtaa aagttaccgg tacgataggg cc






#attccaac  37200













aaagctgtaa agtggtgata acacagtcat aaagaagagg agatagctct gg






#gagaaaag  37260













gtggcccaga aaccagctct gagcctcatg gctgcaggca aggtctgcag gt






#tcctggtc  37320













ctgattgcag gccatttgct gccttgagtg gtggttacac aaggccagcc ct






#gggggtat  37380













cacccagaac acctagtaca cgaatttcag tttagaggac gaagcattac tg






#gagtattg  37440













ttatgcagga aaactttttc ctaaaaatgc cctgaaaaga gagtagccta at






#gcattcaa  37500













tcaaaatgtt tttaagtgga aaacatattg tgtgtacttg atctggcctg ct






#gcttttaa  37560













aagattaaaa ctgggactgg gcatggtggc tcacacctgt aatcccagca ct






#ttgggagg  37620













cagaggcagg tggatcacct gaggtcaaga gttggagacc agcctgacca ag






#atggtgaa  37680













accccatgcc tactaaaaat gcaaaaagtt agccaggctt ggtggcgcat gc






#cggtaatc  37740













ccagctagtt gaggggctga ggcaggggaa tcacttgaac ctgggagccg ga






#ggttgcag  37800













tgagctgaga tcgcatcatt gtactccagc ctgggcaaca agagtgaaac tc






#catctcga  37860













aaacaaacaa acaaacaaaa aaacactggg gccaaagaac tctgtgtgct gt






#atcaccta  37920













accacatttc atgacacggc tagagaagaa tcatgcaaat aaaaatttcc aa






#catgttcg  37980













taaactggga aagtatttca ctggggagtg agcagaaaag taatactata ac






#ctctatat  38040













ctagacaaat gtgaattcag tttcacatat aaatatataa gtgaaaaaat at






#ataaatat  38100













aaataatatg aaataatggt tatctcacca ctttctacat cttttgtgaa ta






#ttttatag  38160













tgctcaaata tattagtgca ctagtatatg tacattacat taaataacta at






#catttatt  38220













aggaggatgt gcttgttttt tgctaataaa gatgataata aaaaaatcct ta






#gacccccc  38280













ctcggtttgt tttcagttag gaattaggga tatttataag aatatcttta aa






#tgacacat  38340













gccttgctct gggacgaggc atctgcatgg gtgacacata tgtgttgtgt gt






#acaggctc  38400













ccagcatttc cagggccctg ctcagaatgt aggccttact gattcttaca ga






#gttacaag  38460













cgctggtgag gttggcgaag tttaggtaaa cacagctggg aatgccccat gg






#cctctggg  38520













tgactttgga catcactgaa ctttaccctt agagatgcat acctgcatct tt






#tttaccct  38580













gatagggcct tccatgatgc tttcaaagtg tttttgtctg cttttcggtt aa






#tagacttt  38640













cacagtagcc aattgaatat attggttaaa tgcatctctt tatacacaga ct






#ggattcaa  38700













actgaggttg tgtctctccc tggctgtgtg acgttgggta tgatccaagt gt






#cagattac  38760













tcaacttcaa aatgaggaca gagcctttcc cttctagggc tgccaggaac at






#tgaatgag  38820













agagtgctgg cagcttagta caggtgttca ttgctcttgt atggtactgt ct






#gtggcacg  38880













gctagataaa atacagtagc cactgattca aatttcaact gaggagtaaa at






#aaactgaa  38940













taacttagaa aagttttctt cttttgaatg actctaagaa tttaaggagc at






#gtgagtgt  39000













tgatggctct aaaagggtaa cagagcccaa ctagctcagt tctcagcatg aa






#aatagtca  39060













tatggcacag actcagtgga gtgggtgcac ttcaataact ggaagcacag at






#gccctaca  39120













gcagcatcaa agatggcact ctaaactact ttcaatcctt taaaataaat gg






#aaacgcac  39180













atttagtatg catatgacaa cacgaaggac ttcgattttg ctgatgcaat ac






#agttttac  39240













aggatttttt atactcaaat tagtaaaatt ctgtattgca tccaaattat aa






#attataat  39300













atcatctaga ttggacatag gaataacgac cactggtatc tgcccagaaa gc






#tctaccgc  39360













ctgtttataa gctcctgcag gagacacaaa aagaagagaa tttgaatata ac






#ttgaaatg  39420













accgtaatct cctgccccaa ctcatttcat taccaaaccg cctctttctt ca






#ttatttct  39480













cctgaagcac aaatctatag agaactcagc tgccagtctc tcccactgca ct






#cagcagtg  39540













aaagggttag gcctaggctt ttcaaacaga ccagtgcttg tatcagccct ta






#aacatctc  39600













tggagaagga aatgggatcc ttctttggta attcattttt gacagttggg ga






#ttaggtgt  39660













tctgtatctg gggggccttg ctgtcttctc tcctcctcct cccactgcag ac






#cctctcct  39720













cccctcccct ctccagctct ctgatgactg cttcatgctc cttccacctg ag






#gactgcca  39780













gcacagccta ttgcaggaac agccaatgag gggctggctg tgctctttta tt






#tataaaat  39840













tataaactca agcaaaatct agactatgtg tccccaagat cagaggagca ca






#aatccctt  39900













gcttacagat tgcatggggg gcacattctt taaaattggt ccctgatcta ga






#ctctagcc  39960













tgagaatcat ctttaagttc agaatttcca ctcatgacct cacatctgtg gg






#ctcccaca  40020













ttgtcttcca aaacacacat ggcatctggc atcaccttca cccccaccct ca






#gagcctca  40080













tctccctgca ggtagatagt caaggcaacc tcttcactct tctgccaagc ct






#cctctcct  40140













cagctcttcc cttcctctct ctttttgaaa atatttttaa ttgtggcaaa at






#atacacaa  40200













cataaaattt accatcttaa tcatgtataa aagtggagtt cagtggcatt aa






#atacattc  40260













acgttgttct atagccataa acaccattca tctccagagc tcctttcatc tt






#gcaaagct  40320













gaaactctgt ccccattaag caatggctct gttttcctcc gttcccccag cc






#cctggcca  40380













ccatcctcag ttttctgtct ctgtgagttt gattactcta agcacctctt at






#aagtggat  40440













catacaatgt atctgtcttt ttgtgactgg cttgtttcac tttccataat gt






#cttcaagg  40500













ttcatccacg ttgcagcata tggcagaaca tctgtccatt tccaggctga at






#ggtactct  40560













tttgtacgtg tggaccacat ttcatttatc cattcatcca cgggagggca ct






#tgggttgc  40620













ttctgctttt tagctattgt gaataacgct gctatgaaca tagctgtatg cc






#tttgtctt  40680













ttaaagccca aatctgatca agtcactccc cagcttaaaa ccttccactg ct






#ccccagca  40740













gtgggataaa ggccagtctc ccctgtaggt ctctcccgcc agccctgctc ag






#tcttcttg  40800













cttgtcatcc ttggctaggc cttgcattgc catagccctc tgcctctgtt ca






#cgctctct  40860













catcttggag catgagcctt ccatcatctc taccagatga actctcattt ct






#tctttcaa  40920













aaaataaaaa acccaaaaaa cccagagatc ccaactgtcc tggtgtctgc at






#agtctgca  40980













gcacacgccc cctccatggc ccttcctcca taagcagaat cactcctcac tg






#ttcctgca  41040













gcacctcctg tgtgcccaca cagctgtcct gcggtgggct gtgtgtgtga gt






#gtgccccc  41100













tctaggacct gagctccttc tggagggtgg gcacagcatc cattcattct gg






#gaatcctg  41160













gtcggcacca tgctagaact tctgcaagtg agtgcctttg gtgctggccc at






#gggagagc  41220













tgttggtaag gcatactttt gcagattcca gttgctgctg aggttgttgc tc






#tttgcaca  41280













agtttcttct agtcaccagt gaagtgacat gtgtggcagg catggcccag gg






#aggctttt  41340













tcataaagaa gaggttgaat ctttggggct gtggtttgaa tatgtccctc aa






#gcttatgt  41400













gttggaaact taatcccaaa tgcaatagtg ttaggaggtg gggcctaatc ac






#aggtgatt  41460













aggtcataag gctctgccct catggatggc ttaacatgtt tagtgaggca gt






#gggttagc  41520













tattgtgaga gtgggcttgt tagaaaattg agtgcagccc cctcttgctt gc






#tggctacc  41580













atgctctctt gcttttctgc cttctgccgt ggggtgacac agcaagaaga cc






#ctccccag  41640













atgctggcac catgccctgg gactttccag ccttcagaac cacgagccag ac






#aaatttct  41700













tttctttata aattacccag tctgtggtat tctgttatag aaacacaaaa tg






#gactaaga  41760













caatcttctt tcatcaagtt agggtaccaa cctttaaaga ctgccagtcc aa






#ggttaaag  41820













gaaacttttc aagagcagtc caaacatgat ctggccctca gctactctcc ag






#ggtcatgc  41880













caccctatca cccactggct cacacagacg ctgaccactg cttagtttct ca






#aactgaag  41940













ttttcctcct cagagctttt gcaaaacctt ttctttgcct ggaaaactcc cc






#ccacaaat  42000













ctttagttgt aggttccttc tcatcttgca gaattattag tttgctcttc aa






#atagtctc  42060













tccagctaga ctatcaactc caggagggca gagttcttct tcgcttcctt ca






#cccatgtg  42120













cccactgagt ccagaactgt atagcagttt gattgaaaaa atccacaggg tg






#gaggatga  42180













gaggaccctg gatcccagcc tcacagcctc ttacttcacc tgtgtgattt tg






#gtcaagtc  42240













ctttattctt cctgggcttt agttttccct tatctaaaat atgagaaaag tt






#cccctctc  42300













ctgggtattc tgggagactc atgtaaaagg cactgagcca gtgcagcaca tc






#tatgacca  42360













ggaagggtca gcttcctgcc ttgcatgaga cacacattcc cttcttcatg ca






#cagttatt  42420













catgagttaa atatgtattg agaagtgggt tctcaggaga tgatgcatcc ac






#agcattgt  42480













ttgtatgcct ctgtctttga tgtccctgcc tgagtcgccc actttagagc cc






#ttctgttc  42540













ttcagaaacc agacttttct ttcaatagtt tcagtaatca atcgatcaat ca






#atcaacca  42600













atcaacagtg ataataatca tgagtgagcc cctgcccgtg ctggctgtgt cc






#tgctgaag  42660













gcacactaag tgctgccctt cccagaagcc tcaggaagct tgcgaagctc ag






#gtgcatgg  42720













atgcctggtg gaatgaggaa gggatgcagc caggtagaga aatgccctgc ca






#tcacttgc  42780













atcagcatct gtgaagagct ggccaggctt ttgctcacag tggttgacac ag






#tcaaggag  42840













caagggcccc gtaggagagg ggagtcaagg gctccgggtg ggaatggagc tg






#ggggctga  42900













tgctggcttc tggagcactg taatgtgact gagaaaggtg aaggagccgt tc






#tgaaaaag  42960













aagaaggcag gagctcgcac agctcttgac tcatcttgac ttctttttcc tg






#cttcatcc  43020













aagcaggtcg actctctcgt gatctcagag acagagtgaa gtcatgagtg gg






#aggggagc  43080













acagaaaata agaccttgat tcccagcatt gggagactcc ctgctcccct ga






#gtctcgga  43140













aaatagcacc cttcaaatgt tttagggatc cagatttgat gaagagatgt ta






#ttttggct  43200













tttagattct taggagagat ttgtctttct caggtcagga agaaaatgct gc






#ccgctgca  43260













cattcttcgg gacagactct tttaattatt actagtttaa tgtatgtttt gc






#ttagttaa  43320













ggaaaacccc tgtggtttct tgacgtgctt cagtattcta actcacagct ga






#ttcagttc  43380













agggggctgg ggagatgtcc tcgacctctg gaaaggaggg tgcatctcta ga






#aataaggc  43440













taagtatgcc actgacactg tctgcataaa cgtgtgtgat ctcaggtcca aa






#ggatgggg  43500













cctggtctaa gccagggacg tgggaaatca ttttcctgtg gcaacttgtg aa






#gaccattc  43560













tgtgaccttg gtgtctctgg gccttctctt agattttcta agttggctag tc






#agtggagc  43620













tgccatccct cctttgccca tgttctactc ccagagttcc tccaagaaat tg






#cggagcaa  43680













tgcctgtttc atgagagctg agtttgctgt gtcttccact tagaaacaac ac






#tgtggacc  43740













aggaggacac acagctccca gggccatcac cacacaaagt gaaggctggt ga






#atccgagg  43800













cttctagccc ttgccgggcc aggcccgcag cactccgctc cccaacccag cc






#gctgcttt  43860













gtcgcaggaa cctcagcagg gcagggtgtt tcctaggagg acatccgatt cc






#cagccatt  43920













cctttcagtg aatcacctga gctcacattc ttttttcttt tatttttgaa gc






#tcttagcc  43980













aatctgcttc gcgatgaacc agttttgctt gaagcagaca aacccgattg tc






#aggagaca  44040













gtgatgattt cttcagtctc tgaggaagag ttttcatttt ccccaattcg ca






#aaaaaagt  44100













caggtccctc cctccctccc tctccgtaga atattttcca tgtgtgttaa ca






#atggctga  44160













gcgtggtaga tgccaggaat ttctgtcaac cctcaaagag gaaagccctg cc






#taatggtc  44220













tgcccgttct tgttcactcc ctgccccagg ctccccaccc gccttctttc tg






#gaaggtat  44280













aaaggctcct gcttatacct ggcactgcac gcttcgctcc ctctgatctc ct






#gactgtca  44340













tgcccagtgt ctcagcctat cattctacct ctaactcgac cttgagtgac ct






#tgagcaag  44400













tttctcagga ttccacctcc aagtcactct ccctttggga tatgcagcac ta






#agttaagc  44460













ttgcctggaa aacatcactt gaagctggaa aaccactttt aacacagcgg ga






#aaagctat  44520













ttgttcagac aggagtgggg tgggtctggg cagagcactg ctctaacttg gc






#catgccgt  44580













ggcagcagct cctttaatgc cactttttcc tggcgcgccc gcggggcctg ga






#gctcagaa  44640













agaggggaac gctccctcgt ctctcaacag ttgctccaga caggtcagca aa






#catggaat  44700













tcagaatgtt cattaaacac tggctgtgtc ttttgtgttc aaaagcaaga ca






#ctctctct  44760













gaaccatggc cccacagaga gtgcagaatg tgtgaaacct gccgggaagg tc






#tggacccc  44820













ttgcggggca gtgggcagca ccgtgcctcc gttcacacca ctcacatggc tg






#tgcctctg  44880













cttccttctg gcatggctgc ttcttcctca ggtctcaacc atctccctca ga






#tgctcttt  44940













cccatgtttg tggctacagg tccccgtgac ctgcagaggc agagcactca cc






#agcagccc  45000













agcctcgttg cgcacccatg tttgcatttg caggccctag aaccactcca ag






#ctccgtgt  45060













ggcgagatgc accctcctgc ccttcactgg ggagctgccc tcctgttcac ag






#cggcacct  45120













gagtcacaca tctggagcca tcctggactg cctcatttcc ccgatggggg gt






#ttccctga  45180













cttcatccat cctgtctttt gggtccccat aataactgac atgggtcggc cc






#gtaccagc  45240













ccctgtgaga agggctttaa ctgccttccc accccctgct catcttagag tc






#tctctata  45300













gtgctgctga aagaatctct aaatcagtgg ttctcaacct cagccgcaca tt






#gagaatca  45360













cctgggaccc ttaaaaaaat cttaactctt ggtccaagaa ttctattaca at






#cggtctgg  45420













gatggggccc tacaggtatt tttttaaagc tctccagttg gtaatgcata gc






#tagagttg  45480













agtatcgctg ttctaacgtg cagatctggt catgttacca gccttttagg tg






#gtcttctt  45540













tggctttctc tatctaaagt tcaaaaccga acatgtgcgc attcagtgca cc






#cattttca  45600













actgtgcatt aacacattca gcccaccagc aagatttatg aaccattttc tg






#ctgttgta  45660













tataacatat catatgcata atggcatagg ttattgtttt cttcaaaata ta






#tgagatgt  45720













gagtccttct acgaactgac tcacactgat tgcccaactt cctctctcga gg






#tctcatcc  45780













tctttccctg cagccgtctc cctcttgcac gcacacacac acacacacac ca






#cacacaca  45840













cacacaccac acacaccagg gtcgatgcca tctaccctgg acttcatctt ga






#actccttc  45900













gagtgtgagt cattactcct ttgtgcacct ctgctttctc ttctcaagat gt






#tcacctgc  45960













ttgaggtcag ttccttgagc gtcttccact tgccatgttc accacagtgc tc






#aacatgcc  46020













tgaatgcatg gatggcgact tctcagatcc tcagtctcct catctgggta at






#aaggcatt  46080













gggttggcgg gtccatctgg tttcttccag ctctgagagt gcatttgctc tg






#tgattcat  46140













tcgttccaca acacttcacc aattaaagag agggtacaaa aggtgaacat cc






#ttggctcc  46200













cagcagatgc tcctcaaaac ctgaaaaatc agataggtga gggaagattg aa






#tgaaaggc  46260













ctcttatgat tctgcagcaa ttttggtggt ttaagaactc tatggaaaaa tc






#atcagtat  46320













ttctggaatt gaagtaaaat ggatagtgag cctctgtgta tgtgaaggcc cg






#catctgga  46380













acatgaaaga acctgtctga tgtgttctag tcaggaaagc aggtagccaa ta






#ctatttat  46440













agaatttaca gaaactgaag attttgtttc tactgatttt caaaatagta tt






#atgtctga  46500













tttttttcct cagaaatata cttcctgctc ttctcaacaa actcatttga aa






#atatgatt  46560













agaacatgat agaattttac tcatttgcca actgcggttc ccatttcaca ta






#ttgttaga  46620













attctgcatg gtggctttgc cctttaacca ctaactgata aatgatgtag tt






#agctttta  46680













aatgtgtgga aaaatataat ttcaggttca accataggtc agaagtacac gt






#gttttgtt  46740













agtctatttg tctctcagtc atctcatgga aaattctcag cttttggtat gg






#aaataatt  46800













ttcttgaagg caatatttgt tgagtgactg acggaatgaa aaacgccagt tg






#cgtaagtg  46860













tgaaaaagat ctgggtgttt tcattggatc caaattccac atgagccaac aa






#cagcgtgg  46920













tgtggaggct ggagcacatt aataagaaca gtgtcctaaa ttcaggaggt aa






#tgctctgc  46980













ccatgccctg tgcagctcag acggtgtgtg cagtgcagta tgtaacccag gg






#cacatttc  47040













aggggcccac agggagctgc agcttgtaag gtggagtgca gccaacagag ca






#gagagtca  47100













gaatccccgc agagtggttg aaggcacaag gatgcgcagc aaggaagaca ga






#cttatagg  47160













tggtgcgact gccatcctct ggtactgaag gtgctatcat ggagggaggg aa






#gtagattg  47220













accctcctgg ctccagagta cggaactcag acaaacggtc agaagcttac ag






#ggaggcca  47280













attttggatc aactttaaga agaatttttt aaaagctaga gcaatcctaa aa






#tggaattt  47340













gctctttata aagttgcgaa tgcctcaccc tggaattgct taagcaaagt tg






#ggacgggc  47400













agttgtgagt aatctccttt ccaatccata cccgcaatca ccagaaacgt gg






#acttccct  47460













gacactgagc acctcttaat taagcatctc ataagtgaac aaaacccagc cc






#ttcaaaga  47520













agtcacttta tttatgtgtg ggtctgcagc ttggatttct tgataatgtt aa






#ataaaact  47580













ccatctactc ttccacaaac acttcaagaa acctaagact tttggccaga gt






#aacaccga  47640













ggtttgagag aaaggatatg tgtgtgagag gtgtggtttc attagaacat at






#tatttgac  47700













ttcatgttga atcaacactt ttgtgcaaaa tgcagtttta ccagcctctt tc






#cttgtttt  47760













ggtcacataa tttaacttaa cattctcggt acttgatttt ctaacataaa at






#gggattga  47820













gaggggaatt ttgaagttcc catggtctgt cctctacatt ctgacagctc at






#tatctctg  47880













cggtattgtt ctcacattta agtgaggtta gcggaggcag aggcctctca gg






#cctgaaga  47940













tagcctctgt tttcagggaa atactagact gtgagatctg tgacactgaa gc






#actaagtt  48000













catctcacaa aagcaacgtg ctctttttaa atggttgatc aaagttactt tc






#aaaaggaa  48060













gtgttagttt ttgttattag ccgaaacaag agctgcttta atgtagtata tt






#taaaatca  48120













tatctcaatt aagatgttat tcaaatacta tttgacccac caatctcatt ac






#tggatata  48180













tacccaaagg aatagaaatc attctattat aaaaacacat ggctgggcac ag






#tggctcac  48240













gcctgtaatc ccagcatttt gggaggccga ggcgggtgga tcacgaggtc ag






#gagttcaa  48300













gaccagcctg gccaagatgg tgaaacctca tctctactaa aaatacaaaa at






#tagccagg  48360













cgcggtggca ggcacctgta atcccagcta ctcggaaggc tgaggcagga aa






#attgcttg  48420













aacgcgggag gcggagtttg cagtgaacag agatgaagcc actgcacttt ag






#cctaggtg  48480













acagagcgag actctgtctc aaaaaaaaaa aaagaaccac ttgcatatac ac






#tattcaca  48540













atagcaaaga cgtggaatca acctaaatgc ccatcggtga tagactgcat aa






#agaaaatg  48600













tggtacatat ataccacgaa atactatgca gccataaaaa agaacaagat ca






#tgtccttt  48660













gcggggacat ggatggaact gcaggtcatt atccttagca aacgaataag aa






#aagaaaac  48720













aaaataccgc atgttatcac ttataagtgg gaggtaaatg atgagaacac aa






#ggatacac  48780













tggggcctac ttgagggtag agggttgaag ggagagaagc agaaaaaata ac






#tattgggg  48840













tactaggctt agtaccaggg tgacaaaata atctgtacaa caaactacta tg






#acacaagt  48900













ttacctgttt aacatacctg cacatgtacc cctgaactta aaaaaatttt ta






#aaaagatg  48960













ctatgcaata aaattctcaa ttaagaattt aacttggtaa atgttcattt aa






#tgatctaa  49020













aaatatgtgt ctggatggct ctagcaaaaa aataaataat aagtttctca ga






#gatggtaa  49080













ggctgaaata aatggggaaa aatctgaatt gtaatccttt ttctgttgga cc






#tggtgttg  49140













gggtttcaca cttgtgggtg aatgtgggcc tcctgtgagc accagcacaa aa






#gactaaac  49200













tgaacaaaag attaaatgtc acctctaaaa ttctgtgcaa caagacttcc ag






#ccacagaa  49260













tgtgcaactc agatttccaa gtaaaaacac accaggaagc agatcttaga tc






#tctgttat  49320













ctccttggca ccagctggta ttcatcctca atgctagcta gagttgaaat aa






#agagtgaa  49380













agaactttct cttttattac ttaataaact tccttttttg agctgtttta gg






#cttacaga  49440













aaaattgagt ggcagtttca gggagttcca gcacggcccc tgtttctttc tc






#atggtccc  49500













tgcaggtttc ccctattatt aacgtctgtc attagcatgg cacatttgtt ac






#aattaatg  49560













agccaatatt gatacattat tcactaaagc ccacaggttg cgttaggggt ca






#ttcttggt  49620













ggtgtacgtt cttcaggtct ggacaaatct ataatgacat gcattcacca tt






#actatatc  49680













acgcagagtc gtctcctggc cctacaagtc ccctccttcc ccacctgctc ac






#tcctcctt  49740













cccaccctcc ccaaactgtg gcaaccattt aacttttgac tgaatggatt ta






#ttcttatt  49800













ctgccttatt gtatgtacac catattttaa taagataaaa taatagtcta ta






#gtagactt  49860













ctgtaaatac tcaatgaata aatacttgca tgaatgcagg aaaaatcaat ca






#gtcttgca  49920













ggatttctta tgcgttacat cgtccttata agaaagcagt cattctcacc ga






#gatgtgct  49980













gagcagatac tggacatgtt ctgacccaga taagggctgg gtggaagtag gg






#ctggagac  50040













acagagaccc agtgccaact tccaggacct cggaagaact gaaggcagag ag






#gtcctctc  50100













agtgtggact gggcctctgc tggcagccac cagcgggcac agagctgatg tg






#tgttatgc  50160













cacgtgggga aaacctacag acgattctga gaaaggctca cagggacacc ct






#ctgcccct  50220













aaaagaacaa tttaactcta atttatttct gtcactctgc attttctgac ct






#ttcccaag  50280













tgtacagttt tatatgcatt taactgccaa attgtcatgt gagattatat gg






#ttatattt  50340













cattaatata ttctagtttg ttcagctgtt cttactgggt gaatttgtgt gg






#tttcctga  50400













catttttgtt tttagtagtg cctcagtagt tttatacata attacgtttc cc






#ttctggat  50460













tatttcctta gtatctagtt caagaagtga aatcgctgga ttcttgtggt aa






#atttttga  50520













atttcacagt ataatgctga ttttctcaaa gtctcacatt ctaagaaagt at






#aatgaggc  50580













aaaacaaaca acaaacatct taagttgatt ttttcctagc atcttttcct tc






#catctttg  50640













cttgtagaat ctagactatt tcatgaaccc aagatataat cagtatcctt ct






#tcagtatg  50700













gccaaagtga gtttctcatt attttacctc cccttcagga aatgactttt ca






#tcttgtgt  50760













tttgggagcc atagatggtt ctgggcagga aactggcttt ggatagaccc ag






#catgtaga  50820













tggctatttg gccttgctcc cagtataacg atgcagttcc ctgtgaaagg gt






#atgagtag  50880













gttttggggc tctggatacc gtgtggcctg aagagacaag ggctcaatgc ca






#actctgcc  50940













tgtttccaac tgtgtaacca tgtgagcgtc aaaaatcatg gacgtgctct gg






#ttaacact  51000













gagtgggagc tcaacaaatt attattttta attgttactt ggacatggcc aa






#gttgacta  51060













cactttatgt tctgctacct gccagtctga aagtgacgcc acagaaggtg aa






#ccgcatgt  51120













tgggagatgc tcctcatctg cttaaatgag gtgcaaacac agcccatgcg cc






#tgctcttc  51180













atgactgtat ctgtaccagc aatatttgta ttggcaaatc acatgcccca gt






#gggaacta  51240













cttaagggga attcaatgga tttcattcct tttatgtaat tggccactta gt






#aatagacg  51300













tgtaggtctc ttgtgtggat aaggattctg ccttttatgt aagatatgtg tt






#gcaattca  51360













gctttcaggt cccagccccg ggaaggctcc aggccttcac aaactggccc ac






#ccacgaga  51420













aggaaagcaa ttgtccaaat gtgggtagct tttcttccca ctgttgtcag ct






#gcttccaa  51480













ttagccccca tatacataat cccagtttgt gtctgtatca gtacaattct cc






#catgtcaa  51540













tgtgaatttt aagccacaga gggaaagggg acagagaata tgctttcatt ca






#gctctcct  51600













cgtctcacac ctcttgccct gcatgcattt ctttgctctg attaaacgag ca






#ttttataa  51660













gccacatttg ctgtgtgaaa ggcaaagtct tccctcccac ggatgacggt ct






#ccagggat  51720













gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgaga gagagagaga ga






#gagagaga  51780













ctgtaaacat atatctctgt gaaacttcat tttccatatg tgaatttttg ga






#accgagac  51840













aaatggaact tagctaaaag atgggaaagg tagactgact ctgacttaat ct






#acttaacc  51900













taccaggcaa tttataactt gatggcctaa tttttgcagc acccagaagc aa






#gcctgttt  51960













cagcacggca aaggctcagc tgctaagtgg gcagcattgt tggaggtgag ca






#gcttaggc  52020













tgactgttca tcaaaggacc aagcgcttga ggttcgctca tcgctggagg cc






#agagtggg  52080













gagggccatt taactgctca aggccatgga actctactgt cagtttcagg ga






#aatttggg  52140













accctggagc acaaaccaaa actccaatta accaggagag gaactcgatc cc






#caggagat  52200













aagtgaagag taagaagtct atctttagaa acaagagatg tccaaggcta ga






#aagatggg  52260













gaaggagggt ggaactgttc tggaagtggg tctcaatctc agcaccagca gc






#tctcaaga  52320













ctttctagag aaggaaactt catttctgaa ttaaaattag tcttcaatga ca






#tggcaggg  52380













atttcggcac actctcttgc gtcataggcc actgtgttgg aggcaggagt gt






#tggctttg  52440













gaggcataga gattaaaatt agagtaacac gtgagcactg aaaaggttaa ac






#agtagaga  52500













catggaggac tcccgacccc catgtacccc tttcttaacc ctttaattaa ga






#tcacagcc  52560













ctagaaatag cttgcaaaat aattaactac tgatcattta taccttagtg ct






#tctgtgag  52620













catgttttct ctttcattgc tgctcatctg catggaaaaa tgtgcatggg tt






#tctgaata  52680













taactccatg gtgcttgctt ccattatatt tgtgccattt ggatcataac tg






#ataagcaa  52740













ccaaagagtc ccatattact gcacgttccc atcgctattt tatgtgaagg tg






#gtcctggg  52800













ggctgttctg aattctcagt ttcctttttt cccctcccca gttctttgaa aa






#tatcagaa  52860













acggacttgt ggcatctttg aaaagctact taaaatgtgc tgctgtgctc tg






#aacttgaa  52920













aatgtgcttt taatacaaag tttgtgcagc ccttgctgct catacgagat ga






#atcttacc  52980













atgtggtgga tgcccgtctc atgccaggca ctgtgctcta agcccattgg tt






#tatttcag  53040













tgcttgaaat tggctttcga gagaggcacc acggttccct ttttacagga ga






#ggaaacac  53100













cagaggatca gagatggaga gtctttctcc acaaactcac agaccccaaa gg






#caagctca  53160













gggttgtcag cttccaaagt ctgcctgctc caggacctca tgttgcatct cc






#attctctt  53220













cactgagggt caaatggaaa gaacacatgg gggtcaagtt tcagaaaata ag






#agaaatga  53280













agaaatatgt gcccggaagc aagaacgacc gacctcatta aactggctcc ct






#tcacctcc  53340













tctcacatct ttttctgcct tttggccaag ttttctctcc cccgcatttc ct






#ccttgatc  53400













tcgtttgaat cctcttccct ggtgaagtca tttaggttca ggctcttatt tt






#actttggt  53460













ccataattta gatcgaacca catgtgctga tgtgattgaa acgatgtgga at






#tctctgga  53520













cagagataga attatggagg ggttagtgtg tgtgtttaag attaaaagac ca






#ggtgtatg  53580













ggaggaaata taatgaacaa aaaatagtat tttaaatgaa tactaaactt gc






#actcatgg  53640













aaaaagttct cttcccatga ggttctcgca aagcatttta ccatcagcac ac






#gcagtttt  53700













tctcagtttt ctgagatggg gccatcttga atccaacaga caacacacag ca






#tcagccag  53760













actaacacaa aggacgtcat gggcatggac gtaaatactg gtgtcaacac ta






#ggtctgca  53820













cctcgagagg agtggagcaa aaggatggag tggcagatga aggtatgctg tt






#cagaaagg  53880













aggcagaaat gaaaggaaga ccatcagtgc gctccacagc ttgaggaccg tc






#ctggaggg  53940













caaatgccag ctgctcactt ctgaaaagaa aaattccagt gaaatgagta ca






#gtcattct  54000













taggattact cacttgatac tgtgtatgtc tcttcttggc ttctcatctc ca






#cacaaaac  54060













cctcaggtgg taaaaatcta attaaaaaaa ttatataaag tcttgtagat tt






#attagcct  54120













gaacataata gatttttttt aagcacgtta agtcttccat ggactaaaag aa






#aacttgta  54180













aacctaagag aacctctatt tttgatatac aaaataatac atttccttaa ac






#tatgatct  54240













tgatactaga attttaatta aaaaatacct gcagtttata tgcaaagtta ta






#gattaatg  54300













cttaaaaata ggttgtatgt agtatccaca ggtcatgttt gactgtcaaa ta






#gatgtaat  54360













tttaattcat aataattgtg tcgtgttctt ccccactaga agccaattat gc






#aagcttca  54420













ccattcacac atggaaaata atttaatgga gtactcattg caatttcact ta






#tccagaat  54480













tggctgttgt tctcagagca gcttgtgttg ccttgttaag gagaatatgt ta






#gtatccag  54540













acatccagaa aggatccttt actgtttcag agtccatttt ccccactttt ga






#aatacaca  54600













cacaaacacc cattcatgca aaccaaacag agattgtaaa gtgattccac tg






#acatttat  54660













gcacttcttt tttctctttg gttcttcaaa ctctcagtca gtgcgcattt ac






#tcttaatt  54720













tagatacggt ttaaacctaa ttagaaacca gaagctcttg tatttccaca aa






#ggattatg  54780













acagccccaa gaaaagatag tgaaaccatt atataacaag ataaaggctt ct






#taacaata  54840













caaggatgga ttttctcatt gatcttagcc ttctgaattt tagaaattgc ca






#tttcaaag  54900













tctaaaacaa aggaaaatca gggaataaaa gaatggtaag tagacacaaa cc






#tactggct  54960













ccatcatttc tgttttagca aataacctgc cacatatacc aatagcccaa ga






#gatgggca  55020













tgtccctgca tttcctggtc aaggtgacaa cactgcgtcc tcctggaaga gg






#tctgccac  55080













tcaccatacc acaaaccaaa tataataaaa tcagaaggca cactatagtg aa






#ttttttag  55140













aggcatgtat tgaaaagcat ctcaaaaagc attctcgaag cttccagaag tc






#aactcaag  55200













ttatctgaaa agtgacactt ttgatgattg ctcgcttaat actgggagag cc






#agatgaag  55260













attcctcccc acttcctcag atgtgcaact ctggaatttc ttagtgttac tg






#gagattcc  55320













tgctgcattc tgggccttta atgcataaac actgagatgt tctaaggaaa tt






#actcccta  55380













gggaggagag gggtggacga ggagtaagct ttgctggtga ctcatgcgct gt






#gtggaaac  55440













tccctgcaca agtgagctgc gcagggtgag tctaaagggt taatgcactt tc






#aaaagcct  55500













ctaatttgtt attccagaag agtaatttac tcactagaag tatctgggtg gc






#tactaaca  55560













catttgtgtc tttaaaaaga tcagttttat tttaagatta aaaatataaa gc






#aagagctg  55620













gaaagtcact aaaaactgac agccagtttc ccattttcaa gagtatttat ta






#aaaggttc  55680













tggttgcaga aggaataaga aatggcttga gatcatgaca cagtgaatca tg






#ttgtaaac  55740













atgttagcta tggctgtgaa ttcaaccagc gatgagttca agcgtcccca ga






#aggtgttg  55800













ggggaattag ggacatggct gtgtttcccc agagaaaagt ggccatttta ct






#ttccctct  55860













tcactaacat gcttttgaca tgcatggcag agctgaaggc aaggggaagg gg






#acaacata  55920













gtaagtgact aagtggcttt tttttttttt tttttgccaa gtgaagctga gt






#catatggc  55980













ctctgtcatt ccaaaactat tctctacggc tgcattcctt tcgctcttgc ct






#tcctttag  56040













aaccctggag aaggcctcct gaagcctggc cctattatgt atcctgacaa ag






#ataaactt  56100













ttccaaaaag ctgcatgttg tttctagcac agtttttcct cgcagtgact ac






#gtgatgaa  56160













agtaccatgc agaggaggtg tctgactgag gcgttcgtgg tgtgtgacag ag






#tcccctgc  56220













acaggacagc cgcactcccc tcttgcgtcc tttcctccca tgtttgcaaa gc






#ctctttcc  56280













ctgtcagcag ggggtgttct ggcagttgac atttctgaaa actacagcct ac






#atttttaa  56340













aaaatccagt aagtgaaaac taaaaaatta ataccgtggt cataatagtg tg






#gcatttga  56400













taactaatga ggcactgtcg tgccagctat tattttcaga catttacagt cc






#ttttttaa  56460













atacaaagaa atatttggtg tgaaatgttc cccgggagct ggtgcaagca ga






#ggcgacag  56520













ggcaagggag cttgggttgt agcctcgaat tcctccggcc agggctaccg tc






#agcctgcg  56580













gcacacaagt aaatcaaata taaaaccaaa atttctgtaa gcaaatcagt tt






#ctaactca  56640













ctgtaacgaa ttatctttcg cacatcacag aggcatctct tttcactgtc ga






#gtttggtt  56700













tgcttggtta caaaaagggc agttcaaaag ctttggttgc tattgtgaaa gt






#cagctgaa  56760













ttccttccac cgtgctgggg tggggtgggg ttcacgcagg ttctcttttg tc






#accagggg  56820













tgctgtggat tcacaagtaa gcaagaggct cctcaggtca agcctctggc tg






#ctccctga  56880













ggtcagctgc ctagcttctc ctcctctgag atagacggga acaaagtctt tg






#atgtgtgc  56940













atttctcaag cttgacaatg atacagctac ataaaaaccc atgatttcat at






#agatattc  57000













caaaacgtaa aagtaaacca tgcatccaca gagacatgga attacagaac tg






#gatgctga  57060













gctggtcact tgggaggcag gcgtccttgc cattggttta tgcctcagcc cc






#accatgca  57120













gtggctggcc aggtgaccta ggccagtcct gcatcctcgg ctcctcacct gc






#ctggtggg  57180













acagtgacat ctctcctgca gcactgctgt cagggtgagg gaggtagggc gc






#agtttcag  57240













aaaaccattg ggctgcacct gcgtgagcac agctgcagga gcaaaagtca ga






#aaggtcag  57300













caaaggattt caggagcaaa ggtcagaaga aaccctcaag gtggttgtgt ct






#gcaggaaa  57360













gtgctgtcgt ctcctgcaat gctttcaaga ctattcagaa gcacagtgtg aa






#gggagagc  57420













cggagcccat ggggaaatga ctccagagtg ttccacgtgt tggaaggcat ct






#gttggaaa  57480













acggacattc aagcaaatag ttgcctgcat agacaacgca gaatgactgg ga






#aagcccca  57540













acaagttacc tactggtaaa tgaggtgaga agcttaaagt gagaacccca tt






#gctgcctc  57600













tttttcactt taaaaacatt taagttttga attatggtaa aatacacgta ag






#atttacta  57660













ctgtaaccat ttttaagtgt acggttcagt agtgttaagt atattcacat tg






#ctaaggaa  57720













ccaatctgct acttttgttt attaattttt tcctgagggg aaatattttt aa






#attttaaa  57780













atatttaatt gacaaataaa aattgtgtat attcaaggtg tagaacatga tt






#tcatatgc  57840













acgtacattg tatactcatt accacaatca aagaaattaa cacatccaac cc






#acccatag  57900













ttgccattgt gtgtgcgcgg atgtgcgtgt atgtgtgtgt atgtgtgcac gt






#gtgcgcct  57960













gtgtgtgtct gtgtgtctct gtgtatacgt gtgtgtacat gtgtgtacgt gt






#gtgttcct  58020













gtgtatgtgt gtctgcgcac gtgtgtatgc atgtatatgg gtatgtgtgt ac






#gtgtgtac  58080













gtgtgtgtgc atgtgtgtat atgtgtgtct gtgggcacag gtgtgcctgt gt






#gtatgtgt  58140













atatgtgtat gtgtgtacat gtatgtacgc gtgtgcatac gtgtgtgtgt gt






#gcacaggt  58200













gtgtatgtgt gtgcctgtgt gtgtgtgtgc atgtgtggtg gggacactaa aa






#atctctca  58260













tcaccttttt agtcaaaaga acagttgttt tggtttggct cttctgtttt aa






#aatatcag  58320













aacaataata atttcccaca gacaaaatcc tcaatcctca ccatccttct at






#ttcctata  58380













ttcatcataa acttcatgct tgatgttgaa attgttttct gaaaatagag aa






#tacaaaga  58440













ggagatttta aaatgtcagt ggcagcccca cactcctttt taatcttatt tc






#ctgatatc  58500













ttgagtttac ttggacgtag agttttcctt gactatggtt atttctggta gt






#agcagctc  58560













cagattaggc aatggttttc ttcagagata gcttagagtg agccccagaa ca






#aggtcaat  58620













gcgaagattg cttgtgtctg cgtgtccagg gcacagtgat cctcatcact ag






#ccgggggg  58680













ctccgtgagg atctgctcct ggtcgtttct gttctgtatc ttctctgcag cc






#cttactga  58740













agccgttacc aactggcaca attcaattcc tactgtaccc atcatgcaca ga






#tggctgaa  58800













gtattgagaa cgctccagtg accgggaggc aatagtctgt ccacatctaa ga






#acacactt  58860













ggaataacct tagagaagag agagagagag agaatgcatg gttagtaggt ta






#tcaaactc  58920













ctatgacttt tcacaggaaa agccctcatc cacaccaact ttaggaatgt gt






#agaaagaa  58980













gggtcaggga caggggtgag tggtgggcag agcagttgga gggcacaggg aa






#aaggcatc  59040













tggtcatgta tttggagtag gaggtcttgc tttactattg aattgcaggg ac






#actttggg  59100













aacagtgttc acttcttttt gcaaccattt cttcagagaa aagtcatgat ac






#tcaagtct  59160













tcttacaaag cagtttgagg ctttgagtac cagactgatt acagagatga gt






#atgaagca  59220













ttattgtagt atttttaagt gaaattcact aaatgcaaat aaacctagca aa






#tgctctat  59280













ggttaatttt tttctaaaat tcagataatt aagacaattc attctcctga aa






#ctgctgtt  59340













catgtaaaaa ggaattttat cgaggtggcc cttgagtgcc aaacagcctg tc






#ctcagctg  59400













caaaatgagt cgttgatgat cctccagcaa gggatacttt ttagctcgtg tg






#gtgattgc  59460













tgcacacggg atatgtgcag caagtatctg ctgagctaat aataaacagc ct






#cagacaga  59520













aagacagtgg gcacaaggtc atgcttaaaa agaccccttg ttctactgca tc






#ccagctcc  59580













ccaccatggg gcctcacagg ccctggtgac caagcacatc agacctggtt ct






#tgctcagt  59640













cctgggagcc acagaaccca gcacgtactt tacccccaag accagactcc ag






#cttggctt  59700













ttgtcctcct ctccaggatt ggtgacctcc taggtcgtga agctgtgatg ag






#caaagaca  59760













cactcctctc cattctccca acttcaggtc cctttgacag tgtcagcagg ca






#tttaaata  59820













gcagaccacc cacagcaggg ctggtagatg cagtgaactc aggaagatgc ct






#gcatagac  59880













tctagtgtta aagacagaat ccttacaagg aacccccata gttacctaac tg






#ctgtctcc  59940













agtggtcata gaagtgtgat aacccactaa tcatcattct ctgtctctct gt






#ctttctca  60000













tacacactta cacacacata cacacaacct tgttgcttaa ttttcagaga gt






#ctactttc  60060













agaaaagcct tcaggaatac atcatgtaca aaactgagaa attacctgaa gt






#atctttaa  60120













atttagtaaa aagttgcatt gttttttgaa catcacactt gaaaagtaca tg






#aatacaaa  60180













catacttagg aaaaaaagct ttaattaatt taaaaaggag aacaatgcta ta






#tgctgtat  60240













cccacctttc tctgaatgtt acattttctc ccctatccca ggctgcatct aa






#gaaaactc  60300













agagggaata tgctatctat cttttccgag caatgaaagc tctgggtttt tt






#ccttgctt  60360













ttcagggcac aatacttctc tttcttcctg gttagacagg ataagttctg ag






#tcccctgg  60420













tatcatcagc ttacttcttc tctgttaaat attcacaaaa aatcactaac tt






#tcatgcct  60480













cagcaaacct ccactgccta aaatatagtg aggtcattca tcttcggaca aa






#ttgcccca  60540













actacggtgg gaaaagaacc aatgtgttgg actatttatc taatttttgt tt






#agttcggg  60600













gatacaaata aatgcataga tacatacaaa catgcgtaca taatagcagc ag






#cagcctgt  60660













gaaacattga caagacctgg agttggaaga ggactttgcc atcctccagt cc






#aacagttg  60720













cctgtcacag attagacgac tgggatgtgc gcaggcgatt atttgcaaac gg






#ccctgagt  60780













cccccagttt atgtcttaat tcgcagccag ggctgattgt agaagcaaat tt






#gcaaacat  60840













gtgcaagaag aaatcacaca tcctagagct tggatttcct cgtttcttgc ta






#tttctatc  60900













cgtagacaga accattgctg agctgttaaa tttgtctcct tcccctatac ca






#gtcttgaa  60960













aaaggaaagg aagtggagca aagaaaaaga aattaataaa gccggcagat cc






#taggagaa  61020













tcttatttaa tccaagcttt gtaaagtttt gctttattcc atggcaacat gg






#gtatacac  61080













atcccaccgg ctgtttcagt ggctcagagc aggtaaggcc tgtgccaaac gc






#cgctagca  61140













ggaggaacaa cgtggagaca gccccagagg tggaacgttg gcccttctgt gg






#ctccggtg  61200













tctcaggacc tccctaaagc ccagccctga cactgagcaa gtttccacca ct






#gttaggaa  61260













gaagtagaaa ggaatttgga gggttggtgt tactgttcaa gagctggaag gc






#ttctgccc  61320













ccattcccat tccattaatt gcgtgaggta gagaactcat agaagatagg aa






#cacatatg  61380













ctgatttcca aaattgcctt tgtatatttt cacgtgaaga ctttaggggc aa






#aagaaaag  61440













aagcaagcat tttgaatatg tgtttcaatt tgccttctgt tatataaaat tg






#tattttgc  61500













ctattctttt ttcattattc ggaaccttca agaaataaat taagttctct ca






#aaaatgtg  61560













ttttttgaaa agaggactaa aacagatggc ctggctgtgt taaacacagg ga






#ccagacca  61620













gcacccacct ctccacctgc cctgccttca ctggcagaat tgtgatccat ca






#tgttctct  61680













gttcaatgtc atcatccctt tcagagcatg ggtctcttcc tttctaggca gt






#cttaccag  61740













gatgcatggg tgtgcctgcg taggcacacg cacagctccc aaggactcta aa






#aaaagata  61800













tttttctgct tatatactaa taatatgtta gagatttatg tttcaaatta gt






#acagaatc  61860













acatggttct ctccaaatta tatttgagag agaaagaata gaacaaaatt ta






#ttttacaa  61920













aaatactcag tacatttagg gcatatacaa agatgttcca gaatgtagct ta






#tctcttta  61980













aagacaatta acacagtttc tgggcaaggc aaggcaaaat attcagtaac tt






#agcaacac  62040













caacagaaga cagccaatat tgcagcacat ttttctcttg gattgggtca ga






#gagtactg  62100













cagagaaaat ggagtagaga gacctgaaat actttcgcac acactgtggt ca






#gtgcagcg  62160













tccactgtgt gccacagtaa tactagaaac tccctggtta ggccttggaa tc






#cagctctc  62220













atttcgtatg tgacctgcag ggaagtaagt taaatgcaca cgttttatca ag






#ttcaaatg  62280













caaacttaat tttaaatgta tgcaacatca gtttaagcgt tgtagctatt ac






#tagcaatt  62340













gtacctatta ctagtctgta ctctgcacaa ctttggagta tactgcctac tc






#aaggtgga  62400













ttttagagct ctatttgtgg cattatatca cggacaaaag cacgttcatc ag






#agtcagag  62460













gaatgtggtg caaatcccag ctgtcccact taccagctgt gggacttgag ta






#agctcctg  62520













aagcagctgc acctgcattt tctggtgggc accatggagc tgtcagcagt gc






#tttcctca  62580













gagggctgcg ggctggatga ggtttgctgg tgcatgtgaa gtgtcaatca tt






#gctctcat  62640













gagtggtgat gctgatgccg ttcccttttt tagggaagtg attttccctt ac






#aaagttac  62700













caacagtttc atgttggccc atttttctat taattgtttc cactaatagg ac






#caacagtg  62760













gtagtcccat cattttatta ctgcttgtcg tagcacaagc agttgcttca tt






#gtgtttag  62820













ataaatattg acggctgctt ttaacagtct gctgttttgt ctccttttga gg






#tccttaaa  62880













gtaatcctta aaaagatagt gcagatggaa agatgtctgg agtcagtgaa cc






#tgccttct  62940













ttcctgtgtg cttgtcagtt tctaaaatgc catacacaaa ggactttcat ga






#tttctttt  63000













taggtacatg attacagttc aattcacttc actgtctgga aaatttcctt at






#aatcagga  63060













tgaaatttct catgttagcc tttcacattt cactactttt agataaggaa tt






#ctcaggct  63120













ttgctatatc tgactgctct tggaggctga gcttttggct aactacctga ct






#actttgtc  63180













gtttctcttc ccttggaatg aagcaaatat ctaacttctc actcattgtt tc






#tgctattt  63240













taccatttag tcatctgtga tttttctaaa tactgaaaga cttccctcaa tt






#caaactat  63300













gtgccggatc aaggaaaggg cagttggata ttgcagacag catagtgcaa tt






#gtgaagag  63360













tgtctgctta ccagccacgc tgccttgcac aagttatcaa gcctctcaac cc






#acttcctc  63420













aatctgtaaa ataggtatga gtgtaggacc ttcccagggg atttttttgt ga






#ctatagaa  63480













tgattctcag aagactttca ggcagtatgt gggtgaggca catgctggaa ag






#gcttctgc  63540













aggtgcagtg atcaatgctt ttctcagtgt gtacatccca taatacagac ac






#gttaccag  63600













aaactcccta gccaggactt tgattgcagc tcacattttg tatatggccc at






#agggaaat  63660













gaagtgtgta ttttttataa agttcaagtg ttaacttaat ttggaattta ct






#atcaaatc  63720













tcagttgtta tgggcattta tagctattaa tacttcgtcc catgtgtccc at






#gaggaaac  63780













caaggaacag aaattaaagt tctttctgga gtcccctgaa tctcgttcct gt






#tcttttgc  63840













accctgttaa ttacatagag acattcacag ctcttctgac cttatcagcg tt






#aaggaaaa  63900













cagaaaacca gcgtgctatt tgttctgtcc cttagtcaag ccttctcaac at






#atattttt  63960













cttccaagat tttgcatgtg cacagggatg cctatcctct acaagaaaca ca






#ttttaggc  64020













aaattataat taaaatgctg tttacatctc ttcaccttta gaatttaaag aa






#tgatcatt  64080













tcttagattg catctcagac acacccttcc cctagtctgg agagggcgag gc






#ccatgggt  64140













actgcaaaca gcctgacgtt gtcaggggcg gtctcaacgg ctcattcacc ac






#atctgcct  64200













cgcgaaggct aagccatgtg ctgttacccc tgctgcgctc tggctcattc ta






#aggtacac  64260













gctattaacc ttgtgagaaa acaaagaggc cagccccacc cttcctgctc ac






#tctgagtc  64320













acggtgaaaa tgtttcagga tctcgggttc gaccatgagt cctgtccagg tc






#caggagga  64380













aattcggaag gaccacatgt tcactctgag atcccacttt catttccctc ct






#ggttgagc  64440













agcattaata ctctggctag atttaaattc tggctttctc cagttagaac tg






#aaagttat  64500













gacaatgtaa tcaaaataga atgtgggttt acagctggcc ccctggcctg gt






#ttgtgaac  64560













ataaaacaga aacagaaagt gtaagtggtg acatcatatt ctctcattca at






#gtgaaagg  64620













ccaccgaagt ctttccagaa ttatttttga gaataatatg aatttttaaa aa






#atacctaa  64680













ttattttaaa tatcgtcttg cttgctcccc aaatacctac tgttttcaac tt






#ggatatac  64740













gacatgatta aagaatatct aatatttggg aatgcatact ttaaccttat aa






#actaccac  64800













tgtaaataga cagactcatt aaagtgaaag gacattttaa atcaattagt aa






#gcaaatca  64860













attaggtggc aaagacaaga ttatttttcc ttatggtagt tgaagaataa tg






#cttaacct  64920













gtcattctaa ttaccaagca cggtgttctc tttggaagat catttcaaca aa






#acattatt  64980













ttcatccaga atttgaacct tgagattgca tggtatttta gaaatctatt tt






#agaaatct  65040













ttggcaaagg ttactattaa aacaatcaca ttcatggaaa atcagtataa ga






#gcaactaa  65100













aataactcac aataccagta aaatcacttt gtcatcttct taagactttt aa






#agagcatt  65160













tgtaagtaac tgaatagaag gccaaagggt gtgtaggtag cccagaccat ca






#gtgggcag  65220













ccagggccag ggcaggggcc acggttgcag cctgcattct tctaaagggc ag






#agcaaatt  65280













aaagttgaag caggagctaa aaaaaaaaaa aaaaatgttt caaagaattc ca






#ccaaccag  65340













aggatactac ctaggacagt ttgggcctaa cttatctgtg aaggcctcca gc






#ttcctcca  65400













caccggtggc cacttttcat tcactctgaa cccttctttg tatggaggtc at






#tttattaa  65460













ttgagctgtg accaacatga cagaatttcc tgttttaggg cttttataat at






#agatagtt  65520













tatatctaat ttcagaatat attcactggg gaatggactt agcaaccact ac






#cacaacaa  65580













tgcaacaatg tgttttggaa caaatttacc aatctgaatt tccccctaga tt






#aggtcaca  65640













ggaacattgc agctgatgta cagctatgtt cctcctgaaa cttggagaca ca






#tcctcttg  65700













agctgggtta taatgggcca cccaaagctc gagttcctgt aatggataca ct






#caggcagc  65760













agaacctacc accgtagtga ggacagcacc cagagccctc agaggccatc ac






#aagtgcac  65820













cacagctgcc ttctctggca cgctcagagc tacacagtgt actctgggat tg






#gaactctt  65880













tatttttttt tcagttgatt tgtaaataag attgcacaaa aatccatgca ca






#tcaactct  65940













ccaaatcaga atttgctgag ctaaaaagag cattaaatta gatgggctgg ct






#ttcaaggg  66000













gtgggggtgc aatagtggaa ctctgcacaa cagttcttta caaagagaca ag






#caagcaca  66060













tcgcgtggaa atttccattc aactggaaat gtccaagcct gtttacctca at






#taattgtc  66120













cttgttcact tgtccagcct agcaattgtc cattagtaat ttgttataaa tg






#agacattt  66180













ggtattaaag catctctttg ggatactggt atggtttatt ataacattct gt






#tagtagtg  66240













ttgtacaagc ttgagatgta ttaatacgaa atccaagctg catgagggct tt






#atttttca  66300













agcctacacc ttgctgaaat tctgaattaa aatatgattc tcagtacaaa tg






#aataaatc  66360













aacagaaatg gtaacgcatg tcaaatattc ttaaaaccca agaaagcctt gt






#aacttcct  66420













tcaatctaat gggaaatgca ggcaaataca agactgatgt ccttgagttt ta






#ttatcaag  66480













actcaagggc accagtaaaa tctagtttca ttggttggaa aaaaaatcct ga






#taagcact  66540













gttaggcata ttaactttaa tgattacaat ttttaggaca ctctgtggcc ta






#gacttaga  66600













aacacaacta atgtccagaa aaagattcct ctttttattc catcatctga ta






#ggcctatt  66660













tttacacata cacaccaacc aaaagtagcc aagcaaacaa aacaacatac tc






#acacccct  66720













tcgcctatta tcatctaggt gattttcaat gctcattgca atgaaaccta ct






#tattgtgc  66780













atggcaccca cccccactga ggaatactgt agtttctttc cctttgaact tc






#attagtag  66840













agcacatggt tcattcactc ctgaagagtt cttcgtatgt cagaatatat at






#actacaac  66900













ataatttcca tcagagctct gaccacccgc ttatctattt tcataatgcc tg






#ccactcca  66960













tcattagctg ttgtcatgta ggctatcaat aaatatatga caaataaaac ag






#ttagggaa  67020













tgagggaaat tgactagcag ccaaagacct aagccatcct ctgcttggac at






#tagaaaac  67080













tgagttcact acagtcataa gatacacaaa ggcagaatgt aagccataca aa






#aatccatg  67140













tcaatcccaa tatgtgagta caactattga acaccatgta ctaatggatg ag






#ttggtaaa  67200













tcattcaatg tcttcatgag gtcaattaca gattattatt tagaccccaa ag






#attccaaa  67260













gatggtattt cggtcagatc ttcatccttt gtaagcctag cagaaaatat gg






#cagtttta  67320













ttgactacta ttctttgctg ggtgtggtat ttttaaactg agacatcagt gt






#gcctagca  67380













cagggcctca agcacacaga aaaattcctt gataataatt aaataaaatt tc






#agcaaaaa  67440













atatcatctt aaggctgtga aattatcttc ctgtgtggct aaaatagtga at






#aaaattca  67500













gcgcaatata aatcatagta caatttcatc actaaatttt ctgatcttga tc






#ttgtcatt  67560













ttacattgga agtaaaaatg tgtcctcctt tttttctctg acagtgaaaa gt






#gtgtgtgt  67620













gttgtgtgcc cttttgcaca ccctgcctca cacttgctgg tctaattcct tc






#cagcatga  67680













ttatgatata attaaatgac agaaatgttt acttccaagt ggaactaagc ca






#gggtaact  67740













cagggtaggg cagctgcttg caccgaaaga ccaagactgc tagagaacta gg






#aaacaggc  67800













ggtgcaagaa ctccaggctc tcatggaaga gcgggaggct tctatggggc tg






#cagaaact  67860













ctttggtgct tggggaaaaa atgggttaaa tgctcttaaa aaagaaacct gg






#gagaggta  67920













gtttccagat gcaggcccgt cttttctttt aaacagaggc agctccgaag ag






#ctggacat  67980













tgaaccctga gcaggaactg gaggccgtca gcgcagcttt gtttggcgag cg






#gagctttg  68040













caagggtgta atgctgcacc agggagacgc tatctgcagg gaccggtgac gc






#cgtgggtg  68100













tggaggggga ggcagtggct ggccctcttg gggtaaggta cgcccaggaa ca






#gtttagaa  68160













taacgtgcgc gagtcaaagg gaagaagaag ctcctgcaga ccttctgggc ac






#tgtgcagg  68220













gtttgctcct gtccaccgtg ccgtgttcct gtcctggggt atttgggtgt gt






#ggcgtgtg  68280













gggaggggag aaggagcaag gcggcaggga ggggatgagg accaccctgt cc






#atgggaca  68340













ggccctgggc cccgcacaca ccccaagccc cgcgtcccgc gtcctcactg tc






#ctgggaca  68400













ccccccaccc caccccaccg ccacagccca gagcggtgcc aggaagccgc ct






#cgacgcag  68460













ccgtatcttg aggctccagc cccatcccca gggtaccacg ccacgtagag ac






#actatttt  68520













tcacttcgtg tttgtcactc ctaaagcatg tgtgctagct gcaccaaccc tg






#ggatgcct  68580













cggtgcatag ggtttatgtg cgtcctcctc cttccctctg agctggtccc cc






#gtggggaa  68640













ctgctgccca gactgacctg cgtccttccg cacgtgcagg aaaatgtcca cg






#tgcacttg  68700













tcagggtggg ggccacacgg gcaccaccac tgatcatctg tgggatcgag tt






#actgccca  68760













tgcagatccc acgtgcaggg cccagtcgct ttggtgagag agtggacgct gt






#ggtgactc  68820













cacggtctgt ggctgtgctc aggaggacag agaggggaca tcctgagatg gt






#ttgggcag  68880













cccgcggatc ctgtgcatgt ccccagagcg tccactttct ccatggagca gt






#ggagtggc  68940













gttgctgaga cagaaagttc aggttctcca ctccccatgc agcccccact cc






#cctgtctc  69000













cggccaggca cgcgtctggg gtggagactc ccggtgcccg gggccctcca ga






#cctctttc  69060













cccaccccag ggagcaggcg ggtacttcta ttccgtttgg cttcagaagg ga






#aaagagaa  69120













cgtaagttca gggagttctc gtccattcct ctcccgtggg ccgggcaggc ag






#cagggaca  69180













gccttcagga gccaggaggg gctcgagctg cgaggccctg gaatgaggca gg






#catgggct  69240













gaggctggag ggaaagcccc gctaaggctg ggcgggggcg ggaaaactta cc






#accagggg  69300













actcgagatg gggaaggaaa ggtcagaaga ggagaggcca ggcacggggt gt






#gggcggcc  69360













tgcagagctg gagcaggtgc tccgcccaga gccaggcatg cacactcaga gt






#aggtggcc  69420













tgtgcagcgg ggaagagggg cgggtcggcg tgctgctgaa gatgcaggag ct






#gcggcctg  69480













ctctgtgcgt gctgaaggtg tggtgagaag cacttacaaa aagaaatgga ct






#gtgttagg  69540













attgcacatt ttactttgtt tctcccaaat acgtgttctt tgaatttttt tc






#cttccagg  69600













gccaggactg gagtgatggt tgagacaggc acgcactggg tcttgtctgc at






#ttacattt  69660













tgagattttg ttcagcatgg attttatggc gtttttttgt ttgtttgttt gt






#tcgttttc  69720













aaaatactgc acggtttatc gtgaagacag ggtcctttgc tgccgtctta ag






#ttttgggc  69780













ccaagaacgt gccccaccct aggcccgggc ctgctggctt catagctctc at






#cattccca  69840













cggaacctta agacctgagg acagaaagga aggaaacaag cccagtagtc cg






#tgaaaatc  69900













cagggtcccg ccactccagg tgtctgcagc agagctgaac acacgtaggc tc






#ttgccagg  69960













aggggcattt gtatgtgctg agcattcctt atattctcaa tatgacgcct tt






#gaaagatc  70020













tgtggtttgc aaatatttac tctcagtcca taacttatct ttccaacctc tt






#accaggct  70080













cttttgctga ataaaagttt taaattttga agtctaatat atttttaatt tt






#tttatttt  70140













atggatcata ctttttgtgt caggtttgag aagtctgcac caaagtatgt cc






#tgtggttt  70200













tcccttaggt catcttcaac aagtttcata gtattttgtt tagatgtaaa tc






#tgtggccc  70260













attttgagtt agtttttgca caagagttga ggtcaaggtt ctttttttgc ct






#gtgatgtt  70320













cagtggctct ggcaccattt gttgaaaaca tgatagccaa tgtcaagact ta






#atagttat  70380













aataatcagg agcttttgtt tctttttgtt ttgtttttag taactgccag tc






#actgcttg  70440













tggtatacat acacaatgga atactattca gtcttaaaaa aaaaaaaaga ag






#gaaatcct  70500













gtcatttgca tacctggagg acattatgtt aagtgaaata agccaggcac ca






#aaagaaaa  70560













acattgcatg atctcactcc ttcatggaat ctaaaaaatt gtattcagag aa






#gcagagag  70620













tggaatggtg gttaccaggg gctgggaagg tgtgagcttg gggagatttg gt






#gaaaggac  70680













atagaatctc agttagacag gaggaataag ttaaagagat ctattgcaca tc






#atggtaac  70740













tgtagttagt gacaatgtat tgtatacatg aaaattgcta agagagtaga tt






#ttaagtgt  70800













tctcaccaca ccaaaaaaag gtatgtgcag taatacagtc attaattagc tt






#gatgtagc  70860













cattccacaa tggatacata tatcaaaaca tcatgttgta taccataaat at






#atactgtc  70920













tctttatgta aatttaaaaa taagataaaa taaatgttat tcacttgtcg tg






#gatgtggt  70980













ggggacaggt gtgggatagc cctccctgta caactaggac ccaggggtga tc






#tagtgaca  71040













ctagccattt atcaggacgt atgggtgcca gtcaggatga taaagcttcc tt






#ttggccac  71100













tatactactt agaaatgccc tgcaaaaggt gcacatcaaa gattgaaagc tc






#aatcctgg  71160













attttaagtg cttcaaaagt gcacttaatt gccacatttt tgtcaaacat tt






#tcccaggt  71220













agtatttttc ctcatgtaaa acaacagcaa tttaatttga acagaaagca tt






#ttgaaaca  71280













tacttttggc agggttcctt gcagatcaga atggaaatga ttaacagggc aa






#ttatcaat  71340













catggacttt tggcggcaga aggaactgta ttgtttggta cagtctgggc ca






#gggccaca  71400













caccgtaacg gagatactct attctgtgga cggttggagg gggctgtgct ga






#gcagggta  71460













actgcatctt ttcctagact gttcacactg ctgccacgaa ggagtcttgt tt






#agactgga  71520













cctggctttc ttcttcgcaa tgagtgttgc agactcccga caaaggccag gt






#ggtaaagt  71580













gtggtgtctg tgagcgagag cctgagatgc ctgagctgac ctgtcctcag cc






#acctgcca  71640













tcgtgcagag gtgagagcag cccctgaatt ctgcccctcg gtctctccat ag






#ctaaagca  71700













aaaccatcct tccgtgctcc caggacaagc aggctattac caaatcaccc ac






#taaccctg  71760













ggcgaggagg ggccatcact gcacaattca tcagtgtctg tgacaggaag ag






#attgtttt  71820













agactggttt tttttttttt atttgcaagc ttttttctct ctccaaaacg tg






#ctgtcagt  71880













gtgttctaat ttactctgta aggaattctg gagctaatca taggctcaca aa






#aagcagca  71940













caggaaagtt tcccagataa catctatttc agtggctttc aaacattttt ga






#ccttacca  72000













aagtaagaaa tacattttaa tatcatggca cacatacagc tgtatctaaa ct






#ttcataat  72060













actgccttta cgatatcact ctgatattgt ctattctttt ctgtttattt tt






#ctttttgt  72120













tccttgttat gctggttgtg acccactcca gtgatttcac aatgcaggct gg






#gtggtgtc  72180













ccacagtttg aaatcccaat ctagggcctt cctctcactg tacaaagtag gt






#aactgggg  72240













acattagtgg atcagtgatc aaaccaaagt tatttgatct taccaagtga ta






#tcaggatg  72300













agaaagctgt tagagtgtca gatatgtgaa ggaacttggg tcattcctga ta






#cctcaaag  72360













agaaaaaagg tagtccttga acacctccta cttgtaaagg atgcacaatc ct






#acatgccc  72420













ctccctttcc tttcctcccc tctgtacccc acccctgccc acattttctt ca






#taagcagc  72480













tttggtgttt tggcttgttt gtttcccttg tctcctacct gtgactttat ag






#ccttttgg  72540













agactcacag caatagttgt atttaaactc agtgggtggc atccaaggct aa






#aaaggaga  72600













ttgcctagac acaaaaccac ccaagggaga aagcaggaca gcatcttact at






#gattgttt  72660













cttgtttctt cctgtctcat aaggattatt acccagggtt ttcatttttt tc






#atttcatg  72720













gttcattttc gctccagtgt agacatacaa tagaccactc gtccctgtgg ct






#ccgggcag  72780













cagcctcatc tgagaccctc ctgagacatc tcgtgcaggg cagccgtagt gt






#gtggcttc  72840













cccagggctg ctctaacaga tcaccatcct tgccatggct taagaagctg ca






#gatttatt  72900













tgcttacagc tctggaagcc agaagtccaa aatcaaggtg tcagtagagt ct






#ctctctct  72960













gaaacctgct gaggatgatg cccctggcct ctccccagcc tctggtgttc cc






#agcagccc  73020













ttggcattcc ttgccttgta gatgcaaaac tccgatctcc acctctatcc tc






#acagtgag  73080













ttctcctgca tgtctgtctc tgtgccttca cattcctctc tgtgtgtctg tg






#tttccatc  73140













tccttatgag gacacccatc actgaatcag ggcccactct ataccagtaa ga






#cctcattt  73200













caactccatt acatcttcaa aaaccccatt ctcaaataag gttacttcac aa






#gtgctgga  73260













ggttaggact tgaacatacc ttattgaaca atccaactga tgacacatag ta






#atttatgc  73320













actcgttctt ggagacgttg actttattta gtagcattaa ccatggcaat gt






#caccagca  73380













tcgctgacag cctgaagcat atgatctcca gaatgtattt caatcatcat gt






#tcacttcc  73440













ttggtattct ttagacaata actcagcctt gaactccagt aaagggtttc cc






#tgggattt  73500













tcttcttgac tcactccact gtggcctccc tcatccagga ctgtaacaga cg






#cctgacgt  73560













cagtggtcta gacctctctg ctgaatgtca tctttggtga atgtcttatg ag






#aaaacaca  73620













tggttggtca ctcttagaag ggcatgaaag cctgtctgca gtataaccaa aa






#caggcaca  73680













tggcgaggca cactgtgcgc atgtgtgtac aattaatatc atggttttaa at






#tattttca  73740













ggccaagggg agatctttgc tgcatctact gaagaaagcg aatctttttc tt






#cctgaaaa  73800













aaaatggcta cttattagtc gaatttgtgt tttaaaaata tgtgaactaa ta






#taatgcag  73860













acatgcatta atgtttaaat atactggaag tttttggtaa aatgaaaccc at






#tgtctctg  73920













ttgattactt tgatgagtca agaagtaaca tcctgggaat gattggccag tt






#taaatgag  73980













tgcctcaggt ttttggaata caagaaatca agaggaaggg attagaacat at






#aggttagc  74040













aagattggga tcctaaaata cagacccaaa tgaatggaac aaaatcaggg aa






#tttattaa  74100













taacagggtc aaggccaaat cagtaacaaa tatcctgagt ggaagaaagg tg






#gtttaaca  74160













aatgccccta tgaaagatag agattggctt accatgatga gatgtaagcc ca






#agttatga  74220













ggttggcaca caaaaccaca aatgtcatag cttaaaacaa cacacacttc tt






#atctctgt  74280













ttctgtgggt cagggtctgg gttctcaggg actcacaaag tatgttttca tc






#tggagctc  74340













caggtcctct tccaggctca taagggttct tggcagaatt cagtttcttg ag






#gctgtagg  74400













actgaggtcc tggctcctag aggccaccct ctccataagc agttcttagc at






#ggccgcct  74460













gcttctccag gcccagtggg aaagcatgtg cctccaggag ggctcagtcc at






#tcttcatg  74520













gcttttacct ggttaagtca ggcccactca ggataacttc attttgtatt aa






#atcaaaac  74580













cagctgattt gggatgttaa ttacatctgc acaacttcaa ctttgccata ta






#acctaacc  74640













atgggactga tatttatcat gcatttgggt caagttgcat taagagatat aa






#taaagctg  74700













gacaagcttc tgttgattag aagagttcag ttacaaggct acacttggga gg






#aatgttta  74760













caaactggaa tggtcagagg atggggaaga cacttgagaa aagtcaagtg ac






#ggatgaag  74820













gcaaatgtgg atatttatct gggagaaaac taagaggagt tataatagct gt






#cttcaaat  74880













atttaaaggg cttttattag gaagaggaat ttggcatatt ggattttgcc tt






#cagagaag  74940













tggagtcctg agatgctctt agccattcat tccagcctcc agggctcacc tg






#ctgtcttc  75000













tgtccaggtt ctcggtagca gggcagtaca gccccatccg tgatcttcca ta






#gtcaggca  75060













tattgtcaca ctcagtgagc ggagagtcaa ccgggaggaa ggcacagttt ct






#ctggaatg  75120













acctacggaa tggtacgctc aaatgcaaat tctccttccc ttccccagtc ct






#tgtccttc  75180













agatggtaat ttaggagctg aaggtcaggg caccagcagc ctttggaagc ct






#acaggaca  75240













acagtcagcc tggctagaaa aaaaaacaat gtcacaggca tgttgtgttt aa






#tcacatga  75300













aggatatttg cattgttttc caactgatgc cagcagacac attgtcagtg gt






#atcatgcc  75360













tggggtatca gagttgacat tgggttgccc cttctctgag gcattcatgt aa






#atcctttt  75420













aagtttataa aacctccatg tggctcctgc atgcttcatc atttgcatgt gt






#ctcttttt  75480













ccaggggagg cagcatgggg agcaggatgc tggtgggctc caggtgcaga ga






#gcagggtg  75540













ggcgtcagac cccaggtcca ctgtgcacgc cctcttgtag agcccgttcc gt






#tgtccatg  75600













agatgaggag tgttcttatc tctaaagtat tatcatgaaa acctaacaat gt






#agaaagac  75660













taaagcacat gggtggtgct tcataaatag tatttctccc actttctgaa aa






#ctcctgct  75720













gaagtaactg cacaagaatc cttgaacatt tagaattctg gttttagcca ta






#ccataaag  75780













tcagtagtgc gtggtggaat tctgctaacg aaaattgcga aggatcaagg ca






#gagtacag  75840













agctggtgtg tagcgggtac cttctgtctg ctggcactag gtattttaca ca






#ttaaatca  75900













gctcgttctc acatcagctc ttttaaaaat aaggaaatga ggagccacag tg






#gcccaact  75960













gatgcagtgg cagaagtaga atttgagctt gtgcagatgt gcctccgtgt tt






#tgtctcct  76020













gagcatgctg ccccaagttt gacaatacca agatttgtac tggaacattc cc






#tcccatcc  76080













ccacccccta gaagcccctc ttcctccctt agatttgaca catagtttga aa






#ccactatt  76140













aactacctta tgagagccac tgtttgtgaa gtgctgacta tgtgccaggt cc






#cgtgccgt  76200













gcaatttttg tgaattatct cgtgtctaca gtgcctcaca atttctctgc tc






#aatacctc  76260













catgttactg ccgaggaaag ggaagctcag agagagtaag taatttgctc ga






#gttaaaga  76320













gctggccagg acagccaggg gcttgcaccc cggagccttc atccactaca ct






#gtcagctg  76380













gtatctcaac cagccattac aggctgtaaa aaaattatat aagatagtct at






#ggtaatgc  76440













agaaaagtga ggttattttg ctccctttcc ctttgaagaa aaaagccctg ga






#aagacata  76500













tcacttgagt atgggaaaaa atgaagctgt ggcttttctg tgagtcaatt ct






#ttcctggc  76560













agcttcttgg aataagacca agtatagcag cagagttttc tgttttaatt tg






#agctgcag  76620













ggtgactttt tttcttctat gctttcatct ctctgtggct tcttttgcct cg






#ttaatttc  76680













atgccctgcc caggcgggct actgtgctgc ccagtcaccc gggtctgggg cg






#gccaccgc  76740













tggccagcag gcaggccctc cagaggcaga ggtggccacg cttaggtcgc tc






#ccgctgtg  76800













gaggcggcac acttgggtgg cagcacagct gtgatgtggc ggcagctggc ag






#ccccatgg  76860













gaaagatgtg tgaagtgtgg ggtttgacga cccatgggag aacagacttt ct






#tcctcttc  76920













ttgttttccc ttcaaagccg tgagtcaacc tcaaattctc tgtctttttt ct






#ccaccccc  76980













tcgtgcctct ctccctcacg ctctgcatct ctcattgcaa gcttgcattt tt






#ttgcacac  77040













aacactatct taatatttct cttttctgca ggcaggaaat gagaagtcat tt






#ttcagggt  77100













cattcaggaa gtcatccaga gttataatgg cccattatct actggtcaga gt






#ttacttag  77160













gctttcacta cttccactgc ccacttgaaa cagggaaaaa tattttcccc cc






#gcgctgtg  77220













agtgtgctat ttagagctga ccacaagcgg ggggaagaga ggatggctcg ga






#tgctgcat  77280













ttccactgag aacacaaggc tggcaaagct tgtctgctgc ccagcaagca ct






#tcaggctc  77340













acaccatttt aggttcactt taagtagttt ctcaattgtt aaaaaaaaaa ca






#aaaaaaaa  77400













aaaacctgta ctctgaggat atgcttataa tcccatagct aacccagaat tt






#cttagaga  77460













actgatcaac atcagcagtg gcacttactg aaaatgcaca ttctcaggcc ct






#gcgtaggg  77520













cctactgagt tagaatatta gagagcaggt ctcagaaaca ttctatccgg ca






#gtcttatt  77580













ctatgcaccc gaagggataa gagccatgct ttcatgaaac atgggttgtg tg






#taaaatgt  77640













ttaaaaggta tggcaaaatg tgtttgattg gcaccaagga tttctggttc ct






#cctagaat  77700













cattaatcaa actttgaagg agaaataaga gagtcggcat tttcttgcac at






#tctttgtg  77760













atgttgtgat gagttggaaa cttcccgatt gggtttatta gagcatgaac ac






#ccaggcac  77820













ccagcttcta gccagccctg tcaggcagag tctcctcgaa gatgtggaaa gg






#actgacca  77880













acagctgagg cctacaggaa cctgagcagg caaggggaga ggcaccccgg aa






#ccaggagc  77940













aatggccttc ccaccctccc tcgtcctctc ctcttctcct tttggagttg ca






#ggccacag  78000













aaaggaagtg acatgagtca ctttgggcct tcttaattcc ttcatcaaag gc






#agcacagg  78060













tgtgtatgtg tgttggtggc taattgaggt aggcccacag aggagataac ag






#atggacat  78120













actatttcct ttcttccatt ctgatataat tcagggtata aacacacaca ca






#cacacaca  78180













cacacattct cacttctttg gcatctacca cacctgcccc agtgcccatt tc






#tctcccac  78240













ctgaataaaa agcccccaca aagcctgagg tacatggaaa ggagcagtgg tc






#tggctccc  78300













aggagtgtga gaagcagcca tgttttcaga ggctgtattc cacttggact tg






#gccctacg  78360













ctgaaggtag gagcggatgg gggaggcccc cttcgcacaa agagccccat ga






#aagagtgc  78420













acagtccagt ctataaaaca gacgcagaaa atgtgtgtag gacttcttcc tg






#aaaaagag  78480













cgtggtgcgt ccagtacctc catgttcatg gaacttccca gtctgcagtt ta






#cccttttg  78540













tgcaactccc ttttggtaaa gccctggtca cacttctggt tgttcagatt at






#acagggat  78600













aattccagag tgattttaaa gtcaactgcc aggcatccgc acttgcaaat ta






#gatgcctg  78660













gcacatgctt gtgttaaggt aataattcat tacaatacaa attacagggg ag






#ttcctctg  78720













ggcatgcgac ctttcccgtc atttggcttt ccctgtgatt atcaggggag ct






#tccatcgt  78780













gctgctaatg ggaccttaac catgtgtcaa cccatggctg taatgctgac ac






#tgttttct  78840













ttctggaatg aaaggccttc gcaattgaaa ccaaaatgtt atccaactca gt






#cctgtccc  78900













tttgacgatg aaaacatcaa gttctggaga ctggccatcc agcctccctg cc






#tcatctcc  78960













cacgccctcc atcatttttt gtctctactt acttatttat ttggctgtat tt






#tacgtaca  79020













tcatgcaaaa atattcctct ttgtaaaaag tataatgatt tcaggaaatt ag






#agggtaaa  79080













aagcaagaac catgctttca ctccactgtc aagagttgtg gaagaatcct tc






#cagcattt  79140













tttctgtgta ttttacatac atacaaatat atgtacaaat aaaggtcgat ca






#tttaggtt  79200













ttgtttatat ttttgtatat atgagcttat gtcattcata catattgttt tg






#cctcttgc  79260













ttttttttaa cttaatttta ctttgcttga gagctttttg aactgaagta cg






#tgtaagtc  79320













agcctatgca tgtaatggct ccctcatctt ctgtgaggct gtcactaaaa ag






#gggattta  79380













gcttgttctg ggctttgcag cccgtacact gggcactgtt catacgtact tc






#tctgtgca  79440













cgcaaaggag ggcttgctag ggaggcctgg cagagggtgc cattcaaata gg






#attttcaa  79500













tggaggaatt tttaaatttt cagttatttg aataagtttt aatatatatc ca






#gaacccca  79560













aatcatcaag tttgttttct tccacatctg tccttccatt tctgaactat tt






#taaggcca  79620













gtcatgtctc atccaagaaa tcccatcctt tcacacaaca ctatctccgt tt






#catggtta  79680













tgaatctcta aaagcatgat ttttaaaaca taatcacaat gctgtcatcg aa






#cttaaaaa  79740













ttagccataa atctcttatg ttacccaaca accagcctac tgacacatct cc






#agttgtct  79800













caaaaatgtg ttttccattg tggtttgtct gaaacatgat ccaaaagtca ga






#cccacctc  79860













tcacctttcc ctaacctgcc ggagcccatg tttctttcca gccaggcttg ga






#gaccacca  79920













cacgggattt gcttcttggg gcctccctct aaccagctat gcaggatgcc ct






#ctttcctg  79980













tcaatacaag ctgctcaaag gactcattca gttcaaattc acctatgtga gc






#ctaggtga  80040













tgctacttat ttatttattt atttatttat ttatttattt atttatttat tt






#tgagatgg  80100













agtctcactc tgttgcccag gctggagttc agtggcataa tctgggctca ct






#gcaagctc  80160













tgcctcccgg gttcaagtga ttctcctgcc tcagcctcct cagtagctga ga






#ttacaggc  80220













acgtgccacc acgcccagct aatttttata gttttagtag agacagggtt tc






#accatgtt  80280













ggtcaggttg gtctcaaact cctgacctcg tgatccaccc acctcggctt cc






#caaagtgc  80340













ttcatgtttt caggagctgt acgtgcattt ttagttttga tgaccaggtc ct






#ttttctgt  80400













tttttaaaga acttcaaatg atctccaggg tacacagcgc ttgtgtgctg at






#gaaaaagc  80460













tggcagtaca aaggccacca gccaaggtca cacagccaaa aagcccctga cc






#tcgggccc  80520













cttcccagac cctgggtctt ttgctgccac atgaatcttc ttcaaggtcc ta






#tgtgtaga  80580













ttttcttgac ttggccatat tatttaggat tcagatataa taacaaaata ga






#tgttaaag  80640













cataacatga aggcatttaa aagggtagaa agcacatgat ttactaaaac ca






#taaatctt  80700













atgacctgaa agtttcacct aatctcttaa aaaataccgt actaaaccct ga






#ttgaaaat  80760













cagagctcag acatacagcc tgagatgcca aaaaatggcc aggcttgtct gt






#tgagaaag  80820













ccatatgtaa ctaactgttt ggaaattcaa aatatatctt atcattttaa aa






#acatcttt  80880













cttctaaaga caatcatctt ggcttcagga atgaggctag taaaaagtga aa






#tactccta  80940













cttgtggaag aaatcctcat tttaaccatg aagaactgaa aaatgcattc tg






#atgttgat  81000













ggacccaacc tatatttggg tattttatga tgtacacaat atacttttgt at






#atgagatt  81060













gttattaaat gtgactttgc tttttcaaga catacaatgt tcctccgggg gt






#caggcact  81120













gtgtttagca ctttgtcctg acctcatctg acttctcagc tgtccctgag ag






#gtaccagt  81180













gtgcaagatc gctgagttgg caagtgatag tgacaatatt ttcaccccaa tt






#tctaattt  81240













aaagaccccg atttctagtt ttgttttgta ttggatttgc acaatttcac gt






#tctgaaag  81300













aggatgccct caactttgca aaatgggcct tttgaatgaa aaggatcagt ca






#tgtcagga  81360













aaagcgctac aatgatgaaa tatgataaat aagtcagtct ttcatctgta at






#tatctact  81420













atggggtaaa aagtgatgaa aactaccatc ttgaaaggtt ctggtgatag tg






#gttcctaa  81480













tgcagtgaaa gatgtgtaag tcaaagattt gtaaccagcc agggaatgag ag






#gcgaagcc  81540













atagctggtg gcgggggcca catctgggtg tggggaggcc acagttgggt tg






#ggggtggg  81600













gcctgcagtt atccacaccc ctcccacctc ccttcgacag tacaggcttc ct






#ggttacct  81660













tccagagagt aaggccaggg agagttgaat aagttgagaa atgtcatgtc ga






#agctattg  81720













gtggaaagag ttccattaat tgacaataca agtccctact acattctaaa at






#ctggtcct  81780













gactagtggc aagccgggcc caggagtagc acttaaacaa tggcaggctt gt






#gttgctgg  81840













caggatactt cagcctcaga ggagctgtgt gcagctgggg agactcacac tc






#agaggatt  81900













tcaaagcaga gggcatctcg tagagcaact tatccaaacc ctgacccact gt






#aaacacac  81960













acacacacac acacacacac acacacacac acacacaccc tgagagagag aa






#agagagag  82020













agataactaa agagagagaa ctaaagtttg gcaaaataat acatgctcta at






#gaaggttt  82080













attaatgatt aatctactcc tagcatttcc tagtccactc tatctcctta aa






#aaaaaatt  82140













ctggttgcag cccactaact tgattgtaca gctgcttaat ggatagcagg ct






#gtaatttt  82200













cagagaactg tttaatgcgg gctacctctg ttcttccatg ctgcttgtgg tt






#cctgctct  82260













gctcaggaca gaatggggag gaaaacaggc tctgcggcac aatattggca ag






#tgaaattt  82320













tgtaaaccgg ccctcccttc cttttgcatt tggtctgaaa attcaattag at






#gctgagtc  82380













ctacaatgta tttgagaagc ccaggagtgc cctagaggat gagactgggt gg






#ctccctgt  82440













caggttgaac atttgcctta attactttgg caagatttgc atcagtggta tt






#agtccctg  82500













cctcacttgg aggcctgcac ttaagtggcc acattcaggc tccaatttcc tg






#gtgatttc  82560













atagtgtagg gcacttgcaa tcaaaactag gcttaaagcc caaccctctt ac






#attttacc  82620













cacccccaca aatgcagcaa ataaaatgac tctgattttc attccctaga cc






#tcttttct  82680













atatttatta cattattgtt aagacagttt ttgaagaaag ctgttttatt ta






#acaaaata  82740













gctttatgga atcaacttca tatatcttct ccgccagatc aaaacaagct cg






#tagtatta  82800













gatgtcaccg agcaccatga caggcagatg aacatcatcc ctgtgcccgg ct






#aatgatag  82860













ctcggcctgc cccggcgtca gccgctcctg gcagggccag cgggcggtgt gg






#gaccggca  82920













ccgtatctcc agcaattcgc agataacaaa tatggttctg atgatgttac ta






#aagatctg  82980













tccctttcaa gattggatta gacattagga atttggaggg ctttttattg ct






#agcatttt  83040













taagaataac caattagagt attgattcta aagtctgaaa gccacatgga ca






#gagttcat  83100













gtaattggct actttatgtg cctcttccta gattgccctg cattttcaaa ac






#aagagcct  83160













ttctatttta atcaaaagaa tccagaatga aatgaggctt tgaaaactca gc






#ctatgttt  83220













gtcttgattt ccttaactga catctagaag aaaatatgag ctcaggggtc cg






#ctgggttc  83280













cttccagcgc ctaagcctgt aagctcttcc tgctggaacc aagctttaaa tg






#cacttgtc  83340













agtcatgtcc catgagaata gatactgcct tccatgtttt tttgttctga tt






#tccgtgtt  83400













tgaaatgatg aaaatcattt ttctgtgctt tttaaaaatg gaattgcttt tg






#tgttggga  83460













attgtgctgt tcatttttac tctacctcgt tttggaatca ctaatgtggc ca






#atttatag  83520













ccaaaaatca gtatcgtaga gtgagcaatg aatggcatgg tgactgtgtg ag






#cgaattca  83580













tgccctccct ccccaccgct cgccccgcgt ctcagtcctc agtgatggta aa






#cagaatga  83640













ggaccttctc ccgaccgtga tgcgcctcag ccctacttcc cttgtccttt cc






#tatcataa  83700













aatcttcttt catagaaatg gtcatttctg ttcatatctg tggactgtaa at






#aacaagga  83760













agtcattttt gaggtgaaaa ctgcacttag actcattcca attttgatgg aa






#acttttag  83820













ctggtggatg gcattttgtt ttgtcttagt tttgcaagga gttatcttaa tt






#tagggaga  83880













tgaaactagt ctgtgatccg aggtctcact tccatacatt tctctcgggc ag






#tgtggctg  83940













cctgaatcat gcctggatgc cacaggtgct tagccagctg gtcctgtcgt aa






#ctgtcact  84000













ggtagctcag ggagtgcaga ggtgccagca gacactatga aattggcctc gt






#aaagcatc  84060













agttatgttg tgatggtggc aaagctgcag gcgagatggg aagtgcagcc ac






#tgagaact  84120













cacagtagag cgtgtgtaac gtaaaaagat gaaacccatt gtacacagct gt






#gtactgcc  84180













tccttgaagt caaatttccc ccattaccaa ggaaaagttt tttctgaagg gg






#gctgcttg  84240













acaggatgac atctggtgat atcatttatt cctttggaaa tcaatctgtg ga






#agtgagtt  84300













tccactgact gatgaggaga aaaatgaatt ggcttcaccc agcatccagc tt






#cttatcct  84360













gggagagata gctcttggtc tgtcatccac gcagctgcct ggtgcaagag cc






#aagtttgt  84420













gcagcctgca gagcactctt cctgagctgt gggctgccag gtcggggggc ag






#ggggggcc  84480













tcactgtgca gcctcctgcc acccactgat catctgggga gactggccta tc






#ctgtcagg  84540













agacgcagtt gcccagacgt tttcaagggc ctaagatgta ggcagttgat cc






#acagattt  84600













ttggagagtc cttgagttgg agattacagg tgacctcaga ggagggagtg ag






#aacatctg  84660













ggtcatgggt ttctactagg agtccacagt gaaaacaaga agaggaattt ac






#gacaagac  84720













agtccagcaa cttcctttct aacttctcct ttcacatatg ctggatactc ca






#agactttg  84780













catttacatg gacatcacag atccactttg agagaagtag ggtaaaaaga aa






#taaataca  84840













tagtgcttta ggtgtatttc tatacatctt aattgatatg ggattacatt tt






#cacttgtg  84900













tttactgtac agactctaga cagatcctgc tcttttgcag gtaaaacaaa ta






#tttcttaa  84960













aacctagaaa gacccaaaac aatttaacag aaacattttg gaccattttg ga






#ccttggca  85020













gttaggcccc agtgcagcag cggcaaccat aaacctctcc ataggtgctg aa






#cccaggtg  85080













atccctggca ccggcagcct tatgtcaggg ctctcttatc gctggttttt at






#ttctccta  85140













ataaaagtga ttaaaagatt catcttttaa agaaagcaag gacacagagg tg






#gattctcc  85200













ctgacgctag cacagctcat gcccaagcca ctcctgcagg gctctggtct aa






#gtgcaaaa  85260













gctggaaaag ctgcaggtcc cgcaagacac agagcaaccc tgcaagccag gt






#caccttcc  85320













ctcttctctg ctgtccgact ggccctccac catgtgacat tcaaaagctc aa






#gttactta  85380













acctctcaaa actcagcatc cttttctgta cagtggggaa gatactggac tg






#ttgtgagg  85440













attaagtgag gagagtggcc caatgaggtt gacagttatt actgtcattg tc






#attatttg  85500













ccttctcaca ggcaggcgtg ccacagtcat tttactgaag ctgcttcagt gg






#gtcctgaa  85560













ttaggccctg tcctttggga gagacagtcc tggttcaaca cacagctccc tg






#cccagggc  85620













agcttgggag tgtgggccag tttcgccttt agaaccacaa ttctctgata tg






#tgcaatga  85680













gagaattaat tatagactca aaggattgca tgcagacaca cacagataca aa






#cacataca  85740













cacaacacac agagttacac acagacatgc tcacaataca cagaaataca ca






#cagacaca  85800













cgcacacagc acacagagat acacacagac acacacacac acacacacag ac






#atacgcac  85860













agatgggcac acacagagac acactcacag agacacacag atacacacag gc






#acacacac  85920













agagagacat acacacagcc cacagggata cacacagaca cacagagaca ta






#cctacaac  85980













acacagagat acacacagtc acacacagag agacatacat acaatacaca ga






#gatacaca  86040













cagagacaca gatacagaca cagacagaca tacacacaga cacgggcaca ca






#cagagaca  86100













cacagacaca cacaggcaca cacgtgcaga taaggtaata ttagctagtt ca






#ggaggaga  86160













aagagataaa gataaagtaa tattagctag ttcaggagga gtgaaagaag cc






#ttgttttt  86220













ctccactttt tatagaagag aaagtgaaga ttcgatttga ggtgagttca gc






#acaaaagc  86280













gtatcccagg ccctctggct ccaactgcag ccctttctac ctcattccca ga






#ccccacct  86340













aagccttttc tcttcaaaat cttctcaggc acactgatac acatacctca ga






#tttttaat  86400













tctccggttg tgttcaccag gtgcttggtc atgattaaga attccgtgat gt






#gtacccca  86460













tgtgtttaaa tttgctgctg agttaacttt gtggcggcct gtggactaga cc






#tctgcaca  86520













tgcaatgcag aacggcaggg ccagatttga aatcctgcta tcttttcggc tg






#ccttgtaa  86580













aaataacatc aggcgatggg gatacgatgc cagaggtcac ctgtgataag tt






#ctgtttat  86640













ggccatttta cttctaggaa gacaggaagt gtcaggatct cagggatcta gg






#aagccaaa  86700













atgtttttcc actctgaaat aaagtgactg accaggagtt cccggccacg ca






#gccctgtg  86760













ggaactgccg cacggccact tttatgaagt ggacacgtgt tggtcccact ga






#aaagaaac  86820













tccccaccca tggctccctc acgctgcagc agaggccctg ccacagcacc tg






#tcagcccc  86880













tgccagcttg caggggcgca ggcgcagagc ggtttgtgcc cttgctggag cc






#agggaagg  86940













gcacagggtc cctcctggag tcatgggagg tgcagccgag gttctatatt aa






#aatacaga  87000













ggctagcaca tgtgcttggg gaatgcagct acagtagtgg aatgaaagtg ct






#gtccgttc  87060













cttacccccc cagctcctca cctgtcctcc acacgcatat ccctggctcc ct






#ttccctag  87120













taaggagact gaattgaaat tgtggcttgc ccgaggctgc atacctgtgc tc






#tttctgaa  87180













gcccaagtca ctggctctag aattctaacc tgtgaggaag ccactgagga tg






#tttgtcaa  87240













aatacatatt tctgtgcctt gccccagttc cacggcccag gaatctgcag tt






#ttcacaag  87300













cacccccagg tgattctggt ggtgtctttg cacttcttca aggcagtact gc






#ctggaacg  87360













cagaatccca gcctcctcta tcctccttgc ctaatggcct ggatgctctc ag






#atctacag  87420













gggaagggaa ggtcacacag tcatcgcaat agtaacctca gctgataaat cc






#tcccccat  87480













aaaacttatt ccccagtgtt ttttaatagg aaacaataaa actgtaacca gc






#ccaaatat  87540













ccatcaaaga gaaaatggag aagtaaatca tcgcacattc acctggacca ga






#tctattgt  87600













aaagccaata atactgaagc cccttccaag gccctgggag tcctaacagt gc






#actggcag  87660













tgtctataat ttatattatg aaatttgcat aaggaaaaca ttttgtctca tt






#tgtgcaat  87720













ttctccttct aaatatacgt gtcactttgt acctgatttc tataagaccc ag






#gacctaca  87780













aaccctgtgt ctgcccctgc agccacccag ggaaggactg cacagcagca ag






#acagattg  87840













ccatggagca tgttgtgccc aactagggac agcgcagata gattctgtaa tt






#tgcctaac  87900













aatgtctata ggatgatccc atttgtcaaa aaaaaaaaag aactgggctt ta






#ttgatgtc  87960













acctaaatgc acctaaactt cttttttgcc ccatgctctt ctgtactctt ga






#tctttccc  88020













caaattttta aaaacatgac actcattccc ttatttttcc tacttagaaa ag






#tgtagatg  88080













gttttatcat aggaagttca aaaaaattaa aatataatga aaaatactca aa






#tagtgcct  88140













cacaacagta actactgcta acataaataa aatccatatt tcctctcata ca






#gaccccag  88200













agttgctttg cctgacagtg tagttgatgg agaaaataat ctttatcctt ag






#cctccatc  88260













tggttgcaga ccataaagac agggaaaaaa tgagggtgtt ggtagcttcg tt






#agaaactg  88320













aaagctcact gattttttca aaacctaaat agcctgtgtt tctccaaata ac






#taatttgc  88380













agccttcggc agccaggact ggcagggatg gggctagggg gactggggag aa






#ctgctctc  88440













tcctgagggt ggtctgaccc gacagcacgc atgaccttcc cacagtcagg aa






#ctgctcag  88500













agacgtgatg gcaactccat agaatgaaat actcttcagc cagtaaaatg ta






#tttttgga  88560













taaatatttg ctttaaaaaa ctttactata tgttgttaaa tgaaaaaaaa ac






#cttaaggc  88620













atcagaaatt atgtgcagta aaatctcact tttgtaaata aatatacctg tt






#tactacgt  88680













atgcataaaa agaatcctga gaaatataag tactgtatgc atattgttgt ta






#agtatttt  88740













ttctgtttgc ttatctataa ttctaatttt gcttcaaaga acaagttact cc






#ggcaatat  88800













aaaaataaaa taactaattt gtcttgtcat caaacagata gtaagaacag gc






#aaacctgg  88860













ccctccacac tgccagcctt ttgtgattca aggcttcagt ttcctccact tg






#ttaaaaag  88920













attcaacaaa gtagttgaaa tagtatgtga accagtaaac cctaaaaggt gt






#ccagtgtt  88980













gtctgtgagc taattaagtg atttgattct gactccccga gtcttctgat tt






#cgaagcag  89040













tggggagtca gacaggagcc tcaggtggcc tctcctgaga ggccctggaa ag






#tgatgaga  89100













acctggcctc tggcagctct tcataaacgt ccatgttttc cctctactct ct






#cactcttt  89160













tcccagggcc tcaaacagaa gatgaaaatc aatttctaaa acagccctct gt






#gtgctctc  89220













tcgtatctct ccttttcaca catcgtggtg gtggctttct ctgtgttcct ct






#gttgattc  89280













agtctctgga attaacggat caggattcca tgcccagaat gctacaaaga ct






#gtgcttga  89340













gttctcccac atctcactca attacacaga agtttcagat tatgtaacag at






#gctgtgct  89400













gggttaggca gagccatctg acttgttttg ctttatttta gaccatgaga tg






#ggtgagtt  89460













tttcttttta atgccacatt cttttaagaa ttaaaaacct ccacttggct gt






#cagcattg  89520













gaaatcagag tgatggtgca agccctgatg aggacaatgt ccttgtctat ga






#aaaggtga  89580













aatcattgct tgaaatcgct aagcaggaca tgcagtccca gatggagggg gg






#aattcggg  89640













agctggttgg aaaagagtat ttggcacttt gcagccttga gaggtgcaga ag






#agacaccg  89700













aggggttcac caccagagcc accattgtca gagaggcgtc cagctgtgtc ca






#cctgggac  89760













tctgccttca gggcttcttg cctggctggg agctgcacag gcagactcct gg






#gacggtgt  89820













gccgacagct ctgggcaccc ccttctagga tctgattcct gaggaatcac aa






#tgtggatt  89880













tcacaatcac ttccagtgtc ttttgccaac ctctgtgaac agatgtgcaa tt






#aaaaaaaa  89940













aaaaagaaag gggcccaatt ctcaacactg taagtggaaa ctttttaatg ga






#aaaggata  90000













ggctaatgaa ttgaatttga aatctgagac agaaccgatg catcaaatgt gc






#tggtgttt  90060













acagataata caaggggggc tgcatcttat ggtttcaatc cttttttaaa tt






#tttgttct  90120













gagagaccca gccagcagac tgccgccagt cttgtcagag atgtcagtgg tg






#gccactct  90180













gaatggaaag cagcatctct cagcatctct gaggcactgc tcctcagcgg ag






#actgtggt  90240













ggctttgcct ttcagcacgc atcctttcta cgatgcctga cagtgcccag gg






#aatgggca  90300













gagctgggag ctctgaagcc ctttcaccta aaccaccctg ggtcacctga cc






#tagttttc  90360













ctcccaattt taattatgtc aggcacttca caaaggcctc cttggggaca cc






#atgagctc  90420













actgtcatca gattgctcca atcacagctg tggcttgcac acaaccgcca tc






#tctgcccc  90480













agcagatgct gtgtgtaaac agttgtatta attacatctc aaaaacatgg tt






#cttgccag  90540













atcctcagga tttgggtgca gcctctgagg tgggtgggag gccctcgagg ga






#gaaatgtc  90600













tgcaggaaat tcttccccta cgagaggtct gttttctaag ttatctaaga gc






#tactgcag  90660













ctgtttactg cagagtgacc ctgctcaaag ctgtggtcac ccaaggcttt ga






#aaggggac  90720













ctccacttcc gccctgggtg gagcaccgtg ctggagaccc acgcctgcca ag






#gcctcatt  90780













gtcatctcca cacgccgtcc ttggggtggg ccactcctgg gacacgcaga ca






#ggaagccg  90840













gccacctgag ccactcggag gctctatcca gagtcagctg ccaagcctca cg






#tcacacat  90900













cactgttagt cttggagggc tggcggggcc ctgaagtcaa ttgaacactt gg






#atgacagg  90960













gaacttgcca ctgccagagg caatatgctc catttttttg acagttccaa ca






#atttttct  91020













ttaaactgtc ataaaaaatt gctgctgtga ataccagtgt cggcgtccct gc






#ctcacctt  91080













tacctggtgc ttttccacca cacaaaactg tttctcctcg tgctggcctt gg






#gcttgcag  91140













acagctgatt cttctcctcc cgcggctgag cagcctcctc cgagcaaccc tc






#tgacaact  91200













ctgctccttc tgacaacctc tgcaagggct gccagatgtg aacaaggggc cc






#gggcagaa  91260













ggtatccagg aagactggaa actcgaggaa gcctgccctg tcctgtccac ca






#gactttac  91320













gcttgcgtca ctgggctttg ggacctaagt cctcgtcatt tgttcctttt gc






#agttccta  91380













ctgttctcag cacttccttc cagcttactg aggtacactc agatgtgata tg






#ccatcggt  91440













acagacacag ttctgctcca gcatttcccc gtgttctttc tgtcgctcta tt






#tactgaat  91500













taccgtgagg atgtggagcg aggctgagtt ctgtatttta acaccatttt aa






#ttctcacc  91560













tactgagaaa tccatcctct tatcactgtg ctttttttaa cctgtcacga at






#ccatgaaa  91620













tcctatcagc cagcctgcat acttcctttt aaggtgcagt tgaatcagga ga






#aacttgcc  91680













gcacatgctg cgtccgggca cagcattggc tgaggctgct gccctgacct gt






#ccgctttg  91740













tagtactgcc cagctatgaa acaggttagc cacacatgac ctgcatttag ga






#gtaacaag  91800













tctgtctgta catgcacata cagcaacttt tttaaactgt ctatattttt tc






#ctgagata  91860













ggtatttata atatctccat cttctttccc attttgaaac ttagaacaag tt






#tgcctgtc  91920













aacagttctc cacagcatac tgtgtattct aggattttct aaggttgagc aa






#cggaggtt  91980













cagcaatttt gacttaattt cttcccatcc cttttccacg cagcccagaa gc






#cttggatc  92040













acgtggtgag gggaagaggt tgtgctatgt cgggaaactc tgtatcgaag ct






#cggctcag  92100













atcatgacat tctcttgact aaaaccctca gtttccatca aacttgtcac tc






#tggcatta  92160













aagcctgtca ctgtgtggct ctgaaaacct ctctgaacgt gttccctgcc tc






#tgccctgc  92220













aggtccctgt gctccacaga agcccactta tgtgacccac ccccactcat ca






#ccaccttc  92280













cctcacccag agcctcagct ccccactccc acctgtaaga cccctactgg aa






#agattccc  92340













acctgcccct caagattaat ctccaaggac atttccaaat tcctctcccc at






#ctctcagc  92400













cagatggctt tgctccctcc aggaacccca gccaccttcg acctccagca gg






#gcactcca  92460













ctccacattc tcctggtctg tctggctcat cttacctgag ccatgctctc ca






#ggtgaagg  92520













actatgtcta actcaactct gctttaaaag cagctaacac attgctcttt gc






#atattgtt  92580













cactcactaa gttgaactgg acttggacat gcacactgaa ctgcagcgtc tg






#ctgcttct  92640













tggtggccca gctcgtcaaa agaataagat ttcagcaaaa caatgtaaca at






#ttttttta  92700













ccaaaagtaa tgttaacaat atatggtttt cccctgatgt ttgcgtcaaa at






#gctttttg  92760













gaaaaaacat ttttcaactc tttagggtca gaattaagca atgaaattta ta






#taccacat  92820













gtataatgtg tatgtttatc taagtatctg ttcatttata tatcttaaat ag






#aaatttta  92880













aaaatttttt taaaactcct gataaacatt ctcaggaggc acactatgta ac






#tgttggtt  92940













gatataccta gctagatggt gaaatcagat tttgtttaaa gcatggagga ga






#gggaaaaa  93000













ttaaatcttg cagattctgc agtccttaac atctttgaaa gaggaacatt tc






#agacaatg  93060













taataagaag gccacgtgct ttgacttctg tagattttaa aaatacttct gt






#atagtttc  93120













ttcttccttt gaagaagttt ggggagtttg ggaagatgga gaaagatata ag






#aatagact  93180













ccccatatgg gtcatgaatt atctttttgc atcagaactc ttagtgcagt tt






#cagtattt  93240













tcttcctcag gagggtgagc tgcttccgaa tgtcctcccc ttctttgagg ca






#tcctctgt  93300













tggtgaactt tgagagcatc catttatgaa gttgatgacc tttcccagtc tc






#tgcaagcc  93360













cttcagtgtg tgtcctctct gagcaaatct gaattgtgtg cttaatacat gg






#aaagggat  93420













ttgggagggt tgctttttaa actgatttct taattaatat tatggtttag tt






#aactagac  93480













agtctcattg cagaagtgca taaccataat atgtcttcaa atatatctcc ct






#tcctaaca  93540













ccctgtaata tacttttgta aagataccct tacagaatgt gatccaccat tt






#atgaacct  93600













gcagcattgc attcagagac taagtgaaaa gctggcagat tttcatttaa ag






#cacaagct  93660













aaggaagaaa gctggtctag aaggagctac agaagggtaa tgcttaggga gg






#gaatgatg  93720













tgcctgtggg tggtggtagt taaatctaac caaagaatga tgtcgtgggt gt






#ttggatat  93780













tggatggtcc acattgggcc acattctttc aaacataaga gtctgtagaa at






#atgacctg  93840













taaaagactc ttaaatattc tggaaactgt ttcttccttg tcacatcctt at






#atatactt  93900













gaacctatgc ctaccagaca tgacatgtga ctattcatac agatttcatc at






#ctctggtt  93960













taagaataaa ggatgctgca tagaaggctc acatctttta attcacaaga ct






#gaaactgt  94020













tctgaaatga cattgtttct aaaaattcat tacttgcatt atattcattt tt






#atttttcc  94080













atgccagaag ggtagaagtt cctgtgctca tattaagaaa cagcaatgtc aa






#tcgaggcc  94140













caactcaaat ccaatttata ggagttataa agggcgtgtg cctgttttgt ct






#agaagcag  94200













tgttgggcag cactgagtag gatagaccac ctgttgctac cgataaagga gc






#agcttctc  94260













gaatgctcct gtctggtagg cactatcccg agtgctttgg cccctcatcc ac






#aatctgtg  94320













tggcaaaagg cattgcaggc aattcagtga ggagaccgag gcatggagag ca






#agtgccat  94380













ggaattccct aaggccgtgc agggagcagg ttgccaagct gggttgaaac cg






#tcctccgt  94440













aggctcccaa ctccgccgtc gctgctactg tgctggatga tgcctggtag at






#gcagatgt  94500













ggagccccat ggattctgag acaggccggg tttcagtcct gccctagctg cc






#tattggct  94560













ggatgacctt ggcaagttga ctttcgtgag cctcatttgt ctcatctctc aa






#ttaagaaa  94620













acctagagcc tatctgtggg ggttatctga aggattccag ggatgcatat gg






#cactgtct  94680













accgcatgcg gtaactgttt cacaaatgat gaggagcgat ttatgttctt ag






#tggaaata  94740













tgtcggcgtg tgaagtccca aagctctgcc ctgcctggct tgatccagtg cc






#taggcact  94800













gcccctcttc ccctctctcc caacccactg taagaggcta ggctgcctca gt






#aactctga  94860













ggggcattga ctcttttcat ccaaaaattc atgttactgc cccacatttt tt






#ctgttgtt  94920













ttacaacgca gtaggaagtg ggcagactgt caggaaaagt gatttatagt ca






#tgtattgc  94980













ttgtgctttg gcttcatttg atccaatgca gatcagctgc actcagaaaa ct






#actcaagt  95040













gaaagagaaa aagtaactga agggggaaat ctggatgagt aagaattcca gg






#gataggaa  95100













tattaatagc aagctttttg cctgatatag tcactttatg ctgcaggggt gc






#ccctttat  95160













aaagtgcttg tacaatggat gtttgctttt gattttggat ttggagtcta at






#gaatgttc  95220













taaattatta ttagaggagc ttgcggttgt tacatgtctg cctttattgc tt






#atttttag  95280













ccatctcccc tgatgtcaaa tgctcaggca agaatgatac attcatttat aa






#tgtggctc  95340













cttcagaaat ataccacata ccttttggtg tggtttgtgg ctgagaagag tg






#gggaatgc  95400













acaagtggaa aactgcagaa agattatgcc ttcatcactt caagtatttg ag






#atgaaact  95460













agatcatttg ctgttgcttt ttattctcat tctaagtgct tttcaaagtc ag






#cgctaaga  95520













ttttaaaatg gttttctgtt gttggcagag agggaattac tctattactt tc






#tgataaaa  95580













cagagtcttt catgatcaaa gagaaccagg ctctagtagt tccagtatcc ta






#acgtggac  95640













actaattgtt tccctccttt tcttcatgaa aacagcttct gcacaaatga ta






#gccttgtg  95700













aactagccat gggcacaact ggagaagcat ttagggagct ttagtgcaaa tt






#gagaccac  95760













ctacacatct gactctacag ggtttgacaa catccagggt gaatcacaaa ac






#atcagtct  95820













aatcagggct tatatagaaa gagtgaaaga actctgattt catcctaaag at






#tatttata  95880













ttaaccattg ttccaaatgc attaactatt ttaatttagt tgttttgatt gt






#taaaaaaa  95940













acacatctgt ttggtagata agacataatt taagacaaat gttctatttg at






#aagctttt  96000













agaaacaact tatttttatt ctttcctgtg agataactca gatgtggaga at






#gtgacaaa  96060













attttaagca taacatgaga agggctgaca cacatagatt tctgtgtgct ta






#cttgaaaa  96120













caacaaaatt taagaatttg gtataggagt tgtatcaggt agtgcagagt cc






#ccaggaga  96180













cctagagacc caggtctggg agcctagcgg caagggctga atgtgggatg ac






#atcagcag  96240













aaactcacag ccactgctat tccaaaaacc cagcagcagc tcagtgcagg gc






#agtgctga  96300













tagtacagtg cctgcaatcc tggagtggat ttggatgtgt caggtacgca ca






#cgctcact  96360













gctcccccag cagtacgttg aacagtgtgc gtccaggtgt ctgtagggcc cc






#tcgcccta  96420













actcacaaaa ccattctggg tcagaagcca ccaatattgt catcatcctc cc






#ttttctga  96480













gaaccctagt aagtccctcc agtggggcaa gcccaccttt tcccttcatt ct






#gtggcaat  96540













atgccttcat ttcctaatca gttttgccct gctcattcaa tgcaaaatgg at






#ctgctttc  96600













cttgggcacc aatatgtcca gggattgttt atcaatcttc agttctgttt cc






#tttacata  96660













tccctccaaa aatcaggcct gcactgcctg tgcactccac aatccacagg cc






#tgaaggaa  96720













atgttatctt tgatgtagag acttaaagta aaactcttca aattaattat tt






#catgcaaa  96780













aggctagtcc tgactctaat tctaagacat gtctcctaaa ctctggaagt ct






#gatgtatc  96840













ctattatcaa catttatcct taatgtgatg gtttatcatt tatcctcaaa gc






#tgcattgt  96900













aaaatgtaca ctgtaaagtg tacattttaa agtcggtttt aaaaaatcat at






#ttagagat  96960













cctggtaaaa atctatcaag tcaagacatt accttattac ccatggaatt gt






#cttcaact  97020













cttacagttc aaatattcct gaattggctt tcacaataaa catcctaaat at






#gtaagtag  97080













aaacatatat attgccaact ttgtgccttc ccaagcaaaa ttaaaataca gg






#aaaagtca  97140













gtttgttttg cccataaata aatatatgtg tgtgtgtatg tgtgtgtata ca






#catacaca  97200













ctcagaaaag atagaagcag cagcatattt tggcagcatc tggtttattg ga






#actcaaac  97260













gttctgattg tgcatacaga ctagttaatg tggtaacaat tatgtatttc tt






#ccctgctc  97320













cttgccttct ttccctcccc agtttttttc ttcctgatag taggtgtgta ct






#tttttcct  97380













atttccattg gcaagccaca tgacaagcaa aacgatcact cgaagaatat tg






#ttccctca  97440













atcaagaaaa atgcccattg ggttttgtta tttgatgtta tttgatgaca ga






#gacctatt  97500













gtttttccat ttttcttttt ttgttttccg tggcacctat ggaattaagc aa






#tataaaaa  97560













atctattatt tcagatgttc acgtctaatg aatttcatgt gaaatactgg ca






#gtataacc  97620













ccaaatagag gaaatttgtg aagagtggat gctgcagggc atgagacatc tg






#cacagagt  97680













tcatctcttc cagcatcttg catgtcccaa gcactgccct gccaggcaga ga






#atgctgca  97740













gatcacggca gtgaattcca gttgttcaga gcacatttga cttccaaatt ct






#caaggcca  97800













cagatttgag gacagaacaa tatttgcatt tgaaattgga agattatttt tt






#gcacaagt  97860













gcctatatgc tatatagagt ttgcccactc tgcattatct tccccctgtt cc






#cccgttat  97920













ctggcacaag ctattcaaaa gacacgccta cttgtaaaat aaatggtttg ca






#aactaagg  97980













aaaatactta aatctcatgt aaatggtact atactatgta taaaaatgtg aa






#gaaacaca  98040













gaacagctca tgaacacctc cactgctgta taaaagaacc atcttttttc tg






#gctcctat  98100













tggatgcctt agaaaaatct gtatttcctc tttagttatt gtgtttgaaa ga






#tgaagttg  98160













agacaaaagt tctattcttt ttaagttggc agaacttctg aaaggtgatt tt






#tagctgca  98220













gtgtgactca ttccaaatgc agaaatctct gaccctgagt tagtctattt gt






#catgcaag  98280













agcctagaaa agccctgagt gataagaaat ggccataggc cattcccaca ga






#attttcaa  98340













caaaaataga atcatgctta tgttctagtc atgacttaga acttataact ca






#tgttcgga  98400













actgtccatg ttcacgcaca ggggccgtat cactccgcca gagctgccct gg






#gtgccggt  98460













gtgcagaggg gtccgagagt gactgtctct tcctctgttg tcgaatgtgt gg






#gttatctc  98520













cataaatggc tgccatgagc atccttgttc acacattttt aggtacttga gt






#gagtgtct  98580













gtggaataat tttgggaagt gaaatctgtg gtcagaggtt tgtgagtttt ac






#atgctaca  98640













ttttcagaag ttgagaaata gcagtaggct gaaggcaagt cgccatgcct gg






#aattcatg  98700













aacactagtt gaaagaactg gcgtgagtta gtcatgacag gagagatggg ga






#agggagtt  98760













gcaggtagga gggccatctt caaattctca aagtatagtc actccaaacc aa






#aattcgat  98820













ttaatctgta ggactccatt ctcaaagcac agtcactcca aaccgaaatt cg






#atttaatc  98880













tgtaggactc caggtggcag aataagaggc aatggatggg tggaagcgaa ac






#agggccaa  98940













agtttgactt catgtgcaac ttcctaagga gtgatttgaa ctccacaaac at






#gaactaag  99000













cacctcaaca caggctgggc aagttgctgt tcttttggag cttacatctt ag






#tggggaaa  99060













gagaaatgcc tatgtaaaca tataaatcag caggatacat tgtgaggacg gt






#cattgctc  99120













agtgagactg caatagagtg atacgctgga gggggctgca agggagaagg tg






#ggagggac  99180













agcatttagc agaatgagca gcacagtccc ataggaagaa gaatttattg cc






#tccttagg  99240













caaataaatt cccaaacctt gaacatcaga aaggaaatag attaatgtgc ac






#agaggatt  99300













aaattatgtg atctgcaaag tcatttaaaa tctatttcca cataaaacat at






#taatgcaa  99360













cctaaacaaa aggggtctgg ataccctcat cttcttccca agcatcaagt ct






#ttctatag  99420













ttaaactgag atgcttttat tcttggaaaa ttttaaggac tatctacagc aa






#tggaagaa  99480













tcgggtgttg ggatgtgttc ccaggtaata atgactgcag gctgatttgg cc






#cttgaggt  99540













gtggcctcat ggccctctcc aaaaaaaatc aaggacctgc tacaaagcac aa






#agccgact  99600













gcaatgcttg ctgcttactg gttagggcag ctcctctttg ccagcgacca ag






#cagaaagc  99660













aagacaagac aggttctgaa gcagtaattc aaagccttcc tcgctttccc at






#gtgagtca  99720













ttgctagtca gaatattacc tttgcagaga ggcttaattc caaatttgct ct






#taaaggga  99780













tatcctctcc tggtttaggt ataaactttt gactcacagg acaaattcta tc






#attccttt  99840













gggcctagga ttgcatttat ttccatgaca aaagggcctg tctggtgttt ca






#gcaaatga  99900













aaacaaaaat ataaagccca tctccttttg aatgagctct aaaacagttc tc






#cactggac  99960













ttcagaacaa gagggagctc tgggctgctg gctggttgtg catttgctgt gg






#gttccctc 100020













cggcaggcga cctctccgcg ctgagaaggt tatccggata accaagtaag aa






#agtacatg 100080













aggaggcaca gaaagaaaaa tgtgagagat aacagcataa acacacagtg ta






#tgttgtta 100140













tgaggcatca catgatgaga tactgctggg gagggaagaa gtgaggagat tc






#ctaggaat 100200













cttatgagaa tttccagaga caacaagttt tgagcttttt tttaatttag aa






#aatttacc 100260













ttatttttaa aagaatatgt aacatatccc atgctataaa attctagaca ta






#gtagattt 100320













aaaacagcat aatggaaaat ataaatatct attttctttt cctatttatg ta






#ttctgtgc 100380













cagtaggaat gtagccaaaa agagagaaaa ggggtctctg cagacatgga tg






#tctctgtg 100440













acttgatcac tgctaaccca agaagataat aaagcagaag catgtatcca gg






#ttgctgca 100500













gccaagcctg cccggtctgc ggggcgtcct cacacatggg gcagctctcc ca






#ccccacac 100560













actgggaaag gcggacagag gctgggcaaa gcccccaatt ttcgttggca ct






#gaccccga 100620













tgatttatag gcctttgttt cccatgttaa atgtcttacg atcattaaat ta






#tttatagc 100680













tcaattagca tgtgtccaaa accaggaagt tcataggaga ctgtgtgact gg






#gaattaag 100740













gagcaaagca actttccagt ctgtgattta ctgggtttcc attctgtttc ct






#gttcggat 100800













ccggaagtag aatttcaaat attgcttttc atgctttatt tgggaccgat tt






#tagccccg 100860













ctctcctttc tcttgccatt cgctggccat tagccaccag cctctgcaca at






#gaccagct 100920













ggcccctggc agatcttggg cccaggtgtg aagtcgctgg agaagcattt ca






#gggccaag 100980













atgggagtga tttcattttc cattgacact atgcagaaat gaaggggatt ca






#agtgcctt 101040













cagaaaagct tccttccagc gaatggagtt ttgggggttt tccagacttg ca






#actgcttt 101100













tattcttgga agcatcattg ttgctttttc cccccttcca tttatatccc ag






#gaactgat 101160













tcagaaacca tagaaattgg atttggaatc gctgaatgct agcagacagc tg






#actgcact 101220













cttcccaaga aaccctgcca gctgggttcg ggtatcgcgc ggtgtgtgct ct






#ctctgcct 101280













ggcccgctga gtcctctaac tctaatggat tccttcttac accaaagtgc ac






#tagaacta 101340













aagtgttttg cttcattctt tagacatttt gtggtttagg gctcaatcag cc






#agggtatg 101400













atttgcaatc cacagtaacc ggtttcagag cagctgccca gcgaggcagg tt






#tcatctcg 101460













cttgctagac gttttgtttt tttttttttc taaacctcac accttttatt ta






#ttagactt 101520













ggattccagt ttcctgagcc tgtttgtgcc actgattaga caggcttgaa gc






#agaaccca 101580













ccaggcttcc tgaataaaat gcagcagtga ttgtattagg gggttttaaa tt






#gctcaaaa 101640













tactgtctaa aaaacactaa aaatcatgtt actttctaga ttgaataaaa tc






#ctatagaa 101700













atgaattcct ggacttgata tgtagcaagc tggcattggc tcgggagtga gt






#gggctcag 101760













ttaagtgagc taagatgaga tggtgcacag gcgagcaccc acctgaggag tg






#tttggatg 101820













ttatgatagc cagctcctct gtaaagacct gtccttctat gtcagcagcc ca






#gcagataa 101880













atgacgtgta aataccacat ttaggagggc ttatgatgat gccaattaat gg






#agaccttt 101940













ttgaaacagg aaggaggtga aacatattcc tttgcttcta catcactgtg tg






#ccaggcac 102000













tgtttacagc atctcgttta accagcagtc accacctgac ggatggctga tg






#tggggtgg 102060













ggtcccaggg tgggattgcg tgatgggctt ggggtctctg gctgatgggt gc






#cagagctg 102120













ggactggaac tcctggcgtg actgaggcag acacctgggc tacccagcct ca






#cccacgac 102180













gccctcacta agtgacccac aggactcacc ggaagcaggg cagcaaggtc cc






#cctacaga 102240













ggtccccact gcaaaccgat acccagctta gacagcagtt ctgcagtcgg cg






#tctcaccc 102300













cttcgggtct cattgtgact cactttgata gccacacgat ttaagggtgg tt






#cagtagtg 102360













atttgatgag tgctgtggct cagggtcatt cccctgccca agcatttcaa at






#tccagaag 102420













ttcatgccct gcatggtggg tgaaaagtct caggccaacc atgagcacac ag






#cagccagg 102480













cgactgaggc agctgcccgg ggtggcacgt tgctcaaacc catcatttgg ag






#tcaaaaca 102540













aacagatgat tagctggggt ggtcactttc aatcaagagt tttcacatcg cc






#tagacatg 102600













gcctcagaat caggcctggt gtggccaggg gctgatctca cagtagacag ga






#agtgtggc 102660













ccgagggcca tggctgcccc ctcagaaggc cctgtggagt ggctggccga gc






#ctcagcag 102720













cctcctgtga agcgaggaag ggtcttcctg ccggcctctg gagatcagta tg






#ggaatgca 102780













caagtaggaa acgctggatg ggaatccctc tgccctgtga taccaaggca gt






#gagtttgt 102840













agactatgga attgctgtcg gagggctctg taaccggcca aggtcacaca gg






#tagccatt 102900













ggtagagcag ggactggaat cccagacccc caacttccag gactgtgcac ct






#ttctttat 102960













cccatacagc cttacagtca agtgccagtg caacacctga ttcccaggtt cc






#agcctttg 103020













tcttttataa tgggaatcaa ccttatcttg acgatccaga gatagtcatc aa






#ggaagatt 103080













aaattatccc cttagactca gagtgaccat atcattttcc ctccacacaa gg






#acactttt 103140













gagaatgaaa aggaggagat gtctgtacca gacgctggat gacaggcacc ga






#caggctgt 103200













ctgccagggg agcagcgatt cctgtatgtt gtagaaagtt tttcaaaagt ca






#ccttggaa 103260













agaggttttg ttccttaacc ttctgttaaa taggaagctc cgtgaatgaa aa






#caactccc 103320













ttccctaaac attctagtaa tgacccaaca ctgccaagcc tgccagctct gc






#ctcatggt 103380













cgtgttgact gtgtgagact atgtgagtgc ctgctacaca gtacgctttc ag






#taaacatg 103440













gtattgcctc gataatccca caaaaatgtc ctattcaaat cacctggcac cc






#aggaaatt 103500













tccttctttt ttttcccagg tgaaatatac agttgaaaac acctgacagc aa






#ttcccctc 103560













tcccatgtgt ttgcaggatg gtggttttgg ttcctccatc tttgatgtgt ac






#aagtgtga 103620













tgttttcccc ccacagacaa gtaaaccaca ttctcttcac attcccaatg tt






#ttgtcaat 103680













gtacctcctt caatagagga tcgataagga aaaaaatcat tgacaatctc aa






#ttagattc 103740













actatttcat ccaaaagcat agcttagaac tctagttttt gttcaacact ct






#tgccctat 103800













gagtgcacag aactttaatt ctgatacaaa catccctgaa tgtttagctt tg






#acagagat 103860













tccaaggtga tttgataaga agcagggctg tgtttgggct ctgggagttt tt






#gatatggt 103920













ttcaagcccc atccaaaacc cacagacctc tagaaagtag gtgcctgcct tc






#ctgcagca 103980













gccctggagc ctgctggggg ctttgagcag ctgctgccaa gccaggcctc ac






#ccgacact 104040













ctgatgggca cggccatggt ggcaggggct tggacgctgc caggtgactc ta






#acttgtgg 104100













ccagggtggg aagcactgct ccacagaggt gccaaaacca ggttccttcc tg






#tgttctca 104160













catttcacag cctcaatgta aaaagtaaga catgggcact ctggaatatt ac






#aaaaatat 104220













agaaaagcat gttatagtaa ataaaaggct cacagaattt tgtcatttag ga






#acaatgat 104280













tattaatata ttagtgtgtg tttttgctca ttaacagtat atcctgagat at






#ttcctata 104340













ccatttaata ttttaaaaga tgtttacact ggccacagta gctcatacct at






#aatcccaa 104400













cactttagag ggcaaggcag gaggatcact tgaggcttaa aaattagcca gg






#tgtagtgg 104460













cacatgcctg tagtcccagc tactcaggaa gctgaggctg gaggatcact tg






#agcccagg 104520













agttcaaggc tgcagtgagc tataattgca ccattgcact ccagcctagg tg






#acacagtg 104580













agaccctgtt tctaaaataa ataataaata aattaaaaca tttaaaaata ca






#tgatgttt 104640













aattattaga ggactcaatt ttatatctat gtatacaata atttttaagt tt






#cttaatat 104700













tggactttta gtaccttttt aaaaatacta tttttaaaaa aatctgtatt tc






#taactttt 104760













tataacaagg aacctttggc tttgagatga ctggggaatc cattctttcc ta






#tagtatcc 104820













atgtccaatg gacttaaagt attaatcaat gtgtttatgt tttgttattt tt






#ctggcatt 104880













acaaaaaatt ctaaatatat tgttaccgcc tgtataaata tcagcttttg ag






#agaaggac 104940













attgtgtaga aataatgaaa cactgcaact tgtatttgta ttattctttt tt






#tttttttt 105000













ttttttgaga tggagtctcg ccctgtcacc caggctggag tgcaatggtg cg






#atctctgc 105060













tcactgcaag ctccgcctcc caggttcaca ccattctcct gcctcagcct cc






#tgagtagc 105120













tgggactaca ggtgcccgcc accgcgccgg gctaattttt tgtattttta gt






#agagacgg 105180













ggtttcacca tggtctcgat ctcctgacct catgatctgc ccgcctcagc ct






#cccaatgc 105240













actgggatta caggcattat attattcttt aaattcacat gagaatttag ta






#tggcttca 105300













aaaaatacca taagttaaaa tatcaccaag actctgttca gacaaaagta tc






#agaaaagt 105360













gagccaggca ctcacatagt ttatagttta taaaagtgag acaggcatga tc






#tcttaacc 105420













tcactatagt cctgtgaata aggtttattt acatttcatt ttacctgcca gg






#attattgt 105480













aaaaacgcca agcacattgc ctacacaaac taaatattca gtcaatggct gc






#tattttca 105540













tgagttcgtt ttaacatata tttattgtcc tctactggat ttaagaagtt at






#atttatta 105600













tcatctaaga ttttagctat tccttctctt aaaaatagat tttataatca at






#ggcagtaa 105660













gggagagtaa ctcgcagttc tctgaatctc aaggggttcc tggaagcctt cc






#tgaaggta 105720













tagtgaaatt tcagcttcac attcccatcc atgagctccc tgcaaatatc cc






#ggtctgct 105780













ctcaggaccc agtgacttac ctatgcagag gctgtagata gcacctggag ct






#tcctgtgt 105840













gccctcctca aactcagcca atgccgtcat acagtagcag gcaggtgtct tt






#gctgggta 105900













gttggactgg atgtccctgg gattgcagaa ctggaatggg gagtgacatc ag






#gaaactat 105960













aatcatcagg acaacatggt ttgccataac tttaagtttt aagcgaccgc ag






#attatgcg 106020













gagagagatg catgcccaca gccatgcttc ccatgtaact ggagaggggt ct






#gaagtttg 106080













aaacaagtgt tcctaggcac gggttacagt gtttgttatc atcatacttg at






#ttagaatg 106140













gggcacaaca tgtggattca tggtaactgt tacaacctta ctcattttaa ta






#cctgaaaa 106200













catgctttcc ccatgctggg aatcgaaaga ttctcctagg aaaagaaagg ct






#tgacaaca 106260













tcgattcaaa aagggcatgc attttcctca tttaaataac tctaatgtgc aa






#gtagatcc 106320













cctgacctca agctcagaag agtccaggcc ttcacacctt ctctgcttct gc






#tctggggc 106380













cagctattga gattcctgtg cccacgcaat gcgcacatcc cacccctggc cg






#ctgtccac 106440













aagaaatcca gttgcaccaa gcaccccact ttttgcacct ctcatttatg ta






#ctcctaag 106500













agcctcacca caactccctt ctaaaaacat gagttcctga ctgggaattc ga






#tgctgccc 106560













aggcagcttt gctcagaggg agcagccttc tagaaatgtt tcaagtaaac tt






#tcaagtat 106620













aactaaattc aaaaaaaaca catacacaca cacacacaca cacaagtcaa ag






#gtgtgtaa 106680













tttggccaat atcacaaacc aattagccct ttgtaagtgg cacccagatc ag






#gacagctg 106740













accataccag caccctagaa gcaccccgtg ctgcctcctg ggacagggct ac






#caccatcc 106800













taaggccagc acgatgggcc agctttgcct gctgttgaat tttgcttaca ta






#gaatcctc 106860













cagtaggtac tcctttgggt caggttcttt cactcaacat tatgtgttga ta






#tttttcca 106920













tgctgtgctg caaaattgta tttcttgcat tccataactg ggcagttcca tc






#ataggaga 106980













ataccacact gcgttcgtcc attctaccgc caatggacat atgggttctt tc






#tcttttct 107040













tgcagttaca agtttatgaa tattgtccca cgtgtccctg gtgaactttt gt






#ttgcattt 107100













ctgttgggta cctcagagtg gcgttgctgg gtcagagggt actggtcgct tt






#agtagctt 107160













tgaaagatat tgccaaaaca ttttccagcg cagttatagc aaattataca cc






#accagcag 107220













tagaaaacat ctcctaattg ctcacagtaa acccccaaag attgccacat ac






#atcttcca 107280













tatcaattac ttaactattc agcaaatttg aagggaaata tatttaatct tt






#ttattcaa 107340













atagtttata aagtggaata gagatgtggg taaaagttgt cttgccacct tt






#ttagatcg 107400













gtaaaagttt gttgaatgca ggcaagaaaa gatgagaaat aatggtaccc aa






#tgaaagac 107460













atagcagtct acaaggaggg gcatttcccg gggtgggggg gacccacact ct






#gtaactcc 107520













cacattcaat tagcatgtta taggtaagct gcagaaaacg aggcagcttg tc






#aaagagga 107580













acggctcttg gccatggttg ctgccctagg aggatatttg atactagcag ag






#ctggggca 107640













accctggagg aaaccacctg gaatgatggg agaactcctc cagggaacat gg






#ccctttaa 107700













tagatctctg ttataaaaaa taatcccaaa gcagccacca gggcatactg ct






#gcgatcaa 107760













gtcctaggcg gtattccctt ctgcgccata gaccctgtgc agagtgccct ca






#acgaagga 107820













gcaaggaaga ccaagtctcc cgagggtttg catatgtgta tgtgattctg ca






#gtcatggt 107880













gaatgacaca gtcagggctg cggaaaagca ttggtaaagt gtatatttga gg






#cttcagaa 107940













gtttgaaaag gctagatttc ctaggccaaa acactgaaaa tttgcaatta ga






#acttcagt 108000













gctgatgctg ggaagactgg agttagtttg agacatgcac ctgtgcagaa ct






#gggccccc 108060













agaaaaggag aaggaaggga atccagacca gagtagggcc tgacaccact ca






#gactcggc 108120













gtgtctataa attagaattg cgttacaatt acactttgac attttagtgg tt






#tttaaagt 108180













gcccagcaca agttaatttt tcattaatga atcctttatt cataaaatgc tt






#agatggag 108240













attacccttt tgagcatttt gccagtgctt ctgaaattaa tggggacctc ct






#gttggagg 108300













acacagtctg ttgcaatagg tgaccactgc tctgaatcta tgtcacctct cc






#aggaccac 108360













gggcacaacc atcacctgag gcatgttgga gatgcagatg gtcaggccct cc






#tagaatct 108420













cagaatctgc attttagcaa agtcctgggt aattcctatg tccattggag tt






#tgagaagc 108480













actggtaatc tcaaatactt taaaagatta ctagagtaag ataggctcag ta






#ggtacctg 108540













aaggcaccat cccaaagacc agagtggtag aagcaggtgg accagcctct ga






#acacattt 108600













ctcccccact ccccggctgt gtggaaggtt gccacctttg gggtagtcat tc






#aacaaaca 108660













cgtgtcaact gtccactatg tgtcaggcca ccactgggca ctggctgtgg ct






#agctggat 108720













agacaccatt tctgccctcc agaaatgtca tgtccactgg cacatgacaa gt






#cactaagt 108780













cattcagagc catgggtgac agctccaggg gccgacaaag gagctgtgat ct






#cacagatc 108840













cacagagaag tgtcccaggg cgggcgggaa ccaggactgc acagggaggg gt






#gaagtgac 108900













acataagaag tcagcccatc agcctgaaat gctcccccaa atcttcccat tc






#agtgtttt 108960













ctcagtagca aactcgtggg aaaattggtt attttactta aaaaactcat ac






#tagaaagc 109020













tagtttaact ttaaaaataa attttaaaaa catttttatt aacaaatcct ac






#ctttcctc 109080













caaagtcaag gagaaaagaa tagaagtgaa caatggacca agtaagccta aa






#actctgct 109140













ctttcccctg ctcattttac agttcaagtg ccattcaatt tatcctggca ag






#aagaggaa 109200













ggcatcatca agaccttaat tttctaatac atctgatctg agaagaatgt ga






#aagctata 109260













aaattaattt ttgatcaata actacaggcc ttttgagaga gtgccctcct aa






#tgaattga 109320













gtacctattt ctccatacac agtgtctatc atgacctaca aacccttttc cc






#atgaggtg 109380













taacagagag agattacagc cttggaactg gatgtcagac tctcctggtt ta






#agacaata 109440













agccatgaca tagagcctga aaccaacaca atcttccgag tggttccaga aa






#catatagg 109500













ggataatgtt ggctctgatg ctgtacatcc ccaacaacca tcaactattt gg






#aaactaga 109560













atttcagcat aattggagtt ggtgttaccc tagcaaatgc tgtgggaaga ga






#gtctcact 109620













gtgtatcttc tcctgtttaa agcctgaatt tgttcagaat gtaatatctc tg






#tttagcca 109680













ctctactgaa actgatctag gaaatgttca aaaaaaggta tcccaaggat cc






#ctttgtag 109740













ctacatctgt gggattcccc tcgctctggc gtggcctggc ccctctgcat tt






#gacaatac 109800













ggtcctatgc ttttgtcttc ctgggctgcg tgaacccacc ctgccctggt tc






#acctctcc 109860













tcttgaccca tccttatcag tgtcttgaaa ggtccttcta ttggaggaca ca






#ttctgttg 109920













cagcaggtga ccactgcccc aaatctgttt cacctcccca gggccatggg ca






#caaccatc 109980













cctggagtgt gttagagatg cagttggcca ggtcctccaa aatctcagaa tc






#tgcatttt 110040













tgcaaagtcc tgggtaactc ctatgtccat gagagtttga gaagtactgg tc






#tcatgagt 110100













tcctgacata caaatagtgc tgaggccagt atgctgactg ggtagccaga ta






#caagtgaa 110160













aaccttcctg ttttttgcaa acctggatgg acccgaggcc gctgacgtgg gc






#caggacaa 110220













gctactcttt ttcagtgttt ctgttgcatc gctgtgtctc tctgtgatca gg






#tgctgccc 110280













tccctggcag gaggactgca gacaggatga ccaagagcac tctacacagc ct






#gctctcca 110340













gtgttggggg acgccaccca ccctcgtggt tcctgttcat ctgcctacac gt






#ggagggcc 110400













caagagggct aatatgtgac tatctccact tcctggtacc ctgtgtgaat aa






#cttcactt 110460













actaaaggga tgttgagcaa ctttattaat aatgaagaaa gcactttggt tt






#gacaaata 110520













atcactccat tttttcattt gaaagttaac tcttgttagt agagaaagca at






#gtattaca 110580













accacaagga cgtttacatg gaaatgaacc atctgcaaag catcccccat tt






#tcctttta 110640













aatcagccaa tgggtggtgg tgggagaaat attcaccaga gtatttaaca tc






#tatccccc 110700













ttcctagact gtcagctcca tccgggcgga gactgttggt atctccacag ca






#cacacagg 110760













gcctggcaca catccggggc tcagtgagca cttgctgaat ggtgaacaga tt






#agctctcc 110820













tgggaacgtt gttgacacat ctcataacac tggtttggag tggagggcat tc






#atcgggct 110880













gcatattcct atttttaatt gtattctcca ctggttacag cacctacagt ta






#taaagaca 110940













ttgttaacat tgcttatagg aagacatttg atggaaatga gtccaaaggc at






#tacggtta 111000













gaaactggcc aggtgtcatt tttgagagat tagataactg ttttccggta ga






#gtgaattg 111060













cctgtttgtt gcaagttggg actttgctgg gctggtttac agggccaagg gg






#aaagagat 111120













aagtggatct tctagtgaga ggtcatctgt tttgaaagcc tggaagattc ca






#tgaactaa 111180













atccaagtct tacaacacag ggaagtgtgt catactgtgc agggatgaag tc






#tccaattt 111240













agcatgaaaa caagagctcc tcacactgtc ctcttcagaa agcccataca at






#ccaaactt 111300













ctgaatgctt agctgcttac aaccatacat agattgaggg ataaaactct ga






#tatggaag 111360













agaaggtaaa cattttttgg cagacattcc caggaaaagg cggctctctt ct






#ctcattgc 111420













tgctgctctt tcagaatcca tttcaacaga ggaggagtca atgggagccc cg






#tgcctctg 111480













gcagatatca tatggcgttt cagtggcatt gtgtgttacc cttcttaggt aa






#cagctcag 111540













ccattagaag aatgtcctac acaccttctc attttctgtg atgagaggaa tg






#tgaggtac 111600













tgcccttcga gagctgtcat ttgtcctagt agccagcagc gtgactgtgc tg






#tcttctgc 111660













tctgtctccc tgtcagcctt ctgcccagcc accaccacta tagttttgtt ct






#ctccattg 111720













gaactcctgg ttcagagaat taccataaaa aacagacccc tagacataca ac






#actctatc 111780













acataatggt gactttgtct tctattttgg attactgagc tttcttgggt aa






#cttccact 111840













aaatcgaagt taatattaga agaacttcct cttactagaa tcgaaaagca tt






#taagtgat 111900













gcagtcaagt ttgtaccata agtaattcag tcatttaaca aatatatatg gc






#ctctgtgc 111960













gacagtgacc ttgactggga atgaagctgt cccatgtggg gcctgttctt ca






#aaggcagt 112020













tccctgctgc ccagttcagt ccagtggatc tgggcatctc tctttaatcc gc






#attagggg 112080













ctctttactg attcttcact atccaaaaag acttggaggg gagacctgag cc






#cacttctg 112140













gaaggaaatg ataacaattt atttagataa tctttgtgca acaagtcaat tc






#actgaaga 112200













gatctgctct ctaggagcct ctgtgacccc accataactg ggaaggctct ac






#ctctccag 112260













tcttcgggcc acatttctct ctggcctgct gtcttcccag cactctcagc ct






#tgctcatg 112320













gagcactcta gtcctccgtc gaccttggcc tttggtaacg tgatttttca cc






#tggcagct 112380













cccatctggt ctcactccct ctttttgtcc agtctgcatg acacagcctc ac






#atcgttag 112440













tgttccctca ctcccctctt actgcccaac ctgcaaagtc catgcctggg cc






#agtgcagc 112500













atgtgtcctc aatgggctgc tggtggcagt ggggggaacc gcacagccac gc






#tgtgtgct 112560













gctgaagaaa tgcacagcct cctaccctcg ccctcaagag gcagccatgg ct






#gcgcattt 112620













ctgcccttct gagctccgct cacttttggc agcagccgtt ccaacctgca tg






#ggatcttc 112680













actctctcac agatgtgctg actcctcctg ctgcctcccc tctctgtgcc tt






#ctcactct 112740













ctgttccctt tgccctttct ccccttttct cctctgccta cctccaagcc at






#ccatcaca 112800













ggacagctca agcatcagat cctctgggac actttcctta gttgttcagt ct






#gatgaggt 112860













gtccctcatc ctctcttagc tgaaaatcag cagctgcctc aacttctttt cc






#agcatgtc 112920













tcatgagtat tgccacaaca gcatctgtca caatgtgggg tagtggctga ct






#tgcttttc 112980













tgccattcaa ctgagttccc tcagtgctgg ggccagcgtg cagtgtcttg ta






#ttcagtat 113040













atagctgatt aattgatgaa ttgattaatt aatggttcac actagcacag tg






#caaccttc 113100













aatgcaaaga tctcatcaaa ataattcaca tggtgggata ttttagaagg at






#gaccaggc 113160













tagtttgtag taagaaaaaa tcaacaagac taggtcagga attctttttt tg






#tctacagg 113220













cttgctatag aagatattga aaatcatcta cctaattacc tttattttat ca






#ggttgtgt 113280













attaaatatc acgtctgggg gaagaaaatg tgatatgtga ttacagacct tt






#cctggtac 113340













aacatagtac gtttcagatt aactcaaggt attgtggtga tattgcggtc aa






#agccaggt 113400













gattaaagag tcattctttg aaacaaatat ctgtgcaatc aattaagaaa tt






#aatttgca 113460













aattttattt gcttagagta attgatatat cattcctttt acaaacaaat at






#aaagaaaa 113520













cttaactaaa aatactgcat atctctttca gattatatat cccagaaagg at






#atattttt 113580













ctcctttctg gtcttccttt ttggtgtagc atctgtagga aatgcatttc tt






#catagcta 113640













agtgtacctc cttgtgaaat atcttcagag tctactggtg cacataagca at






#tgctggca 113700













gcagcttgag ggtctccatc tcacatttat catatgcctt attgcatgag gc






#tttgcaag 113760













aggaggtcta gagctacaat atctcatgga tatgaatgtc aattcaaatc cc






#agtggcag 113820













tttatgaggg ggaaagccta gaagagaaga aacctagagg aatcaagcag ga






#ggggagag 113880













taataaaaga ctagagcagc aggtttttct taactcaaac tagaattaaa tc






#tctgtgtg 113940













tgtgtgcatg tgaatgtgcc cgtatgtgca tgcatgcacg tgtgtaaatg ga






#tgtgtgtg 114000













tgtgtgcatg tgtgtgcaag taagtgtgta tacgtgtgtg ggcatgtatt gt






#gtacatgt 114060













atgtgtgttt tatgcatctg tttgcaagta tgtgtgtatg cacataaaag tg






#tgaatgta 114120













catgtgtgct tggtgtatgt gtgtgtatta atgtatgcgt gtagttctag ag






#tctagtta 114180













gagaaagtgc ataaagaaat agggaaatta acaagaaagc tatagcttaa at






#tataggaa 114240













aaacttttct ccctatcagt catggtttta aaatgttcag acttgatatg tt






#tcccagtg 114300













ctattgtcag aaaatgtccc tatgacattc catactactt caatcaaatc ta






#aaaccttt 114360













gttccaacat gttttattga tatgagtata tttcaaattt ctaccaggtt tt






#tggagagg 114420













tattttggcc ataaaattga ctaaattatt caaaataaaa aatgaataag cc






#tgggccaa 114480













ggcttggaga cttgcttaac tcagttctta aattttcaga ttttcaaaat ta






#caaattta 114540













agctctaaaa tcatggtgct gtgtatgata ttctttgatt gcaacttatg gt






#tgaaaaac 114600













tatagagggc tttatgctaa gagttgtgga tcttaggatt ttcatgaaat ct






#gcattatc 114660













atcatctgca agtttagatg gggcataact gatccaaagg atggatccct cg






#ggggcaat 114720













tcaactggct gattccagcc aagatgacaa cagtcaggat ccgttccctt ct






#gatcatcc 114780













attgggtgcc ctgatttcct ctacagccct agctgaaaga ccagacacta tc






#tcaggctg 114840













gctgccccac atgccttgct ccacaccaaa ttcacagtct ataaacctga gc






#ctccagtg 114900













ctcctactac catactcact cgaacattcc cgattctgac ctggagatgt ca






#acagctac 114960













ttgatgccac tctcttctat ctttctgtag ctaagccatc cccaagtttg tc






#gattcacc 115020













ctctttaacc cctgtcgggg tgtccattgt gccccttcac cctgccatct cc






#ctggtgca 115080













ctgttttgca aagttcagca tacatgagcg tcacctggga accttaataa ag






#tgcagatg 115140













ttgattcagc aaatctggga tgccctcggg ctgcatttcc agcaggctcc tg






#gggatgtc 115200













cccgctgctg tgctgcagat gacactctca gtggtgggac tccaggctct gc






#tgtcgcct 115260













cctaggggtt tctccacact ccctggaggc ctaatgggcc cttctccaca tg






#gcagtaag 115320













atctgttttt gtgtttgtgt ttcaagttgg gagaaggaga ttatttaata ct






#aaaatgtg 115380













caacatggga ttgagaaaac taattattag tcataagttg agtatgcaac at






#tgaaacca 115440













catgctttaa aaaattataa gaaaaaatca tagtatttga aagttacaag ct






#attatggc 115500













taactccatt tatctcagtt agagaagaag agtcacctgt caccagggca ct






#gccagaag 115560













ccaggctcat ttccaacagc actgggtgct ccagctttgg ggtgccagct cc






#tcccataa 115620













agcaaacaca tacctaggga tgatatttct ttgcaagggc tctgccctac ag






#cttgtaca 115680













tctcaagaag ttatgtaatt aaactgtctg ttttgagaaa attgtagatt ca






#cacatact 115740













agctgtaaga aatgatgcgg ataaatccag cgtaccagct ttccccacgg ag






#acgtcttg 115800













cagcgtcaca gccaggatga ggcattgacc caggcgaagt ccagagcacc tg






#tgcgctac 115860













agggcccctt gcactgtgct gtcacagaca cgcccacttc cagatgccat ct






#aggacccc 115920













ctccaaaaag cagaggcatt cttaaaaaca cacatctgca catgttcctc tt






#catttgaa 115980













tctgtcagtg gcttctcagt gcctttcaaa tgaaatctaa agtccttaca ag






#ccttgcag 116040













caggaacctc tccatcccac ttcccctcac actctcagct tcatctctgc ta






#ggctctgt 116100













tcagccaggc agcctttcac agtccctctc ctcctgccct gccaggaagg tc






#ccctgccc 116160













ccaactcttc cccacatgtg gcggggcccc gcttgtcctt agaagcccag ct






#gaactgct 116220













tcctgaagga acccctccag aacctctcag accaggtcag gtttctgcac tc






#ttagatca 116280













tccccatggc ataatcacag ttgtgatgtt gtgatgattc agtgaatgtc tg






#tctcccca 116340













ctggatggta agcttcctga gggcaggaac agcattggtt ccagtcaatg ct






#atgtccca 116400













ggactgttcg tttttgcaca tactaatcct aaaaggacga tgacaacagc aa






#ccacttac 116460













atgacctaga tgctcttctg ggtgttgtgc aaatattaac aatttaatcc tt






#gcaacaat 116520













ccacgaggga ggcattcttc tactcccact taacagacaa ggacagtgaa gc






#tagtaaag 116580













agaagtcatt tgcccaaggg gaccccacta ctgttggcag agctgggtgc aa






#acgcaggc 116640













ttgtgaagcc aggacccatg cattcaaaga ccatgccagg tgcccccact gc






#acacctca 116700













tccccacata ccagtgaggg ggagagaaat gctcctgcac tgcctctgat ta






#actgcttt 116760













cctagaagtc acacatataa aagggattta attctagtgg gattgaatct ca






#atagtttc 116820













cttattaggt tgatttctgt taatagttta agtactggat atacatgaat ta






#gaaaatct 116880













agattattag caaatgcaaa ctataaagta ttttataaat gttatcttgt tt






#gtcagggg 116940













atgagtgaga tattcattat acaaaaagta gtgtggattt tgaggtagaa gg






#tttactaa 117000













ggatcatacc gtagtatgaa atagccacaa acattcagtg aaaccaaaca cc






#cccgctta 117060













acctcaaact aacactaaat aataaggaat agacttgggg gcagtgcaag tg






#tatttcta 117120













atggtgaaaa ccattcccca gtgaaaacta atgtaccatc tagttaataa ga






#gctcctct 117180













gacccacgca catcaatact tacatcccaa tggtgatgtg acattttggg tt






#ttgtattt 117240













cttttgcaaa ttgagctagc atttttgatg agtggcaggg ctctgctacc ca






#acctttgg 117300













acagtttcca agcataaaat cacaattcca gataattctg tcacaaagat ct






#gggtctca 117360













ttaggaagga gaggaagctg ggagatgatc cagtccaacc tcccccaaac ca






#aacatcac 117420













ggccttctca gttgtttcac caaccatcta aatgttttag taattctaaa aa






#ttgatgcg 117480













ctttttccac gaaaggaagt gttaccacat tttccaagtg ggaggcatct at






#atccttac 117540













tccttcatcc tctccttccc accccctcac cccccaccac ccacacaaca tc






#tgcaattc 117600













ttaaactaaa gcacaaattg ttacaaaagt taattgcact ttcaaaggaa tg






#cttgtata 117660













gaaactttct cggcttcaag gaaaaataat acgctttgaa tggctgttca ac






#agcataga 117720













aattagctga gtagaaggca ctcatatagc cattaggacc aatcctttct gc






#cgccaaca 117780













ccccccttat aaagacttga cagtgggcca gaataaacaa cttcaggatg aa






#ttcagttg 117840













agacacaaag tacacacttc cagtttttcc cttctctggt tactggcctc aa






#taaccagg 117900













cagtcaactt aaaaagaaaa acaaaagctt gcttcagatt acagattgca ga






#cttcttat 117960













aatatgtcca tttcaccagg ccccgctctc agccccggga aaggccactg ga






#aaccacct 118020













cacatggtag ggccttgcgg gagccagtaa taaccttatc tccgtcaaca tg






#ttctgtca 118080













gattgaatgg ggcagccaga gaagccagag ttggcacagg aaccaaaaca aa






#ggcttccc 118140













atcctcctgg agtgagcggt tgagcctgga ttggtgctta gacctataat gg






#gtgcaagc 118200













agcgttcatt catagtggct ttctagaccc agggacttgg ccccagccct gc






#tgctccac 118260













tcctcttctt gcttcattac cacgagtctc ctagaccacc gaacgatgcc tg






#catttgaa 118320













agacacttct gctgatcaaa gcagctgatg tgtccctttg cggttcattt ct






#aattgtcc 118380













ccaaggagga gaaattcaaa tagtttatta ctgagagtta aagaaatcca ct






#gaaatatt 118440













ctttggtcta aaattactgt catggcggag cagcttcacc ttagtcattg cc






#cttaaata 118500













tgaaagctat ttaagaaagt ttgcccttaa atatgaaagc tattttaaaa ag






#tttaatga 118560













aagaagagaa tcacaaaaca ttttcaaaaa gcaaaagaaa acctaagaga aa






#agttgaaa 118620













gtaggaattt tttaaagaat atacgacgtg tgttctgtga ctcacccctg ca






#agttattt 118680













gtgtgtattc ccttgcatag taattaataa tgaagcaaag catggcaatg at






#atcttttc 118740













ttgtctagta ttctagaaga ctccatgttt ttggaaaata tcactctagt ta






#gatctcaa 118800













atatattcaa tcagaaaatg ggttttctac aagattctat atctgtagtc aa






#tagcaaat 118860













ataattctat taagctagta ggatgtgata ggaaactaaa acctagggga ga






#ccaaagca 118920













aggaaaaata cttcctcatc caaacttgag agcaatttac cgtcaggcct ac






#tattaata 118980













gatggaatac agattccatt ttcattactc aactgccata ttcattatta ca






#ctgtacag 119040













aaaagggaat cacatctgtt gaaaacttat atatgatgtt catgcatgca tt






#ccagtaat 119100













tcaacaattt ttatttatct ttttattgct tgctaatttt tcaaaataat aa






#gctaaaga 119160













aaacaaaatg tttgtgctgt tctcagatga catgttatct ctttaaagga ca






#aaatgtgc 119220













tgtgaaataa tagaatgctt tcagcactca agtgtgagtg agtgctcata ca






#tgagagaa 119280













agccgtgggg actacagaag ccaagaagca gatctagctg gggaggcctt tg






#cagaggat 119340













gtagttgtgt ggagaggcca cacacgtgga attcccagga gggctgtgga gg






#cggggaat 119400













ctgcaggaaa gcactggggt gagaaacgtg atgagaaaca attattgtct ta






#aaatatct 119460













gcagggctgt aaggtagaga agcaatacgt tgcatctgtg ttaagtcaaa ca






#aaattatc 119520













aagggactgg tttcagctta acataaggaa caattatgtg atagggttgt ca






#ataacaag 119580













agtagactgc ttcttcacac actcctagtc actcagaatg gtccaggagg ag






#tggacaac 119640













catttggtag agtatgggaa ggcaggggcc ctgggtggga gtggtgaggg ta






#gggagtga 119700













gtatcccaat ctagaagtaa attgtgccca gcacggagct gcaacactgc cc






#tgcacaca 119760













aacacacaca aataacaatc cccagcccct gcatttccct ctccggtttc ag






#gaccttgt 119820













atcttacttc aattccttta tttagctgat gatgaaatag gaagagctta gc






#actaagaa 119880













aatccttttg gagtttggcc ttgggggaaa atgaatcact ccaaccaggt ct






#gtcttcta 119940













gaaagtatag gatgaaaggg ctcctcatca catacttcct gacctcctgc ta






#ggcctttc 120000













cctaaaacag gggctggcaa agcacaacct gtgggtcacg cctagcctgc ca






#cctgtttt 120060













tgcaaataaa gttttattgg agcatgacta tatgtatttg cttacagtct gt






#ggctgcgt 120120













tcacactatc ccagcagagt tgaataattg ggacagggac catatgatgg gt






#gaagctga 120180













aaacatttac tctctggctg tattcagagg aggtttactg agcccttctc tg






#agacatgg 120240













caagcgctgc ttcaggctca tgcttcacta gattcaggcc tggggcagta aa






#gagccagc 120300













tcaggatagc actcccgact cactcatttt ttcaggcagg ggagccatct aa






#tgtcaagt 120360













gcctacgtgc aggaactggt ctgttaatta gcagctctcc tcatggaagg ga






#taatatat 120420













tctagaaaca ggagtgcggc cctattgcaa gaatgtcctg agccaaaatt aa






#gattcttc 120480













tatggcagaa acttggctgg ggcttctcct gagttaactt ggtagttgtt ag






#tgattttt 120540













gagtcagttt ttccttgtca acgaccccag gaatgagttt gggattacag gg






#tagccagg 120600













gaaagggaaa gcttcacgcc cgcccccggg acaaggtctg tcttcacact gc






#tacatccc 120660













ttcacccact ttaaaatgaa acttaaaagg aggatttcag ttgagtagga ag






#tgagaaga 120720













gggctcattt taaaacaagc gttaaatgaa aacccacaca cactcagagc ac






#acaaatcc 120780













aaccacgctt acaaaaccat cacagagggt caggcgaggc ccttttctaa at






#gaaaaaga 120840













acaggggtgg agactgttct gagagcatgc tgggttccct gaagggaatt ct






#cagctgta 120900













tgtgccccgc acaggatccc tgctagacac aaggccagct gccttccttt ca






#agccgcag 120960













acgcatccct gtgtccaggc gggctggtca gctgcggtca gcaccagctt cc






#ccgctcca 121020













tggtgaggtc atcacaacat gtgagcagga gggcaggccg gcaacctctg ag






#tgcttaga 121080













gaaagggacg ggattcctcc tgtgcaaccc ctctagtctc actcagactc aa






#gtctgact 121140













aaggggccag gtgctttgac cagggactct cccctctcac ttccctccca gg






#agtcacag 121200













gtacatgagt ccttgtttta caaatgaaga aaacagaccc aacatgatta ag






#atgttgcc 121260













ttcatagggg tggcaccagg attccaaacc atggactcca ctgagcccag tg






#cccactga 121320













catgtgccag taacagtgca gctgcctgtg gttctgtcga ctaaactgcc gg






#cagaggct 121380













ggctttccac cttctttttt tttttttcac tcttcaaaca ctttatgaca tg






#aacataaa 121440













ctactggctg catcgttctg ctgacaacat gacatgtttc tataacttga aa






#aaagcaag 121500













cagtggactg ctcattggta aaattgagtc agtaatcttt taggaaggtt at






#ttttcttc 121560













cttttactgc ttctcatctg ttccccgcag taaagaggac aagatgacga cg






#actcaggg 121620













aacacctcca gcctgaagca gcaccatgcg agcttagacc ttagggtcgg ct






#tagaaacc 121680













acaggcgggg cggcttgggc ccctcggaca ctccctctcg aagctgcttc tc






#cccaagct 121740













accccaaagg cactgagcgc cctctgcccc ccagcaattc aattcactgg ct






#gtcctgct 121800













cctgtcagta ctgagagttg catgtttgac cctcggggga aaagtccaga gg






#ccctgggg 121860













tgtccagcat gctctgaggt ccctgctgct gaccccttgc gctgtcagca tt






#cagagaca 121920













ttcacacagc acagcctccc aggctaacag ctgtcatgga acagtggagc ag






#ctagacgt 121980













ggccattctg tggcccagtg ctgcagaggt caaagggaca agcgcaggga gc






#atctttgc 122040













tttcagaaaa aaaaaaaaaa aaaagaagca cactggtgca ctgacctgct cc






#tggtgtct 122100













ttgtgattgc tcttttcttt cgatttttgg ttgtcttttt ttttttgaaa ga






#ggggcttt 122160













tatgcttttt tcctaatgtt catgggtaaa ccaatgtaaa tgtgtgtatg tt






#tatagaga 122220













tggctttaaa tcgcaattct gcagtagaga ttgatttttt aaaaaacatg gg






#taaaaatt 122280













gaagaaaaat tttaaaagaa catttaaacc atcttgggct aggggtggat at






#gcaccacc 122340













ccacggaagc caaacaaaat ctctctgcag ataaacattt gcaaaaagaa tt






#tccaatcc 122400













caatttttga gtcagagatc ttttatttcc ttgcaaatta catatctgtt tc






#aggatttt 122460













tgactataag aagaatgaat gaagatgtgt ttcttacaga taactatgaa ca






#aaccagga 122520













aggataataa cttgtatccc ccaattcgaa tccagaggat gggaaggcat aa






#aaaaaaga 122580













aatggaagaa actttatttt tagtggtaaa tggtgggact atgtatttta cg






#tatggtga 122640













agtcaccaag cccaacactt ggcacttgta ggcaaggtag tcttctaatc tg






#aatgtgaa 122700













gtattatgtt ttcatttgct tggtaatgag gaatattggt gctttcgtcc ca






#gttctcga 122760













gctgactgac ttctctttct gacgtgtgtt cctttagcac acctctacac tg






#catggctc 122820













tgagatgtcc tgtgactgtt tcatgtgtaa agttgcctcc ccaaaggact ca






#catattcc 122880













ttcagggcag tgagtacttc tgattcatcc ttagcagcta ccttcgcgct ac






#tttactag 122940













atatgttgta gttgaattaa tgaacaaaag aacaagcaac tttggtgcct gg






#tgtgcatc 123000













tcagagcagg gtggagtgag cctggccaaa gggtcatcat gcaacctctg tg






#gctgactc 123060













catctggcca cggagcttct cagccatgct tggtattcac atgacttcta gg






#gcgacagc 123120













tcaaccagca aataaacagc ttcatatggg aaatattact cagcctttgt ca






#tcaaggag 123180













tgagtcacgg gcctgaactg aatagaagat agaggagaaa aggtgtgtgg ac






#tgggtgag 123240













acagcgccca gcgaggtgaa ctcccggcag ccctgcctgt ctttacctgc ac






#atcacctt 123300













gctagggtgc cttcggttgt gagggcctgt ctaggaagag aagagttgca cc






#ctggcagg 123360













cagcactgag ctgtctcatg caaagctgag gaagaaagag tgagctgccc ag






#tgagcctg 123420













ctggggtggt ggaggctggg ctgggctgtg cagtctgcag cccccagcag cc






#cttggcac 123480













ctttctactg cctggtgctc accagctctc cagtaacaaa gagggacgtg aa






#gtcagagg 123540













ggaagggagg tagcacaggg cagtcttgac tttgaacaaa gagctggctt cc






#tgaagtca 123600













gctggccggg ttttgaagcc gattttccag cagtgatctt tgatgccaac cc






#catttagg 123660













aattctgtat ctccccctac cttctaccag atgtctctga gctcaccttt gg






#tgataatc 123720













atgcaatctc cgtcatcccc acgtccacac tgccccattc tgtcccaccc cg






#ggttctgt 123780













ggtgctgtcg gctccccagc gagccaggaa gggagaggcc agctctgctg gg






#gctcctgc 123840













cgccctggct ctgcactgcc cttctctggc aggtctgagg cgccactgga gg






#agccacac 123900













ggccctgaag cagcaaggca gatgccctgg acacagtgga ggcacagagt gc






#aagcaccg 123960













gcctggccca cagacttttg gaggggaagt ggtattattc agttcaaaag ta






#tgcctgtg 124020













tgtaaagaga gagcccctga acatgagtaa gcaaaagtct cagcgcagag at






#tagacaag 124080













tagaatgctg gcccgagagg aggcgtttac tcaccctctg tctaggaagg aa






#agccaggc 124140













ccagcacgct cactgctatc tatcctctca cacagaggga ttttgaatcg aa






#gccagcat 124200













cctgtccttt ctccaatgtc ccctgctcag gagtcaggac tcagcaaggc cc






#accccagc 124260













cacacacaga tacagttcca ggactcagaa ctcagcgagg cccaccccag cc






#acatgcag 124320













gtccagttcc aggattcagg acacagtgag gcccacccga gccacatcca gg






#tccagttc 124380













caggactcag gattcagtga ggcccacccc agccacacac aggtccagtt cc






#aggactca 124440













ggactcagcg aggcccaccc cagccacatg caggtccagt tccaggattc ag






#gacacagt 124500













gaggcccacc ccagccatat ccaggttcag ttccaggtaa atcatctgcc tt






#cctccgtc 124560













caaaagcctt gtttcctgtg tgtccttgtg tttaaaatgg aaacgttatg ag






#aaactgcc 124620













tgccagggca aagggtgctg cccggcacac agtagggact caaaatgaaa ct






#attgtatt 124680













gaatacataa cagatcaacg ggtattgctt tctgaaatct tttttagccc aa






#ttttgttt 124740













cttatagtcc aataacaggt caaattcatt tctgatttac tagccattca gt






#tgcccata 124800













aaaaatggaa agtgatttaa gattattagt ttaaaaacca atgaaggtaa aa






#cagttatc 124860













attgaaggca cataggcaga aatagattgc aatagttgct gccatgtgaa gc






#ctcagtgt 124920













catgctccat atttagagag atctatgatt tctgaggccc tttcatgtcc at






#gatctcag 124980













tactgctcac aactgccctg tgaaattcgc cgagctggcc ccatgtcaat ca






#gagtacac 125040













tgagcactga gacccagcat gttgagataa ctggctagag atcatcccat aa






#tggtacca 125100













tcacaatctt cacactgtag aagtttgatg atgtcactgg aagcatattc ca






#cagtccct 125160













tgtgaactgg ccttcctgtg atcagaagca tcagtgaact cccaagaggg tg






#ggaactcc 125220













caagaggtat tctcactcta cttagtgtat attttacaaa tcacaagctt gg






#ctttggat 125280













tcttttaatg gctagaagga gaatcatggg gttggaagtc caccagtttg gg






#tattctgt 125340













tccctaactc aaaataaaga gatgttattt tcaagtcttc tgcttgttaa ct






#taattaga 125400













gatacatgag tttgcagctg tgctgggcat gccgcagctt ggcatgttta gt






#ccagaagg 125460













catattataa tgtacatgga agattgtcag aaattcaaaa ggactttttg ag






#tatcacat 125520













gtgtattttc aagttccaat atagattcac attcagtttg acaggtatct tt






#ggatgcct 125580













atcagttaag aactatttat tagttgtgga ataaaatagg gtaaaataag ga






#acaactga 125640













ggaaaaaaca taaaatttgc tttgtgaata aaagttgtct tcaaaattat ga






#ctttttcc 125700













atcccacaaa agttttgatt aaacccacaa tgaaaattta aataagtgta tt






#tactttgg 125760













tttaaccact tatttcatta tgactcacaa ctataggttt tctagtttcc at






#tattacaa 125820













actattgtgt ggtttaaatc aatttcatag actagtctag ttctatagtc ac






#aatttata 125880













aaattttttt atgtggtaaa ttgagtgtct tcatagatgt acatgattat tt






#ctcaattt 125940













ttaaggaatg tattttttaa gatagccttc tttagccttc tttaacactg at






#ttttgtaa 126000













attttttaca gattttttta aatttttggt aattttttag cataaagtaa ta






#catggtca 126060













ctatggaaaa cataaaaaca caaaaactat gaagagtaaa taagaaaaac ac






#ccagaaat 126120













ttaccattca gaaaaggtca ttgttaacaa cacggtgtat cttcctcctg tc






#atgcttcc 126180













gtgcatttga gcacatttga gatgtgtata catgttcact ttgagatttt ag






#tatagcaa 126240













aagaaatgac cggtcctgat tcaatgaaac ctctggcaaa ctcgctatat tt






#tccttaca 126300













tatttttaag ttcatcctat aaatgaacta tccattcatc ttatttgaga tt






#ttcttaaa 126360













tctttcagca agaaagcggg aaaaaaatcc tcctctggcc tttaaagcct aa






#ttaaatat 126420













atgactaagc tagaaatatt ttataatgac caaccagaaa gtggcaagga ct






#gtcactct 126480













tcccatacag cccacctcct cctctatctc cctcaggcac acggaaacga ga






#aaggcaga 126540













gaaacccagg acaagtcatc caagactttg gtcacatggc catccattgc tt






#tcacaaca 126600













aaaatataaa tccaacatgt gtgtgtgcat ttcataccag taggtccaat aa






#gctatcta 126660













tatatacaca tatgtgtaca cacacacaca cacatcctta cagacactcc cc






#agcttact 126720













acagtttgac ttaagatttt ttgactttac gatggtgtga aagcaatgca ca






#ttcaatgg 126780













aaaccatact tctaatgttg aattttttat cttttcttgg gttagttgat gt






#ctgatatg 126840













ttactttctt gcgatgccag gcaatggctg ggagccagag ctcccagtca gc






#catgcaat 126900













caagaggcta aacagctgat actatacagt ggactgtgtc accagcattt tg






#gggatatt 126960













gtgttttgtg tttttgaatc ctatcatgtc tacaaaatgc cattttcgac tg






#ctattttc 127020













aatttagggt gggtttatca ggacataacc ctatggaaag ttgaggacca tc






#tgtatatc 127080













tggtagggaa agatggataa caaattcata ggcaaataat aatttcatga tt






#attattaa 127140













gttattccta cttaataata agtagtgatc actgccaggg agcagagaat gc






#aggataat 127200













gtgacagatg taatggtggg tacttaagct aatgtagttg cagaacaggc tt






#ttctagag 127260













ggtaggcctt taagcgtacc tcgaagatgc aaaggaagca aagatgcgaa ga






#tctgggct 127320













ggggatggaa gcagagacaa cttggaggcc aaggggagag actgacaaca gc






#ccagctca 127380













tacctcagca gcctttaatg catagctaag aaaacaacaa attaaaacaa tt






#atagttta 127440













cttagacgat tctaagtgtc taagtggatt tgggcaaatc tggagaaact tg






#ttctaata 127500













ctgtgtctta ataagtaata tagatttgcc caggcttgtg ggcagagtgg ta






#tacacccc 127560













ataatagcag aggaaggcca cagggcctac cctacaaaac cagaggcatt ta






#aaaactta 127620













aaggaggcag attgctttta ttttcagtta aaataaagtg aggagtttct ca






#agaaaaat 127680













aataacgaga ccaccggccc gccctagatg tccaacaaga atgcacagat aa






#cttcgtat 127740













atccactttc ctgaacctgc ccctgacagc caagtggagc acaacaacag ag






#atgaacct 127800













caaaactact gtgctgtgac ataaggcttg ctcaagagga cagtgtggtg tg






#agtccatc 127860













tatgttctaa agcaagcaaa gctattctgt agtgaaaatg gatcaggaca gc






#agttgcct 127920













ctggtgtatg ggggcaggga tcgactggga ggggcatgag ggatgacagt ta






#gggtttcg 127980













atcatgacag gaattcagat tactccagca tgtgcatttg ttaaagctca tc






#aaatgcta 128040













cacttaagat taatcctctc acagtttgtg gatgttacct taaaaacaac aa






#tgatgact 128100













gcaaactaat attgaactct ggttagtgat ataccaatgt gaagtatagt ga






#tatctcta 128160













ctttacttta aaatgcatcc aaaggcagac tagaggacca tatctgacag ac






#agaaaaat 128220













agatatgtga taaggtgaat gtagtaaaat gctaacataa ggatgtttgc gg






#tacaattc 128280













tttcagcttt tctatacatt tataaatcat aataaaattt taggacaaaa ag






#ttagtgct 128340













ttgaagtcct aagtcatagg gcctgctgct cttgatgcag tagaatttgt ct






#tcagattt 128400













gcaaagggta aggcaaacca ctagcatttt gtatggaact tgatgcaaat ac






#ttttaatt 128460













gtctggtttt caaatgtata gacttaaagt aatatcaact ctttctttga at






#caactact 128520













gaaataccta gtcttaaata aatattttta tgtaatcctt aaagtactat gt






#attcattt 128580













ttctttcttc tttcttttct ggtttgataa atattctata aagtaactgt gt






#ttaatggc 128640













caacatttga gtaagtccat atgcagatcc aaacatctca gtttagacaa ta






#acttaaga 128700













caatatagag tggctgacat cccctaacgt gggtccagat gcatgttatg tt






#atgtttct 128760













gttgcattct caatagttaa ctttaataaa agaaagtcaa aagcttatat at






#tttttcaa 128820













tcttcaaaac atttctggga ggttgtctta gttaatttta tgttgctata cc






#catatcac 128880













agactgggta atttataaag aaaataaatg tatttggctc atggttctgg tg






#gctgggaa 128940













gtccaagagc atggcattgg catctgcttg gcagctggtg agggccttca tg






#ctgtgtca 129000













atctatggtg gaaggtcaag agagcatgca tgtgaggtgg tggggaagag aa






#aaagcggg 129060













tttaactcat ccttttatca gggactcact cccgtgatag ctaacccatt ct






#tacatgaa 129120













tggcattaat ccattcctta gggcacagct ctcatgacct aattataata cc






#tcttaaag 129180













tttccacctc tcaacactgt tgcattggtg attaagtttc caataaacgc ac






#tttggaaa 129240













acacattcaa accacagcag agatcaacgt tattgtcacc attttcatat tt






#gaggaaag 129300













catggcacag agagcttgga gaagtacttc aaggtcaccc aatgaggaag tg






#gctaaaca 129360













aaaaccttat cttaaattaa ttaaaaacct cttgctcttt gcagttttgt ct






#taaatcta 129420













cctaatttgt gactgtaatt tttaagtaat ttactcatat aagtggtctc ac






#attaaatt 129480













ttctcattgc tttatatttc taacatgaga tatttggtat aaggatggaa cc






#aagatcat 129540













accttgtttt aattagaaaa cctagaccaa gtcattgtga tcctcatcct ag






#atttcagt 129600













taaatgctgc tgtctccttt tgggtatgtg acaggggaaa gcctcagaag aa






#acaacctt 129660













atgtgttttc ttttgatact ttagtaatta acccaggata gtattcaaga tt






#gacatgcc 129720













ttatattgaa tcaaatagca tatcaactgc cttcttattc tcaagtatag ac






#atgttggg 129780













taattgggca tttaagtttc tttgcaattt tttccattat taacaaaatt aa






#tgagcaac 129840













attctgcata aggtctgttt cctcagaata cgtttcccaa agtggaatca tc






#atgacgta 129900













gaatttaagc atacttactt gtttaaacaa attgtccagt tgcttcccaa aa






#tgttttgt 129960













gaattaagat ttacatcaag aatatgtaat gttgttactg tctcccaaat ac






#aggatctt 130020













tttctgaata taaaagttat acatgctaat tgtagacaat gaagggtcat ta






#tcctcata 130080













gataatgaag tgcttctaat acttgtgctt ttattcattt attcaaaaag tg






#ctaaataa 130140













gccctgaagg ggcttttggg gggtcatttg gggcttattt agcacttttt ga






#ataaataa 130200













ataaaagcac aagtacagtt tttttaaaat actgttttct ataatagatt aa






#tcttaaat 130260













ggcatgtttt cctttatttt actgacaaaa gttacttact ctgtgattga at






#aataaaaa 130320













ttctttggtt cagctgagag aaacttgcaa gctgacgtcc ttgattattt aa






#aatgaaag 130380













cagctgcctg ttttcatctc tctgcatcct gaggaaactc ttctgcaacg tg






#ttccagcc 130440













ctaggttcta gctgaccctg ttcatctgtt tggcacgagg ggcccaacta ac






#acttgcgg 130500













ctacctggac gacagccaat ctagttggaa tgagagttag aggccatagt ct






#gtcagctg 130560













ggaaagcagc ttttattcca aggtgtgcca accgaaaggc cacatgttat tg






#tcacaacc 130620













tggtacctac atcagtgctg acatctttaa gaaccttaga attgggaaat ca






#gtttagcc 130680













ctatctgcat gtgtagccga caaccacaca attgttccaa cttgaggttg ca






#ttcagagc 130740













aacctcattt cccccatact cctgaggaaa agcagaccag agacgctggg tc






#aatccaga 130800













gttatggttg gaaaaatgat ggaataattc tgcccctggt gataggagag ag






#ggactcca 130860













tcttgtcaac tgtcatggtt cccatgtgaa agctatcatt atcactgaaa tt






#gaatgaga 130920













acacagaagg gaagaacagg gaaatcccca cagagttaaa gaggatgtga ag






#attgcttc 130980













atgtttaatg tttgtgtaag tgctttgggt tggttatgtg ctgtctgaac at






#gtgctcat 131040













ttccatggct cattgagagg gcagacagtc caatgatact ctttagaatc at






#tcccatgg 131100













ggaaggaaca aagaagcctg taaaatagaa atgcacatgt aaaaagcatt ga






#agaaagtg 131160













ccagtgtatt gattttggcc atggtttgtg ctctaccacc tggttactgt ga






#ttgcagaa 131220













gtgcctttgc agatgaggaa gaacctggcc aaggctcaat ccaacatcca aa






#gccagagg 131280













ccatatttct tcactcttaa gataatttgg gttcaaatta tagtcccttt ac






#acactctc 131340













tgcctcaaaa ggcccaagac tctcttttgt tatgcttgcc taaacatgcc tt






#tcaaagaa 131400













ctagttctgt aaatacaact ttattataaa cctctccttt gcttttaaaa at






#ggatcacc 131460













acgtccattt ctatggtcca actttgtccc ttaatttaaa attttttctt gg






#attaagtt 131520













tgatgccttg aaacattagg aactcaagca tacaagattg tatgctggtg gt






#gagggaag 131580













taactgtgcc tccgcctgtg ctgggtggat caacatggag tgtggacgag ca






#tagggatg 131640













tgtgggtttc tcactagctg agagtgtttt taaatgttgt attttgatgt tt






#gttatttt 131700













ctgaatattc tacagttaga cctttgattt attctttgat gcattcattt ga






#ataatatt 131760













tttaatctcc agccagttag gtttttaatt tacacttttg tccctgattt ta






#ggtgtagt 131820













gttgtgtaca ctactgccca gtgtatgtta tgtttgtaaa cattcattgc ac






#gcacaaca 131880













atgtgactca caatattttt gagaagtaaa aagttcatta tatagttatt aa






#ctcaaccc 131940













tacagttata ttcgtgaaat accttgtgaa atttattttt tgcctactgg ag






#ctcttaca 132000













ggttaatcct gtcttcaaga ttttcataga attttcatct accacccacc cc






#tttaaatt 132060













tcaacatttt tttattttgg cattttaatg caattcaatg cattataggg ac






#aagctatc 132120













tcttattatg aattgcacct tatataaact taaagatctt ttatcacaaa tt






#tctttgct 132180













gtgtccttta gtgagaattt gtattatcag tcactaaagc tcactaagtt ag






#taagcttt 132240













gcgcccagat gacctgggca ggaatgggtg agtctctgtg tggagagagt ga






#agaaactg 132300













ctacccttaa tacctggacc ttgagggatt gttttatttt agtttttctg ca






#tttctcag 132360













tatttcatgt gatatctgtc tttttcttcc agtttgccaa ggcacgagta ac






#aagctcac 132420













gcagttgggc acttttgaag atcattttct cagcctccag aggatgttca at






#aactgtga 132480













ggtggtcctt gggaatttgg aaattaccta tgtgcagagg aattatgatc tt






#tccttctt 132540













aaaggttggt gactttgatt ttcctacaca aataaaattg gagaaaatct aa






#gtggagaa 132600













aggcctgggc agaattccac ttgaagtgtg tttatttttg ctatggcaat ga






#caagtctt 132660













acagagctac aaacgagagt tttatgagaa agccatttta ccagctaatg tc






#aagtaata 132720













actagaaaag gatatcaaat agaaacaggc taatctggag ttccatgtca tc






#atagacac 132780













tgacgtttat ccctgaccat tacctcagtc atgatgtgct gccatactcg ct






#cttaaaaa 132840













ctttttttaa aagccctgct ttgcaccatt tgcctattcc cttagtgtaa at






#actcctac 132900













tatagctgat ttcaaggtac caagtttcac tcagctggtc acagaattct ta






#tttcacga 132960













taggcgctaa tgaccccata ggagccagct ctgaaggctt cagagtttca ct






#gaattttg 133020













gatggggttt acttagcctt cttctgtttt tcttttacct ttccttttta aa






#taagaaat 133080













aatgcaagac agatacaaag taattctttt taatttccat tttcactgga ga






#gtgttgaa 133140













ccccgtgagg catgagagca cagtgttcca gaacaatgct tactgctcat ta






#tcacaggg 133200













gtcaaaggct aacgtgcagg gattgttgca gatcgtggac atgctgcctc ct






#gtgtccat 133260













gactgcaatc gtctacctat tttacagttg ttgagcactc gtgtgcatta gg






#gttcaact 133320













gggcgtccta gggctccctg gacccatttt agaccttgag ttcttgagtt cc






#tcaaaaga 133380













gaaatcacgc atttatgttt tctcttctta gaccatccag gaggtggctg gt






#tatgtcct 133440













cattgccctc aacacagtgg agcgaattcc tttggaaaac ctgcagatca tc






#agaggaaa 133500













tatgtactac gaaaattcct atgccttagc agtcttatct aactatgatg ca






#aataaaac 133560













cggactgaag gagctgccca tgagaaattt acagggtgag aggctgggat gc






#caaggctg 133620













ggggttcata aatgcagaca gcagttccga tggctcccag cgagcttgtc ac






#tcaattcc 133680













acctcggaga aggcttttat ttttacccag tacacgtgca ctgagtgccg gc






#tgtgtgta 133740













agatactgca ggggaagtta ctgagaagat ggcagatact ggaatgggaa ga






#tttaagcg 133800













gggtaccagt gtttacatgg acatgaaaaa atactgagag atagtaagaa at






#cgtaaaga 133860













ttctgagtaa aagagagtat gaccaaacaa gctgagcagg aatcgtgaat ct






#atgtgtgt 133920













aggcagtgaa taaactgcca gtcttattac ctggacctca aggataaaag ac






#atacagta 133980













aaaatcaacc cacattgagg acagtttcga gagtcgcgct gctacacaga aa






#gccctgtg 134040













taagttaagg atagagaatg aggtgttcta gaactttgaa tttttgtgag ca






#ggactcgt 134100













gaggttcctg tgagaggaaa caatgaagga tgatagaaaa gaagggaaat tg






#attttaaa 134160













aaactggaga tagcagtgat tgtgcctcac tgtgcagtgg gtttggggcc ag






#gaatgtta 134220













aattggtaac ttcatttaac gcccacaacc tttcttcaaa gtaggcactg ta






#cagatgcc 134280













ccttgactta tgatggcatc ctatctggct ggaccccgcc gagggtgaag gc






#gtcattag 134340













gtcggatttc agggctaatt gaatgtatat tgccttcaca ccatggcaaa gt






#cgaaaatc 134400













tgtgttaaat catgctaagc cggggactgg ctgtgctctg ccatcgtaca aa






#taaataaa 134460













tggaagtcaa gtaactccct tgagggcccc agctagtgaa tggagaggcc ag






#ctatggcc 134520













accactctct gccccagggc gctcaacgcc cctcctgtgc catgcagttc tg






#acagggag 134580













gcagtgctgg taggaaaggg gtgtgatgaa aggggtgccc agcagaggga gt






#catatccg 134640













gagtgacagg agcccaacag gggtgcagcg ctggaaccca agccagcacc tc






#tggtcatg 134700













gctcctcagt tcaccgccta taaaattgtg tggttccccc acaccccttg ct






#gctcagag 134760













cagccgcgca catgcttgtg ctgtgcgtgc ctcctgtgag atggcctggt ac






#accggttc 134820













ctacagtgcg cctcacacgc tgtctcggag ggaggcagcc tgtgcgggtg cc






#tggacctc 134880













cgagccagac cctctgggtt cctgcctggc cccgtccctc agcagccaga tg






#gctcggga 134940













gcacattctc caatccctcc gtgtctctgt ttcgtcatct tcaaaaatgt gg






#atggcata 135000













gctgctaaaa aatggtgaca tacttcctag gtggtgcaga aaattaagtg ac






#tgtaggaa 135060













caggcctcag cagctccttc cacttccttg gtatgattgt tttttaaacc aa






#ggctggga 135120













ttgtatagat gcagattagt taatgtgata ccattaatag ctaacctagt gc






#ctgctgca 135180













gggtgagcct cccctaagcc accgggaagc ggctcctgca gcctccctca cg






#tgtgctgg 135240













ccctcctctg gcagtcattg cctgtggtgt gctgaaggcc cagctctgac tg






#tgcctctg 135300













tgctctcctc gccccgcccc ctgctctctc tcaggtcttt ggtctgttgt cc






#gagctgcc 135360













acagcagcct ggacatccct gttggtgttt ccagccctgt cctctcctga gt






#tccatcca 135420













cctgtgcatg gctttttcat gagtgttttc acggatggtt ctgctgtcat ct






#ccaacctg 135480













ataaacaaag caccacgatt cagcccttat gaccccaagc ttccttcctc ag






#ttccttgc 135540













ttctgtgcat ccactgaaga agcctgttcc actgtttccc tgcactgggt ct






#cctgtctg 135600













caggaagcct tcagccctca cttccacact cctctaagat gtgtgcctgt gc






#ccttctgg 135660













ggaagctcat tttcctagca gcctccagga tcttcagggg tgaatccctc ct






#ttcccacg 135720













ttggtactct gtacacacaa catgcccatt ccctgcctgg ggagctgggc at






#tgcttcat 135780













gaatcagagg tcaatttttt ctctattaaa gtcacagatg ctcattgcac ca






#ttgtgaga 135840













atgaatgaag atagtgctta taaatcagcc agcaaggtac ccagcctcac tg






#tgtcaggg 135900













tctccctggg catgaggtgg ttagagtgtg tgacatgtct gtccccaagc ct






#gtcagctc 135960













ccagatcgaa gccagtggat ctcattcatc ctcgcagcgc ccacagcact tg






#cacagggt 136020













tttgtacaca taagtcattc tgtcaatgtt catgtttaat gtcatcagtg ga






#acactccc 136080













actttgtaaa gacttgaatg tgttcatccc tgacttttcc acatcttgtt ag






#ttcttctt 136140













tggaaacagc tgtacagttt caccatcctg tgcatccctg gagtctacct gt






#ctctgtca 136200













tacattcaga ttcttcttgt ttcgtgtcac tctcatatcc ttttctctaa tg






#aaaagctc 136260













cgcctgggca tgcaaggtgg agccctggat gccagcccct cacctggcat cc






#agggctgt 136320













agcactcagg aactgcctcc ctgccctgcc taccccctac atcatgcgac ca






#ttccagtc 136380













cagccaatca gccccttggg acccagctta ccacatgcat atcatttatg ct






#gtgaccac 136440













tgactaaacc attctcttcc ttcctcccca tatttctaaa tttctaatca tt






#gctcaaag 136500













cccaattcag agaaaaccct agctcctcca tggcaccatc attaacaatt tt






#atctggcc 136560













gccccccggg aagttcactg ggctaattgc gggactcttg ttcgcaccat gg






#catctctt 136620













tagcagaaca taaatgcgaa gagcacatgc atccttcatg ggaatttaaa gg






#agctggaa 136680













agagtgctca ccgcagttcc attctcccgc agaaatcctg catggcgccg tg






#cggttcag 136740













caacaaccct gccctgtgca acgtggagag catccagtgg cgggacatag tc






#agcagtga 136800













ctttctcagc aacatgtcga tggacttcca gaaccacctg ggcagctgta ag






#tgtcgcat 136860













acacactatc tctgcctcca gctcctatgg gggacagctc tacagcactg gg






#gcagggga 136920













gagaagccat gtttagtaag tcacattaat cagaaacaaa aagtagtaag ca






#aaatatct 136980













gaccactaga aaagcatgta tttaccacgg acatagagat cgtttttttg tg






#gcgggtgg 137040













cagcccagct ggttggcagt gcaggccacc ggaggcagat cccctgcagg ga






#cagcagag 137100













cacttgtgtc ctgagaagag ctgctgttca tggggctggc agcaccaggg cc






#tctcctag 137160













cctgccctgc tgacactggc cagactccta catgcttctg agtctccaga gg






#ctacccgg 137220













ccctcctgaa gcaccagggc tgaatccacc cccagctgag ggcatgaaca ct






#gccacatg 137280













gagtcacaca cacagctggg cactgccatg gagaggaagt ctgtccatgt tt






#ccttgaat 137340













actggtggcc tggtccctgt cccattcccc agtgaggcag cctgtgggga ag






#cctggcag 137400













ggaaccaggc gcaggtcagc gtggcgccct gactcaggcc agcactgatg gg






#ggactctg 137460













agacgcaagc tcacactcac ccagctcccc tgggctgcgc ccgttcctga tc






#gcttggac 137520













tttctgttct ttagagtaag aagtgatcac catttcctgc ttctttgttt ct






#ccacaact 137580













gtgcagtgga tgcctgtttg ttttctgccc tcagaacaaa aaaaaaaaaa aa






#tagagctg 137640













acgtgaatct tcaaaatcat caactacagg gctttggatt tttgtgtatt tg






#ttttattt 137700













tcattttatg gatggattgt gatgaaatgc ccgtaataca agattttcca tc






#ttaaccat 137760













tgtaagttac aatgtcagtg gcattataca tccacatggg tgtgtggcca tc






#accaccgt 137820













ccacacacag aactctttta tcttgcaaag ctgaaactct acccattaga ca






#gtaactct 137880













ctgctctccc ttccttccca gcctctggcc ctggcaggca acagtccact tg






#atgtctct 137940













atgaatttga ctgctctggg gctctcatac aggtggaatc atgtagtatc tg






#tccttttg 138000













tgtctggctt atttcaccta gcaaaatgtc ccgaaggttt atccatgctg ta






#gcacgtgt 138060













taagaatgtc cttcctcttc atggctgaat aatattccat tgtatgttga ca






#ctacattt 138120













tgtttgtcca ttcacctatc tacagacact ggggttgctt ccatcttttg ac






#tgtttgaa 138180













taatgctgct gtgaacatgg gtattgaggc tctttgtttt atagacatat ta






#ttccacca 138240













gatacccatc ctgacaccta ctatgtttgc aagaaactga aagctttatt tt






#acattgca 138300













aaatttcata ttatgagatc aaggttagca tttcctcagc tgtctggtgg ac






#aatgggga 138360













ggttaaactg tgcacatttt attttttttt aatgaacctg gaacggttat gg






#ggccagtg 138420













tttgccatgg atcaggtcag gcagcccaca atggcaggtc tccatgttct gt






#acaacaac 138480













tgtgggaaag acccacagag aaagtgctgg aaaggggaat gatgggtagg tt






#catgcagt 138540













aaaaagattc aaatactaca gggcattgaa ctataggcca atatagcatt gc






#tttaagaa 138600













taaacaaaaa ataagacagt aagaataagc ctagcaaaat caaaagtcta ta






#aagaactg 138660













acatttcaag ccaataagag aataattcct tattcaataa attgtctgga at






#gacttaac 138720













tattaggggt gaaaatatca aagtgagaga actataaagg gtttttaaaa ag






#gaattagg 138780













tatgttgggt tagtcgcatt ggagagtgca aattcaccat cgacctgata cc






#tgaaattt 138840













cctccttacc atctagaggc aagttgggaa tgctgccagg ctcctgtggt aa






#aggaagct 138900













cctctcttga ctggtgcttt atggctacac gttcctgctc agaatggatc tc






#atttagtc 138960













ttcaccaaaa aaaaaaatct catgagatga tttaagtgtt ttatggacaa ga






#tgtctaaa 139020













actcagaaaa atttcacagt gtgcctagct tttatgttta tgttgaagtt gg






#gcattaga 139080













agttagaatg aatgggttta cttcagagaa aattaaatcc atcacccact cc






#ttgtacta 139140













tgaattccaa atacatatta aatacatata ataaaatatt taatatatat gt






#aagtgcca 139200













gaaggaaaca taaatatgaa tattttgtaa tatcaagttg aagaaaagcc aa






#aatctgac 139260













atcataaaag aaaactttca agtaaaatat gttaatggct accaggaaaa ta






#ttgtgcaa 139320













tgtctgattg ccatgaagag ggttaatatc cttgctatat cactctgtga ag






#tcatcttt 139380













aaaagactaa gaaaaagatg aatctcttaa taaaaacctg gcccagaaca tg






#agcagcct 139440













ctctctctca ctctcactgt ctctctttct gtcacacaca cacacgcaca ca






#tacacaca 139500













cacacacaaa tatggccaag aaataaagta aaatgttatt tctaatgtaa ta






#agtaggtc 139560













aaaatagaaa aagaaagcat cacaccttcc tttgcaaagt atttgggttc ct






#tttgcttt 139620













taaacacctg ggtcagctgg ggtgtcgaga aacagaaatt ctcacgttct gc






#ttgtgggc 139680













atatatgtta ataaaaccaa gcttggcaat atgcctgcaa tatgtatcta aa






#gcttcaaa 139740













gtatgtatag ctttgaccaa tcaatatcac atttcggaat aagagaaaaa ga






#aataatga 139800













aagtgaaaat cataagagat gtagaaacat attcttatac aagaattcct tg






#cagcctta 139860













tttataataa attttgtgaa caaattatat atctaaaaat aagagattgg tt






#gaaaaaat 139920













tatgcagcag ccatgctatt gataatcatg ttagatagaa gcatatttaa ag






#gcatggaa 139980













aaattgccat gttttatatg ggtttttaag gttataacac aatgtatagt gg






#gattccaa 140040













ttcctgtata tacatagact tatatgtcta tattgattaa ctctggatga gt






#ctcatgtc 140100













ttctttttgc tttcttctat tatccatatt ttatacgatg tgcctgcatt tc






#ttttttgt 140160













aacagatggt caatactaga atcataaaca gatcttgttt gtttattggc aa






#atgtttcc 140220













cgttagaaaa agatgcattt ttcttttaaa tatttttatt ttatacaatg at






#tacaagct 140280













tataatagaa atttgaaaat tatatgtgag tacagggtaa aaagttgaaa ga






#atgggatt 140340













gcacgctaca gatctagctg cttttagcac gcctgcgtag gaccttgctt tc






#tctagacc 140400













tctgttgcag tctctctgcc tacctcctca caacgtccat cccccgcggt ca






#ctgtcgtg 140460













atgccagcct ccccggcctt catgtctcta aggagcacca gcgcggcaat ta






#gcgccctt 140520













tgccttggtg gtattctggc ttcacagtca catgggagat caatcgtcag ct






#tttctgtt 140580













tgaaatctaa attcttcctg actgcagggg acctcgggac ccatgaacac ct






#ctagttta 140640













ctatgtcttc acagtaaaag atatctgcat gactggactc tttaacaaat tt






#ggtggtta 140700













acctactctt tctatataga tatagcactt cgaccttcag acttctcaat ac






#tgataaaa 140760













agaaaacacg acagatgaca ggaaaacctt tgcagctata atttgtaatc gg






#ccaattat 140820













aaaaactgca aaaattgacc agatagctaa ggttttacac agtcatgaaa gt






#gatctgca 140880













ctgttaacat ttcaccctct gtgcaccatt ctgtgcttct ctctggtttg ga






#gtctagaa 140940













ggttttattt acaggctatg acttaacaat cccagaacgg ctgacacatg ca






#gtcactca 141000













agactggaca cagcaaggaa gtagtgggtc catgccaaag gctcagccag ac






#gagacact 141060













ctagctgtgg caggagatgc cagggaatgc tccaagccta agcagattgt aa






#acaaggaa 141120













cctcaaattc atgaaaaatt cttgcttatg tggcccatgt cagtaattac tc






#tctgcctc 141180













agtttccgca gctgacatgt aaataaaagc agttcatggt tcatcttctt tt






#cttatcgg 141240













ggtctcaagt gattctacaa accagccagc caaacaatca gagaataagt tg






#aaaagatt 141300













gtcttcattt attgaatgtg cttaactcag gcccgggaaa gggcgtcatc ag






#tttctcat 141360













catttcactg agatatgcat ctattacttt tacatttcag gccaaaagtg tg






#atccaagc 141420













tgtcccaatg ggagctgctg gggtgcagga gaggagaact gccagaaacg ta






#agtcagtg 141480













aacagcctca gacccatgtg tgaccgcccc tctcttcctt cacttgctta gg






#tgattgga 141540













tttgttttcc ctctgaagac tccaaagagt tactttatta cagggtcaga tg






#tgaaccag 141600













taggtgaagg acagtcttgc aaatctcacc gcatgcagtt aatccagggt gg






#gctatttt 141660













gggagcttca gcctatcaca aataagtgaa catcagcagg ggctgggcgc gg






#tggctcac 141720













ccctataatc ccagcacttt gggaggcgga ggcggtcgga tcacgaggtc ag






#gagatcga 141780













gccattctgg ttaacacagt gaaacctcgt ctctactaaa aatacaaaaa at






#tagccggg 141840













cgtggtggcg ggcgcctgta gtcccagcta ctcgggaggc tgaggcagga ga






#atggcatg 141900













aacctgggag gcggagcttg cagtgagccg agattgtgcc actgcattcc ag






#cctgggcg 141960













acagagcgag actccgtctc aaaacaacaa caacaacaac aacaacaata ag






#tgaacatc 142020













agcaagtacc ccagccctgt cctctgaaca cagcacactt tcccaggaat gg






#aagacttg 142080













ctcctgttga cagcagtcac cagacttctt gtttcctctc cctccctggc tt






#tctttggt 142140













acccacctac acagaagcct gagcacgggt tctcatgggg acttttccat gt






#ggaccctg 142200













ctttacgatg gagagggcca ttctcctagg tatggttgtc tggctcagcc tc






#tcagtggc 142260













caaggaacct ggggacatga gctcaaaaac ggacactatg tccttaagct ga






#attgtggg 142320













ggggctgtta ggcccttcta aacactactt cccagcaggt atttttgttc tt






#tgtatgtg 142380













ctttctgcat tgcccaagat gcatctaatt atttagcagg tctcaaagtc ta






#gacttgat 142440













ctcatgagtt ctcttaagtg attaaaaata aatcaggaga aaaaagaggc aa






#tcagaaaa 142500













gggcatggtt tgacttagtt tgaatgtggt ttcgttggaa gcaaatgtgt ct






#tcactttt 142560













tcatgaaaaa gtctgcaagt gctctgcgac atccctggga aatgatccta cc






#ctcactct 142620













tcagctcaca gggaaccttt gctctttttc agtgaccaaa atcatctgtg cc






#cagcagtg 142680













ctccgggcgc tgccgtggca agtcccccag tgactgctgc cacaaccagt gt






#gctgcagg 142740













ctgcacaggc ccccgggaga gcgactgcct ggtaagatgc ccctccagca gc






#ctccctgg 142800













agcaggctgg ggctgcaccc gccccaccca caccaggaca gaagacttcc tg






#tgggggag 142860













ctgtcaatta gcatttgtca taacagacag gatattgccc tctgcctggt ga






#caaagtat 142920













ctttagtatc ctgcctccac cactcactga gaccttggga aaatgatggg ac






#taccatgc 142980













ctccatttcc ttacctgaca atgatgcata acaaagtctc tcccagttga at






#gcttaaat 143040













gatgagatgc ctgtgatgtc cgtcattagg acctgggcac agaacaagca ct






#aaatacta 143100













catgcaagta tttgtcatga atgtgccttg ttgccagcag cacactctct tt






#attgtttg 143160













acttcggcta tacctctaga gacttgacac tgtgaggtcc ctaagagacc ca






#tggagagc 143220













cacacaggtc ttgctggctg gggctgggtt agggcctcct gacacggatc cc






#tcggctcc 143280













tccaccactg ctcaggcacc tcctgagctg caccctgccc tcaaggggtc ct






#gaagtact 143340













cactgtcgcc ccattgctcc agaaagtgcc agcagaagcc ttgctgcccc ag






#cgggctct 143400













gagcagcact ggagggtaca ggtcagaagc gtcttggaag tcctggagac gc






#caaggctg 143460













gtggatgtga ctcctggagt gggagctggt gtgacgaagc ccttcctaag ac






#taaatcca 143520













gagcactctg tggtttcaga gaagattcct aaattccaga gtttggaccc ag






#acccagga 143580













attgtgactt ggttggcctg agctgtttct aatgtgagcc ccagggagaa ga






#ctgtgcgt 143640













ggggttggtc ctaggaaaag ccctcgctgt attgggtctg gctcctttac ac






#ggcattgt 143700













tctagcaagg ctttctgcca ttcagcaata cattataaaa tataccctca at






#tgtacttt 143760













ataagggaag cccaatgtcc tttataaggg aaattaaaca taatttcatt cc






#atagtcac 143820













cgctataatg tgtgaactcc atcatctata cgttagtaaa cagacgtatt tt






#tatcataa 143880













tccataaatt atgataggtg ggacagtgca cctaagaaaa aaatggactt tt






#tagagaag 143940













ggtctttctg actctgcaga gggcgccagc tgggttttcc cacactagtg ga






#acactagg 144000













ctgcaaagac agtaacttgg gctttctgac gggagtcaac accgtgctgc gc






#ttcctccg 144060













tgtgtggcgc tgagtgtact tacctcactt gcccagcgtg tcctctctcc tc






#cataggtc 144120













tgccgcaaat tccgagacga agccacgtgc aaggacacct gccccccact ca






#tgctctac 144180













aaccccacca cgtaccagat ggatgtgaac cccgagggca aatacagctt tg






#gtgccacc 144240













tgcgtgaaga agtgtccccg tgagtcctcc tctgtgggcc ctctaactgg tc






#aggcatcc 144300













ttgtcccgct ctgtctcctg ctgagccctg gagtatccca tcttggagag tc






#tttgggtg 144360













gatgtgtttg ccttgcttgg aggaggcgac cctgtgcccg tccaggcaca ca






#ggcgaggg 144420













gaggggctgg cttgctaccg aggagcgggc aggtggtggc catctccacc ca






#tgggggct 144480













gctcagtgca cagggcagat ctgggtggcc aggccacctc acaggagaaa ca






#cctgctgc 144540













tcagccctca ccactcatcc agcagccaca gccgtgggta ttcagttgtc tg






#ctgggcac 144600













aaagccgtgg gcatgccact gtttagtgct tgtgccaagc aggtatttaa ta






#caccgaaa 144660













tcagagagtc tatcagaaga cctgccttct tgagtggtta aaattctagt ga






#aagttatg 144720













cctcttagga gtattgcaga ggttttgttt ttgtttttat tttgttttgt tt






#taatggtt 144780













tgggtttgag ttttgcttgt ttgtacttac atttgtactg gtggctccag gg






#tttaggga 144840













aattgtgaca taaaataatt cctgacagag aaagcaaaac tttgtctaat ga






#aagagttt 144900













tagaagccac tcttgatctc tagaagggga gattaactga gaaaaaaaat tg






#aaagaaca 144960













attatgaggg ggagatttta ccctgccaga tttgtgtaca tgaaaaattt ta






#cattccgt 145020













atggaaaaaa aaaacacaaa ataataagcc attataaggt aaatgacaaa ca






#aagctaaa 145080













gaaaaatgtg ccacagtgat gacacagata tatctttgag atagggctta ac






#agagcttt 145140













aaaatccata ggaaaacact tcgagcctga gataccaaga gcagatggtt ca






#cagaagaa 145200













tcatcaatgt cctataaata tttttgagga tcttcttggg gaacttaaaa ca






#ggaacagg 145260













ccaggcacag tggctcattg gctcatgcct ttaatcccag cactttggga ga






#ctgaaggg 145320













gctggattgt ctgaggtcag gagtttggga ccagcctggc caacagggtg aa






#acctcgtc 145380













tctactaaaa atacaaaaat tagccgggcg tggtggcgca cgcctgtaat ca






#cagccgct 145440













caggaggctg aggcaggaga attgctttaa cccaggaggc ggaggttgca gt






#gagctgag 145500













atcacaccac tgcactccag cctgggtgac agagcaagac tccatctcag ac






#aaacaaaa 145560













aaggaagaca tagagctcct aaaaataacg cagaagtctg ctattaatac aa






#atgaatta 145620













ctttaaaggt gagagcaggt ggaggagagg gctgaggtgc ctgctgggac gc






#aaaacagc 145680













tggcccctca agggacccag tgtttcctgc catgatgaaa cacctgtatt gt






#ccacattg 145740













cggcctagaa tgttattaaa ctcttgaacg ggattccttc tctatttgca ac






#ctttcatt 145800













ctttgtcctt aaagtaaata aagccaaagg aggatggagc ctttccatca cc






#cctcaaga 145860













ggacctggac cgcctgtgtg aggcccgagc acctggtgcc accgtcatca cc






#ttcctttc 145920













atgctctctt ccccaggtaa ttatgtggtg acagatcacg gctcgtgcgt cc






#gagcctgt 145980













ggggccgaca gctatgagat ggaggaagac ggcgtccgca agtgtaagaa gt






#gcgaaggg 146040













ccttgccgca aaggtaggaa gcccgccggt gtgcggacga ggcttgttct cg






#gctgctga 146100













ggctgggctc tcatgccacc tccaaaggaa cacatcttcc tcttctcatt aa






#aaaacaac 146160













tatacatatc gtttctttaa aacagaagat aaagctgtaa agctaggtta gg






#caatggga 146220













aggcactgaa ggttgtgacg gggtgggggg ctctgatgag aacagtcaca ga






#gccagccc 146280













cgctcagcag ctgccaggtg cccagccctg gggagaatcc agggaaggca ga






#gctggaag 146340













cagtgcagct ccaagcggcc catgggaaat aatgaggaga acgcaaggtc ag






#tgtgaggt 146400













gacagggatg gcatctccta caccgccgta gccccaaagt gtactatagg tc






#ctggtgtc 146460













cccccttccc gcctgcactc tccccagccc cttcagtgtt tgttgagtga at






#gaaggatg 146520













atgtggcagt ggcggttccg gtgaccggaa ttccttcctg cttccctctg cc






#tgtggatc 146580













cctagctatt cttaatccaa caaatgtgaa cggaatacac gtctctctta tc






#tctgcagt 146640













gtgtaacgga ataggtattg gtgaatttaa agactcactc tccataaatg ct






#acgaatat 146700













taaacacttc aaaaactgca cctccatcag tggcgatctc cacatcctgc cg






#gtggcatt 146760













tagggggtga gtcacaggtt cagttgcttg tataaagaaa aacaaaatct gc






#ctttttaa 146820













ctggtagaga ttggtgatca ataatcaccc tgttgtttgt ttcagtgact cc






#ttcacaca 146880













tactcctcct ctggatccac aggaactgga tattctgaaa accgtaaagg aa






#atcacagg 146940













tttgagctga attatcacat gaatataaat gggaaatcag tgttttagag ag






#agaacttt 147000













tcgacatatt tcctgttccc ttggaataaa aacatttctt ctgaaatttt ac






#cgttaatg 147060













gctgatgttt tgatattttt caaaagtgca gtttctcctg caggcaaaag gg






#gacacgtt 147120













aagtccaggc ttgggtcatt cactgcggtg taaacacgct ttctccctcc cg






#cccggccc 147180













cagccagctg ccttggtggc ccataacccc tgagggtaga gggaggggac ag






#gggtaggt 147240













gacaggcagc ctgggcctca ggcttttgaa actggacgcc agagccttgt gg






#ggccacgg 147300













gcaagcctcg ggtctatgac tgccgcctga gctccgcttc cttcctctct aa






#aatgggaa 147360













gattagacca aaataacaag actgttttaa ggttggaatc aaataaggaa aa






#tttgtaaa 147420













gctccttgta tgtgatacca gatccacaat tggcagataa tcgcagcagg ag






#cctcttcg 147480













gggtaatcag atacgcggcg cagcaggggt ctcagggcca cagccagggg gg






#cggcggga 147540













gacatgcgga atcgcagcgg aaggcgggag gcagctgtga actgtggctc gg






#cctgcgtc 147600













cgccctgcgc atgtacactc agagaagatg ataatgaaaa agaaagcaaa tc






#caattttc 147660













ccacttactg ttcatataat acagagtccc tgagagtcta gagtaatgtc tc






#atacaaaa 147720













aagaaactcc tacgtggtgt gtgtctgaag tctttcatct gccttacagg gt






#ttttgctg 147780













attcaggctt ggcctgaaaa caggacggac ctccatgcct ttgagaacct ag






#aaatcata 147840













cgcggcagga ccaagcaaca gtaagttgac cacagccaaa gcctggtaga tt






#acatttgc 147900













ctttttagtt ggaaattagg cttaacagga gagttgctaa gatagggcac ag






#agctcctg 147960













catctctcgc cggcattccc aaatgctatc tcacatgagc aggcacaggg ag






#caagactg 148020













cacgaccact ggcacaggct gtccgctaaa ccacagactt ctcagcgctc gc






#cagtgctt 148080













ctgcttctgt gtccactcca gatcccacat tgcacttagt tgtcaaatct tt






#tcagtcca 148140













tttctaacct atattagctc ctgtgtcttt ccttgtcttt cacggccttg ac






#acttacaa 148200













aacgtgtggg tcaggtactt tgcacactgt ctaaccatgt ctgttcagct gg






#tgttttct 148260













caggatgcaa ttgaggttat gcacatctta tcacagggac cagagagact tt






#ttagcacc 148320













actcttcaag aatttccact ttttcagctt tgacagtgga atagacatgc ag






#gtgctcac 148380













acacaagcat ctttaatatg gtaatggtaa tcatcagttt agtggtgtgg ag






#gaggagat 148440













gggaatctct tagtgaaacc cgccttggaa gcagcctcgt tatgagaact gc






#tgccccta 148500













cttgactctt aaagcactag ataatactgt gcaacattaa agagaataag ag






#tgcgtgaa 148560













atatgcattg cctcccataa actcccttgg ctctgaatct ctgatactaa at






#atgtggct 148620













accgttgctt cccagaaagg cctttttgct ctgaattctc tggaatgctt tc






#tttgacca 148680













agattcttat aaaaataaga gatttagagc aattttcttg gatggctggt at






#gagccagt 148740













tggcttagtt gtagggattt aaacaagata agggttactt acttttcaca tt






#taatgaga 148800













agtctggtga ttccagctcc tactgagaca gggtggccac acgttccagg gt






#gtgactca 148860













ctgaggcccc agacctgccc tgcaaggaaa acctggctct gccctggtgt cc






#tggcctcc 148920













ctgggcatat gtgggggaga attcctaatg gtattggtta caggctccta tg






#cgagacca 148980













ctcatctgtg taggagaaag gaaaaagatg ggggaaagaa gagcagcagg ga






#gaggagaa 149040













gcctctggat gatactctaa ccccctgcca tccaacacct gaacatcagt ct






#cttcatcc 149100













agtgctctca gctggcccag cccccagcct ggggtcagat gagagcttcc tg






#caaatgca 149160













gatctctttc ctgtggctcc ttctcaatta cagacagctc ctccacaagg tg






#cactctgg 149220













ccttgtgctc cctccccaaa ccagcccagc cctcccagcc tgcatcatcg tg






#gtcctgta 149280













ggggctagag gttctcacac ccatcgtggt ctggcagagg ctggtggttc tc






#acacccat 149340













cgtggtccgg caggggctta gtggttctta tacccatcgt ggttcaggag gg






#gctagtgg 149400













ttctcacacc catcgtggtc tggctggggc tagtggttct catgtccacc gc






#gtgctttc 149460













ctgctcctcc aggtggctga ggacatcccc ccttcggtct gaatgacttc ca






#tccagtca 149520













tctgatatac acattggacc acccaatagc atcctagtgt catgttggat gg






#tgaagaaa 149580













atgccacagt tactgctttc agggcctcac aaccttgggc atagcttttt gg






#aggaaggc 149640













cccacttccc aggcatccct cccagacctg gtcagaggcc cctgctcttt gc






#ttccatgt 149700













tgcccacact cactgtgctc ttcacaccgg ctcaaaatga tctgcttacg gg






#gttgtgtc 149760













accaccagat caagcgtcct ggagaggagg aaacatattt aacctgcaca ga






#atttggga 149820













cagagaacct ctagtgtttg ttcaataaat atatgaatgg atagagggac ag






#gttgggtg 149880













gtggatagat ggatgaaccc acacctttga agtgtatttg gctgtttgag ag






#gttagaat 149940













atgttctcaa tttccaggca aaatgaaaat ggagaaaata taatgacatt aa






#ggcatttt 150000













attcatcctc cccatctgcc actgggttaa agatactaaa taaacaagga ac






#tatctttt 150060













gcctggagga actttaaaaa cacctgcagt tttcaaaagg tgcagtgtgt gc






#ctcccaca 150120













gcatgaccta ccatcattgg aaagcagttt gtagtcaatc aaaggtggtc tg






#gagaaaca 150180













aagttttcag ggatacattg tttttataat ttttcaccac atgatttttc tt






#ctctccaa 150240













tgtagtggtc agttttctct tgcagtcgtc agcctgaaca taacatcctt gg






#gattacgc 150300













tccctcaagg agataagtga tggagatgtg ataatttcag gaaacaaaaa tt






#tgtgctat 150360













gcaaatacaa taaactggaa aaaactgttt gggacctccg gtcagaaaac ca






#aaattata 150420













agcaacagag gtgaaaacag ctgcagtaag tcaccgcttt ctgtttagtt ta






#tggagttg 150480













gttctaatgg gtcctttatt tgtatttaga atattgaagg gctattccca tt






#taaattac 150540













ttttttcagt tccttaagaa gcaaattaaa atcttaagat tcctaactgt ga






#aattacca 150600













tgtgaattcc attaaaactt tttccagatc attaccattc aatgggatga at






#ttaccctg 150660













aggtttaggc taccaattat ttgtaatgta agtaactaaa tttagtatta gt






#tatattac 150720













cttttagttg taggtcactc tctgctcatt tcagcctgta aagactacag ct






#acacacat 150780













acacacacag aggaatggaa tgagcacttt acatcaacac ttcctgttct gg






#ctctagag 150840













cctcagcttt tgaagctggt gagagcctgg cctgtgctgg gccttggcca cg






#ggcagcgt 150900













cagctttgag tcaagtgctg gtctggcctc cctagctttg agcctctgtc aa






#ttccctta 150960













atctgtttag gctttggctt cctcatccat agaatggaga tatgaatgat tc






#ctacgccg 151020













tagtgctttg agagaattca gtgaaattcc tgtgtgtaaa acccttccat gg






#tgcctagc 151080













acacagcaca cagccaatgg cccaatggct cctatcagct gtgggatttg tc






#atcagaac 151140













accaccagct ctgctccagg ctgccctggg taccatcaaa acacaccctg tg






#cccagcag 151200













cacctgctcc tctgcacacc tggttccttc agcaggggca gtggccgtgg ga






#gcacagaa 151260













aacatggagt cccatctggt ttaattgatg ccattgccaa aggggaggac tc






#acggcacc 151320













ccctctcggg tgccagggtg cctggctccc accaggagga agacctgtcc tc






#cactgtca 151380













ggcacatttc agtcttccca gcagccagca caactacttt gtccttccag tc






#acggtcgg 151440













cctctgggaa gcccagtctg tgtcctcctc cttcaggggt agccagcatg tc






#tgtgtcac 151500













ccaaggtcat ggagcacagg gcccctcccg ggaaggtgcc gtctcctccg gc






#ccctcggg 151560













tccctgctct gtcactgact gctgtgaccc actctgtctc cgcagaggcc ac






#aggccagg 151620













tctgccatgc cttgtgctcc cccgagggct gctggggccc ggagcccagg ga






#ctgcgtct 151680













cttgccggaa tgtcagccga ggcagggaat gcgtggacaa gtgcaacctt ct






#ggaggggt 151740













aggaggttat ttctttaatc cccttgcgtt gatcaaaaat aaggctccag gt






#tgttgtta 151800













tagctttaca ggcattctgt ttgattttct cttcctttta ttctttgccc tt






#ggcttttg 151860













gaggttttgg gttttctgtg gggagacggg aagttgtttg attgcgttat tt






#ttggcaaa 151920













tttaagcaca ataggaaata agcaagtatt attgcctaat ataatccaat aa






#tttataga 151980













atctcttttc ctggaagtat cttaaatttt tctaagctac aaaaagttcc ta






#agacaaat 152040













gagacagtca tcaatggttc atctagccaa caccgtggcc atttgggctt tt






#ctttgtag 152100













tgcccgattc ctggtgtgtg aaaataaatt aacacaaatt atattgccaa gt






#taatatct 152160













gttttatgtg cccccagcat gtgttgaaca tcaaacagta ccagggactt ta






#aatatacc 152220













cacggacaaa gaaataattc ataatgatgt ttgttgaatt tagttgcaat ca






#ataaaaag 152280













tgcagtttgt gaatgctctg aggttcttga tattgatgta aggctttgaa cg






#acaaatga 152340













ggacaaaaca taaataggaa agtaaaactg aaggatagag gccaaggcca tg






#ttttagaa 152400













gatttaaaga aaaagggaaa tttggtgagc accataggaa ttacagatgg ct






#gtaggaat 152460













tcttcctgtt ttactctctg ggcatggacc acagcttgga tccagaaata tt






#taggagca 152520













ggataagagg accaagttca attctatagg aatcctttag ctgataggct ca






#gaacaaat 152580













cacataattg atagtgctgc ttcaacttca agtaaggaat attgatgcaa tc






#cttacagc 152640













tacaaatgga cagtggtctc atgttttcag ttttcaagtg tttcttaaga gg






#caaggtga 152700













tgaaaacgcc cacgtgggga gccccatgtc cttccattag tgtagagaaa cc






#tggtgtcc 152760













agcagcacct gctccctctg caagcccagc ccccttcagc aagggcagtg ac






#ccagagaa 152820













gaagcacaga agacacaacc ctgtatcaca ttttgtttaa tggtgccatt ga






#ccaaaggg 152880













gaggatgaaa ggcacacact tttttgttgt tttttgagac agagtctcac gc






#catcaccc 152940













aggctggagt gcagtgatgt gatctcaact cactgcaacc tctgccccct ga






#gttcaggt 153000













gattctcctg cctcagcctc ccaactagct ggaattacag gtgtgcacca cc






#atgtccag 153060













ctaatttttt gtagttttag tagagacggg gtttcaccac gttggccagg ct






#ggtctcaa 153120













actcctgacc tcaagtgatc tgcccgcctc ggcctcccaa agtgttggga tt






#ataggcat 153180













aagccactgc acctagccaa ggcacacact ttggagaata aacactcctt gt






#tcgctgct 153240













ggagggtaga actatgcttg actactaggc agagtccagt cttactgaca aa






#cagccgta 153300













catctgttct gtcttttcaa tcaaacatca gcttcttgct taacattgat gt






#gtacatct 153360













tgagggatgt caaaatattg taagctaagt ttttcatacc tgtgttccac ac






#tcaccatt 153420













tttagtaata accattgagc gagttcattc tccctccttc ctttttctat ca






#cttaatct 153480













aaaattatca tttttccagc ttaattttga taaccatgaa tctggtatta ga






#ggcaggga 153540













acacctcctc aggactatct tttcttttat catttggctt gcttacccaa ta






#tgcaaaaa 153600













ctatgctgta gaaaaagcag aaaagatatc ttgattatga atgaagctcc tg






#tgtttact 153660













cagagagaag atgacccagg attcagttaa caaaatcagc tgattatatt ac






#tatatagt 153720













cctggagtcc caactccttg accattacct caagttattt ggaattttga ag






#aggtgatt 153780













tgtgttcctg caataatgtc tcaggggtgg gctgacgggt ttcctcttcc tc






#ctctcagt 153840













gagccaaggg agtttgtgga gaactctgag tgcatacagt gccacccaga gt






#gcctgcct 153900













caggccatga acatcacctg cacaggacgg gtaagagccc cttgctgcta tc






#cacgtcca 153960













tttcatggga agggccttca cagaagccga acagtgatga tggcccaggg ca






#tcctgtgt 154020













gggcaggacg gccatcagag ccacttccca gaggagacgg caggcgctga ca






#gcgctgtc 154080













cgggcagggt gtcggtgaca ttagcacaca cattagcctg cgatgaacat tc






#actctttc 154140













tgctgacacc cccaacctta tctaagctta tcaaatcctc acatttaacg ga






#ggctgttt 154200













tcacctggtt tcccccatcc ctgacctagt cagcattgct ttatcgcttt ca






#tcaaacat 154260













cctcaaattc ttaacattag cttgtaatta attgaagaat ttttaaagaa at






#tgctagca 154320













aaacttttta aactgcacaa ctttgtatct atatgttcaa taacatatag at






#acaatatt 154380













ctttacaata atcttttaaa gaatatgagt gagaattcgg gcccctctca ca






#ccaaatgt 154440













cctgatgttg ttaattctca atgttattat atagggagct ctgttttctt gt






#gagcttca 154500













acagccagtt ctaaatctac taactgaaaa cattttttag acattctcta aa






#ttgggcag 154560













aagatgacag gactgtgttt tgagggatag gctgccagcg tggctgctta ca






#aagtaaag 154620













acttggttta taggtttgca tggtgttggg ttaaatttct gtcattaaaa ta






#attggcga 154680













tattgacata gtcatctaat tatgctggct ctgggcacac acagcccttg ag






#tggacaaa 154740













accaacatga gagaacttag ccaaggggaa agcctttccc tgctggtttt at






#ttctgcta 154800













cttctgaagt gtggggcaca caacctgagc agtgctttta tttgagtccc aa






#tgctttta 154860













tttgagtttt gcaaggttat tccaagtttt acaaatagaa ggtagcgtat ga






#ctcagtcc 154920













ttgatatgcc aaccactgca cagagacttg ccaccttcct gtcactggag aa






#acactcat 154980













gtgggttttc ttaaatttgc ctccctctga gcttcccttt aacttcaact at






#aatatgca 155040













agaaagacta tctgaccata aatacacatt tgggccaatc aagatggttt tg






#ccaaggaa 155100













agatgcccac aatggttaag cagaatgcaa taatgtagag aatatcattt ct






#ttcatgct 155160













ggtgtatatc atatgcattc aaaaacaggg agaacttcta agcaactaac ag






#tgaccata 155220













tcaagcaggt gcaatcacag aataactggt tttctccttt aagaattttt ct






#atcatttg 155280













gctttcccca ctcacacaca ctaaatattt taagtaaaaa gttacttcca tt






#ttgaaaga 155340













gaaaagaaag agacatgcat gaacattttt ctccaccttg gtgcagggac ca






#gacaactg 155400













tatccagtgt gcccactaca ttgacggccc ccactgcgtc aagacctgcc cg






#gcaggagt 155460













catgggagaa aacaacaccc tggtctggaa gtacgcagac gccggccatg tg






#tgccacct 155520













gtgccatcca aactgcacct acgggtgagt ggaaagtgaa ggagaacaga ac






#atttcctc 155580













tcttgcaaat tcagagatca aaaatgtctc ccaagttttc cggcaacaaa tt






#gccgaggt 155640













ttgtatttga gtcagttact taaggtgttt tggtccccac agccatgcca gt






#agcaactt 155700













gcttgtgagc aggcctcagt gcagtgggaa tgactctgcc atgcaccgtg tc






#cccggccg 155760













ggcctgtgtt gtgcaatgct gcacatcaca acaggagggt agggggacaa aa






#gagcacag 155820













gtcctggcag ctgccacagt ctccaggggc ttttgcgttt ctctccagat tt






#ctaaggtt 155880













aacatgggga ttagctgttt tgcaatgaat aaaaggtaac attgcctgga at






#gttgctta 155940













aagacacttt tttaaagcta gttgattgtt aagctgttgc tacttaaatt aa






#aactactt 156000













tgggccagac gcagtggctc acgcctgtaa ttccagcact ttgggattcc aa






#ggcaggca 156060













gatcacttga ggtcaggagc ttgagaccag gctggccaac atggtgaaac cc






#cacctcta 156120













ctaaaaatac acctgtagtc ccagctactc aggaggctga ggcaggagaa tt






#gcttgaac 156180













ccgggaggca gaggttgcag tgagccaaga tctcgccact gcactccagc ct






#gagcacca 156240













agagcgaaac tctgtcgcaa aaaacaaaaa caaaaaaaaa agctactttg ac






#tggaatta 156300













gcagaagcac tctgattgtg tgtatcttat ttactggaat aataaagctg tc






#aatcaaac 156360













tggatcccac tcaacaatca gaaagagaag ttgagctgtc atatagtagt tc






#acacttac 156420













ttctgtttct caaaatcctc agctttgttt ggaactgtta ctcattcttt ct






#ctgaatcc 156480













atctgtatga gttgtgtgcc cttgggcaag ggtcttacct tctctgtgcc tc






#actttctt 156540













ttctgtaaat tgggataata atgctgcata gctcacagga tttttatgac ca






#tgagttaa 156600













gatatgtcat atacttaaaa tggtgcctgg aaaatggtga atactgagtc aa






#tgatagca 156660













tcattgatgg tgggatggtg atgaggaggt gggagtcaca atggtggtgt tg






#atggtggt 156720













gatggtggtg aggaggtggg agtcacagtg gtggtggtgt tgatggtggt ga






#ggaggtgg 156780













gagtcacaat ggtggtggtg atggtgttga tggtggtgag gaggtgggag tc






#acaatggt 156840













ggtagtgatg atggtgttga tggtggtgag gaggtgagag tcacaatgtt gg






#tggtgttg 156900













gtggtggtgg tggtgaggag gtgggagtca caatggtggc agtgttggtg gt






#gaggaggt 156960













gggagtcaca atggtggtag tgatgatggt gttgatggtg gtgaggaggt ga






#gagtcaca 157020













atgttggtgg tgttgatggt ggtgatggtg atgaggaggt gggagtcaca at






#ggtggtga 157080













tgagggtggt gatgatgatg aggaggtggg agtcacaatg gtgtcagtgt tg






#atggtccg 157140













atggtgatga ggaggtggga gtcacaatgt tggtggtgtt gatggtggtg at






#gatgatga 157200













ggaggtggga gtcacaatgg tgtcagtgtt gatggtggcg atggtgatga gg






#aggtggga 157260













gtcacaatgg tggtggtgat gacggtgttg acagtggtga cgaggcggga gt






#cacaatgg 157320













tgtcggtggt gatggtggtg aggaggtggg agtcacaatg gtggtggtgg tg






#atggtggt 157380













gatggtggtg aggaggtggg agtcacaatg gtggtggtgt tgatggtggt ga






#tggtggtg 157440













aggaggtggg agtcacaatg gtggtggtgt tgatggtggt gatggtggtg ag






#gaggtggg 157500













agtcacagtg gtggtggtga tgagggtggt gatggtgatg aggaggtggg ag






#tcacaacg 157560













ttggtggtga tgatggtgtt actggtggtg acgaggtggg agtcacaatg gt






#ggtggtgg 157620













tgatggtggt gaggaggtgg gagtcacagt ggtggtggtg ttgatggtgg tg






#atggtggt 157680













gaggaggtgg gagtcacagt ggtggtggtg ttgatggtgg tgatggtggt ga






#ggaggtga 157740













gagtcacaat ggtagtggcg atgatggtgt tggtggtgag gaggtggaag tc






#acggtggt 157800













ggcgatgatg gtggtgagga cgtgggagta acaacagtgg cagtgacggt ga






#ttgagaca 157860













tgatgatgat ttgtcaactt tctaggaaaa caatcatata atctccaaca gt






#gatatctt 157920













aatatctttt ccaaaagtat cagatcatat tataagggcc aagtttccag aa






#taatatca 157980













gacataatga cagtggacat cagagcttgg catctaaagg taatgggaat ag






#ctctaatg 158040













tctcagcgtg aaaaacaaca tttgctatta gtctgagata ctaattatct ag






#ttaaggaa 158100













gtactcacct atacctagtt tttaactgtt ttttaaaatc tggaattgat tt






#tgaatttt 158160













aacaaatatt tccctgggaa caatgtaaga ttcttcatat tttcgccttt gg






#gtatacca 158220













acatgccagc tctgttggcc actttgtgag ctcgatgaag catggtataa aa






#gatgcttt 158280













gctagtgttt cacgtaatct atttctataa gcaattttgg agctaagcct ct






#gaaacaga 158340













attatattat ctgtatagaa taaatgtttt atcttccccc ttttctttct tc






#tggaatag 158400













atgtgcatca gtatctctgc atcaatatct ctatatcagt atctctgtgt ca






#gtgagcat 158460













atgttgctgg gcttagggga ggtccagaaa gtgattgggt tttggcattt tc






#aatacact 158520













tactttgtat aagaaatagt ttgccaaata tagaaagagg ggatttagtc aa






#gatttaaa 158580













ttaaaaatgt tagtggtcat ttttctaatg tctttctatt ttttcccagg tc






#ctaataaa 158640













tcttcactgt ctgactttag tctcccacta aaactgcatt tcctttctac aa






#tttcaatt 158700













tctccctttg cttcaaataa agtcctgaca ctattcattt gacatatgga at






#tttataaa 158760













tattttcttt agtatgtgtg attacattcc tgattctgag cctttttaga tg






#agtatata 158820













gtttgatata atcttgttat tgccacctgt gtcttctccc aaagccatta at






#tatatagg 158880













aattacacga tagaaatggg tttaattttt aaaatacggc caagtgttga tg






#agagggaa 158940













aattttttta atttctttca ctgagtattt atgacgtgca caacattcct ga






#atatattg 159000













tctctctcat ttctcagatg ggatgtattg ccttctccat ttctattgtt aa






#agaaacac 159060













ttacaggggt ttctttaaca acttgtgaac agcagcatca gagcccagac ta






#cagcataa 159120













gcagctgctg attccaaaag ccctaccttc caaccgggca ggtgcagcca cc






#cagacgag 159180













ggggaggaac cctggaggaa tagctatttc tttttttttt ttgtcgagac gg






#agtcttgt 159240













tctgtcaccc tggctggagt gcagtgccgt gatcttggct cactgcaacc tc






#cacctccc 159300













aggttcaagc aattctcctg cttcagcctc ccgagtagct gggattacag ac






#acctgcca 159360













ccacgcctgg ctaatttttg tatttttagt acagacaggg tttcaccatg tt






#ggccaggc 159420













ttgtcttgat ctcctgacaa gtgatccaca caccttggcc tcccaaagtg ct






#gagattac 159480













aggcgtgagc cactgcgccc agcaggaata tctattttta aatggaactg tg






#ttttcata 159540













gtacacggtg aggagaaagt tgctttgaaa tctttatcct aataaaccaa at






#aatatgaa 159600













aatttgccta ttttaattat atgtaacaaa gtttagttac tgctataatt gc






#aaatatgt 159660













ataaattcct taccaaaaaa aaaagaatca agtgggagcc agagaataat tt






#ttctgaca 159720













gaattaaata acatgctata gctgcttgag ttcatactca atagtcattt ct






#gcagagtt 159780













accgagggcc tcatcagcgt cagcaggagc ccctcgcctt ctgacgctct ca






#catccttc 159840













tctcctgcag ccccgtcctg ccactgtcct tgtccagctt ctcttcaagg gt






#caactggt 159900













ctacctttcc ctacaagtct gtcacagctt cttgttagca atccctatgg tt






#gcccaaaa 159960













gcattttcag agcctgcata agactgcatc ttgtagaaaa tttgcagttt ca






#atctgccc 160020













tccctctgcc gggtgttccc attgtattgc attcagcagg cagggagaga ct






#gctattag 160080













gtctgttcct gagtgactgc tttctgtctc agactgtttg gtgtctgtag ga






#ggtagtgg 160140













ggtgggcagt aacgaggtct cctgtatatt ccacccctac gaagcctgtg tg






#tttggttt 160200













atgaactaag ctcaaaagca ccacaggggt aagactgcag tacatgacac ca






#tggaaaag 160260













agggagcacc cagaccccca aattaagaag agcagtgtag agaacagaga cc






#tggagagc 160320













agagatagaa actgttagga tcagattata gtgttacacc agggctcccc ag






#gcctctca 160380













catattgaaa tgtacttgtc catctttctc caggccagga aatgagagtc tc






#aaagccat 160440













gttattctgc ctttttaaac tatcatcctg taatcaaagt aatgatggca gc






#gtgtccca 160500













ccagagcggg agcccagctg ctcaggagtc atgcttagga tggatccctt ct






#cttctgcc 160560













gtcagagttt cagctgggtt ggggtggatg cagccacctc catgcctggc ct






#tctgcatc 160620













tgtgatcatc acggcctcct cctgccactg agcctcatgc cttcacgtgt ct






#gttccccc 160680













cgcttttcct ttctgccacc cctgcacgtg ggccgccagg ttcccaagag ta






#tcctaccc 160740













atttccttcc ttccactccc tttgccagtg cctctcaccc caactagtag ct






#aaccatca 160800













cccccaggac tgacctcttc ctcctcgctg ccagatgatt gttcaaagca ca






#gaatttgt 160860













cagaaacctg cagggactcc atgctgccag ccttctccgt aattagcatg gc






#cccagtcc 160920













atgcttctag ccttggttcc ttctgcccct ctgtttgaaa ttctagagcc ag






#ctgtggga 160980













caattatctg tgtcaaaagc cagatgtgaa aacatctcaa taacaaactg gc






#tgctttgt 161040













tcaatgctag aacaacgcct gtcacagagt agaaactcaa aaatatttgc tg






#agtgaatg 161100













aacaaatgaa taaatgcata ataaataatt aaccaccaat ccaacatcca ga






#cacatagt 161160













gattttaatt atttaagagt agtttagcat atattgcttt atgatttaat ta






#aaaatctc 161220













caaaatatat gccaaagaag tagaatgaga aaaatgtata tttctctttc ac






#ttcctaca 161280













gatgcactgg gccaggtctt gaaggctgtc caacgaatgg gtaagtgttc ac






#agctctgt 161340













gtcacatgga cctcgtcaag aatgaccaca ctgctgtggg tgaagatgct tt






#cctgcatt 161400













tctgactgtc ctctgtcctg atcaagtttc tatggctctg ggccagccta cc






#ctcagcca 161460













gggtttctgc agagactgcc cagctggttc cacgtggctc cacgtgccaa ct






#ttgtcctc 161520













agtggaggga aagttggaca cacagtgctg gggctgctcc ctgctccgcc gt






#tgctcgat 161580













gcatggcctg cctctgaatt ccttggttcc actggttttg ctgggtcctt ct






#gtgcctct 161640













agctcctctt tttttctgtc cacttacccc attggtccca tcacaagcct gt






#gtgtgagt 161700













ggcctttctg ttcgatgaca acctccagca taggggagtg tttctccttg ct






#ttctttcc 161760













cagacacact gcccagcaaa ggcaaaaggg cttccttcaa catcagctct gg






#ccagtttg 161820













ccagagcaaa gccctgagaa aagcaaggtt gaaaagtctt attcaaactc ac






#caggaaag 161880













agtggtgtta ctctcgatgg cgtctagcca ggaatcatgg aattatacac cg






#agcacctg 161940













tttgccattt tggatgtttc caaacatgaa ccaaacttcc aggcccctct gc






#catctctg 162000













gtaacattta caaagtccct tcctcaccac tgcccttcct tcattttggc at






#gctcctcc 162060













gcccccgagt tgacagccat agctctctct cctgccacca gtgtcacatg at






#cgaggaag 162120













aaggcaactt caaaaagact gggtcccctt ccactcccat ctcttcagtg ag






#ctgctagg 162180













acacccagca gaacttcccc actccacact gcaatctcag ggatcttagt ca






#cggggctt 162240













tccaccatgt ctccacctgg aaaccagtca tggccattcc ttcttacatc tg






#ctcttttc 162300













catctttttc ttctcctcct gttcacccgc ccttactctt gtggcgccct at






#ggatatgc 162360













gctccatagc aaatgattct ttatatctta cggtattcta gtgagctggc ac






#atgtggct 162420













tctggtttcc tctctctgga actagacatg acctctgtgg gagggaggat ta






#aatgcacc 162480













ctacagtctg aggctgcatg atgacatcac tcatcacaat gatgctttct at






#gtctgaat 162540













cctattcctt tataacccct ttcaagctcg ttcagagagt atttcacaca at






#ccatgtgc 162600













tcatcttaaa agccaaggac ccagaggagt ctcagcattg ccaaaaagtc cc






#ttcaccca 162660













gcctggccag aggcagtgcc tggtccatgt gtatggacta tggcacttca at






#tgcatgga 162720













aatactcttg gaatgaacaa aataccaatc catgaaaaag cattattgaa gt






#ctaagtta 162780













ttttttgaat catattttgt taatcaacaa attgaaaaat actcattata tg






#gagaggtc 162840













cagataaagc ctcaatttta aaaaatgagg aaaagtgtgc ctggtagggg ac






#tggggaga 162900













gcttgagaaa gttggaaacg ttgccttaga agcctgtttt ttctcctttt ag






#aagctaca 162960













tagtgtctca ctttccaaga tcattctaca agatgtcagt gcactgaaac at






#gcaggggc 163020













gtgttgagtg ccaaggccat ggaatctgtc agcaacctca cccttccttg tt






#cctccacc 163080













tcattccagg cctaagatcc cgtccatcgc cactgggatg gtgggggccc tc






#ctcttgct 163140













gctggtggtg gccctgggga tcggcctctt catgcgaagg cgccacatcg tt






#cggaagcg 163200













cacgctgcgg aggctgctgc aggagaggga ggtgagtgcc agtcctgggt gg






#gctcagga 163260













gccctcgcac cccgacagga acaagggcca gccccgagaa cgggccatta gc






#agttgtgt 163320













atgttagata cataattgta ttatgatgca gaaagaatct ctgaatgtgc ag






#ttataccc 163380













agttggtgac atgttggtac atccatccga ggaaatggca atgtttctag gc






#tgcaccct 163440













tcaatgtcca caaagctgtg tggcatctgc ttaggacccg gtgcctgtgt gt






#gcatagga 163500













gggaggccag gaagcctggc tgttgatccc atgctggcac tgtggcgaag gc






#gagagatt 163560













cctgctttgg aaaacaccat tgtccacaca gtggctttgt ccatgatgga ct






#tcgccaca 163620













gcccagtcct gtgctggaag ccatgttctc tggaaagagc aacccagcgg ct






#cataagca 163680













taagcgcgtg tgatgtgccc caaccaaacg accgccatgc acaacttccc ta






#ccggagtt 163740













ttcaatccag ttaataggcg tggaaacaga catagaaatt gtgtttgttg aa






#aggtagct 163800













gttcagttaa agaacacctg tatcagagcc tgtgtttcta ccaacttctg tc






#aagctctg 163860













tagagaaggc gtacatttgt ccttccaaat gagctggcaa gtgccgtgtc ct






#ggcaccca 163920













agcccatgcc gtggctgctg gtccccctgc tgggccatgt ctggcactgc tt






#tccagcat 163980













ggtgagggct gaggtgaccc ttgtctctgt gttcttgtcc cccccagctt gt






#ggagcctc 164040













ttacacccag tggagaagct cccaaccaag ctctcttgag gatcttgaag ga






#aactgaat 164100













tcaaaaagat caaagtgctg ggctccggtg cgttcggcac ggtgtataag gt






#aaggtccc 164160













tggcacaggc ctctgggctg ggccgcaggg cctctcatgg tctggtgggg ag






#cccagagt 164220













ccttgcaagc tgtatatttc catcatctac tttactcttt gtttcactga gt






#gtttggga 164280













aactccagtg tttttcccaa gttattgaga ggaaatcttt tataaccaca gt






#aatcagtg 164340













gtcctgtgag accaattcac agaccaaagg catttttatg aaaggggcca tt






#gaccttgc 164400













catggggtgc agcacagggc gggaggaggg ccgcctctca ccgcacggca tc






#agaatgca 164460













gcccagctga aatgggctca tcttcgtttg cttcttctag atcctctttg ca






#tgaaatct 164520













gatttcagtt aggcctagac gcagcatcat taaattctgg atgaaatgat cc






#acacggac 164580













tttataacag gctttacaag cttgagattc ttttatctaa ataatcagtg tg






#attcgtgg 164640













agcccaacag ctgcagggct gcgggggcgt cacagccccc agcaatatca gc






#cttaggtg 164700













cggctccaca gccccagtgt ccctcacctt cggggtgcat cgctggtaac at






#ccacccag 164760













atcactgggc agcatgtggc accatctcac aattgccagt taacgtcttc ct






#tctctctc 164820













tgtcataggg actctggatc ccagaaggtg agaaagttaa aattcccgtc gc






#tatcaagg 164880













aattaagaga agcaacatct ccgaaagcca acaaggaaat cctcgatgtg ag






#tttctgct 164940













ttgctgtgtg ggggtccatg gctctgaacc tcaggcccac cttttctcat gt






#ctggcagc 165000













tgctctgctc tagaccctgc tcatctccac atcctaaatg ttcactttct at






#gtctttcc 165060













ctttctagct ctagtgggta taactccctc cccttagaga cagcactggc ct






#ctcccatg 165120













ctggtatcca ccccaaaagg ctggaaacag gcaattactg gcatctaccc ag






#cactagtt 165180













tcttgacacg catgatgagt gagtgctctt ggtgagcctg gagcatgggt at






#tgtttttg 165240













gtattttttg gatgaagaaa tggaggcata aagaaattgg ctgaccctta ta






#tggctggg 165300













atagggttta agccccttgt tatttctgac tctgaaactt gcattcaatt ca






#ctccacca 165360













agttatctca tctttgaaat ggcttttttt aaaggtgcct agaatatgat gg






#cgtgcagt 165420













ctataaactg ttgcccacct tctgtacttt ctctcagaat aattcacatt ct






#tctccagt 165480













gtctgttgat tgttactttg tggaataagt tcttggaaaa ttccacaaga tt






#attgttat 165540













cttcttacta ccaattctat tgaactttct ccaccttctc tgggccttcc cc






#agccagtg 165600













gtgggaagat gctggctgga gtctgacaga gcctcttcta cactggcctg gg






#cttgctgt 165660













gagttggtgg aaacctttgc tcttgtccca acacagagca agtgaaagag ga






#ggtcaagg 165720













ggctcaggca gcggactagg gaagcagaat cgaggaaaag gaaaaatggc tg






#acttatta 165780













cctcaaaact ctagagaatt tagttgatct tacagccaag aaggacaaaa gc






#cagagagt 165840













aatatcctcc gcctcatgtc taacccacag aatacatagc aagtaaagag aa






#catgggcc 165900













tttataaaaa tgtcttaaga tacaattttt taattggagg aaatctacag tt






#taattttc 165960













tctgggcagc ttttcttcct tttattatag taggggaaat cccatgttga ta






#tacttcta 166020













aatgaaagat gatgaattga tataatacaa taaaaaatct gtaaaattga tg






#atatactt 166080













atcaagaaaa attagctttc attttaacgg tttacaaatt gagtcaagtc ct






#agtaacaa 166140













aatgttaagt ctattaacat aaccacaaga aatacaggaa gacgggcaat ct






#gtgaagcc 166200













tttcacttac aatctctggc ccctcacctg tgctgtgtag gaaaatcttt gt






#gcacaatt 166260













tgcttcctta attcattttt tattcattca acacattcta ataaattata ca






#aaatcatg 166320













ttgaaatgtg aatttcagtg gtatttataa atgcagtgtg aggagggttt gg






#atgtattc 166380













taagacaata gttgtgcttt gggaaggaag cagtgttcac tgaaaagtgc cc






#ccaggacc 166440













ttttaattgg aggaaatatg cttctgtgga gttggaaatg gggtagaaga ta






#gataaggt 166500













caaggcttaa aagttaagtg cacccaacat ctgaagcgtc catgggcctg gc






#atggtggc 166560













tttcgcctgt aatcccagca ctttgggagg ctgaggcagg aggatccctt ga






#gcttagga 166620













gtttgagacc agcctgggca acatactgag acccagtctc tacaaaaaat aa






#aaaattag 166680













ctgggtgtgg tgtctcatgc ctgtagtccc agccactcag gagatgggaa ga






#tggcttga 166740













gtccaggaga tctaggctgc agtgagctaa aatctcacca ctgcactcca gc






#ctgggtga 166800













caaagcaaga ccctgctcaa aaaaatagtt agatataaat attaatatag at






#acctatat 166860













atatctgaat atagatatct atatatactc tgtatatagt tatttagata ta






#taaatata 166920













tatgatatat atttagagag atatatattt agagagatat atatttagag at






#ttatatat 166980













attttatata tatttagaga tatatatctc taaatatata tctctctcta aa






#tatatata 167040













tatctctctc taaatatata tatatcccta aatatattaa ataaataaaa ga






#aataaaag 167100













aaagctcagt ttggcctcct gcttgtcctg tctcctcatc ccctcttccc cc






#tccatcat 167160













tttatttcct tgccccatgt ttcttcactg cggccatgtc ccccctcctc tc






#caatgatg 167220













gatgtcatgt ctgctgcagt cagagggcga caagcctgga gtgttccctg aa






#gcctgtgg 167280













tttgtggttt gtcctgcagc tcaggctgcc caggcctcac cagcaatcct gg






#cgggcagg 167340













gcaccacact gggatggaga gggggaagct ggaggaggca ctttctggta aa






#gaaagcaa 167400













aagccagcag tgcccaggcc aatttcaaca gggagttaaa tagcacctta at






#cctgtggc 167460













aggacagctc atggggccat gtgtgctctt agaaagactc acatgcacgc at






#gcacggca 167520













gcaatgactc catactcacg ttcccctgca gacaccaggc ccccacagcc gg






#cacacaca 167580













ctgcagcccc agttccatgt tgctagcagt ggcttagtga atgagtaaag tt






#cttaaaat 167640













gcaggggaca cctgcccttc attcataagg ctggacgtac acctctcctt aa






#ggagttca 167700













agagctagtg gaatcccaat tcatacggta gagccattca cagatgagag ag






#acaagcca 167760













gaaggaagga accaaaagtc atgtcagcag ttaggacaaa ataacaggct tt






#caaggtca 167820













caaagcctca gggacactcc tgcggtggga ctgggctagg agccatgggg gc






#tccaactg 167880













tgcgctctgc ctgccagcct gtgggtgctg gggctccacg aagattgttg tg






#gaatacca 167940













agcatgcttg ctgtaggtca cggtgcacgt ttactacttc caagacaaac ag






#ccgagaac 168000













aaagctcgct ttagcttctg cgtacaccga acgggacaca cgactgaaca gc






#gttcccat 168060













tgtgcctgct gggtggggag gaagtgatgg cccagtgggt ctatcagatg tt






#agtaggat 168120













ggggcctggc ggggctccag gctctgtgtg gccgacaccc acgccccccg ct






#ctgctccc 168180













cattcccagc cccaggtcag ccctgcgagg ccctgcagca gatgggctgc tc






#aaactgct 168240













ctggtttgca gatttttctt ccctctcaaa tgaatacaat atgttttcaa gt






#ctcaacca 168300













gatcttgaga aaataggaag agccagaggg tttctttggt gttatggttg ta






#cagcttcc 168360













cagactccgg gggagagatg tgatttgtgc tttctggcaa tcccatggcg ta






#ttaaattt 168420













tcataggctt tccagtttaa atttagggta ggcaatggaa gggaacgcaa aa






#cagatttc 168480













taggtgtact gtgtgtgtgt ctcccacgtc taaagtctgt taactggagc ac






#ccaacagg 168540













ccccacaggc tgccttcaca cagaggacct ggggcgcctc cgacccattg gg






#gtgagcag 168600













tgggccatgg agggagccag ggtcaggaga cctggttgtg ggcctgacct ga






#ccctgctc 168660













agggtggcct caggtgggcc gttcacctcg tcagcctcag cttaccctct ga






#ctacagtg 168720













acctcagaca aaatacgctt cctggccctg tccagttctg actttttata aa






#caagcact 168780













tatccaagtt aaagggatat tttcaatatc tactgagtcc acagatatta aa






#tatctcct 168840













ctcttcttta aaattgtggc attatcttta gaatataaaa ggaaaataac ac






#acactctc 168900













cttgaaaata gagagcctaa acactctgca ggaaatattt aaagctatag tt






#tttgtttg 168960













tttgtcttga atgcaagtgg cctggacttt gacttgcttt gagtctttga cc






#ttcatgac 169020













ttcagtacag ttcaaccctg acagttttga agtaggtatg tgcctagatc tg






#ccctagtc 169080













cctgctggaa tgttgaagaa gcaaaggtcc aggccctcag agcacttgcc ac






#gtacttgc 169140













caacagatac ggggcggaga cttgagtcaa cgtaagagca agtgtgtgcc gg






#gtgatccg 169200













acactgcaga gcgccagcta gaccctaagc gtgtgctagg ggctgaccaa gc






#cgttcttt 169260













cctcaaaaac ttggtgggga gggtattttt aaaatcacac aaatatttaa gt






#acagatta 169320













tgatgactgc ctcaaagcag tggctcttca gcttcatcaa gcttcagagt cc






#agagggtt 169380













tgttcatatg gaaggctagg cctgtctcct gcatttcacc ctcttggcct gg






#gggcggga 169440













cccaagaatg tgtggctcta aaaggttccc aggcaatgct gaggctgctt tc






#tgaaggaa 169500













aaactgcaag ataccaggag agtttcattt agattgaaga gtcgaggaag gc






#tcctctga 169560













gaaagagtct gctaaggaag gaggaggtgg gttctgggga cagaggttct cc






#cgtgggta 169620













agggtggagg gaagctctcc tggggagaag gtgggcagga ggaccagagg ct






#ggagggag 169680













gagggcagtc agcctcgggg cttcccagga acagggacgg ccagggcagg gt






#ttagggca 169740













aggaaagcgt gtgagcatat ttgtatttta gtaaatattt acagtttgcc ct






#ccatgtct 169800













gcagtttcat atccatggat tcaatcaacc acaatgaaaa acgttgggga aa






#aaaattgc 169860













atcggtactg aacatatacg gacttttttt cttgtcatta ttccctaaac aa






#tacagcat 169920













aacaattatt cacatagcat ttgcactgta ttaggtacta taggtaatca gg






#agatgctg 169980













tagatgggag gatgtctgta ggttacacac aaatgctgtg ccactttata tc






#aggggctt 170040













gagcatcctc acattttgat atttaaggga ggtcctggaa ccaattcccc ag






#atactgag 170100













ggtccactgt ctgtgtcccc tcgccccacc ttgcctttgt ctcctgtctc ct






#atctccac 170160













cctgcctccc gccagcctgt tgctcctgac ctgcccgggc accctggagc ag






#caccctat 170220













ctcagagcct ggctcagtgt gttcacttct gcagagaaac taacttgccc aa






#gtccacac 170280













tcaaaacata ggcattgctg agatgtgaaa agcagctgtg gatgctttct gc






#tacagtct 170340













gtgtgttctt ttccatatct gaataaaagg tcaccaccat ttgtatttta aa






#gagaaaga 170400













gaatttatgg gtggaaattg gggattccct cattctcagt cagacagaaa ag






#agggcccc 170460













attgtgtgcc tgattgcaaa taaatttagc ttcctcagcc caagaatagc ag






#aagggtta 170520













aaataaagtc tgtatttatg gctctgtcaa aggaaggccc ctgccttggc ag






#ccagccgg 170580













aattagcagg gcagcagatg cctgactcag tgcagcatgg atttcccata gg






#gagcctgg 170640













gggcacagca cagagagacc acttctcttt agaaatgggt cccgggcagc ca






#ggcagcct 170700













ttagtcactg tagattgaat gctctgtcca tttcaaaacc tgggactggt ct






#attgaaag 170760













agcttatcca gctactcttt gcagaggtgc tgtgggcagg gtccccagcc ca






#aatgccca 170820













cccatttccc agagcacagt cagggccaag cctggcctgt ggggaaggga gg






#cctttctc 170880













cctgctggct cggtgctccc cggatgcctt ctccatcgct tgtcctctgc ag






#cacccaca 170940













gccagcgttc ctgatgtgca gggtcagtca ttacccaggg tgttccggac cc






#cacacaga 171000













ttcctacagg ccctcatgat attttaaaac acagcatcct caaccttgag gc






#ggaggtct 171060













tcataacaaa gatactatca gttcccaaac tcagagatca ggtgactccg ac






#tcctcctt 171120













tatccaatgt gctcctcatg gccactgttg cctgggcctc tctgtcatgg gg






#aatcccca 171180













gatgcaccca ggaggggccc tctcccactg catctgtcac ttcacagccc tg






#cgtaaacg 171240













tccctgtgct aggtcttttg caggcacagc ttttcctcca tgagtacgta tt






#ttgaaact 171300













caagatcgca ttcatgcgtc ttcacctgga aggggtccat gtgcccctcc tt






#ctggccac 171360













catgcgaagc cacactgacg tgcctctccc tccctccagg aagcctacgt ga






#tggccagc 171420













gtggacaacc cccacgtgtg ccgcctgctg ggcatctgcc tcacctccac cg






#tgcagctc 171480













atcacgcagc tcatgccctt cggctgcctc ctggactatg tccgggaaca ca






#aagacaat 171540













attggctccc agtacctgct caactggtgt gtgcagatcg caaaggtaat ca






#gggaaggg 171600













agatacgggg aggggagata aggagccagg atcctcacat gcggtctgcg ct






#cctgggat 171660













agcaagagtt tgccatgggg atatgtgtgt gcgtgcatgc agcacacaca ca






#ttccttta 171720













ttttggattc aatcaagttg atcttcttgt gcacaaatca gtgcctgtcc ca






#tctgcatg 171780













tggaaactct catcaatcag ctacctttga agaattttct ctttattgag tg






#ctcagtgt 171840













ggtctgatgt ctctgttctt atttctctgg aattctttgt gaatactgtg gt






#gatttgta 171900













gtggagaagg aatattgctt cccccattca ggacttgata acaaggtaag ca






#agccaggc 171960













caaggccagg aggacccagg tgatagtggt ggagtggagc aggtgccttg ca






#ggaggccc 172020













agtgaggagg tgcaaggagc tgacagaggg cgcagctgct gctgctatgt gg






#ctggggcc 172080













ttggctaagt gtcccccttt ccacaggctc gctccagagc cagggcgggg ct






#gagagagc 172140













agagtggtca ggtagccctg cctgggtgct ggagacaggc acagaacaac aa






#gccaggta 172200













tttcacagct ggtgcggacc cagaaagact tctgcttttg ccccaaaccc ct






#cccatctc 172260













catcccagtc ttgcatcagt tatttgcact caacttgcta agtcctattt tt






#ttctaaca 172320













atgggtatac atttcatccc attgacttta aaggatttgc aggcaggccc tg






#tctctgag 172380













aatacgccgt tgcccgtcat ctctctccga cagcagggca gggggtccag ag






#atgtgcca 172440













gggaccagag ggagggagca gacacccacc cggcctgggc aggtcctcct ca






#ttgcttgc 172500













atccgcctgg ttagcagtgg cagtcagtcc tgccgagtca ttcgtgaggc gc






#tcacccaa 172560













ctccaggcag atgtaaaagg tgacctacaa gaagacaaac aaaaacatct gg






#agcgctct 172620













tatgccagca tctgcccttg acaccaccag gcaggctgtt gctgggagcc gt






#ggtgcttg 172680













ggtaagctcc ttcccatggc agagctcctg ggacgcattg tagaagcagg ga






#ccacctcc 172740













caggataacc agatagcagc acaccctgca cagccccttt tactccagca tc






#atcgggca 172800













ttgatatctc agctgcagcc acaggcggcc cccagcaccc caggaagtgg gg






#agcgctca 172860













tgcttctctg agcacaaaaa tcactgaata tttttgccat tctcatggtc at






#aacccggg 172920













ccacagagta gaacactcct atcactgttg ttagacagtg gtcctgggag ag






#ggtcttgt 172980













gtgcctcgga tgccagggcc tctttttatt gggaggtgct tgttatttct gt






#gtgtggct 173040













gcatttgttt cccaagactg ccacaacaaa tcatcaccaa cttggtagct ca






#acatagca 173100













cagctttatt ccctcctggc tctggaggcc aggtgtctaa aaggccatgc tc






#ccacaatg 173160













gttctgagga ggatccttcc tgcctctctg gcttctggtg gctccagcat cc






#ctgggctg 173220













tggctgcacc tccccatgtc aacctccgtc ttcacaaggc cttttcctgt gt






#ctctgcaa 173280













ccacaggccc ctctcctttc tcttaataaa gataccagtc attgagtttg aa






#aattgcta 173340













agagagtctg ttgtaaatct tcttagcaca aaaaaaaatg acagatatgt ga






#agtggtag 173400













atatattaat tagtttgatt tgatcactcc gctatgtgta taaatgtcaa aa






#caaacatt 173460













gcactccata aatatatata ttaaaaaaga tcccagtcat tgcatttagg ac






#ccacccta 173520













aatccaggat gatttcattt caagactttt aactagattt gcaaaacccc at






#ttccaaat 173580













aaggtcacat tctgcagttt tgggtagacg tgaaatgtgg agacactgtg ca






#acccactg 173640













tcttggggag ggggtggtca gcctggggca gatgttgctg ggtgtggagc ta






#catccact 173700













catgccctga cctggaaccc agacctgctt ccccagctct cctcctggtt at






#ctgaagca 173760













gggaatggag agcactgccc tccttgccca ggcagtctct atcacctggt tt






#tagtttct 173820













tcttagcaca tattgcccca gaatatctgg ttggtttatg gcttacttga gt






#ttgtgcct 173880













acctgtccca accgggaggt gagccctggc tattccccaa acccggccct gc






#atgtggga 173940













gctgcccttc ctccgttcat cagagggggc caacagtcca cagctgttct ta






#atcatctc 174000













ccagtaaccc ccagctccac aaaggtgact ccttacatgg tggagaggtg gt






#cgggccat 174060













ccgtgtgaaa tgtgtatgtg accgttttcc ttaaggggca cgtagtcttg gc






#aggtttcg 174120













ctcaatatag gatgagctca ggactccagt ggactgtgga ttcagatctg ga






#ttctggcg 174180













cattcgccgt gtgaacgggg gcacgttgct ggcctgtctg cgcctcgtct cc






#cgactgtg 174240













gagtgtgttc tgccccttgt ctttctggga ggtagggagg gcagtgagcc cc






#ttcgcatc 174300













gcccaccaca ggcccagcac atggctgatc cccactgagt gttcttttcc tc






#ctttgatc 174360













ccctttggct gacctaggtt ggagcagcca ctaaaatata cccagaaaca tc






#ttcctaat 174420













ctacatctgt gccaaccctc attccctggc gcagcatgac catcacatgc cc






#gccattgt 174480













tcctgatctc tgctgctcat gacctgctct ccagcgctcc ttctcatgct ca






#cattccag 174540













ttggcctgac ctagataagt ggaggtttat ttgaccccaa aaattagcct tc






#tacaaacg 174600













aatataatag tgtccattac agagaataaa cttagtgcgt gtcccattta ag






#cagaagtt 174660













actgaaagcc tgagtttaag tttccagggc ctgaaagttt tccatgacag tt






#ttctgcat 174720













aatattacct acaatttcaa tctgttattt aaagccattc ttgtgtttgt tg






#tactttga 174780













ttagctttat tttgatttga agtcctttta cattacgggc agttaacgct tt






#gtctctgt 174840













tagatttgct ttttagttca caagagaaac ctcattcctc tgtatttgaa ta






#gttgcaat 174900













gatggaacag ctgtccctgg agggaaatga aaacagtgat tccccaaatt gt






#gacaatag 174960













aaatttgctc ttgggttact tacaatgtat ctgagtatta aaaaattttc tt






#tttaaacg 175020













tttgaagtaa aactacccag aaacacttag tggctgacca gaaactaaac tc






#ctggcatc 175080













ctcaaaatgg gatttattgg cttataaatg tcctgtgttg actcacaaag gc






#acaaacta 175140













tctaggtaag ttttcttcta aatgttgatg ggagagctgg ccactgttat gc






#aagtttca 175200













ttgtcctgac taaactgcca aagagattac ataaaattat atcaactaga ca






#aaaggaaa 175260













aaggaaaaaa aacagaggtg tcttgggagg aatccatatg agaccagtag ac






#catgagag 175320













agacatccct tgccatctac aaggaaaatg gattttgttc tccatatgca aa






#accatctc 175380













aggagcttgc ggagacacca cttgcttact agccagaaag agcaggtgcc tc






#ctaaattc 175440













cccacacagg agctcacagt ggctttcatg cactgggatt aagttagact ta






#agaaagcc 175500













tgtctactct tcctgggatt tacaagccag ctagtaaatc ccagaataaa tc






#acacggca 175560













cagtcatcca aagatcccgt catccgtgcc gtttggaaag ccctgctcct gt






#gccaccct 175620













ctccccgtgg agcctcccat gcccaggact gcagagtcct gccattcaga ct






#gcaactca 175680













tctcacattc ttccaaacta tttggacaac agagctttct catcacctaa tg






#cagattac 175740













agtctcacag aattgagtgt tcaggcagac actgatgtgg ttctgtagta ca






#gcaaacaa 175800













tatcagttta cagtcctgag gccaggcctg gtgaacaacg cacggtagcg gt






#ggggcagg 175860













gttctcagaa tgaaactggc ttacacatgg cactctctga ccacaactgt at






#aagcacca 175920













aactacactt agttccatct atgaggtaaa atttaatgca gatgaacatc aa






#agaaaacg 175980













tcaaaggctc ctttttacaa gtacgtgggc tacttaattt ggtccaagtc ca






#ttttaaaa 176040













agccctaggt gctttcacgg ctctgctact gacaagaagc cccagtgcct gt






#gagctgct 176100













aatgggaggg agaggaagat gagctgagtg ggccgggcta tcccgtccac ac






#cgggagac 176160













agggaaggag actccaagct ggtggtgcca gcacattcca ggccactcag gc






#ctattcct 176220













aggtgccagg tcacgaaaac cacgctgaca gatcgtgctg tgtgcgtgtc at






#agcacaca 176280













agcaggactg tgagagagtg aaagtgacac tgggtggagc actgaggaag gg






#ccacagtg 176340













tgttggtgga gataggctgt catggagaag agaccctggc ttgctctaca tt






#gcttccaa 176400













tgcaactgca aggcaggtcc cagagggctc cggccttcgt catccaggtt tg






#ctccctcc 176460













cctcatggct ttcccatcct cagatgagga ctcggcagag cctacccctg ct






#gactaact 176520













gtggccccag ggtggtgact cagccctgca cctcctgatc ccgtctgcac tg






#ggccagag 176580













aggatgactt acccagcacg ttcacatcac acagctttgt ggattcctag gt






#ccaaggac 176640













cagagatttc agttatgtga gttatttttt ttatttgttc ttgcgtattc ca






#caaagggt 176700













cgcagctaaa cttaacctaa tgatcacttt agtatatcac taaaaagaca aa






#gctcacag 176760













tgctgttgaa gcacattcat catctttaga cattttgact agttatttct ta






#agcattta 176820













cctgctagtg ttaagcatca catgaaatac atatagaagt aagacaaaat tt






#cttatctc 176880













cccaagtttg ccaacaaata cagagcagga agggaagcag gtcagagcag ga






#ggcgcagc 176940













tatagtgagg ccaccatgca aggcacaggg agggtgagct ccaagtttga at






#ggaatggg 177000













tctgtcagcc aagccccctg gctctgggaa gatagcagtg aacaagccag at






#ggcccctc 177060













accctccaga gccgtgagtc ctgcagacca aacagcgtga caggtccttt cc






#ctgtccag 177120













gaggcctctg tgggtgagag ttggctgcgg acagggcgtg aaggcacttg ag






#ggtgggga 177180













agtgactctg actgggagat gctgaggaca gggaggaaac caccagataa gg






#gacactgg 177240













ggaggagggg tggacccctc agggccaagc acatggagcc tcatcacaaa gg






#caagatgg 177300













tggccaaatt caaggtcgct gcaaaaggaa tggagaagag agaatagatt tg






#gcatttgg 177360













aggaaatggt gacaatcatg agcacctacc cgggactctc catgggtgct at






#ctctacat 177420













aaactcattc caccctctga ttaatccatt ctacatatgg ggaaacaaag gc






#atgcggtg 177480













tttacgtcac ttgccaagat ctcaggattt gatccaggtg gcctggttcc at






#ggtgcagc 177540













ctctcagcct gcatggatgc cccagctcag agcatgactc tcaggacagg gg






#tcccagca 177600













gccctccctc cctgagcagc agggtgcccg tgctgcacca cttctgtcta gg






#aataggac 177660













attctgacac tttcctgcct cttccgaggt ctagcactta ctctatgcct gc






#ctgggaag 177720













gtggcaagct ggcctgagga acagactctt ccatttttta gggagctcaa gg






#ccacagat 177780













gctctgagat ctggagtcca gagacaggag cggaggcttc tcctggtgac ca






#ctctgctt 177840













aaaaacttca tcagatccgt agtttcagag cccccctgaa ccccatccct ta






#cctctacc 177900













agttgcaggt gggtctctgg ggtggggctg ccctccccac cagcacccca ag






#ggctaaaa 177960













ggttgagggg agaacaccat catttgtaca gggggatcct ggaagatgag gc






#ctgagaaa 178020













gccctgcggg gcccctcacc ttctccctag ctgtggccaa gagtgtctgg cc






#ttgcctgc 178080













ctcaggacca gcccaaagtg gaggtgagag gtgagcccca gcccccaggg ga






#agggtgat 178140













ggtggtcttg gtctcagcat ggttctggta gaggtgggtt attttgaaga tg






#atgaacct 178200













taagcctctt tctgatcttg ctttaaataa atacttctga acaacagcaa ca






#acagaata 178260













gtgttgatag gaaagccctc cactccacca gaaccacgcg gccttctcgt cc






#tcccctcc 178320













tccacttcct tcctaagtca ctgctccatg agctcttcca caggagattt ac






#aaaacaga 178380













acacaaacaa tccagttcct gcctctcact ctgaactcct cccaagactc gt






#ggggtgcg 178440













gcagcccctg ggaacaccca gcccttcaag gtcaaacaca gcccccgccc ct






#cactctgg 178500













ggtaccctgc cagaataagc cccgacagcc atgtggagca gagccttctt tt






#ttgtaagt 178560













ggaagttcca ggctggcttt tcaaatcccc ttttaacctc agtgctgtat tt






#caaaattc 178620













attccagttt tcctgtagta attaacaaaa ataaatattt taatttcaat ta






#aagtgagg 178680













gtctcggaga agaagcagga actgagtttc ctgagaggcc ccgctgaggc tt






#tgttgata 178740













tttcttcctg cgacctctgc tcggaccctg ggagctcaca ggccgtatcg ca






#gctcttat 178800













ctttggggac cagttaaagc ataactgcgc caggcacaga gttgtccttt ca






#aatgtgcc 178860













ggcagtggga cggagaccca tgcgtcaagt ctcctctaag ttcacatggg at






#tctctcct 178920













tgtcccaaag ctgtctctga cttaaaaccc tccaactgat tacctgaatt cc






#agaatatg 178980













tcctgtgctc tctgcccttt cccacgcctt tggtgaagac cggtgttctg ag






#gaaacaga 179040













cactgtgtag aaatggctca ggtcctttaa agccctggtg tgaggagtgg gg






#aagggctg 179100













ggccagaggt cagctggatt tgttagattg acagagtgac gcggacttcc cc






#agaggcac 179160













gggaccaagg tgcatgctca cgctgtctca tgctctcaca cataatgtgt gt






#gtgtgtgt 179220













gtatatatat atacacatat acatatatat atatacacac atatgcatat at






#ataaaacc 179280













ccaagcagcc tctggcttag caggtgcatt tcccagcagg gcaattaaag cc






#atggtccc 179340













agtagtggtc ttggggtctc agggtatttg gtctgtgcag ccacatgctt ca






#gtctctgg 179400













accccaggtc atctaacgag gtggtcgtgt ggggactggg atagaaaagg tg






#tctgcacg 179460













gacgtgtgtg aaagggctgg cacatcgcca gtgctcagca ctgtcagctg ct






#atcaccag 179520













tcattcaatc attcattcat tcattcagtt gttcattctt caacaggccg tt






#ttaaaaat 179580













gtgcccagta taccaaaatc tccgctaagc atttaaagag gcagaatgaa ag






#ttagcagt 179640













ggtggtgaaa cgaagctggg aatgtgctct gagggcctcc ttgtgggctt aa






#tgaatatg 179700













tagaaaccac gcattttaaa tagagaggga gaaagggaga ggttcctggt cc






#tctgcatg 179760













gggacttgtg tgtggctctt tactgtaggc ctgtgccact cctgctcaac ag






#ctaccaca 179820













gaggacgcct tcaacaaatg tgaagaacga acaaaaggta caaatgtgaa ga






#acgaacag 179880













ggtagaaaga aaggagaaag caagggtgag ggtgagaaat caagggacag ag






#aagagaga 179940













agaggagata gcctgggagt tcacacagcc aagaaggtag acactcagtt ga






#accagcaa 180000













gaggctgagc ctaactctcc ctttcgaatg ggcaggagtt catgatattt aa






#taaacaga 180060













ggccttgctc tgtaagagac agggtaccag gcagagagca agtcagcatc gc






#aggagtca 180120













aacgaggcag acagcggggg cagggagctt gcctctgaag gagacccagg ct






#gccagagt 180180













agcagggagt ctgggccagt cctcttttgg gaagcgcttc ctcggcttct gc






#cccccctc 180240













tcctctccct ttccacccac catcctgaca taatacttcc taatctggaa gt






#gttgtcca 180300













gagaagaacc tgctcatttc ctcttaagta ggcagggaag cactaacgtc ca






#gcagcatc 180360













ggaaacccgt aggagcgctc tcggcagtgc agggtgaggg gacagtccat gt






#agtcatga 180420













gacgtgggtg tcaggcaagc gtctcttttc caaaagagaa aaacattaaa gg






#cctcacaa 180480













acggcgccca aagactaatt ctgcatagca tctttgcgag accctaggtt ct






#tatgatga 180540













ctggttttgc ctgagaaaga aaaaatttta attttgcttt gacatgccaa tt






#caacaaat 180600













cattttcaca taatattcat gcaaaaaaaa aacaatttgc cagaaaactt gg






#gaatccat 180660













ccacatctac agcttttccc tgcagtcaca ctacagtggg atccctccat ac






#aggagcgg 180720













cagagtggag caggctagag atgcctgttt gtttctgttt gctgcaccgc ag






#caagcatt 180780













tctgtcgtgc ccactctgta ctagaaagta catgaacatc agccataaag gg






#aactagaa 180840













aggtggccca ccctcttggt ggagagagaa gagagtgtgg tagaaacaat aa






#taagaagt 180900













ctgcagaact tgacccctcc cagcctctcc cacctgccag cctggccctt gc






#agagagat 180960













gcaggctgcc attcttaggc caaagcctgg gacagttggg ctcagcaagg ta






#ggcatccg 181020













tcaagcaagg aggagcaggg gtcagcagtg accccagcag ccagcaggga ga






#aaggtgca 181080













tgtgacaagg acaccagagg ccgtgggtca ggatcagcca gggtcagggt ag






#catttcta 181140













ggaattcact ctgttgggcg ctgtgctggc tgcttctcac atattattcc tt






#tcttactc 181200













tcagagcaga gatttcaatt gcagcgagat tgtggaggca gccagggagg tg






#gggagggt 181260













ggtgtcttct aaaagcattt tcagtatcca tgtggtttca gtaataataa ta






#ataataaa 181320













ccagtgaaaa gtaaaacagg acaaaaatct tcataggcag tgaaccatat ca






#gagagtcc 181380













aagaaagcac aatgagagtg tggcttaaaa accctgaacg acattccttt gc






#accagctt 181440













ggtgaggagg gcatggtccc cgccaccccc cacccccact ttgcagataa ac






#cacatgca 181500













ggaaggtcag cctggcaagt ccagtaagtt caagcccagg tctcaactgg gc






#agcagagc 181560













tcctgctctt ctttgtcctc atatacgagc acctctggac ttaaaacttg ag






#gaactgga 181620













tggagaaaag ttaatggtca gcagcgggtt acatcttctt tcatgcgcct tt






#ccattctt 181680













tggatcagta gtcactaacg ttcgccagcc ataagtcctc gacgtggaga gg






#ctcagagc 181740













ctggcatgaa catgaccctg aattcggatg cagagcttct tcccatgatg at






#ctgtccct 181800













cacagcaggg tcttctctgt ttcagggcat gaactacttg gaggaccgtc gc






#ttggtgca 181860













ccgcgacctg gcagccagga acgtactggt gaaaacaccg cagcatgtca ag






#atcacaga 181920













ttttgggctg gccaaactgc tgggtgcgga agagaaagaa taccatgcag aa






#ggaggcaa 181980













agtaaggagg tggctttagg tcagccagca ttttcctgac accagggacc ag






#gctgcctt 182040













cccactagct gtattgttta acacatgcag gggaggatgc tctccagaca tt






#ctgggtga 182100













gctcgcagca gctgctgctg gcagctgggt ccagccaggg tctcctggta gt






#gtgagcca 182160













gagctgcttt gggaacagta cttgctggga cagtgaatga ggatgttatc cc






#caggtgat 182220













cattagcaaa tgttaggttt cagtctctcc ctgcaggata tataagtccc ct






#tcaatagc 182280













gcaattggga aaggtcacag ctgccttggt ggtccactgc tgtcaaggac ac






#ctaaggaa 182340













caggaaaggc cccatgcgga cccgagctcc cagggctgtc tgtggctcgt gg






#ctgggaca 182400













ggcagcaatg gagtccttct ctcccttcac tggctcggtt tctcttaggg ac






#cctcacag 182460













cactaagggg tgcgcgtccc ctgtcaggcc ctcgaatgcc ctcccacagc ca






#ggcccctc 182520













tgaggtttca ctctggcctg ctgggctcct agcagccacc aacccatgat gc






#tgggccct 182580













gaaaacacac gcagacctgg atgagtgagg ccactgggca caaccagggc tc






#ccagctca 182640













ccagagcagc ctgggacaca gagggtgctc agaaacctac cagagcagcc ct






#gaactccg 182700













tcagactgaa atcccctgtt gccgggagga ggcgccgggc ctgggggacg gg






#tcctgggg 182760













tgatctggct cgtctgtgtg tgtcactcgt aattaggtcc agagtgagtt aa






#ctttttcc 182820













aacagaggga aactaatagt tgtctcactg cctcatctct caccatccca ag






#gtgcctat 182880













caagtggatg gcattggaat caattttaca cagaatctat acccaccaga gt






#gatgtctg 182940













gagctacggt gagtcataat cctgatgcta atgagtttgt actgaggcca ag






#ctggcttt 183000













tattgttagt taatttacat tatatcctct gacatgcaag tattttcttt cg






#agataatg 183060













actaatgata atgtaatcat tgctgtctat ctattgtact gagaaaacac gg






#cagaggaa 183120













atcgagtcca gctgccgtcc aaaagtcact ggagattgca atgagctcgt ct






#ggcagggt 183180













ggggggtatg ggagggaaag agcttaggaa acggctctcc ctgcaaagtc ca






#accaaact 183240













ttaacgttaa ccaaaccatt aatgttgcca tgaatttgaa gtgaaccaga gg






#gaggtggc 183300













agaagaagct taatggggaa tagttccggt agagaaatga ggcttaagat ga






#actaccct 183360













ggcccttatg tgtcagagag aacggcttga caaacacaca ctgaggatgt ct






#gcagggat 183420













aaaagaagaa agggagatga cccttgcttc tcgctctcgg gaggaccatc tg






#gtccggcc 183480













ctggggattc tctgtttcct cttctgaatc ccagtgttgc ccagcactgg cc






#tgtaccca 183540













tcctcacgag ggccgctctc ctcacccggc cctaggtccc tgccctgtcc tg






#agcctaca 183600













ggggcctccc atgttgagaa agtgttgctg acacattgtc tctgaccgct gt






#gccaggca 183660













ttttctgctg aattaccgca cttggtcctt gaatttcacc cagcaactta ct






#gaaaggct 183720













ggaacccatg aacctacccc ttcactgagg aaaatcagtt accccagcca tc






#tacagcga 183780













caggagcaag ggaggagtcg cctcacctct ctagaaatgt gtatttgagg ag






#aacactat 183840













tgaaatgaat ttccaagaat aatctagtca gtattacaaa agcaaaatta tt






#tgggatat 183900













cgtccttttt tacttagtat tttttctttt tcctatagca ttattaactt tc






#tgattttc 183960













caaatacata cacattttta aatttcctga gtctttatct cttctgttaa aa






#tgtaagat 184020













ttatgataca aaggcagaga tttgtgtcca tgaataagtg aagtttggtg tg






#cacctgtg 184080













agctgagcca cctcaattaa tggaacagat aaggaaataa aggtctgctg at






#gcattgtt 184140













atttacagcc attttcagaa tgtatctcct ctccacgagg gaactgcagg gt






#cctgcccc 184200













aagccattta ttttgtcctc aagcagcccg cccctcccac tccaggcaca gc






#ccggtctc 184260













ctgctggtct cccctcttcc cacttgctcc ccctcatcta tgctccagac ag






#aggccaca 184320













tatatttttt aacttttttt tttttttttt tgagacagag tcttgccctg tc






#acccaggc 184380













tggagtgcag tggtgcagtc tcggctcact gcaacctcca cctcccgggt tc






#aagtgatt 184440













ctcctgcctc agcctcctga gtagctggga ttacaggcgc acaccaccat gc






#ccagctaa 184500













ttttttgtat ctctagttga gacagggttt cactatgttg gccaggctgg tc






#tcgaactc 184560













ctgacctcat gatctgcccg cctcggcctc ccaaagtgca tattttttaa ct






#ttatcaga 184620













cttttcattc tctgctcaac atctttcttt ggtcctccag gtatgttcag at






#aaaacctg 184680













agcacctggc catgactgat gggttgctgg gccatctggc cctggcaact ct






#cccgtcca 184740













ccaggtcccc ctcccgtcac gctccaggca tagcctgtgt gtgccagcgc aa






#tgcccaca 184800













ctccatgcac aagtggaagc cctctcaaag tcagtggctt agtgccttga tg






#tggtcaca 184860













cccattctca ggaagtccgt tcccactgaa aacattgtgt gttttcaaca tc






#attgaggc 184920













tgccacggca gattataatc actggcctag gcagcccact ggaactacca ga






#ccatgagc 184980













ctgaattttt tgtttaaaaa tcatatcctg ttttctctac tctctagtct ct






#agtcaagg 185040













tgaattattc aatttaataa attaggggcc tagtgtgttg taccaaggag ct






#aaaaagag 185100













agaactcgca acaccttcca gcccattctc cacctaacac tggctatact gg






#ctctcctc 185160













tctctcgctg tttgttccaa aatctaataa cctgtcttcc cactagaatt ca






#tcatacat 185220













gtttaaaaac ctagttaaat agtagttaaa ctgactgcat agatctggaa at






#gagacagt 185280













ctttctttta caaatccata tagactatga gttgggggca ggggatgaca ca






#agaatcta 185340













ttttcttgcc cccaaaccat tgctttcctt ccaatgttaa gcttgtattc tg






#tgtattaa 185400













ttcaggtggt tccgtttggg aatggcctct gttacccaga gatgggaggg cc






#atcagaac 185460













tcggggttgt ctgaaaaaac actggttcta aaattatcac tgctttcact tg






#tttttaac 185520













catcatagtt gtttgatttt gaaggaaaaa catgagggtt tttattctat gc






#ttgttata 185580













tctatattgt ggtttcgtat tttttagatt ttagtacctg acattttttt aa






#cttttatt 185640













ttaggttcag gggtacatgt gcaggtttgt tatataggta aatttgtgtc at






#gggggttt 185700













gttacacaga ttattttatc acccagggat taagcctagt acccattagt ta






#tttttcct 185760













gatcctctcc ctcctcccat cctccaccgt cctatagacc ccagtgtgtg tt






#gttcccct 185820













ctaagtgtcc atgtgttctc atcatttagc tcccacttat aagtaagaac at






#gcggtatt 185880













tgattttctg ttcctgcatt agtttgctag ggatgatggc ctctagctcc at






#ccatgttc 185940













ttgcaaagta catgatctca ttctcttttg tggctgccta gtgttccatg gt






#gtatatgt 186000













accacatttt ctttatccag tctgtcattg atgggcattt aggttgattc ca






#tgtctttg 186060













ctattgtaaa tagtgctgca gtgaaaatac gcatgcatat gtctttatgg ta






#gaatgatt 186120













tatattcctt tgagtaatgg gattgccggg tcaaatggta gttctgtttt ta






#gctatctg 186180













agaaattgcc acactctttt ccacaataat tgaactaatt tacattccca cc






#aacagtgt 186240













aaaagcattc ctttttctcc acaacctcac cagcatgtgt tgggattttt tt






#tttttttt 186300













acttttcaat aatagccatc tgactggtat gagatggtat ctcagtgtgg tt






#ttgatttt 186360













tatttcttta atgatcagtg atgttaagct ctttttcata tacttgttgg ct






#gcatgtat 186420













gtcttcttct aaaaagtgtc tgctcatgtc ctttgcccac tttttaatgg ga






#ttgtttaa 186480













ttttttcttg tgaatttact taagttcctt atagatgctg gttattagac cc






#ttctcaga 186540













tttgtagctt gcaaaaatgt tcacccattc tgtgggttgt cttcactctg at






#gatagttt 186600













cttttgctgt gcagaagatc ttcagtttag ttagatccca tttgtcaatt tt






#tgcttttg 186660













ttgcaattgc ttgatgtgtt ttcatcatga aatcttagcc cattcctata tc






#cagaatgg 186720













tattacctag gttgtcttcc agggttttta tagtttgggg ttttacattt aa






#gtctttaa 186780













tccatgttga gtttattttt gtgtatggtg taaggaagga gtccagtttc aa






#tcttcttc 186840













atggctagct agtcatcatt tattgagtag ggagtccttt attcattgct tt






#tttttttt 186900













tgtcaacttt gtcaacgatc acatggttgt aggtgtgcag ccttatttct gg






#gctctcta 186960













ttctgtttca ttggtctgta tgtctgtttc tgtactagta ccatgctgtt tt






#ggttactg 187020













tatccctgta gtttaaagtc aggtagcatc atgcttccag ctttgttctt tt






#tgcttagg 187080













attgccttgg caattcaggc tcttttttgg ttccatgtga atttttaaat tg






#tattttct 187140













agttctgtga agaatctcat tggtagtgtg ataggagtaa cattgaatct at






#aaaatact 187200













ttgggcagta tagtcatttt aatgatattg attctttcta tccatgagca tg






#gaatgttt 187260













ttccatttgt ttgtgtcatc tctgatttct ttaagcagtg ttttgtggtt ct






#tattgtag 187320













agatctttca ctttcctggt ttactgtatt tctaggtatt ttattctttt tg






#tggcaatt 187380













gtgaattgaa ttgcattcct gatttggttc tcagcttgac tgttgttggc at






#attggaat 187440













gctaattatt tttgtacatt gattttgtac aactgagtct tcactgaagt tg






#tttatcag 187500













cttaaggggt tttgggcaag actatggggt tttctagata taggatcatg tc






#atctgcaa 187560













acagagatag ctgttttcct ctcttcctgt ttggatgtcc attatttctt tc






#tctcacct 187620













gatttatctg gccaggactt ccaatactat gttaaatagg agtgttgaga ga






#gggaatcc 187680













ttgtcttgtg tcaattttca aggggaatgt tttcaacttt tgcccattca at






#atgatgtt 187740













ggctgtgggt ttgccataga tggctattat gttgaggttt gttctttaaa ta






#cctagttt 187800













attgagaatt ttaaacatgt tgaattttat tgagagcctt ttctgcatct at






#tgagatga 187860













tcatgtggct tttgtcctta gttctgtttg tgtggtgaat cacatttatt ga






#tttgcata 187920













tgttgaacca atcttgcatc ccagggatga agccgacttg attgtggtgg ct






#taagcttt 187980













ttgatgtgct gctggattcg atttgccagt attttgttga ggatttttat gt






#ctatgttc 188040













atcagagata ttggcctgaa gttttctttt tttgtggatc tctgccaagc tt






#tggtatca 188100













ggatgacatt ggcctcatag aatgagttaa ggaagagtcc ctccttctca at






#ttttttgg 188160













aatagtttca gtaggaatgg taccagcttt ttttgtacat cttgtagaat tt






#ggctatga 188220













atccatctag tcttaggctt tgttttggtt ggtaggctat ttattactga tt






#caattttg 188280













gagctcatta ttggtctgtt cagggattca gtttcttcct gaggttttta tt






#tttatcaa 188340













atggaactta acctttttca tttccaattt ttttatgatc taaaaatgtg ca






#gtttacag 188400













ccctgttcag aatctgcatc ttcctcattc tgcagataca ggtccctcag ag






#caggtgac 188460













tgagtgtgta tcctgtctgg agcataatac ttatgctagt agagttactg tt






#gtctttat 188520













tgttaattac caaagtttac cacttatcag tcacttacta cttgctgggc at






#tgcactaa 188580













gcatttcagt tgtattatct tgttgggtcc ttacagcaat cctgtgaaac ag






#atactgct 188640













attaccccac tttatagaga ggtagactga ggcttccagc attgaagcaa at






#tgcccaag 188700













actacagaaa tgtaggtttc taaacatcaa gaaacagtaa ccagtaatga tg






#actaaagc 188760













aagggattgt gattgttcat tcatgatccc actgccttct tttcttgctt ca






#tcctctca 188820













ggggtgaccg tttgggagtt gatgaccttt ggatccaagc catatgacgg aa






#tccctgcc 188880













agcgagatct cctccatcct ggagaaagga gaacgcctcc ctcagccacc ca






#tatgtacc 188940













atcgatgtct acatgatcat ggtcaagtgt gagtgactgg tgggtctgtc ca






#cactgcct 189000













agctgagcct tggtggctgc tcttagccaa acagctgagg cctttgcatc cc






#tggagaaa 189060













tgtcatcaca ttacttaagg caggcacaca aatccagaaa catctgtaaa ta






#ccccttca 189120













agcattcttt taaagacact tcttgactca ttgggcagta tgacctgaca tt






#tgcccatg 189180













tttgcaagca aataaataaa actaaagtct tccgcaagcc attacaccaa aa






#tattctat 189240













tcgctgagtt actcaatgaa ataccgagtt gccctatatt ttgaagcctg tt






#accagaga 189300













gactgaatgt ttttaaatgc atggcagtga gtaacaacat aaggctaata ga






#gtcaacat 189360













ttctgctttg acttaaacct tttaaaccag tggatttatg tgaagtctct gc






#agtgtggc 189420













atttaaacat ttcaatctaa ataagagtgt gtaatttgat tgatgctatt at






#tctaccag 189480













attcacgagt gcagtgggct ctggaggtag cattacatgc atgggatgag ca






#tttgcaaa 189540













agaaagttgt atagggaata tgacagagcc aagttaatgt aaatattaat gc






#ctttctga 189600













actctaggcc acagagttga tcttttttaa cttccttggt ttgggctaag ga






#agctgtga 189660













tccagagaag ccacgtgatt tgtctaaggt cacatagcag tctggcctaa aa






#tagcttga 189720













tatgctgtgg atggaaaata aatgtgatcc ctcaagaggc atgaggattt cc






#aggcagta 189780













gccatacctc caaattgttt aatctggatt tagattgttg ggtagtcaca tg






#cagcagca 189840













cagttaacag tgtgtcctcc tgtggaagtg gccagcacag ccagccctct ca






#cttgcatg 189900













catgcccacc agccttctca cttgcatgca tgcccactgg gtatgtgctg ta






#ctggagac 189960













gccgggggta ggggcccagt cccaacccca aattctttaa agcctatttt tc






#taagttgc 190020













atctggtttc ctacctgaag gaatgctaag ggtggatgtt gagtgaggac ct






#tggtgcag 190080













ggcaccctgc agtcaggata gttcatggag agcaattgta cagacccaca ct






#gctccatc 190140













ccctcaggcg taacacagga tgctgacccc aggaagagtg ggcgtagaaa aa






#ctagaggg 190200













cattattgtt attctgattc aaatgtacag tgctggcatg gtctttaaac ag






#taaccagt 190260













actagctggc caagacagaa aagtctacca caaagacttg gttctttcat ca






#cttatttg 190320













actggaagtg tcgcatcacc aatgccttct ttaagcaatg ccatctttat ca






#tttcttcc 190380













agtgttctaa ttgcactgtt ttttctcatt ccttccccag gctggatgat ag






#acgcagat 190440













agtcgcccaa agttccgtga gttgatcatc gaattctcca aaatggcccg ag






#acccccag 190500













cgctaccttg tcattcaggt acaaattgca gtctgcgctt ccattgggaa ga






#gtccctct 190560













aatgagcatc tcatgtcact gtgttctgtc acatgccagc ctggcctccc tg






#tgtcccag 190620













atcgcattat taaaccctcc agcgcattag agcaagcctc agtaaggcgc ag






#gccacatc 190680













gtgaactaag cagcatccgt gagtggggcc cacccaactc catctccccc tc






#cccgtctg 190740













aactctcctc tggtgctcgt cctcactgtc cggctagcca aagcctcagc tg






#ggtctaag 190800













agagaagcat ggtctattgg gctttggtgt caggcagacg tggcttcaca cc






#cctgactc 190860













tccacttctt cgcatcaccc aggcagccga tccacctatc tccttccata ac






#acaggaat 190920













accaaaacca agctcacagg attgtctcaa agattcaata aaatatgttg ca






#aaatacgc 190980













tccctaacac ctcacagcaa ggtgcacaaa tcgatgaatg ctgcagcttc tt






#ccctttct 191040













gtttcctcag aagctatttg aatctcatgt aggggctttc aagcatcaaa gg






#atggttca 191100













tgttttattt taaggcaccc acatcatgtc atgaggggag gcagctataa tt






#tagagaac 191160













caagggggat ttcattataa caaaattggc aaacacacag gcacctgctg gc






#aatagacc 191220













cctgctccta tagccaagaa gtggaatagc atctctacgg gccattctaa ta






#gcctcaaa 191280













atctctgcac cagggggatg aaagaatgca tttgccaagt cctacagact cc






#aacttcta 191340













ccgtgccctg atggatgaag aagacatgga cgacgtggtg gatgccgacg ag






#tacctcat 191400













cccacagcag ggcttcttca gcagcccctc cacgtcacgg actcccctcc tg






#agctctct 191460













ggtatgaaat ctctgtctct ctctctctca agctgtgtct actcatttga ac






#aaattgaa 191520













ttttagggaa aataaccatc tagtgaaact cacatggaaa tgaagtcaat tt






#taaccaaa 191580













tggtaaaatc aaaatcaaaa taaattaagt gtattaatta ttttgttgca tt






#gcaacaac 191640













ttgattgtaa gccttttagg tccactatgg aatgtaatta aatcaaaact aa






#acctagtt 191700













gctctaaaac taacgattaa gacaaaaatt aaacaccttc acaatatacc ct






#ccatgagg 191760













cacaccacct gcattcagga aaagtggatg agatgtggta caagcattcc at






#gggcaatt 191820













ctctgtttct ttttccagag tgcaaccagc aacaattcca ccgtggcttg ca






#ttgataga 191880













aatggggtat gtatgaacac cttataagcc agaatttaca gctctccact at






#ggctctat 191940













tttacatgga aaatgcctta acctaaataa ttttaaccca gataatcttg ag






#ttttcttc 192000













ctgtgtgggt ttttccctgc acggctgtca cgcctcacag tgccgttcaa ag






#cgtgactc 192060













ctggaccagt agtagcatcg cctggccttg ttagaaacgc catttttcag gc






#cactgccc 192120













cagtttgacc aaatcaggac ctctgggggt ggcacccagt agtctatgtt tg






#agccactt 192180













tccaggtgat gctgatgtct gttgaagtgt gaggccgtgg tctagaccgc ac






#tgtgccat 192240













gcagaaacca ctagccacat gtggctactt caacttaaat gttaatgagt ta






#aaatgaaa 192300













taaaatataa aattcagttt ctcacacatg tgaagtgtcc agtagccaca cg






#tggctagt 192360













ggtgaccgta ttgaagagca ccgctcatag cacacctccc tcactgcgga aa






#gttctgct 192420













gtacagcacc cagcaacagc cctgctgccc aaccctgcag cctgtggccc aa






#gtagcacc 192480













agcacccacc agggtgcaag actctcaagg cctgcccaac ctactaatca ga






#accagcat 192540













ctcaaggaga tctcgggtga tttttgcaaa cactgaagtt ggggcagccc tg






#accggagt 192600













aaccttccct catttcctcc tgcagctgca aagctgtccc atcaaggaag ac






#agcttctt 192660













gcagcgatac agctcagacc ccacaggcgc cttgactgag gacagcatag ac






#gacacctt 192720













cctcccagtg cctggtgagt ggcttgtctg gaaacagtcc tgctcctcaa cc






#tcctcgac 192780













ccactcagca gcagccagtc tccagtgtcc aagccaggtg ctccctccag ca






#tctccaga 192840













gggggaaaca gtggcagatt tgcagacaca gtgaagggcg taaggagcag at






#aaacacat 192900













gaccgagcct gcacaagctc tttgttgtgt ctggttgttt gctgtacctc tg






#ttgtaaga 192960













atgaatctgc aaaatttcta gcttatgaag caaatcacgg acatacacat ct






#gtgtgtgt 193020













gagtgttcat gatgtgtgta catctgtgta tgtgtgtgtg tgtatgtgtg tg






#tttgtgac 193080













agatttgatc cctgttctct ctgctggctc tatcttgacc tgtgaaacgt at






#atttaact 193140













aattaaatat tagttaatat taataaattt taagctttat ccagatactc at






#aacctgct 193200













aacacacaca catatacaca cacatacaca tacacacata tacacacacc ac






#acacatac 193260













acagacacca cacacatacc atacacagac acatacacat gcacacacat at






#acacacac 193320













acctcaaata catacacacc acacacacat acatgtatac acacatacac ac






#accacaca 193380













tacaccacaa aaaccccaca cacatacaca tatacacacc acacacacca ca






#tacacaca 193440













cgtatacaca catatataca cacatacacc atgcatacat acacaccaca ca






#tacataca 193500













gacacaccac acacacgtac acacaacaca caacacagac acacacgtac ac






#acactaca 193560













gacatgtatg cacacataca cacacaccac acatacatac acacagacac at






#atacacta 193620













cacacaccat tacatacaca cgtacacata caccacacac accacacata ca






#cacaccac 193680













acacacatac acacgccaca cacacaccac aaaaaccgca cacacataca aa






#catataca 193740













cactacacca cacatacaca cacacaccac acaccacaca cacacataca ca






#caccacac 193800













acaccacaca tacacgcacc acacatacac acacgtagac acaccacaca ca






#ccacagaa 193860













acacacatta acacaccaca tacacatatg tatgtgcata tacacaccca ca






#ccccacac 193920













acacatgtat aaagatttag atatatataa aacatacgtt atatatatgt tg






#atgtaata 193980













tctaatatct atatatctaa tatgtagttt attagctatc taatatctat gt






#catatata 194040













tcaaatcttt atatataaaa atatgtagaa atctttatac atatgttata tg






#tatataaa 194100













gatttagata tataacatat gtaagttata tatatgttag tgtaatatct aa






#tatatagt 194160













ttattggcta tctaatataa tataaacaga ttatcaatat tataagctat ta






#gaaaaatg 194220













caagttaagg cagatgatat acctctttca caccaactca cacaccaact ac






#acacacac 194280













atacacacag acacacacga cacacaccat acacatgtac acacacacca ca






#tatacaca 194340













aacgtacaca cacaccacac acacatacac accacacaca caacacacat ac






#atacacat 194400













ccacacacca cacatgtaca cacaccacac acacacatac acaccacata ca






#catatgta 194460













tgcacacata cacaccaaca ccacacagac accacacatg cataaacata ta






#gacatata 194520













cacaccacac accatatgta cacatgtaca cacacaccac atatacacac aa






#cacacaca 194580













aatacacaca ccacacacac accacaaaaa ccccacacac acaaacatat ac






#accccaca 194640













catacgcata tatacacaca cacatacaca ccacacacat acacaccaca ca






#cacaccac 194700













acatacacac acgtacacac accacacaca caccacagac acacaccaca ca






#tacataca 194760













catacacaca ccacacacac gtacacacac cacacacaca cagacacaca ta






#gacacacc 194820













acatacacac ccacaccaca cacacacaac tcataccaca catacataca ca






#atagacac 194880













atacacacca cacacaccat acatacacac gtatacacac accacatata ca






#cacacgta 194940













cacacacacc acacacaccc acatgcacac accacacaca catacaaata ta






#caccacac 195000













acacatacac cacacacacg gtgcacatac acacacatat acacacacca ga






#cacacata 195060













ccacatacac atcacacata tatgtataca tgcatacaca tacacacaca ca






#tacacaca 195120













ctctcctcaa ggcagtttat cctctgagaa ctttaaattt acaaaagaca ca






#tatgtcca 195180













ttactttgag aaggacagga aagaacccac tttcttttgc agcaacagca ag






#agggccct 195240













cccaaggctc ctgctccctg tcataagtct ccttgttgag gacattcaca gg






#gttcagaa 195300













cccagggatc ctgcatggga tggtgctttg ctgattactt cacctctgat tt






#ctttccac 195360













tttcagaata cataaaccag tccgttccca aaaggcccgc tggctctgtg ca






#gaatcctg 195420













tctatcacaa tcagcctctg aaccccgcgc ccagcagaga cccacactac ca






#ggaccccc 195480













acagcactgc agtgggcaac cccgagtatc tcaacactgt ccagcccacc tg






#tgtcaaca 195540













gcacattcga cagccctgcc cactgggccc agaaaggcag ccaccaaatt ag






#cctggaca 195600













accctgacta ccagcaggac ttctttccca aggaagccaa gccaaatggc at






#ctttaagg 195660













gctccacagc tgaaaatgca gaatacctaa gggtcgcgcc acaaagcagt ga






#atttattg 195720













gagcatgacc acggaggata gtatgagccc taaaaatcca gactctttcg at






#acccagga 195780













ccaagccaca gcaggtcctc catcccaaca gccatgcccg cattagctct ta






#gacccaca 195840













gactggtttt gcaacgttta caccgactag ccaggaagta cttccacctc gg






#gcacattt 195900













tgggaagttg cattcctttg tcttcaaact gtgaagcatt tacagaaacg ca






#tccagcaa 195960













gaatattgtc cctttgagca gaaatttatc tttcaaagag gtatatttga aa






#aaaaaaaa 196020













aaaagtatat gtgaggattt ttattgattg gggatcttgg agtttttcat tg






#tcgctatt 196080













gatttttact tcaatgggct cttccaacaa ggaagaagct tgctggtagc ac






#ttgctacc 196140













ctgagttcat ccaggcccaa ctgtgagcaa ggagcacaag ccacaagtct tc






#cagaggat 196200













gcttgattcc agtggttctg cttcaaggct tccactgcaa aacactaaag at






#ccaagaag 196260













gccttcatgg ccccagcagg ccggatcggt actgtatcaa gtcatggcag gt






#acagtagg 196320













ataagccact ctgtcccttc ctgggcaaag aagaaacgga ggggatgaat tc






#ttccttag 196380













acttactttt gtaaaaatgt ccccacggta cttactcccc actgatggac ca






#gtggtttc 196440













cagtcatgag cgttagactg acttgtttgt cttccattcc attgttttga aa






#ctcagtat 196500













gccgcccctg tcttgctgtc atgaaatcag caagagagga tgacacatca aa






#taataact 196560













cggattccag cccacattgg attcatcagc atttggacca atagcccaca gc






#tgagaatg 196620













tggaatacct aaggataaca ccgcttttgt tctcgcaaaa acgtatctcc ta






#atttgagg 196680













ctcagatgaa atgcatcagg tcctttgggg catagatcag aagactacaa aa






#atgaagct 196740













gctctgaaat ctcctttagc catcacccca accccccaaa attagtttgt gt






#tacttatg 196800













gaagatagtt ttctcctttt acttcacttc aaaagctttt tactcaaaga gt






#atatgttc 196860













cctccaggtc agctgccccc aaaccccctc cttacgcttt gtcacacaaa aa






#gtgtctct 196920













gccttgagtc atctattcaa gcacttacag ctctggccac aacagggcat tt






#tacaggtg 196980













cgaatgacag tagcattatg agtagtgtga attcaggtag taaatatgaa ac






#tagggttt 197040













gaaattgata atgctttcac aacatttgca gatgttttag aaggaaaaaa gt






#tccttcct 197100













aaaataattt ctctacaatt ggaagattgg aagattcagc tagttaggag cc






#catttttt 197160













cctaatctgt gtgtgccctg taacctgact ggttaacagc agtcctttgt aa






#acagtgtt 197220













ttaaactctc ctagtcaata tccaccccat ccaatttatc aaggaagaaa tg






#gttcagaa 197280













aatattttca gcctacagtt atgttcagtc acacacacat acaaaatgtt cc






#ttttgctt 197340













ttaaagtaat ttttgactcc cagatcagtc agagccccta cagcattgtt aa






#gaaagtat 197400













ttgatttttg tctcaatgaa aataaaacta tattcatttc cactctatta tg






#ctctcaaa 197460













tacccctaag catctatact agcctggtat gggtat      






#                  






#   197496




















<210> SEQ ID NO 11






<211> LENGTH: 4530






<212> TYPE: DNA






<213> ORGANISM: Homo sapiens













<400> SEQUENCE: 11













aattctcgag ctcgtcgacc ggtcgacgag ctcgagggtc gacgagctcg ag






#ggcgcgcg     60













cccggccccc acccctcgca gcaccccgcg ccccgcgccc tcccagccgg gt






#ccagccgg    120













agccatgggg ccggagccgc agtgagcacc atggagctgg cggccttgtg cc






#gctggggg    180













ctcctcctcg ccctcttgcc ccccggagcc gcgagcaccc aagtgtgcac cg






#gcacagac    240













atgaagctgc ggctccctgc cagtcccgag acccacctgg acatgctccg cc






#acctctac    300













cagggctgcc aggtggtgca gggaaacctg gaactcacct acctgcccac ca






#atgccagc    360













ctgtccttcc tgcaggatat ccaggaggtg cagggctacg tgctcatcgc tc






#acaaccaa    420













gtgaggcagg tcccactgca gaggctgcgg attgtgcgag gcacccagct ct






#ttgaggac    480













aactatgccc tggccgtgct agacaatgga gacccgctga acaataccac cc






#ctgtcaca    540













ggggcctccc caggaggcct gcgggagctg cagcttcgaa gcctcacaga ga






#tcttgaaa    600













ggaggggtct tgatccagcg gaacccccag ctctgctacc aggacacgat tt






#tgtggaag    660













gacatcttcc acaagaacaa ccagctggct ctcacactga tagacaccaa cc






#gctctcgg    720













gcctgccacc cctgttctcc gatgtgtaag ggctcccgct gctggggaga ga






#gttctgag    780













gattgtcaga gcctgacgcg cactgtctgt gccggtggct gtgcccgctg ca






#aggggcca    840













ctgcccactg actgctgcca tgagcagtgt gctgccggct gcacgggccc ca






#agcactct    900













gactgcctgg cctgcctcca cttcaaccac agtggcatct gtgagctgca ct






#gcccagcc    960













ctggtcacct acaacacaga cacgtttgag tccatgccca atcccgaggg cc






#ggtataca   1020













ttcggcgcca gctgtgtgac tgcctgtccc tacaactacc tttctacgga cg






#tgggatcc   1080













tgcaccctcg tctgccccct gcacaaccaa gaggtgacag cagaggatgg aa






#cacagcgg   1140













tgtgagaagt gcagcaagcc ctgtgcccga gtgtgctatg gtctgggcat gg






#agcacttg   1200













cgagaggtga gggcagttac cagtgccaat atccaggagt ttgctggctg ca






#agaagatc   1260













tttgggagcc tggcatttct gccggagagc tttgatgggg acccagcctc ca






#acactgcc   1320













ccgctccagc cagagcagct ccaagtgttt gagactctgg aagagatcac ag






#gttaccta   1380













tacatctcag catggccgga cagcctgcct gacctcagcg tcttccagaa cc






#tgcaagta   1440













atccggggac gaattctgca caatggcgcc tactcgctga ccctgcaagg gc






#tgggcatc   1500













agctggctgg ggctgcgctc actgagggaa ctgggcagtg gactggccct ca






#tccaccat   1560













aacacccacc tctgcttcgt gcacacggtg ccctgggacc agctctttcg ga






#acccgcac   1620













caagctctgc tccacactgc caaccggcca gaggacgagt gtgtgggcga gg






#gcctggcc   1680













tgccaccagc tgtgcgcccg agggcactgc tggggtccag ggcccaccca gt






#gtgtcaac   1740













tgcagccagt tccttcgggg ccaggagtgc gtggaggaat gccgagtact gc






#aggggctc   1800













cccagggagt atgtgaatgc caggcactgt ttgccgtgcc accctgagtg tc






#agccccag   1860













aatggctcag tgacctgttt tggaccggag gctgaccagt gtgtggcctg tg






#cccactat   1920













aaggaccctc ccttctgcgt ggcccgctgc cccagcggtg tgaaacctga cc






#tctcctac   1980













atgcccatct ggaagtttcc agatgaggag ggcgcatgcc agccttgccc ca






#tcaactgc   2040













acccactcct gtgtggacct ggatgacaag ggctgccccg ccgagcagag ag






#ccagccct   2100













ctgacgtcca tcgtctctgc ggtggttggc attctgctgg tcgtggtctt gg






#gggtggtc   2160













tttgggatcc tcatcaagcg acggcagcag aagatccgga agtacacgat gc






#ggagactg   2220













ctgcaggaaa cggagctggt ggagccgctg acacctagcg gagcgatgcc ca






#accaggcg   2280













cagatgcgga tcctgaaaga gacggagctg aggaaggtga aggtgcttgg at






#ctggcgct   2340













tttggcacag tctacaaggg catctggatc cctgatgggg agaatgtgaa aa






#ttccagtg   2400













gccatcaaag tgttgaggga aaacacatcc cccaaagcca acaaagaaat ct






#tagacgaa   2460













gcatacgtga tggctggtgt gggctcccca tatgtctccc gccttctggg ca






#tctgcctg   2520













acatccacgg tgcagctggt gacacagctt atgccctatg gctgcctctt ag






#accatgtc   2580













cgggaaaacc gcggacgcct gggctcccag gacctgctga actggtgtat gc






#agattgcc   2640













aaggggatga gctacctgga ggatgtgcgg ctcgtacaca gggacttggc cg






#ctcggaac   2700













gtgctggtca agagtcccaa ccatgtcaaa attacagact tcgggctggc tc






#ggctgctg   2760













gacattgacg agacagagta ccatgcagat gggggcaagg tgcccatcaa gt






#ggatggcg   2820













ctggagtcca ttctccgccg gcggttcacc caccagagtg atgtgtggag tt






#atggtgtg   2880













actgtgtggg agctgatgac ttttggggcc aaaccttacg atgggatccc ag






#cccgggag   2940













atccctgacc tgctggaaaa gggggagcgg ctgccccagc cccccatctg ca






#ccattgat   3000













gtctacatga tcatggtcaa atgttggatg attgactctg aatgtcggcc aa






#gattccgg   3060













gagttggtgt ctgaattctc ccgcatggcc agggaccccc agcgctttgt gg






#tcatccag   3120













aatgaggact tgggcccagc cagtcccttg gacagcacct tctaccgctc ac






#tgctggag   3180













gacgatgaca tgggggacct ggtggatgct gaggagtatc tggtacccca gc






#agggcttc   3240













ttctgtccag accctgcccc gggcgctggg ggcatggtcc accacaggca cc






#gcagctca   3300













tctaccagga gtggcggtgg ggacctgaca ctagggctgg agccctctga ag






#aggaggcc   3360













cccaggtctc cactggcacc ctccgaaggg gctggctccg atgtatttga tg






#gtgacctg   3420













ggaatggggg cagccaaggg gctgcaaagc ctccccacac atgaccccag cc






#ctctacag   3480













cggtacagtg aggaccccac agtacccctg ccctctgaga ctgatggcta cg






#ttgccccc   3540













ctgacctgca gcccccagcc tgaatatgtg aaccagccag atgttcggcc cc






#agccccct   3600













tcgccccgag agggccctct gcctgctgcc cgacctgctg gtgccactct gg






#aaagggcc   3660













aagactctct ccccagggaa gaatggggtc gtcaaagacg tttttgcctt tg






#ggggtgcc   3720













gtggagaacc ccgagtactt gacaccccag ggaggagctg cccctcagcc cc






#accctcct   3780













cctgccttca gcccagcctt cgacaacctc tattactggg accaggaccc ac






#cagagcgg   3840













ggggctccac ccagcacctt caaagggaca cctacggcag agaacccaga gt






#acctgggt   3900













ctggacgtgc cagtgtgaac cagaaggcca agtccgcaga agccctgatg tg






#tcctcagg   3960













gagcagggaa ggcctgactt ctgctggcat caagaggtgg gagggccctc cg






#accacttc   4020













caggggaacc tgccatgcca ggaacctgtc ctaaggaacc ttccttcctg ct






#tgagttcc   4080













cagatggctg gaaggggtcc agcctcgttg gaagaggaac agcactgggg ag






#tctttgtg   4140













gattctgagg ccctgcccaa tgagactcta gggtccagtg gatgccacag cc






#cagcttgg   4200













ccctttcctt ccagatcctg ggtactgaaa gccttaggga agctggcctg ag






#aggggaag   4260













cggccctaag ggagtgtcta agaacaaaag cgacccattc agagactgtc cc






#tgaaacct   4320













agtactgccc cccatgagga aggaacagca atggtgtcag tatccaggct tt






#gtacagag   4380













tgcttttctg tttagttttt actttttttg ttttgttttt ttaaagacga aa






#taaagacc   4440













caggggagaa tgggtgttgt atggggaggc aagtgtgggg ggtccttctc ca






#cacccact   4500













ttgtccattt gcaaatatat tttggaaaac         






#                  






#         4530













Claims
  • 1. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent, for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor sample and non-malignant sample; (d) subjecting the mRNA to amplification using a pair of oligonucleotide primers capable of amplifying a region of the EGFR gene, or a pair of oligonucleotide primers capable of amplifying a region of the HER2-neu gene, to obtain an EGFR tumor amplified sample and a EGFR non-malignant amplified sample, or a HER2-neu tumor amplified sample and a HER2-neu non-malignant amplified sample (e) determining an amount of HER2-neu mRNA in the HER2-neu tumor amplified sample and HER2-neu non-malignant amplified sample or determining the amount of EGFR mRNA in the EGFR tumor amplified sample and EGFR non-malignant amplified sample; (f) obtaining a differential HER2-neu epression level or obtaining a differential EGFR expression level; and (g) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (f) and a threshold level for differential HER2-neu gene expression, or comparing the differential EGFR expression level of step (f) and a threshold level for differential EGFR gene expression.
  • 2. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor sample and non-malignant sample; (d) subjecting the mRNA to amplification using a pair of oligonucleotide primers capable of amplifying a region of the EGFR gene, to obtain an tumor amplified sample and a non-malignant amplified sample; (e) determining the amount of EGFR mRNA in the tumor amplified sample and non-malignant amplified sample; (f) obtaining a differential EGFR expression level; and (g) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential EGFR expression level of step (f) and a threshold level for differential EGFR gene expression.
  • 3. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor sample and non-malignant sample; (d) subjecting the mRNA to amplification using a pair of oligonucleotide primers capable of amplifying a region of the HER2-neu gene, to obtain an tumor amplified sample and a non-malignant amplified sample; (e) determining the amount of HER2-neu mRNA in the tumor amplified sample and non-malignant amplified sample; (f) obtaining a differential HER2-neu expression level; and (g) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (f) and a threshold level for differential HER2-neu gene expression.
  • 4. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor sample and non-malignant sample; (d) subjecting the mRNA to amplification using a pair of oligonucleotide primers capable of amplifying a region of the EGFR gene, and a pair of oligonucleotide primers capable of amplifying a region of the HER2-neu gene, to obtain an EGFR tumor amplified sample and an EGFR non-malignant amplified sample, and a HER2-neu tumor amplified sample and a HER2-neu non-malignant amplified sample (e) determining the amount of HER2-neu mRNA in the HER2-neu tumor amplified sample and HER2-neu non-malignant amplified sample and determining the amount of EGFR mRNA in the EGFR tumor amplified sample and EGFR non-malignant amplified sample; (f) obtaining a differential HER2-neu expression level and obtaining a differential EGFR expression level; and (g) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (f) and a threshold level for differential HER2-neu gene expression, and comparing the differential EGFR expression level of step (f) and a threshold level for differential EGFR gene expression.
  • 5. The method of claim 2, wherein the pair of oligonucleotide primers consists of SEQ ID NO:1 or an oligonucleotide primer at least about 80% identical thereto and SEQ ID NO: 2 or an oligonucleotide primer at least about 80% identical thereto.
  • 6. The method of claim 3, wherein the pair of oligonucleotide primers consists of SEQ ID NO:4 or an oligonucleotide primer at least about 80% identical thereto and SEQ ID NO: 5 or an oligonucleotide primer at least about 80% identical thereto.
  • 7. The method of any one of claims 1, 2, 3, or 4 wherein the tumor is a non-small cell lung cancer tumor.
  • 8. The method of claim 4 wherein the primers consist of both the oligonucleotide primer pair SEQ ID NO: 4 or an oligonucleotide primer at least about 80% identical thereto and SEQ ID NO: 5 or an oligonucleotide primer at least about 80% identical thereto; and oligonucleotide primer pair SEQ ID NO: 1 or an oligonucleotide primer at least about 80% identical thereto and SEQ ID NO: 2 or an oligonucleotide primer at least about 80% identical thereto.
  • 9. The method of any one of claims 1, 2, or 4 wherein the threshold level for differential EGFR gene expression is about 1.8.
  • 10. The method of any one of claims 1, 3, or 4 wherein, the threshold level for differential HER2-neu gene expression is about 1.8.
  • 11. The method of any one of claims 1, 2, 3 or 4 wherein the tissue samples are fixed or fixed and paraffin embedded.
  • 12. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent, for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a non-malignant tissue sample matching said tumor; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the HER2-neu tumor tissue sample and HER2-neu non-malignant tissue sample or determining the amount of EGFR mRNA in the EGFR tumor tissue sample and EGFR non-malignant tissue sample; (e) obtaining a differential HER2-neu expression level or obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression of about 1.8, or comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression of about 1.8.
  • 13. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent, for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the tumor tissue sample and non-malignant tissue sample or determining the amount of EGFR mRNA in the tumor tissue sample and non-malignant tissue sample; (e) obtaining a differential HER2-neu epression level or obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression of about 1.8, or comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression of about 1.8.
  • 14. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of EGFR mRNA in the tumor tissue sample and non-malignant tissue sample; (e) obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression of about 1.8.
  • 15. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the tumor tissue sample and non-malignant tissue sample; (e) obtaining a differential HER2-neu expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression of about 1.8.
  • 16. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the tumor tissue sample and non-malignant tissue sample and determining the amount of EGFR mRNA in the tumor tissue sample and non-malignant amplified sample; (e) obtaining a differential HER2-neu expression level and obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression of about 1.8, and comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression of about 1.8.
  • 17. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent, for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the tumor tissue sample and non-malignant tissue sample or determining the amount of EGFR mRNA in the tumor tissue sample and non-malignant tissue sample; (e) obtaining a differential HER2-neu epression level or obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression, or comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression.
  • 18. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of EGFR mRNA in the tumor tissue sample and non-malignant tissue sample; (e) obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression.
  • 19. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant tissue sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the tumor tissue sample and non-malignant tissue sample; (e) obtaining a differential HER2-neu expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression.
  • 20. A method for determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent for treating a tumor in a patient comprising:(a) obtaining a tissue sample of the tumor; (b) obtaining a matching non-malignant tissue sample; (c) isolating mRNA from the tumor tissue sample and non-malignant sample; wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation; (d) determining the amount of HER2-neu mRNA in the tumor tissue sample and non-malignant tissue sample and determining the amount of EGFR mRNA in the tumor tissue sample and non-malignant amplified sample; (e) obtaining a differential HER2-neu expression level and obtaining a differential EGFR expression level; and (f) determining a chemotherapeutic regimen comprising a receptor tyrosine kinase targeted agent by comparing the differential HER2-neu expression level of step (e) and a threshold level for differential HER2-neu gene expression, and comparing the differential EGFR expression level of step (e) and a threshold level for differential EGFR gene expression.
  • 21. The method of claim 18, wherein step (d) comprises the use of a pair of oligonucleotide primers consisting of SEQ ID NO:1 or an oligonucleotide primer at least about 80% identical thereto and SEQ ID NO: 2 or an oligonucleotide primer at least about 80% identical thereto.
  • 22. The method of claim 19, wherein step (d) comprises the use of a pair of oligonucleotide primers consisting of SEQ ID NO:4 or an oligonucleotide primer at least about 80% identical thereto and SEQ ID NO: 5 or an oligonucleotide primer at least about 80% identical thereto.
  • 23. The method of any one of claims 17, 18, 19, or 20 wherein the tumor is a non-small cell lung cancer tumor.
  • 24. The method of claim 20 wherein wherein step (d) comprises the use of two pairs of oligonucleotide primers consisting of oligonucleotide primer pair SEQ ID NO: 4 or an oligonucleotide primer at least or about 80% identical thereto, and SEQ ID NO: 5 or an oligonucleotide primer at least or about 80% identical thereto, and oligonucleotide primer pair SEQ ID NO: 1 or an oligonucleotide primer at least or about 80% identical thereto, and SEQ ID NO: 2 or an oligonucleotide primer at least or about 80% identical thereto.
  • 25. The method of any one of claims 17, 18, 19, or 20 wherein step (d) comprises the step of amplifying the mRNA isolated from said tumor tissue sample and said non-malignant tissue sample.
  • 26. The method of anyone of claims 17, 18, 19, or 20 wherein, step (c) comprises the step of heating the fixed tumor sample the in the presence of an effective concentration of a chaotropic agent wherein the heating occurs at a temperature from about 75° C. to about 100° C. for a time period of about 5 to about 120 minutes.
  • 27. The method of anyone of claims 1, 2, 3, or 4 wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation and step (c) comprises the step of heating the tissue sample the in the presence of an effective concentration of a chaotropic agent wherein the heating occurs at a temperature from about 50° C. to about 100° C.
  • 28. The method of anyone of claims 17, 18, 19, or 20 wherein said tissue samples are fixed or fixed and paraffin embedded prior to said mRNA isolation and step (c) comprises the step of heating the tissue sample the in the presence of an effective concentration of a chaotropic agent wherein the heating occurs at a temperature from about 50° C. to about 100° C.
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Entry
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