Patent application title: DIAGNOSTIC GENE MARKER PANEL FOR COLORECTAL CANCER
Inventors:
Peter Molloy (Chatswood, AU)
Lawrence Lapointe (New South Wales, AU)
Susanne Pedersen (New South Wales, AU)
IPC8 Class: AC12Q16886FI
USPC Class:
Class name:
Publication date: 2022-07-07
Patent application number: 20220213559
Abstract:
The present invention relates generally to a method of screening for the
onset, predisposition to the onset and/or progression of a neoplasm. More
particularly, the present invention relates to a method of screening for
the onset, predisposition to the onset and/or progression of a neoplasm
by screening for changes to the methylation levels of a panel of gene
markers. The method of the present invention is useful in a range of
applications including, but not limited to, those relating to the
diagnosis and/or monitoring of colorectal neoplasms, such as colorectal
adenocarcinosis.Claims:
1. (canceled)
2. A method of assessing the methylation status of DNA present in a biological sample obtained from a human individual at risk of developing or of recurrence of, or suffering from, a large intestine neoplasm, comprising: assessing the methylation status of an IKZF1 gene by measuring the methylation status of one or more DNA subregions located within the IKZF1 gene, by performing a bisulfite conversion of the one or more DNA subregions, amplifying the bisulfite converted IKZF1 DNA subregions or the complement thereof with oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IKZF1 DNA subregions under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the one or more DNA subregions; and assessing the methylation status of a IRF4 gene by measuring the methylation status of one or more DNA subregions located within the IRF4 gene, by performing a bisulfite conversion of the one or more DNA subregions, amplifying the bisulfite converted IRF4 DNA subregions or the complement thereof with oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IRF4 DNA subregions under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the one or more DNA subregions.
3. The method of claim 2, wherein the one or more DNA subregions located within the IKZF1 gene are SEQ ID NO: 3 or SEQ ID NO: 4 or the complements thereof.
4. The method of claim 2, wherein the one or more DNA subregions located within the IRF4 gene is SEQ ID NO: 5 or the complement thereof.
5. The method of claim 2, wherein the one or more DNA subregions located within the IKZF1 gene is within a nucleic acid sequence as set forth in SEQ ID NO: 3; and the one or more DNA subregions located within the IRF4 gene is within a nucleic acid sequence as set forth in SEQ ID NO: 5.
6. The method of claim 2, wherein measuring the methylation status of the one or more DNA subregions located within the IKZF1 gene comprises measuring the methylation of one or more cytosine residues in the gene region encompassing IKZF 1; and measuring the methylation status of the one or more DNA subregions located within the IRF4 gene comprises measuring the methylation of one or more cytosine residues in the gene region encompassing IRF4.
7. The method of claim 2, wherein measuring the methylation status of the one or more DNA subregions located within the IKZF1 gene consists of measuring the methylation of one or more cytosine residues on the plus strand selected from: TABLE-US-00012 chr7:50343869 chr7:50343872 chr7:50343883 chr7:50343889 chr7:50343890 chr7:50343897 chr7:50343907 chr7:50343909 chr7:50343914 chr7:50343934 chr7:50343939 chr7:50343950 chr7:50343959 chr7:50343805 chr7:50343822 chr7:50343824 chr7:50343826 chr7:50343829 chr7:50343831 chr7:50343833 chr7:50343838 chr7:50343847 chr7:50343850 chr7:50343858 or chr7:50343864
or a corresponding cytosine residue at position n+1 on the opposite strand.
8. The method of claim 2, wherein the large intestine neoplasm is an adenoma or an adenocarcinoma.
9. The method of claim 2, wherein the large intestine neoplasm is a colorectal neoplasia.
10. The method of claim 2, wherein the biological sample is selected from a fecal sample, enema wash, surgical resection, tissue biopsy, or blood sample.
11. The method of claim 2, wherein the biological sample is a plasma sample.
12. The method of claim 2, further comprising administering a cancer treatment to the individual when methylation is measured at one or more cytosines in at least one of the DNA subregions.
13. The method of claim 2, wherein the oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IKZF1 DNA subregions comprise a sequence as set forth in SEQ ID NO: 18 and SEQ ID NO: 23.
14. The method of claim 2, wherein the oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IRF4 DNA subregions comprise a sequence as set forth in SEQ ID NO: 16 and SEQ ID NO: 21.
15. A method of treating a human individual suffering from or at risk of developing or of recurrence of a large intestine neoplasm, comprising: assessing the methylation status of an IKZF1 gene by measuring the methylation status of one or more DNA subregions located within the IKZF1 gene, wherein the subregions are SEQ ID NO: 3 or SEQ ID NO: 4 or the complements thereof, by performing a bisulfite conversion of the one or more DNA subregions, amplifying the bisulfite converted IKZF1 DNA subregions or the complement thereof with oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IKZF1 DNA subregions under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the DNA subregions; and assessing the methylation status of a IRF4 gene by measuring the methylation status of one or more DNA subregions located within the IRF4 gene, wherein the subregions are SEQ ID NO: 5 or the complements thereof, by performing a bisulfite conversion of the one or more DNA subregions, amplifying the bisulfite converted IRF4 DNA subregions or the complement thereof with oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IRF4 DNA subregions under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the DNA subregion; and administering a cancer treatment to the human individual, wherein the human individual has: a methylated IKZF1 DNA subregion that is SEQ ID NO: 3 and/or 4; and/or a methylated IRF4 DNA subregion that is SEQ ID NO: 5.
16. The method of claim 15, further comprising assessing a post-treatment methylation status of DNA present in a biological sample obtained from the individual at a time point subsequent to said administering, comprising: measuring a methylation status of an IKZF1 DNA subregion that is SEQ ID NO: 3 by performing a bisulfite conversion of the DNA subregion, amplifying the bisulfite converted IKZF1 DNA subregion with oligonucleotides that are SEQ ID NO: 18 and SEQ ID NO: 23, and measuring the methylation status of one or more cytosines in the DNA subregion; and measuring a methylation status of a IRF4 DNA subregion that is SEQ ID NO: 5 by performing a bisulfite conversion of the DNA subregion, amplifying the bisulfite converted IRF4 DNA subregion with oligonucleotides that are SEQ ID NO: 16 and SEQ ID NO: 21, and measuring the methylation status of one or more cytosines in the DNA subregion.
17. A method of monitoring the methylation status of DNA in a sample from a human individual suffering from or at risk of developing or of recurrence of a large intestine neoplasm, comprising: assessing a first methylation status of DNA present in a first biological sample obtained at a first time point from a human individual suffering from or at risk of developing a large intestine neoplasm, comprising: measuring a first methylation level status of a DNA subregion located within the IKZF1 gene, wherein the subregion is SEQ ID NO: 3 or SEQ ID NO: 4 or the complement thereof, by performing a bisulfite conversion of the DNA subregion, amplifying the bisulfite converted IKZF1 DNA subregion or the complement thereof with oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IKZF1 DNA subregion under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the DNA subregion; and measuring a first methylation status of a DNA subregion located within the IRF4 gene, wherein the subregion is SEQ ID NO: 5 or the complement thereof, by performing a bisulfite conversion of the DNA subregion, amplifying the bisulfite converted IRF4 DNA subregion or the complement thereof with oligonucleotides comprising a nucleic acid sequence that is complementary to the bisulfite converted IRF4 DNA subregion under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the DNA subregion, and assessing a second methylation status of DNA present in a second biological sample obtained from the individual at a second time point subsequent to the first time point, comprising: measuring a second methylation level status of an IKZF1 DNA subregion that is SEQ ID NO: 3 or SEQ ID NO: 4 or the complement thereof, by performing a bisulfite conversion of the DNA subregion and measuring the methylation status of one or more cytosines in the DNA subregion; and measuring a second methylation level status of a IRF4 DNA subregion that is SEQ ID NO: 5 or the complement thereof, by performing a bisulfite conversion of the DNA subregion and measuring the methylation status of one or more cytosines in the DNA subregion.
18. A method of assessing the methylation status of DNA present in a biological sample obtained from a human individual at risk of developing or of recurrence of, or suffering from, a large intestine neoplasm, consisting of: assessing the methylation status of an IKZF1 gene by measuring the methylation status of one or more DNA subregions located within the IKZF1 gene, wherein the subregions are SEQ ID NO: 3 or SEQ ID NO: 4 or the complements thereof, by performing a bisulfite conversion of the one or more DNA subregions, amplifying the bisulfite converted IKZF1 DNA subregions or the complement thereof with at least one oligonucleotide comprising a nucleic acid sequence that is complementary to a sequence that originates within the bisulfite converted IKZF1 DNA subregions under selective hybridization conditions, and detecting the methylation status of one or more cytosines in the one or more DNA subregions; and assessing the methylation status of a IRF4 gene by measuring the methylation status of one or more DNA subregions located within the IRF4 gene, wherein the subregions are SEQ ID NO: 5 or the complements thereof, by performing a bisulfite conversion of the one or more DNA subregions, amplifying the bisulfite converted IRF4 DNA subregions or the complement thereof with at least one oligonucleotide comprising a nucleic acid sequence that is complementary to a sequence that originates within the bisulfite converted IRF4 DNA subregions under selective hybridization conditions, and measuring the methylation status of one or more cytosines in the one or more DNA subregions.
19. A method of sequencing DNA present in a biological sample comprising: (a) sequencing one or more IKZF1 DNA subregions within the IKZF1 gene in a biological sample, wherein the IKZF1 DNA subregions are SEQ ID NO: 3 or SEQ ID NO: 4 or the complements thereof, by: performing a bisulfite conversion of at least a portion of the IKZF1 gene comprising the one or more IKZF1 DNA subregions, amplifying the bisulfite converted portion of the IKZF1 gene comprising the one or more IKZF1 DNA subregions or the complement thereof with at least one oligonucleotide comprising a nucleic acid sequence that is complementary to a region of the bisulfite converted portion of the IKZF1 gene comprising the one or more IKZF1 DNA subregions under selective hybridization conditions, and sequencing the bisulfite converted portion of the IKZF1 gene comprising the one or more IKZF1 DNA subregions; and (b) sequencing a IRF4 DNA subregion within the IRF4 gene in said biological sample, wherein the IRF4 DNA subregion is SEQ ID NO: 5 or the complement thereof, by: performing a bisulfite conversion of at least a portion of the IRF4 gene comprising the IRF4 DNA subregion, amplifying the bisulfite converted portion of the IRF4 gene comprising the IRF4 DNA subregion or the complement thereof with at least one oligonucleotide comprising a nucleic acid sequence that is complementary to a region of the bisulfite converted portion of the IRF4 gene comprising the IRF4 DNA subregion under selective hybridization conditions, and sequencing the bisulfite converted portion of the IRF4 gene comprising the IRF4 DNA subregion.
Description:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application of U.S. application Ser. No. 14/400,313, filed Nov. 10, 2014, which is a U.S. National Phase Application of PCT International Application Number PCT/AU2013/000481, filed May 10, 2013, designating the United States of America and published in the English language, which is an International Application of and claims the benefit of priority to U.S. Provisional Application No. 61/646,174, filed May 11, 2012, the disclosures of which are hereby expressly incorporated by reference in their entireties.
REFERENCE TO SEQUENCE LISTING
[0002] A Sequence Listing submitted as an ASCII text file via EFS-Web is hereby incorporated by reference in accordance with 35 U.S.C. .sctn. 1.52(e).
FIELD
[0003] The present invention relates generally to a method of screening for the onset, predisposition to the onset and/or progression of a neoplasm. More particularly, the present invention relates to a method of screening for the onset, predisposition to the onset and/or progression of a neoplasm by screening for changes to the methylation levels of a panel of gene markers. The method of the present invention is useful in a range of applications including, but not limited to, those relating to the diagnosis and/or monitoring of colorectal neoplasms, such as colorectal adenocarcinosis.
BACKGROUND
[0004] Colorectal cancer includes cancerous growths in the colon, rectum and appendix. With 655,000 deaths worldwide per year, it is the fourth most common form of cancer in the United States and the third leading cause of cancer-related death in the Western world. Colorectal cancers arise from adenomatous polyps in the colon. These mushroom-shaped growths are usually benign, but some develop into cancer over time. Localized colon cancer is usually diagnosed through colonoscopy.
[0005] Invasive cancers that are confined within the wall of the colon (stages I and II) are curable with surgery. If untreated, they spread to regional lymph nodes (stage III), where up to 73% are curable by surgery and chemotherapy. Cancer that metastasizes to distant sites (stage IV) is usually not curable, although chemotherapy can extend survival, and in rare cases, surgery and chemotherapy together have seen patients through to a cure (Markowitz and Bertagnolli, 2009, N. Engl. J. Med. 361(25): 2449-60). Radiation is used with rectal cancer.
[0006] Colorectal cancer is preceded by adenomas. Adenomas are benign tumors, or neoplasms, of epithelial origin which are derived from glandular tissue or exhibit clearly defined glandular structures. Some adenomas show recognizable tissue elements, such as fibrous tissue (fibroadenomas) and epithelial structure, while others, such as bronchial adenomas, produce active compounds that might give rise to clinical syndromes.
[0007] Adenomas may progress to become an invasive neoplasm and are then termed adenocarcinomas. Accordingly, adenocarcinomas are defined as malignant epithelial tumors arising from glandular structures, which are constituent parts of many organs of the body. The term adenocarcinoma is also applied to tumors showing a glandular growth pattern. These tumors may be sub-classified according to the substances that they produce, for example mucus secreting and serous adenocarcinomas, or to the microscopic arrangement of their cells into patterns, for example papillary and follicular adenocarcinomas. These carcinomas may be solid or cystic (cystadenocarcinomas). Each organ may produce tumors showing a variety of histological types, for example the ovary may produce both mucinous and cystadenocarcinoma.
[0008] Adenomas in different organs behave differently. In general, the overall chance of carcinoma being present within an adenoma (i.e. a focus of cancer having developed within a benign lesion) is approximately 5%. However, this is related to size of an adenoma. For instance, in the large bowel (colon and rectum specifically) occurrence of a cancer within an adenoma is rare in adenomas of less than 1 centimeter. Such a development is estimated at 40 to 50% in adenomas which are greater than 4 centimeters and show certain histopathological change such as villous change, or high-grade dysplasia. Adenomas with higher degrees of dysplasia have a higher incidence of carcinoma. In any given colorectal adenoma, the predictors of the presence of cancer now or the future occurrence of cancer in the organ include size (especially greater than 9mm) degree of change from tubular to villous morphology, presence of high-grade dysplasia and the morphological change described as "serrated adenoma". In any given individual, the additional features of increasing age, familial occurrence of colorectal adenoma or cancer, male gender or multiplicity of adenomas, predict a future increased risk for cancer in the organ--so-called risk factors for cancer. Except for the presence of adenomas and its size, none of these is objectively defined and all those other than number and size are subject to observer error and to confusion as to precise definition of the feature in question. Because such factors can be difficult to assess and define, their value as predictors of current or future risk for cancer is imprecise.
[0009] Once a sporadic adenoma has developed, the chance of a new adenoma occurring is approximately 30% within 26 months.
[0010] The symptoms of colorectal cancer depend on the location of tumor in the bowel, and whether it has metastasized. Unfortunately, many of the symptoms may occur in other diseases as well, and hence symptoms may not be conclusively diagnostic of colorectal cancer.
[0011] Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (new-onset constipation or diarrhea in the absence of another cause), a feeling of incomplete defecation and reduction in diameter of stools. Tenesmus and change in stool shape are both characteristic of rectal cancer. Lower gastrointestinal bleeding, including the passage of bright red blood in the stool, may indicate colorectal cancer, as may the increased presence of mucus. Melena, black stool with a tarry appearance, normally occurs in upper gastrointestinal bleeding (such as from a duodenal ulcer), but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowl.
[0012] A tumor that is large enough to fill the entire lumen of the bowel may cause bowel obstruction. This situation is characterized by constipation, abdominal pain, abdominal distension and vomiting. This occasionally leads to the obstructed and distended bowel perforating and causing peritonitis.
[0013] Certain local effects of colorectal cancer occur when the disease has become more advanced. A large tumor is more likely to be noticed on feeling the abdomen, and it may be noticed by a doctor on physical examination. The disease may invade other organs, and may cause blood or air in the urine or vaginal discharge.
[0014] If a tumor has caused chronic occult bleeding, iron deficiency anemia may occur. This may be experienced as fatigue, palpitations and noticed as pallor. Colorectal cancer may also lead to weight loss, generally due to a decreased appetite.
[0015] More unusual constitutional symptoms are an unexplained fever and one of several paraneoplastic syndromes. The most common paraneoplastic syndrome is thrombosis, usually deep vein thrombosis.
[0016] Colorectal cancer most commonly spreads to the liver. This may go unnoticed, but large deposits in the liver may cause jaundice and abdominal pain (due to stretching of the capsule). If the tumor deposit obstructs the bile duct, the jaundice may be accompanied by other features of biliary obstruction, such as pale stools.
[0017] Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the prognosis. Even modest efforts to implement colorectal cancer screening methods can result in a drop in cancer deaths. Despite this, colorectal cancer screening rates remain low. There are currently several different tests available for this purpose:
[0018] Digital rectal exam: The doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas. It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test.
[0019] Fecal occult blood test: a test for blood in the stool. Two types of tests can be used for detecting occult blood in stools i.e. guaiac based (chemical test) and immunochemical. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable reduction in specificity (Weitzel J N (December 1999). "Genetic cancer risk assessment. Putting it all together". Cancer 86 (11 Suppl): 2483-92).
[0020] Endoscopy:
[0021] Sigmoidoscopy: A lit probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities.
[0022] Colonoscopy: A lit probe called a colonoscope is inserted into the rectum and the entire colon to look for polyps and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyps are found during the procedure they can be removed immediately. Tissue can also be taken for biopsy.
[0023] Double contrast barium enema (DCBE): First, an overnight preparation is taken to cleanse the colon. An enema containing barium sulfate is administered, then air is insufflated into the colon, distending it. The result is a thin layer of barium over the inner lining of the colon which is visible on X-ray films. A cancer or a precancerous polyp can be detected this way. This technique can miss the (less common) flat polyp.
[0024] Virtual colonoscopy replaces X-ray films in the double contrast barium enema (above) with a special computed tomography scan and requires special workstation software in order for the radiologist to interpret. This technique is approaching colonoscopy in sensitivity for polyps. However, any polyps found must still be removed by standard colonoscopy.
[0025] Standard computed axial tomography is an x-ray method that can be used to determine the degree of spread of cancer, but is not sensitive enough to use for screening. Some cancers are found in CAT scans performed for other reasons.
[0026] Blood tests: Measurement of the patient's blood for elevated levels of certain proteins can give an indication of tumor load. In particular, high levels of carcinoembryonic antigen (CEA) in the blood can indicate metastasis of adenocarcinoma. While these tests are frequently false positive or false negative, and are not recommended for screening, they can be useful to assess disease recurrence. CA19-9 and CA 242 biomarkers can indicate e-selectin related metastatic risks, help follow therapeutic progress, and assess disease recurrence. Recently, an assay for detection in plasma of methylated sequences of the Septin 9 gene has also become available to assist in diagnosis of colorectal cancer.
[0027] Positron emission tomography (PET) is a 3-dimensional scanning technology where a radioactive sugar is injected into the patient, the sugar collects in tissues with high metabolic activity, and an image is formed by measuring the emission of radiation from the sugar. Because cancer cells often have very high metabolic rates, this can be used to differentiate benign and malignant tumors. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases.
[0028] Stool DNA testing is an emerging technology in screening for colorectal cancer. Premalignant adenomas and cancers shed DNA markers from their cells which are not degraded during the digestive process and remain stable in the stool. Capture, followed by PCR amplifies the DNA to detectable levels for assay.
[0029] High C-Reactive Protein Levels as Risk Marker
[0030] Despite the existence of these tests, diagnosis remains problematic. Most of the more sensitive tests are quite invasive and expensive and therefore uptake by patients is low. There is therefore an ongoing need to develop simpler and more informative diagnostic protocols or aids to diagnosis that enable one to direct colonoscopy at people more likely to have developed adenomas or carcinomas. A simple and accurate screening test would enable much more widely applicable screening systems to be set up.
[0031] To this end, more recently there have been identified genetic markers which are modulated, in terms of their expression levels, in individuals who have developed a neoplasm of the large intestine. Some of these markers are upregulated in terms of their level of expression, while others are downregulated. However, a feature common to most of these markers, and the use of genetic marker expression levels in general as a diagnostic, is that they often exhibit only moderate levels of sensitivity and specificity. The development of diagnostic protocols which provide high levels of sensitivity and specificity is highly sought after.
[0032] In work leading up to the present invention, it has been unexpectedly determined that the gene markers BCAT1, IKZF1 IRF4, GRASP and CAHM, although each individually being one of a number of gene markers known to exhibit utility in terms of diagnosing colorectal neoplasia development, have in fact been determined to collectively enable a significantly higher level of sensitivity or specificity to be achieved than where any one of these gene markers is analyzed either alone or together with other unrelated gene markers. More specifically, screening for an increase in the level of methylation of any two or more of these five specific markers can be designed so as to achieve a level of specificity or sensitivity not previously achievable.
[0033] Bearing in mind the large number of gene markers which, in differential gene expression analysis studies, have been shown to exhibit modulated expression levels in neoplasia, the identification that five specific markers can in fact collectively provide improved diagnostic outcomes relative either to these markers individually or to other groups of markers is both unexpected and unpredictable.
SUMMARY
[0034] Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.
[0035] As used herein, the term "derived from" shall be taken to indicate that a particular integer or group of integers has originated from the species specified, but has not necessarily been obtained directly from the specified source. Further, as used herein the singular forms of "a", "and" and "the" include plural referents unless the context clearly dictates otherwise.
[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
[0037] The subject specification contains nucleotide sequence information prepared using the program PatentIn Version 3.5, presented herein after the bibliography. Each nucleotide sequence is identified in the sequence listing by the numeric indicator <210> followed by the sequence identifier (e.g. <210>1, <210>2, etc.). The length, type of sequence (DNA, etc.) and source organism for each sequence is indicated by information provided in the numeric indicator fields <211>, <212> and <213>, respectively. Nucleotide sequences referred to in the specification are identified by the indicator SEQ ID NO: followed by the sequence identifier (e.g. SEQ ID NO:1, SEQ ID NO:2, etc.). The sequence identifier referred to in the specification correlates to the information provided in numeric indicator field <400> in the sequence listing, which is followed by the sequence identifier (e.g. <400>1, <400>2, etc.). That is SEQ ID NO:1 as detailed in the specification correlates to the sequence indicated as <400>1 in the sequence listing.
[0038] One aspect of the present invention is directed to a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of a DNA region selected from:
[0039] (i) the region, including 2 kb upstream of the transcription start site, defined by any two or more of Hg19 coordinates:
[0040] (1) chr12:24962958..25102393
[0041] (2) chr7:50344378...50472798
[0042] (3) chr6:391739..411443;
[0043] (4) chr12:52400748..52409671; and
[0044] (5) chr6:163834097..163834982; or
[0045] (ii) the gene region, including 2 kb upstream of any two or more of:
[0046] (1) BCAT1 (2) IKZF1 (3) IRF4 (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0047] In another aspect said method is directed to identifying biological samples in which any one of said DNA regions exhibits a higher level of methylation.
[0048] In still another aspect said method is directed to identifying biological samples in which two or more of said DNA regions exhibit a higher level of methylation.
[0049] In yet another aspect there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0050] the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0051] (1) chr12:24962958..25102393; and
[0052] (2) chr7:50344378...50472798;
[0053] and optionally one or more of (3) chr6:391739..411443, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0054] (ii) the gene region, including 2 kb upstream of:
[0055] (1) BCAT1; and
[0056] (2) IKZF1;
[0057] and optionally one or more of (3) IRF4, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0058] In one embodiment of this aspect, the gene marker panel which is screened for is:
[0059] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0060] (1) chr12:24962958..25102393
[0061] (2) chr7:50344378...50472798; and
[0062] (3) chr6:391739..411443; or
[0063] (ii) the gene region, including 2 kb upstream of:
[0064] (1) BCAT1, (2) IKZFI and (3) IRF4.
[0065] In another embodiment of this aspect, the gene marker panel which is screened for is:
[0066] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0067] (1) chr12:24962958..25102393
[0068] (2) chr7:50344378...50472798 and
[0069] (4) chr12:52400748..52409671; or
[0070] (ii) the gene region, including 2 kb upstream of:
[0071] (1) BCAT1, (2) IKZFI; and (4) GRASP.
[0072] In still another embodiment of this aspect, the gene marker panel which is screened for is:
[0073] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0074] (1) chr12:24962958..25102393
[0075] (2) chr7:50344378...50472798 and
[0076] (5) chr6:163834097..163834982; or
[0077] (ii) the gene region, including 2 kb upstream of:
[0078] (1) BCATI, (2) 1KZF1 and (5) CAHM
[0079] In still yet another embodiment of this aspect, the gene marker panel which is screened for is:
[0080] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0081] (1) chr12:24962958..25102393
[0082] (2) chr7:50344378...50472798
[0083] (3) chr6:391739..411443; and
[0084] (4) chr12:52400748..52409671; or
[0085] (ii) the gene region, including 2 kb upstream of:
[0086] (1) BCAT1, (2) IKZF1, (3) IRF4 and (4) GRASP.
[0087] In yet still another embodiment of this aspect, the gene marker panel which is screened for is:
[0088] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0089] (1) chr12:24962958..25102393
[0090] (2) chr7:50344378...50472798
[0091] (3) chr6:391739..411443; and
[0092] (5) chr6:163834097..163834982; or
[0093] (ii) the gene region, including 2 kb upstream of:
[0094] (1) BCAT1, (2) IKZF1, (3) IRF4 and (5) CAHM
[0095] In a further embodiment of this aspect, the gene marker panel which is screened for is:
[0096] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0097] (1) chr12:24962958..25102393
[0098] (2) chr7:50344378...50472798
[0099] (4) chr12:52400748..52409671 and
[0100] (5) chr6:163834097..163834982; or
[0101] (ii) the gene region, including 2 kb upstream of:
[0102] (1) BCAT1, (2) 1KZF1, (4) GRASP and (5) CAHM
[0103] In yet another further embodiment of this aspect, the gene marker panel which is screened for is:
[0104] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0105] (1) chr12:24962958..25102393
[0106] (2) chr7:50344378...50472798
[0107] (3) chr6:391739..411443
[0108] (4) chr12:52400748..52409671 and
[0109] (5) chr6:163834097..163834982; or
[0110] (ii) the gene region, including 2 kb upstream of:
[0111] (1) BCAT1, (2) IKZF1, (3) IRF4, (4) GRASP and (5) CAHM.
[0112] In another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0113] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0114] (1) chr12:24962958..25102393; and
[0115] (5) chr6:163834097..163834982;
[0116] and optionally one or more of (2) chr7:50344378...50472798, (3) chr6:391739..411443; and (4) chr12:52400748..52409671; or
[0117] (ii) the gene region, including 2 kb upstream of:
[0118] (1) BCAT1; and
[0119] (5) CAHM;
[0120] and optionally one or more of (2) IKZF1, (3) IRF4 and (4) GRASP in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0121] In still another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0122] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0123] (2) chr7:50344378..50472798; and
[0124] (5) chr6:163834097..163834982;
[0125] and optionally one or more of (1) chr12:24962958..25102393, (3) chr6:391739..411443 and (4) chr12:52400748..52409671; or
[0126] (ii) the gene region, including 2 kb upstream of:
[0127] (2) IKZF 1; and
[0128] (5) CAHM;
[0129] and optionally one or more of (1) BCAT1, (3) IRF4 and (4) GRASP in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0130] In a further embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0131] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0132] (1) chr12:24962958..25102393; and
[0133] (3) chr6:391739..411443;
[0134] and optionally one or more of (2) chr7:50344378...50472798, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0135] (ii) the gene region, including 2 kb upstream of:
[0136] (1) BCAT1; and
[0137] (3) IRF4;
[0138] and optionally one or more of (2) IKZF 1, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0139] In yet another further embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0140] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0141] (1) chr12:24962958..25102393; and
[0142] (4) chr12:52400748..52409671;
[0143] and optionally one or more of (2) chr7:50344378...50472798, (3) chr6:391739..411443 and (5) chr6:163834097..163834982; or
[0144] (ii) the gene region, including 2 kb upstream of:
[0145] (1) BCAT1; and
[0146] (4) GRASP;
[0147] and optionally one or more of (2) IKZF1, (3) IRF4 and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0148] In still another further embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0149] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0150] (2) chr7:50344378..50472798; and
[0151] (3) chr6:391739..411443;
[0152] and optionally one or more of (1) chr12:24962958..25102393, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0153] (ii) the gene region, including 2 kb upstream of:
[0154] (2) IKZF 1; and
[0155] (3) IRF4;
[0156] and optionally one or more of (1) BCAT1, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0157] In yet still another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0158] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0159] (2) chr7:50344378..50472798; and
[0160] (4) chr12:52400748..52409671;
[0161] and optionally one or more of (1) chr12:24962958..25102393, (3) chr6:391739..411443 and (5) chr6:163834097..163834982; or
[0162] (ii) the gene region, including 2 kb upstream of:
[0163] (2) IKZF 1; and
[0164] (4) GRASP;
[0165] and optionally one or more of (1) BCAT1, (3) IRF4 and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0166] In still yet another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0167] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0168] (3) chr6:391739..411443; and
[0169] (4) chr12:52400748..52409671;
[0170] and optionally one or more of (1) chr12:24962958..25102393, (2) chr7:50344378...50472798 and (5) chr6:163834097..163834982; or
[0171] (ii) the gene region, including 2 kb upstream of:
[0172] (3) IRF4; and
[0173] (4) GRASP;
[0174] and optionally one or more of (1) BCAT1, (2) IKZF1 and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0175] In another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0176] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0177] (3) chr6:391739..411443; and
[0178] (5) chr6:163834097..163834982;
[0179] and optionally one or more of (1) chr12:24962958..25102393, (2) chr7:50344378...50472798 and (4) chr12:52400748..52409671; or
[0180] (ii) the gene region, including 2 kb upstream of:
[0181] (3) IRF4; and
[0182] (5) CAHM;
[0183] and optionally one or more of (1) BCAT1, (2) IKZF1 and (4) GRASP in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0184] The subregions which have been determined to exhibit particular utility are listed below with reference to the gene and chromosomal region within which they are found:
[0185] (1) BCAT subregions chr12:25101992-25102093 (SEQ ID NO:1 or corresponding minus strand) and chr12:25101909-25101995 (SEQ ID NO:2 or corresponding minus strand)
[0186] (2) IKZF1 subregions: chr7:50343867-50343961 (SEQ ID NO:3 or corresponding minus strand) and chr7:50343804-5033895 (SEQ ID NO:4 or corresponding minus strand)
[0187] (3) IRF4 subregions chr6:392036-392145 (SEQ ID NO:5 or corresponding minus strand)
[0188] (4) GRASP subregions: chr12:52399672-52399922, chr12:52400821-52401051 (SEQ ID NO:6 or corresponding minus strand), chr12:52401407-52401664 (SEQ ID NO:7 or corresponding minus strand) chr12:52400866-52400973 and Chr12:52401107-52401664.
[0189] (5) CAHM subregions: chr6:163834295-163834500 (SEQ ID NO:8 or corresponding minus strand), chr6:163834621-163834906, chr6:163834393-163834455 and chr6:163834393-163834519.
[0190] To the extent that the method of the present invention includes analyzing the methylation of GRASP, the subject residues are:
TABLE-US-00001 chr12:52399713 chr12:52399731 chr12:52399749 chr12:52399783 chr12:52399796 chr12:52399808 chr12:52399823 chr12:52399835 chr12:52399891 chr12:52400847 chr12:52400850 chr12:52400859 chr12:52400866 chr12:52400869 chr12:52400873 chr12:52400881 chr12:52400886 chr12:52400893 chr12:52400895 chr12:52400899 chr12:52400902 chr12:52400907 chr12:52400913 chr12:52400919 chr12:52400932 chr12:52400938 chr12:52400958 chr12:52400962 chr12:52400971 chr12:52400973 chr12:52400976 chr12:52400998 chr12:52401008 chr12:52401010 chr12:52401012 chr12:52401016 chr12:52401019 chr12:52401025 chr12:52401041 chr12:52401044 chr12:52401053 chr12:52401060 chr12:52401064 chr12:52401092 chr12:52401118 chr12:52401438 chr12:52401448 chr12:52401460 chr12:52401465 chr12:52401474 chr12:52401477 chr12:52401479 chr12:52401483 chr12:52401504 chr12:52401514 chr12:52401523 chr12:52401540 chr12:52401553 chr12:52401576 chr12:52401588 chr12:52401595 chr12:52401599 chr12:52401604 chr12:52401606 chr12:52401634 chr12:52401640 chr12:52401644 chr12:52401659 chr12:52401160 chr12:52401165 chr12:52401174 chr12:52401177 chr12:52401179 chr12:52401183 chr12:52401204 chr12:52401215 chr12:52401223 chr12:52401240 chr12:52401253 chr12:52401288 chr12:52401295 chr12:52401299 chr12:52401304 chr12:52401334 chr12:52401340 chr12:52401344 chr12:52401359
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0191] To the extent that the method of the present invention includes analyzing CAHM, the subject residues are:
TABLE-US-00002 chr6: 163834330 chr6: 163834332 chr6: 163834357 chr6: 163834373 chr6: 163834384 chr6: 163834390 chr6: 163834392 chr6: 163834406 chr6: 163834412 chr6: 163834419 chr6: 163834443 chr6: 163834448 chr6: 163834452 chr6: 163834464 chr6: 163834483 chr6: 163834653 chr6: 163834660 chr6: 163834672 chr6: 163834675 chr6: 163834678 chr6: 163834681 chr6: 163834815 chr6: 163834824 chr6: 163834835 chr6:163834840 chr6:163834853 chr6:163834855 chr6:163834858 chr6:163834863 chr6:163834869 chr6:163834872
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0192] To the extent that the method of the present invention includes analyzing IKZF1, the subject residues are:
TABLE-US-00003 chr7: 50343869 chr7:50343872 chr7:50343883 chr7:50343889 chr7:50343890 chr7: 50343897 chr7: 50343907 chr7:50343909 chr7:50343914 chr7:50343934 chr7:50343939 chr7:50343950 chr7:50343959 chr7:50343805 chr7: 50343822 chr7: 50343824 chr7:50343826 chr7: 50343829 chr7:50343831 chr7:50343833 chr7:50343838 chr7: 50343847 chr7:50343850 chr7:50343858 chr7: 50343864 chr7:50343869 chr7: 50343872 chr7: 50343890
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0193] To the extent that the method of the present invention includes analyzing IRF4, the subject residues are:
TABLE-US-00004 chr6:392036 chr6:392047 chr6:392049 chr6:392057 chr6:392060 chr6:392066 chr6:392080 chr6:392094 chr6:392102 chr6:392131
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0194] Another aspect of the present invention is directed to a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the level of expression of a DNA region selected from:
[0195] (i) the region, including 2 kb upstream of the transcription start site, defined by any two or more of Hg19 coordinates:
[0196] (1) chr12:24962958..25102393
[0197] (2) chr7:50344378...50472798
[0198] (3) chr6:391739..411443; or
[0199] (4) chr12:52400748..52409671; and
[0200] (5) chr6:163834097..163834982; or
[0201] (ii) the gene region, including 2 kb upstream of any two or more of:
[0202] (1) BCAT1 (2) IKZF1 (3) IRF4 (4) GRASP and (5) CAHM in a biological sample from said individual wherein a lower level of expression of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a neoplastic state.
BRIEF DESCRIPTION OF THE DRAWINGS
[0203] FIG. 1 depicts the genomic sequence of GRASP.
[0204] FIG. 2 depicts the genomic sequence of CAHM.
[0205] FIG. 3 depicts the genomic sequence of IRF4.
[0206] FIG. 4 depicts the genomic sequence of BCAT1.
[0207] FIG. 5 depicts the genomic sequence of IKZF 1.
DETAILED DESCRIPTION
[0208] The present invention is predicated, in part, on the determination that the change in methylation pattern of a panel of gene markers can provide a higher level of either diagnostic specificity or diagnostic sensitivity when tested collectively than if any one of these markers is tested either in isolation or together with markers other than those specified herein. This finding has therefore now facilitated the development of an improved test for diagnosing, prognosing or monitoring neoplasms of the large intestine based on assessing the methylation of two or more of the gene markers BCAT1, IKZF1, CAHM, GRASP and IRF4.
[0209] In accordance with the present invention, it has been determined that certain specific panels of genes are modulated, in terms of differential changes to their levels of methylation, depending on whether or not the cell in issue is neoplastic or not. It should be understood that the genes in issue are described herein both by reference to their name and their chromosomal coordinates. The chromosomal coordinates are consistent with the human genome database version Hg19 which was released in February 2009 (herein referred to as "Hg19 coordinates").
[0210] Accordingly, one aspect of the present invention is directed to a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of a DNA region selected from:
[0211] (i) the region, including 2 kb upstream of the transcription start site, defined by any two or more of Hg19 coordinates:
[0212] (1) chr12:24962958..25102393
[0213] (2) chr7:50344378...50472798
[0214] (3) chr6:391739..411443;
[0215] (4) chr12:52400748..52409671; and
[0216] (5) chr6:163834097..163834982; or
[0217] (ii) the gene region, including 2 kb upstream of any two or more of:
[0218] (1) BCAT1 (2) IKZF1 (3) IRF4 (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0219] In one embodiment, said method is directed to identifying biological samples in which any one of said DNA regions exhibits a higher level of methylation.
[0220] In another embodiment, said method is directed to identifying biological samples in which two or more of said DNA regions exhibit a higher level of methylation.
[0221] Without limiting the present invention to any one theory or mode of action, the panel of DNA regions (markers) specified herein provide not only an improved diagnostic outcome relative to prior art methods but, in addition, enable the development of a screening method which can be designed to focus on providing either a high level of diagnostic specificity or a high level of diagnostic sensitivity. As would be understood by the person of skill in the art, in the context of diagnostics "sensitivity" defines the proportion of positive results which are correctly identified, that is, the percentage of individuals correctly identified as having the disease in issue. "Specificity", however, defines the proportion of negative results which are correctly identified, that is, the percentage of individuals correctly identified as not having the disease in issue.
[0222] In the context of the present invention it has been determined that screening a patient sample for the methylation status of the specified panel of markers can be designed to provide either a diagnostic result which exhibits a high level of specificity or a diagnostic result which exhibits a high level of sensitivity.
[0223] Where a high level of sensitivity is sought, the screening method is designed to identify samples in which any one of the markers of the panel exhibits increased methylation relative to control levels. That is, not all of the markers are required to exhibit hypermethylation in order to define the result as positive. Where a higher level of sensitivity is sought, the level of specificity is inherently reduced. However, if it is desired to pursue a higher level of specificity (which may reduce the level of sensitivity) then the method is designed to identify samples in which two or more of the panel of DNA regions exhibit increased methylation.
[0224] Accordingly, to the extent that the present invention is directed to embodiments of the method in which "any one of" the DNA regions (markers) of the specified panel exhibits a higher level of methylation, these embodiments are designed to achieve results exhibiting increased sensitivity based on any one of the markers in the panel being hypermethylated. It should be understood that it need not be the same marker which is hypermethylated in each sample. Rather, it is simply that one of the markers which forms part of the panel is hypermethylated. It should also be understood that in relation to some samples, two or more of the markers of the panel may be hypermethylated. These samples should be understood to nevertheless fall within the scope of this embodiment of the invention since this embodiment is not excluding the situation where multiple markers are hypermethylated but is merely including within its scope all those samples where as few as one marker are hypermethylated. Overall these data will provide increased sensitivity but reduced specificity.
[0225] To the extent that the present invention is directed to embodiments of the method in which "two or more" of the DNA regions (markers) of the specified panel exhibit a higher level of methylation, these embodiments are designed to achieve a higher level of specificity. This is achieved by virtue of the fact that at least two, if not more, of the specified panel of markers are determined to be hypermethylated.
[0226] Reference to "large intestine" should be understood as a reference to a cell derived from one of the eight anatomical regions of the large intestine, which regions commence after the terminal region of the ileum, these being:
[0227] (i) the cecum;
[0228] (ii) the ascending colon;
[0229] (iii) the transverse colon;
[0230] (iv) the descending colon;
[0231] (v) the sigmoid colon;
[0232] (vi) the rectum;
[0233] (vii) the splenic flexure; and
[0234] (viii) the hepatic flexure.
[0235] Reference to "neoplasm" should be understood as a reference to a lesion, tumor or other encapsulated or unencapsulated mass or other form of growth which comprises neoplastic cells. A "neoplastic cell" should be understood as a reference to a cell exhibiting abnormal growth. The term "growth" should be understood in its broadest sense and includes reference to proliferation. In this regard, an example of abnormal cell growth is the uncontrolled proliferation of a cell. Another example is failed apoptosis in a cell, thus prolonging its usual life span. The neoplastic cell may be a benign cell or a malignant cell. In a preferred embodiment, the subject neoplasm is an adenoma or an adenocarcinoma. Without limiting the present invention to any one theory or mode of action, an adenoma is generally a benign tumor of epithelial origin which is either derived from epithelial tissue or exhibits clearly defined epithelial structures. These structures may take on a glandular appearance. It can comprise a malignant cell population within the adenoma, such as occurs with the progression of a benign adenoma or benign neoplastic legion to a malignant adenocarcinoma.
[0236] Preferably, said neoplastic cell is an adenoma or adenocarcinoma and even more preferably a colorectal adenoma or adenocarcinoma.
[0237] Reference to "DNA region" should be understood as a reference to a specific section of genomic DNA. These DNA regions are specified either by reference to a gene name or a set of chromosomal coordinates. Both the gene names and the chromosomal coordinates would be well known to, and understood by, the person of skill in the art. As detailed hereinbefore, the chromosomal coordinates correspond to the Hg19 version of the genome. In general, a gene can be routinely identified by reference to its name, via which both its sequences and chromosomal location can be routinely obtained, or by reference to its chromosomal coordinates, via which both the gene name and its sequence can also be routinely obtained.
[0238] Reference to each of the genes/DNA regions detailed above should be understood as a reference to all forms of these molecules and to fragments or variants thereof. As would be appreciated by the person of skill in the art, some genes are known to exhibit allelic variation between individuals or single nucleotide polymorphisms. SNPs encompass insertions and deletions of varying size and simple sequence repeats, such as dinucleotide and trinucleotide repeats. Variants include nucleic acid sequences from the same region sharing at least 90%, 95%, 98%, 99% sequence identity i.e. having one or more deletions, additions, substitutions, inverted sequences etc. relative to the DNA regions described herein. Accordingly, the present invention should be understood to extend to such variants which, in terms of the present diagnostic applications, achieve the same outcome despite the fact that minor genetic variations between the actual nucleic acid sequences may exist between individuals. The present invention should therefore be understood to extend to all forms of DNA which arise from any other mutation, polymorphic or allelic variation.
[0239] It should be understood that the "individual" who is the subject of testing may be any human or non-human mammal. Examples of non-human mammals includes primates, livestock animals (e.g. horses, cattle, sheep, pigs, donkeys), laboratory test animals (e.g. mice, rats, rabbits, guinea pigs), companion animals (e.g. dogs, cats) and captive wild animals (e.g. deer, foxes).
[0240] Preferably the mammal is a human.
[0241] The panel of genes which has been identified demonstrates increased methylation in large intestine neoplastic cells relative to corresponding non-neoplastic cells. This increased methylation is, in some cases, localized to a few specific CpG sites within the DNA region while in other cases it is observed across a wide range of CpG sites. However, although specific regions from all genes exhibit increased methylation and are therefore useful diagnostic markers, it is the analysis of these specific markers as a panel which has provided an independent and very significant improvement over the sensitivity and specificity could be obtainable over these markers are analyzed individually. This improvement is also significant even when considered against the sensitivity and specificity obtainable using other markers known to exhibit increased methylation as a marker of the onset of a large intestine neoplasm. Accordingly, the method of the present invention has now provided a means of achieving a higher level of sensitivity and specificity than has been achievable to date.
[0242] In one aspect there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0243] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0244] (1) chr12:24962958..25102393; and
[0245] (2) chr7:50344378...50472798;
[0246] and optionally one or more of (3) chr6:391739..411443, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0247] (ii) the gene region, including 2 kb upstream of:
[0248] (1) BCAT1; and
[0249] (2) IKZF1;
[0250] and optionally one or more of (3) IRF4, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0251] In one embodiment of this aspect, the gene marker panel which is screened for is:
[0252] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0253] (1) chr12:24962958..25102393
[0254] (2) chr7:50344378...50472798; and
[0255] (3) chr6:391739..411443; or
[0256] (ii) the gene region, including 2 kb upstream of:
[0257] (1) BCAT1, (2) IKZF1 and (3) IRF4.
[0258] In another embodiment of this aspect, the gene marker panel which is screened for is:
[0259] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0260] (1) chr12:24962958..25102393
[0261] (2) chr7:50344378...50472798 and
[0262] (4) chr12:52400748..52409671; or
[0263] (ii) the gene region, including 2 kb upstream of:
[0264] (1) BCAT1, (2) IKZF1; and (4) GRASP.
[0265] In still another embodiment of this aspect, the gene marker panel which is screened for is:
[0266] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0267] (1) chr12:24962958..25102393
[0268] (2) chr7:50344378...50472798 and
[0269] (5) chr6:163834097..163834982; or
[0270] (ii) the gene region, including 2 kb upstream of:
[0271] (1) BCAT1, (2) IKZF1 and (5) CAHM
[0272] In still yet another embodiment of this aspect, the gene marker panel which is screened for is:
[0273] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0274] (1) chr12:24962958..25102393
[0275] (2) chr7:50344378...50472798
[0276] (3) chr6:391739..411443; and
[0277] (4) chr12:52400748..52409671; or
[0278] (ii) the gene region, including 2 kb upstream of:
[0279] (1) BCAT1, (2) IKZF1, (3) IRF4 and (4) GRASP.
[0280] In yet still another embodiment of this aspect, the gene marker panel which is screened for is:
[0281] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0282] (1) chr12:24962958..25102393
[0283] (2) chr7:50344378...50472798
[0284] (3) chr6:391739..411443; and
[0285] (5) chr6:163834097..163834982; or
[0286] (ii) the gene region, including 2 kb upstream of:
[0287] (1) BCAT1, (2) IKZF1, (3) IRF4 and (5) CAHM
[0288] In a further embodiment of this aspect, the gene marker panel which is screened for is:
[0289] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0290] (1) chr12:24962958..25102393
[0291] (2) chr7:50344378...50472798
[0292] (4) chr12:52400748..52409671 and
[0293] (5) chr6:163834097..163834982; or
[0294] (ii) the gene region, including 2 kb upstream of:
[0295] (1) BCAT1, (2) IKZF1, (4) GRASP and (5) CAHM
[0296] In yet another further embodiment of this aspect, the gene marker panel which is screened for is:
[0297] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0298] (1) chr12:24962958..25102393
[0299] (2) chr7:50344378...50472798
[0300] (3) chr6:391739..411443
[0301] (4) chr12:52400748..52409671 and
[0302] (5) chr6:163834097..163834982; or
[0303] (ii) the gene region, including 2 kb upstream of:
[0304] (1) BCAT1, (2) IKZF1, (3) IRF4, (4) GRASP and (5) CAHM
[0305] In another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0306] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0307] (1) chr12:24962958..25102393; and
[0308] (5) chr6:163834097..163834982;
[0309] and optionally one or more of (2) chr7:50344378...50472798, (3) chr6:391739..411443; and (4) chr12:52400748..52409671; or
[0310] (ii) the gene region, including 2 kb upstream of:
[0311] (1) BCAT1; and
[0312] (5) CAHM;
[0313] and optionally one or more of (2) IKZF 1, (3) IRF4 and (4) GRASP in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0314] In still another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0315] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0316] (2) chr7:50344378..50472798; and
[0317] (5) chr6:163834097..163834982;
[0318] and optionally one or more of (1) chr12:24962958..25102393, (3) chr6:391739..411443 and (4) chr12:52400748..52409671; or
[0319] (ii) the gene region, including 2 kb upstream of:
[0320] (2) IKZF 1; and
[0321] (5) CAHM;
[0322] and optionally one or more of (1) BCAT1, (3) IRF4 and (4) GRASP in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0323] In a further embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0324] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0325] (1) chr12:24962958..25102393; and
[0326] (3) chr6:391739..411443;
[0327] and optionally one or more of (2) chr7:50344378...50472798, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0328] (ii) the gene region, including 2 kb upstream of:
[0329] (1) BCAT1; and
[0330] (3) IRF4;
[0331] and optionally one or more of (2) IKZF 1, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0332] In yet another further embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0333] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0334] (1) chr12:24962958..25102393; and
[0335] (4) chr12:52400748..52409671;
[0336] and optionally one or more of (2) chr7:50344378...50472798, (3) chr6:391739..411443 and (5) chr6:163834097..163834982; or
[0337] (ii) the gene region, including 2 kb upstream of:
[0338] (1) BCAT1; and
[0339] (4) GRASP;
[0340] and optionally one or more of (2) IKZF1, (3) IRF4 and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0341] In still another further embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0342] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0343] (2) chr7:50344378..50472798; and
[0344] (3) chr6:391739..411443;
[0345] and optionally one or more of (1) chr12:24962958..25102393, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0346] (ii) the gene region, including 2 kb upstream of:
[0347] (2) IKZF 1; and
[0348] (3) IRF4;
[0349] and optionally one or more of (1) BCAT1, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0350] In yet still another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0351] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0352] (2) chr7:50344378..50472798; and
[0353] (4) chr12:52400748..52409671;
[0354] and optionally one or more of (1) chr12:24962958..25102393, (3) chr6:391739..411443 and (5) chr6:163834097..163834982; or
[0355] (ii) the gene region, including 2 kb upstream of:
[0356] (2) IKZF 1; and
[0357] (4) GRASP;
[0358] and optionally one or more of (1) BCAT1, (3) IRF4 and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0359] In still yet another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0360] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0361] (3) chr6:391739..411443; and
[0362] (4) chr12:52400748..52409671;
[0363] and optionally one or more of (1) chr12:24962958..25102393, (2) chr7:50344378...50472798 and (5) chr6:163834097..163834982; or
[0364] (ii) the gene region, including 2 kb upstream of:
[0365] (3) IRF4; and
[0366] (4) GRASP;
[0367] and optionally one or more of (1) BCAT1, (2) IKZF1 and (5) CAHM in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0368] In another embodiment there is provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the methylation status of:
[0369] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0370] (3) chr6:391739..411443; and
[0371] (5) chr6:163834097..163834982;
[0372] and optionally one or more of (1) chr12:24962958..25102393, (2) chr7:50344378...50472798 and (4) chr12:52400748..52409671; or
[0373] (ii) the gene region, including 2 kb upstream of:
[0374] (3) IRF4; and
[0375] (5) CAHM;
[0376] and optionally one or more of (1) BCAT1, (2) IKZF1 and (4) GRASP in a biological sample from said individual wherein a higher level of methylation of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplastic state.
[0377] In accordance with these aspects and embodiments, in yet another embodiment said control level is a non-neoplastic level.
[0378] In one embodiment, said method is directed to identifying biological samples in which any one of said DNA regions exhibits a higher level of methylation.
[0379] In another embodiment, said method is directed to identifying biological samples in which two or more of said DNA regions exhibits a higher level of methylation.
[0380] Still further, in another embodiment, said large intestine tissue is preferably colorectal tissue.
[0381] In still another embodiment, the neoplasm is malignant, such as a carcinoma.
[0382] In a further embodiment, the neoplasm is non-malignant, such as an adenoma.
[0383] In terms of screening for the methylation of these gene regions, it should be understood that the assays can be designed to screen either the specific regions listed herein (which correspond to the "plus" strand of the gene) or the complementary "minus" strand. It is well within the skill of the person in the art to choose which strand to analyze and to target that strand based on the chromosomal coordinates provided herein. In some circumstances, assays may be established to screen both strands.
[0384] It should be understood that one may screen for the specified panel of markers exclusively or one may elect to additionally screen for other markers, such as other DNA hypermethylation markers, other RNA expression level markers or other protein markers. These other markers may, for example, provide additional information in relation to the health status of the patient in issue.
[0385] Without limiting the present invention to any one theory or mode of action, although measuring the methylation levels across these DNA regions is diagnostic of a large intestine neoplastic condition, it has been determined that discrete subregions are particularly useful in this regard since these subregions contain a high density of CpG dinucleotides which are frequently hypermethylated in large intestine neoplasias, such as colorectal cancers. This finding renders these subregions a particularly useful target for analysis since it both simplifies the screening process due to a shorter more clearly defined region of DNA requiring analysis and, further, the fact that the results from these regions will provide a significantly more definitive result in relation to the presence, or not, of hypermethylation than would be obtained if analysis was performed across the DNA region as a whole. This finding therefore both simplifies the screening process and increases the sensitivity and specificity of large intestine neoplasia diagnosis.
[0386] The subregions which have been determined to exhibit particular utility are listed below with reference to the gene and chromosomal region within which they are found:
[0387] (1) BCAT subregions chr12:25101992-25102093 (SEQ ID NO:1 or corresponding minus strand) and chr12:25101909-25101995 (SEQ ID NO:2 or corresponding minus strand)
[0388] (2) IKZF1 subregions: chr7:50343867-50343961 (SEQ ID NO:3 or corresponding minus strand) and chr7:50343804-5033895 (SEQ ID NO:4 or corresponding minus strand)
[0389] (3) IRF4 subregions chr6:392036-392145 (SEQ ID NO:5 or corresponding minus strand)
[0390] (4) GRASP subregions: chr12:52399672-52399922, chr12:52400821-52401051 (SEQ ID NO:6 or corresponding minus strand), chr12:52401407-52401664 (SEQ ID NO:7 or corresponding minus strand) chr12:52400866-52400973 and Chr12:52401107-52401664.
[0391] (5) CAHM subregions: chr6:163834295-163834500 (SEQ ID NO:8), chr6:163834621-163834906, chr6:163834393-163834455 and chr6:163834393-163834519.
[0392] Without limiting the present invention to any one theory or mode of action, the skilled person may screen one or more subregions for each gene marker.
[0393] In one embodiment, the methylation marker subregions tested for each selected gene marker are:
[0394] (1) The BCAT subregion defined by SEQ ID NO:1 or SEQ ID NO:2 or corresponding minus strand;
[0395] (2) The IKZF1 subregion defined by SEQ ID NO:3 or SEQ ID NO:4 or corresponding minus strand;
[0396] (3) The IRF4 subregion defined by SEQ ID NO:5 or corresponding minus strand;
[0397] (4) The GRASP subregion defined by SEQ ID NO:6 or 7 or corresponding minus strands; and
[0398] (5) The CAHM subregion defined by SEQ ID NO:8 or corresponding minus strand.
[0399] Without limiting the present invention to any one theory or mode of action, DNA methylation is universal in bacteria, plants, and animals. DNA methylation is a type of chemical modification of DNA that is stable over rounds of cell division but does not involve changes in the underlying DNA sequence of the organism. Chromatin and DNA modifications are two important features of epigenetics and play a role in the process of cellular differentiation, allowing cells to stably maintain different characteristics despite containing the same genomic material. In eukaryotic organisms DNA methylation occurs only at the number 5 carbon of the cytosine pyrimidine ring. In mammals, DNA methylation occurs mostly at the number 5 carbon of the cytosine of a CpG dinucleotide. CpG dinucleotides comprise approximately 1% human genome.
[0400] 70-80% of all CpGs are methylated. CpGs may be grouped in clusters called "CpG islands" that are present in the 5' regulatory regions of many genes and are frequently unmethylated. In many disease processes such as cancer, gene promoters and/or CpG islands acquire abnormal hypermethylation, which is associated with heritable transcriptional silencing. DNA methylation may impact the transcription of genes in two ways. First, the methylation of DNA may itself physically impede the binding of transcriptional proteins to the gene, thus blocking transcription. Second, methylated DNA may be bound by proteins known as Methyl-CpG-binding domain proteins (MBDs). MBD proteins then recruit additional proteins to the locus, such as histone deacetylases and other chromatin remodeling proteins that can modify histones, thereby forming compact, inactive chromatin termed silent chromatin. This link between DNA methylation and chromatin structure is very important. In particular, loss of Methyl-CpG-binding Protein 2 (MeCP2) has been implicated in Rett syndrome and Methyl-CpG binding domain protein 2 (MBD2) mediates the transcriptional silencing of hypermethylated genes in cancer.
[0401] In humans, the process of DNA methylation is carried out by three enzymes, DNA methyltransferase 1, 3a and 3b (DNMT1, DNMT3a, DNMT3b). It is thought that DNMT3a and DNMT3b are the de novo methyltransferases that set up DNA methylation patterns early in development. DNMT1 is the proposed maintenance methyltransferase that is responsible for copying DNA methylation patterns to the daughter strands during DNA replication. DNMT3L is a protein that is homologous to the other DNMT3s but has no catalytic activity. Instead, DNMT3L assists the de novo methyltransferases by increasing their ability to bind to DNA and stimulating their activity. Finally, DNMT2 has been identified as an "enigmatic" DNA methyltransferase homolog, containing all 10 sequence motifs common to all DNA methyltransferases; however, DNMT2 may not methylate DNA but instead has been shown to methylate a small RNA.
[0402] "Methylation status" should therefore be understood as a reference to the presence, absence and/or quantity of methylation at a particular nucleotide, or nucleotides, within a DNA region. The methylation status of a particular DNA sequence (e.g. DNA region as described herein) can indicate the methylation state of every base in the sequence or can indicate the methylation state of a subset of the base pairs (e.g., of cytosines or the methylation state of one or more specific restriction enzyme recognition sequences) within the sequence, or can indicate information regarding regional methylation density within the sequence without providing precise information of where in the sequence the methylation occurs. The methylation status can optionally be represented or indicated by a "methylation value." A methylation value can be generated, for example, by quantifying the amount of intact DNA present following restriction digestion with a methylation dependent restriction enzyme. In this example, if a particular sequence in the DNA is quantified using quantitative PCR, an amount of template DNA approximately equal to a mock treated control indicates the sequence is not highly methylated whereas an amount of template substantially less than occurs in the mock treated sample indicates the presence of methylated DNA at the sequence. Accordingly, a value, i.e., a methylation value, for example from the above-described example, represents the methylation status and can thus be used as a quantitative indicator of the methylation status. This is of particular use when it is desirable to compare the methylation status of a sequence in a sample to a threshold value.
[0403] The method of the present invention is predicated on the comparison of the level of methylation of specific DNA regions of a biological sample with the control methylation levels of these DNA regions. The "control level" is the "normal level", which is the level of methylation of the DNA region of a corresponding large intestine cell or cellular population which is not neoplastic or in another biological sample from which DNA may be isolated for assay.
[0404] The normal (or "non-neoplastic") methylation level may be determined using non-neoplastic tissues derived from the same individual who is the subject of testing. However, it would be appreciated that this may be quite invasive for the individual concerned and it is therefore likely to be more convenient to analyze the test results relative to a standard result which reflects individual or collective results obtained from individuals other than the patient in issue. This latter form of analysis is in fact the preferred method of analysis since it enables the design of kits which require the collection and analysis of a single biological sample, being a test sample of interest. The standard results which provide the normal methylation level may be calculated by any suitable means which would be well known to the person of skill in the art. For example, a population of normal tissues can be assessed in terms of the level of methylation of the genes of the present invention, thereby providing a standard value or range of values against which all future test samples are analyzed. It should also be understood that the normal level may be determined from the subjects of a specific cohort and for use with respect to test samples derived from that cohort. Accordingly, there may be determined a number of standard values or ranges which correspond to cohorts which differ in respect of characteristics such as age, gender, ethnicity or health status. Said "normal level" may be a discrete level or a range of levels. An increase in the methylation level of the subject genes relative to normal levels is indicative of the tissue being neoplastic.
[0405] The term "methylation" shall be taken to mean the presence of a methyl group added by the action of a DNA methyl transferase enzyme to a cytosine base or bases in a region of nucleic acid, e.g. genomic DNA. As described herein, there are several methods known to those skilled in the art for determining the level or degree of methylation of nucleic acid.
[0406] By "higher level" is meant that there are a higher number of methylated CpG dinucleotides in the subject diagnosed than in a control sample, that is, either the proportion of DNA molecules methylated at a particular CpG site is higher or there are a higher number of separate CpG sites methylated in the subject. It should be understood that the terms "enhanced" and "increased" are used interchangeably with the term "higher".
[0407] In relation to detecting a "higher level" of methylation, it should be understood that in some situations the normal/control level will in fact correspond to the absence of any detectable methylation while the neoplastic level will correspond to the presence of methylation, per se. In this situation the diagnostic method is relatively simple since one need only screen for the mere presence of methylation (i.e. a qualitative assessment only), rather than assessing the methylation levels relative to a control level of methylation, which analysis necessarily involves a measure of quantification. Without limiting the present invention in any way, it is observed in blood-derived samples, for example, that in the context of some markers the change in methylation of that marker upon the onset of neoplasia is a shift from undetectable levels of methylation to the presence of detectable methylation. In these situations a relatively simple qualitative assessment is enabled where one need only screen a test sample to determine the presence or not of methylation. In the context of the definitions provided herein, reference to "higher level" encompasses both a relative increase in the level of methylation of a marker or the onset of methylation where previously none was evident. As detailed hereinbefore, the control level may be newly assessed for each patient or there may be a standard result against which all test samples are assessed. Where it is known that methylation is not present on the marker of interest, one need only screen for the presence or not of methylation since the control level is the absence of methylation and the "higher level" is thereby the presence of any amount of methylation.
[0408] The present invention is not to be limited by a precise number of methylated residues that are considered to be diagnostic of neoplasia in a subject, because some variation between patient samples will occur. The present invention is also not limited by positioning of the methylated residue.
[0409] Nevertheless, a number of specific cytosine residues which undergo hypermethylation within these subregions have also been identified. In another embodiment, therefore, a screening method can be employed which is specifically directed to assessing the methylation status of one or more of either these residues or the corresponding cytosine at position n+1 on the opposite DNA strand.
[0410] To this end, detailed in Table 1 are the cytosine residues which have been identified in this regard. It should be appreciated by the person of skill in the art that these individual residues are numbered by reference to Hg19, which also corresponds to the numbering of the specific subregions listed hereinbefore and which can be further identified when the coordinate numbering for each subregion is applied to the corresponding subregion sequences which are provided in the sequence listing. It should be understood that these residues have been identified in the context of the subregion DNA. However, there are other residues which are hypermethylated outside the subregions themselves but within the larger DNA region from which the subregions derive. Accordingly, these specified residues represent a particularly useful subset of individual cytosine residues which undergo hypermethylation within the context of the DNA regions and subregions herein disclosed. These individual residues are grouped below according to the DNA region within which they occur. These DNA regions are identified by reference to both the Hg19 chromosomal coordinates and the gene region name.
[0411] To the extent that the method of the present invention includes analyzing the methylation of GRASP, the subject residues are:
TABLE-US-00005 chr12:52399713 chr12:52399731 chr12:52399749 chr12:52399783 chr12:52399796 chr12:52399808 chr12:52399823 chr12:52399835 chr12:52399891 chr12:52400847 chr12:52400850 chr12:52400859 chr12:52400866 chr12:52400869 chr12:52400873 chr12:52400881 chr12:52400886 chr12:52400893 chr12:52400895 chr12:52400899 chr12:52400902 chr12:52400907 chr12:52400913 chr12:52400919 chr12:52400932 chr12:52400938 chr12:52400958 chr12:52400962 chr12:52400971 chr12:52400973 chr12:52400976 chr12:52400998 chr12:52401008 chr12:52401010 chr12:52401012 chr12:52401016 chr12:52401019 chr12:52401025 chr12:52401041 chr12:52401044 chr12:52401053 chr12:52401060 chr12:52401064 chr12:52401092 chr12:52401118 chr12:52401438 chr12:52401448 chr12:52401460 chr12:52401465 chr12:52401474 chr12:52401477 chr12:52401479 chr12:52401483 chr12:52401504 chr12:52401514 chr12:52401523 chr12:52401540 chr12:52401553 chr12:52401576 chr12:52401588 chr12:52401595 chr12:52401599 chr12:52401604 chr12:52401606 chr12:52401634 chr12:52401640 chr12:52401644 chr12:52401659 chr12:52401160 chr12:52401165 chr12:52401174 chr12:52401177 chr12:52401179 chr12:52401183 chr12:52401204 chr12:52401215 chr12:52401223 chr12:52401240 chr12:52401253 chr12:52401288 chr12:52401295 chr12:52401299 chr12:52401304 chr12:52401334 chr12:52401340 chr12:52401344 chr12:52401359
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0412] To the extent that the method of the present invention includes analyzing CAHM, the subject residues are:
TABLE-US-00006 chr6: 163834330 chr6:163834332 chr6: 163834357 chr6: 163834373 chr6:163834384 chr6: 163834390 chr6: 163834392 chr6:163834406 chr6: 163834412 chr6: 163834419 chr6:163834443 chr6: 163834448 chr6: 163834452 chr6:163834464 chr6: 163834483 chr6: 163834653 chr6:163834660 chr6: 163834672 chr6: 163834675 chr6:163834678 chr6: 163834681 chr6: 163834815 chr6:163834824 chr6: 163834835 chr6: 163834840 chr6:163834853 chr6: 163834855 chr6: 163834858 chr6:163834863 chr6: 163834869 chr6: 163834872
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0413] To the extent that the method of the present invention includes analyzing IKZF 1, the subject residues are:
TABLE-US-00007 chr7: 50343869 chr7: 50343872 chr7:50343883 chr7:50343889 chr7:50343890 chr7: 50343897 chr7: 50343907 chr7:50343909 chr7:50343914 chr7:50343934 chr7:50343939 chr7:50343950 chr7:50343959 chr7:50343805 chr7: 50343822 chr7: 50343824 chr7:50343826 chr7: 50343829 chr7:50343831 chr7:50343833 chr7:50343838 chr7: 50343847 chr7:50343850 chr7:50343858 chr7: 50343864 chr7:50343869 chr7: 50343872 chr7: 50343890
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0414] To the extent that the method of the present invention includes analyzing IRF4, the subject residues are:
TABLE-US-00008 chr6:392036 chr6:392047 chr6:392049 chr6:392057 chr6:392060 chr6:392066 chr6:392080 chr6:392094 chr6:392102 chr6:392131
or a corresponding cytosine at position n+1 on the opposite DNA strand.
[0415] The detection method of the present invention can be performed on any suitable biological sample. To this end, reference to a "biological sample" should be understood as a reference to any sample of biological material derived from an animal such as, but not limited to, cellular material, biofluids (e.g. blood), feces, tissue biopsy specimens, surgical specimens or fluid which has been introduced into the body of an animal and subsequently removed (such as, for example, the solution retrieved from an enema wash). The biological sample which is tested according to the method of the present invention may be tested directly or may require some form of treatment prior to testing. For example, a biopsy or surgical sample may require homogenization prior to testing or it may require sectioning for in situ testing of the qualitative expression levels of individual genes. Alternatively, a cell sample may require permeabilization prior to testing. Further, to the extent that the biological sample is not in liquid form, (if such form is required for testing) it may require the addition of a reagent, such as a buffer, to mobilize the sample.
[0416] To the extent that the DNA region of interest is present in a biological sample, the biological sample may be directly tested or else all or some of the nucleic acid present in the biological sample may be isolated prior to testing. In yet another example, the sample may be partially purified or otherwise enriched prior to analysis. For example, to the extent that a biological sample comprises a very diverse cell population, it may be desirable to enrich for a sub-population of particular interest. It is within the scope of the present invention for the target cell population or molecules derived therefrom to be treated prior to testing, for example, inactivation of live virus. It should also be understood that the biological sample may be freshly harvested or it may have been stored (for example by freezing) prior to testing or otherwise treated prior to testing (such as by undergoing culturing).
[0417] The choice of what type of sample is most suitable for testing in accordance with the method disclosed herein will be dependent on the nature of the situation. Preferably, said sample is a fecal (stool) sample, enema wash, surgical resection, tissue biopsy or blood sample (e.g. whole blood, serum or plasma).
[0418] More preferably, said biological sample is a blood sample, biopsy sample or stool sample.
[0419] As detailed hereinbefore, the present invention is designed to screen for a neoplastic cell or cellular population, which is located in the large intestine. Accordingly, reference to "cell or cellular population" should be understood as a reference to an individual cell or a group of cells. Said group of cells may be a diffuse population of cells, a cell suspension, an encapsulated population of cells or a population of cells which take the form of tissue.
[0420] Reference to the "onset" of a neoplasm, such as adenoma or adenocarcinoma, should be understood as a reference to one or more cells of that individual exhibiting dysplasia. In this regard, the adenoma or adenocarcinoma may be well developed in that a mass of dysplastic cells has developed. Alternatively, the adenoma or adenocarcinoma may be at a very early stage in that only relatively few abnormal cell divisions have occurred at the time of diagnosis. The present invention also extends to the assessment of an individual's predisposition to the development of a neoplasm, such as an adenoma or adenocarcinoma. Without limiting the present invention in any way, changed methylation levels may be indicative of that individual's predisposition to developing a neoplasia, such as the future development of an adenoma or adenocarcinoma or another adenoma or adenocarcinoma.
[0421] Although the preferred method is to assess methylation levels for the purpose of diagnosing neoplasia development or predisposition thereto, the detection of converse changes in the levels of said methylation may be desired under certain circumstances, for example, to monitor the effectiveness of therapeutic or prophylactic treatment directed to modulating a neoplastic condition, such as adenoma or adenocarcinoma development. For example, where elevated levels of methylation indicate that an individual has developed a condition characterized by adenoma or adenocarcinoma development, screening for a decrease in the levels of methylation subsequently to the onset of a therapeutic treatment regime may be utilized to indicate successful clearance of the neoplastic cells. In another example, one can use this method to test the tissue at the margins of a tumor resection in order to determine whether the full margin of the tumor has been removed.
[0422] The present method can therefore be used in the diagnosis, prognosis, classification, prediction of disease risk, detection of recurrence of disease, selection of treatment of a number of types of neoplasias and monitoring of neoplasias. A cancer at any stage of progression can be detected, such as primary, metastatic, and recurrent cancers.
[0423] The present invention provides methods for determining whether a mammal (e.g., a human) has a neoplasia of the large intestine, whether a biological sample taken from a mammal contains neoplastic cells or DNA derived from neoplastic cells, estimating the risk or likelihood of a mammal developing a neoplasm, monitoring the efficacy of anti-cancer treatment, or selecting the appropriate anti-cancer treatment in a mammal with cancer. Such methods are based on the determination that neoplastic cells have a different methylation status than normal cells in the DNA regions described herein. Accordingly, by determining whether or not a cell contains differentially methylated sequences in the DNA regions as described herein, it is possible to determine that a cell is neoplastic.
[0424] The method of the invention can be used to evaluate individuals known or suspected to have a neoplasia or as a routine clinical test, i.e., in an individual not necessarily suspected to have a neoplasia. Further diagnostic assays can be performed to confirm the status of neoplasia in the individual.
[0425] Further, the present methods may be used to assess the efficacy of a course of treatment. For example, the efficacy of an anti-cancer treatment can be assessed by monitoring DNA methylation of the sequences described herein over time in a mammal having cancer. For example, a reduction or absence of methylation in any of the diagnostic sequences of the invention in a biological sample taken from a mammal following a treatment, compared to a level in a sample taken from the mammal before, or earlier in, the treatment, indicates efficacious treatment.
[0426] The method of the present invention is therefore useful as a one-time test or as an on-going monitor of those individuals thought to be at risk of neoplasia development or as a monitor of the effectiveness of therapeutic or prophylactic treatment regimens directed to inhibiting or otherwise slowing neoplasia development. In these situations, mapping the modulation of methylation levels in any one or more classes of biological samples is a valuable indicator of the status of an individual or the effectiveness of a therapeutic or prophylactic regime which is currently in use. Accordingly, the method of the present invention should be understood to extend to monitoring for increases or decreases in methylation levels in an individual relative to their normal level (as hereinbefore defined), or relative to one or more earlier methylation levels determined from a biological sample of said individual.
[0427] The methods for detecting neoplasia can comprise the detection of one or more other cancer-associated polynucleotide or polypeptides sequences. Accordingly, detection of methylation by the method of the invention can be used either alone, or in combination with other screening methods for the diagnosis or prognosis of neoplasia.
[0428] Any method for detecting DNA methylation can be used in the methods of the present invention. A number of methods are available for detection of differentially methylated DNA at specific loci in either primary tissue samples or in patient samples such as blood, urine, stool or saliva (reviewed in Kristensen and Hansen Clin Chem. 55:1471-83, 2009; Ammerpohl et al. Biochim Biophys Acta. 1790:847-62, 2009; Shames et al. Cancer Lett. 251:187-98, 2007; Clark et al. Nat Protoc. 1:2353-64, 2006). For analysis of the proportion or extent of DNA methylation in a target gene, DNA is normally treated with sodium bisulfite and regions of interest amplified using primers and PCR conditions that will amplify independently of the methylation status of the DNA. The methylation of the overall amplicon or individual CpG sites can then be assessed by sequencing, including pyrosequencing, restriction enzyme digestion (COBRA) or by melting curve analysis. Alternatively ligation-based methods for analysis of methylation at specific CpG sites may be used. Detection of aberrantly methylated DNA released from tumors and into bodily fluids is being developed as a means of cancer diagnosis. Here, in the case of hypermethylated sequences, it is necessary to use sensitive methods that allow the selective amplification of the methylated DNA sequence from a background of normal cellular DNA that is unmethylated. Such methods based on bisulfite-treated DNA, for example; include methylation selective PCR (MSP), Heavymethyl PCR, Headloop PCR and Helper-dependent chain reaction (PCT/AU2008/001475).
[0429] Briefly, in some embodiments, methods for detecting methylation include randomly shearing or randomly fragmenting the genomic DNA, cutting the DNA with a methylation-dependent or methylation-sensitive restriction enzyme and subsequently selectively identifying and/or analyzing the cut or uncut DNA. Selective identification can include, for example, separating cut and uncut DNA (e.g., by size) and quantifying a sequence of interest that was cut or, alternatively, that was not cut. See, e.g., U.S. Pat. No. 7,186,512. Alternatively, the method can encompass amplifying intact DNA after restriction enzyme digestion, thereby only amplifying DNA that was not cleaved by the restriction enzyme in the area amplified. See, e.g., U.S. patent application Ser. Nos. 10/971,986; 11/071,013; and 10/971,339. In some embodiments, amplification can be performed using primers that are gene specific. Alternatively, adaptors can be added to the ends of the randomly fragmented DNA, the DNA can be digested with a methylation-dependent or methylation-sensitive restriction enzyme, intact DNA can be amplified using primers that hybridize to the adaptor sequences. In this case, a second step can be performed to determine the presence, absence or quantity of a particular gene in an amplified pool of DNA. In some embodiments, the DNA is amplified using real-time, quantitative PCR.
[0430] In some embodiments, the methods comprise quantifying the average methylation density in a target sequence within a population of genomic DNA. In some embodiments, the method comprises contacting genomic DNA with a methylation-dependent restriction enzyme or methylation-sensitive restriction enzyme under conditions that allow for at least some copies of potential restriction enzyme cleavage sites in the locus to remain uncleaved; quantifying intact copies of the locus; and comparing the quantity of amplified product to a control value representing the quantity of methylation of control DNA, thereby quantifying the average methylation density in the locus compared to the methylation density of the control DNA.
[0431] The quantity of methylation of a locus of DNA can be determined by providing a sample of genomic DNA comprising the locus, cleaving the DNA with a restriction enzyme that is either methylation-sensitive or methylation-dependent, and then quantifying the amount of intact DNA or quantifying the amount of cut DNA at the DNA locus of interest. The amount of intact or cut DNA will depend on the initial amount of genomic DNA containing the locus, the amount of methylation in the locus, and the number (i.e., the fraction) of nucleotides in the locus that are methylated in the genomic DNA. The amount of methylation in a DNA locus can be determined by comparing the quantity of intact DNA or cut DNA to a control value representing the quantity of intact DNA or cut DNA in a similarly-treated DNA sample. The control value can represent a known or predicted number of methylated nucleotides. Alternatively, the control value can represent the quantity of intact or cut DNA from the same locus in another (e.g., normal, non-diseased) cell or a second locus.
[0432] By using at least one methylation-sensitive or methylation-dependent restriction enzyme under conditions that allow for at least some copies of potential restriction enzyme cleavage sites in the locus to remain uncleaved and subsequently quantifying the remaining intact copies and comparing the quantity to a control, average methylation density of a locus can be determined. A methylation-sensitive enzyme is one which cuts DNA if its recognition sequence is unmethylated while a methylation-dependent enzyme cuts DNA if its recognition sequence is methylated. If the methylation-sensitive restriction enzyme is contacted to copies of a DNA locus under conditions that allow for at least some copies of potential restriction enzyme cleavage sites in the locus to remain uncleaved, then the remaining intact DNA will be directly proportional to the methylation density, and thus may be compared to a control to determine the relative methylation density of the locus in the sample. Similarly, if a methylation-dependent restriction enzyme is contacted to copies of a DNA locus under conditions that allow for at least some copies of potential restriction enzyme cleavage sites in the locus to remain uncleaved, then the remaining intact DNA will be inversely proportional to the methylation density, and thus may be compared to a control to determine the relative methylation density of the locus in the sample. Such assays are disclosed in, e.g., U.S. patent application Ser. No. 10/971,986.
[0433] Kits for the above methods can include, e.g., one or more of methylation-dependent restriction enzymes, methylation-sensitive restriction enzymes, amplification (e.g., PCR) reagents, probes and/or primers.
[0434] Quantitative amplification methods (e.g., quantitative PCR or quantitative linear amplification) can be used to quantify the amount of intact DNA within a locus flanked by amplification primers following restriction digestion. Methods of quantitative amplification are disclosed in, e.g., U.S. Pat. Nos. 6,180,349; 6,033,854; and 5,972,602, as well as in, e.g., Gibson et al., Genome Research 6:995-1001 (1996); DeGraves, et al., Biotechniques 34(1):106-10, 112-5 (2003); Deiman B, et al., Mol. Biotechnol. 20(2):163-79 (2002). Amplifications may be monitored in "real time."
[0435] Additional methods for detecting DNA methylation can involve genomic sequencing before and after treatment of the DNA with bisulfite. See, e.g., Frommer et al., Proc. Natl. Acad. Sci. USA 89:1827-1831 (1992). When sodium bisulfite is contacted to DNA, unmethylated cytosine is converted to uracil, while methylated cytosine is not modified.
[0436] In some embodiments, restriction enzyme digestion of PCR products amplified from bisulfite-converted DNA is used to detect DNA methylation. See, e.g., Sadri & Hornsby, Nucl. Acids Res. 24:5058-5059 (1996); Xiong & Laird, Nucleic Acids Res. 25:2532-2534 (1997).
[0437] In some embodiments, a methylation-specific PCR ("MSP") reaction is used alone or in combination with other methods to detect DNA methylation. An MSP assay entails initial modification of DNA by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequent amplification with primers specific for methylated verses unmethylated DNA. See, Herman et al. Proc. Natl. Acad. Sci. USA 93:9821-9826 (1996); U.S. Pat. No. 5,786,146.
[0438] In some embodiments, a MethyLight assay is used alone or in combination with other methods to detect DNA methylation (see, Eads et al., Cancer Res. 59:2302-2306 (1999)). Briefly, in the MethyLight process genomic DNA is converted in a sodium bisulfite reaction (the bisulfite process converts unmethylated cytosine residues to uracil). Amplification of a DNA sequence of interest is then performed using PCR primers that hybridize to CpG dinucleotides. By using primers that hybridize only to sequences resulting from bisulfite conversion of methylated DNA, (or alternatively to unmethylated sequences) amplification can indicate methylation status of sequences where the primers hybridize. Furthermore, the amplification product can be detected with a probe that specifically binds to a sequence resulting from bisulfite treatment of a unmethylated DNA. If desired, both primers and probes can be used to detect methylation status. Thus, kits for use with MethyLight can include sodium bisulfite as well as primers or detectably-labeled probes (including but not limited to Taqman or molecular beacon probes) that distinguish between methylated and unmethylated DNA that have been treated with bisulfite. Other kit components can include, e.g., reagents necessary for amplification of DNA including but not limited to, PCR buffers, deoxynucleotides; and a thermostable polymerase.
[0439] In some embodiments, a Ms-SNuPE (Methylation-sensitive Single Nucleotide Primer Extension) reaction is used alone or in combination with other methods to detect DNA methylation (see, Gonzalgo & Jones, Nucleic Acids Res. 25:2529-2531 (1997)). The Ms-SNuPE technique is a quantitative method for assessing methylation differences at specific CpG sites based on bisulfite treatment of DNA, followed by single-nucleotide primer extension (Gonzalgo & Jones, supra). Briefly, genomic DNA is reacted with sodium bisulfite to convert unmethylated cytosine to uracil while leaving 5-methylcytosine unchanged. Amplification of the desired target sequence is then performed using PCR primers specific for bisulfite-converted DNA, and the resulting product is isolated and used as a template for methylation analysis at the CpG site(s) of interest.
[0440] Typical reagents (e.g., as might be found in a typical Ms-SNuPE-based kit) for Ms-SNuPE analysis can include, but are not limited to: PCR primers for specific gene (or methylation-altered DNA sequence or CpG island); optimized PCR buffers and deoxynucleotides; gel extraction kit; positive control primers; Ms-SNuPE primers for a specific gene; reaction buffer (for the Ms-SNuPE reaction); and detectably-labeled nucleotides. Additionally, bisulfite conversion reagents may include: DNA denaturation buffer; sulfonation buffer; DNA recovery regents or kit (e.g., precipitation, ultrafiltration, affinity column); desulfonation buffer; and DNA recovery components.
[0441] Additional methylation detection methods include, but are not limited to, methylated CpG island amplification (see, Toyota et al., Cancer Res. 59:2307-12 (1999)) and those described in, e.g., U.S. Patent Publication 2005/0069879; Rein, et al. Nucleic Acids Res. 26 (10): 2255-64 (1998); Olek, et al. Nat. Genet. 17(3): 275-6 (1997); and PCT Publication No. WO 00/70090.
[0442] More detailed information in relation to several of these generally described methods is provided below:
(a) Probe or Primer Design and/or Production
[0443] Several methods described herein for the diagnosis of a neoplasia use one or more probes and/or primers. Methods for designing probes and/or primers for use in, for example, PCR or hybridization are known in the art and described, for example, in Dieffenbach and Dveksler (Eds) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbor Laboratories, NY, 1995). Furthermore, several software packages are publicly available that design optimal probes and/or primers for a variety of assays, e.g. Primer 3 available from the Center for Genome Research, Cambridge, Mass., USA.
[0444] Clearly, the potential use of the probe or primer should be considered during its design. For example, should the probe or primer be produced for use in a methylation specific PCR or ligase chain reaction (LCR) assay the nucleotide at the 3' end (or 5' end in the case of LCR) should preferably correspond to a methylated nucleotide in a nucleic acid.
[0445] Probes and/or primers useful for detection of a sequence associated with a neoplasia are assessed, for example, to determine those that do not form hairpins, self-prime or form primer dimers (e.g. with another probe or primer used in a detection assay). Furthermore, a probe or primer (or the sequence thereof) is often assessed to determine the temperature at which it denatures from a target nucleic acid (i.e. the melting temperature of the probe or primer, or Tm). Methods for estimating Tm are known in the art and described, for example, in Santa Lucia, Proc. Natl. Acad. Sci. USA, 95: 1460-1465, 1995 or Bresslauer et al., Proc. Natl. Acad. Sci. USA, 83: 3746-3750, 1986.
[0446] Methods for producing/synthesizing a probe or primer of the present invention are known in the art. For example, oligonucleotide synthesis is described, in Gait (Ed) (In: Oligonucleotide Synthesis: A Practical Approach, IRL Press, Oxford, 1984). For example, a probe or primer may be obtained by biological synthesis (e.g. by digestion of a nucleic acid with a restriction endonuclease) or by chemical synthesis. For short sequences (up to about 100 nucleotides) chemical synthesis is preferable.
[0447] For longer sequences standard replication methods employed in molecular biology are useful, such as, for example, the use of M13 for single stranded DNA as described by Messing, Methods Enzymol, 101, 20-78, 1983. Other methods for oligonucleotide synthesis include, for example, phosphotriester and phosphodiester methods (Narang, et al. Meth. Enzymol 68: 90, 1979) and synthesis on a support (Beaucage, et al. Tetrahedron Letters 22:1859-1862, 1981) as well as phosphoramidate technique, Caruthers, M. H., et al., Methods in Enzymology, Vol. 154, pp. 287-314 (1988), and others described in "Synthesis and Applications of DNA and RNA," S. A. Narang, editor, Academic Press, New York, 1987, and the references cited therein. Probes comprising locked nucleic acid (LNA) are synthesized as described, for example, in Nielsen et al. J. Chem. Soc. Perkin Trans., 1:3423, 1997; Singh and Wengel, Chem. Commun. 1247, 1998. While, probes comprising peptide-nucleic acid (PNA) are synthesized as described, for example, in Egholm et al., Am. Chem. Soc., 114:1895, 1992; Egholm et al., Nature, 365:566, 1993; and Orum et al., Nucl. Acids Res., 21:5332, 1993.
(b) Methylation-Sensitive Endonuclease Digestion of DNA
[0448] In one example, the increased methylation in a sample is determined using a process comprising treating the nucleic acid with an amount of a methylation-sensitive restriction endonuclease enzyme under conditions sufficient for nucleic acid to be digested and then detecting the fragments produced. Exemplary methylation-sensitive endonucleases include, for example, HhaI or HpaII. Preferably, assays include internal controls that are digested with a methylation-insensitive enzyme having the same specificity as the methylation-sensitive enzyme employed. For example, the methylation-insensitive enzyme MspI is an isoschizomer of the methylation-sensitive enzyme HpaII.
Hybridization Assay Formats
[0449] In one example, the digestion of nucleic acid is detected by selective hybridization of a probe or primer to the undigested nucleic acid. Alternatively, the probe selectively hybridizes to both digested and undigested nucleic acid but facilitates differentiation between both forms, e.g., by electrophoresis. Suitable detection methods for achieving selective hybridization to a hybridization probe include, for example, Southern or other nucleic acid hybridization (Kawai et al., Mol. Cell. Biol. 14:7421-7427, 1994; Gonzalgo et al., Cancer Res. 57:594-599, 1997).
[0450] Suitable hybridization conditions are determined based on the melting temperature (Tm) of a nucleic acid duplex comprising the probe. The skilled artisan will be aware that optimum hybridization reaction conditions should be determined empirically for each probe, although some generalities can be applied. Preferably, hybridizations employing short oligonucleotide probes are performed at low to medium stringency. In the case of a GC rich probe or primer or a longer probe or primer a high stringency hybridization and/or wash is preferred. A high stringency is defined herein as being a hybridization and/or wash carried out in about 0.1.times.SSC buffer and/or about 0.1% (w/v) SDS, or lower salt concentration, and/or at a temperature of at least 65.degree. C., or equivalent conditions. Reference herein to a particular level of stringency encompasses equivalent conditions using wash/hybridization solutions other than SSC known to those skilled in the art.
[0451] In accordance with the present example, a difference in the fragments produced for the test sample and a negative control sample is indicative of the subject having a neoplasia. Similarly, in cases where the control sample comprises data from a tumor, cancer tissue or a cancerous cell or pre-cancerous cell, similarity, albeit not necessarily absolute identity, between the test sample and the control sample is indicative of a positive diagnosis (i.e. cancer).
Amplification Assay Formats
[0452] In an alternative example, the fragments produced by the restriction enzyme are detected using an amplification system, such as, for example, polymerase chain reaction (PCR), rolling circle amplification (RCA), inverse polymerase chain reaction (iPCR), in situ PCR (Singer-Sam et al., Nucl. Acids Res. 18:687, 1990), strand displacement amplification (SDA) or cycling probe technology.
[0453] Methods of PCR are known in the art and described, for example, by McPherson et al., PCR: A Practical Approach. (series eds, D. Rickwood and B. D. Hames), IRL Press Limited, Oxford. pp 1-253, 1991 and by Dieffenbach (ed) and Dveksler (ed) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbour Laboratories, NY, 1995), the contents of which are each incorporated in their entirety by way of reference. Generally, for PCR two non-complementary nucleic acid primer molecules comprising at least about 18 nucleotides in length, and more preferably at least 20-30 nucleotides in length are hybridized to different strands of a nucleic acid template molecule at their respective annealing sites, and specific nucleic acid molecule copies of the template that intervene the annealing sites are amplified enzymatically. Amplification products may be detected, for example, using electrophoresis and detection with a detectable marker that binds nucleic acids. Alternatively, one or more of the oligonucleotides are labeled with a detectable marker (e.g. a fluorophore) and the amplification product detected using, for example, a lightcycler (Perkin Elmer, Wellesley, Mass., USA, Roche Applied Science, Indianapolis, Ind., USA).
[0454] Strand displacement amplification (SDA) utilizes oligonucleotide primers, a DNA polymerase and a restriction endonuclease to amplify a target sequence. The oligonucleotides are hybridized to a target nucleic acid and the polymerase is used to produce a copy of the region intervening the primer annealing sites. The duplexes of copied nucleic acid and target nucleic acid are then nicked with an endonuclease that specifically recognizes a sequence at the beginning of the copied nucleic acid. The DNA polymerase recognizes the nicked DNA and produces another copy of the target region at the same time displacing the previously generated nucleic acid. The advantage of SDA is that it occurs in an isothermal format, thereby facilitating high-throughput automated analysis.
[0455] Cycling Probe Technology uses a chimeric synthetic primer that comprises DNA-RNA-DNA that is capable of hybridizing to a target sequence. Upon hybridization to a target sequence the RNA-DNA duplex formed is a target for RNaseH thereby cleaving the primer. The cleaved primer is then detected, for example, using mass spectrometry or electrophoresis.
[0456] For primers that flank or are adjacent to a methylation-sensitive endonuclease recognition site, it is preferred that such primers flank only those sites that are hypermethylated in neoplasia to ensure that a diagnostic amplification product is produced. In this regard, an amplification product will only be produced when the restriction site is not cleaved, i.e., when it is methylated. Accordingly, detection of an amplification product indicates that the CpG dinucleotide/s of interest is/are methylated.
[0457] As will be known to the skilled artisan, the precise length of the amplified product will vary depending upon the distance between the primers. Clearly this form of analysis may be used to determine the methylation status of a plurality of CpG dinucleotides provided that each dinucleotide is within a methylation sensitive restriction endonuclease site. In these methods, one or more of the primers may be labeled with a detectable marker to facilitate rapid detection of amplified nucleic acid, for example, a fluorescent label (e.g. Cy5 or Cy3) or a radioisotope (e.g. .sup.32P).
[0458] The amplified nucleic acids are generally analyzed using, for example, non-denaturing agarose gel electrophoresis, non-denaturing polyacrylamide gel electrophoresis, mass spectrometry, liquid chromatography (e.g. HPLC or dHPLC), or capillary electrophoresis. (e.g. MALDI-TOF). High throughput detection methods, such as, for example, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), electrospray ionization (ESI), mass spectrometry (including tandem mass spectrometry, e.g. LC MS/MS), biosensor technology, evanescent fiber-optics technology or DNA chip technology (e.g., WO98/49557; WO 96/17958; Fodor et al., Science 767-773, 1991; U.S. Pat. Nos. 5,143,854; and 5,837,832, the contents of which are all incorporated herein by reference), are especially preferred for all assay formats described herein. Alternatively, amplification of a nucleic acid may be continuously monitored using a melting curve analysis method as described herein and/or in, for example, U.S. Pat. No. 6,174,670, which is incorporated herein by reference.
(c) Other Assay Formats
[0459] In an alternative example, the increased methylation in a sample is determined by performing a process comprising treating chromatin containing the nucleic acid with an amount of DNaseI under conditions sufficient for nucleic acid to be digested and then detecting the fragments produced. This assay format is predicated on the understanding that chromatin containing methylated DNA, e.g., hyper methylated DNA, has a more tightly-closed conformation than non-hyper methylated DNA and, as a consequence, is less susceptible to endonuclease digestion by DNase I.
[0460] In accordance with this method , DNA fragments of different lengths are produced by DNase I digestion of methylated compared to non-methylated DNA. Such different DNA fragments are detected, for example, using an assay described earlier. Alternatively, the DNA fragments are detected using PCR-SSCP essentially as described, for example, in Gregory and Feil, Nucleic Acids Res., 27, e32i-e32iv, 1999. In adapting PCR-SSCP to the present invention, amplification primers flanking or comprising one or more CpG dinucleotides in a nucleic acid that are resistant to DNase I digestion in a neoplasia sample but not resistant to DNase I digestion in a healthy/normal control or healthy/normal test sample are used to amplify the DNase I-generated fragments. In this case, the production of a specific nucleic acid fragment using DNase I is diagnostic of neoplasia, because the DNA is not efficiently degraded. In contrast, template DNA from a healthy/normal subject sample is degraded by the action of DNase I and, as a consequence, amplification fails to produce a discrete amplification product. Alternative methods to PCR-SSCP, such as for example, PCR-dHPLC are also known in the art and contemplated by the present invention.
(d) Selective Mutagenesis of Non Methylated DNA
[0461] In an alternative method the increased methylation in a sample is determined using a process comprising treating the nucleic acid with an amount of a compound that selectively mutates a non-methylated cytosine residue within a CpG dinucleotide under conditions sufficient to induce mutagenesis.
[0462] Preferred compounds mutate cytosine to uracil or thymidine, such as, for example, a salt of bisulfite, e.g., sodium bisulfite or potassium bisulfite (Frommer et al., 1992, supra). Bisulfite treatment of DNA is known to distinguish methylated from non-methylated cytosine residues, by mutating cytosine residues that are not protected by methylation, including cytosine residues that are not within a CpG dinucleotide or that are positioned within a CpG dinucleotide that is not subject to methylation.
Sequence Based Detection
[0463] In one example, the presence of one or more mutated nucleotides or the number of mutated sequences is determined by sequencing mutated DNA. One form of analysis comprises amplifying mutated nucleic acid using an amplification reaction described herein, for example, PCR. The amplified product is then directly sequenced or cloned and the cloned product sequenced. Methods for sequencing DNA are known in the art and include for example, the dideoxy chain termination method or the Maxam-Gilbert method (see Sambrook et al., Molecular Cloning, A Laboratory Manual (2nd Ed., CSHP, New York 1989) or Zyskind et al., Recombinant DNA Laboratory Manual, (Acad. Press, 1988)).
[0464] As the treatment of nucleic acid with a compound, such as, for example, bisulfite results in non-methylated cytosines being mutated to uracil (and hence thymidine after an amplification process), analysis of the sequence determines the presence or absence of a methylated nucleotide. For example, by comparing the sequence obtained using a control sample or a sample that has not been treated with bisulfite, or the known nucleotide sequence of the region of interest with a treated sample facilitates the detection of differences in the nucleotide sequence. Any thymine residue detected at the site of a cytosine in the treated sample compared to a control or untreated sample may be considered to be caused by mutation as a result of bisulfite treatment. Suitable methods for the detection of methylation using sequencing of bisulfite treated nucleic acid are described, for example, in Frommer et al., 1992, supra or Clark et al., Nucl. Acids Res. 22:2990-2997, 1994.
[0465] In another method, the presence of a mutated or non-mutated nucleotide in a bisulfite treated sample is detected using pyrosequencing, such as, for example, as described in Uhlmann et al., Electrophoresis, 23: 4072-4079, 2002. Essentially this method is a form of real-time sequencing that uses a primer that hybridizes to a site adjacent or close to the site of a cytosine that is methylated. Following hybridization of the primer and template in the presence of a DNA polymerase each of four modified deoxynucleotide triphosphates are added separately according to a predetermined dispensation order. Only an added nucleotide that is complementary to the bisulfite treated sample is incorporated and inorganic pyrophosphate (PPi) is liberated. The PPi then drives a reaction resulting in production of detectable levels of light. Such a method allows determination of the identity of a specific nucleotide adjacent to the site of hybridization of the primer.
[0466] Methods of solid phase pyrosequencing are known in the art and reviewed in, for example, Landegren et al., Genome Res., 8(8): 769-776, 1998. Such methods enable the high-throughput detection of methylation of a number of CpG dinucleotides.
[0467] A related method for determining the sequence of a bisulfite treated nucleotide is methylation-sensitive single nucleotide primer extension (Me-SnuPE) or SNaPmeth. Suitable methods are described, for example, in Gonzalgo and Jones, 1997, supra, or Uhlmann et al., Electrophoresis, 23:4072-4079, 2002. An oligonucleotide is used that hybridizes to the region of a nucleic acid adjacent to the site of a cytosine that is methylated. This oligonucleotide is then used in a primer extension protocol with a polymerase and a free nucleotide diphosphate or dideoxynucleotide triphosphate that corresponds to either or any of the possible bases that occur at this site following bisulfite treatment (i.e., thymine or cytosine). Preferably, the nucleotide-diphosphate is labeled with a detectable marker (e.g. a fluorophore). Following primer extension, unbound labeled nucleotide diphosphates are removed, e.g. using size exclusion chromatography or electrophoresis, or hydrolyzed, using for example, alkaline phosphatase, and the incorporation of the labeled nucleotide to the oligonucleotide is detected, indicating the base that is present at the site.
[0468] Clearly other high throughput sequencing methods are encompassed by the present invention. Such methods include, for example, solid phase minisequencing (as described, for example, in Southern et al., Genomics, 13:1008-1017, 1992), or minisequencing with FRET (as described, for example, in Chen and Kwok, Nucleic Acids Res. 25:347-353, 1997).
Restriction Endonuclease-Based Assay Format
[0469] In one method, the presence of a non-mutated sequence is detected using combined bisulfite restriction analysis (COBRA) essentially as described in Xiong and Laird, 2001, supra. This method exploits the differences in restriction enzyme recognition sites between methylated and unmethylated nucleic acid after treatment with a compound that selectively mutates a non-methylated cytosine residue, e.g., bisulfite.
[0470] Following bisulfite treatment a region of interest comprising one or more CpG dinucleotides that are methylated and are included in a restriction endonuclease recognition sequence is amplified using an amplification reaction described herein, e.g., PCR. The amplified product is then contacted with the restriction enzyme that cleaves at the site of the CpG dinucleotide for a time and under conditions sufficient for cleavage to occur. A restriction site may be selected to indicate the presence or absence of methylation. For example, the restriction endonuclease TaqI cleaves the sequence TCGA, following bisulfite treatment of a non-methylated nucleic acid the sequence will be TTGA and, as a consequence, will not be cleaved. The digested and/or non-digested nucleic acid is then detected using a detection means known in the art, such as, for example, electrophoresis and/or mass spectrometry. The cleavage or non-cleavage of the nucleic acid is indicative of cancer in a subject. Clearly, this method may be employed in either a positive read-out or negative read-out system for the diagnosis of a cancer.
Positive Read-Out Assay Format
[0471] In one embodiment, the assay format of the invention comprises a positive read-out system in which DNA from a sample that has been treated, for example, with bisulfite is detected as a positive signal. Preferably, the non-hypermethylated DNA from a healthy or normal control subject is not detected or only weakly detected.
[0472] In a preferred embodiment, the increased methylation in a subject sample is determined using a process comprising:
[0473] (i) treating the nucleic acid with an amount of a compound that selectively mutates a non-methylated cytosine residue under conditions sufficient to induce mutagenesis thereby producing a mutated nucleic acid;
[0474] (ii) hybridizing a nucleic acid to a probe or primer comprising a nucleotide sequence that is complementary to a sequence comprising a methylated cytosine residue under conditions such that selective hybridization to the non-mutated nucleic acid occurs; and
[0475] (iii) detecting the selective hybridization.
[0476] In this context, the term "selective hybridization" means that hybridization of a probe or primer to the non-mutated nucleic acid occurs at a higher frequency or rate, or has a higher maximum reaction velocity, than hybridization of the same probe or primer to the corresponding mutated sequence. Preferably, the probe or primer does not hybridize to the non-methylated sequence carrying the mutation(s) under the reaction conditions used.
Hybridization-Based Assay Format
[0477] In one embodiment, the hybridization is detected using Southern, dot blot, slot blot or other nucleic acid hybridization means (Kawai et al., 1994, supra; Gonzalgo et al., 1997, supra). Subject to appropriate probe selection, such assay formats are generally described herein above and apply mutatis mutandis to the presently described selective mutagenesis approach.
[0478] Preferably, a ligase chain reaction format is employed to distinguish between a mutated and non-mutated nucleic acid. Ligase chain reaction (described in EP 320,308 and U.S. Pat. No. 4,883,750) uses at least two oligonucleotide probes that anneal to a target nucleic acid in such a way that they are juxtaposed on the target nucleic acid. In a ligase chain reaction assay, the target nucleic acid is hybridized to a first probe that is complementary to a diagnostic portion of the target sequence (the diagnostic probe) e.g., a nucleic acid comprising one or more methylated CpG dinucleotide(s), and with a second probe that is complementary to a nucleotide sequence contiguous with the diagnostic portion (the contiguous probe), under conditions wherein the diagnostic probe remains bound substantially only to the target nucleic acid. The diagnostic and contiguous probes can be of different lengths and/or have different melting temperatures such that the stringency of the hybridization can be adjusted to permit their selective hybridization to the target, wherein the probe having the higher melting temperature is hybridized at higher stringency and, following washing to remove unbound and/or non-selectively bound probe, the other probe having the lower melting temperature is hybridized at lower stringency. The diagnostic probe and contiguous probe are then covalently ligated such as, for example, using T4 DNA ligase, to thereby produce a larger target probe that is complementary to the target sequence, and the probes that are not ligated are removed by modifying the hybridization stringency. In this respect, probes that have not been ligated will selectively hybridize under lower stringency hybridization conditions than probes that have been ligated. Accordingly, the stringency of the hybridization can be increased to a stringency that is at least as high as the stringency used to hybridize the longer probe, and preferably at a higher stringency due to the increased length contributed by the shorter probe following ligation.
[0479] In another example, one or both of the probes is labeled such that the presence or absence of the target sequence can be tested by melting the target-probe duplex, eluting the dissociated probe, and testing for the label(s). Where both probes are labeled, different ligands are used to permit distinction between the ligated and unligated probes, in which case the presence of both labels in the same eluate fraction confirms the ligation event. If the target nucleic acid is bound to a solid matrix e.g., in a Southern hybridization, slot blot, dot blot, or microchip assay format, the presence of both the diagnostic and contiguous probes can be determined directly.
[0480] Methylation specific microarrays (MSO) are also useful for differentiating between a mutated and non-mutated sequence. A suitable method is described, for example, in Adorjan et al. Nucl. Acids Res., 30: e21, 2002. MSO uses nucleic acid that has been treated with a compound that selectively mutates a non-methylated cytosine residue (e.g., bisulfite) as template for an amplification reaction that amplifies both mutant and non-mutated nucleic acid. The amplification is performed with at least one primer that comprises a detectable label, such as, for example, a fluorophore, e.g., Cy3 or Cy5.
[0481] To produce a microarray for detection of mutated nucleic acid oligonucleotides are spotted onto, for example, a glass slide, preferably, with a degree of redundancy (for example, as described in Golub et al., Science, 286:531-537, 1999). Preferably, for each CpG dinucleotide analyzed two different oligonucleotides are used. Each oligonucleotide comprises a sequence N.sub.2-16CGN.sub.2-16 or N.sub.2-16TGN.sub.2-16 (wherein N is a number of nucleotides adjacent or juxtaposed to the CpG dinucleotide of interest) reflecting the methylated or non-methylated status of the CpG dinucleotides.
[0482] The labeled amplification products are then hybridized to the oligonucleotides on the microarray under conditions that enable detection of single nucleotide differences. Following washing to remove unbound amplification product, hybridization is detected using, for example, a microarray scanner. Not only does this method allow for determination of the methylation status of a large number of CpG dinucleotides, it is also semi-quantitative, enabling determination of the degree of methylation at each CpG dinucleotide analyzed. As there may be some degree of heterogeneity of methylation in a single sample, such quantification may assist in the diagnosis of cancer.
Amplification-Based Assay Format
[0483] In an alternative example, the hybridization is detected using an amplification system. In methylation-specific PCR formats (MSP; Herman et al. Proc. Natl. Acad. Sci. USA 93:9821-9826, 1992), the hybridization is detected using a process comprising amplifying the bisulfite-treated DNA. Accordingly, by using one or more probe or primer that anneals specifically to the unmutated sequence under moderate and/or high stringency conditions an amplification product is only produced using a sample comprising a methylated nucleotide. Alternate assays that provide for selective amplification of either the methylated or the unmethylated component from a mixture of bisulfite-treated DNA are provided by Cottrell et al., Nucl. Acids Res. 32: e10, 2003 (HeavyMethyl PCR), Rand et al. Nucl. Acids Res. 33:e127, 2005 (Headloop PCR), Rand et al. Epigenetics 1:94-100, 2006 (Bisulfite Differential Denaturation PCR) and PCT/AU07/000389 (End-specific PCR).
[0484] Any amplification assay format described herein can be used, such as, for example, polymerase chain reaction (PCR), rolling circle amplification (RCA), inverse polymerase chain reaction (iPCR), in situ PCR (Singer-Sam et al., 1990, supra), strand displacement amplification, or cycling probe technology. PCR techniques have been developed for detection of gene mutations (Kuppuswamy et al., Proc. Natl. Acad. Sci. USA 88:1143-1147, 1991) and quantitation of allelic-specific expression (Szabo and Mann, Genes Dev. 9: 3097-3108, 1995; and Singer-Sam et al., PCR Methods Appl. 1: 160-163, 1992). Such techniques use internal primers, which anneal to a PCR-generated template and terminate immediately 5' of the single nucleotide to be assayed. Such as format is readily combined with ligase chain reaction as described herein above. The use of a real-time quantitative assay format is also useful. Subject to the selection of appropriate primers, such assay formats are generally described herein above and apply mutatis mutandis to the presently described selective mutagenesis approach.
[0485] Methylation-specific melting-curve analysis (essentially as described in Worm et al., Clin. Chem., 47:1183-1189, 2001) is also contemplated by the present invention. This process exploits the difference in melting temperature in amplification products produced using bisulfite treated methylated or unmethylated nucleic acid. In essence, non-discriminatory amplification of a bisulfite treated sample is performed in the presence of a fluorescent dye that specifically binds to double stranded DNA (e.g., SYBR Green I). By increasing the temperature of the amplification product while monitoring fluorescence the melting properties and thus the sequence of the amplification product is determined. A decrease in the fluorescence reflects melting of at least a domain in the amplification product. The temperature at which the fluorescence decreases is indicative of the nucleotide sequence of the amplified nucleic acid, thereby permitting the nucleotide at the site of one or more CpG dinucleotides to be determined. As the sequence of the nucleic acids amplified using the present invention
[0486] The present invention also encompasses the use of real-time quantitative forms of PCR, such as, for example, TaqMan (Holland et al., Proc. Natl. Acad. Sci. USA, 88:7276-7280, 1991; Lee et al., Nucleic Acid Res. 21:3761-3766, 1993) to perform this embodiment. For example, the MethylLight method of Eads et al., Nucl. Acids Res. 28: E32, 2000 uses a modified TaqMan assay to detect methylation of a CpG dinucleotide. Essentially, this method comprises treating a nucleic acid sample with bisulfite and amplifying nucleic acid comprising one or more CpG dinucleotides that are methylated in a neoplastic cell and not in a control sample using an amplification reaction, e.g., PCR. The amplification reaction is performed in the presence of three oligonucleotides, a forward and reverse primer that flank the region of interest and a probe that hybridizes between the two primers to the site of the one or more methylated CpG dinucleotides. The probe is dual labeled with a 5' fluorescent reporter and a 3' quencher (or vice versa). When the probe is intact, the quencher dye absorbs the fluorescence of the reporter due to their proximity. Following annealing of to the PCR product the probe is cleaved by 5' to 3' exonuclease activity of, for example, Taq DNA polymerase. This cleavage releases the reporter from the quencher thereby resulting in an increased fluorescence signal that can be used to estimate the initial template methylation level. By using a probe or primer that selectively hybridizes to unmutated nucleic acid (i.e. methylated nucleic acid) the level of methylation is determined, e.g., using a standard curve.
[0487] Alternatively, rather than using a labeled probe that requires cleavage, a probe, such as, for example, a Molecular Beacon is used (see, for example, Mhlanga and Malmberg, Methods 25:463-471, 2001). Molecular beacons are single stranded nucleic acid molecules with a stem-and-loop structure. The loop structure is complementary to the region surrounding the one or more CpG dinucleotides that are methylated in a neoplastic sample and not in a control sample. The stem structure is formed by annealing two "arms" complementary to each other, which are on either side of the probe (loop). A fluorescent moiety is bound to one arm and a quenching moiety that suppresses any detectable fluorescence when the molecular beacon is not bound to a target sequence is bound to the other arm. Upon binding of the loop region to its target nucleic acid the arms are separated and fluorescence is detectable. However, even a single base mismatch significantly alters the level of fluorescence detected in a sample. Accordingly, the presence or absence of a particular base is determined by the level of fluorescence detected. Such an assay facilitates detection of one or more unmutated sites (i.e. methylated nucleotides) in a nucleic acid.
[0488] Fluorescently labeled locked nucleic acid (LNA) molecules or fluorescently labeled protein-nucleic acid (PNA) molecules are useful for the detection of nucleotide differences (e.g., as described in Simeonov and Nikiforov, Nucleic Acids Research, 30(17):1-5, 2002). LNA and PNA molecules bind, with high affinity, to nucleic acid, in particular, DNA. Fluorophores (in particular, rhodamine or hexachlorofluorescein) conjugated to the LNA or PNA probe fluoresce at a significantly greater level upon hybridization of the probe to target nucleic acid. However, the level of increase of fluorescence is not enhanced to the same level when even a single nucleotide mismatch occurs. Accordingly, the degree of fluorescence detected in a sample is indicative of the presence of a mismatch between the LNA or PNA probe and the target nucleic acid, such as, in the presence of a mutated cytosine in a methylated CpG dinucleotide. Preferably, fluorescently labeled LNA or PNA technology is used to detect at least a single base change in a nucleic acid that has been previously amplified using, for example, an amplification method known in the art and/or described herein.
[0489] As will be apparent to the skilled artisan, LNA or PNA detection technology is amenable to a high-throughput detection of one or more markers by immobilizing an LNA or PNA probe to a solid support, as described in Orum et al., Clin. Chem. 45:1898-1905, 1999.
[0490] Alternatively, a real-time assay, such as, for example, the so-called HeavyMethyl assay (Cottrell et al., 2003, supra) is used to determine the presence or level of methylation of nucleic acid in a test sample. Essentially, this method uses one or more non-extendible nucleic acid (e.g., oligonucleotide) blockers that bind to bisulfite-treated nucleic acid in a methylation specific manner (i.e., the blocker/s bind specifically to unmutated DNA under moderate to high stringency conditions). An amplification reaction is performed using one or more primers that may optionally be methylation specific but that flank the one or more blockers. In the presence of unmethylated nucleic acid (i.e., non-mutated DNA) the blocker/s bind and no PCR product is produced. Using a TaqMan assay essentially as described supra the level of methylation of nucleic acid in a sample is determined.
[0491] Other amplification-based methods for detecting methylated nucleic acid following treatment with a compound that selectively mutates a non-methylated cytosine residue include, for example, methylation-specific single stranded conformation analysis (MS-SSCA) (Bianco et al., Hum. Mutat., 14:289-293, 1999), methylation-specific denaturing gradient gel electrophoresis (MS-DGGE) (Abrams and Stanton, Methods Enzymol., 212:71-74, 1992) and methylation-specific denaturing high-performance liquid chromatography (MS-DHPLC) (Deng et al. Chin. J. Cancer Res., 12:171-191, 2000). Each of these methods use different techniques for detecting nucleic acid differences in an amplification product based on differences in nucleotide sequence and/or secondary structure. Such methods are clearly contemplated by the present invention.
[0492] As with other amplification-based assay formats, the amplification product is analyzed using a range of procedures, including gel electrophoresis, gel filtration, mass spectrometry, and in the case of labeled primers, by identifying the label in the amplification product. In an alternative embodiment, restriction enzyme digestion of PCR products amplified from bisulfite-converted DNA is performed essentially as described by Sadri and Hornsby, Nucl. Acids Res. 24:5058-5059, 1996; and Xiong and Laird, Nucl. Acids Res. 25:2532-2534, 1997), to analyze the product formed.
[0493] High throughput detection methods, such as, for example, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), electrospray ionization (ESI), Mass spectrometry (including tandem mass spectrometry, e.g. LC MS/MS), biosensor technology, evanescent fiber-optics technology or DNA chip technology, can also be employed.
[0494] As with the other assay formats described herein that utilize hybridization and/or amplification detection systems, combinations of such processes as described herein above are particularly contemplated by the selective mutagenesis-based assay formats of the present invention. In one example, the increased methylation is detected by performing a process comprising:
[0495] (i) treating the nucleic acid with an amount of a compound that selectively mutates a non-methylated cytosine residue within a CpG dinucleotide under conditions sufficient to induce mutagenesis thereby producing a mutated nucleic acid;
[0496] (ii) hybridizing the nucleic acid to two non-overlapping and non-complementary primers each of which comprises a nucleotide sequence that is complementary to a sequence in the DNA comprising a methylated cytosine residue under conditions such that hybridization to the non-mutated nucleic acid occurs;
[0497] (iii) amplifying nucleic acid intervening the hybridized primers thereby producing a DNA fragment consisting of a sequence that comprises a primer sequence;
[0498] (iv) hybridizing the amplified DNA fragment to a probe comprising a nucleotide sequence that corresponds or is complementary to a sequence comprising a methylated cytosine residue under conditions such that hybridization to the non-mutated nucleic acid occurs; and detecting the hybridization.
Negative Read-Out Assays
[0499] In another example, the assay format comprises a negative read-out system in which reduced methylation of DNA from a healthy/normal control sample is detected as a positive signal and preferably, methylated DNA from a neoplastic sample is not detected or is only weakly detected.
[0500] In a preferred embodiment, the reduced methylation is determined using a process comprising:
[0501] (i) treating the nucleic acid with an amount of a compound that selectively mutates a non-methylated cytosine residue within a CpG island under conditions sufficient to induce mutagenesis thereby producing a mutated nucleic acid;
[0502] (ii) hybridizing the nucleic acid to a probe or primer comprising a nucleotide sequence that is complementary to a sequence comprising the mutated cytosine residue under conditions such that selective hybridization to the mutated nucleic acid occurs; and
[0503] (iii) detecting the selective hybridization.
[0504] In this context, the term "selective hybridization" means that hybridization of a probe or primer to the mutated nucleic acid occurs at a higher frequency or rate, or has a higher maximum reaction velocity, than hybridization of the same probe or primer to the corresponding non-mutated sequence. Preferably, the probe or primer does not hybridize to the methylated sequence (or non-mutated sequence) under the reaction conditions used.
Hybridization-Based Assay Format
[0505] In one embodiment the hybridization is detected using Southern, dot blot, slot blot or other nucleic acid hybridization means (Kawai et al., 1994, supra; Gonzalgo et al., 1997, supra). Subject to appropriate probe selection, such assay formats are generally described herein above and apply mutatis mutandis to the presently described selective mutagenesis approach. Preferably, a ligase chain reaction format is employed to distinguish between a non-mutated and mutated nucleic acid. In this respect, the assay requirements and conditions are as described herein above for positive read-out assays and apply mutatis mutandis to the present format. However the selection of probes will differ. For negative read-out assays, one or more probes are selected that selectively hybridize to the mutated sequence rather than the non-mutated sequence.
[0506] Preferably, the ligase chain reaction probe(s) have 3'-terminal and/or 5'-terminal sequences that comprise a CpG dinucleotide that is not methylated in a healthy control sample, but is hypermethylated in cancer, such that the diagnostic probe and contiguous probe are capable of being ligated only when the cytosine of the CpG dinucleotide is mutated to thymidine e.g., in the case of a non-methylated cytosine residue.
[0507] As will be apparent to the skilled artisan the MSO method described supra is amenable to either or both positive and/or negative readout assays. This is because the assay described detects both mutated and non-mutated sequences thereby facilitating determining the level of methylation. However, an assay detecting only methylated or non-methylated sequences is contemplated by the invention.
Amplification-Based Assay Format
[0508] In an alternative example, the hybridization is detected using an amplification system using any amplification assay format as described herein above for positive read-out assay albeit using primers (and probes where applicable) selectively hybridize to a mutated nucleic acid.
[0509] In adapting the HeavyMethyl assay described supra to a negative read-out format, the blockers that bind to bisulfite-treated nucleic acid in a methylation specific manner bind specifically to mutated DNA under moderate to high stringency conditions. An amplification reaction is performed using one or more primers that may optionally be methylation specific (i.e. only bind to mutated nucleic acid) but that flank the one or more blockers. In the presence of methylated nucleic acid (i.e., mutated DNA) the blocker/s bind and no PCR product is produced.
[0510] In one example, the reduced methylation in the normal/healthy control subject is detected by performing a process comprising:
[0511] (i) treating the nucleic acid with an amount of a compound that selectively mutates non-methylated cytosine residues under conditions sufficient to induce mutagenesis thereby producing a mutated nucleic acid;
[0512] (ii) hybridizing the nucleic acid to two non-overlapping and non-complementary primers each of which comprises a nucleotide sequence that is complementary to a sequence in the DNA comprising a mutated cytosine residue under conditions such that hybridization to the mutated nucleic acid occurs;
[0513] (iii) amplifying nucleic acid intervening the hybridized primers thereby producing a DNA fragment consisting of a sequence that comprises a primer sequence;
[0514] (iv) hybridizing the amplified DNA fragment to a probe comprising a nucleotide sequence that corresponds or is complementary to a sequence comprising a mutated cytosine residue under conditions such that hybridization to the mutated nucleic acid occurs; and
[0515] (v) detecting the hybridization.
[0516] As will be apparent to the skilled artisan a negative read-out assay preferably includes a suitable control sample to ensure that the negative result is caused by methylated nucleic acid rather than a reaction failing.
[0517] This invention also provides kits for the detection and/or quantification of the diagnostic sequences of the invention, or expression or methylation thereof using the methods described herein.
[0518] For kits for detection of methylation, the kits of the invention can comprise at least one polynucleotide that hybridizes to at least one of the diagnostic sequences of the invention and at least one reagent for detection of gene methylation. Reagents for detection of methylation include, e.g., sodium bisulfite, polynucleotides designed to hybridize to sequence that is the product of a biomarker sequence of the invention if the biomarker sequence is not methylated (e.g., containing at least one C.fwdarw.U conversion), and/or a methylation-sensitive or methylation-dependent restriction enzyme. The kits may also include control natural or synthetic DNA sequences representing methylated or unmethylated forms of the sequence. The kits can provide solid supports in the form of an assay apparatus that is adapted to use in the assay. The kits may further comprise detectable labels, optionally linked to a polynucleotide, e.g., a probe, in the kit. Other materials useful in the performance of the assays can also be included in the kits, including test tubes, transfer pipettes, and the like. The kits can also include written instructions for the use of one or more of these reagents in any of the assays described herein.
[0519] As detailed hereinbefore, hypermethylation is associated with transcriptional silencing. Accordingly, in addition to the increased level of methylation of these genes providing a basis upon which to screen for the predisposition to or onset of a large intestine neoplasm, the downregulation in the level of expression of these genes is also diagnostically valuable. In accordance with this aspect of the present invention, reference to a gene "expression product" or "expression of a gene" is a reference to either a transcription product (such as primary RNA or mRNA) or a translation product such as protein. In this regard, one can assess changes to the level of expression of a gene either by screening for changes to the level of expression product which is produced (i.e. RNA or protein), changes to the chromatin proteins with which the gene is associated, for example the presence of histone H3 methylated on lysine at amino acid position number 9 or 27 (repressive modifications) or changes to the DNA itself which acts to downregulate expression, such as changes to the methylation of the DNA. These genes and their gene expression products, whether they be RNA transcripts, changes to the DNA which act to downregulate expression or encoded proteins, are collectively referred to as "neoplastic markers".
[0520] Accordingly, another aspect of the present invention is directed to a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the level of expression of a DNA region selected from:
[0521] (i) the region, including 2 kb upstream of the transcription start site, defined by any two or more of Hg19 coordinates:
[0522] (1) chr12:24962958..25102393
[0523] (2) chr7:50344378...50472798
[0524] (3) chr6:391739..411443; or
[0525] (4) chr12:52400748..52409671; and
[0526] (5) chr6:163834097..163834982; or
[0527] (ii) the gene region, including 2 kb upstream of any two or more of:
[0528] (1) BCAT1 (2) IKZF1 (3) IRF4 (4) GRASP and (5) CAHM in a biological sample from said individual wherein a lower level of expression of at least one of the DNA regions of group (i) and/or (ii) relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a neoplastic state.
[0529] In one embodiment, said method is directed to identifying biological samples in which any one of said DNA regions exhibits a higher level of methylation.
[0530] In another embodiment, said method is directed to identifying biological samples in which two or more of said DNA regions exhibits a higher level of methylation.
[0531] The method of this aspect of the present invention is predicated on the comparison of the level of the neoplastic markers of a biological sample with the control levels of these markers. The "control level" may be either a "normal level", which is the level of marker expressed by a corresponding large intestine cell or cellular population which is not neoplastic.
[0532] As detailed hereinbefore, the normal (or "non-neoplastic") level may be determined using tissues derived from the same individual who is the subject of testing. However, it would be appreciated that this may be quite invasive for the individual concerned and it is therefore likely to be more convenient to analyze the test results relative to a standard result which reflects individual or collective results obtained from individuals other than the patient in issue.
[0533] There is more particularly provided a method of screening for the onset or predisposition to the onset of or monitoring a large intestine neoplasm in an individual, said method comprising assessing the level of expression of one or more genes or transcripts selected from:
[0534] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0535] (1) chr12:24962958..25102393; and
[0536] (2) chr7:50344378...50472798;
[0537] and optionally one or more of (3) chr6:391739..411443, (4) chr12:52400748..52409671 and (5) chr6:163834097..163834982; or
[0538] (ii) the gene region, including 2 kb upstream or:
[0539] (1) BCAT1; and
[0540] (2) IKZF1;
[0541] and optionally one or more of (3) IRF4, (4) GRASP and (5) CAHM in a biological sample from said individual wherein a lower level of expression of at least one of the DNA regions of group (i) and/or group (ii) relative to control levels is indicative of a neoplastic large intestine neoplasm or a predisposition to the onset of a neoplastic state.
[0542] Preferably, said control level is a non-neoplastic level.
[0543] In one embodiment of this aspect, the gene marker panel which is screened for is:
[0544] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0545] (1) chr12:24962958..25102393
[0546] (2) chr7:50344378...50472798; and
[0547] (3) chr6:391739..411443; or
[0548] (ii) the gene region, including 2 kb upstream of:
[0549] (1) BCATI (2) IKZF1 and (3) IRF4
[0550] In another embodiment of this aspect, the gene marker panel which is screened for is:
[0551] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0552] (1) chr12:24962958..25102393
[0553] (2) chr7:50344378...50472798; and
[0554] (4) chr12:52400748..52409671; or
[0555] (ii) the gene region, including 2 kb upstream of:
[0556] (1) BCAT1 (2) IKZF1 and (4) GRASP.
[0557] In still another embodiment of this aspect, the gene marker panel which is screened for is:
[0558] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0559] (1) chr12:24962958..25102393
[0560] (2) chr7:50344378...50472798; and
[0561] (5) chr6:163834097..163834982; or
[0562] (ii) the gene region, including 2 kb upstream of:
[0563] (1) BCAT1 (2) IKZF1 and (5) CAHM
[0564] In still yet another embodiment of this aspect, the gene marker panel which is screened for is:
[0565] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0566] (1) chr12:24962958..25102393
[0567] (2) chr7:50344378...50472798
[0568] (3) chr6:391739..411443; and
[0569] (4) chr12:52400748..52409671; or
[0570] (ii) the gene region, including 2 kb upstream of:
[0571] (1) BCAT1 (2) IKZF1 (3) IRF4 and (4) GRASP
[0572] In yet still another embodiment of this aspect, the gene marker panel which is screened for is:
[0573] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0574] (1) chr12:24962958..25102393
[0575] (2) chr7:50344378...50472798
[0576] (3) chr6:391739..411443; and
[0577] (5) chr6:163834097..163834982; or
[0578] (ii) the gene region, including 2 kb upstream of:
[0579] (1) BCAT1 (2) IKZF1 (3) IRF4 and (5) CAHM.
[0580] In a further embodiment of this aspect, the gene marker panel which is screened for is:
[0581] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0582] (1) chr12:24962958..25102393
[0583] (2) chr7:50344378...50472798
[0584] (4) chr12:52400748..52409671; and
[0585] (5) chr6:163834097..163834982; or
[0586] (ii) the gene region, including 2 kb upstream of any one or more of:
[0587] (1) BCAT1 (2) IKZF1 (4) GRASP and (5) CAHM
[0588] In yet another further embodiment of this aspect, the gene marker panel which is screened for is:
[0589] (i) the DNA regions, including 2 kb upstream of the transcription start site, defined by Hg19 coordinates:
[0590] (1) chr12:24962958..25102393
[0591] (2) chr7:50344378...50472798
[0592] (3) chr6:391739..411443; or
[0593] (4) chr12:52400748..52409671; and
[0594] (5) chr6:163834097..163834982; or
[0595] (ii) the gene region, including 2 kb upstream of any one or more of:
[0596] (1) BCAT1 (2) IKZF1 (3) IRF4 (4) GRASP and (5) CAHM.
[0597] In one embodiment, said method is directed to identifying biological samples in which any one of said DNA regions exhibits a higher level of methylation.
[0598] In another embodiment, said method is directed to identifying biological samples in which two or more of said DNA regions exhibits a higher level of methylation.
[0599] As detailed hereinbefore, the present invention is designed to screen for a neoplastic cell or cellular population, which is located in the large intestine. Accordingly, reference to "cell or cellular population" should be understood as a reference to an individual cell or a group of cells. Said group of cells may be a diffuse population of cells, a cell suspension, an encapsulated population of cells or a population of cells which take the form of tissue.
[0600] Reference to "expression" should be understood as a reference to the transcription and/or translation of a nucleic acid molecule. Reference to "RNA" should be understood to encompass reference to any form of RNA, such as primary RNA or mRNA or non-translated RNA (e.g. miRNAs etc.). Without limiting the present invention in any way, the modulation of gene transcription leading to increased or decreased RNA synthesis may also correlate with the translation of some of these RNA transcripts (such as mRNA) to produce a protein product. Accordingly, the present invention also extends to detection methodology which is directed to screening for modulated levels or patterns of the neoplastic marker protein products as an indicator of the neoplastic state of a cell or cellular population. Although one method is to screen for mRNA transcripts and/or the corresponding protein product, it should be understood that the present invention is not limited in this regard and extends to screening for any other form of neoplastic marker expression product such as, for example, a primary RNA transcript.
[0601] In terms of screening for the downregulation of expression of a marker it would also be well known to the person of skill in the art that changes which are detectable at the DNA level are indicative of changes to gene expression activity and therefore changes to expression product levels. Such changes include but are not limited to, changes to DNA methylation. Accordingly, reference herein to "screening the level of expression" and comparison of these "levels of expression" to control "levels of expression" should be understood as a reference to assessing DNA factors which are related to transcription, such as gene/DNA methylation patterns. These have, in part, been described in detail hereinbefore.
[0602] It would also be known to a person skilled in the art that changes in the structure of chromatin are indicative of changes in gene expression. Silencing of gene expression is often associated with modification of chromatin proteins, methylation of lysines at either or both positions 9 and 27 of histone H3 being well studied examples, while active chromatin is marked by acetylation of lysine 9 of histone H3. Thus association of gene sequences with chromatin carrying repressive or active modifications can be used to make an assessment of the expression level of a gene.
[0603] Reference to "nucleic acid molecule" should be understood as a reference to both deoxyribonucleic acid molecules and ribonucleic acid molecules and fragments thereof. The present invention therefore extends to both directly screening for mRNA levels in a biological sample or screening for the complementary cDNA which has been reverse-transcribed from an mRNA population of interest. It is well within the skill of the person of skill in the art to design methodology directed to screening for either DNA or RNA. As detailed above, the method of the present invention also extends to screening for the protein product translated from the subject mRNA or the genomic DNA itself.
[0604] In one preferred embodiment, the level of gene expression is measured by reference to genes which encode a protein product and, more particularly, said level of expression is measured at the protein level.
[0605] In another particularly preferred embodiment, said gene expression is assessed by the association of DNA with chromatin proteins carrying repressive modifications, for example, methylation of lysines 9 or 27 of histone H3.
[0606] The present invention should be understood to encompass methods of detection based on identifying both proteins and/or nucleic acid molecules in one or more biological samples. This may be of particular significance to the extent that some of the neoplastic markers of interest may correspond to genes or gene fragments which do not encode a protein product. Accordingly, to the extent that this occurs it would not be possible to test for a protein and the subject marker would have to be assessed on the basis of transcription expression profiles or changes to genomic DNA.
[0607] The term "protein" should be understood to encompass peptides, polypeptides and proteins (including protein fragments). The protein may be glycosylated or unglycosylated and/or may contain a range of other molecules fused, linked, bound or otherwise associated to the protein such as amino acids, lipids, carbohydrates or other peptides, polypeptides or proteins. Reference herein to a "protein" includes a protein comprising a sequence of amino acids as well as a protein associated with other molecules such as amino acids, lipids, carbohydrates or other peptides, polypeptides or proteins.
[0608] The proteins encoded by the neoplastic markers of the present invention may be in multimeric form meaning that two or more molecules are associated together. Where the same protein molecules are associated together, the complex is a homomultimer. An example of a homomultimer is a homodimer. Where at least one marker protein is associated with at least one non-marker protein, then the complex is a heteromultimer such as a heterodimer.
[0609] Reference to a "fragment" should be understood as a reference to a portion of the subject nucleic acid molecule or protein. This is particularly relevant with respect to screening for modulated RNA levels in stool samples since the subject RNA is likely to have been degraded or otherwise fragmented due to the environment of the gut. One may therefore actually be detecting fragments of the subject RNA molecule, which fragments are identified by virtue of the use of a suitably specific probe.
[0610] Although the preferred method is to detect the expression product or DNA changes of the neoplastic markers for the purpose of diagnosing neoplasia development or predisposition thereto, the detection of converse changes in the levels of said markers may be desired under certain circumstances, for example, to monitor the effectiveness of therapeutic or prophylactic treatment directed to modulating a neoplastic condition, such as adenoma or adenocarcinoma development. For example, where reduced expression of the subject markers indicates that an individual has developed a condition characterized by adenoma or adenocarcinoma development, for example, screening for an increase in the levels of these markers subsequently to the onset of a therapeutic regime may be utilized to indicate reversal or other form of improvement of the subject individual's condition. The method of the present invention is therefore useful as a one off test or as an on-going monitor of those individuals thought to be at risk of neoplasia development or as a monitor of the effectiveness of therapeutic or prophylactic treatment regimens directed to inhibiting or otherwise slowing neoplasia development.
[0611] Means of assessing the subject expressed neoplasm markers in a biological sample can be achieved by any suitable method, which would be well known to the person of skill in the art. To this end, it would be appreciated that to the extent that one is examining either a homogeneous cellular population (such as a tumor biopsy or a cellular population which has been enriched from a heterogeneous starting population) or a tissue section, one may utilize a wide range of techniques such as in situ hybridization, assessment of expression profiles by microassays, immunoassays and the like (hereinafter described in more detail) to detect the absence of or downregulation of the level of expression of one or more markers of interest. However, to the extent that one is screening a heterogenous cellular population or a bodily fluid in which heterogeneous populations of cells are found, such as a blood sample, the absence of or reduction in level of expression of a particular marker may be undetectable due to the inherent expression of the marker by non-neoplastic cells which are present in the sample. That is, a decrease in the level of expression of a subgroup of cells may not be detectable. In this situation, a more appropriate mechanism of detecting a reduction in a neoplastic subpopulation of the expression levels of one or more markers of the present invention is via indirect means, such as the detection of epigenetic changes.
[0612] Methods of detecting changes to gene expression levels (in addition to the methylation analyses hereinbefore described in detail), particularly where the subject biological sample is not contaminated with high numbers of non-neoplastic cells, include but are not limited to:
[0613] In vivo detection.
[0614] Molecular Imaging may be used following administration of imaging probes or reagents capable of disclosing altered expression of the markers in the intestinal tissues.
[0615] Molecular imaging (Moore et al., BBA, 1402:239-249, 1988; Weissleder et al., Nature Medicine 6:351-355, 2000) is the in vivo imaging of molecular expression that correlates with the macro-features currently visualized using "classical" diagnostic imaging techniques such as X-Ray, computed tomography (CT), MRI, Positron Emission Tomography (PET) or endoscopy.
[0616] Detection of downregulation of RNA expression in the cells by Fluorescent In Situ Hybridization (FISH), or in extracts from the cells by technologies such as Quantitative Reverse Transcriptase Polymerase Chain Reaction (QRTPCR) or Flow cytometric qualification of competitive RT-PCR products (Wedemeyer et al., Clinical Chemistry 48:9 1398-1405, 2002).
[0617] Assessment of expression profiles of RNA, for example by array technologies (Alon et al., Proc. Natl. Acad. Sci. USA: 96:6745-6750, June 1999).
[0618] A "microarray" is a linear or multi-dimensional array of preferably discrete regions, each having a defined area, formed on the surface of a solid support. The density of the discrete regions on a microarray is determined by the total numbers of target polynucleotides to be detected on the surface of a single solid phase support. As used herein, a DNA microarray is an array of oligonucleotide probes placed onto a chip or other surfaces used to amplify or clone target polynucleotides. Since the position of each particular group of probes in the array is known, the identities of the target polynucleotides can be determined based on their binding to a particular position in the microarray.
[0619] DNA microarray technology make it possible to conduct a large-scale assay of a plurality of target nucleic acid molecules on a single solid phase support. U.S. Pat. No. 5,837,832 (Chee et al.) and related patent applications describe immobilizing an array of oligonucleotide probes for hybridization and detection of specific nucleic acid sequences in a sample. Target polynucleotides of interest isolated from a tissue of interest are hybridized to the DNA chip and the specific sequences detected based on the target polynucleotides' preference and degree of hybridization at discrete probe locations. One important use of arrays is in the analysis of differential gene expression, where the profile of expression of genes in different cells or tissues, often a tissue of interest and a control tissue, is compared and any differences in gene expression among the respective tissues are identified. Such information is useful for the identification of the types of genes expressed in a particular tissue type and diagnosis of conditions based on the expression profile.
[0620] Measurement of altered neoplastic marker protein levels in cell extracts, for example by immunoassay.
[0621] Testing for proteinaceous neoplastic marker expression product in a biological sample can be performed by any one of a number of suitable methods which are well known to those skilled in the art. Examples of suitable methods include, but are not limited to, antibody screening of tissue sections, biopsy specimens or bodily fluid samples. To the extent that antibody-based methods of diagnosis are used, the presence of the marker protein may be determined in a number of ways such as by Western blotting, ELISA or flow cytometry procedures. These, of course, include both single-site and two-site or "sandwich" assays of the non-competitive types, as well as in the traditional competitive binding assays. These assays also include direct binding of a labeled antibody to a target.
[0622] Determining altered expression of protein neoplastic markers on the cell surface, for example by immunohistochemistry.
[0623] Determining altered protein expression based on any suitable functional test, enzymatic test or immunological test in addition to those detailed in points (iv) and (v) above.
[0624] A person of ordinary skill in the art could determine, as a matter of routine procedure, the appropriateness of applying a given method to a particular type of biological sample.
[0625] A related aspect of the present invention provides a molecular array, which array comprises a plurality of:
[0626] (i) nucleic acid molecules comprising a nucleotide sequence corresponding to any two or more of the neoplastic marker DNA hereinbefore described or a sequence exhibiting at least 80% identity thereto or a functional derivative, fragment, variant or homologue of said nucleic acid molecule; or
[0627] (ii) nucleic acid molecules comprising a nucleotide sequence capable of hybridizing to any one or more of the sequences of (i) under medium stringency conditions or a functional derivative, fragment, variant or homologue of said nucleic acid molecules; or
[0628] (iii) nucleic acid probes or oligonucleotides comprising a nucleotide sequence capable of hybridizing to any two or more of the sequences of (i) under medium stringency conditions or a functional derivative, fragment, variant or homologue of said nucleic acid molecule; or
[0629] (iv) probes capable of binding to any two or more of the proteins encoded by the nucleic acid molecules of (i) or a derivative, fragment or, homologue thereof wherein the level of expression of said marker genes of (i)-(iii) or proteins of (iv) is indicative of the neoplastic state of a cell or cellular subpopulation derived from the large intestine.
[0630] Preferably, said percent identity is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%.
[0631] "Hybridization" refers to the process by which a nucleic acid strand joins with a complementary strand through base pairing. Hybridization reactions can be sensitive and selective so that a particular sequence of interest can be identified even in samples in which it is present at low concentrations. Stringent conditions can be defined by, for example, the concentrations of salt or formamide in the prehybridization and hybridization solutions, or by the hybridization temperature, and are well known in the art. For example, stringency can be increased by reducing the concentration of salt, increasing the concentration of formamide, or raising the hybridization temperature, altering the time of hybridization, as described in detail, below. In alternative aspects, nucleic acids of the invention are defined by their ability to hybridize under various stringency conditions (e.g., high, medium, and low), as set forth herein.
[0632] Reference herein to a low stringency includes and encompasses from at least about 0 to at least about 15% v/v formamide and from at least about 1 M to at least about 2 M salt for hybridization, and at least about 1 M to at least about 2 M salt for washing conditions. Generally, low stringency is at from about 25-30.degree. C. to about 42.degree. C. The temperature may be altered and higher temperatures used to replace formamide and/or to give alternative stringency conditions. Alternative stringency conditions may be applied where necessary, such as medium stringency, which includes and encompasses from at least about 16% v/v to at least about 30% v/v formamide and from at least about 0.5 M to at least about 0.9 M salt for hybridization, and at least about 0.5 M to at least about 0.9 M salt for washing conditions, or high stringency, which includes and encompasses from at least about 31% v/v to at least about 50% v/v formamide and from at least about 0.01 M to at least about 0.15 M salt for hybridization, and at least about 0.01 M to at least about 0.15 M salt for washing conditions. In general, washing is carried out T.sub.m=69.3+0.41 (G+C) % (Marmur and Doty, J. Mol. Biol. 5:109, 1962). However, the T.sub.m of a duplex DNA decreases by 1.degree. C. with every increase of 1% in the number of mismatch base pairs (Bonner and Laskey, Eur. J. Biochem. 46:83, 1974). Formamide is optional in these hybridization conditions. Accordingly, particularly preferred levels of stringency are defined as follows: low stringency is 6.times.SSC buffer, 0.1% w/v SDS at 25-42.degree. C.; a moderate stringency is 2.times.SSC buffer, 0.1% w/v SDS at a temperature in the range 20.degree. C. to 65.degree. C.; high stringency is 0.1.times.SSC buffer, 0.1% w/v SDS at a temperature of at least 65.degree. C.
[0633] Where nucleic acids of the invention are defined by their ability to hybridize under high stringency, these conditions comprise about 50% formamide at about 37.degree. C. to 42.degree. C. In one aspect, nucleic acids of the invention are defined by their ability to hybridize under reduced stringency comprising conditions in about 35% to 25% formamide at about 30.degree. C. to 35.degree. C. Alternatively, nucleic acids of the invention are defined by their ability to hybridize under high stringency comprising conditions at 42.degree. C. in 50% formamide, 5.times.SSPE, 0.3% SDS, and a repetitive sequence blocking nucleic acid, such as cot-1 or salmon sperm DNA (e.g., 200 n/ml sheared and denatured salmon sperm DNA). In one aspect, nucleic acids of the invention are defined by their ability to hybridize under reduced stringency conditions comprising 35% formamide at a reduced temperature of 35.degree. C.
[0634] Preferably, the subject probes are designed to bind to the nucleic acid or protein to which they are directed with a level of specificity which minimizes the incidence of non-specific reactivity. However, it would be appreciated that it may not be possible to eliminate all potential cross-reactivity or non-specific reactivity, this being an inherent limitation of any probe-based system.
[0635] In terms of the probes which are used to detect the subject proteins, they may take any suitable form including antibodies and aptamers.
[0636] A library or array of nucleic acid or protein probes provides rich and highly valuable information. Further, two or more arrays or profiles (information obtained from use of an array) of such sequences are useful tools for comparing a test set of results with a reference, such as another sample or stored calibrator. In using an array, individual probes typically are immobilized at separate locations and allowed to react for binding reactions. Primers associated with assembled sets of markers are useful for either preparing libraries of sequences or directly detecting markers from other biological samples.
[0637] A library (or array, when referring to physically separated nucleic acids corresponding to at least some sequences in a library) of gene markers exhibits highly desirable properties. These properties are associated with specific conditions, and may be characterized as regulatory profiles. A profile, as termed here refers to a set of members that provides diagnostic information of the tissue from which the markers were originally derived. A profile in many instances comprises a series of spots on an array made from deposited sequences.
[0638] A characteristic patient profile is generally prepared by use of an array. An array profile may be compared with one or more other array profiles or other reference profiles. The comparative results can provide rich information pertaining to disease states, developmental state, receptiveness to therapy and other information about the patient.
[0639] Another aspect of the present invention provides a diagnostic kit for assaying biological samples comprising one or more agents for detecting one or more neoplastic markers and reagents useful for facilitating the detection by said agents. Further means may also be included, for example, to receive a biological sample. The agent may be any suitable detecting molecule.
[0640] The present invention is further described by reference to the following non-limiting examples.
EXAMPLE 1
CAHM: Colorectal Adenocarcinoma HyperMethylated
[0641] Single-plex performance:
[0642] 74 normals: 0.8 pg hypermethylated/mL plasma (95% CI: 0.2; 1.4)
[0643] 73 adenomas: 9.1 pg hypermethylated/mL plasma (95% CI: -8; 27)
[0644] 73 cancers: 1788 pg hypermethylated/mL plasma (95% CI: 231; 3344).
[0645] The CAHM assay (threshold cut of 3 pg/mL plasma) is 55% sensitive for colorectal cancer with a 93% specificity (FIG. 1).
GRASP: General Receptor for Phosphoinositides 1-Associated Scaffold Protein.
[0646] Single plex performance:
[0647] 34 normals: 1.3 pg hypermethylated/mL plasma (95% CI: 0.2; 2.5)
[0648] 33 adenomas: 0.1 pg hypermethylated/mL plasma (95% CI: -0.1; 0.4)
[0649] 33 cancers: 670.8 pg hypermethylated/mL plasma (95% CI: -470.7; 1812)
[0650] The GRASP assay is 58% sensitive for colorectal cancer with a 100% specificity using a threshold cut of 20 pg methylated/mL plasma (FIG. 2).
IRF4: Interferon Regulatory Factor 4
[0651] Single plex performance:
[0652] 24 normals: 6 pg hypermethylated/mL plasma (95% CI: 2.9; 9.0)
[0653] 23 adenomas: 3.7 pg hypermethylated/mL plasma (95% CI: -0.4; 8.0)
[0654] 33 cancers: 5340 pg hypermethylated/mL plasma (95% CI: -5369; 16049)
[0655] The IRF4 assay is 57% sensitive for colorectal cancer with a 96% specificity using a threshold cut of 20 pg methylated/mL plasma (FIG. 3).
BCAT1: Branched Chain Amino Acid Transaminase 1, Cytosolic
[0656] Single plex performance summary
[0657] 14 normals: 0 pg hypermethylated/mL plasma (95% CI: na)
[0658] 13 adenomas: 0.4 pg hypermethylated/mL plasma (95% CI: -0.4; 1.3)
[0659] 13 cancers: 4088 pg hypermethylated/mL plasma (95% CI: -4459; 10539)
[0660] The BCAT1 assay is 62% sensitive for colorectal cancer with a 100% specificity using a threshold cut of 3 pg methylated/mL plasma (FIG. 4).
IKZF1: IKAROS Family Zinc Finger 1
[0661] Single plex performance summary
[0662] 14 normals: 0 pg hypermethylated/mL plasma (95% CI: na)
[0663] 13 adenomas: 0 pg hypermethylated/mL plasma (95% CI: na)
[0664] 13 cancers: 113 pg hypermethylated/mL plasma (95% CI: -43; 270)
[0665] The IKZF1 assay is 54% sensitive for colorectal cancer with a 100% specificity using a threshold cut of 3 pg methylated/mL plasma (FIG. 4).
[0666] The methylation levels of the five genes were measured in the same 14 normals, 13 adenomas and 13 cancers. The table below demonstrates the improvement in clinical utility when measuring the methylation in TWO of the genes:
TABLE-US-00009 (% sens; % spec) CAHM>.sub.6 pg/mL GRASP.sub.>20 pg/mL IRF4.sub.>20 pg/mL BCAT.sub.>3 pg/mL IKZF1.sub.>3 pg/mL CAHM>.sub.6 pg/mL 54%; 100% 62%; 100% 69%; 100% 69%; 100% 69%; 100% GRASP.sub.>20 .sub.pg/mL -- 54%; 100% 69%; 100% 77%; 100% 77%; 100% IRF4.sub.>20 .sub.pg/mL -- -- 54%; 100% 85%; 100% 69%; 100% BCAT.sub.>3 .sub.pg/mL -- -- -- 62%; 100% 77%; 100% IKZF1.sub.>3 .sub.pg/mL -- -- -- -- 54%; 100%
[0667] Combining the methylation levels measured in any three of the five genes resulted in:
[0668] CAHM.sub.6 pg/mL-GRASP.sub.20 pg/mL-IRF4.sub.20 pg/mL: 77% sensitivity and 100% specificity
[0669] CAHM.sub.6 pg/mL-GRASP.sub.20 pg/mL-BCAT.sub.3 pg/mL: 77% sensitivity and 100% specificity
[0670] CAHM.sub.6 pg/mL-GRASP.sub.20 pg/mL-IKZF1.sub.3 pg/mL: 77% sensitivity and 100% specificity
[0671] CAHM.sub.6 pg/mL-IKZF1.sub.3 pg/mL-BCAT.sub.3 pg/mL: 77% sensitivity and 100% specificity
[0672] GRASP.sub.20 pg/mL-IKZF1.sub.3 pg/mL-BCAT.sub.3 pg/mL: 85% sensitivity and 100% specificity
[0673] Combining the methylation levels from all five genes results in a 92% sensitivity and 100% specificity:
[0674] Targeted Amplicon Sequences for GRASP, CAHM, IRF4, IKZF1 and BCAT1
[0675] The wild-type DNA sequence of the CAHM MSP amplicon is located on Chromosome 6, plus strand; 163,834,393163,834,455 (Hg19) GAAGGAAGCA TTTCGAGCAC GACTGACGCT CCCCTTATTA TTTGCTAAGC CGCTGCGCTC GGG
[0676] The wild-type DNA sequence of the GRASP MSP amplicon is located on Chromosome 12, plus strand; 52,400,88652,400,973 (Hg19) cggaagtcgc gcccgccgct ccggtcccga ccccgggacc ccctgccgca gccgccaccc ctgggccccc agcggacgag ctgtacgc
[0677] The wild-type DNA sequence of the IKZF1 MSP amplicon is located on Chromosome 7, plus strand; 50,343,86750,343,961 (Hg19) gacgacgcac cctctccgtg tcccgctctg cgcccttctg cgcgccccgc tccctgtacc ggagcagcga tccgggaggc ggccgagagg tg
[0678] The wild-type DNA sequence of the BCAT1 MSP amplicon is located on Chromosome 12, minus strand; 25,101,99225,102,093 (Hg19) gtcttcctgc tgatgcaatc CGctaggtcg cgagtctccg ccgcgagagg gccggtctgc aatccagccc gccacgtgta ctcgccgccg cctcg
[0679] The wild-type DNA sequence of the IRF4 MSP amplicon is located on Chromosome 6, minus strand; 392,036392,145 (Hg19) tgggtgcctt ggacggcccc gcctcagcca ctcctggggc cccgacagtc cggttagctc atcccgtcca gcttgtggcg accccgtcgc aggagcgcgg agggcaggcg
[0680] PCR Protocols Used to Measure the Methylation Levels Across GRASP, CAHM, IRF4, IKZF1 and BCAT1 in Plasma Specimens
Real-Time PCR Protocols GRASP, CAHM, IRF4, BCAT1, IKZF1
TABLE-US-00010
[0681] Real-time PCR protocols GRASP, CAHM, IRF4, BCAT1, IKZF1 CAHM GRASP IRF4 BCAT1 IKZF1 FWD 5`GAAGGA 5`CGGAAG 5`TGGGTG 5`GTTTTTTT 5`GACGACGT Primer AGTATTT TCGCGTTC TTTTGGA GTTGATGT ATTTTTTTCG CGAGTAC GTC CGGTTTC AATTCGTT TGTTTC GATTGAC 200 nM 400 nM AGGTC 200 nM 200 nM final final 200 nM final final final REV 5`CCCGAA 5`GCGTACA 5`CGCCTA 5`CAATACC 5`GCGCACCT primer CGCAACG ACTCGTCC CCCTCCG CGAAACGA CTCGACCG ACTTAA GCTAA CG CGACG 200 nM 200 nM 200 nM 400 nM 200 nM final final final final final Probe na [HEX] [HEX] [HEX] na TTCGATTT TCGTTTA TTCGTCGC CGGGATTT GTTTGTG GAGAGGGT TTTGTCGT GCGATTT CGGTT AGTC CGTCG [BHQ] [BHQ1] [BHQ1] 200 nM 100 nM 200 nM final final final 1x PCR Platinum Platinum Platinum Platinum GoTaq Hot Taq DNA Taq Taq DNA Taq Start buffer. polymerase DNA polymerase DNA 1x buffer (Invitrogen) polymerase (Invitrogen) polymerase contains (Invitrogen) (Invitrogen) 2 mM MgC12 (Promega) Final 4.0 4.0 3.0 4.0 +1.0 MgCL.sub.2 conc. [Mm] dNTPs 0.2 mM 0.2 mM 0.2 mM 0.2 mM -- SYBR 1/120,000 na na na 1/120,000 LC480 cycling conditions 1x 95.degree. C.; 95.degree. C.; 95.degree. C.; 95.degree. C.; 95.degree. C.; 2 min 2 min 2 min 2 min 2 min 3x 92.degree. C.; 92.degree. C.; 50 cycles: 50 cycles: 50 cycles: 15 sec 15 sec 95.degree. C.; 95.degree. C.; 95.degree. C.; 62.degree. C.; 64.degree. C.; 10 15 sec 15 sec 15 sec 15 sec sec 62.degree. C.; 62.degree.C; 72.degree. C.; 72.degree. C.; 61.degree. C.; 30 sec 30 sec 20 sec 20 sec 20 72.degree. C.; 72.degree. C.; sec 30 sec 30 sec 47x 82.degree. C.; 85.degree. C., (w/quant) (w/quant) (w/quant) 15 sec 15 sec 62.degree. C.; 64.degree. C.; 15 sec 15 sec 72.degree. C.; 72.degree. C.; 20 sec 20 sec (w/quant) (w/quant) melt 95.degree. C.; na na na 95.degree. C.; curve 5 sec 5 sec analysis 65.degree. C.; 65.degree. C.; 1 min 1 min 97.degree. C. 97.degree. C. continuous continuous 0.11 deg/sec 0.11 deg/sec Correct <80.degree. C. na na na 82.9-83.2.degree. C. Melt Temp (.degree. C.)
TABLE-US-00011 TABLE 1 Current Resulting sub- bisulphite Oligonucleotide region(s) converted sequences for of sequence measurement interest Coordinates (strands of Genomic (genomic of sub- no longer methylation Gene Strand sequence) region(s) complementary) levels BCAT1 top 5`- 25,101,992- 5`- strand cagtgccCGaggC 25,102,093 tagtgttCGaggCGgC GgCGgCGagtac GgCGagtataCGtgg aCGtggC CGggttgga Gggctggattgcaga ttgtagatCGgttttttCG cCGgccctctCGC CGgCGgagattCGC GgCGgagactCG GatttagC Ggattgtatta CGacctagCGgatt gtaggaagat gcatcagcaggaaga c (SEQ ID NO. 1) minus 3`- 3`- 5`- strand gtcacggGCtccG gttatggGCtttGCtGC gtttttttgttgatg CcGCcGCtcatgt tGCttatgtGCattGCtt taattcgttaggtc GCaccGCc gatttaatg 5`- cgacctaacgtctgG tttgGCtgggagaGCG caatacccgaaa CcgggagaGCGC CtGCttttgaGCGCtg cgacgacg cGCctctgaGCG gattGCttaatgtagttgtt 5`- CtggatcGCctaac tttttg ttcgtcgcgaga gtagtcgtccttctg gggtcggtt 5`- tttttgttgatgtaa ttcgttaggtc 5`- attacaaaccga ccctctcg top 5`- 25,101,909- This sequence 5`- strand agatcccaagggtC 25,101,995 is for agatcccaaggg GtagcccctggcCG measuring CpG tcgtagc tgtggacCGg methylation 5`- gtctgCGgctgcaga levels actgccccaggt gCGCGctccCGg using cttgct ctgcagcaagacctg methylation gggcagt (SEQ ID sensitive restriction NO. 2) enzymes (e.g. HbaII, HhaI (underlined) minus 3`- strand tctagggttcccaGC atcggggaccgGCa cacctgGCc cagacGCcgacgtc tcGCGCcaggGC cgacgtcgttctggac cccgtca IKZF1 top 5`- 50,343,867- 5`- 5`- strand gaCGaCGcaccct 50,343,961 gaCGaCGtatttttttC gacgacgtattttt ctcCGtgtccCGct GtgtttCGttttgCGtttt ttcgtgtttc ctgCGccctt tttgCGCG 5`- ctgC GCGcccCG tttCGttttttgtatCGga gcgcacctctcg ctccctgtacCGgag gtagCGattCGggagg accg cagCGatcCGgga CGgtCGagaggtgC 5`- ggCGgcCGagag Gt tttgtatcggagta gtgCGc (SEQ ID gcgattcgggag NO. 3) minus 3`- 3`- strand ctGCtGCgtggga ttGCtGCgtgggagag gagGCacaggGC GCataggGCgagatG gagacGCgg Cgggaa gaagacGCGCgg gatGCGCgggGCga gGCgagggacatg gggatatgGCtttgttG GCctcgtcGCtag CtagGCtttttGCtgG GCcctccGCcgG CtttttatGCg CtctccacGCg top 5`- 50,343,804- This sequence 5`- strand cCGgagttgCGgct 50,343,895 is for ggagttgcggct gagaCGCGCGc measuring CpG gagac CGCGCG methylation levels 5`- agcCGgggaactC using methylation agagcgggaca GgCGaCGgggC sensitive cggaga GgggaCGggaCG restriction aCGcaccctctcCG enzymes (e.g. tgtccCGctct HbaII, HhaI (SEQ ID NO. 4) (underlined) minus 3`- strand gGCctcaacGCcg actctGCGCGCg GCGCGC tcgGCcccctgaG CcGCtGCcccGC ccctGCcctGCtG CgtgggagagGCa caggGCgaga IRF4 top 5`- 392,036- 5`- 5`- strand CGcctgccctcCG 392,145 CGtttgtttttCGCGtttt gtttttgcgacgg CGctcctgCGaC tgCGaCGgggtCGtt ggtc GgggtCGcc ataagttg 5`- acaagctggaCGgg gaCGggatgagttaatC taaaaccccgac atgagctaacCGga GgattgtCGgggttttag aatccg ctgtCGgggcccca gagtggttgaggCGgg ggagtggctgaggC gtCGtttaaggtattta GgggcCGtccaag gcaccca (SEQ ID NO. 5) minus 3`- 3`- 5`- strand GCggacgggagG GCggatgggagGCG tgggtgttttgga CGCgaggacGCt CgaggatGCtGCttta cggtttc GCcccaGC GCggtgtttg 5`- ggtgttcgacctGCc atttGCtttatttgattgG tagttatttttggg ctactcgattgGCctg CttgataGCtttggggttt gtttcgatagttc acaGCcccggggtc ttattgattttGCtttgGC 5`- ctcaccgactccGCc aggttttgtgggt cgcctaccctcc ccgGCaggttccgtg gcg ggt 5`- tcgtttagtttgtg gcgatttcgtcg GRASP top 5`- 52,400,821- 5`- 5`- strand caggaagctgcagca 52,401,051 taggaagttgtagtagaag cggaagtcgcgt gaaggaggaggCG gaggaggCGgCGgtt tcgtc gCGgcca atttCGga 5`- cccCGgacccCGc tttCGtCGttCGgatttt gcgtacaactcgt CGccCGgactccC CGattCGgaagtCGC ccgctaa GactCGgaagtCG GttCGtCGtttCGgttt 5`- CGccCGcCGctc CGatttCGggattttttgt ttcgatttcgggat CGgtccCGacccC CGtagtCGttatttttgg tttttgtcgtagtc GggaccccctgcC gtttttagCGgaCGagtt 5`- GcagcCGccaccc gtaCGCGgCGttgga cggattttcgattc ctgggcccccagCG ggattattattttgtC Gagt ggaagt gaCGagctgtaCG tgtatCGCGCGttCG CGgCGctggagga tCGtgttCGggggtattt ctatcaccctgcCGa tgtttCGtCGaaaggtg gctgtacCGCGC CGtttttCGttCGttttta GctCGcCGtgtcC ggatttgtttagttttttttC Gggggcaccctgcc Gattttttatagggtttgttg cCGcCGaaaggtg atttCG CGtccccCGccC Gccttcaggatctgct cagcccctctcCGac tccctacagggcctgc tgactcCG (SEQ ID NO. 6) 3`- minus gtccttcgacgtcgtct strand tcctcctccGCcGC 3`- cggtgggG gttttttgatgttgtttttt CctgggGCgGCg ttttttGCtGCtggtgggGC gGCctgaggGCtg ttgggGC aGCctcaGCGCg gGCggGCttgaggG gGCgGCgagGC CtgaGCtttaGCGCg caggGCtgggGCc gGCgGCgagGCtag ctgggggacgGCgt gGCtgggGCtttgggg 5`- cgGCggtggggacc gatgGCgttgGCggtg ggtagggtgtttt cgggggtcGCctG gggatttgggggttGCtt cggatac CtcgacatGCGCc GCttgatatGCGCtG 5`- GCgacctcctgatag Cgattttttgatagtgggat aacgaacgaact tgggacgGCtcgac gGCttgatatgGCGC atacgcgac atgGCGCGCga GCgaGCgGCatagG GCgGCacagGCc CttttgtgggatgggGC cccgtgggacgggG gGCtttttatGCagggg CgGCtttccacGC GCggGCggaagtttta aggggGCggGCg gatgagttggggagagG gaagtcctagacgagt Ctgagggatgttttggatg cggggagagGCtga attgagGC gggatgtcccggacg actgagGC top 5`- 52,401,407- 5`- strand gacagagacagcccc 52,401,664 gatagagatagttttaggta aggcaagttgaaggtc agttgaaggttCGagagt CGagagc tttCGgtgg cccCGgtgggagaa gagaagCGggtCGgt gCGggcCGgtggc ggttgCGtCGCGtgC tgCGcCGCGtgC Gtttttattttgaggaagtg Gttctcactctgagga CGtggggagtC Gttgat agtgCGtggggagc ttCGgatagtatattttttC CGctgactcCGgat GaggggatttttCGatttt agcacacccttcCGa tgggttgggggtttgtCG ggggactcccCGatt tttggttttaCGtttgaCG cctgggctgggggcc taCGgggCGCGagg tgcCGcctggcccc gttattgttttttg aCGtctgaCGtaC gatttttgt GgggCGCGaggg CGgaatCGgaCGtag ccactgctccctggac tgggaggggtCGtagg ttctgtCGgaacCG gaCGcagtgggagg ggtCGcagg (SEQ ID NO. 7) minus 3`- 3`- 5`- strand ctgtctctgtcggggtc ttgtttttgttggggtttgttt cggagttagcgg cgttcaacttccagG aatttttagGCttttgggg ttttttacg Ctctcgggg GCtattttttt 5`- GCcaccctcttcGC tGCttgGCtattgatGC cgataaaaaaaa ccgGCcaccgacG gGCGCatGCaagagt cgaaccga CgGCGCacGCa gagatttttttatGCatttttt 5`- agagtgagactccttc gGCgattgagGCttatt agagtgagaacg acGCacccctcgG gtgtgggaagGCttttttg tacgcggc CgactgagGCctat agggGCtaaggatttgat cgtgtgggaagGCt ttttggatgGCggattgg cccctgagggGCta ggtGCagattGCatG aggacccgacccccg CtttGCGCttttggtgat gacgGCggaccgg gagggatttgaagataG ggtGC agactGC at CtttgGCttGCgttatttt GCcccGCGCtcc ttttaGCgttt cggtgacgagggacc tgaagacaGCcttg GCctGCgtcaccct ccccaGCgtcc top 5`- This sequence 5`- strand gacagagacagcccc is for caagttgaaggt aggcaagttgaaggtc measuring CpG ccgagagc CGagag methylation 5`- ccccCGgtgggag levels cgcacttcctcag agCGggcCGgtgg using agtgaga ctgCGcCGCGta methylation CGttctcactctgagg sensitive aagtgCGtggggag restriction cCGctaactcCGg enzymes (e.g. atagcacacccttcC HbaII, HhaI GaggggactcccC (underlined) Gattcctgggctggg ggcctgcCGcctgg ccccaCGtctgaCG taCGgggCGCGa gggccactgctccctg gacttctgtCGgaac CGgaCGcagtggg aggggtCGcagg minus 3`- strand ctgtctctgtcggggtc cgttcaacttccagG Ctctcgggg GCcaccctcttcGC ccgGCcaccgacG CgGCGCacGCa agagtgagactccttc
acGCacccctcgG CgactgagGCctat cgtgtgggaagGCt cccctgagggGCta aggacccgacccccg gacgGCggaccgg ggtGCagactGCat GCcccGCGCtcc cggtgacgagggacc tgaagacaGCcttg GCctGCgtcaccct ccccaGCgtcc CAHM top 5`- 163,834,295 5`- 5`- strand atctgtaaaaatgttga 163,834,500 atttgtaaaaatgttgattttt gaaggaagtattt cttctgcttttcagacta gttttttagattaCGCGta cgagtacgattg CGCGcac tagtttttttatt acc 5`- agcctctttatttcctac ttttattgCGgttttattttttt cccgaacgcaac tgCGgcttcattccct aCGgaatattgaCGtta gacttaa caCGgaacactgaC tCGCGaaggaagtattt 5`- GccatCGCGaag CGagtaCGattgaCGt gcctctaaaaaa gaagcatttCGagca tttttttattatttgttaagtC acgatcttattaca CGactgaCGctccc GttgCGttCGggtttgg cc cttattatttgctaagc ttaCGatttgtttttagaat CGctgCGctCGg aaCGggaaggtgtaata gtctggctaCGatttg aga ctttcagaataaCGg gaaggtgcaacaaga (SEQ ID NO. 8) minus 3`- strand ctgtctctgtcggggtc cgttcaacttccagG Ctctcgggg GCcaccctcttcGC ccgGCcaccgacG CgGCGCacGCa agagtgagactccttc acGCacccctcgG CgactgagGCctat cgtgtgggaagGCt cccctgagggGCta aggacccgacccccg gacgGCggaccgg ggtGCagactGCat GCcccGCGCtcc cggtgacgagggacc tgaagacaGCcttg GCctGCgtcaccct ccccaGCgtcc CAHM top 5`- 163,834,295 5`- 5`- strand atctgtaaaaatgttga 163,834,500 atttgtaaaaatgttgattttt gaaggaagtattt cttctgcttttcagacta gttttttagattaCGCGta cgagtacgattg CGCGcac tagtttttttatt acc 5`- agcctctttatttcctac ttttattgCGgttttattttttt cccgaacgcaac tgCGgcttcattccct aCGgaatattgaCGtta gacttaa caCGgaacactgaC tCGCGaaggaagtattt 5`- GccatCGCGaag CGagtaCGattgaCGt gcctctaaaaaa gaagcatttCGagca tttttttattatttgttaagtC acgatcttattaca CGactgaCGctccc GttgCGttCGggtttgg cc cttattatttgctaagc ttaCGatttgtttttagaat CGctgCGctCGg aaCGggaaggtgtaata gtctggctaCGatttg aga ctttcagaataaCGg gaaggtgcaacaaga (SEQ ID NO. 8) minus 3`- 3`- 5`- strand tagacatttttacaactg tagatatttttataattgaag gaaacactaacg aagacgaaaagtctg atgaaaagtttgatGCG ccatcg atGCGCg Cgtgttggag 5`- tgtcggagaaataaag aaataaaggatgatGCtg cgtagttagattc gatgacGCcgaagt aagtaagggagtGCtttg gagcgtag aagggagtGCcttgt tgattGCggtaGCGCt 5`- gactGCggtaGCG ttttttgtaaaGCttgtGC aggggagcgtta CttccttcgtaaaGCt tgattGCgaggggaata gtcgtgttcgaaa cgtGCtgactGCga ataaatgatttgGCgatG ggggaataataaacg CgaGCttagattgatG attcgGCgacGCg CtaaatgaaagttttattG aGCccagaccgatG Cttttttatgttgtttt Ctaaacgaaagtctta ttGCccttccacgttg ttct minus 3`- 163,834,621 tgGCatgatgaaaggttg 5`- strand cgGCacgacgaaag 163,834,906 gagagttgtttagtGCttg gtttttttcggcga gtcggagagtcgttta tgGCtttttttggtGCtG taaagc gtGCttgt CtGCtGCtttttttGCa 5`- gGCtttcttcggtGC GCGCGCatgaaggg cgcctctacgaa cGCcGCtGCcctc aGCtGCtgttttGCtttt actctacg cccGCaGCGCG gGCttGCGCgGCtg 5`- CacgaagggaGCc GCttttGCggGCtGC cgtcggtcgagg GCtgtttcGCcctcg gttttaggGCgtttttGCt gcgttc GCccGCGCgGC tGCgGC GCtgtGC cgGCtcccGCgg GCggaGCtttttggagt GCcGCgtctcagg ttgagaataggaGCtga GCgtctccGCctG gaggGCggggtggag CgGCGCcgtGC GCgggGCgttggttttg GCggaGCttttcgg gGCGCgGCattGCt agtttgagaatagga tggGCtGCtggtttttttt GCcgagaggGCg gggtggttgggagGC gggtggagGCggg tgGCat GCgtcggttctggG CGCgGCaccGC ccggGCtGCcggtt cctttcgggtggtcgg gagGCtgGCac
BIBLIOGRAPHY
[0682] Abrams and Stanton, Methods Enzymol., 212:71-74, 1992
[0683] Adorjan et al. Nucl. Acids Res., 30: e21, 2002
[0684] Alon et al., Proc. Natl. Acad. Sci. USA: 96:6745-6750, June 1999
[0685] Ammerpohl et al. Biochim Biophys Acta. 1790:847-62, 2009
[0686] Beaucage, et al. Tetrahedron Letters 22:1859-1862, 1981
[0687] Bianco et al., Hum. Mutat., 14:289-293, 1999
[0688] Bonner and Laskey, Eur. J. Biochem. 46:83, 1974
[0689] Bresslauer et al., Proc. Natl. Acad. Sci. USA, 83: 3746-3750, 1986
[0690] Caruthers, M. H., et al., Methods in Enzymology, Vol. 154, pp. 287-314 (1988)
[0691] Chen and Kwok, Nucleic Acids Res. 25:347-353, 1997
[0692] Clark et al. Nat Protoc. 1:2353-64, 2006
[0693] Clark et al., Nucl. Acids Res. 22:2990-2997, 1994
[0694] Cottrell et al., Nucl. Acids Res. 32: e10, 2003
[0695] DeGraves, et al., Biotechniques 34(1):106-10, 112-5 (2003)
[0696] Deiman B, et al., Mol. Biotechnol. 20(2):163-79 (2002)
[0697] Deng et al. Chin. J. Cancer Res., 12:171-191, 2000
[0698] Dieffenbach (ed) and Dveksler (ed) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbour Laboratories, NY, 1995
[0699] Eads et al., Nucl. Acids Res. 28: E32, 2000
[0700] Egholm et al., Am. Chem. Soc., 114:1895, 1992
[0701] Egholm et al., Nature, 365:566, 1993
[0702] Fodor et al., Science 767-773, 1991
[0703] Frommer et al., Proc. Natl. Acad. Sci. USA 89:1827-1831 (1992)
[0704] Gibson et al., Genome Research 6:995-1001 (1996)
[0705] Golub et al., Science, 286:531-537, 1999
[0706] Gonzalgo & Jones, Nucleic Acids Res. 25:2529-2531 (1997)
[0707] Gonzalgo et al., Cancer Res. 57:594-599, 1997
[0708] Gregory and Feil, Nucleic Acids Res., 27, e32i-e32iv, 1999
[0709] Havelange et al., Blood 2011, 118:2827
[0710] Herman et al. Proc. Natl. Acad. Sci. USA 93:9821-9826 (1996)
[0711] Holland et al., Proc. Natl. Acad. Sci. USA, 88:7276-7280, 1991
[0712] Javierre et al., Mol. Cancer Res. 9(8):1139-51, 2011
[0713] Kawai et al., Mol. Cell. Biol. 14:7421-7427, 1994
[0714] Kibriya et al., BMC 2011, 4:50
[0715] Kristensen and Hansen Clin Chem. 55:1471-83, 2009
[0716] Kuppuswamy et al., Proc. Natl. Acad. Sci. USA 88:1143-1147, 1991
[0717] Landegren et al., Genome Res., 8(8): 769-776, 1998
[0718] Lee et al., Nucleic Acid Res. 21:3761-3766, 1993
[0719] Markowitz and Bertagnolli, 2009, N. Engl. J. Med. 361(25): 2449-60
[0720] Marmur and Doty, J. Mol. Biol. 5:109, 1962
[0721] Martinez et al., Am. J. Surg Pathol. 2012, 36:296
[0722] McPherson et al., PCR: A Practical Approach. (series eds, D. Rickwood and B. D. Hames), IRL Press Limited, Oxford. pp 1-253, 1991
[0723] Messing, Methods Enzymol, 101, 20-78, 1983
[0724] Mhlanga and Malmberg, Methods 25:463-471, 2001
[0725] Moore et al., BBA, 1402:239-249, 1988
[0726] Narang, et al. Meth. Enzymol 68: 90, 1979
[0727] Nevrivy et al. JBC 2000, 275(22):16827-36
[0728] Nielsen et al. J. Chem. Soc. Perkin Trans., 1:3423, 1997
[0729] Olek, et al. Nat. Genet. 17(3): 275-6 (1997)
[0730] Orum et al., Clin. Chem. 45:1898-1905, 1999
[0731] Orum et al., Nucl. Acids Res., 21:5332, 1993
[0732] Oster et al., Int. J. Cancer 2011, 129:2855
[0733] Pathak et al. PLoS One 2011, 6:e22628
[0734] Rand et al. Epigenetics 1:94-100, 2006
[0735] Rand et al. Nucl. Acids Res. 33:e127, 2005
[0736] Rein, et al. Nucleic Acids Res. 26 (10): 2255-64 (1998)
[0737] Sadri & Hornsby, Nucl. Acids Res. 24:5058-5059 (1996)
[0738] Sambrook et al., Molecular Cloning, A Laboratory Manual (2nd Ed., CSHP, New York 1989)
[0739] Santa Lucia, Proc. Natl. Acad. Sci. USA, 95: 1460-1465, 1995
[0740] Shames et al. Cancer Lett. 251:187-98, 2007
[0741] Simeonov and Nikiforov, Nucleic Acids Research, 30(17):1-5, 2002
[0742] Singer-Sam et al., Nucl. Acids Res. 18:687, 1990
[0743] Singer-Sam et al., PCR Methods Appl. 1: 160-163, 1992
[0744] Singh and Wengel, Chem. Commun. 1247, 1998
[0745] Slattery et al., Carcinogenesis 2011, 32:160
[0746] Southern et al., Genomics, 13:1008-1017, 1992
[0747] Szabo and Mann, Genes Dev. 9: 3097-3108, 1995
[0748] Toyota et al., Cancer Res. 59:2307-12 (1999)
[0749] Uhlmann et al., Electrophoresis, 23:4072-4079, 2002
[0750] Wedemeyer et al., Clinical Chemistry 48:9 1398-1405, 2002
[0751] Weissleder et al., Nature Medicine 6:351-355, 2000
[0752] Weitzel J N (December 1999), Cancer 86 (11 Suppl): 2483-92
[0753] Worm et al., Clin. Chem., 47:1183-1189, 2001
[0754] Xiong & Laird, Nucleic Acids Res. 25:2532-2534 (1997)
[0755] Yamashita et al. (Cancer Sci. 2010, 101:1708
[0756] Zyskind et al., Recombinant DNA Laboratory Manual, (Acad. Press, 1988)
Sequence CWU
1
1
931102DNAHomo sapiens 1cagtgcccga ggcggcggcg agtacacgtg gcgggctgga
ttgcagaccg gccctctcgc 60ggcggagact cgcgacctag cggattgcat cagcaggaag
ac 102287DNAHomo sapiens 2agatcccaag ggtcgtagcc
cctggccgtg tggaccgggt ctgcggctgc agagcgcggt 60cccggctgca gcaagacctg
gggcagt 87395DNAHomo sapiens
3gacgacgcac cctctccgtg tcccgctctg cgcccttctg cgcgccccgc tccctgtacc
60ggagcagcga tccgggaggc ggccgagagg tgcgc
95492DNAHomo sapiens 4ccggagttgc ggctgagacg cgcgccgcgc gagccggggg
actcggcgac ggggcgggga 60cgggacgacg caccctctcc gtgtcccgct ct
925110DNAHomo sapiens 5cgcctgccct ccgcgctcct
gcgacggggt cgccacaagc tggacgggat gagctaaccg 60gactgtcggg gccccaggag
tggctgaggc ggggccgtcc aaggcaccca 1106299DNAHomo sapiens
6caggaagctg cagcagaagg aggaggcggc ggccaccccg gaccccgccg cccggactcc
60cgactcggaa gtcgcgcccg ccgctccggt cccgaccccg ggaccccctg ccgcagccgc
120cacccctggg cccccagcgg acgagctgta cgcggcgctg gaggactatc accctgccga
180gctgtaccgc gcgctcgccg tgtccggggg caccctgccc cgccgaaagg tgcgtccccc
240gcccgccttc aggatctgct cagcccctct ccgactccct acagggcctg ctgactccg
2997258DNAHomo sapiens 7gacagagaca gccccaggca agttgaaggt ccgagagccc
ccggtgggag aagcgggccg 60gtggctgcgc cgcgtgcgtt ctcactctga ggaagtgcgt
ggggagccgc tgactccgga 120tagcacaccc ttccgagggg actccccgat tcctgggctg
ggggcctgcc gcctggcccc 180acgtctgacg tacggggcgc gagggccact gctccctgga
cttctgtcgg aaccggacgc 240agtgggaggg gtcgcagg
2588206DNAHomo sapiens 8atctgtaaaa atgttgactt
ctgcttttca gactacgcgc acagcctctt tatttcctac 60tgcggcttca ttccctcacg
gaacactgac gccatcgcga aggaagcatt tcgagcacga 120ctgacgctcc ccttattatt
tgctaagccg ctgcgctcgg gtctggctac gatttgcttt 180cagaataacg ggaaggtgca
acaaga 206963DNAHomo sapiens
9gaaggaagca tttcgagcac gactgacgct ccccttatta tttgctaagc cgctgcgctc
60ggg
631088DNAHomo sapiens 10cggaagtcgc gcccgccgct ccggtcccga ccccgggacc
ccctgccgca gccgccaccc 60ctgggccccc agcggacgag ctgtacgc
881192DNAHomo sapiens 11gacgacgcac cctctccgtg
tcccgctctg cgcccttctg cgcgccccgc tccctgtacc 60ggagcagcga tccgggaggc
ggccgagagg tg 921295DNAHomo sapiens
12gtcttcctgc tgatgcaatc cgctaggtcg cgagtctccg ccgcgagagg gccggtctgc
60aatccagccc gccacgtgta ctcgccgccg cctcg
9513110DNAHomo sapiens 13tgggtgcctt ggacggcccc gcctcagcca ctcctggggc
cccgacagtc cggttagctc 60atcccgtcca gcttgtggcg accccgtcgc aggagcgcgg
agggcaggcg 1101427DNAArtificial SequenceDescription of
Artificial Sequence Synthetic primer 14gaaggaagta tttcgagtac gattgac
271517DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
15cggaagtcgc gttcgtc
171620DNAArtificial SequenceDescription of Artificial Sequence Synthetic
primer 16tgggtgtttt ggacggtttc
201729DNAArtificial SequenceDescription of Artificial Sequence
Synthetic primer 17gtttttttgt tgatgtaatt cgttaggtc
291824DNAArtificial SequenceDescription of Artificial
Sequence Synthetic primer 18gacgacgtat ttttttcgtg tttc
241919DNAArtificial SequenceDescription of
Artificial Sequence Synthetic primer 19cccgaacgca acgacttaa
192020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
20gcgtacaact cgtccgctaa
202115DNAArtificial SequenceDescription of Artificial Sequence Synthetic
primer 21cgcctaccct ccgcg
152220DNAArtificial SequenceDescription of Artificial Sequence
Synthetic primer 22caatacccga aacgacgacg
202316DNAArtificial SequenceDescription of Artificial
Sequence Synthetic primer 23gcgcacctct cgaccg
162428DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 24ttcgatttcg ggattttttg tcgtagtc
282526DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
25tcgtttagtt tgtggcgatt tcgtcg
262621DNAArtificial SequenceDescription of Artificial Sequence Synthetic
probe 26ttcgtcgcga gagggtcggt t
2127102DNAHomo sapiens 27tagtgttcga ggcggcggcg agtatacgtg
gcgggttgga ttgtagatcg gttttttcgc 60ggcggagatt cgcgatttag cggattgtat
tagtaggaag at 10228102DNAHomo sapiens 28gtcttcctgc
tgatgcaatc cgctaggtcg cgagtctccg ccgcgagagg gccggtctgc 60aatccagccc
gccacgtgta ctcgccgccg cctcgggcac tg 10229102DNAHomo
sapiens 29gtttttttgt tgatgtaatt cgttaggtcg cgagttttcg tcgcgagagg
gtcggtttgt 60aatttagttc gttacgtgta ttcgtcgtcg tttcgggtat tg
1023029DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 30gtttttttgt tgatgtaatt cgttaggtc
293120DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
31caatacccga aacgacgacg
203221DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 32ttcgtcgcga gagggtcggt t
213326DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 33tttttgttga tgtaattcgt taggtc
263420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
34attacaaacc gaccctctcg
203519DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 35agatcccaag ggtcgtagc
193618DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 36actgccccag gtcttgct
183787DNAHomo sapiens 37actgccccag
gtcttgctgc agccgggacc gcgctctgca gccgcagacc cggtccacac 60ggccaggggc
tacgaccctt gggatct 873895DNAHomo
sapiens 38gacgacgtat ttttttcgtg tttcgttttg cgtttttttg cgcgtttcgt
tttttgtatc 60ggagtagcga ttcgggaggc ggtcgagagg tgcgt
953924DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 39gacgacgtat ttttttcgtg tttc
244016DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
40gcgcacctct cgaccg
164126DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 41tttgtatcgg agtagcgatt cgggag
264295DNAHomo sapiens 42gcgcacctct cggccgcctc
ccggatcgct gctccggtac agggagcggg gcgcgcagaa 60gggcgcagag cgggacacgg
agagggtgcg tcgtc 954395DNAHomo sapiens
43gcgtattttt cggtcgtttt tcggatcgtt gtttcggtat agggagcggg gcgcgtagaa
60gggcgtagag cgggatacgg agagggtgcg tcgtt
954417DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 44ggagttgcgg ctgagac
174517DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 45agagcgggac acggaga
174692DNAHomo sapiens 46agagcgggac
acggagaggg tgcgtcgtcc cgtccccgcc ccgtcgccga gtcccccggc 60tcgcgcggcg
cgcgtctcag ccgcaactcc gg 9247110DNAHomo
sapiens 47cgtttgtttt tcgcgttttt gcgacggggt cgttataagt tggacgggat
gagttaatcg 60gattgtcggg gttttaggag tggttgaggc ggggtcgttt aaggtattta
1104817DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 48gtttttgcga cggggtc
174918DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
49taaaaccccg acaatccg
1850110DNAHomo sapiens 50tgggtgcctt ggacggcccc gcctcagcca ctcctggggc
cccgacagtc cggttagctc 60atcccgtcca gcttgtggcg accccgtcgc aggagcgcgg
agggcaggcg 11051110DNAHomo sapiens 51tgggtgtttt ggacggtttc
gttttagtta tttttggggt ttcgatagtt cggttagttt 60atttcgttta gtttgtggcg
atttcgtcgt aggagcgcgg agggtaggcg 1105220DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
52tgggtgtttt ggacggtttc
205327DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 53tagttatttt tggggtttcg atagttc
275415DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 54cgcctaccct ccgcg
155526DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
55tcgtttagtt tgtggcgatt tcgtcg
2656299DNAHomo sapiens 56taggaagttg tagtagaagg aggaggcggc ggttatttcg
gatttcgtcg ttcggatttt 60cgattcggaa gtcgcgttcg tcgtttcggt ttcgatttcg
ggattttttg tcgtagtcgt 120tatttttggg tttttagcgg acgagttgta cgcggcgttg
gaggattatt attttgtcga 180gttgtatcgc gcgttcgtcg tgttcggggg tattttgttt
cgtcgaaagg tgcgtttttc 240gttcgttttt aggatttgtt tagttttttt tcgatttttt
atagggtttg ttgatttcg 2995717DNAArtificial SequenceDescription of
Artificial Sequence Synthetic oligonucleotide 57cggaagtcgc gttcgtc
175820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
58gcgtacaact cgtccgctaa
205928DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 59ttcgatttcg ggattttttg tcgtagtc
286020DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 60cggattttcg attcggaagt
2061298DNAHomo sapiens 61cggagtcagc
aggccctgta gggagtcgga gaggggctga gcagatcctg aaggcgggcg 60ggggacgcac
ctttcggcgg ggcagggtgc ccccggacac ggcgagcgcg cggtacagct 120cggcagggtg
atagtcctcc agcgccgcgt acagctcgtc cgctgggggc ccaggggtgg 180cggctgcggc
agggggtccc ggggtcggga ccggagcggc gggcgcgact ccgagtcggg 240agtccgggcg
gcggggtccg gggtggccgc cgcctcctcc ttctgctgca gcttcctg 29862298DNAHomo
sapiens 62cggagttagt aggttttgta gggagtcgga gaggggttga gtagattttg
aaggcgggcg 60ggggacgtat ttttcggcgg ggtagggtgt tttcggatac ggcgagcgcg
cggtatagtt 120cggtagggtg atagtttttt agcgtcgcgt atagttcgtt cgttgggggt
ttaggggtgg 180cggttgcggt agggggtttc ggggtcggga tcggagcggc gggcgcgatt
tcgagtcggg 240agttcgggcg gcggggttcg gggtggtcgt cgtttttttt ttttgttgta
gttttttg 2986320DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 63ggtagggtgt tttcggatac
206421DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
64aacgaacgaa ctatacgcga c
2165258DNAHomo sapiens 65gatagagata gttttaggta agttgaaggt tcgagagttt
tcggtgggag aagcgggtcg 60gtggttgcgt cgcgtgcgtt tttattttga ggaagtgcgt
ggggagtcgt tgatttcgga 120tagtatattt tttcgagggg atttttcgat ttttgggttg
ggggtttgtc gtttggtttt 180acgtttgacg tacggggcgc gagggttatt gttttttgga
tttttgtcgg aatcggacgt 240agtgggaggg gtcgtagg
25866258DNAHomo sapiens 66cctgcgaccc ctcccactgc
gtccggttcc gacagaagtc cagggagcag tggccctcgc 60gccccgtacg tcagacgtgg
ggccaggcgg caggccccca gcccaggaat cggggagtcc 120cctcggaagg gtgtgctatc
cggagtcagc ggctccccac gcacttcctc agagtgagaa 180cgcacgcggc gcagccaccg
gcccgcttct cccaccgggg gctctcggac cttcaacttg 240cctggggctg tctctgtc
25867258DNAHomo sapiens
67tttgcgattt tttttattgc gttcggtttc gatagaagtt tagggagtag tggttttcgc
60gtttcgtacg ttagacgtgg ggttaggcgg taggttttta gtttaggaat cggggagttt
120tttcggaagg gtgtgttatt cggagttagc ggttttttac gtattttttt agagtgagaa
180cgtacgcggc gtagttatcg gttcgttttt tttatcgggg gttttcggat ttttaatttg
240tttggggttg tttttgtt
2586821DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 68cggagttagc ggttttttac g
216920DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 69cgataaaaaa aacgaaccga
207020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
70agagtgagaa cgtacgcggc
2071258DNAHomo sapiens 71gacagagaca gccccaggca agttgaaggt ccgagagccc
ccggtgggag aagcgggccg 60gtggctgcgc cgcgtgcgtt ctcactctga ggaagtgcgt
ggggagccgc tgactccgga 120tagcacaccc ttccgagggg actccccgat tcctgggctg
ggggcctgcc gcctggcccc 180acgtctgacg tacggggcgc gagggccact gctccctgga
cttctgtcgg aaccggacgc 240agtgggaggg gtcgcagg
2587220DNAArtificial SequenceDescription of
Artificial Sequence Synthetic oligonucleotide 72caagttgaag
gtccgagagc
207320DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 73cgcacttcct cagagtgaga
2074258DNAHomo sapiens 74cctgcgaccc ctcccactgc
gtccggttcc gacagaagtc cagggagcag tggccctcgc 60gccccgtacg tcagacgtgg
ggccaggcgg caggccccca gcccaggaat cggggagtcc 120cctcggaagg gtgtgctatc
cggagtcagc ggctccccac gcacttcctc agagtgagaa 180cgcacgcggc gcagccaccg
gcccgcttct cccaccgggg gctctcggac cttcaacttg 240cctggggctg tctctgtc
25875206DNAHomo sapiens
75atttgtaaaa atgttgattt ttgtttttta gattacgcgt atagtttttt tattttttat
60tgcggtttta tttttttacg gaatattgac gttatcgcga aggaagtatt tcgagtacga
120ttgacgtttt ttttattatt tgttaagtcg ttgcgttcgg gtttggttac gatttgtttt
180tagaataacg ggaaggtgta ataaga
2067628DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 76gaaggaagta tttcgagtac gattgacc
287719DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 77cccgaacgca acgacttaa
197828DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
78gcctctaaaa aaacgatctt attacacc
2879206DNAHomo sapiens 79tcttgttgca ccttcccgtt attctgaaag caaatcgtag
ccagacccga gcgcagcggc 60ttagcaaata ataaggggag cgtcagtcgt gctcgaaatg
cttccttcgc gatggcgtca 120gtgttccgtg agggaatgaa gccgcagtag gaaataaaga
ggctgtgcgc gtagtctgaa 180aagcagaagt caacattttt acagat
20680206DNAHomo sapiens 80ttttgttgta ttttttcgtt
attttgaaag taaatcgtag ttagattcga gcgtagcggt 60ttagtaaata ataaggggag
cgttagtcgt gttcgaaatg tttttttcgc gatggcgtta 120gtgtttcgtg agggaatgaa
gtcgtagtag gaaataaaga ggttgtgcgc gtagtttgaa 180aagtagaagt taatattttt
atagat 2068118DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
81gaaacactaa cgccatcg
188221DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 82cgtagttaga ttcgagcgta g
218325DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 83aggggagcgt tagtcgtgtt cgaaa
2584285DNAHomo sapiens 84cacggtcgga
gggctggtgg gctttccttg gccgtcgggc ccgccacggc gcgggtcttg 60gctgcggggc
ggaggtgggg cgggagagcc gaggataaga gtttgaggct tttcgaggcg 120cgtgccgcgg
cgtccgcctc tgcgggactc tgcgccgggc gccctcggcc ggcgcgcccg 180gctcccgctt
tgtcgccgag ggaagcacgc gcgacgcccc tcccgtcgcc gccgtggctt 240ctttcggtgt
tcgtgatttg ctgagaggct ggaaagcagc acggc 28585285DNAHomo
sapiens 85tacggtcgga gggttggtgg gttttttttg gtcgtcgggt tcgttacggc
gcgggttttg 60gttgcggggc ggaggtgggg cgggagagtc gaggataaga gtttgaggtt
tttcgaggcg 120cgtgtcgcgg cgttcgtttt tgcgggattt tgcgtcgggc gttttcggtc
ggcgcgttcg 180gttttcgttt tgtcgtcgag ggaagtacgc gcgacgtttt tttcgtcgtc
gtcgtggttt 240ttttcggtgt tcgtgatttg ttgagaggtt ggaaagtagt acggt
2858620DNAArtificial SequenceDescription of Artificial
Sequence Synthetic oligonucleotide 86gtttttttcg gcgataaagc
208720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic oligonucleotide
87cgcctctacg aaactctacg
208818DNAArtificial SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 88cgtcggtcga gggcgttc
188910924DNAHomo sapiens 89cccacccccc acagatgctg
tctgtcagga gcaggcaaca gacggtcctg gggtccatct 60gtgctaatgc ttcacaatag
agtcccatgt ttccccactg acaccccctc ggcccctcag 120ctgatggcca cttggtggtg
ccaaggcggg aggtgggagg agggagaaga aggcactaag 180agagctacct cttagctcct
ggcagtcctc aatccacccc ggccccccac ccaacaagca 240tcctgccatc tggacttgtg
caatcactga ggggcggaaa agcaccctct tccacccaca 300cctcttgtag gggatggggg
cctagaggac tgggggtggg gaggagaaca cagagtcaag 360gagactagag aagaagactg
agccaggcgc aagaactgag acaggcagga ggcagaaagt 420ctttcctggc ctcgcaggtg
gacgtggcca ttgcccctct gtgctcctta tgccacgtgt 480ctaacacagc acatgtgcaa
ggtaccactc cctaccaggc caagagcctc tgtaacccca 540gtgcccagcc agtacctggc
acacagcagg gcttaaatgt tggacaacat cacagagtgg 600ttagattgca ggctctggaa
ccaggctgcc tggctttgaa tctcagctct gccgctgagt 660gacttagggc aaattactta
tcttctctgg gcctcagttt cctcatctgt aagggaggat 720aatggtgctt atttcgtagg
gttgttatga agaccaagtg agttaatgca tgtatgtaaa 780aggacacaca gaacaaacag
tgtgcatagc acatgctaag tgctcaataa atgttaactg 840tgaaggcata acagatttgg
gaagactggg ggaggaggga ggggacagac aagggcaccg 900cattgccgcc tctgcttctt
ggccgatggg tgttgggaca tggagtcccc agcctgtgct 960gctgacgccc tgtggtggct
agccgctctt tagacaccag acgctgcctt ccacttcctc 1020ctctcacttc ttattcgggc
accactgacg acagagactt cggctgggcc attcccgcct 1080ctcctaccgc ctggcagcca
tggtaacagc ctgggggatg gtccctaaga tggggtcaga 1140gaacggctga gcatggccat
ccccccagcc ctgaactccc actcagcctg ggctcatccc 1200aacctcctga gtcaagtcca
cagtaagcgt ctgtctcctg ggaaggggga tctgaccccg 1260gcatcaggag ctgaggaaag
gtgttgccag cagggatcac tcaagcccct tggaggggac 1320aggccagaac taagcctact
gctttcaggg tttccacctc ttcccttctt cctagacgtg 1380cgaacagggg gcagcctctt
tcagctcttc tggggcagct gcgtcaaggg aaaatcctgg 1440gccctctccc tccctggggg
cttctgcgca gtgagttcag ggagtctcct ccctcctcca 1500tcgggcctcc acccctactc
ctgcgcagcc ccgctgccgc tctccctgcc ctggagtctc 1560ctgcagcccc ttggatctcc
gtgactctcc ctacctcccc gactccccag gcttcttaca 1620gtgacctctt accgtgcccc
actccatgaa tcgccagagc tattcgtccc taaatttcaa 1680accttgcgca atgtcccttc
acagacccct ccaggtatca cgcagccccg agccccgagc 1740cccgccccgg gggcctcatc
ccgccccttc gcgtccgcgg ctcgttttcc cccactgagc 1800gcccagctcc cgcagtttcc
ccggccgtcg agcgccgtgg gcggggctcc agggcggcgg 1860cgcctcgcgg ggagggtcct
ccgtgctggg ggcgaggcca cccgaggcag ctccccgccc 1920gcccccaacc ccgccccgct
ctcggagcct ataaagggag gcgacccgcg gcccgcccgg 1980ctggcatccc ccagccgccg
ccagccccgc cgaggggagc cagcgccgtc tctgaggggc 2040gtccggcgcc ggagccatga
ccctccgccg actcaggaag ctgcagcaga aggaggaggc 2100ggcggccacc ccggaccccg
ccgcccggac tcccgactcg gaagtcgcgc ccgccgctcc 2160ggtcccgacc ccgggacccc
ctgccgcagc cgccacccct gggcccccag cggacgagct 2220gtacgcggcg ctggaggact
atcaccctgc cgagctgtac cgcgcgctcg ccgtgtccgg 2280gggcaccctg ccccgccgaa
aggtgcgtcc cccgcccgcc ttcaggatct gctcagcccc 2340tctccgactc cctacagggc
ctgctgactc cgcagtgccc tctcctcggc gtccgcggag 2400tcccccacct tcttccccgg
cccgctgggt gcctcgactc cccgcgttcc ccgctgctgc 2460gaaggccgtg gccctcgcct
gcacaccgcg cccaggctcg gtggctctta actccgcgcc 2520ccatgcacgc cccctctctc
cctccttgac tcctcccagc accccccttc tcctacccgc 2580tccatctggc tttctgcccc
ccatgccccg cctccccgtg gccaggtgtc ctgggtcccc 2640aggagcccct cgcccgaggg
acagagacag ccccaggcaa gttgaaggtc cgagagcccc 2700cggtgggaga agcgggccgg
tggctgcgcc gcgtgcgttc tcactctgag gaagtgcgtg 2760gggagccgct gactccggat
agcacaccct tccgagggga ctccccgatt cctgggctgg 2820gggcctgccg cctggcccca
cgtctgacgt acggggcgcg agggccactg ctccctggac 2880ttctgtcgga accggacgca
gtgggagggg tcgcagggcg cccgcggggc aggaaggatg 2940cgggccgcgc ccacctctga
gtcccctctg ccagcctctt cctctggccc caggagacct 3000gaggctcaga acctacacaa
caccaggtta agaagagggg cctggtggcc tttcctcacc 3060cagccgccct ccttcgcccc
ggcccccagc tagcccccac acaatgaaca gcttgttgag 3120aatttgcatt ttatgaaaat
catgttgaaa gacaaagggg tctctctgtg ctgcccagtc 3180cttcctccct ggccgtttgg
gaactgtccc cacccctgag gccaatctgg ttctgaacct 3240tctcttcctt gccttgggca
gctttggggg agggttagca aaggcacaga acagaaaggc 3300cctgggctgt gcaggctcca
aagaaaaggg ctgctctggg actggacctc ctcccaggac 3360caaaaagtta gggagggtga
gagactactt tagtttatca aggaccctga agagacagga 3420accttcatct ctcatccttc
ctccacaccc cccaccacca cccctaaaga actcccagtc 3480tcggtccttt agtgagactt
gctgacaagt ttgacatcta agatgttttg tcccagaaag 3540cacaaaatat atggcaatgg
agagagagac ccaggtatag ctgggcacag ctggtcacct 3600gcagctggga tccacaactg
gtccttgaaa cggcctgtac cttaggagac ctggcacctc 3660tgaccccaca ttctggctgg
gattgccagc ccttcgggac agggtccctg accccagccc 3720tcccaagcca ctgtctgtag
ctgagaaatt agatggagag acccaactgg cagaaggtcc 3780tcggagcacc ttgataggtg
agcccagggg acacctatcc tctgaatccc actggggaag 3840agcccctgcc tcagctttgg
gagtctggat ggcctgagcc tctacagaca tgggccctag 3900gggtggagac cattttagaa
taatgatctc cccacctgct gccagtgtgg aaaccagcaa 3960gggcttagag gttcatggat
ctggaaccca ggaggatggt tgtgtccctg cagtcccagg 4020tatgaaggta aggcctgtag
agaaagttga ggagtggtgc cagtagtggc acttggcaaa 4080tagttccacc agcaccaaaa
caggtgtgga tgtggagctg ggaaggggca gacaggaagt 4140gggtcgctgt gtccagggta
acctctcagt gtctgctcaa ggacagtccc gccttacctg 4200ctccttctga ccatcttact
gcccagggct caggattccg ctggaagaat ctcagccaga 4260gtcctgaaca gcagcggtga
gtcaccaaca cccagcccct gccatggtcc aaaggggtga 4320ggtgctgggt tggggggtgc
caggacagca tctcagccta gcgagggtag tcattctcct 4380agcctttaaa catggctccc
ccgctgggag tgagggcagg tgggggtgag ggctgtgtga 4440agggggtggc agagaaagga
ggtagggact tttgagtcat taggtgctct tcaacacacc 4500cccagtccct gccagttacc
cctccctggg gagatctgga tgaacggatg tgggagttgg 4560gagggggtgt aggcaaagtc
tatggggaac gtcctaaccc aggcctcctg ggctcccctg 4620agccctccta gccttggcaa
accccacggg cccagacctt agccaggctg tgtccagctg 4680cttggggctg gctgcccctg
cctccagaat gtcagtcctc ttctggtccc agcctgtggc 4740agccctctta ggagggatct
gagcgtgggc agaagtaggt gctgactcca ggccctggga 4800ccccacagtt tcccttctct
actcatgtcc catccctgat ttgggcttga ctttctctaa 4860aatggatcag caaactgacc
tgctagccag attggcctgt ttggcccttg agctaataat 4920ttttaaagag ttgtaaaaat
aaaaacaaat aacaatatat gacagagatc ataaggggcc 4980tgcaaagaaa gcctaaagta
tttaccattt ggccctttgc agaaaaagtt tgctgaccct 5040tccaaaaaac cctagaacat
tggggtagac gcggaactcc cagccaccct gctccctgcc 5100ccaatagtac agagagggga
aaggcctgct gttcagagtg agaggggctc gagctggagt 5160ggggaggtgc tgctcagcat
ttgggggaat ctctgggtca ggctggaagc ggagaagcct 5220ggtctccagg gcctttccga
ggctgagcta cttgaagggg cctttggagg ctgctttaac 5280tgtgcctctg gctgggcggg
aaggaagggg gtgggagtgg gcagaggaaa ctctgggctc 5340ccccagcagg cgaggatctg
gagcagctcc agaccattgt gtccagcggg caggccttca 5400gtgcgggaag gggcggcctc
gaggctcccc tcccccagcc cccacatctg gtgggctggc 5460cccagcatag ctgggaggag
cagctgtggt cttgctgagc ctcgtgactg gcctctgggg 5520gtggggccag tcctctctcc
aaagctgtgg aacagaggag gctccaggct gtggctgaat 5580ttcgggcctt agctagtcag
taagtggtac tgtagggctc actggaaagc tgggatgggg 5640ctaaaaaact cagccggctc
atccttcagg ggaccggccc ttctctgtgc ttccctccca 5700ccactagagg ctggattggt
tctctgtggc tccatgaggc tgatttcaat tgggtatggg 5760aaagacattc caataatctg
tgatgagact gagctgtcac tggagacaga gtcctgctgg 5820aatgttctag accagttgcc
aatatccagg gaggcccaag ctatgggact tctacacctt 5880ttaatcctaa ttgtcttgac
ccctgtgtct cttgcaggaa agtgctgacg ttggagaagg 5940aggataacca gaccttcggc
tttgagatcc aggtgggaga agctgcacac aggggtcagg 6000ggggttggat gaccagcctg
agggatgaac ggacttgtcc caaccctggg ctgagggtcc 6060ccttgtccat tacagactta
tggccttcac caccgggagg agcagcgtgt ggaaatggtg 6120acctttgtct gccgagttca
tgagtctagc cctgcccagc tggctgggct cacaccaggt 6180ggggcctgag cccaggacac
ccaggtctgg gaaggggata tgaccttact cccaagcaaa 6240gggggtgagc aatctctcct
gaaatcaatt cctcttcctt ttccttcttt gagaaggcca 6300gaaagaagaa tggatagaat
ctgggctttg gatctaggca aatttgccat gtactgtgtg 6360atcttgcaca gccccatcta
caaaatgagg gtaataatgc atccaaacat cacagtgcgg 6420caaggggatt ccctgggcac
actgccaggg cctaattaat ggtggatgat gctgctgctg 6480ctctgattcc tcccagcaac
cctggcagtc agcatgggca ggagccaggg aagaagcaac 6540attccattaa gtctgtttga
tattggggat caggccaatc ctgccccaaa atgggcccag 6600tgctgaggaa ccgatgttac
tcccttttaa aaaattagaa actttttttt tttttaagag 6660acagggcctc agtctgtcac
ccaggctaga gtgcagtggc gtaatcataa ctcactataa 6720ccttgaactc ctgggctcaa
gcgatcctcc tcttgcctct gcctcccaaa gcaatatgtt 6780acttcctcta acaaggaaat
tatgcttcag caggagatcc ctggattgag cagatctaga 6840gtccccaggt tccaggaagg
gcagcctgaa actgtatgaa tcaatccccc ctccaccatc 6900tttgccccta agcccctacc
tccttcccac ttaccagcag cccgtgctag ctatcttagt 6960ccattttctg ttaccataac
agaatacctg atactgggta attataaaga aaagaggttt 7020atttagctca tggttctgga
ggctgggaag ttcaagactg ggtggccgca tcaggtgagg 7080gcctcatgct gcgttctgac
atgatggatg gcatctcatg gcaggaacgc ctgcaagagt 7140ggtgagtagg cacacgcaaa
agagacaaaa catgggtgat cttgctttat agcaacccac 7200tcgccaggta actaaaccag
tcctaccaga gcaagaactc actccccaaa aacagcatgg 7260atcccttcac tgggcagatc
cttcatggcc caaatgccac tttttttgag atggagtttc 7320gctcttgttg cccaggctgg
agtgcaatgg catgatctca gctcactgca gcctctgcct 7380cccagattca agcaattctc
ctgcctcagc ctcccgagta gctgggatta caggcactgg 7440ccaccaagcc cagctcattt
ttgtattttt agtagagatg gggttttgcc ttgttggcca 7500ggctggtctc gaactcctga
cctcaggtga tccacccgcc tcggcctccc aaagtgctgg 7560gattacaggt gtgagccacg
gcgctcggcc ccaaatgcct cttaaaggtc ctaccatctc 7620tcagcactgt tacgttgggg
atgaagcctc aacatgagtt ttggggacaa acaatattta 7680aatggtagca gtagccaagt
ggtatactac aacttctcaa agtagtttca aatccactct 7740ccctccccat catccctgaa
gcatccacag cagggatcca tacccctttt tacagatagg 7800aatggggccc tgacatgggg
cacactgtgc ttgaggtcag gaagctctcc agtggtgcag 7860ggtagcagaa ctatccctct
gggggccagt cattccctgt gcttctctcc caccaccaga 7920ggctggactg attatctgtg
gatccatgag gccatgccat gcctggggcc agggtcggtt 7980cccagctggg tgctgctcac
ctgctcttcc ctgaattgac tgggtcttat ggccagcgtg 8040gactggacag aaataaccaa
atctgagggt agcccagggt cctgggtggg cttagctttg 8100ggacagaact tctttttttt
tttttttttt ttgagacgga gtctcgctct gtcgcccagg 8160ctggagtgca gtggcgcgat
ctcggctcac tgcaagctcc gcctcccggg ttcacgccat 8220tctcctgcct cagcctcccg
agtagctggg actacaggcg cctgctacca cgcccggcta 8280attttttgta tttttagtag
agacggggtt tcaccgtgtt agccaggatg gtctcgatct 8340cctgacctcg tgatccgccc
gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc 8400accgcgcccg gccggacaga
acttcttgag ggcagagtga gggtgttggg tgtgtgaggt 8460ccccaccctt tggctggggt
gctgggcgtg gacaacctgg tagtcactac aggcccacaa 8520gaatggctgt ggttctgtgt
gtttggatcg agtatgagag atgtcagagg agatctacag 8580agaaccatga ggagttggag
gagggagttc aggagtattc cctggagtta ctacccaccc 8640ttctcccctt tctggctaag
gtaggaggct ggtattctag catgccccat ggagcaaatc 8700taaccccctt gtctgcctgg
caggggacac catcgccagc gtcaatggcc tgaatgtgga 8760aggcatccgg catcgagaga
ttgtggacat cattaaggcg tcaggcaatg ttctcaggta 8820tgtctgggag ccgaggtgcc
tgaattcctg agctcagcct cttggtattt cctcagcctg 8880tggctcactc aggctttgat
tctccaacct cagactggaa actctatatg ggacatcaat 8940tcggaaggca gaactggagg
ctcgtctgca gtacctgaag gtaggggaac ctagataacg 9000tccagcctcc accctcctct
tcccaagcct ctgccctgtg gggggtcact tacagctgaa 9060tctcctgtaa ctgaagattt
cttttgtcta ctccctgatc cctcgtctgt acccacgtcc 9120tgctagtttc ctgctagctt
gtgacagtgg ggtggggact gtctcttgca gcaaaccctg 9180tatgagaagt ggggagagta
caggtcccta atggtgcagg agcagcggct ggtgcatggt 9240gagtagatcc cggggtgtga
ggggccactt gttctgctac agacacccca tctgcgcttc 9300cccctcagaa ctggcgggtt
ctagtaaaga acggtttact agtaaacctc cacagtaaag 9360caaggtttgt tgagctacta
ctactttggg tactgccgca gccacatttc tggttattct 9420cacactagcc ctctgcaggt
aagtaacaga tagtgtcatc ttcactttac agaggggaac 9480accagggctc aaagagtttg
tgtcaattat ttccgaggcc cgtttgtgct aagcggcccc 9540cataaggatc tgagtgataa
ttcctgattt gcgggtgagg gaagtagggt ctcaggtttg 9600tgcctggcca gggccacaga
gatggtcagc aggacggagc ggggacgccc cgcccatgcc 9660ctccgaccct ttgcagaggc
caccacggtc caggcctgac ccgcccccta cctctcccgt 9720ctctgcgcag gcctggtggt
gaaggacccc agcatctacg acacgctgga gtcggtgcgc 9780tcctgcctct acggcgcggg
cctgctcccg ggctcgctgc ccttcgggcc tctgctcgcc 9840gtgcccgggc gtccccgcgg
aggcgcccga cgggccaggg gcgacgccga cgacgccgtc 9900taccacacgt gcttcttcgg
ggactccgag ccgccggcgc tgccgccccc gccgcccccg 9960gcccgcgcct tcggcccggg
ccccgccgag acccctgccg tggggccggg ccctgggccg 10020cgggccgcgc tgagccgcag
cgccagtgtg cggtgcgcgg gccctggcgg gggcggaggc 10080gggggcgcgc cgggcgcgct
ctggactgag gctcgcgagc aggccctatg cggccccggc 10140ctgcgcaaaa ccaagtaccg
cagcttccgc cggcggctgc tcaagttcat ccccggactc 10200aaccgctccc tggaggagga
ggagagccag ctgtaggggc gggggcgggc agggaggtat 10260ttatttattt attcgcaaca
gccagcgcta aaagaggggg aggccgagcc aagaggaccc 10320caggagccca gagcagcggg
agagggtcct tcctagcctc ggcccgccgg gtcggttcct 10380ggctggtgtc tgctgaggga
gtggggggcc cagccccttc tcttctcccc cgccaaacca 10440cagtgggagc tggggcaggg
ggagagccag gcaatcgggg gccaaagatg ggggtgctcg 10500cctacagtct gcatctgtag
tgccttgtgg ggtatccagg aacaccctcc cagcagggga 10560tgggaaccct gtcccatgaa
gccctctcct cagctttact tgctcccccg cccttagcct 10620tggggagaaa tggcccgtgg
tgggctgacc ccccaccctc cacacacaca gttccatgac 10680ccagcgggcc cccaggggca
tcaggtgctg gtcctcctcc ctcctggcct cgacccctaa 10740gggcttcgcc cctcccaggg
gcctgtaact aagtcgggtc ctgccaggca gggggcctgt 10800gttctgtgcc ccttgggaga
caggaactgg cgagttcagg tggggtgggg acagcacaga 10860ctgttccacc gttgtgcata
ttgttgcttc tgaaccacaa actgtataaa tggatggttt 10920tttg
10924902886DNAHomo sapiens
90agcataattt cggtctccta cggaatttct ttaaactaac gagccccaca ctgacttcca
60cttagtattg aacagctgca ccaactcccc aaccacgaaa ccccgcttta gtcctcacgg
120gaggggagag ctcccgaacg cggggcggtg ggggtccgcg cagagcaggc tcgggaggcc
180gagcggagga gcggggcccg cgccgggcac acgcgtcctc caggccggcg gcgcggcgtg
240ggcctgctct cgggagggct cggcgaggac caccgagtcc gcgcagcccc cgccgacctc
300tcggaaatgt gaccgccgaa gctagagggg ccgcagggct caccccgcag ccctccgcaa
360cgcgccaact tggacgccag cggcgcgggg tcccggccgg gcagggggcg tccggcaccg
420gcgggtccac cccggcccgc ccgcccgccg caagcccggc ccggcacctc ctttgtgcgc
480cctcctggcc tcccagtccc cccggcgctc ggtcccgccc ggccgtgacc ttcccgccct
540ccccaccatc ccaagcgggg aaaggggccg ccccggcggg ggtcgggccg gggccggggc
600cctggagacg ctcaccttcg tccagcagcc gctcgaggtg gttgaagatc ccgcagaagt
660tgggcaggct gctcatgagc ttcttgtcgt tcatcagctg catcaggtaa tctggggtgg
720gcttcggctt ctccttcgtt tccatttccc cgaccatatt ccaggctccg cagctcactc
780cgcccgccgc cgccgccgcc gccgccggag aggagggagg ggcgggggcg agccccggcc
840gcgggccgct cgggacccgg cgtcccgctc cgcgccggct cccgctctgg ctcccgcgcc
900gagccccggg gcggccggca ccgcgcgctc gcccgccccc cgcaggcact ttccgcccgg
960gcccgacgcg ctcccagccg ccgccgctct cggccgcccg gctcggcgcg tccctcacga
1020ggccggcggg cgggcgggag gcgggtctcg gctggccgag tgcgggcgcg gggcgcgggc
1080tgctggcgcc ggacgaggag gagccggggc cgccgctcgc tcggctggtc gagcccgctc
1140agcgccgccg ccgcctgtgc cgcgggctcg gggggtctct ctgggctggt ccccgccgcg
1200gcgcctctgc cgctgccgcc gcgctccgac tgcgctcctc ctcttcctcc tcctccttct
1260cctcctcctc ctcctcactc acttggcggc ggagttcgcc tcagttcagg cggcgctgcc
1320agcggcggcg gcagcagcgg cggcggcggg gggaggggca gcggcgcggg gagggccggg
1380ggcgggcggc gggcggggcc gcgcagggcg gccgttagcg ggtcccggcc ggcgcgctcc
1440cgctgcctgc tgcccgccgc cccgcgaccg gggcagccgc cggcgccgcg ccccctcctc
1500cctgcctccc cggcggggcg ggcgacgggg gcaacgggag tgtgacggac tgcggcgctc
1560ggcgggcctg ggcgcaagga ctgggtcgcc gccgtgcggg gcgcccgggg cgggtgggtg
1620tgggctgcgg ggccgacggc cgcggggggg gcgcggggct ttccacggca cggggcgggt
1680ggggctgcgg gcgcggtcgg ggctggcgcg gcaggcgaga ggaattccag cgggacgcgc
1740cagcgctgcc tccgcctcgc ctcccgttac tatagttttt tcagaacctc ttatccaccc
1800cgcagaagag aaattttttt ttaacgtcct gttgcttcac gggggacttt cggggtgggc
1860atcacgtggc ccgacacgta gccgtggggc tccagagcgc gtgcgcgcgt cgagcccggt
1920cgccacgccc cttccgaggg tcgctccgcc cccgtcgggc cccgcgagcg cgcggtgggg
1980gaggggaggg ccccggagcg cgcctgcgtg gggcgggggc ggcagccgac taggggctgg
2040gtctggccgt ttagggccgg gtcttggccc gtcgcccacg gtgcggaggg ctggtgggct
2100ttccttggcc gtcgggcccg ccacggcgcg ggtcttggct gcggggcgga ggtggggcgg
2160gagagccgag gataagagtt tgaggctttt cgaggcgcgt gccgcggcgt ccgcctctgc
2220gggactctgc gccgggcgcc ctcggccggc gcgcccggct cccgctttgt cgccgaggga
2280agcacgcgcg acgcccctcc cgtcgccgcc gtggcttctt tcggtgttcg tgatttgctg
2340agaggctgga aagcagcacg gcggagagga gccttgcact cgccaggcgg gaagcctgcg
2400cggacacgcg tgcgcaccca cggggcggcg ggcgggcgtg gggggtccgg gccacgcggg
2460cgacgcgcct ctagggaagc gatcttgttg caccttcccg ttattctgaa agcaaatcgt
2520agccagaccc gagcgcagcg gcttagcaaa taataagggg agcgtcagtc gtgctcgaaa
2580tgcttccttc gcgatggcgt cagtgttccg tgagggaatg aagccgcagt aggaaataaa
2640gaggctgtgc gcgtagtctg aaaagcagaa gtcaacattt ttacagatga agaaagaata
2700cggaggcaag aggtctttct ctgcagtttg gtggatttcc aacatttaga cttgtttgga
2760agaatttcct cagctgcacc aatgaagtcc ttgatctata gaagtcggca gtccctaaat
2820ctacgtctgc attttgttgc aaatccttta taacattcca ttaaaataat gcagagttat
2880ttaata
28869121705DNAHomo sapiens 91agattagcaa ttacatttaa aaacaaggta gtggtgtgaa
ggctcagagt ttcacacaac 60gactgttgtt ctgaactaaa agcagaggat gtggatgagt
gaggggaggg tatgttgaaa 120atgactaaac ccggtgcaga ggacacgtat acgaaagtgc
aaaaagctct catttgccat 180tttttgtcct cagcaaactc ctctctggta tgtttgtgaa
cgtttgaggg aaaggtaaca 240ctgattaaaa tataatgcaa caagaaggca acgatctttg
ctttgttcac tgatgtgttc 300caagtgccta ggacggttcc tgacaagtag caggtgctca
aaatacattt gtcaagtgaa 360taaatctgtg aaaggaaagg aagaaaaaca ggttgtgacc
agaacttttt gtgaacaaaa 420ccctgttgtt tattacatag actttggtaa tggaaaactt
acttgggtga aataaaaaat 480ggcatcctgt taatttctga gaacgtctgt tggttttagg
aaaagcatac ctatccatac 540ctcactacct gttttgctct agcctaaaca tagattcttc
tttggttagg agacattgac 600ccaatatata agattaaaac aaaaactgag aaataagtga
aatcaaaagc ttttcaaaag 660ttgcaggttg acctacggtg gtggtggtct aaaatcatat
agaaaccaga gatctgatgg 720tttacctgaa aatgcgaagt aaatgcacat actcagcatc
tcagacgatc gaaagctcaa 780cgggtgaaag ctcagggggt taattttgcg attaaggaca
tcttggaaaa gtatgtaaaa 840tccctggtcc acttaagtat tattcctatt ttgggctttt
atttatttat tttgagatgg 900agtcttgctc tgtcgcccac ctcggctcac tgcaacttca
gcctcccggg ttcaagcgat 960tctcgtggct cgtcctctca agtagctggg gccacgcccg
gctaattttt gtatttttag 1020tagagatggg gtttcaccgt gttggccagg ctggtctcga
actcctgacc tcaggcgatc 1080caccgcctcg gcctcccaaa gtgctgggat tacaggcttg
agccacagcg cctggcctat 1140tttgggcttt tataccccac tggtaaactg ctttcctcca
ggttgaggtt aaaacgacat 1200cattttaagg tgaactgaag tctggaagtg attaagcact
tggatcctta gggagcctct 1260ccccgccccc atctctttca tgctaagata attaaaactt
cggggccggg gcattgtctg 1320agtcacttca attcaccagc ctaatagatg caaaaggatg
taagcatgtc agacacgcag 1380agacagtatt tgaatcaagc ttaatagctc aagggagctg
ggccatttcc tattttcttt 1440ttagtgagtg cgatgttctc taaacaccgc ggagaggcag
ggttcccggt gatggccttg 1500ccgagggtgc tcccgcaacc tccacctcca gttctctttg
gaccattcct ccgtcttccg 1560ttacacgctc tgcaaagcga agtccccttc gcaccagatt
cccgctacta cacgcccccc 1620atttcccgcc ctggccacat cgctgcagtt tagtgattga
ctggcctcct gaggtcctgg 1680cgcaaaggcg agattcgcat ttcgcacctc gcccttcgcg
ggaaacggcc ccagtgacag 1740tccccgaagc ggcgcgcgcc cggctggagg tgcgctctcc
gggcgcggcg cgcggagggt 1800cgccaagggc gcgggaaccc caccccggcc gcggcagccc
ccagccttca cgccggccct 1860gaggctcgcc cgcccggccg gccccggctc tcggcttgca
aagtccctct ccccagtcca 1920acccccggcc cccacaggcc tcggcgcccc gccccgcccc
aggccccgcc ccagagagtt 1980ctataaagtt cctctttccc acctcgcact ctcagtttca
ccgctcgatc ttgggaccca 2040ccgctgccct cagctccgag tccagggcga ggtaagggct
ggagtcgggc aggaggaggg 2100gtgtgaggct gataccagag aggacccgga gcgcgaacca
gaggttcgac ctccagggca 2160gcgcagggta ccccggcttc ggagcgggaa gggagcgcgc
cccgtcctgg agctccgact 2220cccaccccat ctgcgctgag ccggaggcgc tggtttgggc
tccaaggccc gcctccttgg 2280ctctgcccga gcctccccgc ctgccctccg cgctcctgcg
acggggtcgc cacaagctgg 2340acgggatgag ctaaccggac tgtcggggcc ccaggagtgg
ctgaggcggg gccgtccaag 2400gcacccacac aagacggcac aactgcctgc gagaaacagg
cccggccctg tggaccccaa 2460tccgaggctc cttcccctgc tcttcgttcc taaggggccc
aagctcacgg cggcctccgg 2520cgcggtgctc acccgctggc gcaggaggag gaggagctcc
acatttgggt cgctccgagc 2580cttgcgtgcg gtggcctagc cggcctggcg cggtccctgc
ctcccaggct ccgcagctgt 2640cgtcgccctc tcccgcgccc tccccgcctc cgctctcccg
ggcctgctcc ggggtccggc 2700ggacgctctg cgcgcggaat cccccgtact ggggctgcag
cccccgcgtc tgcgccactt 2760gtcgtttgca gagcccactt agtgcgcgct agctgggcag
ggataggggt cctattcggg 2820gcgaagggtc tggatgcgag cagagaaagc ggagggtgga
ggaacccggg gctgcgcccc 2880tggaacgccc ggccgcaggc gaggtcctcc gcgcgtggag
gccgccaggg gagtggaaac 2940tgacagagtc gcggggaagg ggcgagaagc gggttgggag
tgagcgaagg caagcgagag 3000ctgcgagtga gtgcggaagg agggccagga ggggtggcgg
ctgggtgggg agagagggtg 3060caagacgagc ggcgcgtgtc gggagccttt gggctgcggg
tgcgttacag gagagcaggc 3120gggtaggagc cttcgcgggg gccgagctcg gaaggcggac
ggctgtgccc gcccagggga 3180tgcgcccggg ccggccgcga aggtgccttc ttccgggggc
ccggacgacc ctgacacggc 3240acgcgcgcgc ttcgcagcct caaagactcc ggggcctcgt
ggtcactggc gcaggggatc 3300ggggcggggt gcccggagtg cggtgcctcg tggctgaagg
gcagctcttc tccccgcagt 3360gcagagcaga gcgggcggag gaccccgggc gcgggcgcgg
acggcacgcg gggcatgaac 3420ctggagggcg gcggccgagg cggagagttc ggcatgagcg
cggtgagctg cggcaacggg 3480aagctccgcc agtggctgat cgaccagatc gacagcggca
agtaccccgg gctggtgtgg 3540gagaacgagg agaagagcat cttccgcatc ccctggaagc
acgcgggcaa gcaggactac 3600aaccgcgagg aggacgccgc gctcttcaag gtctccggcc
tcgggagccg gcgggggcgc 3660gccggggagg gcccagagac agagcccggg gtccccggcg
ccgcctccga ggcgagccca 3720ggggaccgcg cggggcggac gggcgggcgg cggaggcatc
aggtggcgtc gccggagccg 3780caggaggagg aaaggaggcc tcggctctca gcgggaccgc
gggggccggg agccgggtcc 3840tgggcgcgtg gaggctgcag ggaaaccgct gaaggcccgg
ccgggcccgg ggaagggcgg 3900ccaaaggctt gaggggtttt gcgcgttcgt ccgtgcgttc
tcgtttccac gcaagcctcc 3960cgcccttcct ccgggctccc gtctgccgcc tccgtccgtg
ggtccccctc gccctctccg 4020tgcgtccgcg cctgtgccgg cggctgtttt cgtctctcac
cgcgtctctg tttctctttt 4080cgctgctttt ctctctgagt ctctctctct ccatgttttt
cctgaggtca gcctctcttc 4140tcgctcctgc tagctctctg cgggtactcc cacctctgtc
tttctctttg tgtgtctctg 4200tctctctctt tcccccatcg cagtggaact cagggcctct
gtctagagct gtctcccttg 4260ccctttgcgc gagtgcacac acgtgtgtcg ttgttacgat
tgttctcccc taaggcagtt 4320tacccagaga actacgtgtc tgggcccagc ccccacctgt
gggcagagca ggggaagggg 4380acttcctccg ggaatttggt ctcaatttgc tctcagagtg
cctcagctgt gctgccatcc 4440agatgtctcc tgtgggtgac agctcacacc acagctgtcc
ttagtcctag gcaagctcac 4500tcagacactg ggtgggtaga gccccctcaa ggaacctccg
catctcactc taccggttat 4560aaatacccag aaaatgtgtc ttcaacttgg cagtgatagg
gtccaagatg gaaaatcatt 4620ttcctagagc atagctgggg tctttcagtt tacgttctga
gcaacggtgt aaatctgaag 4680gacctatgcg ccattctttc ttttagaaat acaatttcaa
gattccttat aaaatatctg 4740tattttgggt ttagcatggt ggctcacacc tgtaatccca
gcactttggg aagatgaggt 4800ggaaggatgc ctatgcaaca tagtgagacc ctgcctctgc
aaaaaataat aattaaaaaa 4860attagccagg catggtggtg aacacctgta ggccgagggc
ccagctactc tagaggctga 4920gataggagga ccctagaact caggagttcg atgctgcggt
gagctatcat cgtgccactg 4980tactctagcc tgggcagcag agcaggactc tgattccaaa
aagaaagcta ataaaccaga 5040catgtatttt gacttttcgt tctcttcatt ctttcccacc
aggcttgggc actgtttaaa 5100ggaaagttcc gagaaggcat cgacaagccg gaccctccca
cctggaagac gcgcctgcgg 5160tgcgctttga acaagagcaa tgactttgag gaactggttg
agcggagcca gctggacatc 5220tcagacccgt acaaagtgta caggattgtt cctgagggag
ccaaaaaagg taggggctct 5280cctgaatttg ggtcacctaa cagaggcagc cagatccttg
aggcacctta acttcattct 5340gagcatcact ttctagcttt ccttttgtat tgcctgcctg
cctgccttct gcctcacagt 5400gaagcccagc ctccttgcct gagttatgtg ggtcacaagt
tgaaattcct gtggggttca 5460gcataggaga attaatcaca ctgtatgcct caatgtatat
gggggggggt gcattgaata 5520tgtgttttcc agttagtctt tcaaaaaaaa aaagaaaaaa
gaaaactgga taacttgtta 5580aaatttactt atctaatagt ctttagtgag tgactatttt
gcagaaaagg agtaatgaga 5640ggaatatctc atcactatgc atggtaataa aactgtcaac
ttttaaagtg taacatggtc 5700agctgaggtg tttattaaaa gtcagattcc tggacccctc
ttttcaagat tctgaccagt 5760gtgtctggaa gagagctcag gaatctgcat ctggaacaaa
tccttcaggt gacctcactt 5820gggaaacatc tggctggcgg ggtcctttat gtcacaaggc
acattcgcat gccatctgtc 5880atgtatttct ttacctgtcc tgtacaactc agaccttgta
gaaaaaaatc agtttaatag 5940catgaaaaaa taacttccca agggagttgc tgaaaaatac
cttatttgtc aacaccgtgt 6000tatgcattct aagaattaaa tgctcaggta tttttacaag
atttgacatt tagttaggtc 6060agttcctgtt tttacgttgt gccatttccc ttttccccaa
acatgtagga gccaagcagc 6120tcaccctgga ggacccgcag atgtccatga gccaccccta
caccatgaca acgccttacc 6180cttcgctccc agcccaggta tggtggaggg cactgggctc
cctgagggcg aggctgtgtg 6240ggccagctgc ccacatggcc agagaaccac agcagcccag
acagcagaac ttgccatttg 6300ctatggctgc tccaacagcc cagaaaaacc ccaggtcact
gaacgaatgt ctcactttcc 6360acacggtgct gccattggtg tggattttaa gttggggagg
gtcgggcgtg tccgcctgtt 6420ggaatatgct tctcaggtct tctgggaaac agatgttttg
tggaagtgga agattttgga 6480agtagtgcct tatcatgtga aaccacaggg cagctgatct
cttcaggctt tcttgatgtg 6540aatgacagct ttgtttcatc cactttggtg ggtaaaagaa
ggcaaattcc cctgtggtac 6600ttttggtgcc aggtttagcc atatgacgaa gctttacata
aaacagtaca agtatctcca 6660ttgtccttta tgatcctcca tgagtgtttt cacttagtct
gatgaagggt tcactccagt 6720cttttcggat gataaaatgc ttcggctgtc agtctaataa
gggattccct gaggagtttg 6780gaggctgtaa gagcaccccc cgtctcaatg ccagtgcttc
ttatctcagc ctctcctgca 6840ctcctttacc cccgtctcga tgccagtgct tcctatctca
gcctctcctg cactccttta 6900cccccgtctc gatgccagtg cttcctatct cagcctctcc
tgcactcctt tacccccgtc 6960tcgatgccag tgcttcttat ctcagcctct cctgcactcc
tttacccccg tctcaatgcc 7020agtgcttcct atctcagcct ctcctgcact cctttaaccc
cgtctcgatg ccagtgcttc 7080ttatctcagc ctctcctgca ctcctttacc cccgtctcaa
tgccagtgct tcctatctca 7140gcctctcctg cactccttta cccccgtctc aatgccagtg
cttcctatct cagcctctcc 7200tgcactcctt tacccccgtc tcgatgccag tgcttcttat
ctcagcctct cctgcactcc 7260tttacccccg tctcgatgcc agtgcttcct atctcagcct
ctcctgcact cctttacccc 7320cgtctcaatg ccagtgcttc ttatctcagc ctctcctgca
ctcctttagc aggttcacaa 7380ctacatgatg ccacccctcg accgaagctg gagggactac
gtcccggatc agccacaccc 7440ggaaatcccg taccaatgtc ccatgacgtt tggaccccgc
ggccaccact ggcaaggccc 7500agcttgtgaa aatggtaagg aggataccag tgcaggaaat
agaagagcta attgctaatg 7560tggccatggg ccatggcgaa tcctggtctg tcctgggcag
caccaaagct ctttcccctt 7620cttagaggct gcgtgtgcag ctcggggaga ggggggtttt
ctcactcctg tgggatggtg 7680gcatcccaca gccaagttta ctctcaggat ccatgctagg
cactgccctt cgtgggatct 7740tatttaaaca ccacagagat cactccaggc agtggaaaac
agccccccac tttttatata 7800gagaggagat tgtggaagct cataaataat aagtagggat
gctgggagat tattgagctg 7860gtatatttct ctcgaatagt ggtgtgttca ttgttgctat
tgttggaatt agaggtgata 7920ctaaaaaagg aacggaaaaa taccatggca aacacataaa
acgtctctac aggtgcctac 7980ctaccactgg gtcccagaaa gacttgctga ttgtggatta
gatgtggtcc cctgccctcg 8040ggagttcccc agacatcaaa atgagctccc tcagcagaag
ctctcattag ctgggtgcag 8100ggagaatcta gcaatgcggt aactcaggcc ttcaggactt
ttgagttagt tacttaaatg 8160gaagtcctga gacaggtcaa cacactgaac cctttggatg
ttttaggaat atttgttcct 8220ttgcaatttg gccttttttt ccccagtcat gttcaggtta
tccttggctg caggtagtga 8280agaggtgtac cactctttaa tgtttgtact gagtggcatg
ttcacaaaaa agctcagaat 8340tcagttgcat tggcttttca agagggattt gcagcaaggg
ctggtttcca atatggtagt 8400ggaggaattg gctaacataa aactagctcc tgaaattcag
acttgcgttt actgctctgg 8460ctctatggaa ttagtaacca tgggaaagag gcaatgctta
gaactgtgta aagtgatgga 8520gtaggtagag acctgtcttg aagcatcggt aacagtaaat
gaagcagcag caagatcagg 8580tgttctgtgc cacattcttt ttccattcat gtttcataca
acattgtctt caggaacatg 8640gttcagtgtt ctcccaaccc acaagagaca agcaaaataa
aaatggacta aataatttgc 8700tagtttttaa ttgggctctt tggcacagac tcaagtagac
ctgaactctc agctctgttg 8760tgaacccgct ttgtgaacaa ggacaaagca tgtcatctgt
ctctgagcct cagtctccct 8820gttagtcagt tacagagaga gcgctccaag tttccttcca
aagctgtgca ctggctcgtt 8880tctccatcag ctttggtttt ccagttggtc tccagctcat
ctttgcctca caagagcgtg 8940ccctgctagt tgctggtgct gggagtgggt gggaaggtga
ttgggcgcca gccccttcct 9000tcccaggctt cacacacaca ccccaggaag ccccgcggtg
cgtcggactc tctgtctaga 9060catcatctga tttttatttg caaatgcagg ttgccaggtg
acaggaacct tttatgcttg 9120tgccccacct gagtcccagg ctcccggagt ccccacagag
ccaagcataa ggtctgccga 9180agccttggcg ttctcaggtg agtgcagggt ttgctcctgg
aggcaccgca ggaggccagc 9240ctctgctgcc agctctgtca tctttgggca gattcgatgg
gactttagac acttgctttg 9300ctccctctgg ggtctggagt agatgtagac acatcctgtg
tgtgaggtga ccagggtgat 9360ttaggagcac cattagaaaa cctgacatca ctgcttgtgg
ttctgctgac cgtttcagcc 9420actggcttga atggagtcat tttggcttct tcactggcac
ctctctgaat ttctaggaat 9480gtgcctttac ctttaccgag ggcccctctt cagccaacat
tctcacgatg tggaataatt 9540gcttggaagt gtagaagggc ttctcatttt gagaagctga
tcatccttcc aggttgagcc 9600acaaataagt cctcctcctc tactccctgg ggacattagt
tctggtccct catctctaaa 9660acattgatgt gcctaagagt aatacacatt ttggtcttcc
tctgaacttt aatatagctt 9720gcaaacaaat atggattcaa tctgattttt aaagttttat
ttctaaaaaa aaaaaaaaaa 9780tccctgcacc atggagatct tacctactat aaagaaggca
cctctaggct tggcaagcac 9840acgtgctata tgtatattta tttttcagat aatattttgg
attgttttta aatgggattt 9900gtttttatat taaaaccaaa tagcttaagg tttggaattc
tcatcttgcc ctctggcatc 9960tttaaaaatc agtgatgaaa aatactaact aaattctgaa
ggtttcaggg aggcgagagt 10020tgtggcactt ttgctgctca gaggggagct ggagtttgac
ctaccagctc tttctagttg 10080tgaatgaggc ttgcaccttt ttttctgagg tgctcgtgag
taactgagga tgccctttgg 10140gaggaggtgc ttctgagcag gaaggcttgt gtttgttttt
agaaactttc aaacccttgt 10200cttgaacacc taagacttgt gtgggtgcct gaagagtagg
aaataaacag ctatttatat 10260ctcggcaacc tcgtgatttc tgatgacatt aaatgaaatg
aaacctgccc cgagaatcac 10320ctcgaatggc caacacccac tctctttggg gcgcactgtc
tgactcgctt tcagacagtg 10380tgttgaagca gagaattgag acagtgatgt gggttaagtc
tcaaaacctg ctgttgagga 10440ataagatagt tttgtgggtt tctttttttg gtatgcatga
tacagattaa ttatcagcca 10500tgagcacatt tattagataa ctgtgattcc cattgatttt
ggggttccat acagttacca 10560gtggcagctg cctcctgtct gtgccactcc cctgcggtct
ggctgaggag cttgtgcaaa 10620cccagcttgg ttctttcaac tcatgggcga tattttaaag
aggcttctga aatcagcaaa 10680acgtttgtaa atggattcat cttgtttaaa gtttcagaga
gcgcagtttt agagttcttt 10740tcaaacttaa acacaaagcc cagtgggaat ttcagcagac
tttacatgaa cttttagagt 10800atttttctca ttaatttctt tcttttcaca agaattaatt
ttgtgataaa aacaccacat 10860atccagtgtg gaaaactaat ttaaaaatca gaaaaacaaa
aatggaaaat aaaaatatca 10920cattctacca cccagaaatc accattaagg cctcagtgct
taccctttaa tgtgtgtatg 10980tgagtgtgtt tatatataaa ttatatagac ataaataatt
aagcacctaa ttctatatat 11040aatttatata tgtacacaca cacacacaca cacacacatt
tgctttttac ctaaatgatg 11100tcatgttatt attttgggga cgtttcaggt atgtggaccg
acttgcttct ttctgaaaca 11160ccgttatatt ttttgctagt ataaattaaa cttagggttc
atttcctcca aagtaaaaat 11220tgatttgctt aaagatgaat tttcattcag tgacacatga
cttaaatgac atcaccacta 11280tcatcatcat aattcacaaa taagacttag caagttctta
atagtgatgc tctataatag 11340gaattcaact tacatttcca gaaaattaat gaaagataca
cttgttcctt aaaaaaagag 11400tcggtggcca catacgtttg taatatgctg gtttagacag
attaaatggg tttctttcca 11460cgggacttct ccaagtgttg accgagctca tgctgtctgt
ggatctctgg gggagacaag 11520ggcacgctgt gtttcccagg cctccttgac gcgggaacct
tttgttcccc cacgggacat 11580gtgggacact agagttccac cacaggtgct tggctctgtg
gagtcgttgg cctcgaggtg 11640gtgtccttgg cccccagcac tgactccgga gctctgtgtt
tgcagactgc cggctgcaca 11700tctgcctgta ctaccgggaa atcctcgtga aggagctgac
cacgtccagc cccgagggct 11760gccggatctc ccatggacat acgtatgacg ccagcaacct
ggaccaggtc ctgttcccct 11820acccagagga caatggccag aggaaaaaca ttgagaagct
gctgagccac ctggagaggg 11880gcgtggtcct ctggatggcc cccgacgggc tctatgcgaa
aagactgtgc cagagcagga 11940tctactggga cgggcccctg gcgctgtgca acgaccggcc
caacaaactg gagagagacc 12000agacctgcaa gctctttgac acacagcagt tcttgtcagg
taaggcacct cgttatctgt 12060tagaatggag gtggtgatgg cctgcctgcc acaggggtca
gaaaccacag ggtccctccc 12120accccaggct gaggtcttcc tcctgttgac ttcggcgccc
actgggcttg gggcttgact 12180ccagtagaga tcttctgtct ggctctgttg tgggcagaga
gtccggatca gatggtccag 12240gtggaccatg gctcaggctg ttctcttgca attctggttt
tcagcagtcg cctcttaaaa 12300cagttccatt tcattgcact atgatctcga caaatacgtc
tgctgatgtg gcggctcttt 12360tcaggttccc agaaaaatca taaaggttgg aagcatattg
ttaacattct tggttgtcag 12420gtgtgtcacc ctcatgcaga tgctggccca cgagtgagac
ggagggtgga gtggactgta 12480ctggttttgc acaggagaag ttataggaga gtgctataag
ttggctctgt gatatgaaca 12540tttctaagca tatttttcag aaccagtgag ttttgttttt
ctaccttgga tttcatgaca 12600attcagcgaa cctctggctg gcttctgtga agcccctcgc
cctgtcatgc tgggcttcct 12660cactggcttt gtggggctgt ccaggtggag ggagcctccc
gcgtgggagg gagctgctct 12720acccgccact cgccacccca ccgccaactc ttcctctgcc
ttttcccagt cctgtccctt 12780cctgagcccc ttcagaaact cctgtgtctt tgatttctca
tgtgcctccc cttttcttga 12840atgtgcttct tcattcaact tatttaaaat aaaaatatga
cacgtctgtg tgctctggca 12900ctgttgacat gtgctcgtac ttctgggtgt aagtgaccca
agtttttgta agctcatcca 12960gattttcttt tggtgcccaa agcaaatatg tccccagata
actaagcttc aggccaggtg 13020tggtggccca tgcctgtaat cccagcactt taggaggctg
aggtgggcag atcacttgag 13080gccaggagtt caagaccagc ctggccaaca tggcaaaacc
ccgtctctac taaagataca 13140aaaattagct gggcgtgatg gtgggcgcct gtaatcccag
ctactcagga ggatgaggca 13200caagaatcgc ttgaacctgt gggaggcgga ggttgcagtg
agctgagatc gcaccacggt 13260gctgcagttt gcaggacaga gcgagactcc attgcccccc
gcaccacaaa aaaataacta 13320agctcacaca gaggctgacc ataggaagag ggagaactgt
gctggttccc cgaggcggcg 13380gcaagtgagg aagtcacctg gggctggaca cctctcattc
taagggcaga accatcccca 13440agccctggcc agggcggtcc catccttctt ggggttgggc
atggtgttca tgggggacca 13500aggaaattga agggcaactg gggggacccc ccctcccctg
tcagcatctc ctgtgtctgc 13560cttgggatct ggaagagctc acatgggcca ggaaggctaa
ggcccactgg gcctggattt 13620ctgaagactc tggaccttgg tgccagtgga ttcagaagat
accacaaggt gagggctttc 13680taatgaaagt gtcacaagga actggcactg gcttttctga
gtgcctcttg ctgggcgttt 13740ttagggaggt agagcccccg tggtgactaa gctggaaggt
gcacattgag tcacaggtgc 13800actgcgtgag agacagcaca ggcagggggt ggacgcctgt
gagtgtcctg gggctgtaga 13860cttgcgcgac tagaacttac tattaatctg tgagcaagag
ctggtcttgg ctttcattcc 13920ttcctctgta accaagggct gtgctctttg cccactgcag
cctctcacct caaagtgttc 13980actgaggttc aaggaggatg ctgtgaacgt aaaaactgca
gctgtgccaa ccagcttctg 14040cataattaag gattcccacc aaacactctc atgttatcta
gggttggagc catgctttct 14100cagagaattg tgccaactcg ccattctgat tagcctgtgt
aggtgtagtc tcagatcacg 14160gcagtgtgaa tgtattttac agattctgac taagtcattt
gggtttgatt tgaattctgg 14220aaaaaaaaaa aagcaggaag tcaaatagtc ctgtaagtta
gctagaaact tctgttcagt 14280tgaagagaac agtggagatc tttgatatct tcctattcag
gtctgcacag cactagggac 14340agcccccagg gcccggcccg agggtgtgta tctgataagg
acgcgtctgt tctgcagaag 14400ctgtagcggc tcctgtgtca actcgtttct tttgcgggcg
tgacatttta ttgtagctac 14460aggcagaaga tttgtcttgt gtacagggga gggagcatgg
gctaaagtca ggggatgggc 14520acttgtcttt ccaacaatgt tccagtccgt tttgtatctt
ttgggtaggt gtggtggctt 14580caggatgtac atgtgtatat ccacaagcgg gaggccaggg
gggctgcccc actcctgttc 14640tcaagtcaag ttactgttcc atccctggag acaggcaaga
agtctactca gagttacaca 14700gttcaggcat agtgacagtg ggactcagct gccgatggct
ggtgctcagt caccacgttg 14760acgttacata ttttctgtgg tgcctgagtt acgtggatgt
ccgcagtagc acagatactg 14820gattatgtgg gctctgtagt gaggggatga ggttttaaaa
tgatcctggg atgtcgaaac 14880attctgattt tttaaatgaa aacttgtcca tggcataaat
tggtcttttg ccattgcgtg 14940actacgtttc ttgttcttta tctcccgact tcactgtggt
ctactacctt ttgaatcttc 15000gtgggtccaa tgctgcaaag cagtgttctt tagctgtcga
ctagttcctc ttgaagaatc 15060gagggagacc gagggccctg gggggaaagc acccaaagga
atgcatacat gctattttgt 15120atctgagatg ttcacatcaa gagccccact cagcggagta
agagtgctca ttcctcttgc 15180agtgttcaga atcacagtaa gctcttgctt cctgtttaac
ctggtgtgtt cggtgatgag 15240ggtttctgaa catggtctct ttcttgtggg cttctacaga
gctgcaagcg tttgctcacc 15300acggccgctc cctgccaaga ttccaggtga ctctatgctt
tggagaggag tttccagacc 15360ctcagaggca aagaaagctc atcacagctc acgtgagtcc
tcagttacac tcctaccata 15420gtggcttcct gttctttgta aaggccagag tttcatttag
aaaagtccca aatgaaaagt 15480aaatgtcaaa tgacctggaa aaataagcgt aacccttaaa
ctagtgaggg aggaagcatg 15540gtccaacgag cagcacagtc tgaggactca cgtgctcctc
ccagacttga gatctgctca 15600tcaaagaacc agggaggaca gcctcaaagg agggtgcctc
tttccccatc ttttttattt 15660ttcaggaaag ttgtcgtatt tccattttat agggattgaa
aaagattgat ggttaaagtt 15720gccctttaaa attctccagg ttaagattgc tgtaagaatg
ctatctagct agtggatctt 15780cattcaatgg aaaagctttt cccaaatgag aaactatcca
ttccctggag gcattttgta 15840ggtctctgca gctgtgtcct agcacctctt ttatttctgg
aattttagaa attatttaat 15900tattgggcat atgatatttg aaagaggctg aatctttcaa
ggaattcaag caaatcagac 15960cctctcgtaa tgttctctag catagctcaa gatgggttca
actgtggcaa gtaacactaa 16020aagggtaggg ttaggattag ggttagagtt ttctttttta
tgagaaaagg tttccataga 16080taacatgaag cattaatttg ccatgggaaa cagaatcttg
aacccttaag acttttgaat 16140ttgaaaactt cacattgcta catacttgca agcattatta
acgggcttgc atgctgagca 16200ataccaggta aaagttacac cccctaacat caaagttctc
atcatgttct agctctgatg 16260ctatttctca ttgagaactg aaatgaaaca tggtttaatc
ttgaacatac aacccccctt 16320cttgatttta aaaacaaaga ccagccaacc aaccagtata
taatcccata gactcaggag 16380ttttctcatg agttctctcc agtgattgac ttaataattg
atatgattgt tgaaataata 16440actgatacat tgttaacaac aggaattgct aaatgactaa
ataaacttgg cattgataag 16500cagcatttaa gaagttgatg atcggccggg cacagtggct
cacgcctgta atcccggcac 16560tttgggaggc tgaggcgggc agatcatgtg gtcaggagtt
cgagaccagc ctgaccaaca 16620tggtgaaacc ccctctctac taaaaataca aaaattagcc
gggcgtggtg gtgcgcacct 16680gtaatcccag ctactcggga ggctgaagca agggagtcac
ttgaacccag gagtcagagc 16740ttgcagtgag ccgagattgc accactgcac tccagcctgg
gtgacagagt gagactctgt 16800ctcaaaaaaa aaacaaaaaa agaagttgat gatcagctca
gctatcacat caatccagtt 16860ttaaagttga catggatgca agtcactgtc ctctaagtca
gggaaagatg gatccccaga 16920tgaccccctc atgctgaaga cgaggctgcg tggtccataa
aatgaataaa cacacgtgta 16980cacctatgag ttccactttt aaaaattatt aatttaattc
atttcaggta cttaggagtt 17040tagcttaagt cgtcatatat aaaatacagt ctctaatatc
atgattgatg gagagcattc 17100agcttgcctt agatgctgta aattcaggaa aagctgaaca
ttaaggcgtt tttgtttttt 17160ggtgagtgtg atccacgcta ataaccagac agtataaatt
tgaggccagt tagcttctct 17220ttttccacaa tagtagtttt gttgttgttt aactttactt
tttatttctt ttacctctgg 17280ttgagaacta tacagattac ctagaaatca aatcattcag
gatgagctcc ttgtttcttt 17340caaactgcag ttgtggaaaa acaaaatcat tggcctaaat
taccctgcag attccctcag 17400acttcctttt aatttgatca ctttacttga tttgatgcag
ttttagttaa atgtacattt 17460taagtggcag tcgatttgaa agtaacatct ttaacccaga
attaagtcac tttggctgtt 17520tttttacatg ttgatctatg gaaggactaa ccaaaaaatt
gcttctttag atggctccaa 17580atatgaaatg ttttgatgtg ttctaggatg taactttggg
ctttacgtta ctgtctcctt 17640agaatctgag tgctgtttaa tagtgagcca gttgcaggat
atctcagtaa tgtcttttta 17700aaatctctta ttaaaggtag aacctctgct agccagacaa
ctatattatt ttgctcaaca 17760aaacagtgga catttcctga ggggctacga tttaccagaa
cacatcagca atccagaaga 17820ttaccacaga tctatccgcc attcctctat tcaagaatga
aaaatgtcaa gatgagtggt 17880tttctttttc cttttttttt tttttttttt gatacgggga
tacggggtct tgctctgtct 17940cccaggctgg agtgcagtga cacaatctca gctcactgtg
acctccgcct cctgggttca 18000agagactctc ctgcctcagc ctccctggta gctgggatta
caggtgtgag ccactgcacc 18060cacccaagac aagtgatttt cattgtaaat atttgacttt
agtgaaagcg tccaattgac 18120tgccctctta ctgttttgag gaattcagaa gtggagattt
cagttcagcg gttgaggaga 18180attgcggcga gacaagcatg gaaaatcagt gacatctgat
tggcagatga gcttatttca 18240aaaggaaggg tggctttgca tttcttgtgt tctgtagact
gccatcattg atgatcactg 18300tgaaaattga ccaagtgatg tgtttacatt tactgaaatg
cgctctttaa tttgttgtag 18360attaggtctt gctggaagac agagaaaact tgcctttcag
tattgacact gactagagtg 18420atgactgctt gtaggtatgt ctgtgccatt tctcagggaa
gtaagatgta aattgaagaa 18480gcctcacacg taaaagaaat gtattaatgt atgtaggagc
tgcagttctt gtggaagaca 18540cttgctgagt gaaggaaatg aatctttgac tgaagccgtg
cctgtagcct tggggaggcc 18600catcccccac ctgccagcgg tttcctggtg tgggtccctc
tgccccgccc tccttcccat 18660tggctttctc tccttggcct ttcctggaag ccagttagta
aacttcctat tttcttgagt 18720caaaaaacat gagcgctact cttggatggg acatttttgt
ctgtcctaca atctagtaat 18780gtctaagtaa tggttaagtt ttcttgtttc tgcatctttt
tgaccctcat tctttagaga 18840tgctaaaatt cttcgcataa agaagaagaa attaaggaac
ataaatctta atacttgaac 18900tgttgccctt ctgtccaagt acttaactat ctgttccctt
cctctgtgcc acgctcctct 18960gtttgtttgg ctgtccagcg atcagccatg gcgacactaa
aggaggagga gccggggact 19020cccaggctgg agagcactgc caggacccac cactggaagc
aggatggagc tgactacgga 19080actgcacact cagtgggctg tttctgctta tttcatctgt
tctatgcttc ctcgtgccaa 19140ttatagtttg acagggcctt aaaattactt ggctttttcc
aaatgcttct atttatagaa 19200tcccaaagac ctccacttgc ttaagtatac ctatcactta
catttttgtg gttttgagaa 19260agtacagcag tagactgggg cgtcacctcc aggccgtttc
tcatactaca ggatatttac 19320tattactccc aggatcagca gaagattgcg tagctctcaa
atgtgtgttc ctgcttttct 19380aatggatatt ttaaattcat tcaacaagca cctagtaagt
gcctgctgta tccctacatt 19440acacagttca gcctttatca agcttagtga gcagtgagca
ctgaaacatt attttttaat 19500gtttaaaaag tttctaatat taaagtcaga atattaatac
aattaatatt aatattaact 19560acagaaaaga caaacagtag agaacagcaa aaaaataaaa
aggatctcct tttttcccag 19620cccaaattct cctctctaaa agtgtccaca agaaggggtg
tttattcttc caacacattt 19680cacttttctg taaatataca taaacttaaa aagaaaacct
catggagtca tcttgcacac 19740actttcatgc agtgctcttt gtagctaaca gtgaagattt
acctcgttct gctcagaggc 19800cttgctgtgg agctccactg ccatgtaccc agtagggttt
gacatttcat tagccatgca 19860acatggatat gtattgggca gcagactgtg tttcgtgaac
tgcagtgatg tatacatctt 19920atagatgcaa agtattttgg ggtatattat cctaagggaa
gataaagatg atattaagaa 19980ctgctgtttc acggggccct tacctgtgac cctctttgct
gaagaatatt taaccccaca 20040cagcacttca aagaagctgt cttggaagtc tgtctcagga
gcaccctgtc ttcttaattc 20100tccaagcgga tgctccattt caattgcttt gtgacttctt
cttctttgtt tttttaaata 20160ttatgctgct ttaacagtgg agctgaattt tctggaaaat
gcttcttggc tggggccact 20220acctcctttc ctatctttac atctatgtgt atgttgactt
tttaaaattc tgagtgatcc 20280agggtatgac ctagggaatg aactagctat gaaatactca
gggttaggaa tcctagcact 20340tgtctcagga ctctgaaaag gaacggcttc ctcattcctt
gtcttgataa agtggaattg 20400gcaaactaga atttagtttg tactcagtgg acagtgctgt
tgaagatttg aggacttgtt 20460aaagagcact gggtcatatg gaaaaaatgt atgtgtctcc
caggtgcatt tcttggttta 20520tgtcttgttc ttgagatttt gtatatttag gaaaacctca
agcagtaatt aatatctcct 20580ggaacactat agagaaccaa gtgaccgact catttacaac
tgaaacctag gaagcccctg 20640agtcctgagc gaaaacagga gagttagtcg ccctacagaa
aacccagcta gactattggg 20700tatgaactaa aaagagactg tgccatggtg agaaaaatgt
aaaatcctac agtgaaatga 20760gcagccctta cagtattgtt accaccaagg gcaggtaggt
attagtgttt gaaaaagctg 20820gtctttgagc gagggcataa atacagctag ccccaggggt
ggaacaactc tgggagtctt 20880gggtactcgc acctcttggc tttgttgatg ctccgccagg
aaggccactt gtgtgtgcgt 20940gtcagttact tttttagtaa caattcagat ccagtgtaaa
cttccgttca ttgctctcca 21000gtcacatgcc cccacttccc cacaggtgaa agtttttctg
aaagtgttgg gattggttaa 21060ggtctttatt tgtattacgt atctcccgaa gtcctctgtg
gccagctgca tctgtctgaa 21120tggtgcgtga aggctctcag accttacaca ccattttgta
agttatgttt tacatgcccc 21180gtttttgaga ctgatctcga tgcaggtgga tctccttgag
atcctgatag cctgttacag 21240gaatgaagta aaggtcagtt tttttttgta ttgattttca
cagctttgag gaacatgcat 21300aagaaatgta gctgaagtag aggggacgtg agagaagggc
caggccggca ggccaaccct 21360cctccaatgg aaattcccgt gttgcttcaa actgagacag
atgggactta acaggcaatg 21420gggtccactt ccccctcttc agcatccccc gtaccccact
ttctgctgaa agaactgcca 21480gcaggtagga ccccagaggc ccccaaatga aagcttgaat
ttcccctact ggctctgcgt 21540tttgctgaga tctgtaggaa aggatgcttc acaaactgag
gtagataatg ctatgctgtc 21600gttggtatac atcatgaatt tttatgtaaa ttgctctgca
aagcaaattg atatgtttga 21660taaatttatg tttttaggta aataaaaact tttaaaaatt
tgtta 2170592139436DNAHomo sapiens 92agtagggagg
tgggcaggag ccagtgatga cggaatggca atcacatttg acctctgatc 60tgtttatttc
ctcctccttg acgtctccat ataaatgtta cacgggcatc cccacactcg 120gatacgcacc
cacagtggct gattcggggg taaccgtgtc atttgcttgc aacactggca 180cctctgccct
gcaccccggg agtgagcagt gagtgaggct cgggtctggg cgctggctcc 240gaatcttcgg
gctgggagag actccaccat ctgggggcgg cctgggggag cagccttagt 300gtcttcctgc
tgatgcaatc cgctaggtcg cgagtctccg ccgcgagagg gccggtctgc 360aatccagccc
gccacgtgta ctcgccgccg cctcgggcac tgccccaggt cttgctgcag 420ccgggaccgc
gctctgcagc cgcagacccg gtccacacgg ccaggggcta cgacccttgg 480gatctgccct
ccgctcagct cgagcttccc tcgtggccga cggaacaatg aaggtaacta 540cttatggttt
tgtccgtgtt ttacaaaaat gtgtgcgtga atcgaaccgg cgatttctcc 600aagaaacata
gttggcaggg aggggaggaa ggcgagacaa ccatggctta tatcccccgc 660aaacgtctca
gtatcttctt tatcaatcgt agtttgcggg gaccgtgcat tctgttcaga 720tttcggttta
acctccactc gcaggacgtg ccttctcgga ctttttcaca ttcgcttttg 780ggaacggagg
tgaaagtctg ctacagctcc ctcccctgct tgtgaagttt ggaaaggaag 840tgagggcttc
tctcagtttc tcctatgcac aggaggtggg gaattttgga gaggaggtct 900ggggatgtcc
cgggctgtaa atgcgctttc ctgcagcgtg tgttcgtgat gcaggaggga 960gcggctggaa
gagttgaccc gggtggagag gggagggaga acgatctttt cactgttaaa 1020agcagaaggc
ccctcttatt ttgtttcttg tggaaattaa agcttctagg agttacaaat 1080gatagacgcc
taagggcatt catttgttaa accagtgagc accctaatgg ctctgatctt 1140gctaatcaag
gataattagc ctagctgcct attatttctg actatttagg tgtagggatg 1200tacaccgttg
agtgttttgt tttcctagtt tcacacactg gaaaactgca atcgcatata 1260aaacccgaag
agcaactttt tccaaggaaa gtgaaggatg ggcagatatt cttgccatct 1320aacattttgg
aattgagatg accataatgc aatctgaact tctggtagga ataaagcctc 1380gtttcagagt
ttctaaggag ggagatgaag cgtggttctc aactgctctt atctacaacc 1440catcccagac
catagtttca cttagaagaa ataatatgta aatagcgcct ttgttgccaa 1500acaaaaactt
tcactacaat taaacagtaa ccgagtggaa actatgcgtt tttgtattca 1560acagagatca
cacaactttt cttctatagt tagaggttct atttctggct tcctcatgct 1620tgtttcattt
cagatgaaaa acacacttta gttgattata gctttagtaa gtaaaaggag 1680aaaactaaga
atgaacagtc ttgcttttcc agctttttcc tgtccatgtg cagttgtggt 1740taattacgcg
tttttgtagg tccaaaaacc cctgtccctt ccacaagata cttttataac 1800atggggaact
aggtaagata tctacaagta gtctcttttc tgtttcctga tatttcctaa 1860gattaagaaa
gaaatgattg tattctaggt atgatcgaag aagtatggaa ggttccatta 1920agttagtttt
atcacaatat ttcaaacatc tttccactta tctcttaaat atgtattgct 1980atcacaagct
tgatttttta aaaaaatgtt atttgcacat ggcatcttga ttgcctttgt 2040cctcagcaaa
ttctccgggc ttaagtcatg catgagcttg tattttaaga cagacacatg 2100cagaatgggc
aacttggata agaaacatag gatatacact gagtagcatg tgtacaaaaa 2160tggtaagtga
gtattatgac ttaataaatt tagatgggga tttaaaaatg atacacatgt 2220aaatgggatt
ggaggcaagg gaagtccgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg 2280tgtgtgtgtg
tggagggaag acgggaggcc tagtggggag agaggtttta cattccagac 2340acaggatgtg
gcccctcagg ctaggctcag agatgtaaag ctagttaagc tggcctaaca 2400aaagggtggt
ggttagaaaa aggaaaaaaa gaggtggggg ttggggagga aaagaattta 2460atgctggcca
atattttcat ctgataagtt tcagtaatga gtaatttcac tggatttcag 2520aactacagag
agaaaagggg aaaaatattt ttcctttttt acgcaagaat ttctcttgct 2580tttcagctca
ttagaaccag atctaattat ttgaaatgag tttaaaacct tattatgaaa 2640ggaagttgaa
aacattcgat cacaattgag ttttgtacta tggactaaaa ccaagatgtg 2700ctttctgtca
gtagctgtgc aactccctga aaaaagaaaa atagcgcaga gcgatctgag 2760ctttgtgaag
gctacacaat ttatcaggcc cagagagata ggagtgtgag acttcagtca 2820cgtccccccg
tacgcatgcg caggagtaat tatttaaaga cattttgttc ctgactaact 2880gcctcactca
ttatgttcct ggaatttgtg atacaaaaaa acaatgttta gcctatcaat 2940agtttatata
gtttatgtta ttttaatata aattcttctc aacttagaaa ctgcctcttt 3000tttcttttaa
aaacccactt gtaactgctg tatatattca gggcaacttg atttggtgtt 3060tcgttggttg
cagtcctcaa atttgacctc aatatactct ctacttatat aaattttgtc 3120tcagttttgt
ccgtaggctg acattccaat tgttttccta attatatatt ttgttcctta 3180tttctcatgt
ctagaaataa agctagggaa gtaaacagct ggaaaactga tagtggtgtt 3240attaacctaa
ctgagagggc tgggcttatg agtaaattat tcctgtgcat aaatgaaaga 3300ttgtttctaa
atggcagcta tgttgagcct ttgtattagt tacatctttt ggggtttcag 3360gttgccagct
tctttaaatg gcctcttctc aactggtata ggaagttgga aaataaagaa 3420ctttctttat
ttccctttag tgttggtaac cacagtttct ttaaataaca gatgcccacc 3480ccagggaaac
ccagtggcat gatcagcctt atgctcagga aggtttggtt gctatactgg 3540agagtgagaa
tctgggacct tccatgatag acataattgt gccagctatc ctctactttc 3600tatatgatgc
tatcattctt ttttcttttc ttttttttga cagaatctca ctgtgttgtt 3660caggctggag
tgccgcagag tgatctctac tcactgcaac ctctgcctcc taggttcaag 3720caattcttgt
gcctcagcct cctgagaagc tgggattacc accatgccca gctaattttc 3780gtattttttt
gtaaagacgg agttttgcca tgttggccag gctggtctgg aactcctggc 3840ctcaagcgat
ctgcccatct cggcctccca aagtgctggg attacaggca tgtgctatca 3900ttctttttga
gcacaggagg aaactatggc tgatctgctc attttactgt caaaaatata 3960ggcagctttt
gtattgtaac attatcccct taacagctgt ccaactggtc tatacatttc 4020acctaacata
tggtaaatgt tcctactgtt ggcctttcct gagcctctgt ccattcaact 4080aaggccactg
caatgggatt gtatgcagtt cagccaagaa ataaatgtga ggtgcaactc 4140acatttttta
aatgtttcaa aattaagcat ttaggtgctt ttattcataa acatgacttt 4200gcaaatattg
gtaaacagtt tcatcataag accttgtcag tgactcacaa tgtcaatggt 4260gaacgcaaag
gagaatctgt cttttctgga acaccaggtt caggtatcag tttcaactat 4320gcttataatt
tgtgctctaa agtccacaaa gctaaattat ctttccccta aaaattgagt 4380actcatatcc
ttaaaatagc ttggaaatta gattacctta tgaatacagc atagcatgtc 4440acataaacgt
ttttctactg ttataccttt ttggtgggaa agactatttt gcaaaacatt 4500tttcttgtgt
tcagtaatta atgggaaaaa caaactctaa aagaaagaga cagttatgtc 4560ccaaaaatac
aggaaaatgg aagaatggaa acagggaaga ccaataaaga aaaaaataga 4620ggaaattaca
agtaataaac tgaagtcata ctgaaaaaca tatggctctt tcttattgaa 4680agttgtgaaa
tacttgcaaa actcagctag ttccattaag aatagtcttt aatctaaaaa 4740gaacaaattc
atttgtcagt tctttatttc ggtgtgtaga tttgaatgtt tcatcaattg 4800catttacggt
ttatccctca gtgtgagaac tgtttttgct gttttgacta taaatggata 4860tctgctttag
gaagacttag gaagcctggg acataggatt acagatcaaa ttctatttga 4920ctccatagaa
gttgagacgg aaggagcacc tgttgggata ttctagacca aacattccac 4980agctgtctct
taacgtgact gacaaagaga cacagttgag acgaagtttg ggtatatcct 5040gggatgaggc
caagggtgga tttgcacagg atggtcacag ggcagttgtt agcattccac 5100cactacataa
aagggtgatt ttgccaagtg catttcattt catttcagtt gatttagata 5160ccaagttata
ttgttttgac tttaggacta gatgtgagtt caggaatttg aaatcataat 5220aaatgtttcc
ttgaactttg aagataaaag gtagagttaa aagacagctg cgaagtctac 5280atggggaagc
ataatacatg actcagggtt ccatggtttt cagtgtcggt gagtgctctg 5340tacacttata
agaatagtgc tggtgtttat agaagaaaca catgcaggtt tgaggcaaga 5400cttccttgct
taattggtgc ttttgctttc cattttctaa atgccatgca aactactttt 5460ttttttttct
tttgttgaga cggagtcttg ctctgtcacc caggctggag tacagtggtg 5520cgatctcggc
tcactgcaag ctccgcctcc tgggttcacg ccattctcct gcctcagctt 5580cctgagtagc
tgggactaca ggcgcccgcc accacgcccg gctaattttt tgtatttttt 5640gtagagacgg
ggtttcacca tgttagccag gaaggtcttg atctcctgac ctcgtgatct 5700gcccgcctcg
gccacccaag gtgctgggat tacaggcgtg agccaccgct cccggcctca 5760aactacttta
actgaaaaca ttcttctaag gaaagcatca gaaaacttac tagaattgct 5820taagaataaa
taaataatac aaataaaaga gcaaaatgag aaagtagaca gactcctagt 5880ctattgtgct
attgatctct ccaggttcta ggctttcttg ggtctgacac cactttgtaa 5940attttttttt
tttttttttt ttttttccag atagggtctc attctgtcac ctaggctgga 6000gtgcagtggt
acaatcatgg ctcacttcag cttcaacctc ctgggctcaa gtgatcttcc 6060tgcctcagct
ccctgagtag ctgggaccac aggcatgtgc caccacgccc ggtgaatttt 6120tgtatttttt
gtagagatgg ggtttctcca tgttgcactg gctggtcttg aactcctggg 6180ctccagtgat
ccacccacct tggcctccaa agtgctggga ttacaggcat ccgtcactgc 6240actgggccag
tttgtaaatc ttatgaaaag tatggccaat cttttgcaaa atgtgcaaac 6300acatatagac
acaaagtttt atatctaaat tattggttat taaagccagg acaatagagt 6360gcatatagca
tggaagacag gtagaaaaga ctgaaatggt ttagttattc agagcagtgg 6420agggctattg
gctcttgcct ttgcagtcag ctgagatatg aaactatata agcagaagct 6480tcacgctgcc
atttgaatat tgaaaatctc cacttttagt tcaagagata aacaaccaat 6540ggtttgtttg
ttcacagcac ataagttatc actttcttct ctgtttcatc ccatcaagat 6600ctaaggtgta
tagttacaga atagaactcg gttcatacca tatgcaccct aatttcttcg 6660atcttcaact
agtttggaag tgtgtgtggg tgttttctta gccaaggtta atatgcaatt 6720tcttagtgga
gtgtaggagt ttggggtgcc tagccttcct acttcccact tagataactt 6780cccctacctg
ttgtacctgt caaaggagaa ggccagtatg gccatgttct ttgcaggtga 6840ctccacctta
gccacagctg attgtaacaa gggtgtatat ttggcccaag tccagccatc 6900tttttttttt
ttttttgagg cggagtcttg ttctgtcacc cacgctggag tgcagtggtg 6960tgattttggc
tcactgcaac ctctgcctcc cgggttcaag caattctcct gcctcagcct 7020cctgagtagc
tgggattaca gacacccacg accacgcttg gctttgtatt tttgtatttt 7080tagtagagac
ggggtttctc catgttggcc aggctggtct agaactcttg acctcaagtg 7140atccgcccgc
cttggcctcc caaactactg ggattacatg cccagccagc catcttttac 7200ttctttctta
ttctcttatt ccacatattc aagcaggtac cacgtcctgt ggactctgtc 7260ttctctgaat
ctataggttc tctctttccc attgccctgc atactggttt atgctctcat 7320tacttctcgc
ttgaattatt ccaaaagtct cccaactggt ctgaagctta attttcatta 7380tgtgctgttc
gatgtcattc caccacgcaa aatctatggc ttctccattg tctcctgagt 7440ttagtttagt
gcatgagacc gtttaaaatc tacctacacc tcttctatgt gcatgcattt 7500ctctagtcat
aagagaggat ttgatctatc tcaaaatgtg ttcttatatt tgcatttact 7560ggtttttaac
tccctccatc ctatctataa tttgcaccat gttgctcacc atgcagccca 7620ctccccagac
accttgtgag aacagtgatc atgtttttgc agtggaatga acatgggcga 7680aaggtgggaa
ggtatgcata gatttacatt ttgaagtcag gaaataagat actgatcaat 7740gctttaattc
gactgtgctt tttacctttt cctctgttgt agcatgaacc ttgccccaaa 7800aagatattga
tcatatgctg caactcctct gcacttacct tttcttctac catggcagga 7860accttgcacc
attgttggtg ctttacagat attggttgag ttaaatcgag agcctatttc 7920tggactttca
agattcagat taattgattc tgttttatac ttctctgttt ttgaatggca 7980catacatctt
tccacacttg gatttctttg aagttaaagc tttaattgac ttccaaaaga 8040cagaggatta
taaaaacaca gagaacagta aagtatttac acggtcttaa tgcctattgc 8100caaacacata
tagctgctat taatgcctat tgccagactc atatagctgc aaactcatgt 8160agcttaatgc
ccattgccaa actcatatag ctgctatata tgtctactgg aaaactcaca 8220tagctggttg
attttaaatt gattgtagga aaattcatac aaaaagatgc tacataggaa 8280tataaactga
acaccacaaa aatcgtaatg aacaaactca gtaatgccag cctgttcaat 8340cactagtttt
cagattaagg cagtatgcaa agggaaacat ccttggaatg gtcttagaat 8400atagaacaaa
gtcatgtgtt tgggaatctt aaccaattcc aatactgttc aacatgtttt 8460tctttgttgc
aaacaatgca gtttttaagc aaactaatga atgcataccc tgacaaacaa 8520atccaacaaa
agaggtactt agagcagtgt tcattgaatc ctagaatttt gaaagaaaaa 8580atctattagg
tcattttggg cttttacttc tgctgaagaa ggattgttct tttgagttta 8640tttttctagc
tttcagttct attccattta aatgcctcga gaaataggac ttctcaaatt 8700ccctgtggag
agttctggca cctactatat tcacttttga aagtctcctg ataactgatt 8760tcctttttct
tttggttata cacatcaact attcatggtt ggctctgctg atagttttcc 8820atgattcttt
atgcttattt aaaagaaatc atataacatt aatcatataa catataacca 8880ttacttggtt
ataaagcatg atattaacta aactggcttt taaaaattca ataacattag 8940agcaaatatt
ttattaatat tgtcagtagt tccatgaata tatagatgta ggatgtcaat 9000aaagtttatg
ccccttaata actgagtgtg ttaatgttgt atttgctggt taactggcac 9060cttccctcct
tttgatcaat gttcttagaa cagtatgtac aggagtactt tagtctacca 9120cttgatattc
aaggacaaca cttcgaagct tgaaatgagg gattgtttta accatattaa 9180cgtaactgca
tagtttgcaa tagatttaat gattcaacat cattgttaat atttagttta 9240attaaaagtg
ccttatatta acttgtacac atgtgaaatg acttatcaac aagattattt 9300attgcagcat
tgtttgtgat tacaaagagt ggaagtcatt tgcatagtca ttaggcgtaa 9360aaaataatga
cattaaaaga aaacaattga ggaaagaacc agtaagctct caggtagaga 9420taaaaagaaa
gttaccgtga gccttttcac tgtatatatt tatatatttg atttttgaca 9480cgtgagttta
ttataatcaa gattgaatga aaaaaattga agccttttaa tgaaattagc 9540ttgacaccag
agtcattatc aagaaaatct gaaatactgg tacctatgca catttgattt 9600tattattttt
agttttatta ttttttgaga cagagtcttg ctctgtcgcc cagactggag 9660tgaagtggtg
tgatctcagc tcactgcaat ctccagcctc ccaggttcaa gcgattctcc 9720tcagcctccc
gagtagctgg gattacagat gcctgccacc atgcttggct agtttttgta 9780tttttagtag
tgacggagtt ttgccatgct ggccaggctg atctcaaact cctgacctca 9840ggtggtccac
ctgcctcagc ctcccaaagt gttgggatta caggcgtgag ccactgcacc 9900cggccattta
agcaaatttt agttaagacc agtaacatat ttttgacagt atttccgaag 9960tgttgtattt
aatttaacta attgaaaatt atctattaag aaagcaagtt aaatgtaatg 10020tgtatacttc
atagtataca cattataatg attcatagta accattatat gaagagtgtc 10080taaacttttc
ttcaaatcta ccatttatat agtacaataa tgaccagcaa acaatggcta 10140agttttactt
aattagacat ttgtgtagct cctaccaagg ctaccagact ttgtacccag 10200taacaggaaa
acagaaataa ttcaagcatt attctcactc ttgagaaaca attctattta 10260gggagatata
cataaaaagc aaaggtggct gggtgcagtg gctcatgcct gtaatcccag 10320cactttggga
ggccaaggca ggcagatcac ttgaggccag gagttcgaga ctagcctgac 10380caacatggtg
aaaccctgtt tctactaaac atacaaaaat tagctgggtg tggtggcatg 10440cacctgcaat
cccagctact gggcaggctg aggcagataa ttgcttgaac ctgggaggtg 10500gaggctacag
tgagctgaga ttgcaccact gtactccagc ctgggtgaca gagcgagact 10560ccatctcaat
gaataaataa ataaataaat aaatagcaaa ggcaataatg tgcatatagt 10620aggtgctaca
gtagaagtct gcacaaggtt ctgtgtatgt ggaaaagaca agtcagaaaa 10680attaggaaag
gctttattgg gaggtgacat ttaagcagaa tcacgaaaga agacctgatg 10740aacatggggg
taagagcact tgtacacaac cccatactcc tgggctcaga ctcacttgct 10800cattccctaa
tcatagaaga ccttgaggaa aagcatgctg gggttccctt ccagcccact 10860ggtaaataca
gagaggccta agcacccaac atcccccagg gaatacacca ctgggactta 10920aagcattggc
aacccagcac ccagttaaat tccccttgtc actgtttcca cattgtcccc 10980atcaccttca
ctctcttgat gctctgcatt ttctctctta actcgaccca cagtagaccc 11040tcccactcaa
atctgccccc aataaccttt gcaaccaata ttaccgcact acactttatc 11100ttccctaagg
gtttcctgct cctcctggtc ttaggtgagg tcatttctct gccagccttt 11160aaagtggaag
ctgctcattt tctctgtccc tcatccaggg ctggagtggg actgatgccc 11220ttcaccctgc
ccagtactgt ttccacatga gactccttgc atagcatctg ctctctgcta 11280ctcagaccag
gagtctgtgc tctctcttcc tctaaccatc attggaagac accccagtcc 11340ctctggcccc
attatccact gtagatttta gcacttacct cctctcttcc ctcccatgtg 11400ctgttttccc
atttatttta aggtgcatgt ggatggccca ttccccttcc tggcatctta 11460atccctttaa
tttctcattt ccattaattt gctacattcc tcatatgcca gctaccccta 11520tggccatatc
ccagaccttt gaatcacaca ccaaattcca tcaagtccta tgagtcattt 11580ttggtccaag
acctatctta catctatgca gtgctatcta ttttaacaac catgtgccca 11640gtttaggcca
ctgtcttctc ttcactgaat atatgtgttc ctgttttttc tcatccccat 11700ttgtttccca
gacacaattt gttctccaga gcagagtgat cacatcagtc acctgctata 11760aaaactcctc
aacccggtgg ggcatggtga ctcacagccc cagcactgta atcccagcac 11820tttgggaggc
tgaggtggga ggatcacttg agcacaggag gagctgaagt gatctgtgat 11880cacgtcactg
cactccagcc tgggctacag agtgacaccc tatctcaaaa acaagcaaac 11940aaacaaacaa
acaaaaacca acaaaaaatt ttttattaag caaaaaacct cttcaacctc 12000ttcctgttat
gttttgaata aaagctaaag tccccaccat gctccagaag ttcccaaggg 12060atctggtcct
tctcatcttt acagcctcat cttgttttgc cgtttccacc tccctcatcc 12120cccaaactct
ttttcttcag ggcctttgca cttgctgatg cctctgcctg gaaggtcttc 12180ttctgattcc
ccatccaggg gtgccttatc accctgccct gccaacctca gattggatgc 12240tacttcctca
aagagaccct tgggactccc atgtttccca ggctttcagt gccctcatct 12300caacttgtaa
tgattgtatt ggggtgatta tttgtatgac tttgggattg atatctgact 12360cttccactag
accatacatt tcttgagagc agagagcata tccagttttt ttaccactgt 12420gcaaccatat
gtcgtccaat gcttggccca taataggggg ttggtgaatg tggtaggctg 12480agtcatagcc
cccaaggatg cccatagcct catccccaga agctttcatg gtaaaaggga 12540ttttgcagat
tgtgattaag ttatggatct tgagatggag agattatcct tgattatcta 12600aataggtcca
atataatcag tagcgtcttt ataagagaga ggcagagggt caaaagcaga 12660atcagagaag
gagatgccac agtggaagca aaggggtgtg tgtgtatgtg tgtgtgtatg 12720tgtgtgtgtg
tgtgtgagag agagagattg agatttaaag agctccatta cttgatctga 12780ggataaggat
gagccaaaga atgcaggtgg cttgtagaag ctggagaagc caagaaaaca 12840ttctcactct
agagcctcca gaaggaatgc agctctgctg acaccttgat ttggaacttc 12900cagaaccata
agataataat tttgtgtagt tttgaggctg ggctcatgcc tgtaattcca 12960gcactttggg
aggccaaggt gggtggatca cttgaggtca ggagtttgag actagcctgg 13020ccaacatggt
gaaaccctgt atgtactaaa tatacaaaaa ttagccaggt gtggtggtgc 13080acgcctatag
acccaactac ttgggaagct ggggcaggag aatcacttga acccgggagg 13140tagagattgc
agtaagctaa gattgtgcca ctgcactcca gcctgggcta cagcgtgaga 13200cttcgtcaga
aaaaaagaat aattttgtat aatttcaggc cacaaagtct gcagtcatct 13260gttacaacag
cagtagtaca cgaatacaga ttttggtacc tggaaatggt gtgctactgt 13320aacagatacc
taaacaatgt ggaagtggct tttgaattgg gtgttgggca gcatgtggaa 13380gaattttgag
aagcatgata ggaaaagcct agcttgcctt agaaagactg ttagtagaag 13440tagggatgtt
aaaggcgctg ctggtgagga cttggaagtg aagagcatgg taaagaaaat 13500gtgtttcatt
ttagagaata tcaaagtcat tgtagaaggt tggcagaagt gtaggttttc 13560ataatgtgtt
gttggtgagg gctgagaaag aaatgaggac catgtttagg gaaactggag 13620gaaaaagatc
cttgtcatac agtggaatga aactgtggaa ttgtgtctta cagttatatg 13680ggaagcagaa
tttgtttgaa cttggatatt tggcttagct ttccaagtaa agtattgaag 13740gtgtagcctg
gttttctctt gctgttttat agtaaaatgc ccgagaaaaa gggataaatt 13800gaggtaggaa
ctgttaagaa aaaggaacaa agacatgatg acttgggaaa ttctcaggat 13860acctggtttg
taaaagatgc tagaattaga agattcattg tcaggaaagt gtgctctgga 13920gaggaagcca
agggtgagtt ccttgtggcg taggttaggg gctgtggcag ggatgcaggg 13980aagagatgat
ggtgacttgg actaggggtc tgacggggta tgggaaaata gagaggaatg 14040agttgattct
gttgggactt tgtattgagt tccttgattc cataagtgga aacacatgta 14100gagctctctt
tcctggccac ctaagctctc tgaccatatc cctgactctc tccagaatgc 14160cttggcttca
tgtccacgtg aggacaaatc atatttttct gcattttgcg tgctggattc 14220ctctctggac
taaagatcca atgagaggtg gtttctagct ttctgctctt tcccacaaca 14280ctccgtcagt
gagtcttctg gatgtcctat aggcaactca ctggatccac ttggtctgtg 14340gaagaatcac
taccacatcc atttcacctt gggcacagac tagaaggtga ggcagtcatg 14400tcctgcagtc
actgggtagc ttacaagtgc taatacagca atagcttaat tagagagaga 14460gagaagaaga
agaatgttat ggagcctgtt tctagagagg aaaccacaat atcttgatca 14520agagacccta
aaactggaag aaccagagca gctggtatca aaatgtggaa aaaactgaga 14580tgtggcaagt
ggtacaactg atagccaagg aggaaaaatt tgtatccccc tgtaatccca 14640gcactttggg
aggctgaaac aggtggatca cctgaggtca ggagttcgag accagcctgg 14700ccaatatggt
gaaaccctgt ctctactaaa aatacaaaaa ttagctgggc gtggtggtgt 14760gcacctatag
tcccagctac ttgggaggct gaggcaggaa aattgcttga acctgggagc 14820agaggttgca
gtgagccaag atcgcaccac tgcactccag cctgggtgac aagagttaaa 14880ctctgtctca
aaaaaataaa aagaaaagtt tgtaccctct tcttttctct tgcctcagga 14940taactgagat
tcttataatg catttattga acaaatattt gaggagtact cattatgtaa 15000gcatcagaca
ctgctcaagg tcttgaggct gtgagggtgt attagtccgt tttcacactg 15060ctataaagaa
ctacctgaga ctgggtgatt tataaagaaa agaggtttaa ctgaattaca 15120gttcatcatg
gccagaaagg cctcaggaaa cttacaatca tggcagaagg tgaagaggaa 15180gcaaggcaca
tcttacatgg tggcaggaga cacagtgaga agggagaagt gccacacttt 15240taaaccatca
gatcttatga tgatatagga gttaagaaga aatcacttag gtagatagtg 15300agggtacggg
agtccttggt aaggcttttc ttttaaatga aaagcagccc cacacataga 15360caagcaagct
gggagcttgc acgggtgaat gccggcagaa actaggaacc agacacgtta 15420agatggcggc
tccattttcc cttctctgcc agccaagtgt acagtaagga gcagacaagc 15480tggtgccggc
caagaggaga attcatgtgc ataataagat tagggtgggg tgaccagcct 15540tcccagtgcg
ctatgtgaac atcatacctg attgaaccaa tctgtgagcc ctatgtaaat 15600cagacaccac
ctcctcaagc ctgactataa aatctggtgc attcgccacc cgccggtgtt 15660tcctctcaga
agtcccctct ctctcattag agagagggct gttttccttt ctccttcttc 15720tgcctattaa
cctgtgctcc taaactccct gtgtgtgtct gttctgaatt ttcccggcat 15780gagaggatga
acctggggta tataccccag aaaacatagc cacttaagtg agaactcact 15840cactattcac
ccccaagatc caatcacctt cgaccaggtt cctcccctgg cgtgagggga 15900ttaaaattcc
acatgaggtt tgagtaggga cacagagcca aaccaaacca tatcagaggg 15960tgaagagcag
gtaaagttgc agctctcctg caacttgcag ggaaaggcca tataacacat 16020ggttatgagc
acaaactggg actggactgc aggtgtgtga gccccagctt tgctattgag 16080tgaccaccag
caagttatta aactgtgcct cagttttttt gtttatgaaa tggtggtatt 16140agtacaaccc
acctctcatg gatgatgtga ggattaaata aaataacatg ttgccaggca 16200cagtggtgca
cacctgtaat ctcggcacat tgggaggctg aggcccgagg gttacttgag 16260gttagaagcc
tgagacctgc ctggccaaca tagcgaaacc tcatctctgc ttaaaataca 16320aaaaaaaaaa
aaaaaaaaaa aaaaaaaaaa ggccaggcgt ggtggctcat gcttgtaatc 16380ccagcacttt
gggaggccga ggcgggtgga tcacaaggtc aggagtttga gaccagcctg 16440gccaatatgg
tgaatccccg tctctactaa aaatacaaaa attagccaag tgtggtggtg 16500ggcacctgta
gtcccagcta ctcgggaggc tgaggcagga gaatcacttg aacctgggag 16560gcagaagttg
cagtgagccg aggttgcgcc actgcactcc agcctgggcg acggagcgag 16620actccatctc
aaaacaaaac aaaaaaacca aaaaaattaa ccaggcatgg tggcacacac 16680ctgtaatccc
agctactcag gaggctgagg caggagaatc acttgaaccc aggaggtgga 16740ggttgcagtg
agttaagatt gtgccactgc actccagcct gtgcgataga aggagacagt 16800ctgcaacaaa
gatccaaaaa caaatataaa gcacttataa cagggtctgg tctgaaataa 16860gtactatgta
agtactgtaa gtattaacta atattattac aatttatcct catatagtaa 16920catatcaaat
attttcagtc agtgatgcaa tatgaataaa atgaaatgat gcagtagtga 16980cagaactgag
agaaagctgg tacaaattta tactgactgg tcagggaaag cttcacagaa 17040aaggtgaact
ttcagctgac acctgagtac catggtctgg aggtaagagt gtcccatgca 17100tatggaacag
caaatgaaac ttcccagagc ataatctgag aggggagatt tcaggagtgg 17160agccacatca
ttgaagttcc ttagtcctgg taagtgtgga ttttattcta agtgtggtga 17220aatgcccctg
agaggttttg agtagtagat ggaattccat ttttaaaagt cactggtgag 17280tcaagtagtg
tactatggtt acattttttt ccccttatac ctcattttgt ttttcctgca 17340gttaattctt
gcattatttc cttttattta cttaccttac tatatattta ttatgaattc 17400tttccaattc
ccaacttcct gacagcctct caatgtaatt ttacttaggt taaatgtatc 17460tgacagttca
ttttcttttt tgtctctgta ctctttctgc taccattctc attcttgcac 17520taatttgtgc
tggtttctct ctgagccagc tgcacagctg cctgcctaag acttcctctt 17580ggcatctttt
accctctctc tgtgttacat ccccggtttt ctgaatcgtg tggcgttctc 17640ctttttactt
tacttcctca tttgtgttgc acgtatgctc tagttgtttt tagataaaga 17700gtgcatcaga
ggtagatgtt ttgattcctt acatgcctga ctttttgttc tacttttgct 17760ctaggttaat
acttgatttt gaataatatc ctaggttaga aatgattttt cgtcagaatt 17820ttaagggaat
tgcttttctg ttgtctagtt tcctgtgtta ctgataggaa gtccaaaggg 17880gctcgtattt
caggtccttt ttatgtgtaa cctgtttttt gttccttgag gtattcaggg 17940tctcttttta
ttgctaattt ggggagcttt atcataacat gggtccttag tcattcatcc 18000tagaaaattt
tcctttccta tatctttgat gatttcgtct cctctgcttt ccctcttttc 18060tcattcttaa
acttctattt gtttgacatt agacctcctt gtttgatctt ctaatttaat 18120ttttctctcc
tagtgtccaa tttttgaggt gggagaaaga tctcatcaat gttatctttc 18180agcctttccc
ctgaatttta aaattttact cttcatattt cttctgatta atcctttaaa 18240aaaatagcat
cctgggccag gtgcagtggc tcacacctgt aatcccagca ctttggaagg 18300ctgagcgggg
agtggatcac ctgaggtcag gagctcaaga ccagtctggc caacatgatg 18360aaaccctgtc
tctactaaaa atacaaaaac ttagccaggc gtggtggtgg gctcctgtag 18420tcccagctac
ttgggaggct gagacaggag aatcaccaga acctgggagg tggaggttgt 18480agtgagctga
gattgtgtgc cattgtactc caacctgggt gacagagcaa gactctatct 18540caaaaaaaaa
aaaaaaaaaa aaagggccct gttccactga ggcttcagtg cggagcatgg 18600agggatacta
cctccaaatt ccaaacacgt ttgacacatc taaagaacct tctaaaggat 18660gactaaacta
attctgcaag ctttagcctc taacttatct ccaatttata tttaatagaa 18720ggctggaaat
tgaacagaaa ggaaataaga ttatttggaa ataaaaaatt gtcagccaag 18780caaggagagc
ttggcatttc tggaaacttc tttaccctgg aagaggtaaa aaagtgattc 18840tcccattccc
ccaacagggc attcactaaa aattaagtga gaaatgcttt gcctagagga 18900tctgtagctt
gcgaacactt gacttgtgcc actggtgtac ggaacatagc agtgtcagct 18960ctgccctggg
acagtcaagg ctggctggtg ctgcctgtgg ttagagtcaa gagaggggtc 19020ttcagtgggt
gcagtttgca gttccagagt ttagtagagc aaagacgtca tgaactatgt 19080gaactctgag
gaaaggtgtc atagaaacac ctcaaaagga cactgtctaa gaaggctact 19140tgctggggca
aggagacccc aggggtcaga ggctgtgtag ggaataatgc cagagctggg 19200gttgaaggag
aatccttaga ggtgagacag aatgtgcatc attgcagtgg ggctgtgcaa 19260ggcagtggtc
tccacaggag gtgaggacaa gggggagggg aggttgtgaa gaatccgtaa 19320gtgaccatga
tgcaatagaa agccagaatt tgggcatttg ccataggaga gggcccccag 19380tgccagatta
taatggtcac agacaaatga gatttttaac catttcctct aattcatggt 19440ccacacttaa
ccccgtgggt cctggaaaca gcagctggag aatggagagg aaagtgatgt 19500gggagagaga
aaactttctt tacccttttc ataactgagt ttatgaagta aactgacagt 19560agaaagataa
ataggagaaa agacataaat ttattttgtg cgtacacatg ggagtcccat 19620aaaatatgag
actcaaagaa aggccagatg attgaagttt atatagtatt cctgagctac 19680agaaaaggaa
tcagggcttg gggcttattg aggggaggtg gtgacaggtt ataagagggt 19740gaggagagga
agtgtatagc aagcataggt tgtcttgtta tgcagataaa aagtctctca 19800ggtgataaaa
gttgtctcag agtcccccat cagaagaata ggtaatagcc tgtgacaagg 19860tctacctgtc
caatcttctc cctggtgata aaatcttccc tggttgatga gattcttatc 19920aaagtttttt
tctttataga tataaatttt gtttacaaaa agacagtttt tcagagctac 19980tcctgtgtct
acagtgtctc agaataacta actggaaata catcaaataa gcatatcctg 20040atgtggcata
ttctggtcat attttgggat ggtgcgtcct gagctccaat gctgaaaaaa 20100caggaacccc
atttctgttg gatgtgccaa cctaaaataa tcaaaagggt cagaatctag 20160tttaaagata
ctttattcaa gtgcaaagtt taaggacagt gctagggaaa cacggatccc 20220aaagaatgga
agtcagcgtt ctgaacttta gaagtttggg attgtttata gagagagagt 20280ttagggaagc
ttaacagaat ttcaacatct ttctgtgtaa ggcttaatgc ctagttacaa 20340tgatctgatt
agtcaaggtg gtcactttca tttgagaaag gcatatttaa catttcacgg 20400gctgggagcg
gtggttcatg cctgtaatct cagcactttg ggaggccgag gcgggcagat 20460catctgaggt
caggagttcg aggccagcct ggccaatatg gggaaacccc ttctctacta 20520aaaatacaat
acaataaaat aaaataaaat aaaaaaaatt agccgggcat ggtgcacgtg 20580cctgtaatcc
cagctacttg ggaagctgag gcaggagaat tgcttgaacc tgggaggcag 20640aggttgtggt
gagctgagat tgcaccattg cactccagcc tgggcaacaa gaatgaaact 20700ccatctcaaa
caacaacaac aacaacaaca acaacaacaa caacaacaac aacaaacatt 20760tcacactgaa
ggtgtaacag tcatgggttt gtattttcgt ttttcttggt tttttttttt 20820tttttttgag
actgtctcgc tctgtattgc aggctggcat ggcacaatca cagctcgctg 20880cagcttcgat
tttgtgggct caagtgatcc taccacctca gtctcccgac tagctgggac 20940cacagtcatg
tgccaccaca cccggctaat ttatttttta tttcttatag agaccagatc 21000ccccttttgc
ccaggctggt ctcaaactcc tggactcaaa caattctcct gcctcagcct 21060cccaaagtgc
ctggattaca ggcatgggct actgtgctca tcccatgggg tcttttgtgc 21120caactggtgt
gagttaggta caggacaata aaggaggcag ttaatccatt aatccataac 21180aaagatcagt
gaagggggaa ggtctggtct ctggtctctc ctagtcattt acagaactag 21240aacgatgaga
agagagtgaa tctataacct aagaagcaga attgcaaaca tgctatgtga 21300ctcagtttcc
agtacttaac ttctcccttg gcataataaa taattttaga gagttttaag 21360aattttgttt
tcttttacag atgttaacaa cctcagcttg ctgggggctg gtggtggtgg 21420ctgctcagac
agtaaagcat tgaatgcaat gtgaggtcaa agttttatta cagatcatac 21480cggtctttta
agtacttgca gcaagatttt cctaatactt aaaagtgact ggaaactcaa 21540taggatcagt
gtgatcttct ccagataggg atggtagatt tttgaaagtg ggtgtgaagg 21600gcagtaatga
gagaaaaata aaactatttc tggttgtact ctcccaagtc aaggtcattc 21660aatgaatggt
tatatagatt tgcatcaaaa gtccctgttt tcagcctcac ctttggaaac 21720acctggattc
tctattctga gactttctga gatgagggaa aggtggcttc tcatcagtat 21780ctccttcttt
gtgcaataca gtttcagttc tttctaatct acagagttag ttccttctct 21840actgtcagct
ttctaccttc caaaatgtgt taatgtcact cattatcatg tttcccattc 21900tctttccctt
atggtttaaa ctttaaaaga caatggtatt tgtttaagtg aatatctaaa 21960aagatgtgga
gaaagattca tgtgttcagt ctaccatgtt taattggagt cactggtaga 22020tttttaagga
aaaataacat tctaggtttt tccagtattg ctatgtagct tgtctatgta 22080gatcaccttg
cattcttctg tttctctctt ataacttgat ttttttcttt tcttttcttt 22140tctttttttt
tcgagacaga gtctcacttt gtcacccagg ctggagtaca gtggcacaat 22200ctcgtctcat
tgctgcctcc atctcctggg ttcaagtgat tctcccacct caccttccca 22260aatagccggg
attacagaca tcttataact tgatttttac tcatttcatt atcatccaag 22320agatgaaatt
taactcaaag caaatgacta ttgtttcaaa tacaaatctt aatcagggag 22380aaaagattat
aacttatagt tgaactgggg tttggagatt atatgtgttt tttaaaatta 22440ttctgtccca
catgtaacat acaagtgagg attttaaaaa tttgtctgca gttttttttt 22500ttttaattga
tcattcttgg gtgtttctcg cagaggggga tttggcaggg tcataggaca 22560atagtggagg
gaaggtcagc agataaacga gtgaacaaag gtctctggtt ttcctaggca 22620gaggaccctg
cggccttccg cagtgtttgt gtccctgggt acttgagatt agggagtggt 22680gatgactctt
aaagagcatg ctgccttcaa gcatctgttt aacaaagcac atcttgcacc 22740gcccttaatc
catttaaccc tgagtggaca cagcacatgt ttcagagagc accgggttgg 22800gggtaaggtc
atagatcaac agcatcccaa ggcagaagaa tttttcttag tacagaacaa 22860aatggagtct
cctatgtcta cttctttcta cacagacaca gcaacaatct gatttctcta 22920tcttttcccc
acatttcccc cttttctatt ccacaaaacc gccattgtca tcatggcccg 22980ttctcaatga
gctgttgggt acacctccca gacggggtgg cggccgggca gaggggctcc 23040tcacttccca
gaaggggtgg cctggcagag gcacccccaa cctccctccc ggacggggcg 23100gctggccagg
cgggggctgc ccccaacttc ccagacgggg tggctgctgg gcggaggggc 23160tctttacttc
tcagatgggg cggctgccgg gtggaggggc tcctcacttc tcagacgggg 23220cggccgggca
gaggcgctcc tcacctccca gacggggcag cagggcagag gcgctcccca 23280catctcagac
gatgggcggc cgggcagaga cgctcctcac ttcctagacg ggatggcagc 23340cgggaagagg
cgctcctcac ttcccagact gggcagccag gcagaggggc tcctcacatc 23400ccagacgatg
ggcagccagg cagagaagct cctcacttcc cagatggggt ggcggccggg 23460cagaggctgc
aatctcggca ctttgggagg ccaaggcagg cggctgggag gtggaggttg 23520tagcgagccg
agatcacgcc actacactcc agcttgggca acattgagca ctgagtgaac 23580gagactccgt
ctgcaatccc ggcacctcgg gaggccgagg ctggcagatc actcccggtt 23640aggagctgga
gaccagcccg gccaacacag cgaaaccccg tctccaccaa aaaaatacga 23700aaaccagtca
ggcatggtgg cgcgcgcctg caatcacagg cactcggcag gctgaggcag 23760gacaatcagg
cagggaggtt gcagtgagca gagatggcag cagtacagtc cagcttcggc 23820ttggcatcag
agggagaccg tggaaagaga gggagaggga gaccgtgggg agagggagag 23880ggggaggggg
agctgcaatt ttttatttag caatttccaa acctattgtg ttaggcaggg 23940ttctccaggg
aaacagaacc aatagggcat atctatatct atatttatat ctttatctat 24000atctatatct
ataatctttc tatctatcta tcaagagatc gagagagaga gatttatttt 24060aaggaattgg
ttcatgtgat tgtgggagct ggcaagtctg aaatccatag ggcaagttgg 24120tcagctggaa
attctggtaa gagttgatgt tgcagtcgtg agtctgaaat ttgcagggca 24180ggtcaggtac
agtatctatt gcaattgcag tcctgaggcc aaattccttc ttcaggaaac 24240ctccgtcttt
tttgctgtta aggccttcaa ctaattggat gaagccctcc cacattgagg 24300gcaatctgct
ttactcaaag tctgctgatt taaatggtaa tcacatctaa aaaatacttt 24360cacagcaaca
tttgaacttg tgttgtctaa gcaattgggc actatagctt agccaagcag 24420acacatgaaa
ttaaccatca ctctgtagag atgaaagaac tactgtttca aaaaacaact 24480gtttttgaat
ccgtcattta tcaacggatt cacccaatgg ttaacctttc tatatgcttt 24540ctctttctcc
caagtactga atcatatgaa aataaattat ggttgtgata tttcctatct 24600aaatacttca
tatgggacat tctcctacat agcacaccta agaagattag tattaattca 24660gagagatcat
gtcatatctg gttcatatat aattttccct agctgacctc aaaatgtgtt 24720tgttttgttt
acatattact ctttatagtt atgtttcttt taatacggat caatatttgt 24780gtgtttttgc
tgctattttt tttaatgaca ttgttttgaa taattcaggc tcattggcta 24840tttcacatcc
tgaatttctc taattttatc tttatgatta gagccaggct ctaattcttg 24900gcaagaataa
cactgaagtg aggttgtgta ctcctaattg ccctgcatca aagacacatg 24960atatgcattg
gttcctgcat tagtcatgtt aagtttgatt agctggtgaa ggtggtcgcc 25020accatttctc
actcttgtaa agggacattt tctcctttta aattaatatg taatttgtgg 25080cacaagactt
tgagactgtg taaatatccc attctctgac aacctttctt ctgatgactt 25140tagcattaac
tgatctaatt atatcattct tggcattgag tagcattctt gtgtaaagaa 25200ggggttctct
ttctctccct cctctcatta taatttgtta ctgttatttt cttacaagtt 25260actaagaatt
actcaaaggc agtatttttc aataaatcat tggtaattta tggtcttctc 25320actctagaaa
agggaggatg ggtcagaaag ctgaggggaa aaaaagggag gaaacgagaa 25380tgtatattat
cgacataatc ggttgaaaat gtctagtgct gtaattatgc catcatgcag 25440attaaaaagc
cacctgtgaa aaatcaactt gtattgtttt gttttgtttg atttttaata 25500aatccttata
gtgtatgaat aaaaattaaa ttaattgatc agtatcttca ctaatggcag 25560agaaggggat
ggactgagca gattctgctt ttcactctga tatttgttaa ttgccctgtg 25620tggtctgaag
acctgggttc tagtaccagc tctccctctg cagacaggtg tgttactttg 25680gtcaaggcaa
tcaatcttct tgatactcag tttggttctc tctgatttga gcataagaaa 25740tatacttgaa
ggccgggcat ggtggcttat gcctgtaatt ccagcactat gggaagccga 25800ggtgggagga
tcgcttgggc tcaggagttt gagaccaggc tgggcaacat ggcaaaacct 25860caactctaca
aaaaacaaac aaaaaattag ccaggcatgg tggtgcacgc ctgtagtccc 25920agctactcag
gaggttgagg caggagaatc ctgggaggca gaggttgcag tgatctgaga 25980ttgtgccact
gcactccagc ctgggagcct gggtgacaga gagagaccct gtctaaaata 26040tatatataca
cacacttgaa tgcttcatgt cccttgctca gtgacagccc cgtcctctgc 26100ttctgcacag
ttgaccaagg cttctcagtc tactcctgtg tagaaaagaa ttaaagcagg 26160cctgaggctg
ctagtcttag aaaggcttgc aaagttggcc cttgtctggt gtctgggaac 26220ttgaatttct
ggagggttct caccattccc tgaaaagaat ggctcacgat gcctaaaata 26280tttgtacaaa
caatgaagtt tctgctgaac atctgcttcc ttctgggagt ctggaatttt 26340aggatgtgct
aggtaggggt gtttacatga cagccccaca taaaaacctt gggcactgag 26400tgtctaatga
gattccctag taagtaatat tttacacata ttatcacaac tcattgctgg 26460aggagttaag
tgcatcctgt gtgactccac tgggagagga ctctgggaag cacatgtctg 26520atttcctttg
tcccatgtgc cttttccttt tgctgatttt tgccttgtaa attttttttt 26580ttttttttga
gagacagagt cttactctgt tgcccagact ggagttcagt ggccccatgt 26640cggctcactg
cagcctctgc ctcctggatt caagcaattc tcctgcctca gcctcccgag 26700tagctgggac
tacaggcgcg cgctgccaca ccggctaatt tttgtatttt tagtagagac 26760ggggtttcac
catgttggcc aggatggtct tgatctcctg acctcgtgat ccgcctgcct 26820cggcctccca
aagtgctgga attataggcc tgggccactg tgcctggcca taatttttat 26880cctgtaataa
attatagtcg aaagtattga gtcctgtgaa tcaacttaga gaatcaccaa 26940actgcttcca
attttctcat atgtaaaatg ggttgctata ataatgatga tatctacctt 27000atagggttgt
tttaagtatg aaaaatatgg tgaaatatgt gtgaaactag gggccggatg 27060taggatgagt
catacagtgg gtggttatta ttacggatca tattaactct tcaggtaaaa 27120accatcttgt
agctgggcaa ggtggcacat gcctgtagtc ccagctactt gggggactga 27180ggcaggtgga
tcgcttgagc ctaggagttc aaggctgtag tacgctatga tcacgtctat 27240caatagccac
tggactccag cctggacaat gtaatgagag tctgtctcaa aaaaaaggaa 27300caatcttgtg
tttgcgtgtg tgctcatgtc tttgttggaa taatactgac acagtcactc 27360aaattaactc
tcaaatcttt gattattcat ttgatgggaa caacaggttt atgtgccagc 27420ttatcaggac
ccctagttct ttcattaaag tgtgtatgtg tgtgtgtatg tgtgtatgtg 27480tgcacatgtg
tgctagtttt cttatctaac gacgaagtcc tttgggaggt ttactttttc 27540attactattt
ttttcatgct ttcctttgat gtgcacctgg caatttatag agccaatgtg 27600tactacatat
tctgctgcag aaaatgacag aggtgaggaa ggagcaggaa gcagatttag 27660aaaggaatgt
tacagtttat caagttgtga ctaatggaag ctattaaaac aaaaggtacc 27720aacccatctt
aaatattcac tgcctctaca actatttttc tataactgtt gttccttgtc 27780agctctgggg
tggagggaat attcctgaat gttttattaa gtaattcaaa gatcttccta 27840ggtatgtgta
tcaaagatcc tatgatgtat ctgtcttgta aattgagact ggcatatatt 27900gggcttacat
tactgggaaa aatgtatgtc atcatcattg gtgaaaaaga gtttccatag 27960cagttttttc
taagtagaga gataaatgaa tcagactttt ggaggaggta tgttttaact 28020cactggagga
tcacaccaag tctgaacatc taaggaaccc tagtggaaaa ctggttttcc 28080tgtatgctgc
tctagcgatc tgaggaaagg cctaaaaaaa gccagtgtcc ctgtgatatt 28140gtgaaataca
tatatgtggt ctttgttcct gtttcctggc atacaagtac taaaaatcct 28200tggaatctcc
aaagtgctgt ctttttgtat attagtgttg actgatagct tcagagtggg 28260gctggtcaag
ttgatcacca atggccagtg gtttaatcag tcatgcctat gtaatgaagc 28320ctccatgaaa
atccaaaggg aatggactgg ggagcttcta agaagtgttt tttaccttcc 28380cgtgagcctc
ctgtgctgaa cacgtggagg gtcacgggaa ggtaagcaaa aattcattca 28440catgctggga
gggtggcaca tcccaactcc acgaggacaa aagctcctgt gctcagaacc 28500cttccagact
tggaccttgt atctcttcat tggcttttat ttgtatttta aaaaatatcc 28560tgagtgataa
actggtagat gtaagtgtct tcctcagttc tgtgaaccac gctagcaaat 28620taatcaaacc
ggaagagggg gtcatggcaa ccccaacttg aaacctgttg gtcagcagtt 28680ccagagacct
gaacttatga ctggttggaa ggacggggtg ctcttgtggg actgagccct 28740caacttgtgg
atctgatgct atctctgggt agacagtgtt ggagctgaat tggaggacac 28800ctagcttgtg
tccactgcag aactgattgc ttgcttcctg ctggggagaa atccctatat 28860attttggggt
ccagaagtct tccgtgttga ttgtttttgt gtgagagcag aggaaaaatg 28920gtttgagagt
ttttcgggaa acagcccctc ttagtatagt ggtagaaaca ctccaaaaat 28980aaaatatgct
accccaaaaa taaaaaatga aaataaaaat aaaaatctgg agtggtcagt 29040ttgccaagag
gatttatgga gcatctaagg tcaagcatta cttctcagcc ctgcagcagg 29100cctctaatta
agccatgcca cagagtgcgg tttgcagaga ggtggagttc ctgtggattc 29160attcttctct
ctaaaattat aaataacgca gcttccaaac atgccatatt acctcacaag 29220gtctaaagac
tcaatatgaa tcttcaactt aacaattata actgacacag attgagatct 29280tcctggatgc
tgaaataggc tttacatgat ttatctcatt tagttctcat aaaactctat 29340tattaatatt
attttacaga tagagaaatg gaagcacaga gagggtaagt gtattagtcc 29400atttttatgc
tgctaataaa gacataccca agacagggta atttatacag aaaaagaggt 29460ttaatggact
cacatttcca catggctggg aggcctcaca atcatggcag aaggcaaaag 29520gcacttctta
cctggtggtg gcaagacaga aaatgagaac caagcgaaag gggtttcccc 29580ttataaaacc
atcaggtaac atgagacaat tattcactac cacagaaact atatggggga 29640aaccgccccc
atgattcagt tatcttccat tgggtccctc ccacaacacg tggagctaca 29700attcaagatg
agatttgtgt ggagacatag ctaacccata tcagtaagta attagacaaa 29760ccttgcaaag
ctagtaagtg gtattgctgg aattaaatct gccaatgtca ctccagagtc 29820tatgtgattt
actggtatat tatagggtct acctataagc ttgataacct tatgttagaa 29880caaataacca
tgacatattc tgttcagtag tttgcatttc cttttgactc ctacagggga 29940ggaggccgag
gttcagggac attaaagtgg ggtttagaga cattaggtgg tttacccaag 30000ctttatctac
tagatactag ataattgtct atctgacaat aaagctagaa cttacaccca 30060gctggacaat
ggagctacag cttaaaacaa aatcttctaa tgagctcaga actcatggct 30120taataagatt
tgggaaaagt cctgcggaca tttcactgtc tatccagaaa tgcgaggaag 30180ttaggagaaa
aggcaaagta tctcatagac agataaaggc agttcagtaa gtagcctgaa 30240taaatagcca
tatttaaaat ctaatttggt tcttttgtgc ctaacacaat tgactttatg 30300ctggtatcta
ttttctgctc tgtctctctt tctgtctcta cttatgtgtg tatgcatgtg 30360ttataaaata
tatcagccca ttgatcaatt tttaatttaa gcaaaaacat ggtagattaa 30420tatattcaat
caatttattg agtagatatt tatcgaggct cacacattta tctgactgtg 30480tactaagcac
tggaaaccca aagagaatga agtcactgcc tagacagttg gaggctgaca 30540cataaacaag
cagggtaata atcaagtgtc ataactagtc tattacatgc aatgttaaac 30600tagcatctct
accatgcaaa acttgtgctc ttggggatac aggaagactt tccagagaag 30660tacacaggac
aggaatgtgt taggaaacca gtcagttccc aggtcctcga tcaggtcaca 30720gtgacttgcg
attctatttt gaacataggt cttaaatctt tattttgata gcaagggttt 30780taaacttttg
atatatgata tacttctgaa aatcaaattt catattctaa aattaagtat 30840ttttgccctt
aactaacttg aacataatac tataatacat taacatatat tattaataat 30900aaataggacc
cctggaagtc caagagagac atgaggctta tttggtatgt taaaatcata 30960caggaagtgt
tgttaaataa gaaatggtgt tacactttct ttgagttata tttatatgga 31020tatgttgtta
atatgtgttc caacattgta tgagattcct aaaaatctga tatggacatc 31080cagtgtggtt
gttgggtcct ctatgagcct agggagcact ggccggttac cttgcatcca 31140ttcatgtcag
cgttggtagt gtcaggcacc cgatggttct tagaagagta cttagctcta 31200ctctgcagtg
tctgaagttg ctggatatat acctgctgta taaactgctg actagggcgc 31260tgcagtttac
ttactgtctt ctcatgggga ccttcccctt caactctttc ctcttgggtt 31320tcacatcttg
ggtggggagt ttcatcctag tagtttgcct gagaatacag gtgaacccac 31380agaacaaagt
ggacttcgaa agcatctcct tggagtgaga ctttgcttct ttctctttgc 31440tagcaccatc
ttgtacctta tcgtcatgaa ctttgttggc tgaatcattc ccatttactt 31500aattgaagag
taagagactg gaacaatgct cactttgatt ttcctggata agagttaaga 31560gttcttgaga
tggcagcttg tttgacacat gaattttctt caaatttgtg cttactacca 31620actgatttgg
tgtggaggag agcccagaga agttccctct ctctgtcaga acaactttgt 31680aacatttatt
aacctgactt ctgccttcaa ttaactgtaa ccttttgcct tccaaattaa 31740aaagttccac
attactccaa aaataaaaag tgaaaataaa aataaaaggc tgatatgtca 31800tggtatatgc
agtaaattgc tttattctga tttttttttc taaaagcctt ttgcaaatcc 31860tgaagtgctg
tgtattcaag gaaattcatg aaagggacct tgacaagtag tcttaaatac 31920aggtttctga
taactttgga gatcacacct ttggactagg taaaaacatc caaaactcgt 31980ctgggcgcag
tggctcacgc ctgtaatccc agcactttgg gaggccaagg caggcggatc 32040acgaggtcag
gagatcgaga ccatcctggc taacacggtg aaaccccatc tctactaaaa 32100acacaaaaac
aaaattagcc gggcgtggtg gcgggcgcct gtagttccag ctacccggca 32160ggctgaggcg
gaagaatggc gcgaagcggc aagacggagc ttgcagtgag ccgagatcgc 32220gccactgcac
tccagcctca aaaaaaaaaa aaaaaaaaaa aaaagtccaa agctctaatg 32280aaaaactgat
gcattcatgc agattgctaa cccaacatca aggagaacga gaattacatg 32340ggactgagtg
aatgaaggat tgaaattact attttaaagg gtttttgttt gaaacattac 32400tgattttttt
tatgttttgt tttccagact caagaaaata ttttttttct tttgagctat 32460ttatagctta
cagcattggg gtaaagtata cttctgtgag caaaatggaa acatttacct 32520ttctttctac
ctgaattctt cagaatttgg aaactattca ttagtgttct tattttctgg 32580caatatagtt
atttgcataa gttcaataag aacctatttt cggctgtgca tggtggctca 32640tgcctgtaat
cccagcacct tgggagggcg aggccggtgg atcacaaggt caggagtttg 32700agaacagcct
ggccaagatg gtgaaacccc gtctctacta aaactacaaa gattaaccag 32760gcgcggtggc
aggcgcctgt aatcccagct actcgggagg ctgaggcagg agaatagctt 32820gaaccttggg
tggcagaggt tgcagtgagc cgagatcgca ccactgcgct ccagcctagg 32880ggacaagagc
gagactctat ctcaaaacaa acaaacaaaa aaacaaaaag caaacaaaca 32940aaaaaagagc
ttattttctt ttgtaactgg acacatggaa acagtggtta ttttaccaag 33000gctttgactg
gaatgtcttt tttttgagtg caaccggact gcttcgaggg attgaggttg 33060actttataca
gccagtagac ttggaaaaag acacacctgg taccttgccc acacaattcc 33120tttatagcgt
ttctaacttt gcaataagta aagaatgtca ctttctgaca ggcccaggga 33180cctcaagata
ttttggagac gttgaaaaga gagcaattca cccaattcat acaggtttta 33240caggcacagt
ctgatggcga atctttggct tggcttcatt gcttcaagag tttgtttttt 33300tgacacggaa
tctcactctg tcacccattc tggagtgcag tggtgagatc ttggctcact 33360gaaacctctg
cttcctggat tcaagtgatt ctcctgcttc agcctcccga gtagctggga 33420ttacaggcat
gtgttgctac tcccagctaa ttttttgtat ttttggtaga gatgaggttt 33480caccatgttg
cccagggtgg tcttgaactc ctgacctcag gtgatccacc cacctcagcc 33540tcccaaagtg
ctgggattac aggcgtgagc cactgtgccc agcccttgag aggtttcaaa 33600agtcttaatc
tgagattcct tatgaaaaaa ttccaacaaa gccaacttaa gagccatccc 33660tgtagaaaat
atatctattt aaatatcgtc tgttttatgc cacaatgttt gttttgcgtt 33720gcaagccgtt
atctcctagg catgggtaat ccactttgag aggaaaatcc agacatcatt 33780gtgcctaatt
tgctgccacc tgtgtctgtg ctggatctta ccagggttag ctttattttc 33840tttcaactgg
caaaattctg ataaagcatg tagcttcacg gtagagcaaa aagtgtaact 33900taattgaaag
tcatgacttt caggagtcta atgatgctaa tatattttct tctagagagg 33960tgtctttatt
gtatgtaatt ccctgaagaa atgtaaagat ttatctaatt cctattgctc 34020tgacaggcgt
gctcaataga agcattgaag taaaataaaa ataacctttt taatctgtgt 34080atttctcttg
cccaccaaga tatttaattt ttttcttgat ctttgctttt gtttatgtga 34140agatatttat
gtctatatca tttctgtata tatcacagaa aagttttcac ttgcttgaca 34200ttttattcta
caatgatttt tagtttaagt ttaaagaatg gctacattca gatttatttt 34260cacaactata
gtcctgctaa actgcctttg ttgaaaactc agtttttata ataaataaaa 34320aatatcaaag
caaaaaaaaa agagccttca tgataaatca ccattcttac tgcactttaa 34380gcagataatc
atgccagaga ctaaactgac tttgcaaata aattagtttt attattatta 34440tctttgtggg
taaaagttgg gatgactgta gaagagaaaa ttatatttca gaagaaaatt 34500ataccatact
tgttattaga ttctagtctt gataattgtt tttttgagtt tttgttattt 34560gcctacaatt
tgggctgaat cctgaattcc ttcctgggta caagtctcca aactaatgtt 34620tcctaatttt
tctaccattt ttctgtcttg gaatcaccaa gccctgcagg ctttagctag 34680acaacttgat
ataaactttg gaagaaataa tgacagcaac ttaatatatg agcagtgttc 34740atgtcagctg
atgtatggat tactcagaag gtttacttga acacctgatt caaactataa 34800tccagaaata
tctgtaagat tgccactgca atctgaagct acttcagaga ctctaggaaa 34860attagtttat
agacaactcc agatgttaat ctttgttttt cttttgtttt catggaaatg 34920ccttttatta
aacatctgat tgcttgattc atagaggcct gactttggtg gaagcaacac 34980cactgcctga
aatgagatat aactgttaac cgtttaattg gagcggcctg ttctcacgac 35040tgcaagacta
gttcaatggc ttataaaata atccacccgc tgggcacagt agttcacacc 35100tgtaatctca
gcactttggg aggctgaggt gggcaaattg cttgagctca ggagttcgag 35160accagccaga
gcaacatggt gaaaccctgt ctctaccaaa aatataaaaa attagccggg 35220catagtagca
tgtgcctgtg gtcccagctc ctcgggaggt ggatgtggga ggattgcctg 35280agcctgggag
gcagagcttg cagtgagctg agattatgac actgcactct agcctgggca 35340atacagtgag
accccatctc aaaaaaaaaa aaaaaagata atctaccaac ccaatttctc 35400aactggggaa
tgttgggctc ctgctctcct gtctctgacc tttcattctc ccttgaggct 35460agccatcaag
actacaaccc ctcttcccca aagtgggcca tagaaacaaa accccttttc 35520cccaaagcca
accataaaac ctaaaaatag tactctaact tccaccaccc ccagcctgtc 35580tgtgtaaggc
cataaagaaa ttatctgact cactttgttt gactgaaggt tataagaccc 35640ccattccaga
gagggtccag caccacaccc agaaggaaga aatgcatgct cagagaggca 35700agaagggtcc
agacagacag gctgtgctgg atttccctgc tcagtctatt agcattagac 35760catacctttt
ttgtccaatc atatttctac gtggctctcc atactttgtt taacctaacc 35820taagggggct
cagggttttg gcctgggcat tgtctgttgg ggaatagagt gagtcatccc 35880cagctcatgg
gtttgcatcc agttcttgtt gtaaaaggcc caaagcctgt tggatggcaa 35940ccctgagcca
tcgtggaagg ggggttccag tttcacaaat agatactcag acagccaaac 36000taccatctac
ttggtgccaa cgtttgcact gtggtcaaag acttacctag cacagactga 36060acaaatcttc
ccatctgtca cataaatgtc cccaagcaat gttgaagcac atgccaggat 36120cggccttgct
aggtcctgct tggtagataa gcaaatggct tccttgtggt gtttttattc 36180tattttgtct
cattaacact acaactttgt gttatctact tgataatctg taattgtaaa 36240tacatacagg
attatgtaat ttgtgtaaat acataatgac agacttctga aaactggtat 36300tttttacttg
gtgtccattt gaagctgttt taggttctgt ggcacatgaa ccaatggcat 36360ttaaaaagca
tactctcctt gctcttaaaa aaacaaacaa aacaaaacaa aaactgtcca 36420ttaaaatttt
tgtatttttg taaagacagg gtttcaccat aaaaatggac agtttccctt 36480atatctttgg
gtcttcgttc tgtaggctct cgtgtcacat aaaattatga tcaaataaat 36540ttgtatgact
tttctcctat taatctgccc cttgtcaatg attttgagca accttctgaa 36600gaaagtgatg
gggaagtatt ccctttgctg ccacaaggta tatatcagat aagtcagtct 36660attttcttga
acatatatca cattcatagg aaaaacactt tttccaaaag attactgtct 36720tcccaaatac
ccacgttctc catttttttt tttttttttt agagatgggg tctcactgtg 36780ttgtccaggc
tagtctcaag cttctggact caagcaatcc tctcacctca gcttcccaaa 36840gtgctgtgat
tacagacata agccatcacg cccggcccca ttttctcctt tgggtgtatg 36900tatattgctc
attgtcaggc atcaaccatt tctcttctct gagatggagt ctcactctgt 36960cacccaggct
ggagtgcagt ggcgcaatct tggctcactg caagctctgc ctccctggtt 37020cacgccattc
tcctgcctca gcctcccgag tagctgggac tacaggtgcc caccactacg 37080cccggctaat
ttttttgtat ttcttttttg gtagagacgg ggtttcaccg tgttagacag 37140gatggtctca
atctcctgac ctcgtgatcc gcccgcctcg gcctcccaaa gtgctgggat 37200tacaggtgtg
agccactgcg cccagccctc ttctaatttt ttatatttat catgtattta 37260ctagaactgg
tttattttcg tgagcatatg ttgtggattc tactataaat aatgcactta 37320ataatcatta
ataaaactta aatcctttcc gtcttgattg tggccttttc tttttgctat 37380taatttcctc
agcataggtt aacctgaact cttaaaagct atttaggtac tggtataaaa 37440caaaattttc
tccaaagcaa tccagtatat aatatctgga ttttaaaaaa gcagcctcat 37500ttaattagga
ttaatttctc ctttcagaag ttaagtgatt ctgtttctgt aaaacgcaaa 37560attataagct
taattgtttt ccacacagga aatgaaattc ctaatctttt tatccagaat 37620cttcatgtgt
ttgtctctct gtccatctgt cactcctttt taaggtacct ggagatgacc 37680tagaggcttg
ccacgcttag ggtttcctcc ctgtgcagaa gaagatggga agtgcaaatg 37740aggacgaggg
gtggggaggg aagagggagt caggtgattc agcaagtgca ggagcccaca 37800gactaagctc
aggaatttgc actttgtctg ctcgcagagt gagtttcatc gtggtgtgta 37860tatattgaga
tatgcaacag actccactgg aatgtcagaa gaacttatgt ttatttttcc 37920tctaacatgt
gggaaagatt aaactgtatt tgtatttaac tcacatagat tggcacgtgc 37980tcattctgtg
tgtcaccctg ccacgctgtc acaaacttcg agcagggtcc tgaggggaga 38040ggagggcata
gctcctgctc ccagggggtt gcctgtgtag ccctgcgcat tcattctctt 38100ccagagggtt
gtgatttgtg gcggtctgtg tgagcctggt taaggagagt tacagattat 38160gtcatctggt
gttaactgat aatctttgca aaagggacat tggctttaag agatgtctgc 38220aaaaaaaact
ctaaacaaac ataaataaaa atttaaaagg ataaagccag aataataatg 38280aaaatattag
taatgtaaaa caaggaaatg tgtcatgttt ttcatgataa ctaatatttt 38340ttcaattttt
tttttttttt aagacagtct cactctgtca ccaggctgga gtcagtagtg 38400cgatcttggc
tcactgcaac ctccacctcc caggttcaca caattctcat gtctcagcct 38460cctgagtagc
tgggtttaca ggcactcgcc accatgccca gctaattttt gtatttttag 38520taaagacagg
gttttaccat gttggccagg ctggtctcaa actcctgacc tcaggtgatc 38580ggccgccttg
gcctcccaaa gtgctgggat tacaggcgtg tgccactgtg cctggcccca 38640gttcttatta
taagttctcc attaaccata tcatgagatt aaaaaaacaa caatgatttc 38700atcggaactg
acaaatagtg ggtgacacaa ttttgatcat caagaagact ttaaaagaag 38760gatttgtatc
actgtcatta ctgattactt ggcccttgtg tatactgggc ctttagctag 38820ggctggtaca
ataaaataac catagttaga aagatatttt aaaggattac ttatttcatg 38880tttatctcac
ccttttatcc ctatttttgg gcatgattta ttattattag gtttttaaat 38940aaataatgaa
ataagcatgt taggtttgca tgctgctttg gttaacattg ctatataacc 39000aaccacccca
aactttgtgg ccttaaaaca ataatttatt tatttattta tttatttatt 39060tatttattta
tttatttatt tttgagacag agtctcgcta tgtcacccag gctggagtgc 39120agcggcatga
tctcggctca ctgcaacctc cacctcctgg gttcaagtga tcctcctgcc 39180tcagcctccc
gtagagctgg gattacaggc acccgccatc aagcccagct aatttttcct 39240ttatttttag
tagagacggg gtttcaccat gttggccagg ttggtctcga actcctgatc 39300tcaggtgata
tgcctgcttt ggcctcccaa agtgctggga ttacaggtgt gagccactgt 39360gcatggccaa
caataattta tttttatctc tcatggtctc tagattgcct gggcccggct 39420gagcagtctg
agtcagcctt atggtctctc atgtgttttt aatcagtcat gaggggccgg 39480catcatctga
aggcttgact gggctggatg tttaagacag ccactcacag ggctgacagt 39540gatgctggat
gttgcactgt tgactaatga gcctgcacgt ggctcctcca tgtgatttgg 39600gctatttata
gctggggtga ctgggttcta ggtggggtag ttccaagatc cttccaagag 39660gaagaaagca
gaaactgcct ggccagttag tgtatatgct tagtcttaga acagtgtcac 39720ttccatattt
ctccatagtc cattaatcaa agcagttaca ggaagcagac agacaggaag 39780ggaaaacaca
atgcaacaga aggagagatt gaagtgttgg cagctgcaag ccaagaaaca 39840cctgggttac
cagaagctag aagaagaaag gtaggattct cccctacagg ttccaaagga 39900agctgggcct
gtccacacct cacctctgga actatgagac aatcactttc tgtgggttta 39960agctacccag
tttgtggcac tttgttacta ccgtcctagg caaatgatac agtaactaca 40020tacacagtac
atagaattgc tcattttact tcgttgaatg ggacttggca ttgaataagc 40080ccaaatgaga
attcttttgt caagattttt ttatggctca cttttccaga gacgtgacat 40140ggcaggagta
aggggagggt ttggcaggta ggaattatac tcatctgtca ttgtcttccc 40200aataccaacc
aggaagcatg taaataatag ctgtgcagtt tgttttctga accaaactgg 40260gccttatttt
ttttaaagaa actttattaa acaaacaaaa acctagaaac actagatgta 40320tatttttaag
gtttctctca cataatatcc taatcatcag tataccgtaa tccaagggct 40380acatataact
gaaaaataaa tgggtcttaa aaaaattaaa acatggtata taacactagc 40440taacatgtac
tgagcagtta ctaagtgcta agtactgcta agtcctttat agatatcttc 40500atgttgagtg
tcgtcactgc ccattactta ctctgagttt aaatatgaga ctcaaaagag 40560gttagtaatt
tgccaaaagt catagggctt ataagtgata gaaccaggat aacgaatctc 40620aaccaaggga
cttcaatgcc caaaccggtg ctcagactgt agccccatgt agttagctat 40680ttacatttga
aaaaattttt aatgtttatt atttttttta agacagggtc ttgctctgtc 40740acctaggctg
gagtggagtg gtgtgatctt ggctcactgc aacctccacc tcctgggctc 40800aagtgatcct
ctcatctcag cctcccaagt agctgggacc acaggtgtat ggcaccacgc 40860ccaactaatt
tgttgtgttc ttggtagagg tgagtttcac catgttgccc aggctggtct 40920tgaactcctg
agctcaagtg acctgcccac ttgcctcacc ctcctaaagt ggggggatta 40980caggtgtgag
ccaccatgcc cggcccagct atttacattt aaatataaat taaaatgaaa 41040caagattaaa
aattcggttt ctcaatcaca ctaaccacac ttgaagtgct cagtagctac 41100atgtggctta
gtggctacct ggcagatata gaacgtttcc atcagcacag aaagttctac 41160tggaaagcat
tgatccaatc tctttgaaca gtcacaatgc atataaagtc cttattatga 41220ctgtacaagg
gaagacaacg agtagaggaa ggcagaaaat aggaaaaaag gaagaagaaa 41280gatttagggt
gagggagagc agttctatga agaaaagaag ctcatatcta ggagtggagt 41340ggaccctgag
aacatgttag tctattatat tctaaacttt ggcagttaaa attccaaagt 41400atattaagta
catgctttct aaaatattag agagctgcag ttcaacagat ttttaactct 41460ccacagcatg
tccggcactg ggtgaggtgg gatggctagg tgaataatat aggcattgtc 41520atgtgtgttc
gtgtgaagag accaccaaac aggctttgtg tgagcaataa agctttttaa 41580tcacctgggt
acaggcgggc cgagtctgaa aagagagtca gcaaagggtg gtgggattat 41640aattagttct
tagaggtttg ggataggcgg tggagtagga acaatttttt gtgggcaggg 41700gatggatctt
acaaagtaca ttctcaaggg cgaggagaat attacaaagt accttaaggg 41760cagggaagga
tattacaaag taccttctca agggtgggga gggtgtatca tacaaagtgc 41820attcacaagg
gtggggaaat atcacaaagt acattatcgc aagggcaggg agggtgtatt 41880gtcacaaagt
caattgatcg gttagggtgg ggcaggaaca aatcacaaca gtggaatgtc 41940atcagttaag
gcaggaacct gctattttca cttttgttga tcttcagttg cttcaggcca 42000tctggatgta
tacgtgcagg tcacagggga tatgatggat tagcttgggc tcagaggcct 42060gacagacatg
aacttcccat cataaaatta gaagagcatt aatcaaatga ttagaataaa 42120atattaccat
tattttgaaa tggcaagcat tgtatgtaaa taaacagcag aggaacccac 42180tgtagcctag
acagggttca gagacgttcc tgccaaggac atggcacagg gactgaacaa 42240ggaaggatga
cagtgcctgg caaaggcagg gaatgttaca ggtatttggg cacctgtgag 42300aaggcctgat
gtccgaaagg actgaaataa attaaatgtg tggggggaga gagaaagaaa 42360gagcctagca
aaaggtgagc tggagagtca gaggcagaag gcagaatctg ggatgggctg 42420ggagcttgcc
aatcattttg tcaaatgggt gatgtgaagc cttgaaggtt ttttgaccaa 42480gaggagatgt
cttcagattt gcgtttgaga cattttcact ggttgtcatg ctaagaatgg 42540cttaaagaga
agcaaggctg gggtcagagg agctgcttgg aagctgtttg gtactaggat 42600gcggataaca
tggttggaga aatggcaact gtcagggtat ttggagcaag aatggataga 42660cattggtgat
catcacttgg atgcatttga gggacaactg ctatgtttct actagagcaa 42720ctacatagag
caggagtaag caacttacag tccacagacc acatttgctc tgtcccgttt 42780ttcaaataca
gtttaatgga aacagagcca tgcccgttct ttcacctatt ctgcatggct 42840gacatcaggc
atggttctaa gtaatataca taagtttcat atattaatgc tcatctatcc 42900cagttgacaa
acatgaagtg ttgctattgt ctcattttac agcggagaaa actgacatag 42960agattctctt
tcgcacccat agcttcagtt accacctcta tgccaatgat tcaataatac 43020ctctaatcca
gacctcttct ctgagcttca gacaggcaga tctctcacag ccagtcttgg 43080agacacttca
gaaatcatag gtcccaaacc agactcctcc tcatcccctc aaacacattc 43140tttttcaaca
ttcctttttt cttagtgaac atcaccaaat agataagcaa gtcagatcca 43200aggaggcctc
cttggcactt ctctcatcct tgtcccacct tatatcatct atttttcttt 43260ttcttttttt
ttgagatggt gtctcactgt gtcacccagg caagtgcagt ggtgtgatcc 43320tggcccactg
cagcctcaac ctcaccaagt tcaggtaatc ctctcacctt aatcccgtga 43380gtagctggga
ctacaggcac atgccaccga gcccggctaa tttttgtatt tttaccagag 43440acagggtttt
gccatgttgc ccaggctgcc accttatctc cattcttgct gaaatctggc 43500tgtttctctc
cacttctatt accaaccacc agccaaatct gacttattaa aaggatcatc 43560tcgtatgtgg
gttctgtaat agcttcttca aaatccattc ctctccaccc agaccctctt 43620ccaatctcca
aactgcagcc aataccttca attctgtcac cgctcctgca tactccacct 43680aatccttaac
ctttcaatgg tttctcttgc ccctaggtta agctaaattg aaaactgcta 43740aagctacagc
ttcttagtgt aactagtaag tacagtgact actatgtctg gtttacttca 43800gctgttgctg
actaatagca cttcttgaat gaagaaatta tattaccgta ctgtagggaa 43860aaatttgtac
ttcaatggaa aactgaatta tttagagcaa acctttaagg ttatctgatt 43920ctgattccat
gggccctttc attgggtctt acattgtttc attgtttttg agttatttta 43980cagatgactg
atagaaatgc aaaataatta ttgcatgcag tcatgcaagt aaaatctgaa 44040ggtcagggtt
caattaactt ctctccccta ctgtggaaga agccaatttc atttgcatat 44100tcatttcaat
atttctgacc tataaacatg cctgttcttt gaaccagttt ttatatctgc 44160ctggtaactt
cattaaatga tttaaataaa ctctataatt tagtttattt tatacctgta 44220tgacagtcag
gcttttacct tatttttgct ttttaaaatt attctttagc tctccctaag 44280gcactacttg
gctggccctt tggctactca ctagcccaag ctccatcctc ttctgtctac 44340cgcagcccca
ggctctcttt tggccctttg ttccagccct cctcagagaa gttcttttgt 44400cctggaactc
actttcatac caggtgctct tcatcccttc ttcctttagt aaatttcttt 44460aatctttcag
atttctgctc aaggatcact tgctgaaagc ctttccaggc ctttctgagt 44520caatacaatc
cattattaga ggctcttaga gcacaggcag cacttgttat aattttacat 44580ctgtctgtgg
gattccttaa cactttctaa cacaattaac acttttctct ctggctgggg 44640gcaatgcatg
ataacaggat gatggtatgc tctcaaccct cccccagcaa ctagcccagt 44700gcttcgaaca
tggtggatag atacaccgtt tttattttag acagattttt gagtagcaag 44760tacctactgc
tcaggagaca gatggactga aaaaatatat ttgggagtca tcagcacata 44820ggtgcagcca
tgaaaatgca cgagaagcaa aaccattggc aggaacaaaa tgaaggctat 44880tagagacctt
atttaggtgg aataattgga cagaagccct taatggggag gaaatagaag 44940cagttaatac
agatggaggc cgggcgccgt ggctcacgcc tgtaatccta gcactttggg 45000aggctgagat
aggtgggtgg cttgagtcca ggagtttgag agcagcctgg gcaacatagc 45060aaaacccggt
ctctacaaaa aatacaaaaa ttagcccggc gtggtggcgc aggcctgtag 45120tcccggctac
tggggaggct gagatgggag aattgcttga accggggagg cggatgttgc 45180aattagacga
gatcgcgcca ctgcactcca gcctgggcga cagagcgaga ctccgtctca 45240aaacaacaag
gacaaaactt atcttataag cgaccctgga cttccaggga cactcgccgc 45300tctatggtgg
tacgtgacct gcctggactc tgtggtcttt ggagcttggg accccacccc 45360agcgtaagag
gcctttctgt gccttgtata aaggagagga aaagtgtagg ttttctgagt 45420tgataagatt
agagctacag tatattatca gtagcgttgt atgaaaccat ttaaaaaacc 45480aaaccggatt
taaccgcttt cacccagaat aaactgccct ccccctcttt ccaagatcaa 45540gtcagcccca
gttaccactt cctattaatt taaaaaccag gaaggctcat aatttaggct 45600gacgttgccc
caggcgaaca ctgcatataa gacaatagct attccaatcc tcctttccct 45660ttctaaaccg
aatagtactt ctaacatcac ttttccagtc ctctttctaa atattgcgat 45720cacgagccta
catcggaaaa ctatgaaaac agtatgattg gagctcttga tggtctgctt 45780tgcctgaaaa
cgatgaaagg cattgagatc tttgggcaga aatggccctt agggaatgcg 45840agcctggtag
ccccataaca ccccgagtta caaattcggt ttgggtaggt ggcgcaggga 45900aatctaaaag
ctggattcac gttctccccc ttcagtttgc acatagcggt cagtggcaga 45960caagagcaga
cgcacaaatg tcaatccccg cccgcaaact ctcgagggca gaaactgctt 46020tttgtcagtt
ggatttggag tcggtggaaa agctgcccta atgtagtttc tccgaggttt 46080ccttagcctt
gaccgagggg cgcttcccgg ccattcacct agaggttgtt taataaacaa 46140ggatgctcgc
gaaatatctg cgcttggaaa ggcgctcgtt cgtggcgcgc attctcgggc 46200ctccgcaagc
gaccccggtg acagggacaa ccgcttcggt tttagcgact gcagacagac 46260tgggacgaga
cggttggagg ctcctcccca agggatgctg gaggggttgc gtcgtaccct 46320gcgcctggcc
ctggcgcgcg gccccaggtc gtggtaccca gcgccctatg ggccgtgcgc 46380cggggcttgg
ccacaccgcc tgctttcgct tccagccgcg cgctccgtgc cactgccgct 46440ctctgcagcc
ccgcgtcccc gcagcctccc catggccagc ccgcttcgct ccgctgcggc 46500ccttgcccgc
caggtacctc gaacccgggc gtttgcggaa ggggggagga ttggaacccg 46560ggtctcggta
gctcgcgggc ctggccgggc gccttgtcgc cgtttcctgc accatcctcc 46620ttcgccttgc
cctccattcc gcctccagcg aggcgtcttc ccttccccgc atccctgccc 46680gaaatctgga
gtcccagcct gcaatctcca cctcttcgag gttcccgctg cccaggtcta 46740gcaccctcat
gggtaacccg ctccggagcg tggcgaggac cgccacgggg gacgtgaggg 46800tagctatgga
ctcgctctga gggaggaggc gggagctgaa tctctgggct gccagaaccc 46860acagccacat
cctacgtgac tctgccaccc caaaatattt tgaccgcagc cttctgcctc 46920cttggatctc
ttccttcccc acccccaccc ccgtagttat ttagcagatt acgcattaaa 46980acaaatgtct
gcaggttttc ccaattagtc ccgcttccct gtgtctttat cttttaaatt 47040gcccactaat
accatgaggt ttaaggtgtg gggtggatgc tgcggcatcg gaggaccctg 47100ctggtggagg
aaatggttca cgcccgtccc cgttcccttt gcaggcttgc tattgtgcgt 47160ctgtgattga
caagaccacg aggctgagcg cgccctggag atttttctat aaatggctta 47220acaccccagt
ctagactatt tgctcggata taagggagac aattgttttt ttgttctttg 47280ccggcgaacc
ctggctctgt agggctgacc tggaatttaa ccagtcttcc ctgagccggc 47340ggaggaggac
aaaaaccgcc gcgaccccgg cagggtggga agtgcagggc agcgctccca 47400agacacgctt
gttggaggtt cgggcctggg tgcttggttg tctgagcctc cttttttgtg 47460tttgcctggg
tcctggagag gagcgcacgg tatcatggtg agcgtcacgt aggttacccc 47520gggtcccgct
tacccacctg catttactta atggtggttt aattcttctt taaggattgc 47580agtaacggat
gctccgcaga gtgtaccgga gaaggaggat caaaagaggt ggtggggact 47640tttaaggtaa
gttgcttgcc agaggcttag tgtctaaagc aacgttcaac tgaataaatc 47700catttcttgt
tgagattcgg ggaaattttc actgtgtggg ttacccagtt cctaggttgt 47760gttgccagac
ttttaaaatt ccactcttag aggaaaaaaa gccatttaga gagtgacagt 47820acattcatca
caacaaaaat tatctagcag ctaattgctg attttatttt gagtcatata 47880tttttcttga
aaaatagtca atgcgtaaat attaaactag ttgtttatca gattccataa 47940tacgtacaaa
ccttcagtct acttgtagaa aaagttaaac tgtgattttt ctctttcagt 48000agcacataac
actctacagt gaaagtgttg cattttcttc ttttctatct gaattgcggg 48060gtttatatag
taaatagctc atacttcaaa cagtgagaaa caaagcacgt tgaaaactgt 48120acaaatacaa
atgtaagatg taatattatt ttttctataa gtctatctcc taccctccct 48180cctcgtggag
gttttagctt cttcttttta tgcctagtgc tgctcttctg cctgtttgag 48240tcactgtcaa
ttgtcatcag acaattgaca cagagtgtcc taatgatctc acatcctggc 48300ggttcagaga
gggaaggaaa cttgactcat cagtttctca cacattgagc tctctcacag 48360tgtgctggag
actgtgccat gcattggaca tccaaaggtg aattcaagat taggtctcta 48420cttgcaagga
atttttattt tatttttctt tttccttctc ttgctgtcat cttagcaagg 48480attttttaaa
aagcaaaatt agaatattgc aatttctttt ctgttttttg agacagggtc 48540tcgctctgtc
acccaggctg gagtgcagtg gcacgatctc agctcactgc aatctctgcc 48600tcccaggttc
aagtgattct cctgcctcag cctcctgagt agctgagatt acaggcatgt 48660gccatcacgc
ccagctaatt ttgtattttt agtagagatg gggttatcac catgttagcc 48720aggctggtct
cgaactcctg gcctcatgca atccacctcc caaagtgctg ggattgcagg 48780cgtgagccac
caagcctagc ctgaagaatt ctttgcaaag aaaaatatca actcaaattt 48840aaataatctt
ttcctttctt tttctttttt ttgagacaga gtcttgttct gttgcccaga 48900ctgaagtgca
gtggcaccat caattaggta tcactttcag ccttgatctc tcagactcaa 48960gtgatcctct
tagcctctca agtacctgag actatcggct tgcatgccat caggcccaac 49020taatttcgtc
attttttgta gagatgggat ctccctgtgt tgcccagact gatctccaac 49080tcctgggctt
gtgcaaccct cccacctcgg cctcccaaaa tgctgggtca caggcataag 49140ccacaatgcc
tggccataaa taatcttttt tatttgttaa tttagatttc tgtatattag 49200gttttattta
ggggaattgc ctgtttacac tcatgtattt acacatcaaa acatgagtta 49260tggtggatgt
attcacagca catatgtaat aaggcatgtg taaaaatgat attgataatt 49320tagggaataa
aaatggtaga ttttatagac catctttgtt tttgatatac ttttctctgt 49380ctcaaaaaac
aaaaacaaaa acaaacaaac aaacaaaata tatatatata gcctacattg 49440ttgttaacta
taatcaccct actctgctat gaacagtaga ctttatcgct tctatctaac 49500tgtatgtttg
tactcattaa ccaacctctc ttcctccacc tacacccttc ccaccccctg 49560ccatcttctg
atatctatca ttctatgagt actctcttcc tccatgagat caactttttt 49620ttttagctct
cacgtatgag tgagaacatg caatatttgt ttttctgggt tttttttttt 49680ttctgtgttt
ggcttatttc gcttaccata atgacttcca gttccatcca tgttgctaca 49740aatgacacga
ttttactctt ttttaatggc tgagtagtat tccattgtgt atatgcacca 49800cattttattt
gttcattgat ggacacttag gtgattccat gtcttgacta ttgtgaatag 49860tgctgtaata
aacatgggac tgcagatatc cctttgatat actgatttcc tttcctttgg 49920aaaataccca
gtagtaggat tgttggttta tatggtcatt ctacttttag tttttttttt 49980ggaaagcttc
ataccatttt ccacagtaga taaactaatt tacattctta ccaacagtgt 50040ataagcgttc
tcttttctct gtatcctcat cagcatctgt tattttttgt ctttctaata 50100ataaccattc
taactgtggt tgcttttgac atatttctct acctttttgt taatctacat 50160catttataac
atttcatatg gccttttggg tctctcttgg gtagttttcg tatttcttct 50220cccctcccca
tttatgatgc agtcatatta catgaggatg cagttttgca gcagggccta 50280gcaatgagat
acgttgttac acatcctggc gaatctttct gtggactcta ggatcctctt 50340catttgcaag
aggtcagcca tctatttctt ccaattcctc cagcttcaca tatctccaca 50400gaatgcaaca
ctgcaaatct gcagttctct tcatgatcct ctttattaga ttttaaaaga 50460gtatctccaa
aagatgaaca tagtgcctaa ggctttccaa atggagtaag aataatgcac 50520aagaacctag
aataaagtta ttaaatgtct gatacagttg taatacagac ttgatttttg 50580aaaaatgtgg
ccaatgaaga gaagagcaaa tgtgctatac gatggtgagc aaaaggtgtt 50640gacaggcctg
gcatggtgac tcacccctgt aatcccagca ctttgggagg ctgaggtggg 50700tggatcattt
gaggtcagga gtttgagact agcctggcca acatggtgaa accctgtttg 50760tattaaaaat
acaaaaatta gccaggtgcg atgacacatg cctgtaatcc cagctacctg 50820ggaggctgag
gcttgagact tgcttgaacc ggggaggcgg aggttgcagc gagccgagat 50880tgtgccactg
cactccagcc tgggcaacag agcaaaaaaa aaaaaaaaaa aaaaaaaaag 50940tgttgactga
accctggctg aaacagtttt caggtgcttt caacaaattt acacttccct 51000gccctgagcc
tccctatttc agaacaaatg attacccaac tgcaaacttt gaattaggaa 51060gttgttttta
atatgccctg tttttctcaa tatttcttgc catttcacaa tcagttattg 51120tggcattcca
attcttccac aaacatatga tgtgaaacat cctgacttcg atgtcatcag 51180ggaatgtgga
gcattggaaa gagacagatt aattatgcag aagaaagtat catttgacaa 51240aatattattt
ttatttatct ttggaaagga aatctagaaa aagaaaatac tttttaaaga 51300acactgataa
aaattgttta taaaatttgt ttcctttagg aaacaaatcg ttcccttaaa 51360actacatttc
atatctgccc caaacgagtc acatgtcttc agctaatatt gcttgtttac 51420gtttgaactt
tattcaattc tatcacctag taatttagta ttcttaggta atttctcttt 51480gagctcaggt
taaaagttgt tatttttagt tttcagagtt gcagaatttt tttttcaagt 51540agagaaaagt
tcatgatgag attctgaagc cacctaatcg tatattactt tgaaaaactg 51600gatatatgcc
gggcgcggta gctcacacct gtaatcccag cactttcaga ggccgaggtg 51660ggtgggtcac
ctgaggtcag gagttcgaga ccagcctggt caacatggtg aaaccccatc 51720tctaccaaaa
atacaaaact tagccgggtg ttgtggcaca tgcctgtagt cccagctact 51780caggaggctg
aagcaggaga atcacttgaa cctgggaggc ggaggttgca gtgagcccag 51840atcacatcac
tgctcttccg cctgggtgac agagtgagac tccatctaaa agaaaaagca 51900aaacaaaaca
aaactggata cagggcagtg cttaggtaca aatcagaaag ttagaggttg 51960ctattcatat
cattaagaaa taatgtgtct tacgaaagaa tgtagcagtt tactgaaata 52020gaagtcatac
ctagaaatgt aataatttat ctttaattgt cagaaattta actgatatta 52080tgaagttcta
attataagaa cacttatttg aggttaaaaa ttaccttatt ctatccctgc 52140tttgccgcta
atttgatctc tctggattag tgggttattg tgggtcctat gggtatttta 52200aggagaggtc
tcagaaaact aaaaattata tatactggat cataatcatt cttgtcaccc 52260actctcatct
ttctgttttt gttttgtgtt ttactaccct tcccctttta ctaagtagtc 52320ttagtagaag
aaaatttgca ttaagtttgt cgtactgtat tgatatggct ccaaatgttt 52380cttagcccag
ggtcctcccc attcactgat aaaagctaac taaggtaaat cacaggtgtt 52440tattgtgcaa
gaatactgtg aaactattca tgtaataaaa agtttgtgtt agaatttcac 52500tctctttaaa
tcctggacat cttctgtgag tgtatctgaa agcagccaga catcttcagt 52560atttaagaaa
ccctttacta ttctgtgtgc taggcactgt gttagctttg gaattcaact 52620gtgaatactc
tagccagact tcttgtctaa atagtccaga ataggggttg ctaaactttc 52680tttctttttt
tttgagatgg agttccactc ttattgccca ggctggagtg cactggtgtg 52740tctctgctga
ctgcaacctc tgcctcccag gttcaagcag ttctcctgcc tcagcctccc 52800aagtagctgg
gattacaggc gcccaccact acactcagtt aatttttgta tttttagtag 52860agacagggtt
gtgctgtttg ccaggttgat ctcaaactcc tgacctttgg tgatccaccc 52920gcctcggcct
cccaaagtgt tgggattcag ggtgtgccac tgtgcccggc ctgctaaact 52980ttcttaaatg
gctagatgat aaatatttta ggcttgaggg ccatcaggtt tctgttacaa 53040ctagttggct
gtgctgccac tgaagataca agaatggcgt gactatgttc caataacatt 53100ttaatttcaa
aacaggccag ctggctgcat ttggtctgca agtaaagtct gcctgacccc 53160ctacctagtc
cagaggacaa cgggagagaa aagggattca aagataaaaa taatttagct 53220ggaatatatt
tctttaaata aacttattat acttagtaaa aagtcttaaa ttaacgtttt 53280tacttgaatt
aaatagtggt aaaacaggct gggcacagtg gctcatgcct gtaatcttag 53340aactttggga
ggtcgaggca ggcagattgc ttaagcccag gagttcgaga ccagcctggg 53400caacatagtg
agtccctatc tctaaaaaaa atacaaaata ataataataa tggtagaaca 53460aagtcaattt
tttattgaaa cttggcattt tattggcata ttacaaagta gcattactag 53520actagcctga
acattacagt aatattctgt ccttaatgcc ttttgtgtca ctgtaatatg 53580agctttctgt
ttgttttgga atatgttttc agcctgaata ttattctaaa aatacaattt 53640actatcattc
ataatatatc aaatgactca cgtagctgca aggcagtgaa ttaaacagaa 53700ttagatcatt
ttaaaaataa tgataagagc tgatgatgta aagtgaaggt ctgtatttaa 53760tttgggaggg
aaaagacttt ttttgtatat tcaaagagat ggagtttgac atcccttcac 53820aacctgttac
aggttgaact tgcccctgtt tttttaactg atcaaaaagt tccttctctt 53880gtgtttcttt
ttttcttctc ttttctcttc ttttcttttc tttttttttt ttctgagaca 53940gagtcttgct
ctgtctccca ggctggagtg cagtggtgcg atcttgactc tctgcaacct 54000ccgcctcccg
ggttcaagtg attttcctgc ctcagcctcc tgagtagctg cgactacagg 54060tgcatgccac
cacgcctggc taatttttag tatttttagt agagacgggg tttcaccatg 54120ttagctagga
tggtctcaat ctccaaacct tgtgatctgc atgcctcggc ttcccaaagt 54180gctggtctcc
tgtgtttttg tcagcattcc acagatgcta taaagttagt ggtggtatcg 54240catgcaattt
gtacgcttaa tgtttggcca tttgcagtgg gcaaactggc tatgtcggga 54300gctggtgaga
tgctgcttgt ggggagttgt ttcctattac tctgatttat ctttgtttaa 54360ataagagttc
ctttgttcac tgtttcctcc acacagaaca gaggatttat atcttagtgt 54420tcattctcaa
ctttcctgtt ttcaaagagg aaaacatttg cttcactttg ctcatttctt 54480ctccagtgca
cccagaggat tttgaaggct tatgccaaca attctttggg gcagttggag 54540tgtaaccatt
gctaaatagc agttcagtac ttaatgacat tcattttagt ttaacaaatc 54600attgtgagtg
ttgccatttt ttattaggga aaacatctct ttcatctttc ccaaatactc 54660aacatgagtc
ctatggtgag agtgaaaaag ggttgtattc tttttttgca tcatcttacc 54720ccatctgcta
ttttgtccct cttctatata tcactgaaat ttggttctga tattctatta 54780ggcagtgtac
attgcagaga ttatgaataa ctggccgaat tctgaatgca ggcatgattt 54840gttcagctca
gagtgttaaa tttctgtgtt agctgctaac ctttaaaagt caattgattt 54900cctttttttt
tttcccctct gtataatcta gccagcgaat gctcagtagc ttttctgtaa 54960atagtgatga
tttttcttcc ccaggctaaa gacctaatag tcacaccagc taccatttta 55020aaggaaaaac
cagaccccaa taatctggtt tttggaactg tgttcacgga tcatatgctg 55080acggtggagt
ggtcctcaga gtttggatgg gagaaacctc atatcaagcc tcttcagaac 55140ctgtcattgc
accctggctc atcagctttg cactatgcag tggaagtaag tacatgggaa 55200ttaaagagag
tgacatgctt gcacttcact gtgggtacta agtagcttct cctgctaaaa 55260tagctcttgg
gcagtatggg ctttatcata tttaccagag gaagccgaaa atgtctttaa 55320aagttttcct
atagacagtt ggattgaaga taaatcttag cagctaattt ttcagataat 55380cttgcatttt
ctgtgacgtc aataaaaaaa ttatttaaag caaatagaaa ggacagctgg 55440tgggaaaatt
ggcaattaaa aagccagcac tgttgataat ttaataagtc acctttcttc 55500ttagatcttc
taataattga gaaagggtca ttgagaacaa tattatgatt tgattttaat 55560gctaactcca
catttttatg accagtaata atgtctagtt atgcatgtta agggacatgt 55620aattaaatgt
cctccttcag ccatgagttg aaataatttt aagcataaaa tgtttaaaga 55680attctttctc
tggtcctttt cagggtgcac aattaaccag atgcacagta tacttcccat 55740tgtcttgatt
ctcattgtat tttacttttg aatgatttgg acatctttcc cagaataata 55800ggggtgctgg
aaataataat agtcttccta ttaagtgcta aaatatggta atagtaaaat 55860attaatagat
taatgataaa ataacaactt ttgtttactg aattcctgca atacgttctg 55920tattatgttc
catatatgaa tcatctcatt taattacctt aagtgagaag gcatgtgatt 55980aagcattcag
gctttgaagt cagacatcct gggctcaaat tcggtctcat ttgctccata 56040ggaaccttta
tgacttgagg aatttaatca tttgtgcttt aatttcttta tctataaaat 56100tggggtagtt
ataatatcta tcttacagtg atctcataag tataaaataa agtaatttat 56160ctaagcatat
agagtcatat ctggtgcata gcgagagccc agttgttagc aataataatt 56220aactcttgaa
gcagtggtct catccattat aaaaggaggc tcagaagagt tgtttcttga 56280ctaatattac
acagcagtaa gggtggagct aaggttccaa tgagaagctt ctttctgtta 56340tatagcccct
acatgtatac accaaaatta ctaggatgct tttgcaatta actccttcaa 56400aattataaat
tcatataatt ttggaaagat attcactgtc catatgtatc cacaaaatgt 56460tgaatttagg
aatctaagtt tctgttccca gctcttcctg ttatgtcaat ttgaatgagt 56520tctttcatta
tttgccacaa gccctcacca tgtcataagg tataataaag aacaggtgaa 56580atgaagtgct
tttatttatt tatttttcag acagattctt gctctgtcac ccaggctgga 56640gtgcagtggc
acgatcgtgg ctcactgcag cctcaaactc ctgggctcaa gcaaacctcg 56700tacctcagcc
tcctgagtag ctgggaccac agacacatgt caccatgtct ggctaatttt 56760tacatatttt
gttgagactg ggttttgcca tgttgcccag gctggtctca aactcctggg 56820ctcaagcaat
cctcttgcct tggcttcttc aagtgctggg atgacagcca tgagccactg 56880ctcctggcta
tgtgctttta aatttgaaag gaataatatg cccaagccca ggtcactggt 56940tctcaaactt
aatgtgcatc agaatcagct ggctacatct ccagagtttc tcatttctaa 57000caagtgtcca
gatcatgtta attttgtcgc tccagggacc acattttggg aattgctggc 57060ctatgggaag
taaatgagaa atgatttaat gtcatttttg gaagttaaaa aagattttgg 57120tggtcactgg
tttttgaaaa ctctttgaag gctgggtggg gtggttcaca tctgtaattt 57180cagcagtttc
ggggagatgg ggttcttggg aaatgagccc tccacccatg ggatctgatg 57240ctatttccac
gtagataatg tcagagtcgt tcaaaccaga gtgactccat cctgaatagg 57300ggctgggtaa
aataaggctg agacctactg ggctgcaaca tgatgagacc ctgactctat 57360tgaaacaaaa
caaaacaaaa caaaacaaaa caaaacaaaa aacggccagg cgaggtggct 57420cacgcctgta
ataccagcac tttgggaggc caaggcgggc ggatcacgag gtcaggagat 57480cgagaccatc
ctggctaaca tggtgaaacc ccatctctac taaaaataga aaaaaaaaaa 57540aaaattagcc
gggcgtggtg gcaggcgcct gtagtccaag ctacttagga ggctgaggca 57600ggaaaatgac
gtgaacccag gaggcggagt ttgcagtgag ccgagatcac gccgctgcac 57660tccacactgg
gtgacagagc aagactccat ctcaaaaaaa aaaaacaaaa acctctttgg 57720ccatctattt
agatgagttg gaatgctact ttgattggtt ttgccaattt agatttttgt 57780aattagggta
gtttaaaaaa actctcaaat tactgttatc ctttgttaaa aaccaaaatc 57840ttttattatt
agtcttctgc ttacaatata agtaaaataa atgttttgta ttaataactg 57900gattgtatat
tgcatggtta ccactatgta acaaaattaa tagcttaaaa ttacaagcgt 57960cattttaaaa
ttatttttca tgtttctggg gttgactagg atggctaagt ggtttttgct 58020tggggtccgt
cacacggttg ctgtcagtgg ctggggttag agtcagctca caggcttcct 58080aactcatatg
gtgctggagg gagtgtctct tagcatgcta atgcttcata atttgtgtat 58140aatgaacagt
gaggatgacc agaggtcact ttcattgcca tctgggctgc aaaactcaag 58200gagttgaagg
ctcttccggc attacttgtt ctccatgtgg tctcctcagg atggcagtca 58260cagagtaggc
agccttctta tgtgctgacc tagggcccaa aatctgtatg tgtcagttga 58320ctgagcccag
atggaagctc tattgctgtt tacgccctag cctcaaaact actctttcaa 58380gaaaaattct
ccaaccgagt ttttcctcta ctctcacacc accacaacaa tagtcaacat 58440aggagacttc
tatgatcaaa ggtgtaggga tttctcccca ccaccaagca gtgaacccca 58500gctgggtgtc
ctccaattca attctcacac tgttattacg ggaaaggtgt cccaatccag 58560tccccaagag
gttcttggat gttgcacaag aaagaatttg gggagagtcc acaaagtaaa 58620ataaaattta
ttaagaaagt aaaggaaaaa aagaatggct actccgtaga cagaggagct 58680ccgagggctg
ctggttggct attttaatgg ttatttcttg atcatttgct aaagaagggg 58740tagattattc
ataaattttc cagaaaaggg atgggcaatt cctggaactg agggttcctc 58800ccctttttag
accttgtagg ttaacttccc accattgcca tggcctctgt aaattgtcgt 58860gacactggta
ggagtgtctg ttagcatgct aatgcattat aattagctta taatgagcag 58920cgaggacggc
cagacatccc tttcattgcc atatgggatt tggcaggttt tggctggctt 58980ctttaccaca
tcttgtttta tcagtggggt ctttgtaacc tgtatgttgt gccgacctcc 59040tatctcatcc
tgtgacctag aatactaacc tcctgagaat gcagcccagt aggtttcagc 59100cttattttac
ccagccccta atcaggatgg agtcgctctg gtccaaacac ctctgacatt 59160atccacctgg
aaatagtgtc agatcccatg ggttaagggc tcattcccca agaccctaac 59220caccctcacc
tggcccagac acaagtcaca agtcctgtcc tctggaatgt ctgactgaga 59280ggcatcaagt
tggagttccc atgaccccct cttctggttt gattaattta ctggagcagc 59340tcacaaaact
cagggaaaca cttaggttta gtggtttatt ataaaggata ctgcaaagtg 59400tatagatgaa
gcgatgtgta gggtgaggta tcgggggata gagtgcaggg cttccatgcc 59460ctcccggggt
gtgccaccct ttaggaacct tcatgtgttc tgctatccgg aagctcactg 59520aactcattct
tttgggtttt tatggaagct tcacgtcaat attccttccc ctggggtatg 59580aggcaggacc
ttcaccggag agggtctttt attttatttc attattttta aaatataaga 59640tggggtcttg
ctatgtagcc tagggtggta ttgaattcct gggcccaagt aagcctcccg 59700cctctgcctc
cgaaagtgct gggactacag gcatgagcca cccagcccct ttggagagga 59760tcttaagact
cacagttaga aaggagggca ggagaaggtc agagagattc tgcttcctgc 59820ccctgaggcc
taacacaccc agcattataa caaaagactg taacaagggc tatgggagtt 59880accagccagg
aactgtaaat cacacagtat tatttctgcc ttactcttat cagtcatgat 59940ggttacaaag
gcctgtccaa gttcaaaagg aggaaaaaag cactccactt cttgatgagg 60000aaggtcaggg
ttctggaaga gcatggggga ctggaaatat tgttcggcca tttcatggaa 60060aatacagtct
gtaatagaca tcagtgataa atggggagat atggtggatg tattgttttc 60120ctctgagtgc
caaattgggt tctaagattt cacaggccag atattattga agtggctacg 60180ttgtctgggg
tatatacctt ggggttcgtc attttgtgcc aggaaaattt aggacaagga 60240ctcacacgag
gagtttagga gtggaggttt aataggcaga agagaaacag aaacagttct 60300ttctgtaggg
agagagggat cttcgaggga aaagaccatc cagcagcaga tgagctggat 60360tttatagtca
ggtttgagga ggaagtgtct gatttactta gggctaacag gttggtttga 60420tcaggtatga
cgtttacata gcacaccggg aagtctggtt gccccaccct aatcctttta 60480tgcaaatgga
ctttcctagt tgattggagc tatcttgtct gctccttact gtacaggtgg 60540ctgacaaaga
gaagggaaga tggagccgcc atcttgaaca tgattgacgc agctgtggat 60600atctatgtct
gcagcttgat tttacaggct gctcttcttt agaaaggggc tgcttttcat 60660taaaacaaaa
accttactga ggactcttgt accctcacta tctgcaggtg atttcttaac 60720tcctgtatca
ttattatagt gtcataggaa tctaggaagt gtgattgcct tctggagaga 60780acttcagggt
ccctggattt tctcactaat catattcatt tcattccctg tttacctgtt 60840taataaatgt
tgagtggcta ctatgtgccc agggctgtgc aaggtgcctg gaataggatg 60900gcaagcaaac
caaccatgac cttgctctca aagaattgtt ttctttcttt cttttttttc 60960tgagacaagg
tcttgctctg tcgcccaggc tggagtgcag tggcctgatc tcagctcact 61020gcaacttcca
cctcctggct tcaacagatt ctcctccctc agcctcccag gtagctggga 61080ttataggtgc
ccaccaccat gcccggctaa tttttgtatt tttagtagag acagggtttc 61140atcatgttgg
ccaggctagt ctcaaactcc tgacctcaag tgatccgcct gcctcagtgc 61200cgagattaca
ggcatgagcc actgcacctg gcctgttttc tgtctttttt ttttaacccc 61260cacatggaaa
gttaggcagg gatttaattt caaagagttt cttcccaaat attgtggtga 61320aacatctagt
ccatttatgt ttcaggcttt ttcatagata ttactgtttc tcttagactg 61380acagacttag
gacatcacat gattgaatgt caacctgact tttaagttca ataatagttt 61440cattttttaa
atgcaaaatt aaataggagt aatatccttg aacatgtttc tccttcactc 61500atcggaccta
ttgagtctag aatccatttt attttgagag ctccaactac atgtggtttc 61560tgttaatatc
tgaaagtaat ttttaatatc tgaaagtttc aaatagtgat aatatttgaa 61620ggtttcaaat
agtggaggag agacgcaaac tgcgagtagg gaacgcggat tgaaggaaat 61680gaaaagttga
taataggcac ttcattttca gattataaca aatatttagt gaaataaagc 61740ataattttaa
aaaatggata agacatgtat gtactattta atgtgtacta ataaatgaat 61800gctcatattt
gccatccaga taaagaaata gaacagttga acatcacaga agccctcgcg 61860tgtcccattc
agatcacaaa ctctatcttt ctactggtaa ccattattct tacttttgtg 61920ataacctttc
tttgctttcc tttatggagt gtgtagattc ttaacactat agttttgcct 61980ctttttgaac
ttcatgtaaa tgaaaaaatg tatatatttt gtgtttgtgt gcatgtgtgt 62040gtgtgtgctt
gcacacgtgt gaatacccct tattgtttga gcttagtatt atgtaagatc 62100taaccaggaa
ggaccaacct aacatttgtg gggcctggga cctaagtata gacagagatg 62160acatggtcca
ctccatatct gttcccatcc cagttctgcc ctgtgctaca aggggtcttc 62220cagacactgc
ataggtaccc ataccacctg caggcagatg acctttgcct gtcctttgga 62280gttaggcctg
ggtaccctac tagtggtgtc tgctcttggg atgataaacc cgaggggctt 62340atcagcttta
tatatatata tatatatata tatatatatt tttttttttt ttttttttag 62400ctagcatctc
tctcgttctt ccaggctgga gagcagtggt gtgatcttgg ctcactgtaa 62460tctccacctc
ctgggttcaa gcgattctcc tgcctcagcc tcccaagtag ctgagattac 62520aggcacgtgc
cactatgcct ggctaatttt tgtattttta gtagagactg ggtttcacca 62580tgttggcatg
tgagccacta tgcccggcct cttttttttt tttttttaag agacagggtc 62640ttactatgtt
gcccaggctg gtgttgaact cctggcctca atagatcctc tgtccttggt 62700ctcccaaagt
gctggctcag tcattatgtt ctttactgcc atccattgca gtataaaaag 62760aataacagtt
ttccctcaga atattcttgg tgaaacagta acaattatta attttattaa 62820atcttggctc
ttgagcaaat gtcattttaa tattctgtgt gataaaatag caatgtcaca 62880taaagtgctt
ttacatactt aagtactatg gttgtctgaa gaaaaaggag ttgtgtgatt 62940gtcttgagtt
tgtaagtgga actacttttt tcatcgagca ccgtttttac ttgaaataac 63000aaagtatgaa
tatgaatgca gatttggcca tttggcagat ttttatttat ttatttgaga 63060caaggtcttg
ctgtgtcacc cagactgggg tgcagctcac tgcagccttt acctcctggg 63120ctcaagtgat
cctcctgcct cagcctcctt agttgctggg accacaggtg tgcagcacca 63180tgctcagcta
atttttaaat tttttgtgga gacaaggtct gaccatgttg cccaggctgg 63240tctcgaactc
ctgggctcca gcaatcctct cgcttcagct tctcaaagtg ctggaattac 63300aggcgtgagc
cacggttccc agctcgcctt ttcatatgtt tattgggttg ctaaatatgt 63360tcttatttga
agtgcccact tgttcaagtt ttttgttcac ttttttattg ctgtctttat 63420aattttttga
tgacaagaaa tatgtttaaa ttaaaggcag ttttgtcaat ctgccttatg 63480tttggaattt
gttgtgtctt taaagactct tttcctgccc ttatattata aagatatctt 63540atagtattga
tattgtcatt cacagttagg tctttaatcc tagaagttga tttttgtatg 63600aagtaagggc
ccaatttatt tttttccacc tatgtatacc cagttttccc agcaccattt 63660aaacgggcgg
tactttcccc tctgatatgt catgatgaca cctttgtcat gtacacatga 63720gtttgcttct
ggatctctat ttgtgttcag ttgttttact tgtctgcata aatgccacag 63780tcttggtttc
tcagtcatta taatgagcct tgcctgctag gaagggtcct tctactttgt 63840tctccaagag
tgccttggat attcttggtc attttctttc catataattt ttagatttgg 63900tttatcaagt
cgataaactt ttgtcatgca gttttttaaa agaaaataaa gtgccctaat 63960gtgatttttt
ttaatttgga ttacattgaa tacataaatc agtttgggga aaatcaacat 64020ctttataata
ttgaggcttt ttatccatga gcatgaaatt gctttctaca ttaataactt 64080ggtaaagttt
tatattttcc ttatggatct ttcacttctt ttgttagatt tttctccacc 64140taagtactgt
atcttttaat tctactgtaa atagtgtttt tattttttaa ctgctgctat 64200tacataggaa
tataattttg catctggcca gcttgcctaa acagatgatt tcaaaatatt 64260atctgtcaga
ttttctgtgt tctctatctc tgtaatcata tcatctatgt tttatgatct 64320atgacagtta
tattttttca tctccaagct gatattttaa atttcattat tcttgcttta 64380tactggttgt
acatattcag ttagagtgat tgcagtaggc aatttgcgat gttcccaatt 64440tgataaggaa
agcttttaca ttttaccatt aagtataacg tttgcgagct tattatagct 64500atcctttgtc
acttagggaa gttatctttg ttttttagtt atctaggaaa ctaaaaaatc 64560agaaaagtta
gtttgatttt atcagataca tctgctacat ctaatgagat gatcatatag 64620tttttttcct
cccataaact gtgaatataa tgaatcacat taattgattt ttttaaatgt 64680taaaccaatc
tccatttctg ggataaattc aacttagtca tgttgtatta gccttttgta 64740tatcttatat
ctataatact gaatgagatt atcatactct ttacatgtat ttgaagccat 64800gtcattaagt
gcatacaatt tttattaaat ttttaattga caaataattg tatttattta 64860tggggtacga
tgtagtgttt tgatatatgt ttacattgta gagtgactaa atcaagctaa 64920ttagcatact
catcactgaa catatttatc atttcttgtg gtgagaacat ttgaaattta 64980atctcttagc
aattttgaaa tatatgatac attattatta actacagtca ccatgctgtg 65040cgataggtct
caaaaactta ttcctcctaa ttgaaatttt gttccctttg accaacatct 65100tccaattccc
caacccctag cctcctctgg taaccaccat tctactctct acttccatta 65160gtttgacttt
ttcagtccac atatgagtga aatcgtgcag tatttgtctt tctgtacttg 65220tcttgtttca
cttagcataa tgtccaacgg gttccccatg tcattgtaaa tgatggaatt 65280ttctttttta
tagctaaata acattccatc atgtatacat accacatttt ctttatcgat 65340tcatctgttg
atggacagtt aggttgcttc tgtatcctgg ctattgtgaa taatgctaca 65400ataaacatga
gagcacagat acctcatgct gatttcaatt cctttggata agggtcccca 65460aaccccaggc
tatggaacag cagtggtatg tgtggcctgt taggtactgg atcgcactgt 65520aggaggtgag
cagctgcgag tgagcattac cacctgagct ccatctcatc tcagatcagt 65580ggcagcatta
ggttctcata ggagtgtgaa ccctattgtg aactgtgcat tgcaggaatc 65640taggtggtgc
actttttatg agaatctaat gcttgatgat ctgaggtaga atgattgcac 65700tctgcaagac
tccccacgct catccctgtg gaaaaattat cttccacaaa actggtccct 65760ggtgccaaaa
aggttgggga ctgctgcttt tggatatata cccagaagtg ggattgctga 65820agcatatggt
agtttaattt taattttaat ttaatttagt ttaattaatt tatttttagc 65880acctaggctg
gaatgcagca gtgcaatcat agctcactgc agcttccaat tcctgacctc 65940aagccatcct
cccaactcag cctcccaaat ttctggaact acaggaatga gccatctcac 66000tcagccctat
ttttagtgtt gggaagaatc tcaaaaagta atgactgtac taatttacac 66060cgctaccctc
agtatacaag ggttccatat cctcactaat acttatcttt tatctttttg 66120atagtagcca
ttctaagtat gtatagtttt aaaattatga agtttaaatt gaaccttagg 66180aagttgctac
tctgtcacca ggctggagtg cagcagcgtg atcttggttc accacaatct 66240ccgcctcctg
ggtttaagca attctcctgg ctcagcctcc caagtagctg ggactacagg 66300cacatgctac
catgcctggc tcatttttat atttttggta gagatgggtt tcaccatgtt 66360gtccaggctg
gtctcgaact cctgacctca agtgatccaa cagccttggc ctcccaacgt 66420gttgggatta
cagacgtgag ccatcacacc cagccttgaa gttgcctttt ttatcttcag 66480tagtgcttct
tggcttaaat tcttttgttt tataaatagt aatggaagct tgccagtttt 66540attttagaaa
gtatttgcag gccaggtgca gtggctcatg cctgtaatcc cagcactttg 66600ggaggccgag
gcaggcacat cacttgagcc caggagttcg agaccagcct aggcaacatg 66660gcaaaacctc
gtctctacaa aaaatacaaa aaattaactt gggcgtggtg gtgcgcgcct 66720gtagtcccag
ctactctgga ggctgaggtg ggaggattgc ttgaacccag ggggtagagg 66780ttgcagtgag
ccaagatctt gccactgaac ttcattcagc ctgggtgaca gagaaaaaca 66840actctgtctc
aaaaaaaaaa aataaataat aaaaaataaa gtatttgcat gatatatctt 66900tttctgtctt
tttgattcag atattgtcag ctgagtccaa tctaacaaac ttatatttta 66960accgaagctt
tagtactgtt atatttaata aactaataat atatttgcac ttaaatacaa 67020catctaattt
tatgcttttt aattatacat gatttgtatt tctttttttc ccatgtaagt 67080ttttagggta
tacatcttta aaggccttac ttttcattat cgttcagttt aacttatttt 67140ctaatttcca
tttttcttct gtgacctatg gtttagttag tggtggattt attttccaaa 67200atatggatgg
tgtccagtca aacttttggt attgatttct ggcttatctt gtgtttggaa 67260aatatgtgaa
ttctacagct ggtctgtgta agagttctct gtatcagtta gggaagtttg 67320ttcttcctgt
tgttcatatc ttgcatatct ttactaaggt ttagcctgtt tgttctataa 67380attacttaga
gaagctgtgt taaattttcc cactaaaatt attgattttt gtctttctct 67440gtatttatca
gtatgtatct actgaagtct tttcaaatcc ctgatcagtg gtttgttcag 67500gacagcactt
tgattgaggg aggtgacgtg gcttaacata gtatggtctt gagctgcctg 67560gtttctgtga
tttagggact gaaccagctc tggtcacatc tggattatct actatccagc 67620attcaaatga
accagattac atgaaaggat atgggggtac tctttggggg ccacggtgcc 67680acaaggcctt
tggtttcgat ctccattgcc tagggaatta acctgtgctg tgtgattcta 67740gatgttttct
tcctgctccc ttaaataaca cctaaatgtg ttattcagca gtgtggctcc 67800tgctaagcag
aggagaactc ggaattccta ccaaattctg ataataaaat aactttcctc 67860cacctcaacc
attgttttta ccagtcctgt caactgttag ctttcctgga tttaatgatc 67920tcaagttgag
gtcaatgtca acagctttat gggatgaata agatgaacgc ccataggaaa 67980gtcagtctct
tgaacacggg ttgttttctt ttggttaccc tctaagattt tttctctttg 68040atctccagtt
atttgaagga ttgaaggcat ttcgaggagt agataataaa attcgactgt 68100ttcagccaaa
cctcaacatg gatagaatgt atcgctctgc tgtgagggca actctgccgg 68160tatgtaagtg
taggagtttc ttttgtgttt cttttaatgt aacgggtcac ggtgttgacc 68220accaaataaa
taatttctga atagttagat aaatattcag tacaaaccat atgaacatta 68280acattatttc
tgatctactt tagttaggta aaaatacaag aaaatggccg ggcacggtgg 68340ttcactccta
taatcccagc actctgggag actgaggtgg gtggatcact tgaaaccagg 68400aattggagac
aagcctggcc aacatggtga aacaccatct ctgcaaaaaa tacaaaaatt 68460agccgggttt
ggtggcacat gcctgtggtc ccatcggtgt ggctgaggca tgagaattgc 68520ttgaacctgg
caggtggagg ctgcagtgag ccaagataat cacatcactg ccctccagcc 68580taagccgcaa
agtgagactc tgtaaaaaaa aaaaacaaaa aacaaaaaac ccaagaaaat 68640aatatcattt
ggcaattcca caatttttta aaatcagtgt ctgtggggga ttcatatgca 68700agtgagagat
gaaagagtaa ggaagaaaaa tgtatctcaa cctaaaataa tatttgaaga 68760ccacatgaaa
ttaatattga aaatggaaaa tatggtgtgc agcacaggta ttttgcggat 68820attttgccta
attgctttag atgctagcaa gatatagtaa cttaattatt ttgatatttt 68880atcttaagta
atgttttgag ataaaaagat atcaaaatgg tttctcatgg ccattgaatc 68940gtggctgtca
caatgtttct tatggagcag aaatcattgt aagatgggtt agattttttt 69000tttgagagag
agtctcactc tgtcacccaa gctatagtgc agtggcacaa tcttggctca 69060ctacaacctc
cacctccggg gttcaagtga ttcttgtgcc tcagcctcct tagtatctgg 69120gattacaagt
gcacgcagcc atgcccagct taattttttt aaaaattatt tttagtggag 69180acatgatttc
accatgttag ccaggctgga cttgaacttc tggcctcaag tgatctgcct 69240gcctcagcct
cccaaagttc tgggattaca ggcatgagcc accgtgccca gcttcaggga 69300tttagcccaa
cctatgcatt caggaagcct gaggacggct aaatccaagt gttcttcatt 69360cctctgccta
tttttgtaac ccgcatttca cccatctcct ttggaggcca taatatagta 69420gcagagggga
aattaaggta aattctttgg actagggcat agtttcgctc ttcttctcat 69480tacagctaga
tcactgggga aaagtcttta aaatggggct ggaaggaaag ggaagtaata 69540tttgttagac
atcaattttg ctaccaaact gtgttatgta gtttcacatt ccttatctgt 69600gtaatcacag
cagtaaggcg ttgctaagaa gattatttgt tgtacagttt attagtgcct 69660ttgtacagag
aagaaaactt gagtccagag agattaaatg acttgtctga agtcacaaag 69720agcaaaagga
cagggcaaga aattagatcc aggtgttttt attcctggtc aagttctctt 69780ctcactgaat
tctgtctcta gacagcaata ccaggggctg aggcaggtgc tacagggttc 69840acctatatga
ttggcagtcc caatttctat aacattacta cattattatt gctgttacag 69900gtcaatattt
aaatagacaa attctgactt catgagcttt actcagatgc ttatgactga 69960ctcatttcta
ccttaggtga cccatcacat ctctgaaagt atgtttctct actttgcaag 70020tgagcagaga
ctaaattatt ttatgaagta tcacccatct agtagatgta attttttttt 70080ctttagaaat
aaagtgctct ttgcttttgc ccattttcct attgggttat ctatctcttc 70140attgactttg
gggatatcca aatatatata ccagttaaaa ttctttgttg atcatgctac 70200caataacttc
acccagtttg ttgctttaca tcttttgaag aacggaagtc tttaagtttc 70260aaatagtcac
attttatcca tttttttcct tcatgatttg tgttttacat ctcctactta 70320agaatccttt
cctaccttaa ggtcacagag atattttgta ctttttaaat aaagtcttag 70380tattttgtca
catttaagta tatcatctaa ttagaattga ttggggggta tggtaagatg 70440tagggatcta
atcttatctt tcacatgtgg atagctcgtc atcccatcac aatttttggg 70500gggaaaatca
gaaaaaattg tttggtttta ttattacttt aaaatttttt ttattggtac 70560cataaattat
acatatttat gaggtacact gatgttttca tgcatgcata taatgtgtaa 70620tgattaggac
aaataagaaa gaaataaata aaaattagga taattaggat atccatcacc 70680tcaaacattt
cttatttttt tgtgttggga ttattaattt tttaacagtt taaatgcttc 70740agtgaggatc
atttattatt gccacattgt gagaaaattc tgtcatttat tatgtttttc 70800attctttcag
gtatttgaca aagaagagct cttagagtgt attcaacagc ttgtgaaatt 70860ggatcaagaa
tgggtcccat attcaacatc tgctagtctg tatattcgtc ctacattcat 70920tggaactgag
gtgcaaactg actctttatt ttggggtact ttgctgggca agttattatt 70980gtttattgtt
gtttgaaact tctagcatat agtttgcagt agccccccag tagcatcatt 71040aatgacttct
tccttctgat tgtcaagatt agaggtagca aacattttct gtgaagcgcc 71100aatcagtaaa
tattttttgg ctttgtggcc atatagtttc taataagaaa ttagatccct 71160acctcttacc
ataccccaaa atcaattata attcgattat atacttaaat gtgacaaaat 71220actaagacgt
ttattaagaa atacaaaata tctctgtgac cttaggtagg aaatgatttt 71280ttttttttga
ggtctctctc tggttttttt tttttgccca cgttgtcgct taggctgggg 71340tgcagtgatg
caatcacggc tgactgcagc tttgacctcc tgggctcaag tgatcctcct 71400gcctcagctt
cccaagtagc tagtactaca ggcatgtgct accatgccta gctaattttt 71460aaattttttg
tagagatgat gtctcactct gttgtcctgg ctggtctcaa actcctggcc 71520tctagcaatc
ctcccacctt ggcctcccaa agtcctggga ttacaggcat gagccacttc 71580acctgaccgg
agaggattct taaactctgc cattttagta ctaaagcagc catagacagc 71640acataaatga
gtaaatgcag tgctgtttgc cttgcccaat taagactagt cattattttc 71700taagtttaca
agtgcagtgc ctcccattgt ggcagtactt ctctgaggta gaaatggttt 71760taaaatttag
gggagggaga gctgctaatt ttcattttca tgaggtcttg ggattacttg 71820gcatggagtg
agaatggagg ttccccttcc cacatagaaa aatggtgaaa ataaagttca 71880cagtgggagt
taaggaagga aattgaagag ctgggatggt aggtttaaat aacatgacct 71940tatgatttcc
tggtgggtca cagtctcttg gttgggtgcc cttgtgaata aaggcatgga 72000ttgggcatgc
ctggaggggc caaggccttt tgagcggacg agtatgttta tatgaagacc 72060ctgtcacctg
tctctggtat ctgctaggca gctgtggctt gagagtgtga tattgaggga 72120taattgatgg
aaggagattg aatgtggctg gcaggtaaag agatagggaa catatggaga 72180tatttagaat
aagagagtgt gagatagagc gcttttgcta tagcctagcc attctgttct 72240ctactaagtg
ttgcggggtt accaggtttt ctactaggct gtatgaatgc aaaaggtaga 72300gagatatata
gggccatgga ataaataccg aagtgttttc tttggtatcc ttgatacctt 72360tcgaaagccg
tgtaaggatc tagataatga atttcgtgaa ttgcagtctc tctgacaagt 72420tttaaagaat
aggaacaatt ttaaaaagtc atctacttcc ataagttttt tgacatttta 72480agataattga
attttttttt ttcagctttt aagttccagg gtacatgtgc aggtaggtgt 72540gttatatagg
taaatgtaag ccatggtggt ttgctgtaca aatcaaccca tcacctaggt 72600attaagccca
gcatccatta gctattcttc ctgatgctct tcctcctccc gccccttccg 72660acagacccta
gtatgtgctg ctccctgcat gtgcccatgt gttctcattg ttcagctccc 72720acttataaga
gaacatgcag tgtttggttt tcttttaata ttatttttaa ctttatgata 72780ggaaggagta
ctttttaaag ttggttgaaa cattgttact gatctcaaag cactaccttc 72840cagttattct
gagatacttt ttcagtctaa gatctgatac tcctattcct ggtttgttga 72900gagtttttgt
catgaatgga tgttggattt tgtcaattgc tttttttgaa tctcttgaca 72960tgattatgtg
gttttgtact ttattacatt attaatgaat gaattatatc aatttatttt 73020tggatgttaa
atcaacctta ttttcctaag ctaaatccta cttggtcatt gtgaataatc 73080cattttttta
tcttgctata ttcagtttgc taatatttta agaatttttg tttcactgtt 73140catgaaatat
attgatctag ttttcatttt tcttttcttt cttttttttt ttttttttta 73200catctccctc
ctcttcctct tgatctagtt ttctaataca gctgcactcc aacttacgat 73260ggtcctactt
aggagttttt gactgtatga tgtttgaaaa caatatgagt ttagtagaaa 73320cttactttga
gtacacatac cattctgttt ttttgctttt agtacagtat tcaataaatt 73380atgtgagata
accaatactt tattataaaa taatacactt ttagatgatt ctgccctacc 73440ataggctaat
gtaattgttc tgagcacatt taagatagga taagctaaga tacgatggat 73500gtttggtagg
ttaggtatat taaatgcatt ttcaccttaa ggatattttc aacttaggat 73560gagtttattg
agttgtaacc ccatcacaag ttgaggaaca tctatgtatc taattccatg 73620attcagtaaa
ttctttagac tgccaaaatc ctgtaatcta gagttagaca agatcttaaa 73680tcaggttttg
tggtccatct tgtagtcatg atcattctca ctattaggga attcttaact 73740ttttgcattt
gaatcaccga ggtgttattt aaaatacaca tatggaatcc aagctccaga 73800gactctgagt
agatctggtg agtgattgtg atgcctgccc acattcaaga accttagtac 73860aaaagccctg
ctgaatggtt ctctttcact atacactcta tcaacttatg tacttgatca 73920cactttggac
ctcaaaatca ataattttta aaaatctact tcctaagttg tgaggtacga 73980attgaaggaa
ataatgaata ctatttgggg agtcaacatt atttattaac gaataccatt 74040tggggagccg
acattattta tatttggttg gtatatttgt atcaactatc attttctaat 74100taatggtata
ggcagaataa accatcactt gtgattcaga aaggaacatg atacaaataa 74160catccaataa
tgtatatgga tttaaataga tctgccccct acagatgtta cgcaattcat 74220gttggtaatg
atcattcatt aggttttcgt ggtggctaca tttgatatgt gaagtactgg 74280ctggaagact
ggtgccagta gcttcaggtt tgctgggatt ctttcatcag agatgactag 74340ctttacttat
ctttttatgt tgcatgtttc tatgatgggc ctatcctgtc attgtcttca 74400tagtataatt
gcaagctcaa ctctgtcagt tatgtgattt tttttttttt tttggtcctg 74460tcttgctttt
ggctgacttc tatatgtttt tatttcatgt ccttttcata gttagattaa 74520ctgggtctta
tgtccaagag atattttgat ttctttgaat gaataaatct atgttaggct 74580actgtattag
gttttataga cacctagttg atcacttgtg tccagtctct attccctggt 74640atggtagttg
ctgtgtttat agaacattga ggattctaca atggacacat tggtgttggg 74700ccccagccca
gacccaaatc gaaatttcta gagccaggat cagagactct gcattcaaca 74760aactctccag
agatttcata accactttta aaggactcac catcccaaac cttgttaagg 74820aatgaaatat
atgtctgcca gtaatttcag tgctttaagt cattgaaagc tgaactttta 74880atggcaccaa
agtggaaata tttatataat tgaaagctaa acttcatcct aatggcagtg 74940ttgagttcac
ttccataggc cctgatataa cagtctaata ttattgtttt tcacataaaa 75000taagattcag
tcactgccat ataattaggg agtggctctg ctattggatg gacttaaaat 75060atttcattat
gtttgccaag ctctgtctct ttacatgttt tataattaac tgatccttca 75120tttttatttt
gttttatttt atttttgaga tagagtctcg cttggttgcc caggctggag 75180tgcaatggtg
caatcttggc tcattgcaac ctctgcttcc caggttcaag tgattctcct 75240gcctcagcct
cctgattagc ggggactaca ggtgcgtgcc accatgccca gctaattttt 75300gtacttttag
tagagacggg gtttcaccat gttggccagg ctggtcccaa actcctgacc 75360tcaggtgttc
tgcccacctc ggcctcccaa agtgctggat tacaggcatg agccaccatg 75420cccggcctcc
ttcattttta ataatcttca tagatacata cttgttgtac taatgttttt 75480gtgcagttcc
tcatgataaa taattaaatc aattactaaa atccttatag atttatgatg 75540ataataaatg
gaagtgtgta ttattgaaac atgtttaatt aactgttcat atataaccag 75600tgagtaggga
ttggcaatta aaaataccag gctaccagtg catggaaatt tgaagaaaac 75660aacaacctga
aattcagaat actccaaaat ctgaaacttt ttgagcactg acatgactaa 75720aaatgctcat
tggagcattt cagatttcat tttttcagat tagggatgct gaattggtaa 75780gcataatgca
gattaatcca aaatctgaaa aaaatcctaa atcaaaaaca gttttggtca 75840gaagctttgt
ggataaggga tagtccaagc tttttggact gaagcttttt ggataaggta 75900tagcctataa
tacataaata cataatacag gataatcact gacctgaatg tatagcatca 75960gtatggtaca
caaatattta aatccatgta ctttgttgga tattatgtta tataaacttc 76020ttgtaaaaag
tttagagagt aaaatcattc acattaccaa aagatttctc atatttataa 76080aaaggattat
agcagcattt taatcagtat ctcctaaagt atttatttat gggttgttaa 76140atctaaaaga
gaaactacag tctggagggc tctaaactac tgctgattac atatcagttg 76200ggaattaaga
gaaaatctca gatcataata tttaaataaa aacatttaca tgaatgattt 76260ctaagttttc
actttactag acaagaaact aaaattatat gactgtcatg ttcaatattg 76320gatacttaac
aacactacat ccaaggaagc caggttttgc tgattttaac ctcgtcctgt 76380tgagtaactc
catgcaggta cagtggtaca aacacatgtg gacacacaga cccagacctt 76440tatttcctcg
gggattctgg taagtgtaga ggtgtcttga ccatagtcaa tagcagaaat 76500atgcacaacc
acaagctctg aaattccatt tgattgttgc tcttagcctt ccacttttta 76560ggcatatgtc
agtcccattt catcccaccc actctctcca tttgggaggt ggtagagtga 76620gacaatactg
aactatacca gggctgagaa taagtgtctt tgaaaagggt cgaatctgtg 76680atgctagaga
cagccctgga aactgtcagg agttagccca accaggactg tgaccagatc 76740ccaggctgtc
caccacagat ttgcaggcta cctgcagatg tgactttttc aaatgtactc 76800aaagacaagc
tgactttggc taatgcagaa attaattaat tcctcttttt cagtaaactt 76860tatcctccta
cacttagatt gtctgtaagt acatctctgg agttgagctc aactagaaag 76920aagctgtctg
catttagtta ataccagcat tggatgcaca caatataatt tgaataatgt 76980agagcaacat
tttaatcatc tctcataagc agtttcccca tttgcaactt cctgggaaat 77040cttacattat
gaaatgttca ttagaactcc cattttaaaa ccctgctgcc attttgtgag 77100tgggcagaag
aaaggctgga gatgagattt gtctgtctca aatgattcac tccttcattt 77160ctggttcact
ccacagggag cttaaggaca tgtgcgtttc atagacatgc ctttcttttc 77220cttttatcac
cttgttaaat cttaagattg aacatacaat tcagcctgta atcatatcaa 77280ttcccatgaa
aaatattttc cttattcact gcctctattt gtgcttatac atctgatcat 77340ctttttcctt
tactttacaa ttagtttcta tgaacagaag aatctgaaag atttaaagac 77400tagttagcac
agcagcaatt tataaatcat taatttgggt actgtctata catttaatgt 77460gttctttttc
atagtcctat gtgaaataca tatacatata tatatattcc actgtttata 77520aacaatattc
agttttattt gcataactca atatatttta tattaacagc tccgttttta 77580gtgtcttaag
acatcgagtc tgtttttaga gatacagtct atttgccttg attttagcct 77640gttataatca
gcttattatt atctggccac tcttaccagt gagtatcatc ttgaggctgt 77700tcttgctcat
ttcaacttgt cacaggggat gttttttact ctttggagtt taggtacacc 77760aggttattaa
ttatgctcct gattcatggt acttccatca tggggcatat aaggtccctg 77820tctttgtttt
attcccttct atcttcattc accactctca tttcctctct ctccactaga 77880aataattctc
aggaatcaaa ttaatattat tctggcttat atgtgttttt aaaaatctca 77940tcgcttttta
tacatgtaat tttaatttat gtaagagact ttgtcctaca gatttcattg 78000tgtttcttct
ctttttcgcc cagcactgtg tgttccattt ctatccagtc tactatgtgt 78060acatcaagtc
catcatttct aactgttgca tagttcatga tgcgaggcat cttccacatt 78120gtatcccaat
tccctaactg gaatcccagt tccctgctac ctcacacaat gctccagtga 78180acagctggaa
aatcatacaa cccaaggaat tattgaaagt gattatatcc cagcaaaagg 78240cccaggccca
tcttacactt ccaccccaag aaggtactgc tacttttcgg gaatggcctg 78300gtctccttgg
cgaaattggc atttgatctg ttctcatcac tgtcgtctgg catcagaagt 78360gaccccactt
gtcaggcact gtactcagtg ctttccatgc actaactctg ataacaatct 78420tttttttttc
tttttttgag acagagtctt gctctgttgc ccaggctgga gtgcagttgt 78480gtgatctcag
ctcactgcaa cctccacctc ccaaattcaa gcgattctcc tgcctcagcc 78540tccccagtag
ctgggactac aggcgtgcac cactacacct ggctaatttt tgtattttta 78600gtagagatgg
ggtttcacca tgttggccag gctggtcttg aaatcctgac ctcaggtgat 78660ccacttgacc
tcccaaagtg ctggaattgc aggcaagagc cactgagctt ggcctgataa 78720caatcttgtg
agcaggtgct tatgcagtat tttagggatg tgaaagtaag gtccaaagcg 78780gtgaaataag
agcctgtatt ctcttaacct ccatcccgca acatctttta tgtgtcagtc 78840cctgcactaa
gtctagggat actgtgctga gcaaaaacta tcttcttgct ttcacagagc 78900tcagtgtctg
gcagggggtc agactttcat aatataaacc cactaaatga gtgcatattg 78960atggcggtca
ctgctgtgaa gaagtgggaa tggttagcat ggaaacatag ccccaatggg 79020ggcgactaag
ttctttccca tctcattcta ctatgtctac tttcatctct acttttttct 79080tttctgagct
atcagctttc ttgctctcaa ctatatttga tgtatttaac cagattttat 79140atattgtatt
atgtatttta taacatgtat atatatcata taacatacac atatacatac 79200atacacacag
ccaattaagt ctcaagttca attacaatgc ttctaagttt aggactattc 79260attttcattt
tggcagagaa attatctggt aaaaaattca agtagaacca aaggtataca 79320atagatggga
agtttccttt tcactctcac actctcattt ccatccaggg ttctacaatt 79380catctccttc
caagcaattc ctattgccag cttttcttat accctttcag aaatacacac 79440acacacacac
acacatatat acacacacac acacacaccc ttacatgtgt ttgtacatta 79500tctctctttt
tacaaaattg gcagtgattc tttgtcctgt ttctgccact actcaaaaat 79560tttaaaacaa
attacacacc tataaacata caatttaaag aaaagagtga aagtgaaaat 79620ctaaggaccc
agcacatggt taagatgaga gcatgatggg ttcaatggaa agcctttgtg 79680tacctttctc
ctttgcctcc gttccctctc caatagagtc aaccacgttg gaggttatag 79740cacttccttc
tttatgtccc cccatctccc atctggtatg gtattctctt ttactgcaga 79800tggacatttt
ggcagacata tgtagttgct tctctttggt atttacctag gagttgaagt 79860gctgggtcac
agggtgtatg tatatttcac tttagtagat actgctgttg taggactttc 79920tccttagttt
agctaaagat ggggtccttg tcccaaggcc atgaaaaatt aggctcgcag 79980acaatttgaa
aggtgagaat aatggaactt attgggaaaa aagggaaaca gggactcccc 80040acaaagccag
ggtcctgcta gcatgcttcc tgccttgcag attgaatccc aggtaccacc 80100caggaagagg
aggggccagg ctcctcccca ctgtgaatgg tgtgaccgtc tgtggctccc 80160cagtgtgcac
tcctcccagt gtgcaggccg gttggagttt ctctggggtc ttcttcccac 80220ttggctgtct
cactgccaaa ctcccaaagt gcttatacca gtttactctc ccatcagtgg 80280tgtatgtatt
tgcttcattt ctttgccaat actgatactg tcttattaac tttcctcatt 80340ctaatgtata
cagtcttgtg ttatttgtgg tttaatttcc ctgagaacca attatgttga 80400gtaccttttc
ataggtttac cagctacaga agtcctcttg tgaagtgcct ttgcaagtct 80460tttgtctttt
taattttttg catctttgta tattctaggt ataaatcctt tgatacatat 80520atcacaaata
acttcctagt ctatggcaaa tcctatgttg gataaacgta ctgcaaatag 80580tttcccagtc
tgtggctagc ttctgtgtct gtgtcttgct ttgtcacttt cttactgata 80640tcttttgatg
aacagaagta cttagtttta aagtagttaa agttttcttt atgttttata 80700ctttttatgc
attttaaaga aattttttgt tactccaagg tcatacaggt taaataaatt 80760cttactccaa
gaacattctt ttaaagtttt gctttttttc atttaaatga aatccatatg 80820aaagtgaact
ttgttatcaa gtaacatata caatttcttt tatttttctg cacggagacc 80880aagttgtccc
atcaccattt attgagtggt ctatcctttc ctcactgatt acagtgccag 80940ttttgatatg
tcatgtttcc atagatgaag aatattttgg ggctctctat ctgtaccttc 81000ctttttaaaa
aatataaata gtggtgatac tatgaacaat tttgtttgta ttattgtttt 81060ttgcacttaa
aatttgtctt ggagatcttt tcattttggc acatacggat acacccctat 81120ttttttttcc
attttcctag atgtggggta tccattggac atatgtaccg tactgaattt 81180aatatagaat
gtcataaatt acaagatgta acattatttt atacactgag atggagaatc 81240aaactgcaac
gcagtacttc cctgatcatc ctgagtgatt catgagttag ttatactagc 81300ctcttatttc
tttgaggtgt acgttttctg agggaatctg ccatttctcc tgccatgagt 81360tgcattgctt
ggctcgtgat aggcattttt atttttgcat gtaattttgt aacaaatgct 81420aacactgctt
tatcttcttt ttgtttttgt ttattgagac ggagtcttgc tctgtttccc 81480aggctggagt
gcagtggtgc aatctcggct cactgcaacc tctgtctccc aggttcaagc 81540gattctcctg
cctcagcctc ctgagtagct gggattacag gcatgtgcca ccatgctcgg 81600ctactttttg
tattttttgt agagatgggg tttcaccatg ttggtcaggc ttgtcttgaa 81660ctcctgacct
caggtgatct gccccactca gcctcccaaa gtgctgggat tacaggtgtg 81720agccaccagc
cagctttatc tttttaaagg tttcttccta ttgtgggttt cattagaggg 81780cttggttgtt
gctttgcaag aaaacattga cttgcttttg tttaatagtc ttataaatat 81840ttgtttcact
aacatcaaat acatgccatg ctcctgcttt tgagcttttc tgtgcagtaa 81900cttttcttct
cagtgctaaa tcataagttt ttaaagacat ttaacatggc acactcaaca 81960tgtgtcacca
atgcccatag ccactggaag tatcatcagt gtcaacagct atgacgtttg 82020gcaatgacag
ctttgccata actgctgctt agccaataac aattgtggaa tgctgagtcc 82080agatctcaaa
catgttaaag gtaaaaaaaa aaaaaaaaaa aagatatttt cgagtctgta 82140aaacatggta
gcgtatccgg aattggtggg ttcttggtct cactgacttc aagaatgaag 82200ccatggaccc
tcgcggtaag tgttacagtt cttaaaggtg tcgtgtctgg agtttgttcc 82260ttctgatgtt
cagatgtgtt cggagtttct tccttctggt aggttcgtgg tctcgttggc 82320tcaggagtga
agctgcggac ctttgcggtg agtgttgcag ctcttaaggc ggcatgtctg 82380gagttgttcg
ttccttgcgg tgggttcgtg gtctcgctgg cttcaggagt gaagctgcag 82440accttcccag
tgagtgttac agctcataaa ggcagtgtgg acccaaagag tgagcagcag 82500caagatttac
tgcaaagagc gagagaacaa agcttccaca gtatggaagg ggaccccagc 82560aggttgccac
tgctggctca ggcagcctgc ttttattctc ttatctggcc ccacccacat 82620cctgctgatt
ggtccatttt acagagagct gattggtctg ttttgtcagg gtgctgattg 82680gtgcatttac
aatccctgag ctagacacaa aagttctcca cctccccact ggattagcta 82740gataaagagt
gttgattgat gtatttacaa accctgagct agacacagag tgctgactgg 82800tgcatttaca
aaccttgagc tagatacaga gcgccgattg gtgtatttac aatctcttag 82860ccagacgtaa
agattctcca agtccccact agactcagga gcccagctgg cttcacccag 82920tgtatcttgc
accagggctg caggtggagc tgcctgccag tcccgcgccg tgcacccgca 82980ctcctcagcc
ctcgggctgt tgatgggacc aggcactgtg gagtgggggt ggcactcgtc 83040agggagactc
aggccgcaca ggatcccaca gcggtggcgg ggggcgggag gctcaggcat 83100ggcaggctgc
aggtcccgag ccctgccctg cagggaggca gctaaggcct ggcgagaaat 83160ctggcccggc
gagaaatcta gcgcggcgcc ggtgggccag cactgctggg ggacccggtg 83220caccctccgc
agctgctggc ctgggtgcta agcccctcac tgcccggggc tggcagggcc 83280agccggtcgc
tccgaatgtg gggcctgcca agcccactcc cacccggaac tccagctggc 83340ccacaagcac
catgcgcagc ccgggttccc gcccatgcct ctccctccac acctccctgc 83400aaactgaggg
agccagctcc ggccttggcc agcccagaga atggctccca cagtgcagcg 83460gcaggctgaa
gggctcctca agcgcggtca gaatgggcgc cgaggccgag gaggcaccga 83520gagcgagtga
gggctgggag ggctgccagc actgtcatct ctcagtagca taatttatat 83580aaccagtctc
ttgttgatta accattatat tattgataca acaaatataa gaactgttac 83640tagtaaattg
agtaaagcag gaaaattaaa tttggtctct tactgatcaa ccattattag 83700attgttgata
acaacggtta taatgttgat caaccgttat attgttgata caattatatt 83760tgatgtattt
aaccagattt tatatattat attctatatt ttataacatg tatatgtatc 83820atataacata
cacatataca tacacacaca cagccaatat aatttcactc tcagtttctt 83880gttaatcaac
tattatattg ttgatacaac aaatataaga actgttacta gtaaattgaa 83940taaagcagga
aaattacatt tgggagcctt aaagatgtag gttttcttca agaaatttat 84000gttatagtta
tatcccctgt tgcatgtgaa gacatacatt caaggatact tactgcagct 84060cacacaattt
gctgataggt tggatgtggg tgtgagagaa gagatgctgt tttccttttg 84120ggcgatggca
actggatagt aatcagttac taagatggag aagaatgaga aagaagtctt 84180tttttgtttg
tttgttggag tgatatgggt agaataaaga gttaaaacag tcatgcatgt 84240aggtactata
gatgtgaaag tctattattc aggggagagt ttggaattta agggatagat 84300tcttgtcttt
aagcataaaa atgcctttga aggtgagaaa ctagattaca tctttaaggg 84360gagaactgta
gatagagatg aaaagaaggc aaggactaac ccctggggca ggtcagcatt 84420tagaagaaag
ggagtttgta aaatgctaag ctgtctgaga agtagcagcc tgcaaggtag 84480aaagaaaaac
aagagaggtt tagtggactg gaaaccaagt gaacctggaa accacaagca 84540gctgtggcaa
atcctgccac agtgagatga ggcctgagaa ctgagtattg gatttgtcaa 84600tgtggaaggc
cttggtgatc ttgataagca tgtgttagta gggtggtggg gttgcagtgt 84660ttgggatttg
agagagaatg agagaatggg tagctgtgat gctgaatatg tataaatgtc 84720aggaggaatt
ctgctgcaca gtgggacaga gaatggacgc ctccctggaa tgggatagat 84780gctaaaggga
gtgtgtgtct tagttgggag atattatggc atatctctaa gctaatagta 84840attagccaga
aggaagggaa aactgatagt taaaatgttc aaaagatttc tcacattcct 84900atcatagttc
tccttctaag ggtgaccacg taagcaggca gggacatgtg actaagtaga 84960gcagcatcca
acccccacct tgcacggtca cacacatact gctccattga caccatagtg 85020tcttggtgtg
agctcttcat tacttgactc aatatcttct tcctcatctt ctcagctggg 85080gttgttgggt
atatcttcat tgcagatatt agcatccttt gtggtcttct ttgtctttct 85140attctagggc
cagcacagtg ggaggcctag tcaactgagc caaactggat ataaccacaa 85200ggtcaaaggc
aggagccagt gaggagatct tggttttgag gtcattcctg gtgcgataat 85260aaccatcctg
tagcattttc ttgtcactta gagaaggcat tagcaaactt tttttgtaat 85320ggtcttaata
gtaaatattt ttgactttgt aggctatata gctactcacc tctgctttta 85380tagtacaaaa
gcagccatag acaattcata aataaatgaa catgttccaa taaaagcaat 85440aaaaacaggc
agcagtctga agtttgtcga ctcctgattt ggaatcattc cagaaagtga 85500aataaaagca
tggcttcttt tttttttttg agacaaggtc ctgctctgtc acccaggctg 85560gagtacagtg
gtgtcatcat agctcactac agctttgacc tgctgggctc aagtaatcct 85620cccacctcag
cctcctgagt gtctaggatt acaggcatgt gacatcacac ctggctgatt 85680tttaaatttt
ttgtattgat ggggtcttgc tatgttgcca aggctcacct caaactcctg 85740gtctcaagtg
attctcctgc cccaggattc ccaaagtgct ggaattaaag gtgggggcca 85800ctgtgcccag
ccaaagcatg gcctttctaa gggtgactca ctgtagcacc tcctgagtac 85860tttcctatca
agtatcctgg accacttttt aaataattca ttctaaaatc catatttagg 85920attgattcca
aatttgccaa cctgtatttc ccaaataact ggcatgataa ttcttgtctt 85980tttcccaaat
gctcattttc cactcttcaa acgttgagtg ttgactgaag ttctgtggtc 86040atgtttacag
tcatttttat gctctttgta ttgtacatat ggaatgtatt taccatttct 86100gttagcaatg
atttcttgca aaaacaataa cacttgctag ttttgcgtgc ttaaaaatat 86160cgagccctgg
cgctctctac atattatcta atgtaatcct tatattaacc ctgtgagtag 86220tcattatcac
ttcttttaca caggaggaag ttagagaaga gtgttaagtg ttcttttagt 86280cttttccact
ttgtctttag ttttctctta gctgttcttt taaattctaa ggtcattctt 86340atctaaaaac
ttaaaagagt tgatcagcct ttttatcaag tgttaaattt ataccatctt 86400ttttctttga
acagggctgg caaataaacc tggatttatc ccttagccct gttacagcaa 86460gtctcagaaa
atttggactt cagcttcccc agtgatacat tttcaaatgc ctatgtatgg 86520attgcccatt
agtttattgg ctagaactaa aggaaatcag gcaagagaca aaggacattt 86580tctctagggt
gtcagtcaat gcaaaatgtt aggactagca tcagattttt ttttttttac 86640aaatgaaaat
aattgaagtg tggtagaagt tcctctagtt ctggcagtcc taaatattgt 86700taactgaaga
atgatggggc tcataaattt ggaaaggaga gagaggggaa aagagaacgg 86760gaatttatgc
tgagcagggt ggctaagtat atatattcaa caggctatag gaggagctat 86820tagtattcac
gaaggggtgg cacacacata catagtaggc taacgtgtat gcagcatgca 86880tcacaagtca
ctttggggtg gagccttaac atttaatgta ttacagttag ggcctataca 86940tcaaaaggtg
aagcagagga cacgaaagcc ctctgtgttc agcctctgta gactggccag 87000aaccactctg
tggtcagagg tctcttatca ggaaagaatt cttgttgttg tgttgaaact 87060gcaaaaggga
ggggcagtgt caggcaggtg gttgatacca gtctttcaga agcactggtt 87120tctgtttaac
ttttagagaa gaaagcttaa ttggagtgtt actggaaagg gataccagtc 87180tagaccacaa
gagaggattc ttggatctca cacaagaaag aattcagggt gagtccacag 87240agtaagatca
aatcaagttt attagagaag tagagaaaga aaagaatggc tgctccataa 87300gcagagcagc
actgaaggct tctggttggc tatttttatg gttatttctt gattatatgc 87360taagcaaggg
gtggattatt catgaatttt cctggaaagg ggtggggaat tcccagaact 87420gagggtttct
ctttctttta gaccatatag ggtaagttct ggatgttgcc atggcatttg 87480taaactgcca
tggcactggt gggaatgtct tttagcatgc taatgcatta taaatagcct 87540aagataagct
gtgaggatga ccagaggtca atttcctcac catcttagtt ttggctggct 87600tctttactgc
ttcctgtttt ttcagtgggt tctttgtgac ctgtatctgt cttgtaatgt 87660cctatctcat
cctgtaacta agaatgcctg acctcttagg aatggagcac aggtggtctc 87720agctcatttt
atctatcccc tattcaagat ggagttgctc tggtttaaat agttctgaca 87780tattttcccc
aataccccca aagggaccct taatcccaaa atttgcagac agatgaagat 87840ccatcttctg
tagcttcttc tggctgaata caggtgatga tatttttgcg taactattca 87900gggtagagag
gagctcagtg agaaagcatc agtatggtga aggccattcc taactcccga 87960gttctcacaa
aaggtgatat ctggaagatt aataagtgtt caatttaaga aaacgttgag 88020tagtcttatc
ctgcattgct acacaaagag taccacagca atatattcta caacagtaaa 88080gcaaaataag
tataattatc ccaactaaac taaataacaa gcctttccat gaactaggca 88140gttgttggaa
ccaagcttat atggggttgc tagccaattc caacacatgt tcagaattaa 88200aatactgatc
cagatattta tgttaccctt ctgtttcttc tgagcagcag ctagagatca 88260ctggttggtt
cataggaaca aacagggtca atctaaatgg cagaaaaaac tcgaaacaat 88320gaatgggact
agagttgaat aacaagtata ccatagtttc tgaaacataa tttttctctc 88380tccagtctcc
catttctatt gaaaacaaat catggtagga ctgatttgtt tgcacagtaa 88440gctttagtct
tattatgctt ggcctggtta tttgtataaa gcatagcaat aataattatt 88500tgccacgtag
gctttttaaa aattgacttt gatgtaactt tgttccataa gaaatctcag 88560attagacttt
ctaaagcctt gagctgagac acagatttat ctgtgcctgc aaatacttgt 88620atgagttgtg
tgaattctcc ttttgagatc ccaagataac tggagctcct aggcctgtca 88680gaaagtgaca
ttctttactt accacaggtc aggaaccctg taaaggaatt gaatagacaa 88740ggtatgaggc
cagcttttcc cagaggcttt catcagttct gtaagtcaac tttgattcct 88800taaagcaatc
tgtttatatt tgaaagaatg ccattccagt caaagccctg gtaaaacagg 88860cagtgtctct
aattgtgtcc tgttacaaag gaaaacagat ttttattgca catatgcaaa 88920ttactatgct
gccataagtt aagaatactc acaaatagtt ttcaaattct tgagaaatca 88980ggtagaaaga
aatatgctcc aaagttttct cataggagta taatttactc aatttttaac 89040aactgtaaat
agctcaaaaa aaaaggtttc ttgactctga aaaatgaaac aaaggatcag 89100caacatttta
agcaaaaagt cactagaagg ttattttgtt cttttattag tttagtccat 89160gctgttaatt
cctgtttgct caatatttat gaacatattg gtttcccaag ggagactctt 89220gaaagttttt
ttcctctcta tcttaatggc acactttaca aaatttttca gaaacctgca 89280tttaagagcc
ctctatctga ttataaacca tcttttaaag aggatcaaaa caagacaaca 89340attttctgtg
gataacataa agtcttagga aagccgtggt taaagacaca attgactaga 89400aattttggtt
acttctgtgg catacaacaa ttttacataa cagttataat tattactgat 89460aacataaact
aagtcatatc agaatttagg agtttcccat aattttggag cacataccaa 89520taacatattt
atacaaatac aactcaaaga aagctaaaca ccatttcata tttgacagtg 89580cttcctgtat
gattttaata taccaagtaa gccaaatatg tcatttttgg acttaagggg 89640acctcatatc
taaagtattg accagatcag gaaaaggcat aatatagaat ttgattttgg 89700aaagtttgtc
aaatatcaaa gatttaaaac acttgatatt ataaaatcga atcccaggtc 89760actgtaaagt
catttattta gccaaaatga taatacaaag attttccaaa agcaaaatcc 89820tttttttttt
tttttttttt tgagacgagt ctggctctgt cgcccagctg gagttcagtg 89880gcgccatctc
ggctcactgc aagctccgtc tcccgggttc acaccattct cctgcctcag 89940cctccggggt
agctgggact acaggcaccc gccactacgc ttggctaatt tttttgtgtt 90000tttagtagag
acggggtttc accatgttag ccaggatggt ctccatcttc tgacctcgtg 90060atccacccgc
ctcagcctcc caaagtgctg gtattacagg cgtgagccac tgcgcccagc 90120aagcaaaatc
ctttactcat tgatagaggg aagacagctt tccaaacaat gtctcacttt 90180ttcttcttta
ttttgttgtt tattcaaaag gcaaacaaaa atcttccatg atcttttaat 90240attacatgaa
aattttgttc aagagagaaa gccaaatttc atctttgcat taatgaatgt 90300caaatccaat
tcttaagaaa accttgtaga caaattattc aatcttaatc aattttacca 90360tgagataaga
ttctcataaa ccttttgtag tcctttacaa tttttttttg ttgttgttaa 90420agagcagatt
aatgctctaa gaaaaccctg ttgtgctttt attccaatgt tctatttatg 90480gaaaaactga
ataataccct ttaactttag ctaatatttt aacacacaga atttctttta 90540caagattaat
tttcactgac ctcccacaac ttactcaaac ctttagcttt atcctatgta 90600acttaaaaca
gtcttttaac tctgtaaact aggcaataag accacattcc catgccttct 90660tataatcttt
taccaaaaac acattctatt ttccttacac gccttgcagg taacactgtt 90720tctctggtag
cctcaattac atgtgctaca atgttaactc ttagcaactt ttatatttgg 90780tgaaaagtct
gataaataag tggttttaat tatgtaccag gtgtggagcc taggacgcca 90840gacagaagtg
cagataaggt ctgagtcttt ccagcatagc tagggggcat ggccaactcc 90900acatgtcccc
aggccctacc tagaatctaa tggctccaaa gcaggtgagt tgaacaatta 90960tcaagttaaa
gaagcagttt atggcattga agcattcagc aaatctaatt taatctgacc 91020taatttagac
cagatgtcta aattttgaag acatttttat tttaccaata tatttgattc 91080tctttatttc
ccaaagatta ttaaagtccc atgaattaaa aggtgttaaa gtttttattt 91140ttctgacaaa
atattcaatt taagtgctta tttttcaagc caattaatta gagctctttt 91200ctatgcatat
cacacataca acacacaaaa atacacagac agaagaccca gtagctgtta 91260attttttcat
ttgccagctt ttaagaatct taattggatt actggcttca gggtggagca 91320acgtgtgggg
acagagccgg gaaaacatgc agtttctggg gcctaataaa caggtgcagt 91380tagaaggcaa
aacagattcc ccaaaattac agatctcatt tttatattgg attctggatc 91440ccaaaaagag
ggaatcagcc catcccctct gggagttttg gaaggtgtag aagaatgttt 91500ccataccttc
taggtggcca agagcatgct tctctgatcc aaacgtgcac agagtggggt 91560attcccctat
aactgctatt agccttccct taaagcatat ttcctgccta gttattacac 91620accaaggtta
aaagctctcc cataatgcaa agtaatttct gataccccta caagtaaaaa 91680acattaggta
acacaatgca aatcagagca atgccttgga ttttgagagg gatttgcttg 91740ccttcaattc
ctggggttcc atgaggaaaa cagatttttc ccaaaatgga gcctgtggtg 91800ctccctcagt
tttttctaag gaagcccagg ctgttagaaa tgatcttagg tcctctcaat 91860gtgggcatca
agagtggcaa gaaaacaaaa tgagaaaaac aattcagttg actgagaaga 91920aaaaactttt
atctagaaaa aaatcaatat aaaacctgcc agatagatag atagatagat 91980aatcttggac
atcactttta attaagctga cttttaacca aatctcttat tatcagactc 92040tagccaggac
aaacagctaa tatttctggc ttttgaactt taccaaaagt aacctcccag 92100gtgaaaccaa
taagccttaa ctaaggttat gatttaacca caggtgtggg aggtattttc 92160aaagaggtgg
taagcagttt ttacaagatc tggaacctcc aaacatagct cagagaaagg 92220aagattcaag
acagggagtc agaagttgtt catgagggga agataattaa taaatggcaa 92280aggtcacata
gatatcaaac cagaaaggac tcattcccga agctaggaat tgaatccagg 92340ccaccactgt
gaaatagcaa agccttagtt actgagctgc agtactgcac agtctccatt 92400gctcctccga
gaaggagcct agagcagcca attttgagct tgcaaaggct tttaactgct 92460caagataatt
tttaggacta attgacagga accccaaaat tcacaccctc tggatggcag 92520agatcaggag
aaagtacccc cacgtggtta caaggtcaag ctttcaagga cataaaacaa 92580gacgagaggg
aaacttcatc cagtttttgt ttcagggacc tgcagaaaag tttgtaactg 92640accagtttgc
gggccagctt gaagaccaga tttgtaggat tcctaggcct gcattctatc 92700ctgtggctag
ctagggctgc cataatagaa tattacagac taggcagctt caaccacagg 92760tgtttatttt
ctcactgctc caaagtctag aagtccaaga tgagggtgcc tgtaaagctg 92820atttctggta
agagctctcc tggcttgtag atggccacct tctccctatg tcctctctgg 92880gcctttcctc
tatctggcca agggagctat ctctggtgtc ttttcctctt cttataagga 92940cagcaggcct
atggattaag gcctcacttt catgtcttca tttaagttta attacctctt 93000taaaggcccg
atgtccaaat acagtcacac cgtgggttag gatttcaaca taggaatttt 93060agggacacaa
ttcaacccat aataggaggg cattggaagg agagtgttcc aggcagagga 93120agtagtgcag
tagagcatat ggaagtagga aagtgaggag caatggaagg ggttcagtat 93180ggtttgagcg
tggggtgtgt agagggtgaa ggctatttca cccagtgcag taagctctat 93240catccacacc
ggggttttac agtgggagaa aggagggtgt ttatttgcag gtcaagaagc 93300aaacagaatc
agggagctca tgcttaagac ctgaactcca cagtggctta catgtaaggt 93360gcagaggtta
caggcaaagg catcaatcaa cacatggaag ccatatattg gtttggccta 93420aaaaggtggg
atatcctgaa gtaggggctt acaggttaca ggtaaatcca aatattttct 93480gatttgcaca
ttgtttaagg aaggggatat ttgtctaaag atgggatcag caggccaggt 93540gtggtggctc
atgcttgtaa cctcagcact ttgaaaggct gaagaaggag ggtaacttga 93600ggccaggatt
tcaagaccag cctagtcaac atggcaagac tctgtctcta aaaaaaataa 93660aaaagaaaaa
aagaaaaaga aaaaaaataa agatggaatc agcagaaagg aatgttaggt 93720ctggcccatg
ggcggacttc ctccagactt ctcagaaaga aatttaagac aaagaatggt 93780gccaggcgtg
gtagttcacg cctgtaatcc cagcactttg ggaggctgag gagggtggat 93840cacttgaggt
cagggatttg agaccagcct ggccaacatg gtgaaacccc atctctacta 93900aaaatacaaa
aactagccgg gtgtggtggt gcacgcctgt aatcccagct cctcaggagg 93960ctgaggcagg
agaatcgctt gaacctggga ggtggaggtt gcagtgagcc aagattgcgc 94020cactgcactc
caccctgggc aagagagcga gacttgagac tccatctaaa aaaacaaaat 94080ggaaaacaaa
gaatggtgat aattcagtcc tcaattcctt ttcttttttt tttctttctt 94140tttttttttt
tttaactgct cctgcggagc agggctacct catagccagt atgtccagag 94200ttgtctcagt
tccctcgtta tctgtggtct ggaggatcca tatgatggtg atccaggttc 94260tgaaaaacaa
ctctggaaca tctgttaaga tgttatcttt agtttctata ggaaaccaaa 94320catcttctga
ctctgacctc cttggtgatt attttaagct actgtttccc tttttgctta 94380tcgagttgct
catttacttc tcaaggctag caggatgact ggactttctc ttgaaggaac 94440tcaagctgtt
cctttatttt tatgctcagg ggcggggggc actcagcagg tccctaagag 94500gtatccccgc
tgtgtctcac tatgggtgaa ggctcagcgg gaagaaagct agataccagt 94560tggaactctc
ttaaagtaag gagatcttgg gtactttatt aatatttttt tcaagctttg 94620gtaaagtatg
aaataactct ggattaagag gagaagaact agaacttaat aaccatgaca 94680tttgggcaaa
ttgtttgaag cctcagtttc ctcaacctaa aaataggaat tataactttt 94740tgaattgttc
tgttgtatga gataatgaca gtgaaatatt ttggagccaa aaagcaatgc 94800atactattgg
gggttattat tattttttga tctttcagca agccagctat agtagctttt 94860cctatataaa
cacagtatga attcagtgcc ctcgctttcc tgaccctcac agcattcaag 94920ccctgtatgg
accgctgagc tctcccttga agcacccctt agtccagtat tctttactat 94980tttccccttt
aacaatttaa acttctttca aaacaactgg cagtagtttt ttaaaaaaga 95040aaacaggcta
ctcttcaaat taaaaaaaaa attgtcttgc tttaggaaaa atgttcttct 95100gtcttttcca
attatcttat ttcttctgcc tctcatctgc cttgcctagg cagaattatt 95160ctcaagcctg
cacatgctgc tgtgcctctc tggcttctag gccaaaacat aggctaatag 95220tactcttctc
agctcactga gctctttcct gccgtcattc aaatcacctc tgaaatcctg 95280ccttttgata
aagtaatttc tgactgatca gaggaaagtg atgattttct ctgtgacatg 95340tctttttatt
ttccatcaca ctcagtgtct tgtccttcta tgcaacatat ccatgtattt 95400aaaaaccctt
gtatatgtat ttgccatgta tttgtgaggt atagctcgtg aagtaaaaaa 95460agtctttatt
tttttaaaca catcatcatt tcagcttcaa agtcaatgtg gtctcttgag 95520aagttaaata
tgctgcattt gaaattttat gtttctcatt tttcatgttt ttttttaaag 95580ccccttttaa
ttcctcatgt atttgaatat tccaggaagc tagtagagta aaaagccaaa 95640gtgttaaagt
gtttataagg aatgtgactc atcgaaattg actcacacaa ttcatcagct 95700attgtcatcc
atatgttctc attatttatg tggcttttgc tttatttaat cagatgactg 95760aacttatcat
cgtgggattt tgcttgtagt tgtttaatat tatataataa aatactcttg 95820tgtgaaacaa
gttaattgac tttttttaat taaaaaaaat ttatgtgaga gtcaggagtt 95880acatgtgcaa
gtttgttaca tgggtatatg ttgtgataca aagattttag cttctaagga 95940tctcattgcc
caagtagtga acgtagtaca ctataggtag tatttctaaa cacttttccc 96000ctccccctct
tttggaatcc ctagtgttta ttgttcccat ctttgtgtct atatgtacct 96060aatgcttagc
tctcacttat aagtgcggac gtgtgatatt ttggttttct gtttctgtgt 96120taattcattt
aggatagaga gactccagct gcagctgtgt tgctacaaat gacatgagtt 96180cattcttttt
tatggctgca tagtattcca tggtttatat gtatcacatt ttctttattc 96240agtccaccat
tgatggtcac ctgggttgat tccatgtctt tgttgttgtg gacagggctg 96300tgataaacat
atgagtgcag ttaccttttt ttgtataaca gttcataata aaatactctt 96360aacagtagca
cagaatttag attgcttttc aggctagaag ggataattga aacatagaaa 96420aaaataatga
ctcctaagca tagaaacaga cccaatcata aagctctctt cctctctttc 96480tgcctagtgt
tagatcttat tcattgtctt aaagcactgt gaccattttc agtgaaatca 96540cagttttatt
catgaaaaga caatgaattg gtgtaagtaa tcatttgagg atgaaggtga 96600ctagtctgtg
atcaacacca gtacttgaag tacttgtaaa acatgaattg accttggtta 96660aattgcagaa
aataaagtat tagtatacat aaacacattt tctctcagca ttgaaaagtt 96720atagtctata
atttacctgc ttgctaagaa taaaaatatt acttagaggt ttatcaagac 96780cttttttcta
caaatggatt taatgtacag aattattcca ttttctatct gtgctctgta 96840tactaccacc
tagtggaata aaatgcaaat ttacctgtca aaatcaggag aagaaaatga 96900accaggggaa
atttatttca ggaaaaaatt ttcataacac gttattgtta cttcttttag 96960tataatgtag
tttgcataaa atacattagt ttggagtgaa aaaagtccca gccatttttg 97020tgatagctat
taaaatgcta ttagtttgtc cacaaataag ctattctatt cagaaactta 97080gaagctaggt
aaattattga gatgatgcca gcatattata tctctaaatt atgttaagaa 97140gcttctctaa
attcctcatc actagggtgt attagtccat tttcacactg ctataaagaa 97200ctacctgaga
ctgggtaatt tatgaagaaa agaggtttaa ttgactcaca gttctgcagg 97260cttaacagga
agcatgactg ggagacctca ggaaacatac agtggaagaa ggtgaaaggg 97320aagcaaggac
cttctcatgg cagcaggaga gggagagcac aggggaagtg ccacacactt 97380ttaaaccatc
agatctcagg agaactcact cactctcaca agcacagcag ggaggaaatt 97440cacccccacg
atcctatcat ctcacactgg gcccctcctc caatttgaca tgagatatgg 97500gcagggacac
aaatccaaac cgtatcatag gatttgttaa aaaaatctaa catgttctgc 97560ttcaaggcac
ccatgaaatg aaggtgtcat ttcttaactg agaggttaaa taaaagtgca 97620gagataagat
ggttaagttt tatcgtagct gggaagaaaa gcgggtgtgt gtattatgct 97680taggtttttc
ctcccaaaca atgaaaccca aaaaggcaaa tgaagcttta aggcgcttta 97740tcctttactg
gtaggatggt cctcctttaa tcttcagtct ctgttaaaga acaaacacaa 97800gctaacaatc
aaaacctgtt gttgcttgct gacggatttc tctaacatag tcttccatca 97860accatcatag
gtttgttgtg gccacccagg ccctttggtc gtcatgttcc catggaatgc 97920taatgaaatt
accttcccat ttcctaaggt gacatgcctt tcagatggca ttggtgtgtg 97980cttgtgtaaa
cacatttttt tgtgctcatg aatattttac ctgcctgatt ttggtgatct 98040gagtgttgag
cagtgggtga gggatggtgg ggcaatgggt agtaagggga agtttaattg 98100aagttcagat
aaaaatatcc ctccagaaac attacaaagc cacaaaatca gctgaagttg 98160agtcttctat
tgtaaagatt ctctttcttc tcctgacaga tccccattcc tatccaggta 98220gaccaggctc
tagtgaagat tggacacaag tggtttatat cccgaagctc ttaacctaag 98280agtcctgcct
tgttttttta cttcatgtgg tcttatattg ctgaggatag cccagtgatc 98340atttctacct
taatatgtag ccttcaaaac gttgggtctc tcagttttct tccttaataa 98400acaatgaacc
ctaattattt ataactgctc ttgtgatgga ggaattggca tgattttgca 98460ttgtgggctt
ctggctttac agtgtttgtg ggaaagatgg tcttctatct ttgttattta 98520taagtcattc
attccctgtt tttttgaaga tattgttaaa taaaaaaact tcagctgaat 98580taaatttaaa
agtttttaat tgagcaaaga accattctca attcgggcag ccttcccatc 98640cagagtagtc
cctgtgactt cagtgcagcc acatggtgga agaggattta tggacagagg 98700aaggaaagtg
acatacagga aacagaaaag agattcagaa acagctgaat tggttataac 98760tcagcgtttg
ccttatttga acatggtttg aacagttggc cacgtttgat tggccaaaac 98820tcagtaattg
gcacaagagt aggctaccat ctgtttataa tgtccactta ggttatagtt 98880catgatgtgc
aaagaaacct ttaagctgag cttaaaatgt aatgaggcag ctgtaggcta 98940aacttgattt
aacagtactt atccctctgt tgaaattgca ctcttgctac ctgctagttg 99000atgtgggcag
gtgtgctaat gacacattcg cctgcaccta ccacctgctg aagaccctgc 99060catgtcctga
agcagtcact taggctatga aacagaagga tgagttagag aagtaaatat 99120tatattttac
cccccaaagc ctaaaaccat gtctaggttc tcccctttct caattcccaa 99180tcatgcaacc
ttgaaaggtg ttatatagat agttgttaga aatatgtctg tcctccaaaa 99240ccctactaac
acgcaaaaat ggacaaatct agcttttttg ctaaaatcct aacaactcag 99300aaagcaaagc
aaaatgaaat gtatgtactc cattctcagg atttccttct taaaaaccac 99360taggctttgt
gtaactcaat tttaaaagta tggtaatagc tcctgtaatt cgatggcttc 99420ttctgggaga
cagatataaa tctattctag actttaagac tggtgtccac attttaagtt 99480acagttgtat
gtacttctac tttgttgcag ccttctcttg gagtcaagaa gcctaccaaa 99540gccctgctct
ttgtactctt gagcccagtg ggaccttatt tttcaagtgg aacctttaat 99600ccagtgtccc
tgtgggccaa tcccaagtat gtaagagcct ggaaaggtgg aactggggac 99660tgcaagatgg
gagggtaagt aaatctgtgt ctctgtctaa aggaaagaca ccttcatgac 99720catttagtta
gtgccatttc acttcagtat gaacacatat aatacttttc aaactttaat 99780gctcattgtg
tttcatggtt aattttcagt ttaatctttc agcaagccag ctgtagtagc 99840ttttcctata
taaacgcagt atgaattcag tgccctcgct tttagatgtg ctagtttaaa 99900ggatagccca
tggccctttg taagggagaa acactggata tgatatctag ggaagaactg 99960aagtaagaaa
ctacaacaag catcacatcg gtgctttgga taaacttccc ctgggcgctg 100020gtctctggct
gcaggctgac ggctggcatt aaaaagcatc tggtcctggg acccaggctc 100080tcagttggct
ccagggagtc atgtctgggg aaggtgcccg cttcactgaa gtgctgtctt 100140cattgccaca
gattgtggcc acacctgctg ccaactggct gcgggacagc cctgctttgg 100200ctctgtcagg
ccagtctcat aggccatatg tagctggcag gaaataaaag agcatttgaa 100260aagtgttgga
cgatttcagg ggtggacttg gccatgagtt gggaatgccc ctatgggtga 100320acgagaataa
ctggtttaag cagcatgggt tcttgctttg catgtatcaa atggtgctgt 100380ttgcatactc
agggcagcag ctgtcctaga aggtgactcc atggcagtct tgtgggccct 100440ggtaggacat
ttaggtccag gaggcagggg agagtcacat gacgtgctgc tggggtatta 100500gaggcaatga
ccactggctt tgacccctct gtagtcttgc tgtatttcct ttttcttttc 100560tctcctcacc
tacccaaatt aaaaaagaac ggttataaaa gtcatcccca ctggcaactt 100620tagcaactgc
attccctcaa tgggtagaga aatccaaatg gagtgcatta aaactaggaa 100680gtctattctc
cttctggctt agagcacacc ttcctgtgtc ctaggctagc caggttgaaa 100740actccttttt
ttgactcttg atttcttttt ttactggttc aaacttcttc gcagagcatg 100800tgcctatgta
ccactgcata ccatatatat accatatata gagagtaaat aaacagtctt 100860gatgaaaagt
aataaggaaa aagtttccct gtttaaaata ttgctttcta gctccccgac 100920ctgtttagga
aaaagataac ctggggacac agaaattgca gggcaatctt tattaaccgg 100980tatttgggca
ggttgtaatt tattttgtaa acaatgattt aatgcactat tgcagaatac 101040atgatcactg
taggccagtt aaaaattaat gttttcagta ccacacagag tgaaccctaa 101100tgtaaactgt
ggacttgtgg accacactaa tgcaagatga taataagaag aaaaactgag 101160agggtgttcg
ggaaggggta taatagggga attctgttac cttttgctca atttctctgt 101220gaatctaaaa
gtactctaaa ataataaaat ctattataaa aatatttgat tcattaggct 101280caggtggact
atgatccatg gaaattgact tgaaatctct taggaaagga agagaccgga 101340gaagaaagta
ttgaactcat aaattaaaaa tggcaagagg gaaggtggta accaaaagga 101400tgggcattta
acctatatgc ctatcacttc caaaaagttc tagggccgtc tcctcctatg 101460cttctgacct
ggagaggtac aaggggaaca aaatattccg catttaatat tatcctgttg 101520agttggcaaa
gacatttgga gtcaacttta gttttgtgta ttattacatc tgtaaaccta 101580attaagtcaa
cagttaccct tgacacctgt agtcaactgg tattattaaa taactattga 101640gtctcataaa
gtcaagaact ttctgctttc tatctaagtg aatctagggc agagactgag 101700catcaggatt
ctttagcatg cagccaagct tgagaagcac tgagctagag aaaggtcttg 101760cactgtagaa
acagctttag ttccaggtga ttccttggtt aatttgggag gaataaggct 101820ttctgtcact
ctctctctct ttctctcttt ttctctctct cttgcacatg cacacgtgca 101880cacacacaca
caaattatct ctcttagttt tttctttttt ccttgcattc tgattctgca 101940tttaagagta
caagctttga agtcagaaag acctggctta aaaacctaac tgtcataatg 102000gtgcgtaaat
gtcgttatag atttgtccaa acccatagaa tgtacaccag gaatgaacac 102060taatgaaaac
tctagacttc aggtgataat ggtatgtcaa tgtggttcat taatttcagc 102120aaatgtacca
ctctggtgtg aggcattggt aatggtagaa actattcatt tggatgggga 102180gaaagggata
tgggaaatct ttgtacttgc ctttcagttt tggtgggaac ctaaaactgc 102240tctgaaaaaa
acctgaagtc tttaaaaaca aaccaaccta attgccttgg gcatgttact 102300taactgctct
atgtatcagt ttcctcattt ttaaagttga ggcaataata ccttgcacag 102360attaagtgag
ataatagaaa gtgcctagga tagtacttgg catatagaaa gctctcagca 102420aatgcagtat
gataacctaa tggttaaaag cttgggttta ggagtcaaat gtctgggagt 102480tacacactta
actatctgtg agatcttcta caactgaatc ctctctccaa gtcttccaat 102540gaacaataaa
gtctagggtt gtttttagat gactcaatga aataatgtag ttaagtactt 102600agcacccagt
ctggcaggta tgggttgcat atctcttatc tgaaatgctt gggaccagat 102660gtgttttgga
tttcaaattt tggagtattt ctctttgggc atccctaatc caaaaaattc 102720gaaatccaaa
ttgagcatca tgttggcacc gaaaaagttt tagattttag agcatttcaa 102780agttttaaat
tagggatcct caacctgtag taaactctca cagtcactga tgttgtgagg 102840ttttctcact
ttctcatttc atttcctgga ctctctttat cttagaagaa atcagttaaa 102900ttttacataa
tagaatttat tcttttggag ggatgtattt aatatgtcta ttctcccaga 102960taacctattt
aaaaccatat tgaaatgttt ctatgtcaac agctttctta ctttttcatt 103020tttctgtttc
ctccaagaac atgtttctct tatgaatatt ggcagcacat gggcgggaac 103080ccaactatat
taccatggta tcagttatcc tgtggacatt aataatacag cttacacctg 103140tgagagaact
ctgggaaaat taaaacttgt ttgggggaat aaagaccatc tacagaatat 103200aataatacat
caatcaatca attaaaactt aaacataaaa aacccttttc ttttcagtgc 103260attgaaatag
tcactgtctt taatcctctt tccttgctca gtgcttcatg aagctgagga 103320gccatggttt
taattcagct acactttcag aaatgtgtat gcatttgtat ttagaagctt 103380ctttgaaagg
ctaaatattc atcctgtaag aattctctat gtgtttttta atacagtcta 103440aagggcattt
tgtatatgaa aaaataattt attttcaggt agggtaaaac ttcactgctt 103500cactacttcg
tagttgtgtc tacgaatgag aaaaaattca aataaaatag ttattattat 103560tagtttttag
agatgcagtc ttgctgtgtt gcccaggctg gtctgggact tctggcctca 103620agccatcctc
ctgcctcggt gtcctgagtc actgggatta caggcatgag ccaccacacc 103680ccactgaaat
agttattttt taaaaaactt aatttcatta ggatgtaaca gtctcatgta 103740actcatcctt
tggcttttat tgttattatt tattttttcc aagcaaccca atgagatata 103800taaagcagat
atttttatct gccagataat taaatgaggg aaaaataagg actaacttgc 103860ttaagttcac
atataccaaa tagtggaaat gcaagagctg tcctcaggtc tgttaacaac 103920aaacctgtgg
tctttctacc agacgtcccc tgcaatctgg tttatactca ttattaaaaa 103980gcatttgtaa
tttaactcag ttatctattt actatcagtt atgaataagg attatttgac 104040tttttatggt
cattaaacaa tagcttccta tctgttgtct ttgtcttttt aatttttatt 104100tattttattg
tttttttaat agcttcctat ctgtatacca gacttgcttc atctccacat 104160tgaccaagaa
tttatatttt gtcatctgta tttagaagca tatgttttaa gcgtctttta 104220atggctcttt
tttttttttt gctgggaggg gacagtctcg ctctgtctcc taggctggag 104280tgcagtggca
ccatctcagc tcactgcaac ctccgcctcc ctggtgtgag tggtgctcct 104340gcctcagcct
cccgagtagg tgggattaca ggcgtggtcc accaaaccca gctagttttt 104400tatatttttg
gtagagacag ggtttcacca tgttagccag gctggtctgg aactcctgac 104460ctcaagtaac
ttgcccacct cagcctccca aagtgctgag attacaggta tgagccactg 104520tgcctggccc
ttttaaggac tctttttttt tttttttttt tttttgagac agtctcactc 104580tgtcgctcag
actggagtgc agtggcgcga tctcggctca ctgcaagctc cacctcccgg 104640gttcacgcca
ttctcctgcc tcagcctccc gagtagctgg gactacaggc gccagccacc 104700acgcccggat
aatttttagt atttttagta gagacgaggt ttcaccgtgt tagccaggat 104760ggtctcaatc
tcctgacctc atgatccggc cgtctcgcct cccaaagtgc tgggattaca 104820ggcgtgagcc
accgcgcctg gcccttttaa ggactcttaa cattaccttg gtgtgagtca 104880acctcatcgt
gctccaatgg caatcaccat agtatgatgt ctattttcca cagcttactg 104940gaatatttca
gctattagtc aatattcttt cagttgcaag tcagaaaacc aacttgaaat 105000tattatttat
ttatttattt atttttttga gacggaattt tgctcttgtt gcccaggctg 105060gagtgccatg
gcacaatctc ggctcactgc aacctccgcc tcccgagttc aagcaattct 105120cctgcctcag
cctccagagt agctgggatt acaggcatgg gccaccactc ccggctaatt 105180tttttgttat
ttttagtaga gacggggttt ctccatgttg gtcaggatgg tctcaaactc 105240ccaacctcag
gtgatctgcc cacctcagcc tcccaaagtg ctgggattac aggcatgagc 105300caccgtgccc
ggcctggaaa tgatcttaag cagacaaggg cttatgaaac taggatgcta 105360ggggctaaag
caattatttc caagtttctt gtgtcctttg cacatccccc tttttcttcc 105420cttcttcctc
tgcctctggt cagagcttct ggctccatgt tggcctaggg ctctcccact 105480tcagccgctt
tcttctgtga agtgtggtga tcatggacac agccgacccc agttttacag 105540cataccaagt
aagcaacccc agaagggaga aaatgcctgt atttcaggtt atagacatta 105600aaatgagtga
atgcacccaa aaaaggaatc atgtgactgt cttaggttat atgcccaccc 105660tttaactcag
ctgcagcagg gcaagatgct atattgtcat cagttgtggt agggcaagat 105720gctatattat
cagtccaagc agaatgacat agctctatag aaagactatg tttttataag 105780agtatggaat
atagtgcaga tgaaaacagt agatatacac taacatgtgg ctctaatgtt 105840taatttttat
tttttttgag acagagtctc actgtgtcac ccaggctgga gtgcagtggt 105900gctatcttgg
ctcactgcaa cttttgcctc ccgagttaag atgattctcc tccctcagcc 105960tccctagcag
ctgagattat aggcacccgc caccacgccc agctaattct tgtattttca 106020gtagagacat
ggtttcacca tgttggccgg gctggtctcg aactcctgac ctcagtgatc 106080cgcccatctt
aggctcctaa agtgctagga ttacagacat aagccaccgc gcctggcctc 106140atgctcaact
tttatttaga caacagtaca aattgtaatt ttacccagat gtaaaagagt 106200ctaagagacc
taaatagata ttttgtggta gattacatta atgtaatgta atgtaatgta 106260ggagttttac
attactacat ttgtagttgt tttagttgtt tttcattgtt tgtttctgtg 106320tatttctggg
gatttcatgg tgcaacagga ggactagagt ttattcccga tccctgactg 106380tcttacggca
gtacttctca gacctactga gttatacaac caggggtgta gggaggcaag 106440cagtcatcac
atttatttga ggactctcat gttttgtcta aaatattcat ccttatttta 106500taatatactc
cataattttc ccatataagt ttagataaaa gatgatacct taaaagtatt 106560ataacactaa
attgtcattc cgggaaaatg tgctgtgttc ctttcatttt aaataatctg 106620agatgaatgg
tgcaggctga gaaaaatagg cttttgaaat actttttggt caacatcgag 106680acttttaaca
tttgtcctat cttttagggg aatttagaca ttgggcatta tgtattcctt 106740ggatacatta
aaaggtgtta gataagagcg ctcacacttg ctgctcttct attgcaactt 106800gacagaagtt
acttctctaa accttagttt ctcatctgaa caatggaaat aatgatagtg 106860tctatctcat
agtattggtg tgagatttaa atgaaataat tcatgtaaaa ttgcttggtg 106920tgtggaaaca
tagtaacttt taactgttct cattaacttg gctatttacc tgtgttcttc 106980tatcattaca
tttcaagtta aaatttcaag gtttcacgtt gttctctctc caatgaatgc 107040agttaaatca
cttagatttt ctaatgagtt ttcctttaat gttatgcagt tgactagaga 107100gtgtatatat
attaagaaca taataccttc actatgtcca catgtgaatt aagagcttga 107160ggctatcaga
gggtagaaga tgagggagtg gggatgaagt atgtttgtaa cctgtgtatt 107220ttctctttct
taaaggaatt acggctcatc tctttttgcc caatgtgaag cagtagataa 107280tgggtgtcag
caggtcctgt ggctctatgg agaggaccat cagatcactg aagtgggaac 107340tatgaatctt
tttctttact ggataaatga agatggaggt aatccactca gatttcactg 107400tgtgcatttc
tcagtcattt tcaacaggac cagaaagaca agagctagaa acttagtaca 107460agggagtaag
tagcacagtt ccaaaggcta agtaaggact actgtgcttt tgctgcccaa 107520atagacacaa
gtttcttttt tttctttctt tcttttttaa agaggtggag tctcactatg 107580tcacccaggc
tgcagtgcaa tggtgtgatc tcagctcact gcaccctggt tcaagcaatt 107640ctcctgcctc
agcctcccga gtagctggga ttgcaggagc ctgccaccat gcccagctaa 107700tttttgtatt
ttttttttta gtagagatag ggtttcacca tgttggtcag gctggtcttg 107760aactcctgac
ctcaggtgat ccaccggcct tggcctccca aagtgctggg attacaggtg 107820tgagccactg
cacccggccg agtttcgatt taaagaagct ctagaggttt tttgtttttc 107880gttttttgtt
tttctggctc tagatgtact gattattgag atactgagat gtcacattaa 107940gggatttaag
ttaccatgat tggaagattt gcttccttat cccttctgca gttccccaac 108000aattttccta
tctgaacacc ttgcattgag acacaggtct cagatcaggt caatggtcat 108060tcaccatata
ccgtatataa aatgctagag taataaatgc agtgtactga ttctactgga 108120aggattttgt
gtactctctg gctgtaattg ttttaacaat tgttgccttt tctacatatt 108180ttgaaaatgt
atcacaatct ctccaaattt actctagaac tcaatctgat taaagagcac 108240cattttaaaa
gataaatcaa tgtatcttgg gattgtaact agatcctggt tcattcaaga 108300caatttcata
tatccactat agatatcaat atttctctat tatctttaat atcctgagta 108360ctcattactt
ttctttgctg ttttttttta ttagttggca gagaccatag gggttcagtg 108420aagtgttggc
aacgtgtatg atattgaatt aaatggccaa cggtgggaga aaaacaggca 108480tttatttcta
ttagaatttt gataatcata ccaaatttag aagcgtattt ttagacttgt 108540ttacattctt
aggttgttca tttcacagta gtaattatag agactagaaa tataaatgat 108600gtttccaaat
acttatgaag tctcagtgtt agtagtttca attaaatttt ttaaaatgca 108660gtttatattt
gaaagtagct acagtagcct ctcttgctct aatgttattt ggctacaaaa 108720agaggaaaat
ggtaatttag atgtggctga attcagagct aagtactaat tttagtgtta 108780gttgcagaga
ctaacaagat gagtcttata ctgcagtcag aggtagaata aacagaagat 108840atggtgagta
agccttgtcc tgggcttggc cattggtagt ccttggcata tgaaaaacca 108900gatacagatc
attctcatcc ttccattcct gctgtttgta cttggcactg tttgaaaata 108960aaatttatac
aggaatattt atgatttata aatttgagtt actgtatgtg acatataaca 109020aaagctacac
ttggaagatt gtagccagtg ttgacctctg cacttagaag ataataggcc 109080gattcaaccc
ttcttcccat ctgcccactc ttacccccac cccaaactcc accaaaaaac 109140cacacagctc
aaaacaaaaa cagttacatc attcagaggt ggtaccatca ttatttttat 109200ggatgggaga
tgtcagaatt taagtacact ctgaatcaga gctacatgat ttaaccagaa 109260acaccagaaa
ctgtcctggt ggaaaattgt tctttatcca aacaataatc atgaaacatt 109320tccaccatgg
cttttaaagg tcagaataga aatgagtgag tttgtcttct gcctcttgca 109380aaatatacaa
gaccttaaga ctgttagtta ctattcagat tatggttgcc tgggataact 109440ttagttttaa
tatactcctt cactttgggg atgttcatct aacagaacaa ataaaattca 109500gaataaggag
aaaggaaata gaatatatat ttgaagtaaa tagaatgtta ggaaaaacct 109560ttgggctaaa
aaaaaagaca tgcaattctg aagtaacttt gatttatatc atatgatttt 109620aagaaaatac
aatgaacaaa cgagttgaaa atcagcacaa tactgatttt cacaaacgtt 109680accgatagga
ggtataaaca gagttctttc ggtaatagcc tgccgtcttt tcatgagcgc 109740ccacacacac
tgctcctgtt ggttgagatg gctggtgcag gaaggtggat ggggtggtgg 109800atagtgtgtg
ttcaaagcac agtgctgtgc acagtcacta tgtgtggcac tcagcttgta 109860actcatggga
gttttgattt cagtaacagc acccatggtg gcaagatcac acatcatcac 109920tctgttgatg
agtaatttaa cccatacgct tgctattcac catttgaaca aagcattgta 109980tcatatcctg
gaccctggag ataccctgaa aaataagacc caggccttgt ggttgagttc 110040acagtcactt
tgggaaaaca accacagcag tgaatctcgg tattgctcag gccacatcat 110100gagtcttctc
ggacacgtca ggcgtgtata cggactcgac ttggagcact cttcctcaga 110160tgtctgtacc
gcttgctctt tgacatcctc caaatctttg cttacaaatc ccattctcag 110220tctggctttc
cttgagctct taatcaaaat cataaactcc atttcccatt tctcctcagc 110280attccagcat
tctccattgc ttttccttct ttgtttcccc ctgtgtagtc taacatacta 110340tcaacacaat
aaatgtttac ctgtgtctat tagaaagtaa gcagggagat atgtcagttt 110400tgttcactgc
tgtattcata gagcttaaaa cggtaaacag cactcaatat gtatttgtag 110460aataaatggc
taattgtgct gatggtgttt agggcactta tgcagaccta cattcctggt 110520ttccattagt
gtttgacttt gggaagtcac agatgaatcc tgctgttatt gcttctaaat 110580tcctcatctc
ctaaaaatga cttctttgtc aaaaacaagc tgcatttgta ggttctgttt 110640tcctcatgtt
gggcaatctg gagtgatttc tggctcttgt aagtatgttt gtggttgcag 110700aggaaaatga
atatttctca cccaaatgtt gtcatgtcat catctctgtc tggcaaccag 110760agaagcagat
gttctgttcc ttgacctcag gctagtggtt acagttctgg gtgttaaaca 110820tgtttcacaa
aacagcactt gcacatgcgg ggctgctgtt ttcatttaac ttcatgtagt 110880ctcagggctc
agcaagcttt aggaaaggtc cggtttgggg gcactggaag tgtgtgtgtg 110940tgtgtacata
tatatacaca cacaaataga tccatacatt tatgtatcta gttggctagc 111000tattgcaaaa
cacatgttta ttttgagatc atcaacactt ctaaacatga caaagagtag 111060ccctaagaac
attgccaaga acaaattttc tcctttccag aaagcaattt tcagcagatg 111120attttcagaa
acaaaattca aaaaagccat actgctgtat cctagcaaag ataacttatt 111180cgtttatttt
ttactcaaaa acatttatta tatacactct gggctaggca caatgcccag 111240ttttgaggat
agaaggatga agatagagtt tggtattcca gatagagctt gattgttggg 111300catgtctgat
gtaaccccag tggagtgggc gagcctagaa ccaccatgta ttgagggaga 111360gggtggtggc
ctcagtgtca ggactcacta gattcagact cctgggtgtc agaagtgggg 111420aggaaaggga
gatgctgagt gccagagggt actgtaagga gagcttgtgc agctgatgga 111480tcatgcatga
tgcctgtgaa caattgtcct actagacctc acagtagtta gggatgtctg 111540cagtcatctc
acagtagagc agtagctcag ctttggagtt ttgtttcttg aatgtcttct 111600tttttaaccg
tacacgtgct tgagctcact ctgataagcc cattacattt gaatctcaga 111660gagcaaaggc
agcatctcca tacttgttgc tgatgctcca ccaggtttga aaatcactaa 111720agatagactc
ttaggctggg tgcggtggct cacatctgta atctcagcac tttgggaggc 111780cgaagtgggc
agatcatctg agctcaggag ttcgagacca gcctgaccaa catggtgaaa 111840ccccgtctct
actaaaaata caaaaattag ccaggcgtgg tggcgcgtac ctgtaatccc 111900agctactcag
gaggctgagg caggagaatc acttgaccct gggaggcaga gggtgcagtg 111960agctgagatg
gtgccactgc actccagcct gggtaaccta aaaaaaaaaa aaaaaaaaaa 112020aaattagact
ttccaagggc agcgtggaag cagtgaccag cctgagtagg cacgcacact 112080tcttggggat
agcctcctcc atagcattct tagaaggttt ggtaatgacc agtttttctg 112140agtaagaccc
tatctacatt attctaatta gtaaccacct ttcatctgct aaggtaaatt 112200ttcacttcag
aatattcctc ttaagaccat gcaataactc ttactgtttg ttggtggaaa 112260accatctcat
tattttactg gttaagggta aactgaagat gattagataa ctttccttcc 112320ttccctcccc
ccttcctccc ttccttctct ttcttccttc ctttctccct ccctccctcc 112380ctctctcttt
ctttccttct ctctttcttt tcttttcttt tttctttctt tctttctttt 112440ttctttcttc
cttccttcgt tccttcctcc ctccctccct ctctctcttt ctttctttct 112500cttttctttc
tttctttctt tctttctttc tttctttctt tctttctttc tctctttctt 112560ttctttcttt
ctttctttct ctttctcttt ccttccttcc ttcctttctt tctctctctc 112620tccttccttc
cttccttctt tccttccttc cttctttcct tccttccttc tttcttcttt 112680ttttaaataa
gggtctacct gaagtgtgaa ctgatttggg aaatttgatc atgcagaaca 112740gtaaaatttt
ctttatgttt gttgctagca aaattgtgat ggttttttaa aaaaatggct 112800attgataata
aggcatgcct aatgtagtga aagtttgaaa atgtcccaat ttctgattga 112860cagaagaaga
actggcaact cctccactag atggcatcat tcttccagga gtgacaaggc 112920ggtgcattct
ggacctggca catcagtggg tgggtgcctt tgatatgaac aacttttgta 112980agcctgaaat
aaaaaataat caaaataagc ccagcctagt gttgaaataa tatcctgtgg 113040ttccaaccaa
tgttatctaa tctttaaatt ctaacgtgaa tgaaaagtat tcttctagaa 113100gggctttctt
ggcaagacta ttaaaataag tattgttgat agcaagggca gagagaaacc 113160agtttagcaa
gatgtcatag tggagaagta ttctagtagt agtctcagtc taccaggtat 113220ctcccaccaa
cttttgtctg gttcatacct gatgtgcttc catccagaca ttccttaact 113280tcccaagtct
gtgttgcttc caaatggcaa tgatacttct tcctttcctt tatttatacc 113340agtgtaacca
tgcttgccgt agaaatgaaa taatttcact gacatataaa tgtttactaa 113400tataacatta
ttggtttgac tgccttcttt ttctctctgt cctaccccca tcctccaaaa 113460ttcatataca
tgcctatttt aaaatcagaa catgcaagca aatgtaaagt tgttttcagt 113520agactttcaa
attcgtgtga cacaggcaag catattaaac aatttggtgg accgggtgca 113580gtggttcatg
cctataattc tagcattttg ggaggccaag gcaggaggat cacttaagcc 113640caggaattcg
agaccagcct gggcaacata gtgagacccc gaatctacaa aaaaatcaaa 113700aacattagct
gaacatggtg gtacatgcct gtagtcccag ctacttggag gggctgaggt 113760gggaggatgg
cataagatct ggaggtcaag gtcgcagtga gctatgatca agccactgca 113820ctacagcctg
aatacagggt gagaccatgt ctctaaaagt aaattaaata aataaataaa 113880taaataaata
aataaataaa taaataaaat aaaatttaaa aaggtttggt tttggaaatg 113940acgtaatgta
ttcaagacaa attattgaat gaattgggtg tctggtaaag gttcttggat 114000ggaacttttg
acccaggtgt taaaatggtc tccaaagaac atgaaaaggc tttgagctta 114060ctgtggtcaa
agagtactag tagtaatagg acaaatgttt agaaacacac acgttatcta 114120ggagcatacc
agcatggttt ctctggaaaa gactttcaaa atagatgaaa tgtgctataa 114180ataattctac
aaaaccctga agtagacaag acccaactgc tacatgctgg ctggcgcatt 114240gggcatgaca
tttacaaacc gttggtataa ttttcaaaca gcttgccctg tcctaaatat 114300gtttgcaatt
ggaaagatat ttttgaagct cagtaatttt tgttttatta aagaaaaata 114360tcaaccaagt
acagaaggtt cgacgacaag ttgcaagtgg aaatactttc ccacactaat 114420gatttgctag
catgaaaaat aggttattat ggaggaaatt ttttcttgac ttcatagctg 114480taatttattt
taaaagctat tttaaaacat gagacgtgaa atgccaagag gcatgtaggg 114540ggtcaccact
atttgccaga taggggaaat tgtccaaaga taagtaaggg tgagcagagc 114600aaaaacaatt
ctgcttattt acaaaagagt tttcttttct tttctttttc aggacacaga 114660actcagcttg
ttttcaatta atttgcctga ttttctgcag ttcatttact tttgaacaac 114720ataattgcaa
ttgtagactg agagaaattg aaactttcaa agagccatat ttctattgca 114780gatatatttt
cctgctcttc caaatctact tacagcatga gttcttcttt taaatattca 114840aatattttga
atattgccaa gagctttgat ttccattttt atctcttgtg ggtttataaa 114900ttaagaaaaa
atactcatct tattttttta aacctctcta tttttattgc cctttattca 114960aataacttgt
tgacaaactt tgaacttgaa ccactgaggt aaaagaacaa gaattaaaca 115020gatagtttaa
acacatagct taaaaggatc tttttcccat ttcctatcct tgagcaaaga 115080atatattcaa
acactttggc agaagtcaat gaggttatac cactaattcc atgatgaaaa 115140tcaactgaat
gtgatactga aagagaagga agagaattgt cactgtaaag tcaactgtta 115200gtcatattag
gaaaaaaaat acatacaata caatttctca aataaagtcc aaatatacat 115260tcaacgttta
aaaataatga gtatttcaga tatttgaact cagtctgttc tttattccat 115320aaaagatata
ggtaagccgt gcacagtggc tcacaactat aatcccagca ctttggcact 115380ttgggaggct
gaggtgggag gatcacatga gcccagcctg ggcaacatag ggagacccct 115440atctttacaa
aataaaatat aaaatataaa acctagttgg gcatggcagc atacacctgt 115500agtcccaggt
gctcaggaga ctgagacagg aggatcactt gggcctggga ggtcgaggct 115560gcaatgagcc
aagattatgc cactgcattc cagcctgggt gacagggcaa gaccctgtct 115620taaaaaaaaa
aaaaaaagaa agagacaaac gtagaaagag taccaaattt ggagccaatc 115680agatcagacc
tgggttcaaa ttgagtttct gtcacttact tcctttgtgg ccctggagat 115740gcccttcaac
ctccttgaac cttagtttcc tcatctgtaa aatggggatg atagtactca 115800cccttaaaat
tacagaactt ggcataatag cgggtgcttg ataaatggta gctataatta 115860ttaatattat
ataatacatt gttctccttt atggtaaagt aggttttaag acactgattt 115920ttttgttttg
ttttgttttt ggagacagag tctcactccg tcacccaggc tggactgcag 115980tgacgtgatc
ttggttcact gcaacctctg cctcctgagt tcaagcgatt ctcctgcctc 116040agcctcctga
gtagctggga ttacaggcac ccgccaccat gcctggctaa tttttgtatt 116100tttagtagag
acagggtttt accaggttgg ccaggctggt ctcaaactcc tgacctcaag 116160taatctgcct
gcctcagcct ccccaaatgc agagattaca ggcatgagcc accgtgcccg 116220gcctaagaca
ctgttaacac ggagcatgca tcaagcagca tttgggatgc atcaattttg 116280tgagacttta
tacaagttaa caaataagaa ggcaaaaaag aaggcatatg ttaaagtata 116340ccatgtgtct
tgtggtgata atcttatatt ttatattctg ataatctcat atataaatct 116400gtgaccttga
agtaggttac ttaacacctc gatgtgttca ccagtaagat ggtgtgccac 116460ttccagcttt
cccttaaagg atgattgtga ccttgtctaa gtgcaatcag aatgttaagc 116520agaacagtaa
gtattgcaat tgttttgcat gccttttcct ttaaaatata cttgttattt 116580tttatattcc
atgcagggtg aatttaaggt gtcagagaga tacctcacca tggatgactt 116640gacaacagcc
ctggagggga acagagtgag agagatgttt ggctctggta cagcctgtgt 116700tgtttgccca
gtttctgata tactgtacaa aggcgaggta cgacaagtat ttcctcattt 116760cctatcattt
ccaatcacat taaattacat ttaatttaag tgtatgaata aaattgtatc 116820tggacccaga
cccaagatgc aaaagttttg tcgttgttgt tgtttttctt tattttaaag 116880agatggagtc
tcgctgtgtt gcccaggctg gagtgcagtg gctattcact ggtgtgatca 116940tagctcactg
cagcctcaaa ctcctgggct cacgcaatcc ttctgcttca gcctcctgag 117000ttgctgggat
tacaggagtg cgccaccgca ccatgctagg tcttttttgt tgttgttttt 117060gttttttaac
ttggcactac aaaaaaaata actgggacag tttatccaga tgaaactgta 117120ttagcatata
tctactatgt ttccagtgat ttcatgtaag cttaaacatg gtgggaagtt 117180agttttgtcc
ttggacacgt gtaagatctg tcttacctac atgtcgggat tggagctatg 117240ccgacagtct
tctactcttc tctcttcctt cctaccagct cactagggaa ggctctatag 117300gtagttacat
ttcagtttct ggttaaccaa aagtacttcc aaaccactgg attaggaatg 117360gcaaatagtt
atggaaaatg cattcgagtg gtcaatccct tgattttttt ttactattaa 117420tgctgttatc
attaatagta agtagaccac tttacaagaa ttattcattg gcaaacctgg 117480tgcatttact
aaaatcttac aaaaggaatt tgaggatttg gttggaagaa atgttctcct 117540cttagtaaat
tagtctgatt ttatatgtgc catacttttg ttttcttgtc aaattgtttt 117600gcttttcact
ttataacaaa gctccaatac ttatgattaa cattggcatc taactttata 117660acttaaaggc
atgtaagtat tagtcttata atgtgaactg gcttaagtta ttcatattat 117720agcagatcct
tgaacaacac agggattagg ggtgtcaacc cccatgcagt tgaaaaatcc 117780acatacaact
ttttttgttt gtttgttttt ttaaacgggg tctttctctg tcacctgtac 117840tggagtgcag
gggcacaatc tcggctcact gcaacctccg cctcccaagc tcaagcgatc 117900ctctcacctc
agtctcccaa gtagctggga ccacaggtgt gcaccaccac acccagctaa 117960ttttagtatt
ttttgtagag acggggtttc aagatgtttc acaggctggt ctcaaactct 118020tgagttcaag
tgattcacct gccttgacct cccaaagtgc tggtattaca ggcgtgagtc 118080accatgcccg
gcccacatat aacttttgac ttcccaaaaa cttaactact agtagcctgc 118140tgttcaccgg
aagccttatc aacaacaaaa acagtcgatt ggcacatatt ttgtatgtta 118200tgtatgttat
atatgtattc ttacaataaa gtaagttacg aaaatcatgg ggaagggaaa 118260atatatttac
tattcattac atggaagtgg atcatcataa aggtcttcat cctcattgtc 118320catcatgttg
agtaggctga ggaggaggag gaggaggagg gattggtctt gctgttttag 118380gagtggcaga
ggcagaagaa agtccacgta taagtgaact tgtgtagttc aaacccgtgt 118440tgttcaagtg
tcaaccgtaa atgcaaactc cactggtttt caaattttac tttagagtta 118500ttttccctca
gctgattgga gttttgctca actcctctga ctttaataat ggctgcttca 118560tttgttgagg
ttttagaact tgcttttaag ggattgctct tgacataatt gcatcaacag 118620atagactgtt
tcatgggaga agaattgttc tgtttcatgt caatacttac attgataaga 118680atgcatcaag
gtaatgtgat ccatccactg aagttgtcat taggccagat tttttttaag 118740ttgaattatt
atttcacttc tagaaataag aagtttataa agtttagcat aattttaatg 118800atccaggctt
aggaagcatt tacagccaaa aagtaagtat atataattat catattatac 118860taaagggtat
aatatgaaaa gtgtttgaga gcacagacta tctcctaaaa tcaaactatc 118920aaaacctgca
agccagcaag gcatgagtag gcatgactca gatacaaatt agaagcatga 118980aatctctttc
agccatgcat ttaatcatgc tatccaatat tgtggaggta gtggcccctg 119040gaagtttacc
ttgggccaga gataggtata gaagcccctt ttatgaagtc atagacttgc 119100tttaatttat
gctcccagaa tgacttgcat taaactgtgg caaaatatct ttgagttctc 119160atattagcca
gagggttaat atgtagaaga caatcattca tccttacaga ttctcagaat 119220cttggaagag
gtagggttct ttaagtttag ccactatttt aggtaactgt agctcctcct 119280tggttcttca
aatgatcctg aaggctggta tacaaaccag ttatgcccta aaattaattg 119340gtaggtaggc
aatgtataac ctgtcattgg ctagttttta ttcaaatttt ggatatgaaa 119400gtctttggca
taaggtgcta gcactcagag tcagtaggtt ttagtgctat tccttaactt 119460cagtggaatt
gccttagtat agcagaattg cttgagtgtc ttatctgtta tcaccatata 119520catgagtacc
ctcaaattat ctcatttccc tttcttttgt agacaataca cattccaact 119580atggagaatg
gtcctaagct ggcaagccgc atcttgagca aattaactga tatccaggta 119640aagcttttct
tttcttttct tttctttcct tttcttttct tttttttatg tcaccttatt 119700tctgtcagag
cttacaacta aattatattt caatgaagag gattaaataa tacaatttga 119760gatcaataag
ttaaatttaa ggaagatatt cccaacacaa tgtgtgggca tgagcaaagc 119820agaaatggga
aagaagatgt atgttttaaa aaaagaaaga aaatattgtt caggactcca 119880cattacttaa
cattaaaaaa tagatgtaat ttttggtaac atttaaaaat ctcattaaga 119940aggataacat
aacttttgtt aaaaaaagga agaaaaaatt tgaaagtaga agcaacttca 120000ggaagaaaat
tacagtgcat gtgattccaa cactgagata taatcactgt taatttttta 120060tgtcttttta
tttttgagct ggagtttcac tcttgttgcc caggctggag tacgatggca 120120cgatcttggc
tcactgcaac ctctgcctcc cgggttcaag caattttcct acctcagcct 120180cccgagtagc
tgggattata ggtgtgcgcc accatgccca gctaattttt gtgtttttag 120240tagagatggg
atttcaccat gttggccagg ctggtcttga actcctgacc taaggtaatc 120300cacctgcctt
ggcctcctaa attgttggga ttacaggcat gaaccactgt gccctgccat 120360tttttgatgt
cttaaccttc aatattttgt aagcatttat atactttatt tatttattta 120420tttatttatt
tatttattta cttatttatt tttgagacta agtctcgctg tgtcacccag 120480gctggagaac
agtggcatga tctcagctca ctacaacctc cacctcctgg gttcaagcga 120540ttcttctgcc
tcagcctccc gagtagctgg gattacaggt ctcatgccac cgttcccggc 120600taatttttgt
atttttagta gagatgaggt tttgccctgt tggccaggct ggtcttgaac 120660tcttgacctc
aggtgatcca cccgccttgg cttcccaaag tgctgggatt acagccgtga 120720gccaccatgc
ccagccagta tacttttaga tagttatttt ttcctaacaa aatgggatca 120780tattgtacat
aattttgtta catgtttttt cactgaataa atgctttgct tttttatatc 120840aataagtagt
tttctccaac accatttata aagtttaatt gaattccatt atattgatgt 120900accataattt
ttttaaaaaa ttatattatt gaacatttat gttgttggca attttttttt 120960cactagtatg
gacagtacat cctcgattac ttcctaagga taaatctggg atcaaagagt 121020atacacgtct
attttttcat actgctaact ttgttttgcc tatttttttt ctgagcaata 121080atctacagta
atgcctcatc aggcagttaa gcaggcatgc taaataccag ataacactgg 121140gctactcaga
aaagagatta tcctgtaatt tgcaagcatt tcacaagtta gaagactttg 121200ttgaagccag
ttactatcct tgtcaattag taaaaatatc caagagggcc tgagacttac 121260attgaaaagt
aaaataaagt ttgatcattt gagtgatgtc ggatggcatt aagtcatgaa 121320actaagtgaa
acttaaaggt ggctgagaat gcaacaggcc tccagagagc aatggaggtc 121380cttgggtagt
gataaaaatg gcatttctgg ctgggtgcag tggctcacac ctataatccc 121440aacactatgg
gaggccaaga caggaggatc gcttgaggcc aggtgttcaa gactagccta 121500ggcaacatag
tgagaacctt cctctaaaaa aagggaaata aaataaaaat aaaagtttaa 121560aagagagttt
aaaaggcagt tttaaaagag acttactcag caagttttct gccaaattta 121620cagtattaaa
aagaaagaaa gtgtgttttt gtttctgttt gtttttttga gacagagtct 121680tactctgttg
ctcaggctgg ggtgcagtgg tgcaatctca gctcactgca acccctgcct 121740cctgggttca
agtgattctt gtgcctcagc ctcccacaca gcagggatta tgggcatgca 121800ccatcatgcc
tggctaattt ttgtattttt agtagagtcg aggtttcgcc atgttggcca 121860ggctggtctc
aaactcctag cctcaagtga tttgcccacc ttagcctccc aaagtgctga 121920gattacaggc
atgagccacc gcaccctggc cttgattgtg gttttttaat caatgagctg 121980ccatacttct
gctctccagc aaaggttttc tatgagaatt ttctgtaagc taagtaaagg 122040aatatcttaa
tattggaaga aataaaattt agtcagagtt gttttctacc tttgtacaca 122100gcaacactta
caagtaattt gaagagtagc taataaaaat ttctgcatgg atggcttagg 122160cattttaatt
tttttaaggt tgcctgagta aatctgaaaa taataaatta ttacagtttt 122220gctcaaataa
agaacacaaa tagaacaaaa aatacataac tggctagatt acatgaaagc 122280ctttttccaa
aacagaggtt tagaggccag ggcaaatagg caggaaaaat aaataaaggg 122340catccaaatt
ggaaaagaag aagttaaatt agctttctta gcagatgaca ttatcttaca 122400cctagaaaaa
cctaaagact ccctcaaaaa acctgtagaa ctgataaatg aattcagtaa 122460agttgcagga
tataaaatca acatataaaa atcagtagaa tttatatatg ctaacagtga 122520acaatctgaa
aaagaaatca agaaagcaat cccatttata atagccacaa aaagtataaa 122580atacctagga
atcaatctaa ccaaagacat gagagatcta tacaaggaaa agtataaaac 122640tatgatttaa
aaaattgaag aaaacacaca aaggtggaaa gatattccat attcatggat 122700tggaagaatt
aattttgtta aaatgactat actacacaaa gcaatttaca gattcaatgc 122760aatccctatt
aaaatactga tgactttctt cacagaaata gaaaaaacaa tcctaaaatg 122820tatatggagc
taaaaagacc ccaaatagcc aaagcaatct tgagcaaaaa gaacaaagtt 122880agaatcacca
cactacctta cttcaaaatt tattataaaa ctataataac caaaacagca 122940tagtactgat
ataaaaacag acatagtaga ccagtgggac agaatagaga acccagatac 123000ctaagtccac
atgtttacaa ccaactcatc tttgacaaag gtgccaagaa ctgtaacggg 123060gaagacagtc
ttttcaataa atggtgctgg gaaaattgga taattatatg cagaagaatg 123120aaactagatt
cgcttctctt accatacaca gaaatcaaat gaaagtatat taatgacttg 123180aatcttagac
ctgaaactat gaaattactt gaagaaaaca ttaaggaaat gcttcaggac 123240attggtctaa
gcaaagatct cattctgtca ctcaggctgg agtgtagtgg catgaacctg 123300gctcattgtg
gcattgacct cctgggctca agcaattctc ccaccttggc tttccatgta 123360gctagaacca
caggtgcatg ccaccacatt ccactaattt ttaaattttt tgtagagatg 123420gagtctcacc
atcttgccca ggctggtctc gaactcctga actcaaggga tcctcctgtc 123480tcagcctccc
aaagtgctga gattactagc ataagccact gtccctggcc agcgaagatt 123540tcttatgtaa
gacctgaaaa agcataggct atcaaagcaa aaataggcaa ttgggattat 123600gtcaagctgg
aaagcttctc cacagcaaag aaaacaatcc acaaagggaa tagattaccc 123660aaagaatgga
tgaaaatatt tgcaaactat caatctgaca agggattaat aaccagagtc 123720tataaggagc
tcaaacaact gtataggaaa aatctagtaa tctggtttta aaatgggcat 123780gagacctgat
tagaaaactc aacagaaaaa aaaatttgat taaaaatgga taaaagatct 123840gaatggacat
ttctcaaaag aagacagaca aatggccagg aggtacatga aaaaatgcgc 123900aacatcacta
attatcagag aaatgcaaaa caaaaccaca atgtaaaatc cacttgccct 123960agttaaaatg
gcttgtatta aaaaaaaaaa aaaaaacagg caataacaga tgctgggagg 124020atgtggagaa
agggaaccat catatattgt tggttgaaat ataaatagta cagccactat 124080ggagaacagt
atggagggtc ctccaaaaat aaaagtagaa ctagaacttc cgtgtgatcc 124140agcaattcta
ccaccgggta tatatccaaa agaaaaaaat tagtatatca aagagatatc 124200tgcactccca
tgtttattgc aatagtattc acaatagcca agatatggaa ttaacctaaa 124260tgtctgtcaa
cagataaatg gataaagaga atgtggcata aagatatata tatatatata 124320tatacacaca
cacacacaca cacacacaat gtggtactat tcagccataa aaaagaatga 124380aatcctgtca
tttgcagcaa catgtatgga actggaggcc attttgttaa gtgaaataag 124440cgagggaccg
aaagacaaac atcacatgtt ctcatgcagg tgctaaaaaa gtagatccta 124500tgaagacaga
gagtagatta gaggttacca gaggccgaga aggggagtgg gaagtagagg 124560ataaaggaaa
aaaacaagaa tataaatgta tttattacca ttaaactgaa catttaaaaa 124620ttgtaaagat
ggtaaattat atatgtgtat tttatcttaa ttaaaatttt aaaaatcagg 124680agtttagaaa
tttttaagag aagtgtgccc atagtgataa gaaagaaaga cccttttgga 124740aaattttctt
gaacaaatta tacagtattt tcttaaacaa attgtacatt ctgtagcagt 124800taatacacca
aataagattt cagggttacc tcttggagat tgtatgaaat aaaaacattt 124860aggtgggcat
gatggctcat tcctgtaatc ctaaaacttt gggaggctga tgcaggaaca 124920atacttgagg
ctagtacttc aagacgagcc taggcaacat agtaagaccc agtctccaca 124980aaacaaccaa
aaaaaatagc aagtgtggtg gcacacacct gtagttccag ctactcagga 125040ggctgaggca
ggaggaacac ttgaggccag gaatgtgaga ctgcagtggg ctatgattgt 125100gccacagcac
tccactccag ccttcactgt agaaagagac cctgtctcga aaggaaggag 125160ggagggaggg
agggagggag ggagggaggg aatgaaggaa ggaaggaagg aaggaaggaa 125220ggaaggaaat
gtaaactcat ttgatttggc tgtaaaggat taatagaaaa ggaaaacgta 125280gtcactaggc
tgagaaaaat tgaactctat tgaattggta taaagatcta agtggaggtg 125340tttggcagac
atgatcatga agctttcact gaggaaggaa actctaggag gcaaaagcag 125400aaatgcaact
catcaaaatt gaaatggtga caaaatatgt gcattcaaac ctgaaagtga 125460ctgaaagaga
agcccaaaca cacaattttg gggtaagatg ggaaaccatt accaaagttc 125520tcagaaagag
catttttaaa agtaagatta tagaagccaa aaggatatgt agtagtctgt 125580tctcacactg
ctgtaacgaa ctacctgaga ctgggtagtt tgtaaagaaa agaggtttta 125640ttgacgctca
gttctgcagg ccatacagga gacatggctg gggaggcctc aggaaactta 125700cagtcatggc
ggaaggcaaa ggggaagcca gtacatatta catggtggga acaggaggag 125760gagagggagg
gtgggaggtg ccactcactt tttaaaacaa acagatctcc ttagaactca 125820ctcactatca
tgagaacagc aagggggagg tttgctccca tgatgcaatt acctgacacc 125880aggcccttcc
tccaacatgg gggattacaa ttccacatga gatttgggtg gggacacaaa 125940ttcaaaccat
atcagaatgt tagtgactaa agtaaatgtt cttgtttaac tctttaatgt 126000gtatattgag
tgcaagccat atgcaggggc tattctaggt actggtggtt tactcaagaa 126060aaagggggca
aaaaaatgaa gaaggtggcc aggcatggtg gcttacgcct gtaatcccaa 126120cactttggga
gactgagacg tgagaattgc ttgagcccag gagtttgaga tcagcctggt 126180aacatggcaa
atccctgtct ctacaaaaaa atgcaaacaa acaaacaaac aaacaaacaa 126240attaatcggg
catggtgtca catgtctgta gtcccagcta caggttgagg tgggaagatg 126300ccttaagcct
agggaggttg aggctgcagt cagccatgat agcaccactg cactccagcc 126360tgggcaacag
agtgagaccc catctgaaaa aaaaagaagt caaaacaaat gaaaaaaaaa 126420aaaaagtcaa
aacaaatatt cagtgtaaat gtgagaccat gtaaaaaagt ttaaaagtaa 126480aatatatagt
ttaagcagag gatgggagac ggggaaaaaa ccttttctcc ctaactttat 126540atactccctc
tataaattag tgcttatggc caataagaaa tgaataattt cttttttcac 126600cgttggtagt
aaagtataat ggtagttaac acaaaaaact aaatgatata ttcagaacct 126660catactaaac
aaagaaacaa aggcatgcaa tcacaggaca ggtggaaaca gtggttctga 126720actaaccaca
aaccagaact accaaatgtg ctacaaattg tttagtaaca aaggaccatc 126780ccttcagaat
tgaagagcac gtctcagtta tctcatgcct atgtgcatgg aacttaaagt 126840ctcaaaatta
ctcttacaag atggcaaatt gaggctgtca gctaagctcc tagattgtct 126900gtttctccaa
gaaaaataaa tttcagtaat tattaaggaa aaagcataga attgcatcat 126960gttttacatt
tcattacttt tggcatgaca tgggagcatg gatgttttct acaaagtgct 127020ctgataaatt
gaagaagagg ccaacaacag ccaccgaaaa aaccttcaag attcttgcca 127080gtatggctca
ggggaaaaat tccctcataa ccacagattt gacttttcaa cttctgtact 127140tctgcatatg
agtaataatc tctgaggtta agtattcatc ccatttagct aattgtccac 127200ataactccct
gggtcttaga ttgctctata aatacctcct aagagaagaa tttttcaaat 127260gacagtttcg
tttttccttt ttcttctttt aaagcaacaa agaaaagcac gtctgtgttt 127320atatttaacc
aaacttaaac ttggagagca ttggccgtgt tgtcgacgtg tttcttttct 127380ctactgttaa
attccttact gttccagtta ctcaccatca tactcacctt tgcctctgcc 127440acttggggtc
ctctgttctg cagttgtgtt ctgctctctg atgcctccag gttttgctgc 127500accttctaga
aattgctcac ctggataagg ccttggctgt cctttatgac tcatctcgtt 127560cagaagcctt
ttgaatctct cttgaagaat attccctttg ctcagtccaa atacacattc 127620actcacttga
atgctgcttc ttcctccagt ttcacagtgc tggggatgat cccgtaaggc 127680ctttaaatta
cattataatt agtcatgcac ttctctctgc tctggggctg tttgaatcgt 127740tcactctctt
tatacctcca gtgttcagca cagagcctag ggtataatgc gtatgcagta 127800atgtttcttg
aaggagtgaa tgggcaagtg aaacaccaaa caaatactaa agagcaaaac 127860atgtattgct
cttgtatatt aacacattcc gagaagagat gggaggaagg tcttgaataa 127920tatcaaatta
tttcttaaga gatcttgatt tagatttttt tcaaaatgag atacatgttg 127980acactgctgt
caacaaataa tcacataaaa gctagagcct ggcttttaag tatcaggggg 128040agcatgtgtg
aataatcagc attgctgctg ttgaagctcc ataaagtggg aagcagcgac 128100tgcaaagatc
cagagatgga catctgaagc ataggaaagg ggcagcttga atgagatagg 128160agcaggatct
gtattgattg caggtcacca gatagaatta aaaaaatcta tgttctcact 128220agtggctaca
gttttcaagg acaaatgact attagtggtt attgtatttt tcttgttttc 128280aatggagcag
ctccatgact tagttacata agaagttaaa ggctccaccc ccttccctac 128340caatgtctta
agctgtcctc cgtgtgcata caaactttgt ttccagactg ccctcgtgtg 128400actcagtccc
tggaccagct tcccagcccc ttctgtttcc agcacatcct cctccacgtg 128460ttacaggatt
acaaagcttt gcacagcctt tcaatagggt ttagagcaag aatgacagat 128520tgctacctgg
taggcagcac tgactatagt tttattggcg ttgcgtagag tgactgcatg 128580acatgcaggt
tgtgcttttg ttttgccagg aatttaaagg catttagcaa agccgtatga 128640aattatctgc
cttatgtacc tcgaatgtga ggtaatgaac ttgtcattag tcgtgtttta 128700gtttagtgtt
ctcgctggaa tttgcaaaag attaaaattc tgcacatttc attaagtctt 128760ccacatgggc
tcaaaatacc atcccgcagg ctcgacctga cttgccacgt tgctttgaca 128820ccatctctga
ttccagtgaa caaaactaag taagtgtgac ttacagccgc cctaccaaac 128880attgaaggtg
tgagcctgca ctgttgtttt gtaatgacaa tgacaagagt ataatgacaa 128940gagtataatg
acatcctagt ccatgaagac atgttttctc ttttccctcc ctctatgtat 129000acttacttac
tcttaaggaa ataatataat ttctatttct gcttaaatct gccatctcta 129060cttagaatta
ttttcccttg aaaaattaaa ttgcattatc catcagccaa atggaaaatc 129120tgattactaa
atgcctactt ctagacatta tgaattacct gtaatatcac atttcttggg 129180cacttctcag
aatgctatga ttttacataa aagcataaat tacagaatga gaagagtaaa 129240gcttagtgca
tattatgcag gttcgcagag tgatatgtgg cctacgactg tcattgtaat 129300caaaattgat
ttttgatcat ttataaaact aaaacaacta attgaaagca aatttacttt 129360aactgatgaa
attcaagatg aagtgacagt agtcatgaat cacagttctg tagatctgct 129420aaaatgccaa
tgaactgtta ttaatggtga aagtgtttaa tatattaatg ggaatccaag 129480taaggaaaat
aaaacacata ttttgccctt accttaagtc atgttgacat catacataaa 129540tcaggtagaa
tttgaagatg tttcatccag cattcatcat gaagcaacag agtcaatagc 129600gggcagttac
agtctgtagg caatgctttc tggtgtggat tatgcaagaa acttacagtc 129660atttggcttc
ctttattccc ctttgcatgt aaactaccag gtggtaggta gacccattct 129720tggctgccag
tatttttacc acttggatag attctgctct ctgaggtctt taagacaaac 129780acagcacatg
tacattgtga tataggagaa agaacatcag acagaggcag agaactgggc 129840ttgtcaaaat
taagggtgac ctagagcctt agtgtcctta tatgtaagat gagaagcttg 129900gattaaaatt
cattgctcct tacacttgat ttttatgcag cagaactttc ttcaaaagag 129960atcactcctg
gaatcccaat atacaaaatg gataaaagta ggattgttct gaagtaaaga 130020agtaaaatcc
agagccccac ttatttgagt catctcctac cttttagatg gttattaaca 130080ttgtttctag
ttcagaaatt ctgatgtttt atattaattt aaactaaagt taaattagga 130140ctagaagagc
catttcgtgt gaaaatagac atagtctgag tgatttaggc aaacccatag 130200tgacagattt
agtggcctga tacactggct tggaaagatc tgttccaagt cagtctcaat 130260acacaaggct
cggtgaacac atggcgagca gtcttggtgg tggtcaagaa catggaattt 130320gctgtgagag
agagcttggt tagggtctgg gctcttccat ctgttaactg caaacttgag 130380caagttattc
aatctcccta atattcagtt ttctcattca taaaatggat tgataatggt 130440accttctatg
tacagttact gtgggtatta aatgaggtaa taagcctgta aaactcctgg 130500catgatgaca
ttggcctaca ttaattgctc acagagtgag aacttattat aaacacaggc 130560atttttgttg
aatgactgac tgattgaatg aatgaatata gaactagctt tctatttgtg 130620atgtatggaa
tatctctatt tcatttaatt tcattttgaa tattaaaatt caggcttgct 130680tttaaaccaa
agtatttgct gatgcaaaga atgaaattct gactatgata cagttacata 130740acttttgaag
aaataagaaa aatgctaaca cagcatgaac aactttgatt tagagaacag 130800agtctctgtt
aaaatccatg ggacttgtca acttcatatt tttgtttatg agcataaaac 130860actctttagt
gcatgtcgga atcatttgat gcttgctgaa tcacaggttg ctggaaccca 130920tccccagatt
ctgattcagt ctgagatgag gtctgggaat ttgcattttt aacttgttgt 130980ctggtgatgc
tgatgctagt ggtctgagaa tacactttga ggatcacttt ttcacagtaa 131040aagtcacagt
cattaagcaa gttaactcaa tgagaaatga taatgaaaag gcatgtacct 131100aaatagataa
aggacctata ccagctatga atttgagttc agcaataatt gtaaaatttg 131160taattctttt
caggtatttg gtttttaaaa aactccctat gtatgctttt atcttatgtt 131220ttatatggtg
tccctctttt cctctctttc tctctaatcc agtttttaat gtgaacatgt 131280ttaatgtgaa
aatgttgttc aaagcagaag cgaacctttt gtgtaacctt ggcggtatta 131340agtttgtttg
taagctattt ctgccctgtt agcttctgta ctgaaacacg ttttcttgct 131400tttgttgcag
tatggaagag aagagagcga ctggacaatt gtgctatcct gaatggaaaa 131460tagaggatac
aatggaaaat agaggatacc aactgtatgc tactgggaca gactgttgca 131520tttgaattgt
gatagatttc tttggctacc tgtgcataat gtagtttgta gtatcaatgt 131580gttacaagag
tgattgtttc ttcatgccag agaaaatgaa ttgcaatcat caaatggtgt 131640ttcataactt
ggtagtagta acttacctta ccttacctag aaaaacatta atgtaagcca 131700tataacatgg
gattttcctc aatgatttta gtgcctcctt ttgtacttca ctcagatact 131760aaatagtagt
ttattcttta atataagtta cattctgctc ctcaaacaaa tgcaattttt 131820tgtgtgtgtt
tgaaagctaa tttgagaaaa tttcataggt tacatttcct gcagcctatc 131880tttatccaca
gaaagtgttt tctttttttt aaatcaagac ttttaaaact ggatttcctc 131940ccatcactgt
tttttgaagg tcctccaagt ccgtgttaag gtaaatatct gttttcttcc 132000tgatgtcaca
gcctgagcat actctgtgca ttaggaagac ctgagtgcat ttcccaccat 132060tgtcctttcc
acattatgtt gtagctggct ggctgtcagg cgactacaag actgagggtc 132120ttgtgcctta
tagatctttg tatcccccat ggctgacata tagtaggtac tcagtaaatg 132180gttttataat
gaatcagtga acattttgct tctatagaag tgtaccttct ttgtttctat 132240attatgaaac
ctctttatta gaatttgtga ttgattctga cagtgtatag atttacctta 132300tattgtcttt
attttccatg agctactaag tcattagaga tactctgaag catagttagt 132360ttaggaaatc
acttcatatt gattgtatta gaattatctt ggaattgaag atatatccct 132420agagcagggg
accccaaccc ccaggccatg ggccacacag caggaagagg tgagtggtgg 132480gccattgagg
agcttcatct gtatttatgg ctacttccca tcactcgaat taccacctga 132540actccacctc
ttgtcagctc agtggcagca ttagattctc ataggagcac aaatcctatt 132600gtgaactctg
catgcaaggg atctaggcta tgcgctcctt atgagaatct aatgcttgat 132660gacctgaggt
gtaacagttt catcctgaaa ccacccttca ccctgcagtc tgtggaaaaa 132720ttgtcttcca
caaaactggt ccctggtgcc aaaaatgttg gggaccactg ctctagagag 132780aggtcatgat
atcataccaa ccaaatggaa atgacaaatg ttttatgtca agtgttaatt 132840gcagaaataa
atcttttttt tttttttttg gtagaaaaca aagaggcata ctctgatttt 132900tatactctgt
ttttgcaggt gctcttttct ttgaatggag atttgatgag caagtggtta 132960ggatgcaggg
agagctacta tgggtgatat tttccttgtt taggagctgt gagttaaaat 133020tgtatccttt
gtggtttatc taaggaaagt caaatcttga cagaaaacat ttttccttgg 133080aaggtcaact
ctcagacatt gtattttggt ttccctcagt cctcataact tccttcttgc 133140tgaacatatt
ttattctctt ttcagagaag gaaaataaaa aggattctaa aagtttgatg 133200cattggaaaa
atttccttga ggcatttagc aacacataga aaatgggctt tgattctttt 133260ccaaaacttt
tagccatagg gtcttttata gacagggata gtaaaatgaa aattgagaaa 133320tataagatga
aaaggaatga taaaaatatc ttttaggggg cttttaattg gtgatctgaa 133380atcttgggag
aagctgttct tttcaggcct gaggtgctct tgactgtcgc ctgcgcactg 133440tgtaccccga
gcaacattct aagggtgtgc tttcgccttg gctaactcct ttgacctcat 133500tcttcatata
gtagtctagg aaaaagttgc aggtaattta aactgtctag tggtacatag 133560taactaaatt
tctattccta tgagaaatga gaattattta tttgccatca acacatttta 133620tactttgcat
ctccaaattt attgtggcga gacttgtcca ttgtgaaagt tagagaacat 133680tatgtttgta
tcatttcttt cataaaacct caagagcatt tttaagccct tttcatcaga 133740cccagtgaaa
actaaggata gatgtttaaa aactggaggt ctcctgataa ggagaacaca 133800atccaccatt
gtcatttaag taataagaca ggaaattgac cttgacgctt tcttgttaaa 133860tagatttaac
aggaacatct gcacatcttt tttccttgtg cactatttgt ttaattgcag 133920tggattaata
cagcaagagt gccacattat aactaggcaa ttatccattc ttcaagactt 133980agttattgtc
acactaattg atcgtttaag gcataagatg gtctagcatt aggaacatgt 134040gaagctaatc
tgctcaaaaa gatcaacaaa ttaatattgt tgctgatatt tgcataattg 134100gctgcaatta
tttaatgttt aattgggttg atcaaatgag attcagcaat tcacaagtgc 134160attaatataa
acagaactgg tggcacttaa aatgataatg attaacttat attgcatgtt 134220ctcttccttt
cacttttttc agtttctaca tttcagaccg agcttgtcag cttttttgaa 134280aacacatcag
tagaaaccaa gattttaaaa tgaagtgtca agacaaaggc aaaacctgag 134340cagttcctaa
aaagatttgc tgttagaaat tttctttgtg gcagtcattt attaaggatt 134400caactcgtga
tacaccaaaa gaagagttga cttcagagat gtgttccatg ctctctagca 134460caggaatgaa
taaatttata acacctgctt tagcctttgt tttcaaaagc acaaaggaaa 134520agtgaaaggg
aaagagaaac aagtgactga gaagtcttgt taaggaatca ggttttttct 134580acctggtaaa
cattctctat tcttttctca aaagattgct gtaagaaaaa atgtaagaca 134640aaaaaaaaaa
aaaaaaacaa acagaggcag aggcaggcag tagcaagaaa gcagagcgta 134700acatcagcta
gatggtaaca tgcaatgtca gctctcttga agacatggga aacctaagtt 134760acaccttggg
ttaaaattct tcaccatatt agttttgttg cttcataaaa tttacctaag 134820caagtggtct
tgcttgcctc aaatccaagc agtcttgaac acttggaggc aattaatgag 134880tatatcttag
tcaaaagaat tgttggagct ttttattaaa gctacagttt cagttctgct 134940tttggggaat
tgtgctatga aagcagctgc caaaataagc tcatttattt tcttcaatcc 135000cactcagtgc
tcagtcacta tattctgttt cctttttttt tttcaagttg catatttggt 135060ttccccttat
gattgggaaa gatgaatttt cagcagaaaa cattgtttgt tcactttcaa 135120agagtgatag
tttctaaaac atttagagca ataaatattc atcagaggta ccaagtaagc 135180cggcagaaga
gttaagggtt agagaaatcc cttatttcat gtcttgactc taaaattatc 135240aaagtacttt
tccttgtaat gtggatttct tcttatgcgg atatgcaaaa acttcagtta 135300tacgtagtaa
tgctagcagg taattttagt agacatttta taacaactgt cactttgttt 135360cgccacatgt
agagtttgtt cagctatttt ccagatatct ccccacaaaa ggaggcaaag 135420ggtaccagct
tttcaatgag cattacctat tacttggcaa agatgatgaa gactctatta 135480atagttcatt
tgataaatgt tgacataacc aacaatagag attaggaagt tagttttaag 135540aaatcaatgg
catatagaca ttaccctcat ggagtttgta ttctactact tgaactgatt 135600gtagctataa
aagcatagtt agatagctga atagttagat cataagcaaa gaaggccaga 135660acacatctct
tatcaagaaa tcaatgaata gtttatctca tttttaaagc aactttatcc 135720ttctttaatt
ccttcctttc ttctagtgca aaactactta ataaggttgg tgtttaggtt 135780agtgttcaca
ccattcctca tctggtgtga attaccttct ctttctttac tatttactac 135840caacctagta
catgtgttga ctgaattctt ttcaaacaat gttgagttat catggtgcac 135900ctaataaatt
aacaccacag attacagcat ccttgctgat tttctcagca aagccagatt 135960agatggaaat
aaacaaagaa aatgatccta gagtgaattt ttctagaaaa tatctattat 136020gaaccatgct
gtttaaagta ttagcttgaa ggtgatggat ccagctattc agaaaataac 136080tttcatataa
ccatgatttt gcacagtatg aggtcttaaa tgtgtggaaa gagataaatt 136140ttttatcatt
accacaaacc ccttttaaag attcaaaggt ggaagaaagt gatttatttt 136200ttctcttcag
catacatata taaaagactt gtcagatgtt taatttgggg aggttgataa 136260tgaaacatat
caacagagta tagtagttat agtagtgttt gtgggtaaat aatttcctgg 136320ggtcagacat
atataaacat atttgcttca aaatgataaa ggcatgaaat cagtcttaaa 136380aattgaaatg
ggggtgatgg gggagaaaaa gaagaacaaa tttgaagtgc cctttcaaat 136440ctgctggata
caagtattga agttttaagt catcttattc tgtctgaaag tgtatttttc 136500attctacaat
agacccaatc aacaagacgt ataacttgag ttgcatgatg ttcagtttat 136560gtaatctact
gttgggatgg taagaattga tgtaggctgt ggtgtaagaa tgaattaaaa 136620tatagtttca
ctggcttttc tctacatatc cactatcaca atggctaggt ttcctgttgc 136680tcactattgg
attctggaga aaaatttaat gaaagatgat atcagaggaa gaataagtgg 136740aggtagagaa
gaaaggaatg atagaggagg ggaaaaaaac aaaacatatt tttgtgttat 136800ccaaaggagc
tttttcctta ttctgtcaag cattgagatc ttcttcagct ttcaatgtag 136860ttgctaaata
caaataatgc tactaggtag tgactaaata tagcaaacac ttcatcagat 136920attagaatta
ggtcacacta ttgaggttat aatctgaagg ttgtgttaca tagaaaccac 136980tttagattat
tatcaacttg gactaggctt tattttataa tagcatagta agtaatatct 137040attgtgtcat
ttcttcaacc attttattct aagatccatg aagcttcttg aggccaaata 137100aaataataag
tttagacaag aagtagattg tgactttttt cccttagaga tactatttac 137160tatctcctat
cctgataggt ggaaggttta ctgaattgga aattggttga ctattagttt 137220ttaactaaaa
tgtgcaataa cacattgcag tttcctcaaa ctagtttcct atgatcatta 137280aactcattct
cagggttaag aaaggaatgt aaatttctgc ctcaatttgt acttcatcaa 137340taagtttttg
aagagtgcag atttttagtc aggtcttaaa aataaactca caaatctgga 137400tgcatttcta
aattctgcaa atgtttcctg gggtgactta acaaggaata atcccacaat 137460atacctagct
acctaataca tggagctggg gctcaaccca ctgtttttaa ggatttgcgc 137520ttacttgtgg
ctgaggaaaa ataagtagtt cgaggaagta gtttttaaat gtgagcttat 137580agatagaaac
agaatatcaa cttaattatg aaattgttag aacctgttct cttgtatctg 137640aatctgattg
caattactat tgtactgata gactccagcc attgcaagtc tcagatatct 137700tagctgtgta
gtgattcttg aaattctttt taagaaaaat tgagtagaaa gaaataaacc 137760ctttgtaaat
gaggcttggc ttttgtgaaa gatcatccgc aggctatgtt aaaaggattt 137820tagctcacta
aaagtgtaat aatggaaatg tggaaaatat cgtaggtaaa ggaaactacc 137880tcatgctctg
aaggttttgt agaagcacaa ttaaacatct aaaatggctt tgttacacca 137940gagccatctg
gtgtgaagaa ctctatattt gtatgttgag agggcatgga ataattgtat 138000tttgctggca
atagacacat tctttattat ttgcagattc ctcatcaaat ctgtaattat 138060gcacagtttc
tgttatcaat aaaacaaaag aatcctgttt gtgtggtttc atgaaatcag 138120cattgttgaa
tgcatgaagt aataatgcta aattaacatt tttatgatgt ctcaaggttt 138180ctggtcaagg
gaagtaaatg taggatagta tttttacacc aaaatgacac agagagaatt 138240gagcacacca
gaaagaccag aaaccacacc actggataga gattcaatat gtttcttttt 138300caaacatttg
gacaagaaaa aaatgggcat ttaaaaattc ttccttcccc tggttatgga 138360tttatctgta
gtaaaactta gctttgtcgt ttgagatttg cacagaatgg ggggagtaga 138420ttacctcttc
ccattcattg tcataatgga tctacatcac tgataaacac catacttcta 138480tatgtggtta
actagcttta gaataaaaga cactttaaaa agtaaaaggc ctagagatct 138540tcaatgaagt
gtccctttta gccaaaccag gccttgcaga aattgtcctc aaaagcacca 138600agggagaaca
aagccaagtg cagaattacc caagggtcac acattttgta ttcattttct 138660tataatttgc
ccaaatgatt tgaagtacag caaaacctga agttttgcaa agagttactg 138720taaactgaac
ttaaaaatgt cagagtgctc ggtgacccac ttctccagac cctgtcaacc 138780tgtgaaaata
ttggccttta ttcagatctc tcaagaagtt acgcgcagag tttggaaggt 138840ctaggcaaag
gttattagtc aagtgttctt acagtgtcaa cgctcaattc ccacaagcgt 138900gagaaagaga
gacctgtcat tcctgagggt gatgacatac atttactgga gcttatataa 138960tttatcagat
aagacagcag tttccttcag ggtagaaagt gtgttttcta cattgattta 139020gtacaaaaca
aaaagaaaag gggatatttc aaattttata attatttttc tgctaagctg 139080attcagtgtg
atttaagcat atttttcaaa tcatgaatct gattccatat acatatgtgc 139140cttatattgt
gataatttat ttttaagtga aatatgctat catagcctga ctttatgtat 139200agtggtgaca
acttgcagga tcgcatttct gtaaccaaac ggccgacagc tgaggtgtag 139260atgcttccta
tggtctgtag aataatcact gggcttgttc tctagctatg tctgtatgca 139320atcgcgacag
tgttgatcaa aacccatgat cattctctcc aaaggtcttt gtcactaagc 139380cactagggat
tctgaaaagt tcgtgagctg aaacaaataa attgagttgg aagatt
13943693130421DNAHomo sapiensmodified_base(28255)..(68254)a, c, t, g,
unknown or other 93cctgtctctg gtgtgccctg gcccccgact tggaggcctc ctgggccagg
ccaagacctt 60ccccggcagc gatggtctcc agccacactc aactgccctg aagggacatt
tcctgcttat 120tcccttgccc ggctgtgtcc tccacccgga aggcctgtgc cttcttcgcc
tgcatgtcct 180accctgagga ggctcccttg gtctttcatc gctctcccta tgggtcttca
cgccttcccg 240aaccaccgcg cccaagcagg agcacgttct cggccctctt cacagggcgc
tcctcctcac 300aggggtgccc gggattttta ttctgtgcct tcctggtggc tcctacaagt
ctggaagggc 360aggaggcgca tctcactcct ctgggtcccc tcccctagcg cctggcggga
gcccaggctg 420catttgtgga attcatgact ttttctctcc tgctcaagct gaacacattg
ctggctcctg 480ctcgggtgga gcccggctaa ttagagtgag gggctccccg tagggcgaag
gggtgcgctg 540tcagatgtgg cattcccgtt ttacggagac acacggtgtc ttacacgcca
gggagaggtc 600tgagacgcaa agagccgtcg agcgggctgc gggattgctt cgctgtcacc
tccgcctgca 660gccacccttc cgcacgcact tgtgtgtgca cccaggccaa catggaaggc
gccatcctaa 720cttctgccgt gagcaggtgg gagggaagag agacgagagg tattccattg
gttgtctggg 780aaaatgaatt gcaccttccc ctcccttgcg gaggatcaac ttttcccacc
ccctcgggtg 840ggcactcgca tcctggggcc ggagcctgaa cccgggagcc aaggggcccc
agttccaggg 900acgtgaagct gagcgtacag cgggcgctcc cagacactgg ggaaagtgct
ttacgatgtc 960ccgagtccct ccagtctcgc cagcggggcg agcgtgaggg tgccccgacc
gaccagcggc 1020cccgggtgca gggtggcggg cccggcggcg cgcgtccccc tccccctcct
ggcggcccgc 1080acgtgtcgcc cgcgccgcgc ccccacgggt tacgcgcggg tcccgcagcg
ccgcggccga 1140gccgggctgc ccggcccgcg gacacagcgc cggccgccgc atcccgtgcg
gggccgcggc 1200gcgatgctgc gctggaatga ggaagcgcgg cggcgagggg agggcccggg
cgcggtgcgc 1260gcgggggtgg cggcggcgcg ccgagcgggc ccggcgcggg cgagcgggct
gcagccggcg 1320gcggcgccag caggtacggc ccgcacccgc cgccgccccg gcggcctttg
ggggctgagc 1380cggagcccgg cgcgattgca aagttttcgt gcgcggcccc tctggcccgg
agttgcggct 1440gagacgcgcg ccgcgcgagc cgggggactc ggcgacgggg cggggacggg
acgacgcacc 1500ctctccgtgt cccgctctgc gcccttctgc gcgccccgct ccctgtaccg
gagcagcgat 1560ccgggaggcg gccgagaggt gcgcgcgggg ccgagccggc tgcggggcag
gtcgagcagg 1620gaccgccagc gtgcgtcacc ccaaagtttg cggggtggca gggcgcgcgc
tctggccacc 1680cgccgctctg ggcggcagct ggtggcaacg caagggcgcg gcgggggcgg
ccggcgcgga 1740gggggccagg tacggggccc gcgggcggcg ctgtgcgcgc ggggcagccg
gtcggccggg 1800agcgcgaaag cctggtctga gccggctggg ggcggggagt gtggcggaga
aatggggaac 1860aatgcgagtg agcaacttca ggaagtcatt gtgaaagaaa gctgggaaga
gctccgcggc 1920caagttagca ggacactcta acaagtgact gcgcggcccg cgcccggggc
ggtgactgcg 1980gcaagccccc tgggtccccg cgcggcgcat cccagcctgg gcgggacgct
cggccgcggc 2040gaggcgggca agcctggcag ggcagaggga gccccggctc cgaggttgct
cttcgcaccc 2100gaggatcagt cttggcccca aagcgcgacg cacaaatcca cgtgagtgtt
ttcaaattga 2160atttcaatag gaaaacttgg ggtaactggt gaatttaaaa aaaaaaaaac
acagtaaaga 2220aaagcggtaa ggttggtaga ccctggtgtc gctcaggtcc gcctctcttt
tctgaggaca 2280gtgagagagt tcacttctgt caagcgtctg ttgctctgca ctgtgccagc
aggtgcagga 2340ccaggccgac atgggacact tctgagcagc cccgctgtca ccaggagagg
agttctagct 2400cccaaccata tttaaattta tgtagaccta catataccca cggaagtcag
cctttataaa 2460gtcgtgtgta aagagttttc cttatatttg agccgggagc tttcttttta
tactataaat 2520atgatgagat cgagtctgaa cttaatttct gcaagagagg aattatcccg
gctttgaaaa 2580gttagtcctt ttgctgaccg caggtttgac gctcaagtca ccaaaccttc
tcaggaaaac 2640ccttagtaat attaaggcat caggttactt gcggttatat ttgaaatgta
ttttaaatat 2700ttgtcaagca tcgctgctga tgcctaagga acctcgtgag ggcttgtttt
tccttctaat 2760ttggaggcat ctaatgaccg aaaaccgtag cgattccata gggtctgacc
aggcacagct 2820ttcaaatgca gcttccctct ctctagggac tgcagcccac ccagactgaa
tttcaatgcg 2880gtgcgctttg cttaggttac ccactcacaa tttcccactg cgccgcaggc
agtatatttc 2940agctttgaga taccttgttt taaaattcca gacaaaatgg tgttgaggaa
atgtctcctt 3000actagtccca tcaacttctg ttaaaagagg aaaatttatg gaatttgaaa
atactgcgta 3060tgatatttaa actttcatag acattcaaat gcttttaagg ccaggttcaa
tttggttatg 3120agtcgagggg tgggggggac ccacatagaa atgtcctggg tcctcttgag
tttatttctt 3180tgtttgaaga tgtttgttca atgagtttta ttgtactcat cttttatatg
gaattttaaa 3240aagtaacaat ttcagtatta tttatattag aatgtgtcag aattatttcc
gtgacaaatc 3300agatcatttg ggctatggct taaaatgtac acgaggcaaa tattcatgac
aagaagattc 3360accttcttac gctggcatct tgtaaaatgc agaacaagtt aaagaaataa
tgtgtacaca 3420tacaaataat gatgtcacat taaaaatact acactattct tgcttgatgg
aatgtatctg 3480atttccaatt tcaccatgaa catatttcat acatttttta catgaaaaaa
aacgtgactc 3540ttaagtctca cagtcaatca gagctggtga ccagaacatt ttattgaact
aaatggtcat 3600gttttcttcc ccttttgttt cacggtgaga gttgaaggaa ggagtttaga
aactctccag 3660tacttgttta attcatcagt gttctaatta gagtggtacc tcttggaaaa
ctacacaccc 3720ccctaatgca gaaacatcat agcaataatc acccaccctc agggtctcca
ggagaccaca 3780agggctgcag ataaaagtct ggatgtgtta ggtttgaccc tttcgaagag
ttttacacag 3840gctcctaaag agaagatcag ctgtggccgt ttgtagccat ttcctttgtc
gaaaaactaa 3900gatcgcagtg aatgtattag ccaagaggtc taaagccctg ttgtactgca
ggccactgtc 3960ttccttgttt gactagagac ttggagtttg agaacagtgg ttctttggtt
tggatacatt 4020ttttgttctt gatttggatg tgtgtgtttc atgcgtggtt aatatagcat
attttcaata 4080taaatgtcaa aaattttgaa ataggaaaga actctctata tattaatgta
cttatacaca 4140cacttcaaga ttatgcattt attaacagat acatgaaata aattccatgt
gcatatgcac 4200atatgcacac agagcgtgca cacacacagc atgcacacag cgtggagtga
gaggcatggg 4260gcagtgtgga agagttttaa catcaaacag acctgaaatg agtattaaag
gcccccttta 4320tttttaaact tttactaaaa caagatggat ttccctatgt tatataatgg
tgaattttag 4380gcataaataa cgttttttga gtgttgcata attgtacgta ttaatgtaat
gtaactgtgg 4440ttaacgaaga attcatcaag gatatcactg ttttgtggca tttttttttt
cctcctctaa 4500tctttggact tgtgaaataa tttcactatg aaataaatgt tggttcttgt
catattctaa 4560gggagattga tgtaagtggc tccactccag cttacagaag gtaaaccacg
acctttttgc 4620gttctctgaa aacgcttgtc ttccgatgcc tctgtttcta agactgacaa
gcactctggg 4680ggcactgtga cgcctgcttc tagcggcaga gttgctgcag ctcctgtcct
ggctgtgaac 4740attgttctct ctctggtgtc tctatgttca taactacaga gacttcagct
ctattccatt 4800tcatatttgt gctgaataat cattccattt tatgggagaa aacacaagat
gtaaaagcaa 4860caagtgaccc atcctttgaa gcttacaaga agagaaacat taatctattt
cacgtcttga 4920aaacagatca gttttatttt gctcaaaaag ggcacatgta catttttgat
ctaggtctta 4980gaaacgtaga gtttcagagg atcagcatta tacacactgt cacacacaca
cacacttaaa 5040attcagatga ggaacaagat aggaatgagg ttttgttagg gacgcagagc
acctaaaacc 5100aaaggatatc gacagtaaca aagctgtttt tactgtagtg ctgactgaac
actcatgctg 5160gtgtcttcat gtggaccatg gctttcttgt atttctttgc agtttaataa
atgacttcat 5220atctcaggtt acctttccac atctcctgga atatatgttt atgtccttaa
agtttcagtg 5280tcgtcacttt agtagcttta gtttgagttt ttaaatgttt ggtaatattc
caacaaatat 5340tttttaagac attatgaaac cttatgaagt gccatatatt acaagtgaga
taaaacagca 5400agcaaaagaa ggtttgcaga aggtttttaa gtggcgaagt gcgggcctgc
ccattttggt 5460gtctccttgg tggttactcc tgagaagggc ctggaggaag agcaactgag
gcctaatcta 5520caggcaactg ccaaattgtt tcagttgacg tttttccctc tcatgtttga
ctataataaa 5580taggtagttg ccagtggagc cttcagccaa ccacctggta ataaactgtt
aaaaatggtg 5640caaaccctag gtcacaggtg tgggggccat ttgtcttgcc tgttaacagg
cctggcctta 5700attcttttct cccatggcca tttctgcctt tggggaactc acaattcctg
ttgactaaaa 5760gagcaccctt ttccaccaca agcctgacaa atcagacgtc cacataattt
ctgaactcgt 5820tttggttagg acaggaagca caggctccct tcctgtctgt gttttcctaa
gagaaaacgg 5880tcttccctcc ttttttgcat atttggcaag tggttccacc tttctctgca
ccctggtgga 5940gtgtgaaggc agcagaggaa ccttttggag gaggaagagg acacagaggc
cctgtagcca 6000ggcaccaaga tccctcccag gtggctgggt ctgaggggaa ctccgagcag
ccctaggtcc 6060tcaaagtctg gatttgtgtg gaaaaggcag ctctcacttg gccttggcga
ggcctcggtt 6120ggttggtgag tgccacacgg tttctttgtg tgcttgcatg gattggaata
gccattgtgt 6180tcttccgtct tccctgctgg tgtttccaca gtgggtggcc tgagcccaga
gcagctcccc 6240atatccctgt gcaggccacc tgtctcgggt gatggagagc atcattatgc
tccgtctgaa 6300cgctctgctt tcggatggcc ccatgctcca cctcctgata gctcgtggcg
cggggccacg 6360gcttaacaaa tggctgaaaa tgggtcctaa ttagtggaaa agtgctttct
tcatattttc 6420tcactcgagt gtgcagtgat tcatttttct tctgcaatca gctcactgct
aaagtaaatc 6480tgactctctt cccgccattg cacaccaaaa gttaactcta atgggtagga
ggttaggttt 6540gttgagagag caatgcagta aaaagagggg atccaatgtg gtcttgtctg
tctggtcttc 6600ctttcttcgt tttttcctcc cttgtcttct ctgtcattcc cttccctcca
tttgccttgc 6660ctttcctgtc cttcccttcc cttccttccc ctctttcttt ctataattgg
tggggggttt 6720gcacagactg ccaaaacact aagaactgtg taaagtgttt ttgaatggcc
ttacacatat 6780tgaagtagat ttttatgctc catttttgag atcacacact aaaatctata
cctttaaagc 6840attttctgtt agtttgaaac tatttgaaaa tgaacaatgt ggtttagatt
agagtcctgt 6900tctgaagcta ggagttccac tatgaatatt gatttatcag tttttgacaa
atttttgttg 6960ttataccaga ttttcactgg caaacctaga gcaaataaaa ttccacataa
gatacttccc 7020tagacctaat gggaaaaatg tttaatttag agtctttagg agaaatgaga
atgaggaatt 7080gaccttttgt aagcttactt ctgaggcact ctgaagtgtg ttccagtgct
tttaatggaa 7140actagagaga gccagcaacc ccctagtgtg agccccactt ttaaccggaa
aaagtgacct 7200tttcctcctc ctttgtgctg agttttgcgt agggcagaaa attaagctga
tattcaaaga 7260gattcactgc aaaaacatat tgataaatcg tatattctat ttcattaaat
taaaaccata 7320ctgctaatta tctcaggttg ttaaacataa ggcaattaat tatcatttta
aaagttggta 7380ggaagttgtg agtacttttg cagtatgagt gttttcccgc tttagtatga
ggttgtgtat 7440gtttgcttga atttacagaa ttttcacttt aagagcagac aatgttttgt
taaagaaatg 7500aaatttgcta aaaaggagca tgtaaagtga aacattaaaa ataaataatt
tcaacttact 7560taagagctgc agaaaaatct gattgctgtg tttaaaatga attttcccac
atttcgctct 7620cttatggaca ggagcatttt ctgtcaggtt ataaataaag acatgcccat
tttttgtacc 7680cccacaaatg aggaagttgt aagctctctg aggttttact gatgagcccc
ctccccctgg 7740gtttgcatga agagatcata ggccacaaat aaaggactac aaaatggggt
ctaaactatc 7800ctggtggggc ctgataccca cgtttcgcat ggaccttacg atgtgatgaa
tggttttggc 7860atgagtgtct taagaatgct tccagattcg ggttacagga cagccagcgc
tgagctccct 7920attgcagaac aaagtaggaa tctagaactt tcttgctaac aggatccagc
taaaacacca 7980agttagattc ttaaatgatg ttcttttctg tcattatttg attgttgtca
gtagcagtaa 8040ttgttaccaa gccattgatg cttctattct tccctttgcc cttctgagac
acagctcatt 8100ttgacttcag tggaacccct cgaaggtggg gtgatgagca aggtgaattt
tcaaagtaaa 8160gctactaaga gaccaaacta caatttaagg aacctgattt ttgaatcaaa
ttccatatac 8220tgtgggtata gttcaacata gattaatttc ttatagttat tatgaaaaaa
atctcatctt 8280gatgatagct gataattttg tgggtgtcgt aaacaaaaca gaggtcagaa
ttcagtccct 8340tggggaaaat ttccaattag taggaaacca agtggcctac cttagtttga
agacacccat 8400caggatgtct gcaccttttc atcctctctg gaggaaagac taaataccca
ttattgtata 8460taggtcaggc caaagcagcc ttttatattg caaggaataa gaggtaaata
gatatatgtg 8520caacaatgaa tcccctaatg tgtttactct agaacacatg ttctttctgt
atttatatgt 8580agattttgta gatcttgtct taccacctgc taatggtaga tactgtatct
aaataagttg 8640aggaaaattt atagtaccta ggaatgtgtc ctcagtgggc caatcaatca
atcatgactt 8700caggttattt ttaataaata tacacgtatg ggttcataaa caatgggatg
ttcttgtgaa 8760gatctaaata attttacttc tttgggacta aataaaatat agcttttgcc
aaataaactc 8820acacaagcac ttattttaat agaagtcaaa tggctttgca gaaacttcag
ttttacaggt 8880gcattgtttg aaatgttacg ggtatacaag tggatttctc tattatgtac
agtgttaagt 8940ttgagtttca aaatgtccac ctgaaatgat ttacttgtac gttaagataa
tttaactgct 9000aagaaggcaa gataaagcat tctttgtgac accatatggc cttgctgagg
gaaaaactta 9060ctgttataag tttgtgttta tctctctttt taaaaaaaaa tgaagaaaaa
aacgtttaaa 9120ataatgggaa cacagcagtt cctggggtcc tctgtctctt tatcttatta
tagtaaatta 9180ccaaaaaaat aatgacctgg ggcatgtctg tgtggaccct tcttttagag
gcagtttctg 9240tgttttgtaa agctgtaggt tctattttca ttgcacttca tattgctgca
cagctcctga 9300ccatgcatga aggtcctctg aaatcggtaa gagggcagaa gaaaatgatt
ctaaacttag 9360atttttttaa cttaagtgat gaagtgtgaa acgccattta tatttgagga
agctacctag 9420gaagtggctc atgtcgatgg cccaaatcag aagagggcct gtaaaagctt
ctatcaattt 9480tgactgtgta tgcttctacc atggcggctc aataaacagc agtattagtt
taagagtgga 9540tggtacagta gtatagacgg gaagcctctc ctctccgtgt gaaccgtgca
cccctatgag 9600agggtagaga caatacaata tgcctgtaac gtcaggacag acagtcatgg
ccagcttgaa 9660ctccagccct gggcttcttg cagcaacaaa cgtgaacaca gaggactgtc
tccaactcca 9720ctttctctat ttttaaaaca actttttgaa tacagtatct gccatctttt
cttatacctc 9780actttgaaac aggtggctcc actgtggcat ttaaaatgtt ctgtttcttt
tccctctgta 9840tcaaatacct ctttaccaag aaaacattca aacagcatag tttttaactg
tattttgaaa 9900ggtttcctta gttccctttg acccttcctc ttttgcatat cagttcctgg
ccataaaaat 9960aaaaaatgct aggacagaat tgcacatctg agctgatttg ccctcaaaaa
gtttcacagt 10020ggaacaaacc gcaggaggag ttttctgtgg ctcagttaaa tgtcggggga
gggtggtgtg 10080aaagccaaat tggattcctg ctttcctgtt taaatcttgt ttttcattgt
tatttgcacc 10140agcaatactc tgtggaataa tcatgaaaat gtgtagattg gcagctaatt
tttgaaaaat 10200gaaaagaatc agaaatgaaa taagagtgct cggaagtttt tatgttctct
caacctgttt 10260tgtcaaattg ttacgaaaac ctataaggtc tctttgacta gatacaaaga
ctttgcacat 10320tgccttagct ttctcttgaa gcatttcctt ttttaaaata cagtgtaatt
cacagtgata 10380tgatagattt gcaaaagtaa aatctaccag tctgaagatg aaaggacttg
tctcttagca 10440ggaataatgg gttttattaa agaggtctgt gacctaaggc attttaaata
aattacaggc 10500ttggtccctg tctcccccat gtatctactc ccttcaatat aagcatcatt
gagtatttaa 10560ggaaataacc ccaaatgtaa ctctagtgta gcttcacttg tcagggagga
aaaagtaaat 10620agcatacatt tggccaaata accagaactt tactgtagaa gttttatgat
gaaatttgcc 10680tttagtgcag agtattacaa agatcatgtt tagtttctag cagtatataa
gtagcatcca 10740tccttatctg tcatgcattt ggagtgtgcg acccctgcac tgggctgcaa
cattctgatg 10800ggcaagagtg ctagggagaa agaggcatca ccatcagact gcacgggttc
aagtgtcagc 10860tctgtggttg attagctgtg tgacctgggg aaagctattt ctcttagcct
tggttctctc 10920atctataaaa tggagataat gatgcagatg ccttgggttt aattgggaga
gttaaagaca 10980catttacata tttagcaagt aggtgttgaa ttctagctct acattggaca
ctatgccagg 11040tgctcaaata aacaagtgga caagacagac aacacccatg gtcttatgag
gcttaaccat 11100ttgcctcttc aatgccagaa acttagtagg ttgattagat aaagccagtg
agtaccagta 11160tccttttctt tgcagccttt tcctggcaca ctaaaaatac tcagtacata
tgaaatatca 11220ctggacaaag aatccccctt agagtaccag tggagaagga aggcatttgc
ttaaaagcaa 11280accaacagaa agacattgta aggcagttgt ttaagtctca gagacctata
atttttttct 11340tttttctttt ttttcatctc gctctgtcgc ccaggctgga gtgcagtggc
acaatctcag 11400ctcactgcaa gctccacctt ccgggttcat gccattcttc tgcctcagcc
tcccaagtag 11460cagagactac aggcgcccgc caccacacct ggctaatttt ttgtattttt
agtggagacg 11520gggtttcgcc gtgttagcca ggatggtctt gatctcctga cctcatgatc
cgcctgcctc 11580ggcctcccaa agtgctggga ttactggcat gagccaccac gcccggcaac
tacaattgtt 11640cttaaagctt gtagaattac tgtgtgctac caacagacag gctaattttg
agtgaccctc 11700agtactttgt acagttaatt tggcacgctg tgtacttagt ggctttttaa
cagctataaa 11760tttgggctgc tagaaaagta gtaaagttgt gattcttgac aggcatctat
ctgcattttc 11820atttttactt catttgtcta gactcagctt gtcagaatta tggaagagac
tccttgtgtc 11880agggcaagca ctgtgaagag aggtattcac tgtcagaaaa gagaggggag
ctggaggcag 11940ctcagaggcc tgagacccgc ctccacagga gccccagcag gttcggtgga
gctctggcca 12000cactctcctt tgggatgctg aagtcagaat gagttcactt cccagccagt
cttgccaagg 12060ctcctcacct ggaagcagca actgcccagg gctgttggat gtttctcccc
aggggacagc 12120caggtcccag tcccgcctcg gtgtggaagg aggaaaggca gggtccagga
agctgtttca 12180ggacaggccc aaggtccccc agggatgcct ttcagggtca gcggaggctg
taaatcagca 12240gggcccacac ggcctggaag aggcccctgt gctgtcggct tgcccggctt
gcccggctcc 12300tagtccggct tctgctcctc ctttgtaaag ttatggatat gctaatagtt
tccaactgag 12360actaggaaag taagtcctac ttgacactgt ttggtcagaa agagggagag
aaaggagaag 12420gacagagaga gactgagaga gagacagtct cagacaaagg gagacggagg
gagggaggga 12480gagacagaga aagagatggg aggtaggtgt gggaggaggg agagatgcag
aaggcagagg 12540aaagacagac agagatttag acctcccaag tcagtgagca gtccagagtt
ggagtggagg 12600gtgcctggtg gcttgtgact gcagactcca ctccccgctc ctagaggcac
agccatggac 12660agcttctgtc acgttggccc tgcacttatc tctgcatcta tttccccttg
tgcaagattc 12720agaactgcat gctccaaaaa aacaataaaa gcattcatgt tcataagaat
tgcacaggta 12780aaaggtagtt tgctgatatt gttgtatttt ttactatcgc ttcttttagg
tcttgcctga 12840aattgtttgg gtttcccagg caaagtagaa aactgcggta cgtttctgtg
aaataattat 12900tccttctggc atctcccttt acagacctac tgatcttgat ttttcattta
ggtgaaagtt 12960tgtgaaaaca tgccattagc ttgctttgtg attaactcct tttactgaat
gtgagctcct 13020tttaaattga ggccatatca agcttaaatt ccatatttta cccggcactc
tgcatttctt 13080ccatgtggga gaggaggggc tcagtaagtg ctttgtaaaa tacacagccg
aagtgatgca 13140cgtgctaaca aaggagtgtg acaggactta agtgcccttc tagacacttc
aggctcccct 13200ttgtaagctg tcttggaaga ggccacattt cctttccctc aaacagtttc
tcattgtttg 13260attattcttt tagcctttct ctggaagcaa agccactttt acgagaaagt
cactgctttt 13320tcatctcaag agatgcaagt ttggagtttg gggaagtttt caggtgcccg
tcaagtcatc 13380ctttatgatg tcagacgagt caggccacag aattcacagg gctcagtgca
gaccgaaaac 13440ttgaggcctc ttgttcagaa attattaaaa attttggtga acatcacccc
aagcaaagag 13500atcccctaag caccagcccc caagcaactg cactcataag cccatgaagc
cccctgctgt 13560cagaaacaat gtggttgaaa ttgtgtatgc acttggaagt gagatggatt
gcaaaacaca 13620ggtctccatg ctggggcagg agtggtgata gggcatggag tggaaatgtc
cagcaggccc 13680acgtgcgaaa atgcagagct ctctggctct tgcagacttg gctgctgaca
atagacgcgc 13740tccaggaagg tgctcgctgt ggtgtgatct gctgcccacc cctagctccc
tccaggagac 13800tggtgcgggg actgtttgca aatgactgca aaagtaagaa ggttcccaca
gagcagagct 13860tgatttgggg accagccgag ggcagtttgt caggattccg gcttgaaact
gttctcacat 13920ctcaccgcct gaaaggacga gtgtgtccag aggacttagc attgatcacc
tctgtctcca 13980tgcagcaaac tcagaggctc agcccgcatt ccactggaag ggcgtttgcc
agtggtgttg 14040gttggaagag ccttgacttt gccttaggaa acatcttttt ttaagaattg
aaaataactt 14100gagtatgcaa cagtagggca tttgttatat aaattagttg actagtgtgt
agccagtaaa 14160atgatgatgg tggtgtgtat ttgttaaata aaaagatatg tgtggtatta
aattaaaaaa 14220tattttaaaa caacatattt gtaatctgtt tagtgtcctc tttttgtaaa
aagtacagaa 14280ataaatatac agaaaaaata gtagtcctaa gtggtagaaa ttatgagcat
tttcttgcct 14340ttaaaaaaag ttgtaaaaga ttgtatcatt tatgtagcaa aaagttttaa
gtcagcattc 14400taaaaatttc gtgttgttat agttgctgtg acaagattta acttctgtat
gcttcaccaa 14460tcaatacaga ggtatttaag acccggtgtg tgataggccg cgctaaaata
ctatacacat 14520cttcagaaaa ctagagaact aacttctaac ttcctatatt agtgtggcac
ggctgttaca 14580aagatttttc tcatttgagt ctatcttgct tctttatcat tgttttgaca
gtttcagaag 14640aatcgtggct tttccccttt tttacagtaa aggtacctga gactcttgac
gtattgcttt 14700ttggaaatgc ttgtgctggt cacatgcttg catctgggct agtgtgtctg
gcttccgtgt 14760gctggtggat gcttactctg ttttctgaaa tactttttct gtacagtggc
cactagctgt 14820actcctaagc cacacaccta ccttgaaaat tcatgtcact tttagaaata
gataaaagcc 14880cctcccatcc agaaaaagtg actatcatgt atatcctcat catgactaat
actgatattc 14940ctgaaattga aaatacatat tccatatgta ccataaaagg tattaaagat
atatggagtg 15000atagatatat tatatataac acttctaccc tcacagtttt cagcctaatt
gagagggtaa 15060gatccctgaa tcatccatca gtttttcagg tctctgctga aagcaggcca
cagctcagat 15120ccacacatct gaaccagaga cagaggtggc caaaaataaa aagggggaca
gggggacaac 15180ctggtttaga gtcaacaaat agactgcatt ttctggttag tgaaggagct
ctcctgaaag 15240tcatatacca gagcataaat gagcagattt ccttgaggtc accttctgct
ggccatagct 15300ttcttatctg tggagctgcc agctgtcatc cactttgggg cacctgagac
tgccgagcgg 15360caggccagga cccaagtgcg aaaacacaga acaccttttt gtttctactc
cactgatgct 15420ggggttctct ccctggtgtt tgtggctcgt agtacactct gtggaacatt
cactatggtc 15480atcgaagggc agcatcttcc cagttgtttc tttcttttct tttttttttt
taatttaaac 15540cgatctgaga agccagccat ctgtcagcaa aacaggaagg ctcgggctgt
ctcctgggct 15600cgttttgctg ccgtagtgag cgtcacttct ccccgtgtaa gagtgctggt
gaaggctgag 15660gcaagggccc agaaagattg agggacaaag acaggagcgc ccgcattgcc
catctgccag 15720gctggaggtg tattcattat tgatggaggt agtgcagttg ctgctcagat
atgcagccct 15780gcctgggtaa atgagacatt cttcagcaaa ttgcttcgtt ttttgattgc
tgattgtacg 15840cgtgtcacca agctgactca aggttcatcg atgcatgctc agtaaattag
aaagaacata 15900actatggatc agccaagaga atgaattctg tgcctacaat gacccagggc
catttaattt 15960tctgcttaat tttgttgcag tcagtttgca ttttgggtta ttatgcagta
ggaaattaac 16020aataaataac aaatttggtc ctcctgtgct tgtaatgata tttttataaa
tctttgtaat 16080gctgttttta aaaggatcaa ggtctgtgcc agtctgatac tccagcaagt
atgtgaggag 16140gaaaatgcat tattcttgct agataacctt gttgttaaat agcatagggg
ttctttatct 16200ctctctcttt ctcatatctt attagtattt ttgctttaaa ctaaaatccc
ttcctctctt 16260tctcagataa cctgaggacc atggatgctg atgagggtca agacatgtcc
caagtttcag 16320gtgagacctt atgagatagc tgtgtgggaa gttcatgaga aaagcttccc
tggggccgga 16380agtcacagtg cttggtatgc tcatggggga ggaatagggg ctattctgca
aaagaaaaga 16440ccatgatgga atttgcctga gtgtttcctt cacctgttac aaattatctc
actttgagct 16500gaacagaaag cctccaagat gaaattagtt ttactgttaa acttcaggaa
aaaaaaacgg 16560gaagagttaa atacattttt gtactgttgg aaggaaaaat ggctgattgg
tttaaaaccc 16620aaacacatgc caatgatggt acttaaagag agagagagag agaagcttga
aaaacataat 16680tgttgggcac agtcatgact gtttgttcat taagcatgga cacaacattg
ctcccctttg 16740ccatatatct tttcaagccg tattggatat agctcttctc atccaggaga
cccaggaagt 16800ggagaagtct gtagtaggaa aagcctaagg gtaggtcaca gactgtgacc
atttggcagc 16860actgagggtg gacggcgagc cagtccaaca aaaccgcaca gttccccagt
gcatggacat 16920aggaagacag ctttctatct ggccctgtat ccagaggcgt cagccccagt
agcagctttc 16980atggactttg gggttttcgg tatttcatat ttttgagcct cacagactca
cagccagccc 17040cagaggctga cttatatttg agaaagttct cagtggcacc ttgccttggc
tgagcgccct 17100cgtgttttga agtttctatg ggattctaca agttggtgct cctgatgaag
accaggacct 17160atgtgtggct gctcccctgc ttggtggttt ccctggggaa ggtgcaggag
aggatcttct 17220gagttccatg gaactggaga tagatctgcc aatcacaggc ttccttctcc
accactcctc 17280agccgctcta ttcatgtttc agattttgga cttaaactct cccaggtgca
aagaacaaac 17340aaaaggctag cttatttttc ttttagagtg aggcttcgta tttattacaa
tataattgcc 17400acattctttg tgtaattctc acatttatat cttaaatata attctcatga
atgagaatta 17460tataattctc tttttgtata tcattgaata ttttcactta atttttaatt
tttttaatcg 17520tcacaaaata attgtgtaca tagacacaaa ataattgggt acatagtgat
gttgtgatat 17580atacaatgta tagtaatcgg atcaggtaaa tcagcatatt catcatctca
aacatttatc 17640gtttctttgt attaggaaca ttcgacatct tccttctagc tatttgaaac
tatatattat 17700tgttgactac agtcatcctg caatggtgta gaacactaga acttattctt
cctacctagc 17760tgtaattttg tctcctttaa caaatctctc cctatcttcc actcccccga
cctttccagc 17820ctctattagc ctctgtccta ctttctactt ataatgatga cagcagcatt
tgttagtttc 17880cacatgtgag tgagaacatg tggcttttta acttttagaa tgtggtattc
aggcacttca 17940tggtacagtt ggtaaaagtg aaaatgtgtc caaaagtttg tgattatcta
tataaacaaa 18000aatggtataa atacaaatat caattttgca ttgaagaact taccttagag
gtatattctc 18060acaagtgcac agagcattta agcatttgtt cactgcagca ttgttatcag
tattttaaaa 18120ctatggtaca tccatgtact tccacataca gctcttaaaa ataaggagga
tatgaatgaa 18180ctagtatgaa aagaagtcca aatacatgtg aaagtgagaa tagcatggtt
ctggatggta 18240tgcaaagtat gatctcgttc ttttaaaaga aaataaatta catacacata
catattttct 18300atatgcttgc ccataacgtt taggaaaatt cttgggtgat atttattaac
ctggacttcc 18360tcttggaaga ctgatggtag aaggaagggg acgagttagg gaagaggagg
agaaggaaaa 18420ctttgctttt catcttctac cttttagcat tatttgaatt tattttcctt
aagcgtttac 18480tttgtttcgt aaacaaaaaa gcacaaaaac aaaaaacgag ttaaatggga
aaaaaagcag 18540tttagctctt tatagcctct catttggctt cgccagcctc tcactgcagc
ctcagagagc 18600tggtctggga aacactggta gatgaggact gtaatcctca ctcatggaag
aggatctcat 18660tcactgggtt tgctgactgt gactagaagt gattagggtg tcaaaaaacc
caagcatgtt 18720aaaaatttcc agaggccaaa aagatgcttt cattgttctg ctcttctttt
ccttgtcgct 18780ttcactttgg gtagcttcta aattggtatt ttgcatggtg catttaaaga
aaatgagacc 18840cctttggcca atgcaggagt ctacactctg atattctaga gtcaaagctg
aatgctgaca 18900cctaggaatt catctctaga atgtttatat aaggaatagc ccctcagtat
tccgatctcg 18960tatcttagta acgaaactaa caaaagcctg attctcctct ggtagttttc
ttgtctttac 19020cataatacaa aataagtaat ttgttctgca ccctgactgt tcaaaggata
gggtagctgg 19080gggcggggac aagaatggag accttattac ataagacttc ctgaaaaagg
aaactctgtt 19140tttgtttgaa atgatttggt ctgaaattta gtttgtgtac acttaccaaa
gggattccta 19200tttctaaaac actcatactg cttttgattc ctgttaacct ttgagcactc
tacgtaatga 19260tgagagcact taaagagtca tgtcactttt agtaaagaat caaaggatac
tttttctact 19320tcttcgagtt tgatctctgc ttctccagtt aaaaccagta tttgtttttt
tcatttctaa 19380agttggaaga aatgacagtt agttatggca taaggatgta catttaacca
aataggagtt 19440gacattcttg gtaagaaatc ttaccaagat tatgttatag attataagaa
atcttaacaa 19500gaatatgttc ctaaatcatc ctcttttccc ataaaatatt aaagtatcag
caatttcata 19560ggattcaacc taatgtatgc gaaatgctag ataaacagat aaatacttaa
tatctggctt 19620tttttcaaag cactgggtta tttgttcctt gagatttatc ctaaatgtgg
gctataccct 19680ggtttacagt gtctcacaga tgtgtagtag tagacactcc ataagtgttt
actgacttga 19740atccacaggg tactgagaaa atgctactga tagacttgga ggagagcata
tctaaagcaa 19800gctacccttt cctttagggc acgtctcact aattctttgg gtaaagcgta
tttttcttcc 19860ttttgtgttt ttggcagtct ttccaaaaat acgtgttata cctatgcatt
attttttggt 19920ttggtttcta aagaaagagt cagccggtgg gaaagtgaag gatgtgggaa
ctgagagatc 19980tgcatcagca tcccacctct acctcccacg atgggacctg agacagttat
ttttgcctcc 20040tggaccacta tagtatcatc tgtaacagga gggacttgag ccagttgatc
tctaaggttc 20100ctctggcacc tgtgacccta aatagatatt ggatattggt ttaatgctat
ttgtagtgtg 20160tttttttggg gatatggaaa ccagaagttt gtttccataa acataaacat
aaactgtata 20220tatctaaagg atatggaaac ctttagatat atataatctg cttacgtaaa
gaaggtttgt 20280atatattgca gtgtcaatgg gaatatttta tcaagttaag catagtaaat
cacattgatt 20340aaatgctttg tatttaccaa acattaccca aagtgttttc tcctttcaac
ctcacaagga 20400cccacagaag aaaatacagt tatcatttcc aacctgcagg gagctgagac
acagagaatt 20460taagcaactg accggaagtc caacagggag tcagagattg ctctggggtg
tgatccccac 20520ttggacccta gagtggaagc ttctccacta ctttatagag ttgagattct
atattttgag 20580cttgtattta cccagagaat tatatcctct tgggcaattg tgtataataa
aacctcatgc 20640atttaggaga ggcgggatga cagaactttg ttgagtgaat tataatctac
ttgagaaatt 20700atttgcttac attttataag ctaattatac catatctcat ccagttttcc
cagaacactt 20760ctcataggta atgctttatt tgaaacatag gccataggta agttaagtgt
aaatgtgtat 20820ttttataatt taaccagaag tttatttcat ttttctaaat aagtgaaatt
gtattgcatc 20880ttctaaatta ttctatttaa acacttgatg tcttgctgtc tccgtctctg
tgtgtttgca 20940tgtcattgta catgttctta ggaaaagtgt gggagcttga cgcaatatat
accttatgtt 21000tctatgtgca tatagtttac caaataatac cataagttta cttagcatat
tagaatccat 21060gcacattatt tttattttat cttcaccgca accctgtggg atagaccaaa
atcatgcttt 21120tcagcctcct ttttccactt gaggaaagga gtcttaaaaa agggaccagt
ctcatgttcc 21180cattcgtctt acaactaatt ggtcaagcca gaaagccaga actatgtcct
gggtcactaa 21240ctcctagtca ctgtgtgtta gtatttgaga tgcctgttgg cttgatttag
tcatttattt 21300tttagtgttt tataatcctt gcatactttt acattttaaa tggttaacca
ggcaaattgg 21360tttaaaatca gtgcataaaa atactgtgcc tatcatgatg ggtttcatga
agtgataact 21420tttcatcatg gagatcctca gctgtcacag aagatgaggg gccctgggta
cagaggctca 21480cgtgagggat gaaagtctca gcagcccgga cttacacttt ggggctttta
ggcaaatcag 21540acaacctctt aagaactatc actgagttca ggcaaggcga gcttgaatta
acacagggcc 21600cttggtgggc atgtgaatat atctcacttc actaccatcc agttctgact
ctttactaga 21660tgcccctgta cataccaaga ctgatttttt attctccctt ctccccatgt
ggtttcttct 21720gcatagagag ttcctattga tcagtctgac ccatggtatt ttagaattgc
gatccctact 21780gtttcattat tcctttttct cccccatgtt gaaaaaaata aatgtcctga
gatgcaagat 21840cagggacact ggagcactga catttagttc agtgcaggaa ctgaaggcag
atgtaattct 21900taagaagcgt acctgttatt atgaaccatc ctcaacaaat tgtagtggat
cttgttttct 21960catagataca gcagttaaat tttttaataa aagtaactaa gagttatttg
gatgtatttt 22020agcatgcact gagcggaaag tacgacattt cttcattggg taagtcctga
ttctttatga 22080tcctcacttg gttccagggc cccatgcatc taagggtgtc tcagagcatc
ctgcagtgct 22140ccagcatgat cgcagggaaa agctatagga ggaaaagagt caataaagtt
tagtttctca 22200acctcccacc tccaccccat aataatgaca gctggttaat catgagacgc
gtgcacaccc 22260cacacgccct gtacatgttt actcattggg atagcatgtc aggccagaag
gctccatggt 22320catttctatg aaggtacttt agcaggtctt caagaaggca agtggcctgg
gtccctgcct 22380ccccaaattg caagctccct gctttatgta ggagacctat gtgtatatta
cagttctgtg 22440taagattatt ttgttattct tacccccaca cccacccccc aaccccccgc
tgccaccaaa 22500aaaaaaaaaa aaaaattcct ctgacaacct tcataaagtc ctgggagttt
gaacaccatt 22560gctctaggaa gtcatcttat acaaaaataa gagttgtgag gtggttcata
tacctcctgc 22620gttctcctat ttggagtttt tccccattta tgaaagaggt gaaaacgcta
agatatttag 22680caattattac tttaaacatt ttctatttat aggccgggcg cagtggctca
tgcctgtaat 22740cccagcgctt gggaggccaa ggcaggcaga tcacgaggtc aggagatcga
gaccatcttg 22800gctaacacgg tgaaaccctg tctctactaa aaaaatacaa aaatttagtt
gggcatggtg 22860ggggatacct gtggtcccag ctactcggga ggctgagaca ggagaatggc
ttgaacctgg 22920gaggccgagc ttgcagtgag ccaagatcgc gccactgcac tccagcctgg
gtgacagagc 22980aagactctgt ctcgaaaaaa aaaaaaaatt ctatttacag cagtgaaaat
agtagtgact 23040taatgcacat tgccaaggct ttagcataac atgaacactt tcactcaatg
tctctctggc 23100cttttgtttt tccttgggaa attcttataa tcctgctccg tctttaacta
ttcattttgt 23160attggctatc caaatatacc caataatgct ctttctgaaa atatgccaat
tgtggtaatt 23220acagctaagc tggaatatta aattgtgatg tctgttttcc agagaatgaa
gtagtattcc 23280ccagagcata ggcttggtgc ctgtgcaggt tctattttaa atattccagg
aagggttgtt 23340ttatatactg aggatgattt tactggtctt gccagtcgtc tgaaatgctg
gtattactct 23400tgtggaaggt ttattcaaac aaacaaggac atttcacaca atacctagtc
atgtttttca 23460gacattttaa tgtttggttc atcatttgca cacactctca aaaatctagg
tttgtctatg 23520tgttcatatc attttgcctg ttgccagctc agtcagcagg cacactctcc
caggctgttg 23580ctgttttgtt agacttcttc aggaccttca tctaaaatgg tcttccacac
gtagctatac 23640tgcataagtt cacatcatct gtttcttgca tgtgggttgt gtctcaactc
aagtttaagt 23700tagatttgga agggcggaaa ctataggagt tgcagcttca gtggagaaaa
gagcatttcc 23760tactagttat ggcttcccaa ggaaggttag attcctcaga gtaggagtga
ttccccaatg 23820ctagaacctt tggtcaaata taattctaat ccagtcaaaa taaatacagg
tattctgtaa 23880aacccgattt cattttgtaa atcctacttt gtatagtata agcaattttt
gtatttgtgt 23940ggattatatt ttattttcct atttcaaaga gaagaatttg tattagcaga
ctccctttgc 24000atgcggagag gggatcattt tcccagtagg catggggttc ccttccattc
cttgtccagt 24060cttcttttcc ccactaagtt aagtcaaact aagcagctgg taagatattc
cctggttctt 24120gcaaagaaag tgagcagatg gcagaatgta tagctctaag cagaatacct
ggtgtggtat 24180cctcaaacac aaattgacag gagggtgtgg tgtggcaagc tcattgtggg
ggtaaattgg 24240aataagctta cagggggaag agttgacaaa agataggaag aaccttaaaa
atatagatgc 24300cttttatgca gtgataaaat gtctagatat ttatactgtg gtgattatta
ggaatatgtg 24360caaagattgg ctattaggat gttcattaca gtgttgttta ataattataa
aaggacagaa 24420agcaatgtgg actcaaaaat aggaaaagaa tttaaataaa tcctagtgta
cccgttatac 24480atgaaattat ggaaatatga ccctgagcat ggaaatatgt acatgagaat
gtctaaaagc 24540tagttcattt tgaaaaacaa aataatgtca cctcatatta tttatagtat
ataaagatga 24600ttttaagagt ggcagtgtct gggattatag gtgattgtat ttcttccctt
ttgcacatct 24660atgttctctc atttgtattg tgtggggaga agtgactttt tttataaaaa
gaaaaaggta 24720tatgcatccc agcagagaag cactggctcc acccagtacc tgcctcctca
tgccaccctc 24780tcaagccaaa agccggggga agcccaggca ccttgaccat gaccgcccga
gactcacact 24840tcttctttct catcagggaa ggaaagcccc cctgtaagcg atactccaga
tgagggcgat 24900gagcccatgc cgatccccga ggacctctcc accacctcgg gaggacagca
aagctccaag 24960agtgacagag tcgtgggtaa gtgggtcacc agcggcctct gtgcctgtga
aacctttatc 25020tctttgtatt tttccaagac agtgatgaag ggatgcaagt cattttatcc
attgtgttcc 25080ctcaactggc atattaaaga aatatggcac aaagatcagc aggatggggg
tcctctggtg 25140tgtgggagga tggacactca caggccagca tggccgtgag agccacacac
cccgcaaaat 25200gtccaagttg aggagcaatc ctgcccaggg acgcgtctct gtcactgtcc
tctgtcctca 25260ctgcacttgc aggaatatca aatgttatgg attgtagatc gtgaaaatta
cacacttacg 25320tgttttggca acagtgcttt tcagtgtttg gggttagaac aagccacatc
tggccatttt 25380atgttatccc tctaatctct agttcttaaa tttcagattt aactgaaaat
agaaagtttc 25440ataaatggta atttttaaat gttagaaaaa aatcaaagca cacatttaca
taccttttcc 25500ataaaaaagt gtgtgtgaaa ccatctgcaa ctccactggt taacttacac
atgcgacagt 25560ttgtgtttgg aaaacttcac ccaccctctt tatttcaaga aaccaaagac
ggagagaagt 25620tcagtgaatt aaccaaggtg aaatgacaga gtcagaattg aactgaattt
ctgactgaaa 25680aactagttct cgctccatta taccatgttc taatgagcta atgagtcaac
agttccctgg 25740aatacctgtt ttcttcttta aaaagagaaa gagctgtgat actgagagct
acctattggc 25800ataaaagaat atgaaggaca tacaggtaaa atgaggtaga ctggatcaat
gtgggtcagc 25860tacataagcc cccatagcca aggagggaac atgtatgtaa aattctcagg
cttatgagaa 25920tcacaactgt atgtctatag gacatcctaa tgcaataatg ggaaaatgtg
ataactgaat 25980tttatctaca tgtatagaaa acatattttg ggccgggcat ggtggctcaa
gcttgtaatc 26040ccagcacttt gggaggccga ggctggcgga tcacaaggtc aggaaatcga
gaccatcctg 26100gctaacacgg tgaaaccctg tctctactaa aaatacaaaa aattagccgg
gcgtagtggt 26160gggcgcctgt agtcccagct actcgggagg ctgaggcagg agaatggcgt
gaacccggca 26220ggcggagctt gcagtgagcc gagattgcgc cactgcactc cagcctggat
gacagagcca 26280gactccatct caaaaaaaaa aaaaaaaaag aaaaagtaaa gaaaacatat
tttgtatgtt 26340ttttatgtgt cttagaaacc aagtggacta ggtataatgg ttcttttttt
ttttaactca 26400gcagcacagt taatggcaca aacagataaa gatggtggct aaagccattt
ggtgtagatg 26460aatccagaaa acaagtacat ttatgaatta ttttacccta ttggaaaatg
gctactatat 26520gtggaaagta gaggggaaga gaaatgaact tgtgaattat ctactctatt
ctaccaaaga 26580aagatacata tatcatttca gggttttcca aagttgggat gcaaaggatc
atgtttcatt 26640ttaatttatg tatttatttt tgagattgtc ttctatgtat tgcaagtgat
actggtttta 26700ccatgcactg taccactacg agggttcctt tcaaaacaca ttcatataaa
ttaaaaaatc 26760agtttaaata aaaacatcaa gtcaatagta gtacatagat atgataaaag
tttgcaaaag 26820tggcacagga atagtcattg ggtggtgatg ttccctgatt tttttagtcc
ctgaagcacc 26880cagcgccaag ggtactgttc ttcctgctta acacaggagc aaacagatgc
tcacaccctg 26940cccaagaaca cagaggctca gggactgaac cagaagaaat gatccattaa
ccatgtaaat 27000gaacagagag cctggatgtc agagtgagga ggccagctcg ggtcgctgtg
gagaaagaga 27060tgggctctcc ctggaatccc tgcagctgcc cttagaggct gtgagccatc
gtggctaggg 27120catctttaga gaactgaaag tcaggccgat tcctggagag tgaagaatag
cacacgtgcc 27180ttcaaaacag tgtcagtatc ctgtccctta cggacgtcat attgttggtg
ggttttcctg 27240ggtgggagat cacccagtat ctggttggca ttactgatgg gttcccagag
ctgtcttttg 27300gttcaaagtc ctgccctcgg tcccagctgc ccccagcaca ggtgtcacct
tggagtcagg 27360ggcgggtttg tcatagccca tgggtcctgg ccctgccctt tatcatgttt
gacatgattt 27420tcagtctact tttccttcag gatgtaattt agaaaatatg atttcagaat
tgtgaaattt 27480aaaaacccta gaaaacctct ttgctttgct tgtaaatagc agttgatgca
gccctgtgga 27540caggcgggaa cagccatgtg acgtgggcac tgagatgatt tgggagattg
aatgctcctc 27600agtggggcta gaggccacag gagtgatagg ttactgtaaa gaaagcaaaa
aagatgcaaa 27660agcctacatg acaaaccagg cacgacacaa aggagaggct tgagaagagg
aagtgaagga 27720gggagaggat tccacaagac cgaagtgccc aaggagacat ggagggaaga
gagggctctt 27780cacagagctg agtttagaga ccaccctcca tggttctgga aggaaaccag
ccagctttca 27840tatgtggtga caggctgttc attaatttgt agtgtacagc attaaataaa
tgaagtatgt 27900agagaacatt aggaaacaat ataaaaaggt aggggaattc gtggataaag
ggaataacct 27960gggtaccata tttcatcaca ttattccatg ggaataagtc atcagtgcaa
aggactgtaa 28020ggagtgcaca gcaggaaatg aaaagacaga agcagtgggg ccgagaggag
gaaatggagt 28080tgctgaaatg cagggtgagc agcaggggcg gagagtgccc tgtgggtaag
gcacacctca 28140gaagggacag gtccaggccc tctcctccct ggcctggagc ttctggcaag
gcttttcttc 28200tctgagcctc actttcctct tttgaaggtg gcaatagtaa ctgaacctgc
atcannnnnn 28260nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28320nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28380nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28440nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28500nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28560nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28620nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28680nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28740nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28800nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28860nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28920nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 28980nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29040nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29100nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29160nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29220nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29280nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29340nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29400nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29460nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
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nnnnnnnnnn 29580nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29640nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 29700nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
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nnnnnnnnnn 30000nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
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nnnnnnnnnn 30360nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 30420nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 30480nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
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nnnnnnnnnn 62220nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62280nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62340nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62400nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62460nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62520nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62580nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62640nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62700nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62760nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62820nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62880nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 62940nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63000nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63060nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63120nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63180nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63240nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63300nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63360nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63420nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63480nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63540nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63600nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63660nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63720nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63780nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63840nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63900nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 63960nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64020nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64080nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64140nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64200nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64260nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64320nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64380nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64440nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64500nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64560nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64620nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64680nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64740nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64800nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64860nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64920nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 64980nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65040nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65100nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65160nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65220nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65280nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65340nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65400nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65460nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65520nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65580nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65640nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65700nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65760nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65820nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65880nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 65940nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66000nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66060nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66120nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66180nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66240nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66300nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66360nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66420nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66480nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66540nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66600nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66660nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66720nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66780nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66840nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66900nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 66960nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67020nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67080nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67140nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67200nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67260nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67320nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67380nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67440nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67500nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67560nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67620nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67680nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67740nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67800nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67860nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67920nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 67980nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 68040nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 68100nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 68160nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
nnnnnnnnnn 68220nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnaagctt tgattgggcc
gttactgtct 68280tttgaccttt cttgtttgct tgcccttttg tttctttcct cctttttcct
tccttcctgt 68340ctttcttctt ccttccttcc tttcttcctt tttcttttta attttcctcc
tttctctttc 68400tcctttcttt ccttccttct ttcctctttt tttctttcct ccctccctcc
ctttctttct 68460tccttccttt ctttcttccc tccttccctc cccaccctcc ctcccttccc
ctcgtctccc 68520ttcccctcgt ctcccttccc ctcccctccc tccctccctt cctccttttt
ctttcccttt 68580cctccttcct tccttcctct cttcttttct ccatcccttt cttcctttta
acatttgatc 68640atgggtacca tttcatcaag attctgttac ttaggtccaa ggactagtga
ccaaattgtt 68700tttcccagga gtaaactttt ctacaagaca tagagaaatg actgccagtg
ccatcaggca 68760caccatcctg tgtgataggt aacctaaaat aatggtacag cggggagtaa
ctggaagagt 68820cacaactaca caaatctctt gcattttcct gatcattaaa tgaattaggg
atttcctggt 68880ttgagatttg tggacaagga gaactacttc tttgtacaag aggcttgtgc
caggagaaga 68940cacgctgtgg ttacaatgtt actgtctcta gctatggtca tttcatgtct
ttaactgagt 69000gtacctagag tgtaatacag tgcagcagtg atgggctgaa ggcctaatgc
accagcacac 69060atgcctggaa gacctaacgt tgagaatccg catttttttc atcactcaca
tttattttgc 69120atctccctgt tttgattacc ttcagagacc caagcacttg cttttgtata
tttgagtctg 69180ggttttattt tccttttaga aatagtccaa aatcctttta gagcctagac
ctttgaataa 69240agtgctaact taacctgagg aatgctgttt ttttgttcac aaataaggct
taattgtgaa 69300gtcgtgagaa ttgctttctg agctgactta taaatttacc cacctctttt
tccccaaacc 69360cccaaaaaat cctccagaag gtgagcccag cttgttgtaa aagattttga
agcagaagtc 69420ctgggtttaa gcttcagttc tctgccttac cagaatcggg atgtgtgggg
caggcctacc 69480tcctctttct tcatctgcaa aatacattga atgaaatcat attttttcct
aagtatatga 69540catgtaaagt ggtatttcaa aaactcatta atctgcatga ccaggtcaga
aaagacacac 69600cttttgcctt gtgtctagtg tgtgactgtc ctcacatgta gatgacccag
gccacatccg 69660ctgatgttgt cttcctttac ttctttgtcc cttccaatga ctcctttatg
aagtcaatca 69720gcagtgtttc taagccaggt tccttctctt cacacatccc caacccacag
ggcaagtcat 69780ccacattttg cctctctatt ttttgtgctt tgggaaacac attttacaac
ttccaaacta 69840tttgcctaag ttcatctgag cacatctaga attattccac tcctctgcat
cagtgctaaa 69900agtacaatca tgtataagct gttatactcc cgttattttg tacctcatgt
gcaggtagat 69960tgcaagttcc ttgcaggcag gtactacatc tacttgaatt gcttcacgat
cacataacac 70020aatgcagtgt taaaagtaga aaagtaattg acatcttgac taacagaaac
actaaattca 70080gtgtattgtg atgatacctt tttaagagat aggctataga aatagaaaat
catcttagtt 70140ggaattgaaa gtcaagaagc aacattttaa gtaagagatg aaaatactta
aaagggaaag 70200gagcagtgct tacacagatg aggggaaaaa ataaaatgta tcatctaaaa
atttaaatca 70260aatatattag gttggtgcaa aagtaactgc gatttttgcc attaaaagta
atagcaaaaa 70320ccacggttac ttttgcacca acctaataga tgggaaaaat aagaggaatg
aatattttaa 70380gctttgctat ataattaaaa tattcttaga agtctggagt ctgtgaaggt
cacaccctct 70440ggtcttctcc cagcccatag ggtataaata atctgaattg acggcatcca
gggatctcag 70500aaattattag tacatcccac agtgaattac caccttacta aaatattcat
gggtatatac 70560tatggatttg ttttatccta tttagtctta aaaactataa agaaatctgc
aggcttatta 70620acatattact cagaatcata ttgtctccaa agcacaaact gaatcagtta
caagatattg 70680gactagagat catggcaaat cagaggtaca taagacctag ttccgttgtg
gagctaaaca 70740aactgcagag acctaaaggg aagccttgca ccacactcta ggtttggagc
tcaggttttg 70800agtggtgtca gcactccaga acacatggga tccccgggag gtggaaattg
agccgtcttt 70860ggagaatcag ctaatgagac agatgcatgt taaatgtctg ttgtggccca
ggcactctgc 70920taggcagagg ggtgaaccag aagaatgaga ttcatggggc caaagaattt
gccttctggt 70980gtaagaaaag atggaggcag cttggcagaa agaaaaaaaa ggtaaaagat
agaaatgaaa 71040tacagaataa tctatctcct catcccacaa gcaattctgc ctggtttgtg
gctcacgcct 71100gtaatcccag cactttggga ggccgaggca ggaggatcac ttgaggtcag
gagttcgaga 71160ctagcctgga ccacaaggtg aaacctcatc tctactaaaa atgcaaaaaa
atttagggcc 71220gggtgcagtg gcagttctgc ctggtttgaa catctggttc agttaaaata
cttcatgaaa 71280atatttagct tgatgcactg aaatccatca ctgcttttgt gggatgcact
gactgcagtc 71340tgactgttct cctagtggaa aggggagcaa tagcttctgt ctgcatgtgc
atgaaacaga 71400tggaaattta gaagagattc tagtgcagac aacttcatcc cacccccgct
gcccacagag 71460ctagccatgt gcacggtgtg tttgaacaat gttatgttgc tgctgtgcac
agagatcccc 71520agtctcataa aacatactgg atggaaggct gtcgagagat catcaggccc
cagtgcataa 71580gttcttccta agcatcctta acaggtgatc acctcgccta ttgagaaccc
tcaggaggca 71640gcccacttac ggaagcactg attgttacaa aagccctgaa ctaaatctgc
ttgtctctaa 71700agccagccct gcagatgtct gcagtgtaac tactttctct tctctcaagc
agttcagccc 71760ttcaaatcat tgacaacagc tctacaaagc cctctaaata gcccgttctc
ctggctaaag 71820tgtgttggtt tcctcagcat atgatgaaat aaacaccatg atgcctttgc
cttgcttttt 71880cttgctggtc tcactcttcc ctggcattct tcaatgtgcc caagtccttc
ctagaacatt 71940gcacccaaag ggccttcctg gtctttccag ggaatgcaga atgaaaaaga
aatcccatcc 72000cctgcctcga aaggagctct tctgtgtgta agtgtacctt ccccctcagg
gcataatggg 72060aaacagtttg ccaaagctaa ctgtgtaatt tcacatgact cactgccgtt
agtctgagaa 72120agcatggcat attaaactca ttttccatgc ttcccaactt tatttactat
tccatttctg 72180aggggcagag agctgagcag gaataacacc ttccttgctc ctcctaatgg
ggcacatgtg 72240cacatataaa attgtgttcg atctttgcag ccacgaccca tgttaactgt
caactgagaa 72300ctcatgagtc agtttctcag gaacagccct gaagacatta tctcctgcat
cttgtatttg 72360tgcctttgat atttggaggg aagggtagga tctggcaatt atcgttatct
catttggttc 72420agtgtatttc atttcagcct gttaagatct tttggaaata ctgtatgtgc
tagttacagg 72480gacagtgata aataagacag cattcctgtc cttgagatgc tatttccaca
gctccatgag 72540atgcctagtt aaaaacagag ccttttttgg aaacagccta ctaatctgtt
aaaataataa 72600tggaaaaaga taaagttagc atacctgagc tgcaagggct gcctcctggt
ctgatctctg 72660ataaggatca gatcctagag cctctgagat ccctgtcctc cctgtctgca
caagcactcg 72720cagaaggaga aacagtttac ggtggttcat catgactttg aaccaagctt
aaagtcaaag 72780tcatactctt taaaccattg gaaaccaagt ttttgcgagt tgcctaaagt
gggcaaaaat 72840cccacaatgc acctgagcac aagcaggaaa acatgccatt gtctccccag
gagccctcct 72900tgacttctac tttactttat ccattgacac tagtcttata agtagctttg
tctgtccaat 72960ttttaattga atttcgtttt tattttcgtg agtggaaata tcactttgaa
agaaatcagt 73020cctctcctga aatccagaat tcctggagct cagtttacat gtttgacgcg
tgtcacatga 73080ttccacaagt cactcaaggg caggaggatt accatcgata cggaaagatt
tcttagaaag 73140cttaagtgaa agggaaacca gggagaaagt gtgcttcgtg agaataggta
tgcggacggc 73200tctttgtgac gctctgtgca accctcgtgt ttgcattgaa ccaagctgtg
ctgcagatgg 73260acacccatcc catttccccg actcatacca gggaggccca ctttgcaagg
tacacagagg 73320ggaccacaga gcagggggcc atgcagggga ccaagggaca ttttagtgta
accaaagtgt 73380gaagtatgcc ctttatttca aaagaataaa gaaaatcaca ggttttcccg
ctgatatgcc 73440agggacattt ccaagagaat tccttttttg agagaaatct cctttgatat
cccatcagtc 73500agccatactg cataattgtt agatagtgaa agaaattcat tttttaagtt
tgtcagaaaa 73560ataaattctt tgaagtctta aattgttgcc tccggacatg acatatctgg
ctcttccaga 73620atccatgtta gtcctagctg aggaagaagg agaaggagag gggcgtttgt
tgattattga 73680ttttgtaaga tgccccacac gttggctatt agcagaattc tcacttctaa
aaggaaaatg 73740agtgtgagct atgttcaatg agaaacagtt atttttggga cattctttga
ggtaaaacac 73800ctccttaaga tgctgcttcc ttattgctat gggaccaaga ttagagcaag
aacatagtgg 73860ttttcagacc ctggacatca tccacagccg cagcagaggc cctgcccact
tgaacaatga 73920gacaggccac cattttgttt cgagaatgag caaagtgaac caccatgcca
gatattgtta 73980agtcagcaac tcttctgaag atggacatag taaaaaataa acaaacaagg
cagcacttga 74040gatggtcatg gcagagcaat ctcaacaagc gatttgttat tttgcacagt
gatgtaccca 74100ctcattgaat aaaatgcacc agaaccatgc actacagatg ctaaggagag
ttgtccttca 74160acaaaggaga taggccccac tggccgtggg gcagtttatg ttatttggtc
cttgtcatgg 74220gcaggcatgg ccctttctat gcttcacaga tgaggaaggt ccctggcaca
ggtccagtct 74280ccagcatggc ctagaggtgg caggtgctac ttagcatcgc cagcctcctg
cttggtcatg 74340gggtcagcca gtttataaca cgaacggagg ttaatgaact gatcttccca
tcgcacaact 74400ggtatgaacc cacatcttct gattataaat cttttgctct ttaactctta
gtcattacca 74460ctgtctagtg taggcctgtg tgttcatggc ctttgttgcc accaaaagat
caactattag 74520ctgaataaca tactgagaca tgttggtgtt gtgttctaaa tagcactagt
aaactgttag 74580ggaaatctga ctatatagct actatccagt ctagtttttc ttgcgaagtg
tttgttgagt 74640gtgtaatgag gagtaaggaa ggtgaataag aaatggcctg agtctttata
aaataagcaa 74700ggagagaaaa cagttttgat gagaagcgca tggaattttt agaagatagg
acgtgtatta 74760tgtacctata agaatgggta ggattttaga agagatggat ggggaaaagg
aacagggagt 74820gggaacaaaa cgtggaccaa ggaagagcag gtttagccat ggaagcctca
ccgccggctt 74880tggtttatcg tgggccaagg ggacagaccc tgtggggagg gctggcagca
gggaggtctt 74940ccagaagtct atcctgcagg cagtaacagc cacccagtct ataagctgag
tgggcatggg 75000ggtgatgggg aatgggtggg gagttattgg ggtaacttac cccaaaatga
tagctagctg 75060gaaccattta ttctattgca ttttatcaat aaatcttata ggaagtacca
tcctagtgaa 75120aaccctgtca cattgagggc attcatgctt atgttttaaa acatgttatt
gggtctatga 75180aaaataaggc tgaaacctat gagcaccctc catgcaaagt ttcagtcaag
actttggaaa 75240caagacagtg tcttactcac tttataaatt cattcagaaa gccgtaggtt
tgaaaattcc 75300aaacttagat gtaagaagct ctgagaaaca catgaaatca cccccacatc
agtagagatg 75360tctcagcaga catgggaaga ggggcagcag ggtgtaggga ggtggggcag
ccccggggtg 75420ggccttgcag gctgggcttg aatcccatgg ccaccaccgt ccgctgggag
gcctggagcc 75480ggctgcccac tctctgacca gcacatgttg atgctgtatc cttgaaggga
ccgtggtctg 75540acatcctgtg atgcagacct gaatccagca cccacagggt ctgcacattc
cctctttgag 75600gtggagccca gctccagagg ctggtccctg actctgtttc tcaagaagcc
tgtacagatg 75660ttcccctcac cactgtttcc agtcaccttt ggctttcacg gtgcagatgc
taagtttgat 75720tttcagagcc catctgggaa tttagtgaac tgaacaggta gcatttctga
acccacccat 75780aacccatgcc ctccccactg attttgaaag agagtttgct gcaggtgact
ttgcagctgg 75840gtagagaatc ttggggcagg attccgaggc aggcagatga gtgaggataa
attgggttct 75900gacggcacgt tacaccagtg gactctaacg acgacctcac ctcgtgcaca
gataattctg 75960ccttgtgctt aaccgttaga aatgtgtcac tgaagtgtga acatattatg
ctgttagatt 76020tcccatcatt tctgttcttt cattccctct catttgcatt ggttactcat
aaatgtagat 76080ctttggtatg atttgtacaa ctgccgggtg tcaatctgtg aaagaaatag
cagagcaagc 76140tgggctctgg tagcgcttta tccctgcgtg ctggcttgcc cgggttgact
cagaggcagt 76200ctcacattca gctgcgctgg ggccaaggac ccagggagcc aagtgtgttt
ctgttttctg 76260tatttagcaa tttaagacct gcgtttaaat actagctatg cattctagca
aaagaggttt 76320atattttaac acagtaactc ttaattgttt aattcagttc gtgtgttacc
tctcggaata 76380aaatagtgga agccaattaa ctatagactt cattagtttg gatttaagat
caccaaaaca 76440tttaccacat ctcaattgtt cattacatgc tctctctttt ttaatgcagt
ttttataata 76500tggggagtgg gggtgtggat ttaaccatta tatttttatg atattgggag
tagatttaac 76560cattatgtaa attggatttt ttaattttaa aaagtcactt atcttgatgt
aaaatcatgt 76620cttagtaacc ttgataaact aagttttgca tgattacacc ttaaggttaa
aacatatttc 76680atttcatcat ttcccagaag gggcactgaa ttcacccatt tcctgttttt
catctcagaa 76740tgttctgtgt ttcctccata tctactttcc cggcagcagg accctggaag
cagtcacacc 76800aacctcattt accccacctg agatttgtgc gctttgaaca tagttgcaat
caaatcaaca 76860atatctttgc tcagaaatgg atatgtgaag taaaatgtgc tgccctgttc
atgtatgaaa 76920tcattcagct agctggccag tgagcccttc attgcaacaa agatttttct
agagcccctg 76980cactatctgg ggctatgtca ggcctcacac tcctgctcac acgtttggag
gctaccttgg 77040ccagtattac cttaatccag catttagggg aaggagcatt tcaagactaa
attttctaaa 77100ctgctcaagc ctacctcatt ttatttcttg tgtattttaa cacttttgga
tgaggactct 77160tcctagaacc tactaacaat tcccccccgc ccccatgcca agattcttta
aagactttct 77220tgaaaacgct tcagtctttt cttcttagct caaaagtact atcctaaata
ctagctctgg 77280cattacaggg agttaatttg tgggcacaca cagtaaatta taaacccctt
aagcagagaa 77340gattgtatta tcagtttatt agttttctta ttcattcctt cagcacacat
ttctgttgcc 77400tccaatgcag cagagaaatt gacttctaca gtttccacaa cagtccagat
ttcaactgtg 77460tagtgctctt tcagccagaa agtacacttg tgtttccctg gccataggtc
ctgaacctca 77520cttctgaaaa gtcattgtgc atagagagct aatagctgta ccctaaatga
tcctggcttt 77580gaattctctt atctgcttgg atagtattat ctgtctcttc ctctgcattc
taatttgcta 77640cttctaatct gctgggaatt acaataagaa agaaccattt aatcattttt
acaactgtgc 77700ctaaagagag tgtgtgtaag tgccgagaga gtgtatgagg gacttgccca
tgagtaaatg 77760catgaatttt aggtcaaggg ttttttgctt ctcttttggt tgattacctc
agagatcagt 77820tttactttct ttctcattct tgacctatca tcactagctg atatggatga
tgtgtacaac 77880ttctgagtaa gaataatgtc aatgggacgg gatgggattg gctggtgatt
ctgttgatct 77940taaagtttat atattttaag tttagtgttt cagaatgaga ccaaagcggt
gacattttca 78000acctcttcgg tctctcttca gttttttcat tttaagtttt tgttgtgctt
ctatcactta 78060aaggaagcct ccaagttgaa atcaaatact aatgacattt ttatctaatg
tataaatgtg 78120tttttattat ttattaggaa atttatttta cttggccctc agccatgaca
tatcatggca 78180taatcactat cctaaatttg tatatcttat ccttgcataa ggtaagactt
tctatgaatt 78240acacatattt gtattttcct ctcttacata ttttaagaat ttttttatac
tttgttttct 78300gcaaatgaaa tattgctcat aagccaggtg atggctgtcc acgcctcttt
tcccctgctt 78360acccttgctt agatcttatg gtagaatctt ttcatagaag acacagaaag
acatgaaaga 78420aagagctgga gaagcctgag gggctgccca gtgagtggtc tgctaggatg
ctgtgccaca 78480gcccaggcac aggaggcagg gagagcaatg gggcccttcc cttccaccaa
cattcagcag 78540aatttgcagc tccatgtttc caaagcttcc agggcacttg catttagaga
gagagagcaa 78600gcaagctgcc tttcctcttc ctcagttctg ccagccacac tcttgccatg
atgagcagtt 78660tcagccaaaa gctccttccc ctgccctaac acctcctgca aggcctgagg
tctggaagcc 78720acctgcgcct gctggcccct cctttcttgt ttctgcaatg gatgttgtgg
ccctgtgagg 78780gagaagagaa aaagaagttg ccctcctccc tctatcctca cctcctgcca
tgctgtcacc 78840cttataagag agaagggcta accatccagg ctaatcctcc agtgatgcag
gagaggacat 78900cctggccgga agagtcagag cttccaggtg agctcaggtg ggtcagcccc
cgaggctgtg 78960aagagcccag gggccagtag atgccacttt tgctccagga agaatcttca
actgtgtcct 79020ttttattcaa ggggctctct tttcagcgaa tctctagatg tactagtcac
aaacactcgc 79080atttattaaa atgtatccat gatcccacaa tccttttaca tatttctctc
caggagtatc 79140acatttctga gggccctgtg cctgttttct gcaggaagtt gctgttgtcc
cgggtccccc 79200tgcccccagc acctctgtta caagaagcag acccttcatg ccacactggg
acccagggag 79260gccccaagcc aggatgctgg gatcttagta aaggttggaa tgatgtcaga
acatagagga 79320ggcagaattc cccccatagc atcatcctgg agggcgctga tttgtgtgct
ctgccaggtt 79380catctgtgac tcaggattta aaagccccag gtgtggtgtc ccttctgtgc
ctgcaaggtg 79440cgtctttagc agttctccct ggtgtggaag gatcagtggt tcttgcagcc
taggcaccct 79500ccacagcaag cccaacacag gtgctgtgag cagctggttc atgaacggtg
atcctgggga 79560gaagaggagg atgaaaatgg aaaaccagtg caaaggtgtg tcatccagtt
ggttactgct 79620gtgggtgccc gggcttccat cccaccagag cccccactag ccagggcagc
ctggcggagg 79680tgagcatcat tctgctttct ggctgcacct gtgtggacag agcccgttcc
aaagcctccc 79740aggcacaggg cagacatcaa gcaaggggca gagctggggc gagggctctg
ggtgcccccg 79800ttattgaaca caggcctgaa gggagcctaa gaggtggctg gcaggagata
ctacaaggca 79860gaaagacagg gcagcagtct ttgtactgta cgtttttgtt ttttaagaga
gaacaaaaag 79920tcaaggttga gagatgagaa atactcttgc caaaaagaga acaccaaaat
cctggagtca 79980cgggtcttcc attaccctct ctagcatttc tgcttgtctt ttccctagta
ttggtgaaga 80040atttttaaag taaccaaccc ataccgttgg ttacaggccc tgtggtcacc
aggctgtctc 80100cccatgatgg ggatggagag tggttagtgc agaaacttag acctcccctc
cagcttgttg 80160aatgccctga agtttatcta gaagggaaga tactcaagcg taggatttca
gtgatgcatt 80220tggacagcat cagtactatg cttcagcgtc aaaaacgtca ctttgggtag
gaacaataca 80280taatgcgtgg caatgccttt tgtgacacct gttcaggaga ttcccatagg
aagcttctga 80340ggcagagtcc tcaggtgagg agggggacag gcctgggtct tgggggaagg
tggagatgac 80400cagcctcatg cctctctccc cagtggcctc agtctccatc aggcaaatct
tgagaagcct 80460cctccattct gcaggcaaat gactgagatg tgtgagctct gcttcccaac
aggcggaaat 80520tcacatgggg aagggcacct gtgaatggcc ttctagaact atcaggaagt
tctggattta 80580gtaccctgtg agagcagatg gtcctgggtg cactcggatg atcctgccta
gccagctgga 80640ttgcagagtg gtcatcatta tcagtgagct attgaggggt tgagagcagt
cagtgtcatg 80700tataaggatg ggttggggta ccggccaacg cccgccttga ggcctggccg
ccggatggga 80760ggcgagagca caagagagtc ctggctaggt gtgccccgct ctgcagggcc
acaccatcca 80820ctggaaaccc tgtgcccact gggctgcgtg ctaagaggct gtggccaatg
ctcttgtcca 80880aattttactg aatctgcagt ctctcttaat tcactccaaa gtttaatgtg
ttagcttgcg 80940aataaataaa taaataaata aataaataaa taaatggaaa gaaacagtcc
tcagaaagtc 81000ccagtcaaat tttaattcca acagatattc agcagtttcc tctaagaaca
atgagagttc 81060tggggctagc cagtgtttct cttggaaaat aaggaagagg gaaagcggtg
cattcattta 81120aaaacctgcc ctagggaggc agcgttccct gtgaactccg aggccacagt
gagcagagca 81180ggctggaggc ctcccggctg tcctgcccct cctgccacat gcctgtgaaa
atgctagata 81240aggacttttt ctcagcaact tccacgctcc ttcagtgggg atgtctttga
ctcagagctc 81300tgccactggt tatctccacg aacagaaaat gccacagatg ggttaattca
ctgtgttgtt 81360ctcattttcc ctcagtttca ggcttttctc tccttgcctg ttttcctcgc
ttaaaaaatg 81420atgtgggggt ccctaaacgc atctaccccg atagatttat gttttctttt
ccattagtcc 81480actttgcgtc tcagccctaa aattaagttt ttgattataa tgtaaggaag
ttttaccata 81540ttttaactct ggctttttaa atacaaaaga aaaataacag aatggccttc
tagaactatc 81600aggaacttct ggatctagta ccctgtgggg acagatggtc tggagccagc
gcacttggat 81660gatctctctc agccatctgg accatagagt gaacttgtta ctgtccctcc
aaggctgaca 81720actatgagct catactcttc tagcagttta atttagaccc aagaaaggct
gtgtgtgtgt 81780gaatttgtga gagtgtgtga gtgtgtcttt gtgcctgtgt ttctgtgtgt
gtctgtgtgt 81840acatgtgtgt ctgtggggtg tgtctgtgtg tgcacggctg tgtgtctgtg
cgtgtgcatg 81900gctttgtctg tgtgtgtgcg cacgcactct gctaagctac tcaatgcaat
tccttactct 81960tacttccctt tctgtcactt ctccataatt ctttgtattt cggttgggct
ggtatctcgc 82020ggcggcttcc tcttttcctg cattcctata tttcattatt tgctcttgtt
cctcttctag 82080ggcttttaca atatagccag gaggatgtgg aaacccagtt acaagatgac
acacaagcac 82140agtgtcacaa tcgctgtgct tgggccctac ctcctggaga ccagggtggg
acggtgtctc 82200tggatatgga gggaagggcg gaagatcacg gggtggcaga aggcccgact
gtccggtctt 82260ctggaagctg gggtctcgtg gtcgctgggc tggtggtgct ctaaaaccta
gagtaaccga 82320gagcaggatg actgcacccc tgactgccga ctcaccgggc ttcggagggc
catgggtgtg 82380tgattccact tgtgatcctc ctacttcccc agcccaccct ggtggtctcc
cacttctctc 82440tctctgcctg tggagtgtta taaccgactc cttcttctag gcatctccat
cccaacccca 82500gaccagttcc cttaaaccac ctcccaccac aggaccccca caagcaggga
cctctcacag 82560ttcctgttgc ctggggactt catctcagct tccaaggcct ctggaaccag
gccctgcatc 82620ctgggcatga ctgtccccat gattctctga gccagccacc accccaccac
ccccccaccg 82680ccaagtccac tgctgaccct gctgtagccc cccacctcca cttgttgaga
ttccctcttc 82740ctgcttctca ttttgaatgt cacccttctg tgacttctca caacccccct
gccacccctc 82800cctccagttg gcatggctta gtcttcctaa gaacatgtgc tgcttcccag
tacccagggc 82860tgctgtgcac cgtggcacgt gagtttcggt gcatcttcct cctgctgttt
ataaattgca 82920acatccctgg acagatcttg gattttccct ctataatttc tctggagact
ccctcggggt 82980ttgcacacac atctgtggaa tgcccaagtt ggagatggtc ctccctgatg
tgtagtgtgg 83040gctattcaga gggcctcatt tcataaactc attaacagct aggacgcgaa
gacttggaga 83100agttagctca ggacacacgg agtgggaggg aggcaacgag ttaagaaatg
ggctttggag 83160tgcctcgaat ttggcctcca cttttctttt ctactgtctt acctggtctt
aggcaggtcg 83220ggtgaccatc tggagtcgga gtttctctca tttgtaaagc gggggtgata
tttttctcac 83280agggctgctt caagggttaa caaagttaat gtctaggaag gacatagcat
agcaccttca 83340cctggttgca agcccctgga gtcacatggc aacagctgtg gaaccaggta
aatgacttga 83400cttacatgtt acacgctctt agttgttcga tttgtaaatg ggaagagtgt
gtgacccaaa 83460ttagtcgttt ccagatattt cctggtaaat ggttgttgaa tcataaaact
agaaagatgg 83520gaaagaaagg gaggaacccc ccttacttcg aagaagtgtt gttgatgtga
aggacaggac 83580tttttgagac actctcatcc taagaaacag ctgatatcta ctaggaaaaa
acatgacatt 83640tgaagtttct tcctaagaga tgtgaggttt tgacagaagt gccaggaagc
cagaggtgtg 83700tgagtagtgg gccaatctcg cgtgaaggct gtgggacggg gcaggagagg
ggcagccagc 83760atttcctgag cgccagctaa tggcggggac ctggcacctt tgctctgtga
ctctccagct 83820gtatggtgac atgaggctgg cgttttcttt ggtttcatac gtgaggaagc
tgaggcttgg 83880tgatgtcctg tgcatggctc ggactccaga gctactcaga ggcagaggcc
gtctgtaaac 83940accttcaggt ggttggaggc agggtgctgc agccaatgct gatcactcac
aagccaaggc 84000tttattgtaa gggctaaata aaataacata tgcctagcat ttatacagca
cggggctttt 84060taggaaatag tgagacgacc atggagaggt ggaggaagag agaagggaaa
gaagaaaaag 84120aaaaaaaaag ccttaaagag tttcttaaga gaactatata ttacaaagtc
cttggagttt 84180tttttccctg gttagacata agtttacatg aaacgttaaa cggcttaaag
tagccacatc 84240tccttcctta tgtcttctca cagccacttg tgagtttctt atcaagatac
agaattatgg 84300ccaagtgcgg tagctcacac gtgtaatccc agcactttga gagactgagg
tggaaggatc 84360atgtgtgctc aggagtttca gaccaaccta ggcaatatgg taaaaccctg
tctctacaaa 84420aaaatacaaa aattagctgg gcatggtggc atattccaat agttccaggc
actcgggagg 84480ctgagacagg aggattgctt gagcccaaga ggtcaagact gcagtgagct
gtgatcgagc 84540cactgcacta cagcctgggc cacagagcaa gatcctgtct caaaaaataa
aataaaataa 84600aataaattct gcaacaagtc acaattcctt gctcagaaat ctctacaggt
gtgcttcttt 84660gttaagaaat ggaggaaaca tgaatttcat cctgacttct gagtcttgta
gagaccagat 84720ctgactcctg cagccttctg cccacagagc tggcaggcgg gggaatgtgc
gcagagtgag 84780gaggagctga tctgacattc cgaacagtgg agactgctgc ctatttggcc
gcaccactgt 84840ccttctgcat ggaaaagtca cagtaaataa tggactctct acctgtgagt
cgattttact 84900gagctgcctt tttaaatata tgtgtagaaa gggcgatctc tgtgtgtcat
ttgcacatgt 84960acatacacat gtacacacgt gcacacgtgg tcactcatgt acacatgtgt
gtgcaccagt 85020gcaccagacc agatgcaccc acccaattcc acgctcctca gccccttgct
ttcctctgca 85080gacagccagt tcagctacag ttatgccaga ttgcctgcac tctgatcttt
accatcacca 85140gactctcagc ttgagctcat gcctgagaaa tccactttct gggaggaagg
cagaagaaac 85200tgccaaggca ggactgaaga cttgacctcc acctgtagtg gggtcaggtc
accagaggct 85260ggctgactcc ccaggatttc tcagcagagt attacacaaa taccccttcc
ttaaagatta 85320gcaaccactt aaagacacaa agtgtgcagg actgtaccca tggccgagag
cggcgggatt 85380aagagggcaa ctgagttgtt cttcccatcc ctcctcctct gtgctgagtc
accttctgct 85440tggaattctg acagggaccc gttgggcttc tggaagggag ggacagcaga
ggatccaccc 85500tctgtgtgtc ctgggggaga ttacttatct ctggcctccc tgaagcaggg
cctgggcttc 85560tggaatcttt gaggctgaca ccctgccagc cctggggatg agagggaatg
gccgtgtctg 85620tctgcagagc ctgaggagga gctgagcaca gcctccagag ttctcttcag
ttgatcgctt 85680aggtggacaa aggccacaga aatggattta aactcctcag ccctttcttt
gcatgtttgt 85740tctcatttga agtcagaagt gatatgtcct acacctcaag aacgtgtgaa
atgcacatac 85800aataacccca tttcaggaag ccaagtccag cttaacagtc aaaacatttc
cttcagtctt 85860tagtccttca ctttgccgaa ctccctttta caccggcagc aacagtttaa
cctgttgctt 85920ctgtaagagt gtgctactgg gaaaaccaca tctaaaacac gtgtgcagtt
acatcagcta 85980gagcacatgc taaacagttg atcaaaggct cttgccttgt ggcccacgct
gcagacactc 86040tgacgactgc cgagctccgc agccccatgt cgtcccttcc gcactgcctg
ctgtgcctct 86100cctctccatg tggcagggaa cacagccagt catcaccatg tggctctgcc
cggcgctgcc 86160ccagcatgtc ctgacagggc ctagatatgg aaaggtggct ctccatgcac
acaccccaag 86220cccctcctgc ccgccgtgtg acccacactc ttatgggcag cccagttatt
ttgtagcatt 86280tcccttcctt atcattttgg cccagtgatc cagcacaaat ctcccttatt
agaataaaat 86340ttggaatgac aaaattaaat ttcatttttc acttatattg aggacctcac
actcttcacc 86400cctgccacga tccctgacaa gagccttcct atctaatcat tgttcctcca
gccctcttag 86460ttttcttcag cctttcttga ttgcctgaat gtccctttcc cttctccttt
taaagcatga 86520accaagcttt cttaccccgt tctcattatc atttttgcat tttcttcttt
gcatatgatt 86580ctccttaaat tataaaactt gggggtaatt tctagaggtg ccatcatagt
gcttctgtct 86640actcagtgtc tttagaatca gcaaatatca tttttacaaa aaagtagtat
ttcttccaaa 86700aaagagtaag caagaaggtt acaacactgg gaaaatatcc ctaagcctgt
tcttcaacct 86760gttgaatgtt ttcccctaaa ttgttatatg gagatcctgg acccggaagt
tggctgacat 86820gaaacaggcc tagcagggca gctgaggaaa tgctccaacc tcaggatcca
ggaagattgc 86880acatggcacc aaaacaatca tttaaaagct aatcctggcc aggcacagtg
gctcacgcct 86940gtaatcccag cactttggga ggccgaggtg ggctgatcac aaggtcaaga
gatcgagacc 87000atcctgacca acatggtgaa accccatctc taccaaaagt acaaatatta
gctgggcatg 87060gtggtgcgcg cctgtagtcc cagctacccg ggaggctgag gcaggagaat
cacttgaacc 87120cgggaggagg aggttgcagt gagccaagat catgccactg cactccagcc
tggtgacaga 87180gcaagactcc atctcaaaaa agaaaaaaaa agctaatccc ataaaagaac
catcattttg 87240aacctgctgt ttcctttctt gtactcttta gaagtaccca tttctccctt
tctaagccat 87300aggtgtatta attggagctt tttctatctt aattagttca ctgtgaacaa
ttaaaattgt 87360gttaataaaa caaaaacaaa aataggactg gtgcctagtt gtactacatg
aagagagaaa 87420gggccagaca ttggtttttc ctaatcttct gtcaagttct ccaaatcatc
tgctctggaa 87480ggtagctcca acagctggga tttgaagtaa agcatagtga ctttggccat
cactgacatg 87540tcccatttga agcaaccaaa actgtccctc gacctgacac tcatccctga
aacaccatga 87600gggtaagtga ggcgcttcgg aaggtccact caaccccatt gccagataga
gtaagtgtct 87660gccaggggca tttggagctg aagggaagac tgtacagact cacggtttgc
aggcactgaa 87720ggcgttttcc tgccttcttt ttcaccttca gtggacttgc aaagcactag
ccctattgtt 87780tttcccatct gggaaacatg gtgaatgttg gttggttgta gctaatccta
tgggtcttga 87840ggtctttgtt gacaagaagg tagatgttat ctttatctgc gtgtggcttt
ctactaaaac 87900atgagctaca gggctctctt ttttgtttta aagcattttt ccataaggtt
cacccttact 87960attgcttatc tgaataatat tacctgctga gaagtttatt cattgctcac
cagttgtagg 88020gagattttga cacaggactg gaggattttt ttctcatcgt aacagtgcag
acccatggaa 88080agcttggaag cagttgtgac cggataagag caggttgagg atgataatct
tagggcaatg 88140agcaggttga ttgagagggg tgcctgaaag caaggtcccc atgatgcaag
caaacaaact 88200cacatgccag acggtggaca ggaaacacag gcaggatgtg gtgcaggctg
ggctgccttg 88260gctgggcaaa ggcaggggct tcatggccat gctgggatgt gacgtggttg
gaaaacaata 88320agaatggaga cctctccaaa gacctcagac ataatttggc catgagaggc
aagggtagag 88380gcgagccccc tgtgggttgg aatgtatgga atccagatga agcaccatca
acatgcatgg 88440gctacatagg agagctgggt ctgggggaaa agatgggatt tgggtttggg
tgtgcatgtt 88500ccaggcatgg agggaagaat gggcagaatg acgaggatca agccctggtg
gagcccccag 88560accagggccc tgggcatatt tccacttgcc ttcttctgca aacttttgtg
tgcctgttgg 88620gtggaaggta ctatgctggg gccatccagg atccggagca gtgtaagaca
tcatggcctg 88680catggtgtga cccttgacat ctgaaaagaa cgagctggtg gagtgggaag
gagacaagtg 88740gcagcagagt tgacatcatc aggactgact gcaggacagg cggtgaaacg
agccactgag 88800gagttaccca gtgccctggg gagcttagat gtgagactta caccacccag
cactccccag 88860ctctgtgtcc ctgggtccca ctgaacttga ttgtatttta gttgcctctt
ttctaagacc 88920ggagcaacaa taccttcctt gagtgtgcat gtgcagtcca tagatggcag
ccagtgttct 88980cttcccatga gaagactctg agcctcctca ctagagggtg gtctaaaaac
aaatggatcc 89040atccacagaa ggtctgaaag gttttcatag aatcttgact tggtagcact
tcaggatcta 89100actcgtgctt tccagaagtg tggcctgtgg tgttctgtct ggagtatttg
gtcctcccat 89160ccacctccac cttgctgtcc tgtcctgtga ctctcactag ctcagtcacc
gggtcaggaa 89220gccctgccat gaaatgctag atttggaggc attgccaagg taccacaaac
catactcaaa 89280caaggtcata atagactagt gatctcactg tggctaacag gttcatgtga
tttaaagaat 89340gacagcattt tttctaaatt ttataaattt tataaatttc tcctaaatac
aaatctgaat 89400gtgtttacct ttagacagat tttcccagaa aattgtcagt gttctcgaat
ttgaaagtag 89460atcagatctc ctccctctag ttttgaaaat ctcaagtagg tttagcctct
ccccagagtg 89520acaacggcac aagaagttta taattttatg cacagctaaa tgcaaactga
aaagtgtggt 89580ttgtgggtat ttcatttttc ccataatgtt catcaatttg gcaattcaaa
taggattcag 89640aatccaaggt gttcgcagca ttttatatga aaatgtgcct gagagtttgg
ggaatagaaa 89700ttcttaccaa ataagttaaa tttgctcttg ataagaatat attttgtaaa
atgtagaaaa 89760ctgagaaaaa aagtttgaca cctgttttat ctgcatcctt ttattaaaca
gtggcctgaa 89820tttactaaag gacagagaac agggttgaga ggtaatcact gaataatagc
ttcgctaatc 89880ccacagtgac tgcttcttat gacaagcaag agggtcaact tagaggcagg
actgtcttca 89940ggggcaaaag caagtcagca cctacaaacc tctccaagag agtgagaaaa
agcaggttgt 90000atggctcatt ttgcagcttg ccagaagcaa tgtgggaata ttgtcagact
gcacagacct 90060ggggccagct ggctcctaga gtgcgaggag ctctcagtga ctgctgtgca
tactcacctg 90120ctctgtgact ttgttcagtc cctaccctgg atgtgtggtg aagggtgcca
ggcttagctg 90180ctggaccagt gaggtccctg agggggcagg gctaagaggt gtagcagtcg
cacttgacca 90240gtcattgatt cactggttgg gaatttgttc attgagggga caccattact
ccccatgcct 90300cacgtgcagg tgagtgtgtg tatatttgca ttaacacaca aacacactta
tgtgtgtccc 90360tgtatgtgca gctgcagtac cttacacatc ttccagtgcc tctcaagcat
cataaaaaca 90420gcttccacaa aacctctact acccacctgg catccacaga gctcccagtg
attggctccc 90480aaaagatact gaactttggc atggaacaga gtgagtttcc acatttgctg
ttgtacataa 90540ttacctgtcc agctagaata gtacacactt cttttactga gcccagaagt
ttatgtgcct 90600gaacacggat ggtacaggaa caagggtgag cgcttatcaa ttcagcatta
ctctggagac 90660atgaaacaaa ctaataggta cagctatatt ttgtttttta aacaattttg
tgaaccacat 90720atttgggaca aaaatcaaca agtaaatttg aattacacta ggcaaaggac
tgattctttt 90780gaaacgtgat tgacattcaa cgtctaactt tccaaaagaa gacatacatg
tggcccacaa 90840tcatatgaaa taaagttcat catcattgat cattagagaa atgcaaatca
aaaccacaat 90900gagataccat ctcacaccag tcagaatggt tattaataaa aagtcaaaga
atgacagttg 90960ctggtgaggt tgtagagaaa aaggaacgct tatacactgt tgaggggatt
gtaaattagt 91020tcaaccatgt ggaagacagt gtggcaattc ctcaaagacc tatataccat
ttgacccagc 91080aatcccatta ctgcatatat acccaaagga atatgagtca ttctaccgta
agacacatgc 91140acgcatttgt ttgttgcagc actattcacg atagcaaaaa catggaatca
acctacatgc 91200ccatcaatga tagactggat aaagaaaatg tggtacatat accccatgga
atactatgca 91260gccataagaa aaagaatgag atcatgccct ttgcaggaac atggatggag
ctggaggcca 91320ttatccttag caaactaacc caggaacaga aaaccaagtg cagatgttct
cacttttaag 91380tgtgagctga atgaggagaa tacatgggca catagagggg cctatcagag
ggtggagggt 91440gggagaagga agagtatcag aaaaaataac aggtagtaga tttaataccg
gatgacaaaa 91500caatctgtat aacaaacccc catgacatga gtttacctat ataacaaacc
cgcacatgta 91560ctcctgaact taaaagttaa attaaaaaaa aattaatgtc taataatata
ttacagtatt 91620cttcatattc aatggcaatg tgtgaagtgg gaagtgtctt gacagaattc
ggtgtttcaa 91680ggcttacact ttgatgccca agactgcaca aggctacatt ttctactggt
gagacaaatt 91740ccagacgcat tgcattcaga tctaatctct tagctcctta atcttcaggg
tactggtaaa 91800catgaagacc tccccagtgc tgtagtcatc atgatatgta cagcaggtgg
ctgagctctg 91860gatgtagact gcagggatat attaggaagt taattctcaa ggcaagtcat
cttcaagcac 91920catatcagca tgatcagcaa tataagtagt atctcagtgc tttgttgttt
agtcagagtt 91980ttgtactcta tcacccattg taatgttcct atttgcaaaa ggtaatacat
accctttaaa 92040acatctttgc tttttctccc attatcgaga tgctagcagc ttcataaagc
agaataacta 92100agggcaaaca gattatataa agggttggag ctcaatgaag acaacaagaa
cagcaaaggt 92160tattgtaaaa ctggctgctt gcaggccaac aagcacatcc atatggaggc
aatcagttta 92220tgctacctct gtctgtttga tgggattcat aatattgact ttatccatta
gatttggact 92280accagggaat aaaataagca gatggagagt aaggatttgc taggaaataa
ttcagccagt 92340cactttgaaa gctgttcaag aaacagcttt caaagtgtct ctcaaactat
gtttgcccat 92400tatcccaata atttatttcc caataatttc atgggaaaag aaggaagttc
tgtggtcaga 92460taaatctgga aaacactggt ttaagcaaag ttcagtaggt ctgcttccct
gcaggtcacc 92520tcagagtctt tactctgcta acctaggaac tcatccaaca agtttaattt
aacagctaca 92580ctgtgtacgt cactttaaca gtcactgagc tgtgactctt gggggaaaga
ttgtgcgtgt 92640gtgtgtgtgt gtgtacacat gtgtgcacat gtgcagaatc taccaaatct
taagagaaag 92700gaacatgctg ggaaactgtc ctgtgaaaga gaatagaaac ctgaagattt
gaggcagtga 92760tagcatttat gaaagcagca gataaggact aatcaccaaa aggggtagct
cttttgttgg 92820ttggggaaaa caggaatttt tcccccaccc aatgtgctgc attttctaat
tttctatgaa 92880cacttcctaa gaaaaagctg aatgaagaac atttgcgatg caatcagctc
attaagaaac 92940acgcactttt gtggagatac gtgctgtccc aggagatgct ctgcgaggag
ccgagtgttt 93000ggactggagc tgctgaatgg tttctcacag ttctagaatg tttggggctg
caccctctaa 93060gatgttgaac ccatcagtaa ttgctccaaa ccactttatg ggatataatg
ctgtgagttg 93120acacctgagg ggattgtggt cctgttcatg agtaattact tttctgttgc
ctatagaagg 93180gccagcaata gcagatgagt agctgaacag tggttttgag taataaaacg
ttctttttta 93240aaaaaaagta atgctttctg ttaaactctg actatactct ctcctggtat
cacaacccag 93300ctttcttttt gccttcttta ttgcagttac atatggggct gatgacttta
gggatttcca 93360tgcaataatt cccaaatctt tctctcgtaa gtatatgcct tgcttctgga
aaacaaaagc 93420atgccttcat ctcctatcat gtaaatatcg tacgtgcatg ttccttcatc
aacccccgag 93480atacattaaa tattcactgt tctattcgtt agacacctac catatcattt
ttgggtattt 93540ataccataaa gtgcaaaacg aaggtctagg cagttgtgcg gtgtcctggg
agcatggcag 93600tggagtaaca gtaagggttg gagtcacagt agcactgatg ggattgttac
ttcgcagatg 93660ctgctggaca gctttgagat tactcctgta atccttttta ttgagtgtga
ggataaaatg 93720gccatatttt ctgtcaccaa caaagaactg aacatggttt caagataatt
tttacaattt 93780tgtgggacag gagaaggaga tatgctcttc atctgtggtt ctggagtatt
aatttcagaa 93840ctgagaagag aaaattgcag gcctccaggc cgttattctg tggtgcatcg
ctgctggagc 93900caacgtactg ttcctgcttg gtgcccgcag gaccttctct gatctgagct
gttaaaccaa 93960aaacagatgt gaatttcatt tttctttttt agatattgag ctgataaatg
ataaatatat 94020ttgggtaaca tcctcaaatg agtactttaa agaacagaga gtgcttttga
aaatgtatag 94080agagctgaat atttaaagcc atacaagttg ataatcccct taggacctgt
attagtaaat 94140cctctaatac tataaagcaa catcagaaaa caggtcgcat ttgttaacac
tgtgacaatt 94200ataattatag gctctaattt gaacagtgcc agtaacagtt aaagacaggt
gtctgacatc 94260ctggttatca aaaactatct ggtgtctaag gaatttaaca gtatcaaagt
acatcttttt 94320gctcacaaac tagattggct acttttccag cctatagaag ttacagaaat
ctttctttta 94380ctgatattcc tttgattcca ctttaaagca atagcttgat acctactttt
tgagatgtat 94440atgtatgtac ttgtaaatgc ttatatatgt gtatttgttt acacgtgagc
ttatatgaac 94500atataaaaca ttatggtatt ggacagagaa atgatattga tttgaagaat
catattgttg 94560aagtattttg agaagtcaaa tgcacttgag agtaagctaa tgcatcctaa
aacatgtttc 94620tgtgaagtct gaggaaggtg tcagccagag catatgttga agcagaccct
tcagtgaagc 94680cttcagtctg taagaatcgc tgcatgtgaa gatgtgttaa tgttatgata
gttacagttt 94740ttataaaaga gatgatatac acttggatat gctttctgtc tatatttatg
caaatgtgtc 94800cataaggtat tggtgtctct ctttctctcc cactctcccc agtgttggaa
ttgtgactat 94860cttctcacac aagcggctac ttggtcttga tgccttcccc cgcaaaacag
caaccaaact 94920gttctgggcc aatatcacca ccttgtggtc atgatgaaga attgccccct
ttgccctcaa 94980cacctctttt cttcttgaaa attaaaaaca acccctttca ccccctctac
tgtccttatt 95040ccagtttgtg tccgtagttg ctggaggaaa gaaaatgcct attgctcttt
tttttattct 95100ctttatctgt ttactcttct gcctttcttt tctctccctg acttcattcc
atttaaaggc 95160cttaaattgc aaataacgaa aaaagtattt tctaataata taccctagtg
ggacgaaaac 95220aaccttctac attttaaatg atattaagtt ataataaatg gttccatgaa
ctttaaaacg 95280cttaaaagtt ttataaatct cttttagagg caacacaaaa atatctatat
atatatcttc 95340tcttcacctc aaattttcat ttaattaccg tgattcaaga tatatcttaa
atatttccat 95400ttcatttgat ttttacttgc tagtcaccag tgttgcaaga atatttctgt
accatttttc 95460aagtaaaata ttgagcattt caagcttaca tggcctaaac tcacactaga
gtgactactt 95520cggactatct tttcaatgga aaaatgcgtt ctgagtacca aacatttact
ttttcagtaa 95580atatgaagac acattctaaa aaggaaaggg aaatgaagag gaagcttaat
tcattggtca 95640ggtggggact aacagtgtac attataccta tgcattaaaa aatgtttaat
tatccatgag 95700cacatacagt gcctggcaca gattcaggcc tcttggctcc tcttggcatc
tgagttcctt 95760ggattctcca gattcttcaa tccaaacttg tctatctacc aaagtccacc
ttccatacag 95820gggtgtgggg tctctcttag tactgttggg tgccaataac atagaagccc
tccaagatag 95880gtcaatgaga ttttaatttt tcccaacttt aaatagcatc tgggaaggaa
agcagctttt 95940gactaggagt ttgaaaacat ccactcttca tatttattgt cacatttatt
gagtaataaa 96000attgggctct tgtccattat ctctcagtca atgaaagagc ccacggtggg
catgagccag 96060agtgttccgg agaaagagag gaccagtctc catttcatgt tctatattta
atcagttcaa 96120ttcagcacct tactgagttt gacatttttc taagtaatgg ggtggggggt
tacaaaatat 96180ttataactat ctttcctatc ttcagggaga tgtaccattt cactgaagca
ataccacagc 96240taagcagttc cagctccgag taacagagga aggagtgagc gatttaggaa
ctcacagaag 96300ggcacggcca ggcaactcgg gccctggcaa atgttccata gagacagcat
ccatggggtt 96360gaaccaagca caatgcctgc aaatcgggca ggcgggttca tggaattgat
tctagggcag 96420gtatgatcag caccatttaa ggagtggcag ttgttaagaa actgaaggga
tttctcatat 96480ggcattttca acagaattca gcaggagcct tgcatatccc ttgggatggg
ttccggggta 96540ttatggagct gccaggaggt gctcagcttc agtaagtgcc agtcattcct
tcccaacctc 96600ctccttcatt agtggaagta tcagctggtg tcattgcctt cttcaggagg
atggatttca 96660aaatgaaggg ccaacaaaac tcacattctc gcagagcctc cgtcacaact
gcatgtgttc 96720actgccatca acaggccaac acccacttgt tcttttcttc taggtaaagg
aaaaggtctg 96780tgggacaaag gccctgaact cctcactcct tgaatgggag gcatattggt
ggaggctgtc 96840acacaactac aggtggcagg aacctgccat cagggttccc atcagcctcc
agggcttgct 96900tctctgccct gtgtgtggac accttccatc actggaaacc cctctctcag
aagaaccact 96960tcttgccctc atctcccact tgcctctcct cggcaccttc tccaccctca
ggggccaagc 97020tgaggaagtg tgcatcctgt gccaccaacc ttgctcgcag gaattagttt
cagtccccag 97080tgactgactc ttccaaacct gcaccagcct atgctgccct tttgaaagga
ggcgtgcgta 97140cagcctggct ggtacagaag attccagatt tcagtgacta caggacgctg
tcaccccttc 97200tgtttttctt ttttctgtcc acatctctga ttgagcatac cttcagggaa
aaccccagaa 97260acctttttca cacttacatg ggaagccaag acactctcat cctgggcttg
tgtttttaaa 97320atctatattt taatttcaca ggtccttaca tttatgacta atagatttca
gattttgaga 97380tacaatctgt agttgcaact tatgaagata gtttcaagcc ctgatttctg
tcatctatga 97440aaacagtaag caagttgctt gtattctcct cctagctgga taagagaccc
ccgttttcat 97500ggacagcctc cttgggtgga cagaagtctc ctgatcttgt ctatgtaacc
agcacccact 97560ttgcattttt ccgcaaagaa aagaggagct taaccccatt tacgggaaat
ccacgcactg 97620cttgaatctt acgcgccccg tggtgacggt gttgcccact ctgttccctt
cccaccaaat 97680cctgccagca cctggcagtc atccagtcct tgtcttagac ttcaccaacc
tttcccgtca 97740taacatggct tagaagttgt ccgaatagtg ctagaagctt tcagccctgg
aatgctcagc 97800atctgccatc taacttccat ttaaaacgtt ttgagcattt gctgatacag
gttcctctgt 97860cctttcccca ttattttcag ttccttggcc ttgcccatag tgatctgtgg
atattgtctg 97920catactcttt tttagaaacc tagagcatcg cagtgtcctt aattttcctc
ttcaaactct 97980atatattcct gagctgatca tccctactgc tgttcctaca gaactgtgtg
actaatcttc 98040tatatatgtc cctacatcta gccatctagg tggagatcta ggtacctatc
tccctaaaat 98100tgtacttggt atccacattg acctcaggac agtatgtgat aggctcttgt
gccttttcga 98160ctaggagttt gaaaacatcc actcttcata tttattgtca catttgttga
ataataaaat 98220tgggctcttg tccattatgt ctcagtcagt gaaagagccc agggtgggcc
tgagccagag 98280tgtttgtgtc cctagttctc ttttggttct gttacagctc tcagtgacag
tgtcattgag 98340gctaacaagg acagagtact gctttcagcc accatttgtc caatgagtgg
ctgatctcca 98400ggcctctggc tttgagaaca tctgtgatat ctaaggcagc atccattgtg
ggctttcccc 98460catgcttctg tttccttcct gtcacatagc tttgcctcct cctgcaagca
gcctgctgta 98520gcagaaccgg tgttcctgaa gccagaaacc caaaggtcgt gtccaatgct
tccctgctgt 98580tctgctcccc acctgcaagc gcccacacac tgatcaacag cacacgccat
agagcatgcc 98640aaagaatccc agaaatactc attcttaatg atccagaaga acaagtgata
gcttctggca 98700agttctaata ggccatatgt gcccatggga aagcaagagt caattctctc
tagctggttg 98760cctctgaatt tatgaagtca agccgcgtag gggaacatgc caagaggatt
atcccaatgc 98820ctgttctgcg tggtgtcctt tttctagcct cggaagcact aggcctacac
cttcgctata 98880gccctcgtct tagcgcctgt atttgaaaaa cttgccacac caatcttaat
ttgctccatt 98940gtgttctaat ctcattttaa aaaccacaag gtaaatgatt aaaaataatc
ttagattaag 99000gagtacacag atctttgcag cctcattgtg tttccagagc gggctagtgt
agacactggt 99060gaacaaggag ggcctagaga attagctttc tcccagaaag atgcacagcc
tctacctgag 99120agtaccaatt ccagagaact caatggtcat taagcaccat tgcctcgaca
gccagccagc 99180ctcacttgcc tgcctatctc ctttattttc caagtatctt gtccctggca
gtggggagag 99240gttagcagga ggctgctcag atgctctcgg tctctgatct tcaggatctg
aaggggagag 99300catttgaaga atccccattg ctggatttct caggacaatc ctgcataatg
ccaggatctg 99360atggaggaga caggcagctc tgttaatcct ctggtgcatc ctcacttctg
tggtctccaa 99420gtccaccatg tcccagttaa ttcatttcat tattcatctg taagtcattt
ccctaaagag 99480ctaataagaa aacactggca gtacaatcag ccctccatat ccatgggttc
agcctctgga 99540aattcaaccc actgtggctt gaaaatacag tattcaagag acatggaacc
tgtggatata 99600gaaggcagat ttttcgtatc cataggttct atagggccat tttagggact
tgcacatcta 99660cagaccttca ggagtctcag aactgatgca ctgcagatac caagagatga
ctgtaagtgg 99720ttaggaattt ggatgctggg gccaggctgc ctgcagttac cttccagctc
tgccacttgc 99780cagctatgtg accttagcaa gttgttcaac ctctctgtgc cttggcttct
tcaactgtaa 99840aataggataa tgatagcact tcccttatgg agtccttgtg aaggttaaat
ggcagagtac 99900aattaatgtg ctgtgtgccc agcgtgtggt attggggtta ggtgaaagac
tgtactggga 99960tcactggggg tgagcctcca tgtgccatgc cccaaccact atcctcagct
aacttcttgt 100020ctgtcagtgt taggctggtg ctataataat ttccattttc atggatgagg
aaatcaaggc 100080acagagaagt tacatgactt gcctaagatc tcagtgcttt taaatagtgc
agctaagatt 100140ccagaccagg tatttttatt tcagtgtctg gactgtagat ctctaaatcg
agaggaactc 100200cctgaataaa ataagcttgg agtgctgtta actaagttgg ttatttaaga
cagttgttct 100260cagtcctcag tgtacattag aatcttctgg agggtatgtt aaaacagact
gctgggccca 100320ccgagagttc ctgagcctgc aactctgggt tgagcctgag agtctgtgct
tctagtaagt 100380tctcaggtga tgcttatgct gcttctccca aattttgaga accattgatt
gaaaatgttg 100440atcaaaaatt atgtggtcta ggctgagcac agtggctcac aactgtaatc
tcaacacttt 100500gggaggccaa gtcaggtgga tcactgagct caggagttcg agagcagcct
ggtcaacatg 100560acaagaccca tctctacaaa aaacaccaaa aaaaaatggc tggatgtggt
ggtgcacacc 100620tgtagtcaca actactgggg aggctgaggt gggaggatca cttgagcccg
ggagacagag 100680caagaccctg tctcaaaaaa gaaacattta gtcttgattg tcatctatct
cattgatcat 100740tttacttggc aaaatttacc tacttactct tattagtctg taaaaatggt
tattaaaatg 100800gtggctttca gtgtaactac aaattctctt agtcattata gtgttggatt
caccaatgta 100860tcatcagtca gtgtttctga agtgtgtaaa tgaaataact cctactttct
ttaggaagaa 100920aaatattcaa atgacataat taccttgtga tgtgtgactt aaaggtaaca
gtaatgcaga 100980gtcaatagtg gtcattgtat tcaagacact aaaagttcac ctcccacccc
ccccccccac 101040ccaccaccca acaaacacac aagcttcttt ccctttggaa aaaaaagctc
ttccagatac 101100ctacattcat aaactatccc aattaaccct tcagcaagtg gaagaagtgt
aagaaaggat 101160acctcttctt tagaacacag ggtttgtttt tatgttattt aagataaaca
ggaattcaaa 101220tggtcatgta ccaaagcaac acaaagaact tccggaaatc tgaaagggaa
ctgtggtcag 101280aactctgagc atttttatgt ttactgagtt ttgtcccaaa gtttattaat
gtttacatgc 101340cacaaggaaa ggtagcatca caataagaga cgtttttcag gcttgataac
cacttattag 101400gtattttgcc aaacaagttc acacatccta gagagctgga ttgtgtgacc
cagaacccac 101460cctctagggc aaggtgccca tctgatgggt agggtgtagg agtaggcctc
agaccactcc 101520tgacgtgaac ctgcttaaag tgagggccca attctaaagt gggaactatg
taaatacctt 101580tctagtgcat tttcagataa tcgccactgg gcctatggat ggagagggct
ggcagatctc 101640cctgtaaccc caggtgcatc ccgaggcctg ccaccgaagc ccactcaagg
ctgaatgcac 101700ggcgagctca ggctgctctc cccttggtat ttgctaagaa cttctgttta
gtagctctcc 101760acacctattt gattgtcttt ttgctgctgt gttgttttgt tgagtttttt
ttttgcaatg 101820acactgagtg gcctcctgta ttgtttcttt cagccagtaa tgttaaagta
gagactcaga 101880gtgatgaaga gaatgggcgt gcctgtgaaa tgaatgggga agaatgtgcg
gaggatttac 101940gaatgcttga tgcctcggga gagaaaatga atggctccca cagggaccaa
ggcagctcgg 102000ctttgtcggg agttggaggc attcgacttc ctaacggaaa actaaagtgt
gatatctgtg 102060ggatcatttg catcgggccc aatgtgctca tggttcacaa aagaagccac
actggtaagg 102120cctggctcag tttttccttt agtggcctgg agaaggtgca tggggtttga
aggaggaaag 102180catcctgtct tccttgtgtt ctgagcatgt ttctaattga ctggtagctc
agttgttgca 102240agcgattggt tccaagtggt accgagtcat agagtccttg ttctggtaca
gccttgtaaa 102300ggacttctca acacgtacca attccaccct ataaataaaa caagggaaaa
gtgaacagca 102360tcacatgaga ggcttggcga gggctgctat tatagtaaca catactaagt
agtctcagct 102420gagccctcag ggtacgtgtg ctgagtggtc accctccaca aaacaaaaaa
tcctgataca 102480ccaaaactta ctcctcaaag tttccactga gaaaccatga gtaaaatgtg
tgtttaaatt 102540gtatccaaac taacagggtt tgatgtttag aaacaataat caatgatgga
atagcagcaa 102600aatcgagttt tcagaaagac ctcagatgag ctttcaaatg gcttgccctc
taacaggaaa 102660gactttgaat cagatgcttc tattgccact ggttatcagc tcaaattcct
aaagaacttc 102720atcccaaata ccctgtcttg ctgaaaggtt tactggaagt ataagagaat
gtcatgttct 102780gtgtccagaa aggaaggaac acgggcaccc tagtgtcagc gagttgtgct
caggctcaca 102840ggatgccccc tcaccagagg cgtgggaaca cggcgagccc cagctggccg
cgctctgcca 102900ctgtttctaa tagccggtca cgttgatgga agtgtcacag agttgtccaa
cagaactgtc 102960cagtcagaaa accaccactc atggtgctgg agtgtcttag aagtaaaata
tgaataacac 103020acacttattt aactataggc aggaggtttc ttatgaattg aagagaaact
tttctttgcg 103080tgggaagctg ttctaaagtt gggtaaaaca caatagatcc accacctcta
gcagccactg 103140atagctgaaa cgtgaaacat agagacccta agctatcact gcctctgagc
tggcattgtt 103200aggtcatcat aaagctagcg tctcccactg caaaacccaa gaggaaaaaa
atagttgaaa 103260atcctatttt aaaggcctag cagattctat aagatacctt gggaaaatga
tgacgatgac 103320ttgaaatcag accctcgtat gctgcttccg tgggggcgaa caaaaatatg
ttcatcaaaa 103380attaagcaga aatgcagaaa attttgtgag ccaaaaaagc tgtgttatca
ggaaatgcag 103440atatttgtgg ggttgtaatt ttttatattt gaatcgggcg gttttcaaaa
tgatctattc 103500catttgtagt gtatctgaaa acctataaaa ataagttgat atcaatagat
atccatcttc 103560cataaaaatt caacttctaa aattaagcaa actttgcttt ttctaatggc
ccctttatcc 103620tcaaattacc cactgaaata gacggatcac actcagccct aagtgaagca
agcgtgcatg 103680agagtagtcc cagcctcgcc tttgtaatga ggtggaaatt aacatgaagg
taggctaccc 103740tgtgatagac acttaacagg atactcgggg acccatggta atacatccct
gataaggaat 103800agacctcaca aatgaactac ttgcctgtta attcatttaa agcctgactg
tacagtgaaa 103860attctcttaa ataaatattt gataagtgaa tcaaattctg gcttactaaa
ttgccaaaat 103920ataatgactg cctgccttga taaaaagaat aattacattt aatgaataaa
cctgccaagt 103980acagatatgc caggtggcac ctgctgtttg ctgctcactt ctcccaacaa
atagcagcta 104040ggtgccacct gcacaccaat aagctgagtt tttcacttac ggaacaaata
actttcagaa 104100gtcaatttta tagtttctgc cttgcccttt gttaaaaaaa tacacacact
tgaagcaatg 104160aactcatgaa ttgttttcat catgcatttc cacttgccta aatataaagg
gtcccaggta 104220gatacagaaa tacctggttt ggccaaactt ggtttgaata actagacatg
ctagaaaagg 104280ttttcatttt cctgggatct gagtggaata tgttagaaaa ggcatgcttt
ctgaattctc 104340tatgcttaaa acatttctag agcagtgctt ctcaaacttg aaagagcatg
taaatcacct 104400gagatctcgt gaacatacaa ctctgcttca gacctggggg gaggcaggag
agcaagcatt 104460cctaacaagc tcccagcttg tggagcacag agccgcctca ggcagcaggg
cagtgcagct 104520gagcagtgac agtgaacagg gccattcaga gggctctcca cctggggctt
aggtacgacg 104580ggaatcccca ctggacaggc taggacttgc actgtggcca ttgttcctcc
tcctgcccat 104640ggctgagtca gcttctcagt cccttccagg atacactgag aggattcagg
ggcggtctcg 104700cctctgccca tatccccacg ttggtgaagt accactggcg ccattttcta
atcagctcat 104760cggcaccagc acgtcacttc ccctgttgtg cagctcagtt ttatatttct
gactcgggtg 104820taatagtaac atcttcccca ccaatgtctc agggttattg tgagaaccag
agaggagaga 104880ggtaggaagg aagcaggaaa tgcagggtgc aaatacacca cattattatt
ctaaataatg 104940ggatttttaa taacaaagac caagaagatt gtctgtgcct atctagttcc
catctgtaag 105000ataaaaaggt gcagtccctg agcctcctaa aaacagcacc ctaatggcac
tgctcctccc 105060aggtatgatt gcagtagacc tacgtcagtt cttgcagttc aaacacattt
tttcactttc 105120ttctgaaatg ccctcaaatt ctatgacata gtatccatga agacttccct
ttttacccag 105180tgaagttact agagggggtt caaaccttct tacagagggt tcctaaaatg
ggagatctgt 105240ggagtcattg ggattaaaaa ttaaatttca aattcatgac atcaatgtcc
tcatcccagt 105300taaataaaag taaatacaac cttgaagaaa tttgacctac tcagctgcaa
tagctgttga 105360cctgcagaag gcaaatgatg gaccccggcc acgcaagaac acacatggcg
tgggctgcgt 105420tcttgtgccc cagctccatg gacgtgtctt cttagctgtg gacccctcca
aaggaaactg 105480cttgagtgga gtgctctgta ttgtcactcc tgggaatgct ctcttaacac
ccccatgcct 105540tgtgctatgt gttcatacca gcataggcac tcagaagcaa aaaaggtttc
cagtgaaatt 105600tgtttgcagg caggtattaa gacatcagac actgcaggat ccaagtgaac
ccctgcccgc 105660ctgcctgcct gccctgctct gctctgcaga agggcatgtg tctgtagcaa
tctgcccttt 105720ctgtctgcga tgggcagaga ccctggctct gcctcctgtt ttccctgtag
ccctccagac 105780ctggggagag acatgggact ccagcacctg cccagcacgg aagggggtct
ttcccaggtg 105840taagtgtagg gctgcattca ctaatttagg gtcataccac aaacactgtt
gtgtcaccag 105900gatgttgtca catgcttatt gtgagcattt ttgtgacatg agctttctcc
tgagaggcca 105960ccctgtccaa atgagagctg tagttggagg cacatccgtc tcatgctgcc
tgggtctccc 106020tgcaccagct cactctactt ttccttttta tccacttgga gttaaatgca
cacatttatg 106080cacaagtgca cagaaggccc agaactgttc ctaatagata attaaatgat
ctctctccag 106140tggaaactct cctgggctac ctggctgcta gctgttttag cctcttcatc
cagtattgat 106200ttacatgcat cggtttgtaa ctcagacagt atagttagtt agtttgtttc
accatcacct 106260tccaacctgc ttacgtttaa actccttctc tctgcttagc taatacagat
ttctgtaagg 106320atttggagaa ataccagata cctcctggtt agtatcagga cctctccatt
ggcctataat 106380tgaacatcac tgtaaattag tttcagcttt tatagtaatg catctaaccc
gccagcttaa 106440aaaaaaagtg atgataatca tgaaattcaa gtgtcaatat agacttttaa
atctggtgtg 106500gatgttaata gtgccagata tgcttctgtg taatcatttt tgagaagtgc
tgtcttcttt 106560accataatca cattaatcaa tcgggaaatg gttaaataga cattttaata
cattgttttt 106620tcctgagaaa aaaagtgact ccaggaaata tgttgttaca atatctcaac
accaggaatt 106680gtggtcacat agcattcttc ttctaaataa agcatttgtt ttacaaaaga
gtttcatgtt 106740tacttaaacg tgacaaatgt atcactcttc gaagtgagag ttaaatgaaa
tgttccctga 106800tttagattcc aagacctgtg actactcagt aggacaatag catatttctt
ttactcagat 106860acctgtttat ccctttgtca gctccagaat ggagacacag gtgctgccac
acagaggaga 106920gggtcaggtg ttttcttagt cacaaatgca gcagtctcac ccctgaaaga
attccttcat 106980aacaactaaa ttgcacctct tagaatacct gtacttaaaa tataatttgt
cttctatgga 107040tatagacaaa taatagctta aatgttttag gatttgtaaa gaaagaaaaa
gctagaaatc 107100tcaatgcaac tctgacttgt atgtcctgcc ataggaaggt ttgggacttt
tctttggaag 107160atgggaggct tccttcacag tttcttaact tctcatttta ttcaatcttt
ctccatctct 107220ctctctcttt ctctcatcct cacgctctct gtctgtctct ctcctgattt
gtctgcttag 107280ggacagacag gtaatggaga agaaattgaa agggaaaata cagggaaaat
gtaaatgaaa 107340agaagttatt ataactgtta taatgaagtg cctttcattt aaatataaga
atgtaacgct 107400gaaatgaact tgtgatcctg aaatgcattt ttaatgagtt tcctttttat
tttgctgctt 107460cagtggcata ttttaaagac cctttgaaaa aagccacatt aaaaaacccc
accaaatgcc 107520acaacacgca aaattggata ttggtttatt ccaaaactgc tgatcaggaa
gagtggctct 107580tcatcacaaa atgttgcagt cactttattt aaatgagttt gaatttgcat
tgtgatgtgc 107640cattctgatt tagggaaaaa aaattagatt ttcagatcaa attgacccag
ccagtgaagc 107700gttaaggagc tggcaggttt agtctgaaag cctcatgttc tatcaaacct
gcagccggtg 107760gaagtcacca ggcccccgtg ggaaacaact ttctcgtagc atcgtcctca
tgtccccacg 107820ctgagtttag ttctcaccag ctctcctctc tccgtcccag gagaacggcc
cttccagtgc 107880aatcagtgcg gggcctcatt cacccagaag ggcaacctgc tccggcacat
caagctgcat 107940tccggggaga agcccttcaa atgccacctc tgcaactacg cctgccgccg
gagggacgcc 108000ctcactggcc acctgaggac gcactccggt aggtcccctg gatgcagtcc
ggggctgtct 108060gggtgtcccg ggattcctcc actctgcccg cctgggtccc ggattgtgtc
cttgctggct 108120aaccctgagt ccctcccagc tcgcagtcct gcatcgggtg tgagctgttg
cttctttgac 108180attgccccat cccccctccc catattctcc ttttcccact gcaccaggga
gattgggcgc 108240aggaccccca tgcacataca cacacagaag tctcacctta ggtagcatgt
ttcagaacag 108300gcctcctcat cccgtttgtc aggctggtat ggtttcccta aaggattttg
cgggaaatgt 108360tttcaccaag tgtactgcta agacccaaaa cgttttcaag tacaattctt
tctgttgtta 108420agtcccgctt tggagtgttt tacacaggtg taatggatag cttttttgca
gagctggtag 108480agaagggtga tttagggcgc acccacccag actgagcccc gtgtggctct
cacaccaaaa 108540accagccaag gccacagtta cagaggccag tctggggctg ttaccagatt
ttagacagca 108600gcctttctct ttgaattaga cagttaaagt acaacccaca taatctggag
tcttgacaag 108660atcatcatag gcataaacgc tctatcattc tcaaaacagt ctcagcctgc
aaagttcaaa 108720tccactaaag tttggttaga tcctctgcct cctgagaaat ggtcctgggt
gtttcattat 108780ccagcagtcc cataattcta cagggcagag gaagagaggg ctcttggccg
gcctgtcatg 108840gatcatgttt gcctacagtg tggtctatac aacatgacat ggcacaggtc
tccttcatac 108900cgtccagttg gggatatttg ctgtagcata ctgcatgaga cttcggaggc
gaaaggttga 108960tggcttttgt ccttcccctc aaggagcttc ctgccccagc cagccaccag
ccagggccct 109020tctccaagca gcagcctctc taagccggtg ccctggggga tggcaatgcc
tcagaccagc 109080tactcctcac ccaccctggg tagcaggata aggaggagcc tccctcaggg
aggcagacgt 109140gtgttctttg tgaaatatct gcagcggccc aggccatctc ttcccaaatg
tgatgcgtgt 109200atttgatggt tgagggtttt agaggctgct cattgtgtcc atctctttat
cacacattta 109260ctgagcaccc ctgggtgccc attctgcaca gaagacctca ggtgcacaca
aggaaagcac 109320caatgtgtta caggaggcat gacagagtgt ctgaggggac agtgggagca
taaggaaggg 109380gacagtgggt cctggggtgg aaagtcagga gagacttccc atagaaggga
ggggcttctg 109440aagtacatgc tggaaggcga gtgtctgagg tttgctttag agacattcta
aactagtgtg 109500tgagtcggca gtaatcccag agaggggtgc ggcacccatg ttggcaagaa
ctcggtctca 109560ctcctggcag gtggtccctg cagtagttca cccagttggc tggagacaaa
aaggagagga 109620gtcacagggg ctggtgcatc acctcctctc catcctgacc tccttcctgg
cggtgcacat 109680ggagaaggat ccccacatgc tcgccatcag aaaattgtca tgatttgggt
gatttgactt 109740cctaaaaact tccaagaaag gagctatacc aagctgagga gttgcttgcc
cgagagggcg 109800ggcagatcag caggggggcc atggagtggg acacttgcct tgttacagag
ggacagggag 109860aacaggtggt tcccctgaga taggaagaca gtagcatgac ggtgagcatc
tttaaatgtt 109920cacatgggtg atgagcatgt atggtggtcc cacctggaga caaaggtggt
acctgggcct 109980gataagcaag gcccatggag gcctcagcta agagaactgt gcagtctgtc
tgccatgcta 110040accagtggtc taggaagaag cttcacatct gttgtttcta aggagccatg
tagacataga 110100cacagttggc agcaatattg ccttgggtta gtgggaagca ccacttccca
tgtcagtgga 110160aaacacagac actcgttctt aggttgacac caaccatagg tcatcatcac
tcctagatta 110220ctctgattgc aatggaatct ctcatgccca tcagtcctta aaagcagagc
tgctctcttt 110280cctttcttgt tgtggagtta ggaacatgta gtggagtatt ttatgttatt
ctggctccag 110340gcctatgtat ttcatttgag gcatgatggt ttcctattct aagtaccact
aagtattgag 110400tagttataaa atggtggtag actttggact gtgtatttct attctggatc
cacggatgag 110460caagtggaga aaacccatca tggatgcagg gctgctgggg atctgtctgt
ccgaaaatgc 110520tatagagaca cacactgctc ttggggaaaa aaacagtgat gatttcttca
aaatgatttc 110580actgaagtga aataaggact ttggccttgc tctggcaaat tcaaatgtgg
ccacactcta 110640ctccattgtg gaatggtgac tcccctgtcc catgaaaaac caggatcaac
atcacagctt 110700tctctagcaa ctggtggtgg cctgaggtct tatgaactag catgttagca
gggatagagt 110760tagggaattt gtccgatgct gacagcaaga gggtgctggg ggagctggag
gggtggagaa 110820gtgatctccc ttcctgcctc atggcttcct ttggaagttg caagcttaga
atttctttcc 110880caaagaatat tggactatgc ttcaagagac acttgagttc agttgcttac
agtgaacata 110940cttcttatgt tccagagtta aactcaatca tattttcaga aaaatagata
ttcagacatc 111000atgtcatatt tacaggaagc tatttgatca tggaatttac tgaagtgaca
gctttttcag 111060gaaagggtat cgagtggtta tctatatcct attaatttct aaaagcaatg
ctcaataaaa 111120tgtgcaattt taggcaatat tctgtgtttc aacattattt ccttatgttg
ggggtacatc 111180actttatata gataaagaaa gatccttttc attctctatt aaatggtcga
gaagtcaaat 111240tttggctttc atgttggtct tcttactgta gcttctgttc acctaagaaa
gagatttaac 111300caacataagc tttggctaaa ccattgtacc aaacatttct atttggatgc
tcttaacttt 111360tatacaatac tttgaaatgt gttcaataaa acaacatgag aaagaagtag
aagattctgc 111420tattaggttg gaaattgata ttccttacat aagtgattaa agatacttta
ttcagtttat 111480cccttaaaat ggtatctact gaagtcctta aacttaggca tgatattaat
tcctggctag 111540tctttctttt tcctaaaata tcactcaata aaatccaaga aggactaaaa
ctcattatat 111600agaactgcac tgcccaatac agcagccact agccacatgc agtattttta
attataataa 111660gttaaaatta aacaaaatta aaacttcagc cctcagtggc actagccaca
ctttttgtgt 111720ccaacagcta catatggctg gtggctgcca tattggacag cactaataga
gagcatttct 111780atcatcatag gaagttctgt tgaacaaggc tgatctggaa gctacaccat
cctaaagctc 111840tttggcaaga aagcagagct tttccataag ctcagtttat gaacaatata
ttttgtattt 111900tctatgtata tgtatatgag aatacgtata catagaaata tatgaaaata
catatacata 111960taaatataca tatacataaa atagaaatac atatacatag aaaatacaaa
atattttgta 112020ttacatatac atatgcatgg aaatacaaaa tattttgtat tatataatgc
aaatgtaaga 112080tatatttata ttatgtaaga aaatacattt gtgcaataaa acgcttattt
cattcaagca 112140tatttgtcca gcatggtttc ttagagactg aagttaccca gtttagcacc
tggaactgaa 112200ttcactctgg ctgtgttaga tgtagcacca gcgtcatgac agatccagcc
cacagcatag 112260actgaggcct actctggagg caaatctgca gacaatgtgg ccaacacatg
ggccttcctc 112320acatctctgt ccagtcgctg gcatccacgt tataacacag cagtggctcg
ttttctccag 112380ttaaaggcta ggcttccgtg attgaagcag gagagaattt ggtagtcagt
aaagtagaca 112440aactaagaca aaacaagagt cgcatgagtt cttggtacaa ttaaagaaac
ccttggccac 112500caacgttttt aaattcagga atttcaccaa gtccgtaaca gttttagctc
tcaagggtag 112560aatttttttt ttaacttttt tggtaataat tgtattgcat gcattcccct
tacacagaag 112620gctggcattt aattggggtc ttgaactcaa ttgtgttttc tgcagttggt
aaacctcaca 112680aatgtggata ttgtggccga agctataaac agcgaagctc tttagaggaa
cataaagagc 112740gctgccacaa ctacttggaa agcatgggcc ttccgggcac actgtaccca
ggtaagcgct 112800gctgctcgga ggccagcctg gtgggctctc cccccagcac ggtggggaag
gagggcgctc 112860tgcatgcagc cttaggagca gagccttggg cctgcttcct gccggggcta
ggagggaggg 112920aagtttttgg ccaatagcat cagtttcacc agaagcacgt tgtgcttccc
agctttctag 112980gtcctcatct gaccagagag agcttgattt taaaaccctt cccacttcca
atcgggagaa 113040actcctagga tagcagtgac cttgaaagtt ttggggttgt tttttggatg
ttggtgattt 113100taaaacaaca acaaaaaaaa cacctcaagt agtgatattt ctttgtaaac
aaaataaaat 113160gtaaaatatt gttttgaaac aattttttaa caaagttgat caaataagaa
ctttcaggct 113220gtgattttaa gcatcagttc agactgaggg cagggtatcc actcctgcat
ggagtgtgag 113280gttgaagttt gttggaagcc cctggtagtt gataatattg aggttgttga
aggatgagag 113340gaaaggtcgc ttctttctta ggagctgtga tgctccactg tattgcataa
cgagatagca 113400cttgattcag accccagagc ctgtagaata aatgatgtgg agagagtatt
gaaaaaggct 113460ggatttatct gggggaatgg caatgttata aaaggttctt ccctaatttt
ttaagagata 113520agcaatttat aaagagatca aataaaacta atctctttca aaacagtatt
catttagcac 113580tacccctgga aaaatcatca ctagactgtg agtcgaaatt taacgaatgg
aggaaaattt 113640attaagcctc attcaccttt cggactttaa caaatggttc aaaagggaaa
attcaccaga 113700gtaccctcag attattaatg gcagatgaga gcaggaaaaa agaatgttga
gaatggctaa 113760aaattgattc caattagtct tggcatggag aggcaacatc tcacctggcc
agagccctgc 113820agccagagtg ctgtctcctc tgccagtcag ccagggatct ggggcttaca
ggcgattcct 113880ccaggcctca atcttctcac ctgtgaaatg ggaagatacc attaaattgt
catttggctt 113940ctttcaaaat ctcaggtcta gaatggaaag gcattgaagg tgagtggaag
agaagaaact 114000ggatgttaaa ataataataa tgtaacagtt attaattcac atggccagac
cccagggcag 114060aagactaatg gacgagagga tgattatgtt cctttgaaat aaaatgtcaa
cattcaaata 114120ttgttttttt ctgtaaaaaa taagtgaatg ggtcttggaa ggaagtgctc
ctaatgatgt 114180agtttacata ttaatgctta ataaaccatt ttatttactc aacaaatatt
cactgaggac 114240ttataatcaa taataccaag ccctattgaa tacagtaatc taatatacac
atagaattga 114300aaagacaaaa tgaacaaaag aaacagacag tatatcattt ctgtttcctc
cactgttttc 114360attactaaag aaacaagctg cagtacacag ccggctgaga gctgcttccg
ggggagcagg 114420agaagcagca ctcatttcac tgagacctgg gtttgagttc tctgtttttg
aatgtgaccc 114480agagctcatc gcttaaatgc gactgataat tcgtgcctgg ccaccctcat
agcagcgctc 114540tgaaagaaac ataaaggagt ggatacacgt gtgagcagga gcctagacat
gtgtcaggta 114600cttacctaaa catggatgtt taggtcactg acatactgac accatcaagc
taattcttct 114660ctattggtct ctatgtcagt aaggctacgt gccagtaatg tgtattaaat
attaccctgt 114720ggtgagtatc aatttcaccc taaaatgttc atttattccc tttggtggtt
aagttacttg 114780gactaccaca gtgatgcctc tatgtcccca cactcaggag gtatgaaagc
gtctctagga 114840aggagcagtg gtctggtctc agtgtggcag cagacaaagc caggctcgca
cttaattaca 114900ttgaattatt tctgtctggt atggcctcaa aaggtgcaaa atgatcataa
atatctttcg 114960acagtcacct ttggtttttg cccttgccag cacctggccc ttgtaggtgc
tgctggttta 115020aggaacttgg agtattaagg ggatccataa aaggactttg acagaagtct
tcctgaactg 115080tgcttagggc caggaaggca ggcaggggct tggtcatttc agctgtgctg
tacccggatg 115140agtggaaact gtgccttctg atgcatctct cctcctctgt tcccctctaa
gaaccccttg 115200tctgtgctca gatggatgag caagtagtct cttctcccac cccaaaaacc
tccttagatg 115260gggtggattc agtaaaatca aagcctcagt taggcaatat aggaaaagat
gaatttttgt 115320gaatataatt ttctttagta aaaggctttt ggtcacctct tataatttct
caatgtcttt 115380atggaaaaaa taagtttctc ttgagccttt ggtgcacaaa cagagtcacc
agcccttgga 115440ggtgcatgca tctaatgaca gagcagcctg tgactcgcga gcatcaggct
cacttgttcc 115500ttgctgtgat tgactctggg gggtggaggc ttttgggagg ccctgcgcca
tggtgcagag 115560gaagacccct gacctctggg agccctgggc aggctgtggg tgtggcttgg
cagagaagga 115620tggacatgtc aggaagcata ttagcttaat agatgaagtg tgtgaccagt
gtaattgggt 115680tttatggatt tatatttatc ttgcatataa atcagggtgt ggcctatata
tgtttgccca 115740tttaataaaa aacacatatt ccaaatgtta aaatataaaa tataccagca
acaatagcca 115800atttgaaata tatgttttca aagtaacatt cataatagca atgaagacat
aaatacttag 115860aaatgaagaa aaccagcaag ccatagtgag gcaagaaaga aaacatggga
gattggagag 115920gtagagaggt ctggatgccg tccatgggcc tctgcccaaa ttagtgtatc
atttcaacat 115980aaaactggct tgtaaatttt actggaatct ggtaaccatg tatcataaag
tatctggata 116040tatacatgag ataattggca actttttaga agaagaataa tgtcaagtga
tgtatgaaaa 116100tgtagctgaa atggatggaa ctctttgaag aatagacaaa caaatcaata
atagagatgg 116160ataccctact gaagacccca tgataaatca gcatgaaata tccgaggcag
gaggaagcat 116220aaggcaggaa cggtattgga agaattgatc aggcatttaa gataatcagt
ttacattatc 116280atctccttat acactaggat aaattgccgg gaaatgaaag agttatattt
ttataactcc 116340aaccacaata actgatgtaa atatagatcc agctatgcag gatacaaagt
tgtatcttca 116400attatggaaa gagatgacat agaacaattg agaatgacta gaaatggccc
acacatcagc 116460atttacctcc ataatttcta aattttctac agcagtcagg ggtgctttga
ttttcaggag 116520tttgttgtat gctcagggat aaggggctct gggtttttcc tccacattgc
ccagatctgc 116580tgtaggctct tgggggccac atttttgtat ctccgttcac tgtgctggtc
catgaagtca 116640gatgttagat cacacagttc tttgcgtctc agagggctgc tgttagggac
tgactgaggt 116700agcagatttg ggagtattat gaaaagttaa aaggacttgt caaagggaca
tcaatactta 116760atcccagtcc agcctctggt gatggtggtg gtgcctgtgc atttggactt
aaagaggatg 116820atgtgtggtg agcagctgtt ggaggaagaa gcatttgcag gtggctggtc
attggcattg 116880ctccggctgc ctctgcctgt ctggaagtgt tgctgggaag attagaatta
atctctagga 116940agggcctggc tcttgtaggc acttaacaaa tgtcagattt aacattggac
gcgactgaac 117000cctttaaaca taagcctttc taaactggcc tctctgtctt tgactttagt
cattaaagaa 117060gaaactaatc acagtgaaat ggcagaagac ctgtgcaaga taggatcaga
gagatctctc 117120gtgctggaca gactagcaag taacgtcgcc aaacgtaaga gctctatgcc
tcagaaattt 117180cttggtaaga gttaaatgtt tgctgtctct taaaaaaaaa ctatgtgggt
gttttagatg 117240caagtagaaa tgagttgagg gtggaagaaa gggaaaaaaa tcttattttt
tcaaaaggaa 117300aaattggtaa gcttaacatt ccttaaatat cttagaattt tttccaataa
gtatcttaaa 117360aataacaaac ctcccatcag tttttcctag atttgatttt gcagcatctg
gggcctgccc 117420tgtgatctgc ctgtggacat cgctcttagg ggcggctgca ccagcgtgca
cagggtggag 117480agtttgggcc tggctcgtcc gggggacacc acactgcagg acactccagg
cctggccggc 117540ttctcagagc ttcagatcct catttttcat atgaagctcc taatgctccc
cttatggggg 117600actctgaagg gttaatggga ggaatcatac agtgactgac ccctgagaag
tgtccagtga 117660agacagggct tagctaggat tgctgttttg cctaatgctc tgcgggatta
aaaaaaaaga 117720agaagaagaa caagaccatt cgtctctcta ggagcattgc ccagagtagg
tattagacac 117780accaacacca ccatccagcc agacgctgca gggacagtga gccagggtcc
gagtggaaag 117840gcgctaggct tgggaaccag ctcagagtca atacagagcc accgccactc
accaactctg 117900tcagcttagt aaaatggctc tgcccctaga gccctggttc catcctttag
tatctcacag 117960ggtgattgtg aatatcccat gactccaaga ttgagaaaac gtttagaatc
cctcggtgtg 118020aaggttaact ctgtccggaa agaggaccag taaaagcttc atgaggctga
gatgcacttt 118080ggaagaggaa tagagtttca gcacattcta ggtgttggag gaatggggga
atctaggcag 118140atgtttaaaa tcaatgagaa accagaatgc tgaccatgag ggttggagtg
ggggcctaag 118200gacatgacgg aggagcaggg tgtgttccca gcttaactca ggtacccatg
gggaagcagg 118260aaaagtgaag gtgtcctagg cagctctgcc acaggatgaa tggcttcaga
tgccaggtga 118320gcgagggacc cttcattcag tcagcaggaa agaagcactg gcatattttt
tatgagaaca 118380aaggctagga tagtaaagac agcaagtacc aaaaaatgac tggaaaaggg
agactgtgga 118440ggcagtggca gcaggcatgg aaagaagggc ttgtgaaggg gaaggggtgg
tgtcagagga 118500acatagggct gggggcaggg attaggtgag ggaaaccatg agtcacactg
attctagagt 118560agtgtgccct tgatgaaaag gataacacca ggttctagga aaagatgggg
ttctgttttt 118620gacgtgttga ttttcaagga cttctggtgt ttgtgacaca tggggaaatt
gtggtgggag 118680agaggtgggg ccagaacagg ggctggtgag gccaagggtc ccagagggca
cctgttgacc 118740tgcaggatga catgaagggg gaaggacaga ggcaaggcca agtcctgggc
accagcctcc 118800ctcttgcagc ttcaaatagg gctccatttt gaccttttga ttaattagag
gtttgtcata 118860ggttgggggt tgagaggagc aagggagaga aggattcagt gtacaaaaag
aatgaaagcc 118920actggctgag ccagtgggga gttgtccaca cacacatgag cctttggacc
atgagaacga 118980gggaggcctt gccttcctga acggagtagg agtgaggtcc tgtgctgagc
gtaagcagtg 119040ggattcccac agcactgggc acagagccca cgggctgcct cctgagcagc
cagcatctgc 119100ctggggtgga cacagtgaca gagagatggg tggtgactgg ggtatgggca
gagataaggc 119160agcaagtgtg tgcaagggga gtgaagggtt actgacctta agaagcaggg
atggcgtcct 119220ctgtcaggtg aggagcctgg agaatgcttt ggtgaatgaa cgtttgcagc
cccttttagc 119280ttttggagac ttgaaaccaa aggagagatt catctgtgaa actctactgg
agccactccc 119340caacccccac ccttgtgaga ccacaatgtg ggcgttggct tgagatgctt
ctgtgttagt 119400agaagaaata aacaacacag tgctctgatg aggcaaagcg aagatgaaaa
aggagttccc 119460aggggacata gtaggaacag tggacgaggg tagcagaaga ggagtttgga
gcaaaagact 119520cacaagcagc tgcataatct gttggtgctt ggcagttcat ttgtaaaaat
gatgcctctt 119580cctgccctaa aatacctacc ttacccccgc ttcaacttga tgagatttcc
atcagtcact 119640cccaatgtgt cacagcttct gcagccctaa aattaaaagg tgagtgagtc
tctgaggccc 119700ctctccactt ctcggatgct gagtttagcc ttcatgtgaa tgtggaaaga
ctaggaatac 119760agctgttatc acacaagctg gcccaatagt ggttcagttg agagagcccc
atccttcaga 119820gtcagctcca gctaggagtg actggtggcc ttgagcatgg tgctgggctt
agtgttgcca 119880tctgtggaat gggtgtgggt ctgttgccct gcctcctccc agagctattc
tgaggctcag 119940aaggggtgat ggatgtgatg gtgctcccaa cactagaaag catcttaaga
atgtaagatt 120000ttcatgatga ctgttgctca gagtggctat tatagttttg ctttattgtt
ctataaccta 120060tgattaaaat ttttacctta aactttgacg tgagtgtgaa taagtatttg
ttttgccagc 120120aacattcctc accactgggg ccattaaaga tctccccctc tgagaccatc
aaatacaggt 120180caacaggact gattaatcta attagaaaag ggcttgtatt aaatagcaat
gataattgtt 120240gtttttagtc tgtctggtgt ttgacttggg aacgttttta aaatagagaa
aagcacaaag 120300aggaaaacaa caattaccaa tattcctgct acccattata attatctagg
tatattttct 120360tcttttgtaa gaaaaagaaa ccctgttata ttgttaaaat aacacaaagt
taatataaag 120420aattttaatg caaagattaa tgttttcaaa tcaccacaaa acccaacatc
cagaaattac 120480caatattaaa agtagaaaag tatcattcta aatattttct gttgcatatg
tatgtgagtg 120540gataggctga tgaattaggt ggattgatgg ataggtaaat atgaaataaa
tactttcata 120600aatattccaa cttatcatac atgccttaaa ttcaagaggt gaaaaaagac
ccaaacaaaa 120660ctagagaagc ggcttatttt aaatatcctc tgacataaag gaatattata
tttaaaggat 120720cctctaagat taaaaatatg tactatgaaa aacattaaga aatttgaatt
ttttttaatc 120780catttgtttc aatttaagca gcatctactg gctcactgct ttgaaaaata
aggacagtat 120840tccagttcac attcagtgtt ccagtgttca cattatctta ttatttttac
attgtccagc 120900tttgtaatat tcacattcta ttctgtaatc ataattcata gtagtttagt
tatttattac 120960taactctatt taaatagatt caaggatcag accctgccct tttcttctta
tttatgttta 121020ttttgattaa tctcttaatt gattggactt tacattcaag caactttttt
aaaaaaaagt 121080ttctatagat gttctatttc tatcattgta ttgtttttga ggatgttggc
ctgttgcctt 121140tgtatttgat gagcattttg acagagtcta tggtcttggg ccactctttc
tttttctccc 121200ttgagaactt tttagatttt gctgatggca ttgcttgttg aatgttgctg
tggaaacatc 121260aagtctagtg taactgtttc ttcttcaagg tgatttgcat tttattcctg
aatgcctgag 121320ggttctttat ttaaccttga agttaaatac cctaattagg atgtatcttg
gtctattcat 121380tcggaataaa aaattcctgc cattttgtct agagagtccc ttttttttct
ctttatttct 121440gggaaattct cttttatata aatatgtttt gttccatcta ttgtgatctc
tgttgaggga 121500taccagttgt ccatatgtta gataatttgt cttccatatc tgttaacagt
tcttaaagtt 121560ttttgtttat ttctttgtct atttttacat ttactcactg ttctcttgtg
gttttcctct 121620gtcagtaatt taatttttag tagttcctgt tctattactt gctattttta
atccatgcat 121680taattttata ataatattat tttgctcctt attttgtctc ctgagacccg
aaatctcttt 121740tttcctctta ctctgttgct tttgcatttt attttgaata cttttaaaat
tgattccatg 121800ttatgaagca attatgaggc atttcctctc ttgttggaat taacgatttt
ttcccctagg 121860agggactcta tggtctgtgt tttacttcct ttcttcccct gtatttctag
aaaatatttt 121920cctagtaacc ctgacatttc ttttcatctt gcttattcta gttggtctga
tatagcttga 121980ttgacatttc agccttcttc ccactatatt tttttttcct gtgagagcta
ttgggttttc 122040taaatcctga aagaatgcca aagatggggt tggaggagtt tggtgaggca
aagtgcagcc 122100tttgttaaaa tacttttcct ttgctctctc tccctcatct gaaatttagt
taaataccct 122160aagccatcag cactgtacct agttggggaa tgctttcatc cccacaggag
attctctggg 122220gctttgggcc atcttcccct tcagtgtaga ccacagagga ctttgcttct
gtcccaggga 122280gcccgcaggg gctcacttct ccatgttcat ctgattcttg tcagccaagg
tttcaaatgc 122340ttttctgatc agaacaggga aaagatacct atctgaatca tgtctttata
gatatgaggc 122400tatgagggaa aattctgagg ttattcttga ctcacaccta aagatttgga
aatgagatta 122460gcagcaaagc tttgccctac atctcatgtc agaattttct gtttctttct
agtctttgag 122520tgtatgtgtg ttctcacaca cgccataatg aaatgcatat tatatataat
tatgtgtata 122580tataatattc tatgactata catgacatgt tcctttagct gattgctgtt
aagagaaatt 122640tataggtttt tatttttctt gttttgttgg gtattaagga agagaaattc
tatggtaatt 122700ttcatgtggc acagtaatct ggcatatatg ttgatttttt tcctacaccc
atttgttgtg 122760ataccaagtt tgaaaacaac agatttcagt ggttgcttgg gaaaccacag
aaccatgact 122820tggggagaga caggatgatt aggtgggaaa gcaccctttt ggtggggctg
taaagacttt 122880tatatttagc aaaattggct acaaagtcca ttcccctcct tttcttgcct
tgatttggta 122940gagggataga cttggataca aactagaatg gattcattct tctctggagt
tagtgtaaca 123000agacatttag ctgctcaaca caaaaacaga aacaaaaaaa ttgtgtggtt
tcagcagtgc 123060tatacaatta ctttttctga cctttaatgg agagaaacac cacttctttg
gtccctacca 123120tcagcttcat agggttttca tcctgttctg tttctgggag ggcgtaactg
gccatgcaca 123180agtttttttt ctctaatcag agtatgtgcc acttctgacc accagtagat
gaaaacgaat 123240ggaaaccagg ctattatatg atacatatcc attacaaaat aagacatgaa
actcaaaggt 123300actttatggt ataatggggc atatattcct ggacaattct taatggtcac
agattttata 123360aaaggactat tagtaaatgt atgaattaca gagtaattta tccttctgtt
agtaagaacc 123420agctgatgac ctcagtgtca ggtgcatcgt ggaaggtgtt gggaccttcc
cttgccacca 123480ccctcaccag ccatcatcag ccataacctg cacattgggg aagttttgac
ttatccctca 123540cttttgcccc tcttcaagct gttctttcca cagtgaatga gaaggccact
tcttccttca 123600aacctttcag tggtttccat tttcctttag acaaagtctc tgcctagctg
gcctctgcct 123660gcccctcctg cctacctctc gagcactgcc cccacctagg gctctggttc
cccaaccttc 123720actcggtcct gccacacctc ccagcccctt ctcccttcag aactttcctt
cttgttgtcc 123780ccaacactgg gacacaaaac cctccttatc aaccctcctt atctggctga
ctcttacaag 123840atcagaaacc tgtgtaatgc tctcatggca cgctcccctt gtcttcgtgg
atttctcaga 123900tgggaaggaa ttatccatgc aatcacacat aaacttctac ctaccctccc
ctagtagctg 123960tctgctgcta aggatgggga ccattctcac ttactcactg ttctgtccct
ctgcccagtc 124020cagatgtgtt gaaggatgga aatatacaga gtagtggtaa aatataaacc
gttcagacat 124080tccaaggatg ggctcatgtg ctttgactca ttaatgtacc actgctgaaa
acagaacaca 124140gccgcagtct tgccagtaag agtgcagtta ctgtaattaa tgaatttgct
aattaagcca 124200tgatttcata ctgaacttat gaccaacata ttgagaaggt gtgtcttcaa
gaaaatttat 124260tttttgtatt aagatattta ctccaaagct aattgaagaa gccaaatcta
ggctctggtt 124320tcaccattgc cagggaaatg agctcatgga ctcctatgaa ctgatgatgt
tagatcagaa 124380gtttctcaag gccagggccc aatcactgct gaggcgtcaa cagtagttcc
ttgtacatca 124440ataattctca ttacttttaa aaaataacag atgaatagca actattttcc
ctgtagctcc 124500cttgctgtgc ctcctaccct ccaccacatg tttctgggga gccctgcttc
gggcctgcca 124560actacagaga attacttttg agtatccctt ccactctcat ctcaagacag
agttcatcta 124620cctttgggtt atttgtcaaa aatgtgtcat tttattacaa aaaatataca
atcatcatgt 124680attttgatta aattttacac tagattatta aaattattaa atacaattat
taaaattaat 124740aatttaacat atcacatatt ttaaatatat tgtatataat gaataataat
ataattattg 124800tctattttaa ttcaataaat gtatagtaag ttagccagtt gtaaattact
gagaacactc 124860tactgaaaaa gcatcatttc aaatacacta tttaaaatat taaatgaaat
acaataacat 124920aattaaacta atctttggtt cccctattta tgtattcatt tatccaacaa
aatctcctta 124980agtgcttata atgggtaggt cctggctcgg tgtcccctag acagacgcat
gggccttccc 125040ccagcccgtc agtatggtgc aggtgtgatg tgtccgcagg tgtgtgtgta
tgtgtgcagg 125100tgtggggtcc gcaggcgtgc tgggccccca ggccgtgttc cccttcccct
ccccggttgt 125160agatttcagc tgttgctgcc agacctgacc ggttccggag gtggccgcgc
cccactcact 125220gtcgcctgct ttccacaggg gacaagggcc tgtccgacac gccctacgac
agcagcgcca 125280gctacgagaa ggagaacgaa atgatgaagt cccacgtgat ggaccaagcc
atcaacaacg 125340ccatcaacta cctgggggcc gagtccctgc gcccgctggt gcagacgccc
ccgggcggtt 125400ccgaggtggt cccggtcatc agcccgatgt accagctgca caagccgctc
gcggagggca 125460ccccgcgctc caaccactcg gcccaggaca gcgccgtgga gaacctgctg
ctgctctcca 125520aggccaagtt ggtgccctcg gagcgcgagg cgtccccgag caacagctgc
caagactcca 125580cggacaccga gagcaacaac gaggagcagc gcagcggtct catctacctg
accaaccaca 125640tcgccccgca cgcgcgcaac gggctgtcgc tcaaggagga gcaccgcgcc
tacgacctgc 125700tgcgcgccgc ctccgagaac tcgcaggacg cgctccgcgt ggtcagcacc
agcggggagc 125760agatgaaggt gtacaagtgc gaacactgcc gggtgctctt cctggatcac
gtcatgtaca 125820ccatccacat gggctgccac ggcttccgtg atccttttga gtgcaacatg
tgcggctacc 125880acagccagga ccggtacgag ttctcgtcgc acataacgcg aggggagcac
cgcttccaca 125940tgagctaaag ccctcccgcg cccccacccc agaccccgag ccaccccagg
aaaagcacaa 126000ggactgccgc cttctcgctc ccgccagcag catagactgg actggaccag
acaatgttgt 126060gtttggattt gtaactgttt tttgtttttt gtttgagttg gttgattggg
gtttgatttg 126120cttttgaaaa gatttttatt tttagaggca gggctgcatt gggagcatcc
agaactgcta 126180ccttcctaga tgtttcccca gaccgctggc tgagattccc tcacctgtcg
cttcctagaa 126240tccccttctc caaacgatta gtctaaattt tcagagagaa atagataaaa
cacgccacag 126300cctgggaagg agcgtgctct accctgtgct aagcacgggg ttcgcgcacc
aggtgtcttt 126360ttccagtccc cagaagcaga gagcacagcc cctgctgtgt gggtctgcag
gtgagcagac 126420aggacaggtg tgccgccacc caagtgccaa gacacagcag ggccaacaac
ctgtgcccag 126480gccagcttcg agctacatgc atctagggcg gagaggctgc acttgtgaga
gaaaatacta 126540tttcaagtca tattctgcgt aggaaaatga attggttggg gaaagtcgtg
tctgtcagac 126600tgccctgggt ggagggagac gccgggctag agcctttggg atcgtcctgg
attcactggc 126660tttgcggagg ctgctcagat ggcctgagcc tcccgaggct tgctgccccg
taggaggaga 126720ctgtcttccc gtgggcatat ctggggagcc ctgttccccg ctttttcact
cccatacctt 126780taatggcccc caaaatctgt cactacaatt taaacaccag tcccgaaatt
tggatcttct 126840ttctttttga atctctcaaa cggcaacatt cctcagaaac caaagcttta
tttcaaatct 126900cttccttccc tggctggttc catctagtac cagaggcctc ttttcctgaa
gaaatccaat 126960cctagccctc attttaatta tgtacatctg tttgtagcca caagcctgaa
tttctcagtg 127020ttggtaagtt tctttaccta ccctcactat atattattct cgttttaaaa
cccataaagg 127080agtgatttag aacagtcatt aattttcaac tcaatgaaat atgtgaagcc
cagcatctct 127140gttgctaaca cacagagctc acctgtttga aaccaagctt tcaaacatgt
tgaagctctt 127200tactgtaaag gcaagccagc atgtgtgtcc acacatacat aggatggctg
gctctgcacc 127260tgtaggatat tggaatgcac agggcaattg agggactgag ccagaccttc
ggagagtaat 127320gccaccagat cccctaggaa agaggaggca aatggcactg caggtgagaa
ccccgcccat 127380ccgtgctatg acatggaggc actgaagccc gaggaaggtg tgtggagatt
ctaatcccaa 127440caagcaaggg tctccttcaa gattaatgct atcaatcatt aaggtcatta
ctctcaacca 127500cctaggcaat gaagaatata ccatttcaaa tatttacagt acttgtcttc
accaacactg 127560tcccaaggtg aaatgaagca acagagagga aattgtacat aagtacctca
gcatttaatc 127620caaacagggg ttcttagtct cagcactatg acattttggg ctgactactt
atttgttagg 127680cgggagctct cctgtgcatt gtaggataat tagcagtatc cctggtggct
acccaataga 127740cgccagtagc accccgaatt gacaacccaa actctccaga catcaccaac
tgtcccctgc 127800gaggagaaat cactcctggg ggagaaccac tgacccaaat gaattctaaa
ccaatcaaat 127860gtctgggaag ccctccaaga aaaaaaatag aaaagcactt gaagaatatt
cccaatattc 127920ccggtcagca gtatcaaggc tgacttgtgt tcatgtggag tcattataaa
ttctataaat 127980caattattcc ccttcggtct taaaaatata tttcctcata aacatttgag
ttttgttgaa 128040aagatggagt ttacaaagat accattcttg agtcatggat ttctctgctc
acagaagggt 128100gtggcatttg gaaacgggaa taaacaaaat tgctgcacca atgcactgag
tgaaggaaga 128160gagacagagg atcaagggct ttagacagca ctccttcaat atgcaatcac
agagaaagat 128220gcgccttatc caagttaata tctctaaggt gagagccttc ttagagtcag
tttgttgcaa 128280atttcaccta ctctgttctt ttccatccat ccccctgagt cagttggttg
aagggagtta 128340ttttttcaag tggaattcaa acaaagctca aaccagaact gtaaatagtg
attgcaggaa 128400ttcttttcta aactgctttg ccctttcctc tcactgcctt ttatagccaa
tataaatgtc 128460tctttgcaca ccttttgttg tggttttata ttgtaacacc atttttcttt
gaaactattg 128520tatttaaagt aaggtttcat attatgtcag caagtaatta acttatgttt
aaaaggtggc 128580catatcatgt accaaaagtt gctgaagttt ctcttctagc tggtaaagta
ggagtttgca 128640tgacttcaca ctttttttgc gtagtttctt ctgttgtatg atggcgtgag
tgtgtgtctt 128700gggtaccgct gtgtactact gtgtgcctag attccatgca ctctcgttgt
gtttgaagta 128760aatattggag accggagggt aacaggttgg cctgttgatt acagctagta
atcgctgtgt 128820cttgttccgc cccctccctg acaccccagc ttcccaggat gtggaaagcc
tggatctcag 128880ctccttgccc catatccctt ctgtaatttg tacctaaaga gtgtgattat
cctaattcaa 128940gagtcactaa aactcatcac attatcattg catatcagca aagggtaaag
tcctagcacc 129000aattgcttca cataccagca tgttccattt ccaatttaga attagccaca
taataaaatc 129060ttagaatctt ccttgagaaa gagctgcctg agatgtagtt ttgttatatg
gttccccacc 129120gaccattttt gtgctttttt cttgttttgt tttgttttga ctgcactgtg
agttttgtag 129180tgtcctcttc ttgccaaaac aaacgcgaga tgaactggac ttatgtagac
aaatcgtgat 129240gccagtgtat ccttcctttc ttcagttcca gcaataatga atggtcaact
tttttaaaat 129300ctagatctct ctcattcatt tcaatgtatt tttactttaa gatgaaccaa
aattattaga 129360cttatttaag atgtacaggc atcagaaaaa agaagcacat aatgcttttg
gtgcgatggc 129420actcactgtg aacatgtgta accacatatt aatatgcaat attgtttcca
atactttcta 129480atacagtttt ttataatgtt gtgtgtggtg attgttcagg tcgaatctgt
tgtatccagt 129540acagctttag gtcttcagct gcccttctgg cgagtacatg cacaggattg
taaatgagaa 129600atgcagtcat atttccagtc tgcctctatg atgatgttaa attattgctg
tttagctgtg 129660aacaagggat gtaccactgg aggaatagag tatccttttg tacacatttt
gaaatgcttc 129720ttctgtagtg atagaacaaa taaatgcaac gaatactctg tctgccctat
cccgtgaagt 129780ccacactggc gtaagagaag gcccagcaga gcaggaatct gcctagactt
tctcccaatg 129840agatcccaat atgagaggga gaagagatgg gcctcaggac agctgcaata
ccacttggga 129900acacatgtgg tgtcttgatg tggccagcgc agcagttcag cacaacgtac
ctcccatcta 129960caacagtgct ggacgtggga attctaagtc ccagtcttga gggtgggtgg
agatggaggg 130020caacaagaga tacatttcca gttctccact gcagcatgct tcagtcattc
tgtgagtggc 130080cgggcccagg gccctcacaa tttcactacc ttgtctttta catagtcata
agaattatcc 130140tcaacatagc cttttgacgc tgtaaatctt gagtattcat ttaccctttt
ctgatctcct 130200ggaaacagct gcctgcctgc attgcacttc tcttcccgag gagtggggta
aatttaaaag 130260tcaagttata gtttggatgt tagtatagaa ttttgaaatt gggaattaaa
aatcaggact 130320ggggactggg agaccaaaaa tttctgatcc catttctgat ggatgtgtca
caccttttct 130380gtcaaaataa aatgtcttgg aggttatgac tccttggtga a
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