METHODS FOR DISEASE DETECTION
20220411878 · 2022-12-29
Inventors
Cpc classification
International classification
Abstract
The present disclosure provides, among other things, methods for cancer detection (e.g., screening) and compositions related thereto. In various embodiments, the present disclosure provides methods for colorectal and/or advanced adenoma detection (e.g., screening) and compositions related thereto. In various embodiments, the present disclosure provides methods for screening that include analysis of methylation status of one or more methylation biomarkers, and compositions related thereto. In various embodiments, the present disclosure provides methods for detection (e.g., screening) that include detecting (e.g., screening) methylation status of one or more methylation biomarkers in cfDNA, e.g., in ctDNA. In various embodiments, the present disclosure provides methods for screening that include detecting (e.g., screening) methylation status of one or more methylation biomarkers in cfDNA, e.g., in ctDNA, using next-generation sequencing techniques.
Claims
1. A method of detecting advanced adenoma in a human subject, the method comprising: determining a methylation status of each of two or more markers identified in DNA from a sample obtained from the subject, and determining whether the subject has advanced adenoma based at least in part on the determined methylation status of each of the two or more markers, wherein each of at least two of the two or more markers is a methylation locus comprising at least a portion of a differentially methylated region (DMR) selected from the DMRs of
2. The method of claim 1, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs of Table 15: TABLE-US-00033 chr start end SEQ ID NO. 7 100785927 100786167 SEQ ID NO.: 221 14 97412990 97413410 SEQ ID NO.: 374 wherein each said portion comprises at least three (3) CpGs.
3. The method of claim 1, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs of Table 16: TABLE-US-00034 chr start end SEQ ID NO. 7 100785927 100786167 SEQ ID NO.: 221 14 97412990 97413410 SEQ ID NO.: 374 20 3083167 3083587 SEQ ID NO.: 411 8 37797956 37798676 SEQ ID NO.: 329 wherein each said portion comprises at least three (3) CpGs.
4. The method of claim 1, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs of Table 17: TABLE-US-00035 chr start end SEQ ID NO. 7 100785927 100786167 SEQ ID NO.: 221 14 97412990 97413410 SEQ ID NO.: 374 20 3083167 3083587 SEQ ID NO.: 411 8 37797956 37798676 SEQ ID NO.: 329 16 57091834 57092014 SEQ ID NO.: 387 4 7940020 7940200 SEQ ID NO.: 287 19 40811045 40811585 SEQ ID NO.: 403 1 154567391 154567691 SEQ ID NO.: 246 14 105364294 105364612 SEQ ID NO.: 376 9 61862430 61863030 SEQ ID NO.: 338 wherein each said portion comprises at least three (3) CpGs.
5. The method of claim 1, wherein the sample is a tissue sample, a blood sample, a stool sample, or a blood product sample.
6. The method of claim 1, wherein the sample comprises DNA that is isolated from blood or plasma of the human subject.
7. The method of claim 1, wherein the DNA is cell-free DNA (cfDNA) of the human subject.
8. The method of claim 1, wherein the method comprises determining the methylation status of each of the one or more markers using next generation sequencing (NGS).
9. The method of claim 1, wherein the method comprises using one or more capture baits that enrich for a target region to capture one or more corresponding methylation locus/loci.
10. The method of claim 1, wherein each methylation locus is equal to or less than 3000 bp in length.
11.-12. (canceled)
13. A method of detecting colorectal cancer in a human subject, the method comprising: determining a methylation status of each of two or more markers identified in DNA from a sample obtained from the subject, and determining whether the subject has colorectal cancer based at least in part on the determined methylation status of each of the two or more markers, wherein each of at least two of the two or more markers is a methylation locus comprising at least a portion of a differentially methylated region (DMR) selected from the DMRs of
14. The method of claim 13, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs of Table 8: TABLE-US-00036 chr start end SEQ ID NO. 7 96997902 96999222 SEQ ID NO.: 92 8 96145538 96145718 SEQ ID NO.: 108 each said portion comprising at least three (3) CpGs.
15. The method of claim 13, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs of Table 9: TABLE-US-00037 chr start end SEQ ID NO. 7 96997902 96999222 SEQ ID NO.: 92 8 96145538 96145718 SEQ ID NO.: 108 2 100322218 100322818 SEQ ID NO.: 28 2 29115776 29116791 SEQ ID NO.: 17 each said portion comprising at least three (3) CpGs.
16. The method of claim 13, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs of Table 10: TABLE-US-00038 chr start end SEQ ID NO. 7 96997902 96999222 SEQ ID NO.: 92 8 96145538 96145718 SEQ ID NO.: 108 2 100322218 100322818 SEQ ID NO.: 28 2 29115776 29116791 SEQ ID NO.: 17 2 88765502 88766042 SEQ ID NO.: 25 4 153249541 153249721 SEQ ID NO.: 55 2 86790271 86790811 SEQ ID NO.: 24 2 176094518 176094878 SEQ ID NO.: 35 3 37453325 37453874 SEQ ID NO.: 41 each said portion comprising at least three (3) CpGs.
17. The method of claim 13, wherein the sample is a tissue sample, a blood sample, a stool sample, or a blood product sample.
18. The method of claim 13, wherein the sample comprises DNA that is isolated from blood or plasma of the human subject.
19. The method of claim 13, wherein the DNA is cell-free DNA (cfDNA) of the human subject.
20. The method of claim 13, wherein the method comprises determining the methylation status of each of the one or more markers using next generation sequencing (NGS).
21. The method of claim 13, wherein the method comprises using one or more capture baits that enrich for a target region to capture one or more corresponding methylation locus/loci.
22. The method of claim 13, wherein each methylation locus is equal to or less than 3000 bp in length.
23. A method of detecting colorectal cancer in a human subject, the method comprising: determining a methylation status for both of the following in deoxyribonucleic acid (DNA) from a sample of a human subject: (i) a methylation locus within gene DLX6-AS1; and (ii) a methylation locus within gene GDF6; and diagnosing colorectal cancer in the human subject based on at least said determined methylation status.
24. The method of claim 23, comprising determining a methylation status for a methylation locus within gene DLX6-AS1, wherein the methylation locus within gene DLX6-AS1 comprises at least a portion of [chr7: 96997902-96999222] (SEQ ID NO.: 92), said portion comprising at least three (3) CpGs, wherein the methylation locus within gene DLX6-AS1 has a length equal to or less than 5000 bp.
25. The method of claim 23, comprising determining a methylation status for a methylation locus within gene GDF6, wherein the methylation locus within gene GDF6 comprises at least a portion of [chr8: 96145538-96145718](SEQ ID NO.: 108), said portion comprising at least three (3) CpGs, wherein the methylation locus within gene GDF6 has a length equal to or less than 5000 bp.
26.-205. (canceled)
206. The method of claim 1, wherein the method comprises determining a methylation status of at least a portion of each of the following DMRs: TABLE-US-00039 chr start end SEQ ID NO. 14 97412990 97413410 SEQ ID NO.: 374 8 37797956 37798676 SEQ ID NO.: 329 16 57091834 57092014 SEQ ID NO.: 387 4 7940020 7940200 SEQ ID NO.: 287 1 154567391 154567691 SEQ ID NO.: 246 wherein each said portion comprises at least three (3) CpGs.
207. The method of claim 13, wherein the method comprises determining a methylation status of at least a portion of the DMR chr2:100322218-100322818 (SEQ ID NO.: 28), wherein said portion comprises at least three (3) CpGs.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0236] The foregoing and other objects, aspects, features, and advantages of the present disclosure will become more apparent and better understood by referring to the following description taken in conjunction with the accompanying drawings, in which:
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DETAILED DESCRIPTION
[0256] It is contemplated that systems, architectures, devices, methods, and processes of the claimed invention encompass variations and adaptations developed using information from the embodiments described herein. Adaptation and/or modification of the systems, architectures, devices, methods, and processes described herein may be performed, as contemplated by this description.
[0257] Throughout the description, where articles, devices, systems, and architectures are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are articles, devices, systems, and architectures of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.
[0258] It should be understood that the order of steps or order for performing certain action is immaterial so long as the invention remains operable. Moreover, two or more steps or actions may be conducted simultaneously.
[0259] The mention herein of any publication, for example, in the Background section, is not an admission that the publication serves as prior art with respect to any of the claims presented herein. The Background section is presented for purposes of clarity and is not meant as a description of prior art with respect to any claim.
[0260] Documents are incorporated herein by reference as noted. Where there is any discrepancy in the meaning of a particular term, the meaning provided in the Definition section above is controlling.
[0261] Headers are provided for the convenience of the reader—the presence and/or placement of a header is not intended to limit the scope of the subject matter described herein.
Detection of Methylation in Colorectal Neoplasias Using a UDX Colon Test
[0262] Advanced adenomas (AA) are precursors of colorectal cancer (CRC) with around 85% of the sporadic cancers originating from them. In certain embodiments, AAs are defined by the presence of four polyp features including a diameter of >1.0 cm, villous architecture, serrated adenoma with dysplasia and/or high-grade dysplasia. Of these, high-grade dysplasia is generally believed to be the most highly associated with progression to cancer, making its detection and removal important for prevention of colorectal cancer.
[0263] Several screening options such as fecal immunochemical test (FIT) and Cologuard (that combines FIT test and stool-based biomarkers) are available for the early detection of colorectal cancer. However, their adenoma detection rates remain low at 24% and 42% respectively (Imperiale T F, et al. N Engl J Med 370; 14, 2014). Furthermore, FIT and Cologuard require stool handling and frequent testing, which results in low adherence rates to the screening program. Only around 65% of the eligible patients take part of the screening, leaving large proportion of eligible patients unscreened. A simple, noninvasive blood-based CRC screening test with high sensitivity would increase screening adherence rates as well as improve the AA detection rates, which would substantially improve CRC control efforts. Blood based screenings are believed to have >90% adherence rates at baseline.
[0264] In certain embodiments, methods, systems, and techniques described herein are used to conduct a UDX Colon test. The UDX Colon test is qualitative next generation sequencing (NGS)-based in vitro diagnostic that uses high throughput, targeted hybridization-based capture with bioinformatics processes to detect methylation in more than 300 colorectal neoplasia (e.g., colorectal cancer, advanced adenoma) associated methylation loci in DNA, e.g., cfDNA of a human subject. In certain embodiments, a UDX Colon test utilizes cell-free DNA (cfDNA) from plasma of whole blood in order to identify methylated loci.
[0265] A positive result may indicate a presence of colorectal cancer (CRC) or advanced adenoma (AA). A positive result may be followed by diagnostic colonoscopy or other diagnosis-confirmatory assay. A UDX Colon test may be used to detect (e.g., screen) for a colorectal neoplasia in adults 45 years or older, who are at an average risk for CRC.
[0266] In certain embodiments, a UDX Colon Test includes reagents, software, procedures, or a combination thereof, for testing cfDNA from whole blood samples.
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Detection of Colorectal Cancer and Advanced Adenoma
[0268] In various embodiments, a methylation biomarker of the present disclosure used for detection of colorectal cancer is selected from a methylation locus that is or includes at least a portion of a DMR listed in
[0269] In various embodiments, a methylation biomarker of the present disclosure used for detection of advanced adenoma is selected from a methylation locus that is or includes at least a portion of a DMR listed in
[0270] For the avoidance of any doubt, any methylation biomarker provided herein in either
[0271] In some embodiments, said methylation biomarker can be or include a single methylation locus. In some embodiments, a methylation biomarker can be or include two or more methylation loci. In some embodiments, a methylation biomarker can be or include a single differentially methylated region (DMR) (e.g., (i) a DMR selected from those listed in
[0272] In some instances, a methylation locus is or includes a gene, such as a gene provided in
[0273] In some instances, a methylation locus is or includes a coding region of a gene, such as a coding region of a gene provided in
[0274] In some instances, a methylation locus is or includes a promoter, enhancer, and/or other regulatory region of a gene, such as a gene provided in
[0275] In some embodiments, a methylation locus is or includes a non-coding sequence. In some embodiments, a methylation locus is or includes one or more exons, and/or one or more introns.
[0276] In some embodiments, a methylation locus includes a DNA region extending a predetermined number of nucleotides upstream of a coding sequence, and/or a DNA region extending a predetermined number of nucleotides downstream of a coding sequence. In various instances, a predetermined number of nucleotides upstream and/or downstream and be or include, e.g., 500 bp, 1 kb, 2 kb, 3 kb, 4 kb, 5 kb, 10 kb, 20 kb, 30 kb, 40 kb, 50 kb, 75 kb, or 100 kb. Those of skill in the art will appreciate that methylation biomarkers capable of impacting expression of a coding sequence may typically be within any of these distances of the coding sequence, upstream and/or downstream.
[0277] Those of skill in the art will appreciate that a methylation locus identified as a methylation biomarker need not necessarily be assayed in a single experiment, reaction, or amplicon. A single methylation locus identified as a colorectal cancer methylation biomarker can be assayed, e.g., in a method including separate amplification (or providing oligonucleotide primers and conditions sufficient for amplification of) of one or more distinct or overlapping DNA regions within a methylation locus, e.g., one or more distinct or overlapping DMRs. Those of skill in the art will further appreciate that a methylation locus identified as a methylation biomarker need not be analyzed for methylation status of each nucleotide, nor each CpG, present within the methylation locus. Rather, a methylation locus that is a methylation biomarker may be analyzed, e.g., by analysis of a single DNA region within the methylation locus, e.g., by analysis of a single DMR within the methylation locus.
[0278] DMRs of the present disclosure can be a methylation locus or include a portion of a methylation locus. In some instances, a DMR is a DNA region with a methylation locus that is, e.g., 1 to 5,000 bp in length. In various embodiments, a DMR is a DNA region with a methylation locus that is equal to or less than 5000 bp, 4,000 bp, 3,000 bp, 2,000 bp, 1,000 bp, 950 bp, 900 bp, 850 bp, 800 bp, 750 bp, 700 bp, 650 bp, 600 bp, 550 bp, 500 bp, 450 bp, 400 bp, 350 bp, 300 bp, 250 bp, 200 bp, 150 bp, 100 bp, 50 bp, 40 bp, 30 bp, 20 bp, or 10 bp in length. In some embodiments, a DMR is 1, 2, 3, 4, 5, 6, 7, 8 or 9 bp in length.
[0279] Methylation biomarkers, including without limitation methylation loci and DMRs provided herein, can include at least one methylation site that is a colorectal cancer biomarker.
[0280] For clarity, those of skill in the art will appreciate that term methylation biomarker is used broadly, such that a methylation locus can be a methylation biomarker that includes one or more DMRs, each of which DMRs is also itself a methylation biomarker, and each of which DMRs can include one or more methylation sites, each of which methylation sites is also itself a methylation biomarker. Moreover, a methylation biomarker can include two or more methylation loci. Accordingly, status as a methylation biomarker does not turn on the contiguousness of nucleic acids included in a biomarker, but rather on the existence of a change in methylation status for included DNA region(s) between a first state and a second state, such as between colorectal cancer and controls, advanced adenoma and controls, or both colorectal cancer and advanced adenoma and controls.
[0281] As provided herein, a methylation locus can be any of one or more methylation loci each of which methylation loci is, includes, or is a portion of a gene (or specific DMR) identified in
[0282] In some embodiments, a methylation biomarker includes two or more methylation loci, each of which is, includes, or is a portion of a gene identified in
[0283] In various embodiments, a methylation biomarker can be or include one or more individual nucleotides (e.g., a single individual cytosine residue in the context of a CpG) or a plurality of individual cytosine residues (e.g., of a plurality of CpGs) present within one or more methylation loci (e.g, one or more DMRs) provided herein. Thus, in certain embodiments a methylation biomarker is or includes methylation status of a plurality of individual methylation sites.
[0284] In various embodiments, a methylation biomarker is, includes, or is characterized by change in methylation status that is a change in the methylation of one or more methylation sites within one or more methylation loci (e.g., one or more DMRs). In various embodiments, a methylation biomarker is or includes a change in methylation status that is a change in the number of methylated sites within one or more methylation loci (e.g., one or more DMRs)(e.g., one or more CpG sites). In various embodiments, a methylation biomarker is or includes a change in methylation status that is a change in the frequency of methylation sites within one or more methylation loci (e.g., one or more DMRs). In various embodiments, a methylation biomarker is or includes a change in methylation status that is a change in the pattern of methylation sites within one or more methylation loci (e.g., one or more DMRs).
[0285] In various embodiments, methylation status of one or more methylation loci (e.g., one or more DMRs) is expressed as a fraction or percentage of the one or more methylation loci (e.g., the one or more DMRs) present in a sample that are methylated, e.g., as a fraction of the number of individual DNA strands of DNA in a sample that are methylated at one or more particular methylation loci (e.g., one or more particular DMRs). Those of skill in the art will appreciate that, in some instances, the fraction or percentage of methylation can be calculated from the ratio of methylated DMRs to unmethylated DMRs for one or more analyzed DMRs, e.g., within a sample.
[0286] In various embodiments, methylation status of one or more methylation loci (e.g., one or more DMRs) is compared to a reference methylation status value and/or to methylation status of the one or more methylation loci (e.g., one or more DMRs) in a reference sample or a group of reference samples. For example, in certain embodiments, the group of reference samples is a plurality of samples obtained from individuals where said samples are known to represent a particular state (e.g., a “normal” non-cancer state, or a cancer state). In certain instances, a reference is a non-contemporaneous sample from the same source, e.g., a prior sample from the same source, e.g., from the same subject. In certain instances, a reference for the methylation status of one or more methylation loci (e.g., one or more DMRs) is the methylation status of the one or more methylation loci (e.g., one or more DMRs) in a sample (e.g., a sample from a subject), or a plurality of samples, known to represent a particular state (e.g., a cancer state or a non-cancer state). Thus, a reference can be or include one or more predetermined thresholds, which thresholds can be quantitative (e.g., a methylation value) or qualitative. Those of skill in the art will appreciate that a reference measurement is typically produced by measurement using a methodology identical to, similar to, or comparable to that by which the non-reference measurement was taken.
[0287] In various embodiments, methylation status of one or more methylation loci (e.g., one or more DMRs) is compared to a reference methylation status value and/or to methylation status of the one or more methylation loci (e.g., one or more DMRs) in a reference sample. In certain instances, a reference is a non-contemporaneous sample from the same source, e.g., a prior sample from the same source, e.g., from the same subject. In certain instances, a reference for the methylation status of one or more methylation loci (e.g., one or more DMRs) is the methylation status of the one or more methylation loci (e.g., one or more DMRs) in a sample (e.g., a sample from a subject), or a plurality of samples, known to represent a particular state (e.g., a cancer state or a non-cancer state). Thus, a reference can be or include one or more predetermined thresholds, which thresholds can be quantitative (e.g., a methylation value) or qualitative. Those of skill in the art will appreciate that a reference measurement is typically produced by measurement using a methodology identical to, similar to, or comparable to that by which the non-reference measurement was taken.
[0288] In various embodiments, a methylation status of a methylation loci may be based on methylation of one or more reads (e.g., obtained using a NGS technique) mapped to the methylation loci. For example, when analyzing sequencing data obtained from a sequencing technique, e.g., a NGS sequencing technique, e.g., a targeted NGS sequencing technique, sequencing data may include an inferred or probabilistic sequence of base pairs of a DNA fragment. The inferred or probabilistic sequence of base pairs of the DNA fragment is known as a read. The read may be mapped to a methylation loci (e.g., a DMR, a mutation marker) reference sequence, for example, in a genome (e.g., a reference genome, e.g., a reference bisulfite converted genome). Based on a comparison of the read sequence to a reference sequence, individual CpGs or cytosine residues may be identified as being hypermethylated or hypomethylated as compared to a reference state. In certain embodiments, a read-wise methylation value (e.g., a read-wise methylation score) is determined for a read, based pre-determined minimal thresholds that takes into account a number of methylation sites (e.g., CpGs) and a percentage of methylation In certain embodiments, a read-wise methylation value is a binary value.
Advanced Adenomas
[0289] In certain embodiments, methods and compositions presented herein are useful for screening for advanced adenomas. Advanced adenomas include, without limitation: neoplastic adenomatous growth in colon and/or in rectum, adenomas located in the proximal part of the colon, adenomas located in the distal part of the colon and/or rectum, adenomas of low grade dysplasia, adenomas of high grade dysplasia, neoplastic growth(s) of colorectum tissue that shows signs of high grade dysplasia of any size, neoplastic growth(s) of colorectum tissue having a size greater than or equal to 10 mm of any histology and/or dysplasia grade, neoplastic growth(s) of colorectum tissue with villious histological type of any type of dysplasia and any size, and colorectum tissue having a serrated histological type with any dysplasia grade and/or size.
Colorectal Cancers
[0290] In certain embodiments, methods and compositions of the present disclosure are useful for screening for colorectal cancer. Colorectal cancers include, without limitation, colon cancer, rectal cancer, and combinations thereof. Colorectal cancers include metastatic colorectal cancers and non-metastatic colorectal cancers. Colorectal cancers include cancer located in the proximal part of the colon cancer and cancer located in the distal part of the colon.
[0291] Colorectal cancers include colorectal cancers at any of the various possible stages known in the art, including, e.g., Stage I, Stage II, Stage III, and Stage IV colorectal cancers (e.g., stages 0, I, IIA, IIB, IIC, IIIA, IIIB, IIIC, IVA, IVB, and IVC). Colorectal cancers include all stages of the Tumor/Node/Metastasis (TNM) staging system. With respect to colorectal cancer, T can refer to whether the tumor grown into the wall of the colon or rectum, and if so by how many layers; N can refer to whether the tumor has spread to lymph nodes, and if so how many lymph nodes and where they are located; and M can refer to whether the cancer has spread to other parts of the body, and if so which parts and to what extent. Particular stages of T, N, and M are known in the art. T stages can include TX, T0, Tis, T1, T2, T3, T4a, and T4b; N stages can include NX, N0, N1a, N1b, N1c, N2a, and N2b; M stages can include M0, M1a, and M1b. Moreover, grades of colorectal cancer can include GX, G1, G2, G3, and G4. Various means of staging cancer, and colorectal cancer in particular, are well known in the art summarized, e.g., on the world wide web at cancer.net/cancer-types/colorectal-cancer/stages.
[0292] In certain instances, the present disclosure includes screening of early stage colorectal cancer. Early stage colorectal cancers can include, e.g., colorectal cancers localized within a subject, e.g., in that they have not yet spread to lymph nodes of the subject, e.g., lymph nodes near to the cancer (stage NO), and have not spread to distant sites (stage M0). Early stage cancers include colorectal cancers corresponding to, e.g., Stages 0 to II C.
[0293] Thus, colorectal cancers of the present disclosure include, among other things, pre-malignant colorectal cancer and malignant colorectal cancer. Methods and compositions of the present disclosure are useful for screening of colorectal cancer in all of its forms and stages, including without limitation those named herein or otherwise known in the art, as well as all subsets thereof. Accordingly, the person of skill in art will appreciate that all references to colorectal cancer provided here include, without limitation, colorectal cancer in all of its forms and stages, including without limitation those named herein or otherwise known in the art, as well as all subsets thereof.
Subjects and Samples
[0294] A sample analyzed using methods and compositions provided herein can be any biological sample and/or any sample including nucleic acids. In various particular embodiments, a sample analyzed using methods and compositions provided herein can be a sample from a mammal. In various particular embodiments, a sample analyzed using methods and compositions provided herein can be a sample from a human subject. In various particular embodiments, a sample analyzed using methods and compositions provided herein can be a sample form a mouse, rat, pig, horse, chicken, or cow.
[0295] In various instances, a human subject is a subject diagnosed or seeking diagnosis as having, diagnosed as or seeking diagnosis as at risk of having, and/or diagnosed as or seeking diagnosis as at immediate risk of having, a colorectal neoplasm (e.g., colorectal cancer, advanced adenoma). In various instances, a human subject is a subjected identified as a subject in need of screening for a colorectal neoplasm (e.g., colorectal cancer, advanced adenoma). In certain instances, a human subject is a subject identified as in need of colorectal cancer screening by a medical practitioner. In various instances, a human subject is identified as in need of colorectal cancer screening due to age, e.g., due to an age equal to or greater than 40 years, e.g., an age equal to or greater than 49, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 years, though in some instances a subject 18 years old or older may be identified as at risk and/or in need of screening for a colorectal neoplasm (e.g., colorectal cancer, advanced adenoma). In various instances, a human subject is identified as being high risk and/or in need of screening for a colorectal neoplasm (e.g., colorectal cancer, advanced adenoma) based on, without limitation, familial history, prior diagnoses, and/or an evaluation by a medical practitioner. In various instances, a human subject is a subject not diagnosed as having, not at risk of having, not at immediate risk of having, not diagnosed as having, and/or not seeking diagnosis for a cancer such as a colorectal cancer, or any combination thereof.
[0296] A sample from a subject, e.g., a human or other mammalian subject, can be a sample of, e.g., blood, blood component (e.g., plasma, buffy coat), cfDNA (cell free DNA), ctDNA (circulating tumor DNA), stool, or tissue (e.g., advanced adenoma and/or colorectal tissue). In some particular embodiments, a sample is an excretion or bodily fluid of a subject (e.g., stool, blood, plasma, lymph, or urine of a subject) or a tissue sample of a colorectal neoplasm, such as a colonic polyp, an advanced adenoma, and/or colorectal cancer. A sample from a subject can be a cell or tissue sample, e.g., a cell or tissue sample that is of a cancer or includes cancer cells, e.g., of a tumor or of a metastatic tissue. For example, the sample may include colorectal cells, polyp cells, or glandular cells. In various embodiments, a sample from a subject, e.g., a human or other mammalian subject, can be obtained by biopsy (e.g., colonoscopy resection, fine needle aspiration or tissue biopsy) or surgery.
[0297] In various particular embodiments, a sample is a sample of cell-free DNA (cfDNA). cfDNA is typically found in biological fluids (e.g., plasma, serum, or urine) in short, double-stranded fragments. The concentration of cfDNA is typically low, but can significantly increase under particular conditions, including without limitation pregnancy, autoimmune disorder, myocardial infraction, and cancer. Circulating tumor DNA (ctDNA) is the component of circulating DNA specifically derived from cancer cells. ctDNA can be present in human fluids. For example in some instances, ctDNA can be found bound to and/or associated with leukocytes and erythrocytes. In some instances, ctDNA can be found not bound to and/or associated with leukocytes and erythrocytes. Various tests for detection of tumor-derived cfDNA are based on detection of genetic or epigenetic modifications that are characteristic of cancer (e.g., of a relevant cancer). Genetic or epigenetic modifications characteristic of cancer can include, without limitation, oncogenic or cancer-associated mutations in tumor-suppressor genes, activated oncogenes, hypermethylation, and/or chromosomal disorders. Detection of genetic or epigenetic modifications characteristic of cancer or pre-cancer can confirm that detected cfDNA is ctDNA.
[0298] cfDNA and ctDNA provide a real-time or nearly real-time metric of the methylation status of a source tissue. cfDNA and ctDNA have a half-life in blood of about 2 hours, such that a sample taken at a given time provides a relatively timely reflection of the status of a source tissue.
[0299] Various methods of isolating nucleic acids from a sample (e.g., of isolating cfDNA from blood or plasma) are known in the art. Nucleic acids can be isolated, e.g., without limitation, standard DNA purification techniques, by direct gene capture (e.g., by clarification of a sample to remove assay-inhibiting agents and capturing a target nucleic acid, if present, from the clarified sample with a capture agent to produce a capture complex, and isolating the capture complex to recover the target nucleic acid).
[0300] In certain embodiments, a sample may have a required minimum amount of DNA (e.g., cfDNA, gDNA) (e.g., DNA fragments) for later determining a methylation status. For example, in certain embodiments, a sample may be required to have at least 5 ng, at least 10 ng, at least 20 ng (or more) DNA.
Methods of Measuring Methylation Status
[0301] Methylation status can be measured by a variety of methods known in the art and/or by methods provided in this specification. Those of skill in the art will appreciate that a method for measuring methylation status can generally be applied to samples from any source and of any kind, and will further be aware of processing steps available to modify a sample into a form suitable for measurement by a given methodology.
[0302] In certain embodiments, the processing steps involve fragmenting or shearing DNA of the sample. For example, genomic DNA (e.g., gDNA) obtained from a cell, tissue, or other source may require fragmentation prior to sequencing. In certain embodiments, DNA may be fragmented prior to measurement of methylation status using a physical method (e.g., using an ultra-sonicator, a nebulizer technique, hydrodynamic shearing, etc.). In certain embodiments, DNA may be fragmented using an enzymatic method (e.g., using an endonuclease or a transposase). Certain samples, e.g., cfDNA samples, may not require fragmentation. cfDNA fragments are about 200 bp in length and may be appropriate for certain methods provided herein. DNA fragments of about 100-1000 bp in length are suitable for analysis in certain NGS techniques described herein including, for example, Illumina® based techniques. Certain technologies may require DNA fragments of about 100-1000 bp range. In contrast, DNA fragments of about 10 kb or longer are suitable for long read sequencing technologies.
[0303] Methods of measuring methylation status include, without limitation, methods including whole genome bisulfite sequencing, targeted bisulfite sequencing, targeted enzymatic methylation sequencing, methylation-status-specific polymerase chain reaction (PCR), methods including mass spectrometry, methylation arrays, methods including methylation-specific nucleases, methods including mass-based separation, methods including target-specific capture (e.g., hybrid capture), and methods including methylation-specific oligonucleotide primers. Certain particular assays for methylation utilize a bisulfite reagent (e.g., hydrogen sulfite ions) or enzymatic conversion reagents (e.g., Tet methylcytosine dioxygenase 2).
[0304] Bisulfite reagents can include, among other things, bisulfite, disulfite, hydrogen sulfite, sodium metabisulphite, or combinations thereof, which reagents can be useful in distinguishing methylated and unmethylated nucleic acids. Bisulfite interacts differently with cytosine and 5-methylcytosine. In typical bisulfite-based methods, contacting of DNA (e.g., single stranded DNA, double stranded DNA) with bisulfite deaminates (e.g., converts) unmethylated cytosine to uracil, while methylated cytosine remains unaffected. Methylated cytosines, but not unmethylated cytosines, are selectively retained. Thus, in a bisulfite processed sample, uracil residues stand in place of, and thus provide an identifying signal for, unmethylated cytosine residues, while remaining (methylated) cytosine residues thus provide an identifying signal for methylated cytosine residues. Bisulfite processed samples can be analyzed, e.g., by next generation sequencing (NGS) or other methods disclosed herein.
[0305] In some embodiments, bisulfite processed samples may be treated using a bisulfite ratio of bisulfite to DNA that is at least. In certain embodiments, the bisulfite processed sample comprises single stranded DNA fragments or double stranded DNA fragments.
[0306] In some embodiments, bisulfite treatment includes subjecting DNA fragments (e.g., double stranded DNA) to one or more denaturation-conversion cycles in order to convert unmethylation cytosines to uracils in the DNA fragments. Denaturation converts double stranded DNA fragments in the sample to single stranded DNA fragments. Conversion changes the unmethylated cytosines of the single stranded DNA into uracils. In some embodiments, only one denaturation-conversion cycle are performed. In some embodiments, two, three, four, five, six, seven, eight, nine, ten, fifteen, twenty, or more denaturation-conversion cycles are performed. In some embodiments, the temperature of the denaturation step is performed at a temperature of about 80-100° C. (e.g., about 90-97° C., e.g., about 96° C.). In some embodiments, the denaturation step is performed for less than 10 minutes (e.g., less than 5 minutes, less than 5 minutes, less than 2 minutes, or less). In certain embodiments, the conversion step is performed for less than 2.5 hr (e.g., less than 2 hr, less than 1 hr, less than 30 minutes, less than 15 minutes, or less). In certain embodiments, the conversion step is performed at a temperature of 55 to 65° C. In certain embodiments, the converted DNA fragments may be stored at a temperature of about 4° C. after performing the denaturation-conversion cycle(s). In some embodiments, bisulfite treatment may be applied prior to library preparation. In some embodiments, bisfulfite treatment may be applied after library preparation.
[0307] Enzymatic conversion reagents can include Tet methylcytosine dioxygenase 2 (TET2). TET2 oxidizes 5-methylcytosine and thus protects it from the consecutive deamination by APOBEC. APOBEC deaminates unmethylated cytosine to uracil, while oxidized 5-methylcytosine remains unaffected. Thus, in a TET2 processed sample, uracil residues stand in place of, and thus provide an identifying signal for, unmethylated cytosine residues, while remaining (methylated) cytosine residues thus provide an identifying signal for methylated cytosine residues. TET2 processed samples can be analyzed, e.g., by next generation sequencing (NGS). In certain embodiments, APOBEC refers to a member (or plurality of members) of the Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) family. In certain embodiments, APOBEC may refer to APOBEC-1, APOBEC-2, APOBEC-3A, APOBEC-3B, APOBEC-3C, APOBEC-3D, APOBEC-3E, APOBEC-3F, APOBEC-3G. APOBEC-3H, APOBEC-4, and/or Activation-induced (cytidine) deaminase (AID).
[0308] Methods of measuring methylation status can include, without limitation, massively parallel sequencing (e.g., next-generation sequencing) to determine methylation state, e.g., sequencing by—synthesis, real-time (e.g., single-molecule) sequencing, bead emulsion sequencing, nanopore sequencing, or other sequencing techniques known in the art. In some embodiments, a method of measuring methylation status can include whole-genome sequencing, e.g., measuring whole genome methylation status from bisulfite or enzymatically treated material with base-pair resolution.
[0309] In some embodiments, a method of measuring methylation status includes reduced representation bisulfite sequencing e.g., utilizing use of restriction enzymes to measure methylation status of high CpG content regions from bisulfite or enzymatically treated material with base-pair resolution.
[0310] In some embodiments, a method of measuring methylation status can include targeted sequencing e.g., measuring methylation status of pre-selected genomic location from bisulfite or enzymatically treated material with base-pair resolution.
[0311] In some embodiments, the pre-selection (capture) (e.g., enrichment) of regions of interest (e.g., DMRs) can be done by complementary in vitro synthesized oligonucleotide sequences (e.g., capture baits/probes). Capture probes (e.g., oligonucleotide capture probes, oligonucleotide capture baits) are useful in targeted sequencing (e.g., NGS) techniques to enrich for particular regions of interest in an oligonucleotide (e.g., DNA) sequence. For example, enrichment of target regions is useful when sequences of particular pre-determined regions of DNA are sequenced. In certain embodiments, capture probes are about 10 to 1000 bp long (e.g., about 10 to about 200 bp long) (e.g., about 120 bp long). In certain embodiments, one or more capture probes are targeted to capture a region of interest (e.g., a genomic marker) corresponding to one or more methylation loci (e.g., methylation loci comprising at least a portion of one or more DMRs, e.g., as found in
[0312] In certain embodiments, capture probes are evaluated (e.g., prior to sequencing) for their ability to target multiple regions of the genome of interest. For example, when designing a capture probe to target a particular region of interest (e.g., a DMR), the ability for a capture probe to target multiple regions of the genome may be considered. As discussed herein, mismatches in pairing (e.g., non-Watson-Crick pairing) allow for capture probes to hybridize to other, unintended regions of a genome. In addition, a particular target sequence may be repeated elsewhere in a genome. Repeat sequences are common for sequences that are highly repetitive. In certain embodiments, capture probes are designed such that they only target a few similar regions of the genome. In certain embodiments, capture probes may hybridize to 500 or fewer, 100 or fewer, 50 or fewer, 10 or fewer, 5 or fewer similar regions in a genome. In certain embodiments, a similar region to the target of region of interest is calculated using a 24 bp window moving around a genome and matching the region of the window to a reference sequence according to sequence order similarity. Other size windows and/or techniques may be used.
[0313] For example, hybrid-capture of one or more DNA fragments (e.g., ctDNA, fragmented gDNA) may be performed using capture probes targeted to predetermined regions of interested of a genome. In certain embodiments, capture probes target at least 2 (e.g, at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 50, 75, 100, 150, or more) predetermined regions of interest (e.g., genomic markers, e.g., DMRs). In certain embodiments, the capture probes overlap. In certain embodiments, the overlapping probes overlap at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60% or more.
[0314] In certain embodiments, the capture probes are nucleic acid probes (e.g., DNA probes, RNA probes). In some embodiments, a method may also include identifying mutated regions (e.g., individual nucleotide bases) using targeted sequencing e.g., determining the presence of a mutation in one or more pre-selected genomic locations (e.g., a genomic marker, e.g., a mutation marker). In certain embodiments, mutations may also be identified from bisulfite or enzymatically treated DNA with base-pair resolution.
[0315] In some embodiments, a method for measuring methylation status can include Illumina Methylation Assays e.g., measuring over 850,000 methylation sites quantitatively across a genome at single-nucleotide resolution.
[0316] Various methylation assay procedures can be used in conjunction with bisulfite treatment to determine methylation status of a target sequence such as a DMR. Such assays can include, among others, Methylation-Specific Restriction Enzyme qPCR, sequencing of bisulfite-treated nucleic acid, PCR (e.g., with sequence-specific amplification), Methylation Specific Nuclease-assisted Minor-allele Enrichment PCR, and Methylation-Sensitive High Resolution Melting. In some embodiments, DMRs are amplified from converted (e.g., bisulfite or enzyme converted) DNA fragments for library preparation.
[0317] In some embodiments, a sequencing library may be prepared using converted (e.g., bisulfite or enzyme converted) oligonucleotide fragments (e.g., cfDNA, gDNA fragments, synthetic nucleotide sequences, etc.) according to, e.g., an Illumina protocol, an Accel-NGS® Methyl-Seq DNA Library Kit (Swift Bioscience) protocol, a transpose-based Nextera XT protocol, or the like. In some embodiments, the oligonucleotide fragments are DNA fragments which have been converted (e.g., bisulfite or enzyme converted). In certain embodiments, DNA fragments used in preparation of a sequencing library may be single stranded DNA fragments or double stranded DNA fragments. In certain embodiments, a library may be prepared by attaching adapters to DNA fragments. Adapters contain short (e.g., about 100 to about 1000 bp) sequences (e.g., oligonucleotide sequences) that allow oligonucleotide fragments of a library (e.g., a DNA library) to bind to and generate clusters on a flow cell used in, for example, next generation sequencing (NGS). Adapters may be ligated to library fragments prior to NGS. In certain embodiments, a ligase enzyme covalently links the adapter and library fragments. In certain embodiments, adapters are attached to either one or both of the 5′ and 3′ ends of converted DNA fragments. In certain embodiments, the attaching step is performed such that at least 40%, at least 50%, at least 60%, at least 70% of the converted DNA fragments are attached to adapter. In certain embodiments, the attaching step is performed such that at least 40%, at least 50%, at least 60%, at least 70% of the converted DNA fragments have an adapter attached at both the 5′ and 3′ ends
[0318] In certain embodiments, adapters used herein contain a sequence of oligonucleotides that aid in sample identification. For example, in certain embodiments, adapters include a sample index. A sample index is a short sequence (e.g., about 8 to about 10 bases) of nucleic acids (e.g., DNA, RNA) that serve as sample identifiers and allow for, among other things, multiplexing and/or pooling of multiple samples in a single sequencing run and/or on a flow cell (e.g., used in a NGS technique). In certain embodiments, an adapter at a 5′ end, a 3′ end, or both of a converted single stranded DNA fragment includes a sample index. In certain embodiments, an adapter sequence may include a molecular barcode. A molecular barcode may serve as a unique molecular identifier to identify a target molecule during, for example, DNA sequencing. In certain embodiments, DNA barcodes may be randomly generated. In certain embodiments, DNA barcodes may be predetermined or predesigned. In certain embodiments, the DNA barcodes are different on each DNA fragment. In certain embodiments, the DNA barcodes may be the same for two single stranded DNA fragments that are not complementary to one another (e.g., in a Watson-Crick pair with each other) in the biological sample. In certain embodiments, DNA fragments may be amplified (e.g., using PCR) after ligation of adapters to DNA fragments. In certain embodiments, at least 40% (e.g., at least at least 50%, at least 60%, at least 70%) of the converted DNA fragments have an adapter attached at both the 5′ and 3′ ends.
[0319] In certain embodiments, high-throughput and/or next-generation sequencing (NGS) techniques are used to achieve base-pair level resolution of an oligonucleotide (e.g., a DNA) sequence, permitting analysis of methylation status and/or identification of mutations. For example, in certain embodiments, NGS may include single-end or paired-end sequencing. In single-end sequencing, a technique reads a sequenced fragment in one direction—from one end of a fragment to the opposite end of the fragment. In certain embodiments, this produces a single DNA sequence that then may be aligned to a reference sequence. In paired-end sequencing, a sequenced fragment is read in a first direction from one end of the fragment to the opposite end of the fragment. The sequenced fragment may be read until a specified read length is reached. Then, the sequenced fragment is read in a second direction, which is opposite to the first direction. In certain embodiments, having multiple read pairs may help to improve read alignment and/or identify mutations (e.g., insertions, deletions, inversion, etc.) that may not be detected by single-end reading.
[0320] Another method, that can be used for methylation detection includes PCR amplification with methylation-specific oligonucleotide primers (MSP methods), e.g., as applied to bisulfite-treated sample (see, e.g., Herman 1992 Proc. Natl. Acad. Sci. USA 93: 9821-9826, which is herein incorporated by reference with respect to methods of determining methylation status). Use of methylation-status-specific oligonucleotide primers for amplification of bisulfite-treated DNA allows differentiation between methylated and unmethylated nucleic acids. Oligonucleotide primer pairs for use in MSP methods include at least one oligonucleotide primer capable of hybridizing with sequence that includes a methylation site, e.g., a CpG site. An oligonucleotide primer that includes a T residue at a position complementary to a cytosine residue will selectively hybridize to templates in which the cytosine was unmethylated prior to bisulfite treatment, while an oligonucleotide primer that includes a G residue at a position complementary to a cytosine residue will selectively hybridize to templates in which the cytosine was methylated cytosine prior to bisulfite treatment. MSP results can be obtained with or without sequencing amplicons, e.g., using gel electrophoresis. MSP (methylation-specific PCR) allows for highly sensitive detection (detection level of 0.1% of the alleles, with full specificity) of locus-specific DNA methylation, using PCR amplification of bisulfite-converted DNA.
[0321] Another method that can be used to determine methylation status after bisulfite treatment of a sample is Methylation-Sensitive High Resolution Melting (MS-HRM) PCR (see, e.g., Hussmann 2018 Methods Mol Biol. 1708:551-571, which is herein incorporated by reference with respect to methods of determining methylation status). MS-HRM is an in-tube, PCR-based method to detect methylation levels at specific loci of interest based on hybridization melting. Bisulfite treatment of the DNA prior to performing MS-HRM ensures a different base composition between methylated and unmethylated DNA, which is used to separate the resulting amplicons by high resolution melting. A unique primer design facilitates a high sensitivity of the assays enabling detection of down to 0.1-1% methylated alleles in an unmethylated background. Oligonucleotide primers for MS-HRM assays are designed to be complementary to the methylated allele, and a specific annealing temperature enables these primers to anneal both to the methylated and the unmethylated alleles thereby increasing the sensitivity of the assays.
[0322] Another method that can be used to determine methylation status after bisulfite treatment of a sample is Quantitative Multiplex Methylation-Specific PCR (QM-MSP). QM-MSP uses methylation specific primers for sensitive quantification of DNA methylation (see, e.g., Fackler 2018 Methods Mol Biol. 1708:473-496, which is herein incorporated by reference with respect to methods of determining methylation status). QM-MSP is a two-step PCR approach, where in the first step, one pair of gene-specific primers (forward and reverse) amplifies the methylated and unmethylated copies of the same gene simultaneously and in multiplex, in one PCR reaction. This methylation-independent amplification step produces amplicons of up to 10.sup.9 copies per μL after 36 cycles of PCR. In the second step, the amplicons of the first reaction are quantified with a standard curve using real-time PCR and two independent fluorophores to detect methylated/unmethylated DNA of each gene in the same well (e.g., 6FAM and VIC). One methylated copy is detectable in 100,000 reference gene copies.
[0323] Another method that can be used to determine methylation status after bisulfite treatment of a sample is Methylation Specific Nuclease-assisted Minor-allele Enrichment (MS-NaME) (see, e.g., Liu 2017 Nucleic Acids Res. 45(6):e39, which is herein incorporated by reference with respect to methods of determining methylation status). Ms-NaME is based on selective hybridization of probes to target sequences in the presence of DNA nuclease specific to double-stranded (ds) DNA (DSN), such that hybridization results in regions of double-stranded DNA that are subsequently digested by the DSN. Thus, oligonucleotide probes targeting unmethylated sequences generate local double stranded regions resulting to digestion of unmethylated targets; oligonucleotide probes capable of hybridizing to methylated sequences generate local double-stranded regions that result in digestion of methylated targets, leaving methylated targets intact. Moreover, oligonucleotide probes can direct DSN activity to multiple targets in bisulfite-treated DNA, simultaneously. Subsequent amplification can enrich non-digested sequences. Ms-NaME can be used, either independently or in combination with other techniques provided herein.
[0324] Another method that can be used to determine methylation status after bisulfite treatment of a sample is Methylation-sensitive Single Nucleotide Primer Extension (Ms-SNuPE™) (see, e.g., Gonzalgo 2007 Nat Protoc. 2(8):1931-6, which is herein incorporated by reference with respect to methods of determining methylation status). In Ms-SNuPE, strand-specific PCR is performed to generate a DNA template for quantitative methylation analysis using Ms-SNuPE. SNuPE is then performed with oligonucleotide(s) designed to hybridize immediately upstream of the CpG site(s) being interrogated. Reaction products can be electrophoresed on polyacrylamide gels for visualization and quantitation by phosphor-image analysis. Amplicons can also carry a directly or indirectly detectable labels such as a fluorescent label, radionuclide, or a detachable molecule fragment or other entity having a mass that can be distinguished by mass spectrometry. Detection may be carried out and/or visualized by means of, e.g., matrix assisted laser desorption/ionization mass spectrometry (MALDI) or using electron spray mass spectrometry (ESI).
[0325] Certain methods that can be used to determine methylation status after bisulfite treatment of a sample utilize a first oligonucleotide primer, a second oligonucleotide primer, and an oligonucleotide probe in an amplification-based method. For instance, the oligonucleotide primers and probe can be used in a method of real-time polymerase chain reaction (PCR) or droplet digital PCR (ddPCR). In various instances, the first oligonucleotide primer, the second oligonucleotide primer, and/or the oligonucleotide probe selectively hybridize methylated DNA and/or unmethylated DNA, such that amplification or probe signal indicate methylation status of a sample.
[0326] Other bisulfite-based methods for detecting methylation status (e.g., the presence of level of 5-methylcytosine) are disclosed, e.g., in Frommer (1992 Proc Natl Acad Sci USA. 1; 89(5):1827-31, which is herein incorporated by reference with respect to methods of determining methylation status).
[0327] In certain MSRE-qPCR embodiments, the amount of total DNA is measured in an aliquot of sample in native (e.g., undigested) form using, e.g., real-time PCR or digital PCR.
[0328] Various amplification technologies can be used alone or in conjunction with other techniques described herein for detection of methylation status. Those of skill in the art, having reviewed the present specification, will understand how to combine various amplification technologies known in the art and/or described herein together with various other technologies for methylation status determination known in the art and/or provided herein. Amplification technologies include, without limitation, PCR, e.g., quantitative PCR (qPCR), real-time PCR, and/or digital PCR. Those of skill in the art will appreciate that polymerase amplification can multiplex amplification of multiple targets in a single reaction. PCR amplicons are typically 100 to 2000 base pairs in length. In various instances, an amplification technology is sufficient to determine methylations status.
[0329] Digital PCR (dPCR) based methods involve dividing and distributing a sample across wells of a plate with 96-, 384-, or more wells, or in individual emulsion droplets (ddPCR) e.g., using a microfluidic device, such that some wells include one or more copies of template and others include no copies of template. Thus, the average number of template molecules per well is less than one prior to amplification. The number of wells in which amplification of template occurs provides a measure of template concentration. If the sample has been contacted with MSRE, the number of wells in which amplification of template occurs provides a measure of the concentration of methylated template.
[0330] In various embodiments a fluorescence-based real-time PCR assay, such as MethyLight™, can be used to measure methylation status (see, e.g., Campan 2018 Methods Mol Biol. 1708:497-513, which is herein incorporated by reference with respect to methods of determining methylation status). MethyLight is a quantitative, fluorescence-based, real-time PCR method to sensitively detect and quantify DNA methylation of candidate regions of the genome. MethyLight is uniquely suited for detecting low-frequency methylated DNA regions against a high background of unmethylated DNA, as it combines methylation-specific priming with methylation-specific fluorescent probing. Additionally, MethyLight can be combined with Digital PCR, for the highly sensitive detection of individual methylated molecules, with use in disease detection and screening.
[0331] Real-time PCR-based methods for use in determining methylation status typically include a step of generating a standard curve for unmethylated DNA based on analysis of external standards. A standard curve can be constructed from at least two points and can permit comparison of a real-time Ct value for digested DNA and/or a real-time Ct value for undigested DNA to known quantitative standards. In particular instances, sample Ct values can be determined for MSRE-digested and/or undigested samples or sample aliquots, and the genomic equivalents of DNA can be calculated from the standard curve. Ct values of MSRE-digested and undigested DNA can be evaluated to identify amplicons digested (e.g., efficiently digested; e.g., yielding a Ct value of 45). Amplicons not amplified under either digested or undigested conditions can also be identified. Corrected Ct values for amplicons of interest can then be directly compared across conditions to establish relative differences in methylation status between conditions. Alternatively or additionally, delta-difference between the Ct values of digested and undigested DNA can be used to establish relative differences in methylation status between conditions.
[0332] In certain particular embodiments, targeted bisulfite sequencing (e.g., using hybrid capture) among other techniques, can be used to determine the methylation status of a methylation biomarker for a disease and/or condition. For example, a colorectal neoplasm (e.g., advanced adenoma and/or colorectal cancer) methylation biomarker that is or includes a single methylation locus. In certain particular embodiments, targeted bisulfite sequencing, among other techniques, can be used to determine the methylation status of a methylation biomarker that is or includes two or more methylation loci.
[0333] Those of skill in the art will appreciate that in embodiments in which a plurality of methylation loci (e.g., a plurality of DMRs) are analyzed for methylation status in a method of screening for colorectal cancer provided herein, methylation status of each methylation locus can be measured or represented in any of a variety of forms, and the methylation statuses of a plurality of methylation loci (preferably each measured and/or represented in a same, similar, or comparable manner) be together or cumulatively analyzed or represented in any of a variety of forms. In various embodiments, methylation status of each methylation locus can be measured as methylation portion. In various embodiments, methylation status of each methylation locus can be represented as the percentage value of methylated reads from total sequencing reads compared against reference sample. In various embodiments, methylation status of each methylation locus can be represented as a qualitative comparison to a reference, e.g., by identification of each methylation locus as hypermethylated or hypomethylated.
[0334] In some embodiments in which a single methylation locus is analyzed, hypermethylation of the single methylation locus constitutes a diagnosis that a subject is suffering from or possibly suffering from a condition (e.g., cancer) (e.g., advanced adenoma, colorectal cancer), while absence of hypermethylation of the single methylation locus constitutes a diagnosis that the subject is likely not suffering from a condition. In some embodiments, hypermethylation of a single methylation locus (e.g., a single DMR) of a plurality of analyzed methylation loci constitutes a diagnosis that a subject is suffering from or possibly suffering from the condition, while the absence of hypermethylation at any methylation locus of a plurality of analyzed methylation loci constitutes a diagnosis that a subject is likely not suffering from the condition. In some embodiments, hypermethylation of a determined percentage (e.g., a predetermined percentage) of methylation loci (e.g., at least 10% (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%)) of a plurality of analyzed methylation loci constitutes a diagnosis that a subject is suffering from or possibly suffering from the condition, while the absence of hypermethylation of a determined percentage (e.g., a predetermined percentage) of methylation loci (e.g., at least 10% (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%)) of a plurality of analyzed methylation loci constitutes a diagnosis that a subject is not likely suffering from the condition. In some embodiments, hypermethylation of a determined number (e.g., a predetermined number) of methylation loci (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 50, 100, 150, or more DMRs) of a plurality of analyzed methylation loci (e.g 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 50, 100, 150, or more DMRs) constitutes a diagnosis that a subject is suffering from or possibly suffering from the condition, while the absence of hypermethylation of a determined number (e.g., a predetermined number) of methylation loci (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 50, 100, 150, or more DMRs) of a plurality of analyzed methylation loci (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 50, 100, 150, or more DMRs) constitutes a diagnosis that a subject is not likely suffering from the condition.
[0335] In some embodiments, methylation status of a plurality of methylation loci (e.g., a plurality of DMRs) is measured qualitatively or quantitatively and the measurement for each of the plurality of methylation loci are combined to provide a diagnosis. In some embodiments, the quantitatively measured methylation status of each of a plurality of methylation loci is individually weighted, and weighted values are combined to provide a single value that can be comparative to a reference in order to provide a diagnosis.
[0336] In some embodiments, methylation status may include determination of methylated and/or unmethylated reads mapped to a genomic region (e.g., a DMR). For example, when using particular sequencing technologies as disclosed herein (e.g., NGS, whole genome bisulfite sequencing, etc.), sequence reads are produced. A sequence read is an inferred sequence of base pairs (e.g., a probabilistic sequence) corresponding to all or part of a sequenced oligonucleotide (e.g., DNA) fragment (e.g., cfDNA fragments, gDNA fragments). In certain embodiments, sequence reads may be mapped (e.g., aligned) to a particular region of interest using a reference sequence (e.g., a bisulfite converted reference sequence) in order to determine if there are any alterations or variations in a read. Alterations may include methylation and/or mutations. A region of interest may include one or more genomic markers including a methylation marker (e.g., a DMR), a mutation marker, or other marker as disclosed herein.
[0337] For example, in the case of bisulfite or enzymatically treated DNA fragments, treatment converts unmethylated cytosines to uracils, while methylated cytosines are not converted to uracils. Accordingly, a sequence read produced for a DNA fragment that has methylated cytosines will be different from a sequence read produced for the same DNA fragment that does not have methylated cytosine. Methylation at sites where a cytosine nucleotide is followed by a guanine nucleotide (e.g., CpG sites) may be of particular interest.
Quality Control Protocol
[0338] In certain embodiments, quality control steps may be implemented. Quality control steps are used to determine whether or not particular steps or processes were conducted within particular parameters. In certain embodiments, quality control steps may be used to determine the validity of results of a given analysis. In addition or alternatively, quality control steps may be used to determine sequenced data quality. For example, quality control steps may be used to determine read coverage of one or more regions of DNA. Quantitative metrics for quality control include, but are not limited to AT dropout rate, GC dropout rate, bisulfite conversion rate (e.g., bisulfite conversion efficiency), and the like. Failure to meet a threshold quality control condition (e.g., a minimum conversion rate, a maximum CG dropout rate, etc.) may indicate, for example, that one or more of the conversion steps were not performed within appropriate parameters.
[0339] For example, in the methods described herein, various steps of a conversion protocol may be optimized to decrease AT and/or GC dropout rate. As is understood by those of skill in the art, AT and GC dropout metrics indicate the degree of inadequate coverage of a particular target region based on its AT or GC content. In certain embodiments, samples having a low GC dropout rate is useful in identifying which samples were processed appropriately. For example, a GC dropout rate found to be less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, or less may be useful in identifying appropriately processed samples.
[0340] In certain embodiments, a quality control step may involve determining an on and/or off-target ratio. Sequence reads that align to a region of interest (e.g., a DMR) are considered to be on-target, while sequence reads that do not align to the region of interest (e.g., a DMR) are considered to be off-target. In certain embodiments, the on-target ratio is represented as a percentage of on-target bases to the total number of aligned bases. In certain embodiments, the on-target ratio is represented as a percentage of on-target and near-target bases to the total number of aligned bases. Near-target bases may be a base within a certain number of bases (e.g., within 500 bp, within 200 bp, within 100 bp) of the target region. In certain embodiments, the on-target ratio is at least 10%, least 20%, least 30%, least 40%, least 50%, least 60%, least 70%, at least 80%, at least 90%, at least 95%, at least 99% or more for a sequencing experiment to pass quality control. In certain embodiments, the off-target ratio is represented as a percentage of off-target bases to the total number of aligned bases. In certain embodiments, an off-target ratio is less than 95%, less than 90%, less than 85%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, less than 1% for a sequencing experiment to pass quality control.
[0341] In certain embodiments, a quality control step may include determining quality scores for mapped sequence reads. A quality score is a value which quantifies a probability that a sequence read is incorrectly mapped. For example, when mapping short or repetitive sequences, it is possible that a sequence will be mapped to multiple places in a reference genome. The quality score considers the best alignment of the sequence read to the reference genome as compared to other possible alignments of the sequence read to the reference genome. In certain embodiments, the quality score is a Mapping Quality (MAPQ) score. The MAPQ is the negative, log-scaled probability that a read is misaligned. A high score indicates a high confidence that a read is aligned correctly, while a low score indicates a low confidence that a read is aligned correctly. In certain embodiments, the MAPQ score may be calculated using the following equation:
MAPQ score=−10 log.sub.10 Pr{mapping position is wrong}.
[0342] In certain embodiments, the MAPQ score is rounded to the nearest integer. In certain embodiments Pr is a probability that the sequence read is incorrectly mapped as obtained from an alignment (e.g., mapping) tool. In certain embodiments, the scaling factor is 1 (instead of 10), or another number.
Artificial Spike-In Control
[0343] Control nucleic acid (e.g., DNA) molecules (e.g., “spike-in controls”) may be used to evaluate or estimate conversion efficiency of unmethylated and methylated cytosines to uracils. Control nucleic acid molecules may be used in sequencing methods involving conversion (e.g., bisulfite or enzymatic conversion) of DNA samples.
[0344] When DNA is subjected to conversion (e.g., bisulfite or enzymatic conversion) as described herein, conversion may be incomplete. That is, some number of unmethylated cytosines may not be converted to uracils. If the conversion is not complete such that unmethylated cytosines are not mostly converted, the unconverted unmethylated cytosines may be identified as methylated when the DNA sequenced. Accordingly, in order to determine whether or not bisulfite conversion is complete, a control DNA molecule may be subjected to conversion along with DNA fragments from a sample. In certain embodiments, sequencing the converted control DNA molecules (e.g., using an NGS technique as described herein) generates a plurality of control sequence reads. Control sequence reads may be used to determine conversion rates of unmethylated and/or methylated cytosines to uracils.
[0345] Prior techniques did not recognize that controls (e.g., a control DNA molecule) were useful to include in each sample. Rather, they presumed that conversion efficiencies remained relatively consistent between samples for a given run. However, the inventors have identified that conversion rate of unmethylated cytosines to uracils in DNA fragments may vary significantly from on sample to another. For example, conversion efficiency may range from 10% to 110% within a single batch of processed samples. Note, there can be overconversion such that conversion efficiency can be greater than 100%, e.g., the conversion efficiency is 110% when 10% of the methylated cytosine gets converted. In certain embodiments, the conversion efficiency ranges from 30% to 110%. In other embodiments, the conversion efficiency ranges from 50% to 100%.
[0346] In certain embodiments, a control DNA molecule may be added to a sample after fragmentation and before conversion using e.g., bisulfite or enzymatic reagents. In certain embodiments, a plurality (e.g., two, three, four or more) control DNA sequences may be added to DNA fragments of a sample. A control DNA molecule may be a known sequence. For example, the sequence, number of methylated bases, and number of unmethylated bases of the control sequence had been determined prior to addition of the control DNA molecule to the sample. In certain embodiments, a control sequence may be a DNA sequence which is produced in vitro to contain artificially methylated or unmethylated nucleotides (e.g., methylated cytosines). In certain embodiments, a control sequence may be a DNA sequence which is produced to contain completely unmethylated DNA nucleotides.
[0347] A high conversion efficiency of the spike-in control sequence may be used to infer the conversion efficiency of a DNA fragments undergoing the same conversion process as a spike-in control. For example, deamination of at least at least 98% of unmethylated cytosines in the unmethylated spike-in control DNA sequence indicates that conversion efficiency is high and that a sample may pass a quality control assessment. In certain embodiments, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% of unmethylated cytosines of a plurality of DNA fragments of a control DNA sequence are converted into uracils. A high conversion efficiency is important as it is ideal for all (or nearly all) of the unmethylated cytosines to be converted to uracils when subjecting DNA to bisulfite or enzymatic treatments. As described above, unconverted, unmethylated cytosines may serve as a source of noise in the data.
[0348] In addition, conversion of methylated cytosines to uracils is undesirable when DNA is treated using a conversion process. Conversion of methylated cytosines of a spike-in control is indicative that methylated cytosines have been converted to uracils in a DNA sample subjected to the same treatment as the methylated spike-in control. Methylated cytosines in a methylated spike-in control should not convert to uracils. For the same reasons as described above, methylated cytosines being converted to uracils may result in misidentification of purportedly unmethylated cytosines during methylation analysis. In certain embodiments, at most 5%, at most 4%, at most 3%, at most 2% or at most 1% of methylated cytosines of a plurality of DNA fragments of a control DNA sequence are converted into uracils. For example, deamination of at most 2% of methylated cytosines in a methylated spike-in control DNA sequence indicates that conversion efficiency is high and that a sample may pass a quality control assessment.
Identifying Mutations
[0349] In certain embodiments as disclosed herein, genomic mutations may be identified in one or more predetermined mutation biomarkers. In various embodiments, a mutation biomarker of the present disclosure is used for further detection (e.g., screening) and/or classification of a condition in addition to methylation biomarkers. In certain embodiments, information regarding a methylation status of one or more colorectal cancer biomarkers may be combined with a mutation biomarker in order to further classify the identified colorectal cancer. In addition or alternatively, mutation biomarkers may be used to determine or recommend (e.g., either for or against) a particular course of treatment for the identified disease and/or condition.
[0350] In certain embodiments, identifying genomic mutations may be performed using a sequencing technique as discussed herein (e.g., a NGS sequencing technique). In certain embodiments, oligonucleotides (e.g., cfDNA fragments, gDNA fragments) are sequenced to a read depth sufficient to detect a genomic mutation (e.g., in a mutation biomarker, in a tumor markers) at a frequency in a sample as low as 1.0%, 0.75%, 0.5%, 0.25%, 0.1%, 0.075%, 0.05%, 0.025%, 0.01%, or 0.005%.
[0351] Genomic mutations generally include any variation in nucleotide base pair sequences of DNA as is understood in the art. A mutation in a nucleic acid may, in some embodiments, include a single nucleotide variant, an inversion, a deletion, an insertion, a transversion, a translocation, a fusion, a truncation, an amplification, or a combination thereof, as compared to a reference DNA sequence.
[0352]
[0353] By way of example, NRAS_p.A146, listed in the first row of
[0354] Mutations may be identified using NGS sequencing techniques (e.g., targeted NGS sequencing techniques, hybridization NGS sequencing techniques, or the like) or other sequencing techniques disclosed herein. In certain embodiments as disclosed herein, mutations may be identified in converted (e.g., bisulfite or enzymatic converted) DNA fragments. In certain embodiments, mutations and methylated loci may be identified in parallel (e.g., simultaneously) using a single sequencing assay (e.g., an NGS assay). In certain embodiments, one or more capture probes are targeted to capture and/or enrich for a region of interest of an oligonucleotide (e.g., DNA) sequence corresponding to one or more mutations markers (e.g., mutation regions and sites as found in
[0355] In certain embodiments, mutation markers contain low GC content regions. Due to the low GC content, sufficient coverage of a region may not be obtained when sequencing a low GC content region using protocols adapted for high GC content regions. For example, targeted NGS sequencing (e.g., targeted bisulfite sequencing) of a low GC content region using only 1× tiling density of a target region may not provide sufficient coverage of a mutation region. Tiling (e.g., tiling density, tiling frequency) refers to a number of probes targeted to a region. Increased probe tiling density (e.g., through increasing the number of probes targeting a region) may be used in order to provide additional coverage for a region. For example, coverage of a low GC content region may be improved through increased tiling. Accordingly, increasing tiling density of a region to at least 2× tiling (e.g., 3×, 4× or more) may be beneficial in enhancing enrichment of a targeted region. For example, with 2× tiling, a region covered by a probe may be covered with at two probes which overlap with one another. In addition or alternatively, probes may be overlapped to permit enhanced coverage of a region. For example, probes may be overlapped by at least 10%, 20%, 30%, 40%, 50% or more. The amount which two probes overlap with one another may depend on desired tiling density, sequence of a targeted region, or other factors. For the avoidance of doubt, tiling and/or overlap of probes may also be changed over high GC content regions (e.g., methylation loci) as well.
Exemplary Deduplication Steps
[0356] In certain embodiments as discussed herein, duplicate sequences are found in sequencing data. Duplicate sequences arise from a number of potential sources as discussed herein, and accordingly may need to be removed from sequencing data. Duplicates are particularly important to remove in an analysis as signals from cancer are low. Cancer signals would get lost in noise if duplicates are not removed.
[0357] For example, in certain embodiments sequencing data may include a large number of reads obtained from sequencing oligonucleotide fragments (e.g., DNA fragments, e.g., cfDNA, gDNA fragments) of a sample. Multiple reads corresponding to a particular DNA fragment may result in false variant calls (e.g., identification of multiple variants of the same DNA fragment), which would interfere with the identification of a methylated CpG site and/or a mutation. In certain embodiments, duplicate sequences are removed prior to determining read-wise methylation values. In certain embodiments, a bioinformatics package (e.g., Picard, SAMTools) may be used to mark and remove duplicates from sequencing data.
[0358]
[0359] In certain embodiments, PCR duplicates (also known as library duplicates) and/or over-sequencing duplicates may also be removed (1340). PCR duplicates and over-sequencing duplicates are sequence reads that result from sequencing two or more copies of the exact same DNA fragment. PCR duplicates and over-sequencing duplicates may arise during library preparation. In certain embodiments, sequence reads are considered PCR duplicates or over-sequencing duplicates if the sequence reads have (1) a 5′ end coordinate, (2) a 3′ end coordinate, and (3) a methylation level that are the same, wherein the 5′ end coordinate and the 3′ end coordinate of a sequence read correspond to the position at which the 5′-most nucleotide and the 3′-most nucleotide, respectively, of the sequence read map to a reference sequence. Finally, the deduplicated reads are quality filtered (1350), which results in the removal of additional reads.
[0360] In certain embodiments, deduplicating sequence reads does not comprise removing duplicate sequence reads that have a different methylation level. For example, a sample may have two sequence reads that are identical. However, one sequence read may have a CpG site that is methylated, while the same CpG site in the other strand is not methylated. In certain embodiments, both strands may be kept for further bioinformatics analysis. Without wishing to be bound to any particular theory, a presence of different methylation levels within duplicate fragments may be due to sequencing errors or a different source of one fragment.
Applications
[0361] Methods and compositions of the present disclosure can be used in any of a variety of applications. For example, methods and compositions of the present disclosure can be used to screen, or aid in screening for a condition (e.g., cancer). In particular, the methods and compositions can be used to screen, or aid in screening for a colorectal neoplasm, e.g., advanced adenoma and/or colorectal cancer. In various instances, screening using methods and compositions of the present disclosure can detect any stage of colorectal cancer, including without limitation early-stage colorectal cancer. In some embodiments, screening using methods and compositions of the present disclosure is applied to individuals 40 years of age or older, e.g., 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 years or older. In particular, individuals 40 years of age or older are of interest for colorectal cancer and/or advanced adenoma screening. In some embodiments, screening using methods and compositions of the present disclosure is applied to individuals 18 years of age or older, e.g., 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 years or older. In some embodiments, screening using methods and compositions of the present disclosure is applied to individuals 18 to 40 years of age. In various embodiments, screening using methods and compositions of the present disclosure is applied to individuals experiencing abdominal pain or discomfort, e.g., experiencing undiagnosed or incompletely diagnosed abdominal pain or discomfort. In various embodiments, screening using methods and compositions of the present disclosure is applied to individuals experiencing no symptoms likely to be associated with a cancer or a colorectal neoplasm such as advanced adenoma, polyposis, and/or colorectal cancer. Thus, in certain embodiments, screening using methods and compositions of the present disclosure is fully or partially preventative or prophylactic, at least with respect to later or non-early stages of cancer.
[0362] In various embodiments, cancer screening using methods and compositions of the present disclosure can be applied to an asymptomatic human subject. In particular, a subject can be referred to as “asymptomatic” if the subject does not report, and/or demonstrate by non-invasively observable indicia (e.g., without one, several, or all of device-based probing, tissue sample analysis, bodily fluid analysis, surgery, or cancer screening), sufficient characteristics of the condition to support a medically reasonable suspicion that the subject is likely suffering from the condition. Detection of a colorectal neoplasm such as advanced adenoma and/or early stage colorectal cancer is particularly likely in asymptomatic individuals screened in accordance with methods and compositions of the present disclosure.
[0363] Those of skill in the art will appreciate that regular, preventative, and/or prophylactic screening for a colorectal neoplasm such as advanced adenoma and/or colorectal cancer improves diagnosis. As noted above, early stage cancers include, according to at least one system of cancer staging, Stages 0 to II C of colorectal cancer. Thus, the present disclosure provides, among other things, methods and compositions particularly useful for the diagnosis and treatment of colorectal neoplasms including advanced adenoma, polyposis and/or early stage colorectal cancer. Generally, and particularly in embodiments in which screening in accordance with the present disclosure is carried out annually, and/or in which a subject is asymptomatic at time of screening, methods and compositions of the present invention are especially likely to detect early stage colorectal cancer.
[0364] In various embodiments colorectal cancer screening in accordance with the present disclosure is performed once for a given subject or multiple times for a given subject. In various embodiments, colorectal cancer screening in accordance with the present disclosure is performed on a regular basis, e.g., every six months, annually, every two years, every three years, every four years, every five years, or every ten years.
[0365] In various embodiments, screening using methods and compositions disclosed herein will provide a diagnosis of a condition (e.g., a type or class of a colorectal neoplasm). In other instances, screening for colorectal neoplasms using methods and compositions disclosed herein will be indicative of having one or more conditions, but not definitive for diagnosis of a particular condition. For example, screening may be used to classify a subject as having one or more conditions or combination of conditions including, but not limited to, advanced adenoma and/or colorectal cancer. In various instances, screening using methods and compositions of the present disclosure can be followed by a further diagnosis-confirmatory assay, which further assay can confirm, support, undermine, or reject a diagnosis resulting from prior screening, e.g., screening in accordance with the present disclosure.
[0366] In various embodiments, screening in accordance with methods and compositions of the present disclosure reduces colorectal cancer mortality, e.g., by early colorectal cancer diagnosis. Data supports that colorectal cancer screening reduces colorectal cancer mortality, which effect persisted for over 30 years (see, e.g., Shaukat 2013 N Engl J Med. 369(12):1106-14). Moreover, colorectal cancer is particularly difficult to treat at least in part because colorectal cancer, absent timely screening, may not be detected until cancer is past early stages. For at least this reason, treatment of colorectal cancer is often unsuccessful. To maximize population-wide improvement of colorectal cancer outcomes, utilization of screening in accordance with the present disclosure can be paired with, e.g., recruitment of eligible subjects to ensure widespread screening.
[0367] In various embodiments, screening of colorectal neoplasms including one or more methods and/or compositions disclosed herein is followed by treatment of colorectal cancer, e.g., treatment of early stage colorectal cancer. In various embodiments, treatment of colorectal cancer, e.g., early stage colorectal cancer, includes administration of a therapeutic regimen including one or more of surgery, radiation therapy, and chemotherapy. In various embodiments, treatment of colorectal cancer, e.g., early stage colorectal cancer, includes administration of a therapeutic regimen including one or more of treatments provided herein for treatment of stage 0 colorectal cancer, stage I colorectal cancer, and/or stage II colorectal cancer.
[0368] In various embodiments, treatment of colorectal cancer includes treatment of early stage colorectal cancer, e.g., stage 0 colorectal cancer or stage I colorectal cancer, by one or more of surgical removal of cancerous tissue e.g., by local excision (e.g., by colonoscope), partial colectomy, or complete colectomy.
[0369] In various embodiments, treatment of colorectal cancer includes treatment of early stage colorectal cancer, e.g., stage II colorectal cancer, by one or more of surgical removal of cancerous tissue (e.g., by local excision (e.g., by colonoscope), partial colectomy, or complete colectomy), surgery to remove lymph nodes near to identified colorectal cancer tissue, and chemotherapy (e.g., administration of one or more of 5-FU and leucovorin, oxaliplatin, or capecitabine).
[0370] In various embodiments, treatment of colorectal cancer includes treatment of stage III colorectal cancer, by one or more of surgical removal of cancerous tissue (e.g., by local excision (e.g., by colonoscopy-based excision), partial colectomy, or complete colectomy), surgical removal of lymph nodes near to identified colorectal cancer tissue, chemotherapy (e.g., administration of one or more of 5-FU, leucovorin, oxaliplatin, capecitabine, e.g., in a combination of (i) 5-FU and leucovorin, (ii) 5-FU, leucovorin, and oxaliplatin (e.g., FOLFOX), or (iii) capecitabine and oxaliplatin (e.g., CAPEOX)), and radiation therapy.
[0371] In various embodiments, treatment of colorectal cancer includes treatment of stage IV colorectal cancer, by one or more of surgical removal of cancerous tissue (e.g., by local excision (e.g., by colonoscope), partial colectomy, or complete colectomy), surgical removal of lymph nodes near to identified colorectal cancer tissue, surgical removal of metastases, chemotherapy (e.g., administration of one or more of 5-FU, leucovorin, oxaliplatin, capecitabine, irinotecan, VEGF-targeted therapeutic agent (e.g., bevacizumab, ziv-aflibercept, or ramucirumab), EGFR-targeted therapeutic agent (e.g., cetuximab or panitumumab), Regorafenib, trifluridine, and tipiracil, e.g., in a combination of or including (i) 5-FU and leucovorin, (ii) 5-FU, leucovorin, and oxaliplatin (e.g., FOLFOX), (iii) capecitabine and oxaliplatin (e.g., CAPEOX), (iv) leucovorin, 5-FU, oxaliplatin, and irinotecan (FOLFOXIRI), and (v) trifluridine and tipiracil (Lonsurf)), radiation therapy, hepatic artery infusion (e.g., if cancer has metastasized to liver), ablation of tumors, embolization of tumors, colon stent, colorectomy, colostomy (e.g., diverting colostomy), and immunotherapy (e.g., pembrolizumab).
[0372] Those of skill in the art that treatments of colorectal cancer provided herein can be utilized, e.g., as determined by a medical practitioner, alone or in any combination, in any order, regimen, and/or therapeutic program. Those of skill in the art will further appreciate that advanced treatment options may be appropriate for earlier stage cancers in subjects previously having suffered a cancer or colorectal cancer, e.g., subjects diagnosed as having a recurrent colorectal cancer.
[0373] In some embodiments, methods and compositions for colorectal neoplasm screening provided herein can inform treatment and/or payment (e.g., reimbursement for or reduction of cost of medical care, such as screening or treatment) decisions and/or actions, e.g., by individuals, healthcare facilities, healthcare practitioners, health insurance providers, governmental bodies, or other parties interested in healthcare cost.
[0374] In some embodiments, methods and compositions for colorectal neoplasm screening provided herein can inform decision making relating to whether health insurance providers reimburse a healthcare cost payer or recipient (or not), e.g., for (1) screening itself (e.g., reimbursement for screening otherwise unavailable, available only for periodic/regular screening, or available only for temporally- and/or incidentally-motivated screening); and/or for (2) treatment, including initiating, maintaining, and/or altering therapy, e.g., based on screening results. For example, in some embodiments, methods and compositions for colorectal neoplasm screening provided herein are used as the basis for, to contribute to, or support a determination as to whether a reimbursement or cost reduction will be provided to a healthcare cost payer or recipient. In some instances, a party seeking reimbursement or cost reduction can provide results of a screen conducted in accordance with the present specification together with a request for such reimbursement or cost reduction of a healthcare cost. In some instances, a party making a determination as to whether or not to provide a reimbursement or cost reduction of a healthcare cost will reach a determination based in whole or in part upon receipt and/or review of results of a screen conducted in accordance with the present specification.
[0375] For the avoidance of any doubt, those of skill in the art will appreciate from the present disclosure that methods and compositions for colorectal cancer diagnosis of the present specification are at least for in vitro use. Accordingly, all aspects and embodiments of the present disclosure can be performed and/or used at least in vitro.
Kits
[0376] The present disclosure includes, among other things, kits including one or more compositions for use in screening as provided herein, optionally in combination with instructions for use thereof in screening (e.g., screening for advanced adenoma, colorectal cancer, other cancers, or other diseases or conditions associated with an aberrant methylation status, e.g., neurodegenerative diseases, gastrointestinal disorders, and the like). In various embodiments, a kit for screening a diseases or conditions associated with an aberrant methylation status can include one or more oligonucleotide probes (e.g., one or more biotinylated oligonucleotide probes). In certain embodiments, the kit for screening optionally includes one or more bisulfite conversion reagents as disclosed herein. In certain embodiments, the kit for screening optionally includes one or more enzymatic conversion reagents as disclosed herein. In certain embodiments, the kit for screening may include one or more adapters as described herein. In certain embodiments, the kit may include one or more reagents used in library preparation. In certain embodiments, the kit may include software (e.g., for analyzing methylation status of DMRs).
EXAMPLES
Example 1: Identification of Markers Associated with Colorectal Cancer and Advanced Adenoma
[0377] The purpose of this Example was to identify differentially methylated regions (DMRs) in DNA of colorectal cancer and colonic adenoma samples (e.g., samples from subjects having advanced adenoma). Identification of DMRs was performed by comparing DNA of subjects having colorectal cancer and/or colonic adenomas with matching control samples. This comparison allowed for development of methods that would elucidate colorectal cancer and advanced adenoma related methylation patterns from cell-free (cfDNA).
[0378] Whole genome bisulfite sequencing (WGBS) was used to identify differences in methylation status in samples of genomic DNA (gDNA) and cfDNA obtained from a variety of sources. gDNA was obtained from tissue samples with different histological backgrounds (e.g., colorectal cancer, colonic adenoma, lung cancer, breast cancer, pancreatic cancer, gastric cancer, and matching controls) and buffy coat samples.
[0379] Genomic DNA (gDNA) from tissue and buffy coat samples was extracted using a DNeasy Blood & Tissue kit (Qiagen) according to a manufacturer's protocol. Extracted gDNA was then further processed in order to fragment it. For example, gDNA was fragmented into segments having lengths of about 400 bp with a Covaris S220 ultra-sonicator.
[0380] cfDNA from plasma samples was extracted using QIAamp Circulating Nucleic Acid kit (Qiagen) according to the manufacturer's protocol.
[0381] The extracted and fragmented gDNA (genomic DNA) and cfDNA was bisulfite-converted with EZ DNA Methylation-Lightning kit (ZymoResearch). Sequencing libraries were prepared from the bisulfite converted DNA fragments by using Accel-NGS Methyl-seq DNA library kit (Swift Biosciences). The converted DNA fragments were sequenced with average depth of 37.5× with NovaSeq6000 (Illumina) equipment, using paired-end sequencing. For this experiment, paired-end sequencing was conducted such that 150 bp of each end of a converted DNA fragment was covered (e.g., 2×150). The sequenced reads were aligned to a bisulfite-converted human genome (Ensembl 91 assembly) using Bisulfite Read Mapper with Bowtie 2. The following steps were used to align sequenced reads to a bisulfite-converted human genome: [0382] 1. Evaluation of the sequencing quality [0383] 2. Alignment to a reference genome (hG38) [0384] 3. Deduplication and cleaning from adapter dimers [0385] 4. Methylation calling (e.g., identification of methylated nucleic acids)
[0386] Differentially methylated region analysis was done by comparing beta ((3) values of individual CpGs of the colon cancer and/or colonic adenoma tissue samples to a matching control tissue. The β-value reflects methylation level of CpG reads in a sample. A (3 value of 0 indicates no methylated reads were found at a specific CpG location, while a (3 value of 1 indicates that all reads were fully methylated. Individual CpG methylation value scores were combined into regions of having a minimum of 3 CpGs within 50 bp distance of one another. The q-value of the region, which is the p-value corrected with a between-group label permutation test, was evaluated in order to select for regions of DNA from subjects with colorectal cancer and/or colonic adenoma which were significantly differently methylated from the same region in DNA obtained from a control subject. A q-value <0.05 was considered to show high statistical significance of a differentially methylated region (DMR). Significant regions were further evaluated to determine if there was a significant methylation signal compared to tissue samples with non-colorectal cancer origin, control tissue samples of non-colorectal origin, buffy coat samples, and cfDNA from healthy individuals.
[0387] In total, 6061 DMRs were initially identified as being significant for colorectal cancer and/or advanced adenoma. These DMRs include regions that are more indicative of colorectal cancer, DMRs that are more indicative of different histological subtypes of colonic adenomas, and regions that are indicative of both colorectal cancer and advanced adenoma.
[0388] Further cancer signal analysis was done using on the selected target regions from whole genome sequencing data using a read-wise signal scoring method. Thresholds were calculated in tissue-control paired samples to allow maximum separation between cancer and control reads. The calculated scores were applied to each read obtained from plasma cfDNA of subjects.
Example 2: Feature Evaluation and Algorithm Development
[0389] The purpose of this Example was to identify which differentially methylated regions (DMRs) from Example 1 were more indicative of colorectal cancer and/or advanced adenoma and could be used for subsequent panel development. The work performed in this Example evaluated about 2000 DMRs that were found to be more indicative of colorectal cancer. The initial target regions and a prediction model were employed on the sample set of about 2000 DMRs in a train-verification setting. Results obtained from the larger sample set served as basis for further QC pipeline definition and optimization of cancer signal detection methods described herein.
Methods
[0390]
[0391] Sample Set
[0392] The study was conducted under the approval of The Research Ethics Committee of the Virgen del Rocio Hospital of Sevilla, Spain (Ethical Committee Approval ref: 2014PI/155). All patients provided written informed consent prior to sample collection.
[0393] Patient Cohorts
[0394] Blood samples were collected in endoscopy units and clinics from average risk patients prior to colonoscopy for screening or due to fecal occult blood (pre-colonoscopy samples). CRC (colorectal cancer) numbers were enriched through prospective enrollment of CRC patients from oncology units before CRC treatment, and samples obtained from biobanks (post-colonoscopy samples). The stage of the colorectal cancer patients was defined as per the AJCC Cancer Staging Manual 8th Edition, which is incorporated by reference in its entirety.
[0395] Pre-colonoscopy blood samples were collected a maximum of 60 days prior to colonoscopy through the day of colonoscopy, but prior to administration of any sedatives for the procedure. In order to include a patient, the colonoscopy had to reach the cecum and visibility had to be “Good” or “Excellent” for each segment of the colorectum. Patients were assigned to a condition group based on colonoscopy and pathology findings. Colonoscopy and pathology findings included findings of colorectal cancer (CRC), advanced adenoma (AA), non-advanced adenoma (NAA), hyperplastic polyps, or healthy (e.g., “normal”) colorectum. Subjects having AA were defined as subjects having an adenoma equal to or greater than 1 cm, tubulovillous histology, high-grade dysplasia, and/or serrated adenoma with dysplasia, carcinoma in situ.
[0396] Blood samples from post-colonoscopy patients awaiting CRC treatment were collected at least 3 days after colonoscopy. The average time for collection was 15 days post-colonoscopy. The time for collection ranged from 3 to 75 days.
Study Inclusion Criteria
[0397] Participants could be female or male and were required to be at least 45 years of age.
Study Exclusion Criteria
[0398] The exclusion criteria were: (1) prior diagnosis of cancer, except for patients with newly diagnosed colorectal cancer, (2) family history of CRC, (3) personal or family history of genetic cancer predisposition, (4) prior diagnosis of benign gastrointestinal disease, (5) pregnancy, and (6) for participants with colorectal cancer, current or prior therapy for the current cancer. Current or prior therapy included: surgical management beyond that required to establish diagnosis, chemotherapy, immunotherapy, hormone therapy, and/or radiation therapy.
Plasma Sample Collection Protocol
[0399] Plasma samples were collected using one of two methods. In the first method, plasma was collected using K2 EDTA Tubes. Plasma collected with these types of tubes was extracted with double-spin centrifugation within 2 hours of collection. In the second method, plasma was collected with Cell-Free DNA BCT® Streck tubes. Plasma was then extracted with double-spin centrifugation within 2 days of collection. In both methods, plasma was stored at −80° C. until it was analyzed.
cfDNA Extraction from Plasma and Quality Control Samples
[0400] cfDNA was extracted from 4 mL of human plasma using a QIAamp MinElute ccfDNA Midi Kit (Qiagen) according to the manufacturer's specifications.
[0401] cfDNA concentration was measured using the Qubit® dsDNA HS Assay Kit (Thermo Fisher Scientific).
[0402] cfDNA quality was assessed with DNF-474 NGS fragment kit on a Fragment Analyzer (Agilent).
[0403] A minimum 10 ng of extracted cfDNA is required to pass into next step.
Bisulfite and Enzymatic Conversion of DNA
[0404] Between 10 ng and 20 ng of cfDNA from each of patient was bisulfite treated using an optimized EZ DNA Methylation-Direct Kit (Zymo). NEB Next Enzymatic Methyl-seq Conversion Module (NEB) kit was used together with formamide denaturation on 16 replicate samples. Results from the replicate samples prepared with an enzymatic method are compared with bisulfite converted samples in Example 3. Deamination of the cfDNA helps in identification of methylated and unmethylated cytosine residues, particularly at CpG sites.
[0405] The NEB kit is an enzyme-based alternative method to bisulfite conversion for deamination of the cfDNA. In the enzymatic method, TET2 oxidizes methylated cytosines (both 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC)). Following oxidation, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) was used to treat the DNA. Unmodified cytosines (e.g., unmethylated cytosines unaffected by TET2 oxidation), are deaminated to uracils.
[0406] In the enzymatic method, 10 μl of TET2 reaction buffer, 1 μl DTT (Dithiothreitol), 1 μl oxidation supplement and 1 μl of TET2 were added to 28 μl of DNA. 5 μl of diluted Fe(II) solution was added and incubated for 1 h at 37° C. DNA oxidation was then stopped. Oxidized DNA was then cleaned. 4 μl of formamide was added to 16 μl of oxidized DNA for denaturation. The following was then added to 20 μl of denatured DNA: 68 μl of water, 10 μl APOBEC Reaction Buffer, 1 μl BSA, and 1 μl APOBEC. The solution was then incubated at 37° C. for 3 hours.
[0407] An optimized version of the EZ DNA Methylation-Direct Kit (Zymo) protocol was used as is presented below. The optimized version of the protocol contains various quality controls and experimental parameters which are important to maintaining the integrity of the sequenced cfDNA and/or identifying if any errors are present in the processes.
[0408] Artificially methylated and unmethylated spike-in (Premium RRBS kit [Diagenode]) control sequences were added to all cfDNA samples prior to conversion of the cfDNA. The spike-in control sequences were added in using a 1:10000 ratio (by volume) of spike-in control to cfDNA.
[0409] In the optimized version of the protocol presented below, the ratio of the CT Conversion Reagent to sample is lower than a standard ratio. For example, in a standard protocol, 20 μl of sample and 130 μl of CT Conversion Reagent may be used. In the protocol presented below, 117 μl CT conversion reagent was used for 330 of sample. The increased amount of sample accounted for low amounts of starting material. In addition, increasing the amount of sample and/or decreasing the amount of bisulfite reagent may be done to compensate for the aggressive nature of the bisulfite reagent, which may further fragment the DNA.
[0410] Additionally, the temperatures of the denaturation and conversion cycles and number of denaturation-conversion cycles were changed. In a standard protocol, a denaturation-conversion cycle is run a single time. In addition under standard protocols, denaturation is conducted at 98° C. for 8 mins, while conversion is conducted at 64° C. for 3.5 hours.
[0411] CT Conversion Reagent was a reagent which contained sodium metabisulphite. The reagent was used in bisulfite conversion of cfDNA. As provided by the manufacturer, each tube of CT Conversion Reagent was designed for 10 separate DNA treatments. CT Conversion Reagent was prepared as follows:
[0412] 1. 790 μl of M-Solubilization Buffer and 300 μl of M-Dilution Buffer was added to a tube of CT Conversion Reagent.
[0413] 2. The solution was mixed at room temperature with frequent vortexing or shaking for 10 minutes (Keep in the dark).
[0414] 3. 160 μl of M-Reaction Buffer was added to the solution and mixed for an additional 1 minute.
[0415] Note: It was normal to see trace amounts of undissolved reagent in the CT Conversion Reagent. The CT Conversion Reagent was light sensitive, its exposure to light was minimized. [0416] 117 μl CT conversion reagent was added to 330 of sample. The solution was pipetted up and down about 5-times. [0417] The sample was mixed by inversion and then centrifuged briefly to ensure no droplets were in the cap or sides of the tube. [0418] The samples were put in the thermocycler and run using the following protocol:
TABLE-US-00013 Cycle Step Temperature Time Cycles Denaturation 95° C. 1 min 20 Conversion 60° C. 10 min Hold 4° C. O/N / [0419] If the samples were not ready, the M-Wash buffer was prepared by adding 24 ml of 100% ethanol to the 6 ml M-Wash Buffer concentrate (D5020) or 96 ml of 100% ethanol to the 24 ml M-Wash Buffer concentrate (D5021). [0420] 600 μl of M-Binding Buffer was added into a Zymo-Spin™ IC Column and the column was placed into a provided Collection Tube. [0421] The sample was loaded into the Zymo-Spin™ IC Column containing the M-Binding Buffer. The cap was closed and the sample was mixed by inverting the column several times. [0422] The column was centrifuged at full speed (13000 g) for 1 min. The flow-through was discarded. [0423] 100 μl of M-Wash Buffer was added to the column. The column was centrifuged at full speed (13000 g) for 1 min. [0424] 200 μl of M-Desulphonation Buffer was added to the column and incubated at room temperature (20-30° C.) for exactly 30 minutes. After this incubation period, the column was centrifuged at full speed (13000 g) for 1 min. [0425] 200 μl of M-Wash Buffer was added to the column. The column was centrifuged at full speed (13000 g) for 1 min. The flow-through was discarded. [0426] Another 200 μl of M-Wash Buffer was added to the column and the column was centrifuged at a higher speed (15000 g) for 1.5 min. [0427] The column was placed into a 1.5 ml microcentrifuge tube. 17 μl of M-Elution Buffer was added directly to the column matrix and incubated for 2 min. The column was centrifuged for 1.5 min at full speed (20000 g) to elute the DNA. [0428] A second elution was performed by transferring the eluate to the column membrane and waiting for 2 min. The column was centrifuged for 1.5 min at full speed (20000 g) to elute the DNA. [0429] 150 of each bisulfited cfDNA sample was transferred to 8-strip tubes with RNAse/DNAse-free cap and frozen at −20° C. for subsequent library preparation.
[0430] Converted cfDNA quality was assessed using RNA 6000 Pico Kit (Agilent) on a Fragment Analyzer™ (Agilent).
Library Preparation
[0431] Converted cfDNA was used as input for NGS (next generation sequencing) library preparation. The Accel-NGS® Methyl-Seq DNA Library Kit (Swift Bioscience) was used to prepare a library using the converted cfDNA.
[0432] Optimal library amplification was assessed by qPCR using KAPA SYBR® FAST (Sigma-Aldrich) on LightCycler® 96 System (Roche). qPCR was used to measure a total concentration of a prepared library, as described herein. The minimum amount of library material required was about 200 ng. qPCR determines the optimal number of PCR cycles that may need to be performed in order to obtain the minimum amount of library material. The generated DNA libraries were first purified on IP-Star® Compact Automated System (Diagenode Cat #B03000002) using Agencourt® AMPure® XP (Beckman Coulter), then quantified using Qubit™ dsDNA HS Assay Kit (Thermo Fisher Scientific) and finally their size assessed with High Sensitivity NGS Fragment Analysis Kit (DNF-474) on a Fragment Analyzer™ (Agilent).
Hybrid Capture
[0433] 120-bp biotinylated DNA probes were designed for targeted (e.g., selective) enrichment of bisulfite or enzymatically-converted DNA. 120-bp probes were designed to target either hypermethylated fragments (100% methylated CpGs) or hypomethylated fragments (100% unmethylated CpGs) of pre-determined regions (e.g., methylation markers, mutation markers). Probes were designed such that there were at least one probe per strand and one probe per methylation status. That is, there were two probes targeting the coding strand and two probes targeting the non-coding strand. One of the two probes in each pair targeted a methlyated fragment, while the other probe targeted an unmethylated fragment. For capturing partially methylated regions, a mismatch count of 8 is used for the probe and target region (e.g., up to about 8 bases may be mismatched (e.g., form non-Watson-Crick base pairings) between a DNA fragment belonging to a target region and a capture probe).
[0434] In this experiment, probes for methylation targets were designed using 1× tiling density. Probes for mutation targets were designed using 3× tiling density with each base in the target being covered by at least 3 different probes (e.g., where there is substantial overlap between the probes). The mutation probes were designed using 3× tiling to assure higher capture efficiency for low CG content regions (e.g., regions having from about 30% to about 40% GC content) that otherwise would be under-represented. Tiling density refers to the coverage of the target region by probes. For example, probes designed having 1× tiling density would cover each base of the target region at least once. Probes with 3× tiling density would cover the target region at least 3×.
[0435] A custom algorithm aligned candidate probes to the genome and scored the number potential of on- and off-target mapping events. Probes with >250 genomic regions globally mapping to off-target regions, were omitted from the final panel design. Biotinylated probes were synthesized and combined into a final targeted methylation panel. Off-target mapping was done also after the initial assay design and testing. Targets were omitted if they caused more than 1% off-target capture in an actual panel.
[0436] Purified libraries (about 187.5 ng each) were pooled together in 8-plex, dried using concentrator plus (Eppendorf) and captured using a Fast Hybridization Target Enrichment Protocol by Twist® and a customized panel probes as described herein, which was designed to capture methylation and mutation targets of interest. Fragments bound to biotinylated probes were captured using streptavidin coated beads.
[0437] The captured fragments from the purified libraries were reamplified using PCR amplification for 11 cycles following manufacturer's protocol. The amplified libraries were then purified with Twist beads.
[0438] An exemplary method describing the Twist Fast Hybridization Target Enrichment protocol is presented below. Of note, maintaining a temperature of 70° C. the Fast Wash Buffer 1 during steps (e.g., steps 23-28) was important for GC rich regions. Differences in temperatures at these steps lead to higher than expected GC dropout rates (e.g., a GC dropout rate greater than 6%). For example, when the Fast Wash Buffer 1 was used at 65° C., GC dropout rates were about 30%, which was surprisingly high. Accordingly, minimizing pipetting time and maintaining the temperature of the Fast Wash Buffer 1 and sample-Fast Wash Buffer 1 mixtures were important.
Twist Fast Hybridization Target Enrichment Protocol
[0439] Before Beginning
[0440] All required reagents were thawed on ice, then pulse-vortex for 2 seconds to mix and pulse-spin.
[0441] In preparation for hybridization of capture probes with library pools, library pools were also thawed on ice:
[0442] From the Twist Fast Hybridization Reagents: [0443] Fast Hybridization Mix [0444] Hybridization Enhancer
[0445] 1. The concentration of each amplified, indexed library was used to calculate the volume (in μl) of each library needed for hybridization. The calculated volumes from each amplified, indexed library were transferred to a hybridization reaction tube (e.g., a 0.2-ml thin-walled PCR strip-tube, a 96-well plate) for each hybridization reaction to be performed.
[0446] Preparation of the Pre-Hybridization Solution
[0447] 2. The following volumes of reagents were added to each amplified indexed library to create a pre-hybridization solution as shown in Table 1 below. The solution was mixed by flicking the tubes.
TABLE-US-00014 TABLE 1 Volumes of Reagents for Pre-Hybridization Solution Reagent Volume Twist Probe Panel 4 μL Optional: Secondary Panel (if a secondary 4 μL panel is not used, do not add water as the entire solution will be dried) Universal Blocker 8 μL Blocker Solution 5 μL
[0448] 3. Tubes were pulse-spun and it was ensured that there were a minimal number of bubbles present in the solution.
[0449] 4. The pre-hybridization solution (including library, probes, blockers) were dried in the tubes used for the hybridization reaction using a SpeedVac system (or a similar evaporator device) using low or no-heat.
[0450] IMPORTANT: Step 12 to 18 (below) were performed concurrently to the pre-hybridization solution dry down and for hybridizations under 30 minutes.
[0451] The aliquoted libraries and hybridization reaction solution from Step 1 were used, as well as the thawed Fast Hybridization Mix and Hybridization Enhancer.
[0452] IMPORTANT: Before proceeding with this step, the compatibility of the thermal cycler and PCR tubes or plates were tested by incubating them at 95° C. for up to 5 minutes to ensure they did not crack under heat and pressure. The tightness of the thermal cycler lid was adjusted and/or a spacer specific to the thermal cycler model was used.
[0453] Reagents Required [0454] Dried hybridization reaction (from Step 4) [0455] Reagents thawed: [0456] Fast Hybridization Mix [0457] Hybridization Enhancer
[0458] Before Beginning
[0459] A 96-well thermocycler was programmed with the following conditions in Table 2 and the heated lid was set to 85° C.:
TABLE-US-00015 TABLE 2 Thermocycler Program Steps. Step Temperature Time 1 95° C. HOLD 2 95° C. 5 min 3 60° C. 15 min to 4 hours
[0460] Resuspending the Pre-Hybridization Solution
[0461] 5. The Fast Hybridization Mix was heated to 65° C. for 10 minutes, or until all precipitate was dissolved. The mix was vortexed and used immediately. The Fast Hybridization Mix was not allowed to cool to room temperature.
[0462] 6. The dried pre-hybridization solution from Step 4 was resuspended in 20 μl Fast Hybridization Mix.
[0463] Some notes to consider when following this process are presented as follows. If this resuspended solution required transfer into a secondary vessel for hybridization, the resuspended solution was mixed by flicking and an additional 5 minutes was added to incubation for resuspension. Fast Hybridization Mix is viscous. The mix was pipetted slowly to ensure accuracy. Small white particles present in the capture probes did not affect the final capture product.
[0464] 7. Tubes were pulse-spun and it was ensured that there were no bubbles present.
[0465] 8. 30 μl Hybridization Enhancer was added to the top of the pre-hybridization solution.
[0466] 9. Tubes were pulse-spun to ensure all solution was at the bottom of the tubes.
[0467] NOTE: Hybridization Enhancer settled on top of the hybridization reaction after the pulse-spin. This did not affect the final capture product.
[0468] Tubes were transferred to the preheated thermocycler. The program was then moved to Steps 2 and 3 of the thermocycler program.
[0469] IMPORTANT: Tubes were sealed tightly to prevent evaporation over the incubation time period.
[0470] Binding Hybridized Targets to Streptavidin Beads
[0471] Reagents Required [0472] Hybridization reactions prepared as above. [0473] From the Twist Fast Wash Buffers: [0474] Fast Binding Buffer [0475] Fast Wash Buffer 1 [0476] Wash Buffer 2 [0477] From Twist Binding and Purification Beads: [0478] Streptavidin Binding Beads
[0479] Before Beginning
[0480] The following reagents were inspected for precipitate. If a precipitate was observed, the reagent was heated at 48° C. until the precipitate was dissolved: [0481] Fast Binding Buffer [0482] Fast Wash Buffer 1 [0483] Wash Buffer 2
[0484] For each hybridization reaction: [0485] Preheat 450 μl Fast Wash Buffer 1 to 70° C. [0486] Preheat 700 μl Wash Buffer 2 to 48° C.
[0487] The Streptavidin Binding Beads were equilibrated to room temperature for at least 30 minutes.
[0488] It was important to maintain the temperature of the Fast Wash Buffer 1 at 70° C. Accordingly, pipetting time was minimized. Additionally, the Fast Wash Buffer 1 stayed on a heating block for the whole time of pipetting.
[0489] In preparation for the steps of Post-Capture PCR Amplification, Purification, and Performing QC: [0490] DNA Purification Beads (from the Twist Binding and Purification Beads) were equilibrated to room temperature for at least 30 minutes [0491] KAPA HiFi HotStart ReadyMix was thawed on ice [0492] Amplification Primers (from the Twist Fast Hybridization and Wash Kit) were thawed on ice
[0493] Once these reagents were thawed, the reagents were pulse-vortex for 2 seconds to mix.
[0494] Preparation of the Beads
[0495] 12. The pre-equilibrated Streptavidin Binding Beads were vortexed until mixed.
[0496] 13. 100 μl Streptavidin Binding Beads were added to a 1.5-ml microcentrifuge tube. One tube was prepared for each hybridization reaction.
[0497] 14. 200 μl Fast Binding Buffer was added to each of the tubes and mixed by pipetting.
[0498] 15. The tubes were placed on a magnetic stand for 1 minute, then removed. The clear supernatant was discarded. The bead pellet was not disturbed. The tube was removed from the magnetic stand.
[0499] 16. The wash steps (Steps 14 and 15) were repeated two more times for a total of three washes.
[0500] 17. After removing the clear supernatant from the third wash, a final 200 μl Fast Binding Buffer was added. The beads were resuspended by vortexing until homogenized.
[0501] 18. After the hybridization was complete, the thermal cycler lid was opened and the volume each hybridization reaction was quickly transfered (including Hybridization Enhancer) into a corresponding tube of washed Streptavidin Binding Beads from Step 18. The solution was mixed by pipetting and flicking.
[0502] NOTE: Rapid transfer directly from the thermal cycler at 60° C. was a critical step for minimizing off-target binding. The tubes of hybridization reaction were not removed from the thermal cycler or otherwise allowed to cool to less than 60° C. before transferring the solution to the washed Streptavidin Binding Beads.
[0503] Bind the Targets
[0504] 19. The tubes of the hybridization reaction were mixed with the Streptavidin Binding Beads for 30 minutes at room temperature on a shaker, rocker, or rotator at a speed sufficient to keep the solution mixed.
[0505] NOTE: The solutions were not vortexed. Aggressive mixing was not required.
[0506] 20. The tubes containing the hybridization reaction with Streptavidin Binding Beads were removed from the mixer and pulse-spun to ensure all solution was at the bottom of the tubes.
[0507] 21. The tubes were placed on a magnetic stand for 1 minute.
[0508] 22. The clear supernatant including the Hybridization Enhancer was removed and discarded. The bead pellet was not disturbed.
[0509] NOTE: A trace amount of Hybridization Enhancer was visible after supernatant removal and throughout each wash step in certain samples. It did not affect the final capture product.
[0510] 23. The tubes were removed from the magnetic stand and 200 μl preheated Fast Wash Buffer 1 was added. The solution was mixed by pipetting.
[0511] 24. The tubes were incubated for 5 minutes at 70° C.
[0512] 25. The tubes were placed on a magnetic stand for 1 minute.
[0513] 26. The clear supernatant was removed and discarded. The bead pellet was not disturbed.
[0514] 27. The tubes were removed from the magnetic stand and an additional 200 μl of preheated Fast Wash Buffer 1 was added. The solutions were mixed by pipetting.
[0515] 28. The tubes were incubated for 5 minutes at 70° C.
[0516] 29. The entire volume from Step 28 (˜200 μl) was transferred into a new 1.5-ml microcentrifuge tube, with one per hybridization reaction. The tubes were placed on a magnetic stand for 1 minute.
[0517] NOTE: A tube transfer was required at this step as it reduced background due to non-targeted library that may stick to the surface of the tube.
[0518] 30. The clear supernatant was removed and discarded. The bead pellet was not disturbed.
[0519] 31. The tubes were removed from the magnetic stand and 200 μl of 48° C. Wash Buffer 2 was added to each. The solution was mix by pipetting, and then pulse-spun to ensure all solution was at the bottom of the tubes.
[0520] 32. The tubes were incubated for 5 minutes at 48° C.
[0521] 33. The tubes were placed on a magnetic stand for 1 minute.
[0522] 34. The clear supernatant was removed and discarded. The bead pellet was not disturbed.
[0523] 35. The wash (Steps 31-34) was performed two more times, for a total of three washes.
[0524] 36. After the final wash, a 10 μl pipette was used to remove all traces of supernatant. The next step was immediately followed. The beads were not allowed to dry.
[0525] 37. The tubes were removed from the magnetic stand and 45 μl water was added. The solution was mixed by pipetting until homogenized. The solution, hereafter referred to as the Streptavidin Binding Bead slurry, was incubated on ice.
[0526] Post-Capture PCR Amplification, Purification, and Performing QC
[0527] Reagents Required [0528] Streptavidin Binding Bead slurry (from Step 38) [0529] Ethanol [0530] Molecular biology grade water
[0531] Reagents thawed and equilibrated: [0532] DNA Purification Beads [0533] KAPA HiFi HotStart ReadyMix (or equivalent) [0534] Amplification Primers [0535] Agilent Bioanalyzer High Sensitivity DNA Kit (or equivalent) [0536] Thermo Fisher Scientific Qubit dsDNA High Sensitivity Quantitation Assay.
[0537] Before Beginning
[0538] 500 μl 80% ethanol was prepared for each Streptavidin Binding Bead slurry to be processed.
[0539] Preparing the Beads, Thermocycler, and PCR Mix
[0540] 38. A thermocycler was programmed with the following conditions as presented in Table 3 below. The heated lid was set to 105° C. As stated above, PCR amplification was performed for 11 cycles according to the below program. However, for certain samples more or fewer cycles were run based on the results of the results of a qPCR assessment performed as discussed above.
TABLE-US-00016 TABLE 3 Thermocycler conditions for PCR. Step Temperature Time Number of Cycles 1. Initialization 98° C. 45 sec 1 2. Denaturation 98° C. 15 sec 11 Annealing 60° C. 30 sec Extension 72° C. 30 sec 3. Final Extension 72° C. 1 minute 1 4. Final Hold 4° C. HOLD —
[0541] NOTE: The number of amplification cycles varied depending on hybridization reaction size.
[0542] 39. If the Streptavidin Binding Bead slurry settled, it was mixed by pipetting.
[0543] 40. 22.5 μl of the Streptavidin Binding Bead slurry was transferred to a 0.2-ml thin-walled PCR strip-tube(s).
[0544] 41. The solution was kept on ice until ready to use in the next step.
[0545] NOTE: The remaining 22.5 μl water/Streptavidin Binding Bead slurry was stored at −20° C. for future use.
[0546] A PCR mixture was prepared by adding the following reagents to the tubes containing the Streptavidin Binding Bead slurry. The solution was mixed by pipetting.
PCR Amplification
[0547] 42. The tubes were pulse-spun and transferred to the thermocycler. The cycling program was then started.
[0548] 43. When the thermal cycler program was completed, the tubes were removed from the block and followed by purification steps.
[0549] 44. DNA Purification Beads were vortexed to mix.
[0550] 45. 90 μl (1.8×) homogenized DNA Purification Beads was added to each of the tubes from Step 44. The solution was mixed well by vortexing.
[0551] NOTE: It was not necessary to recover supernatant or remove Streptavidin Binding Beads from the amplified PCR product.
[0552] 46. The solution was incubated for 5 minutes at room temperature.
[0553] 47. The tubes were placed on a magnetic plate for 1 minute.
[0554] 48. Without removing the tubes from the magnetic plate, the clear supernatant was removed and discarded.
[0555] 49. The DNA Purification Bead pellet was washed with 200 μl freshly prepared 80% ethanol for 1 minute, then removed. The ethanol was discarded. This wash was repeated once, for a total of two washes, while the tube was kept on the magnetic plate.
[0556] 50. Using a 10 μl pipet, all residual ethanol was removed. The bead pellet was not disturbed.
[0557] 51. The bead pellet was air-dried on a magnetic plate for 5-10 minutes or until the bead pellet was dry. Care was taken to not overdry the bead pellet.
[0558] 52. The tubes from the magnetic plate were removed and 32 μl water was added. The solution was mixed by pipetting until homogenized and incubated at room temperature for 2 minutes.
[0559] 53. The tubes were placed on a magnetic plate and let stand for 3 minutes or until the beads fully pelleted.
[0560] 54. 30 μl of the clear supernatant containing the enriched library was transferred to a clean thin-walled PCR 0.2-ml strip-tube, while making sure not to disturb the bead pellet.
[0561] 55. Each enriched library was validated and quantified using an Agilent Bioanalyzer High Sensitivity DNA Kit and a Thermo Fisher Scientific Qubit dsDNA High Sensitivity Quantitation Assay.
[0562] NOTE: When using the Agilent Bioanalyzer High Sensitivity DNA Kit, 0.5 μl of the final sample was loaded.
[0563] 56. Average fragment length was about 375-425 bp using a range setting of 150-1,000 bp. Final concentration for samples was greater than or equal to 15 ng/μl, but this depended on the hybridization reaction size, hybridization time, and number of PCR cycles used.
[0564] The captured library pools were then pooled together to be sequenced on Illumina NovaSeq SP PE150 (1 lane each 96 samples).
Bioinformatics Workflow
Sequencing Data Analysis
[0565] The bioinformatics workflow included genome preparation according to pre-determined regions of interest. The alignment was conducted for pre-determined regions of interest and sequences not within these regions are discarded. A bioinformatics workflow (700) used herein is shown in
[0566] The final outputs of the bioinformatics workflow were: [0567] .bam files that include trimmed, aligned, deduplicated and quality filtered reads for the targets (e.g., methylation and/or mutation markers) of interest; [0568] .bam files that include trimmed, aligned, deduplicated and quality filtered reads for the spike-in control sequences. Spike-in control sequences were used for conversion quality control (e.g., determination of a conversion rate, e.g., conversion efficiency); and [0569] .xsl files with summaries of statistics per sample and per region analyzed (used for sample and region quality control).
Cancer Signal Deduction and Prediction Algorithm
[0570] .bam files of the samples were further used for assigning read-wise methylation values. Pre-defined thresholds based on reads having a minimum pre-determined CpG number and a minimum methylation percentage were applied to each sequencing read in a target region of interest. Each read in each target region (e.g., a DMR) received a score of 1 or 0 depending on whether the read passed a threshold or not. The scores were then summed to find a total number of reads of a DMR that passed the threshold condition. Read-wise methylation values were further normalized using an effective library size of an individual sample. The resulting values were log 2 transformed and used as inputs in prediction algorithm building, training, and validation.
Colorectal Cancer Model
[0571] A training set of colorectal cancer samples and colonoscopy negative control samples was used for initial feature filtering using a 50-fold Monte Carlo cross-validation. In each iteration, 50% of the samples were used as training samples and 50% of the samples were used as validation samples. Sequential Backward Selection (SBS) was used for dimensionality reduction to avoid overfitting by reducing the complexity of the further prediction model building with random forest. Sequential backwards selection learns which features (e.g., DMRs) are most informative at each step, and then chooses the next feature depending on the already selected features. SBS is a sequential process where features from the full feature subset were removed until the new feature subspace contained a set of features upon which a model did not improve. A set of 203 marker regions (listed in
Advanced Adenoma Model
[0572] Preliminary analysis of markers for advanced adenoma detection potential was developed similarly to the colorectal cancer model. Using a pre-selected region list and AMBER score thresholds defined on colorectal cancer tissue samples, results obtained from advanced adenoma and control samples were evaluated separately in cross-validation setting. 50-fold Monte Carlo cross-validation was used in each iteration as above. In each iteration, 50% of the samples were used as training and 50% of samples were used for testing and validation. Sequential Backward Selection (SBS) was used for dimensionality reduction to avoid overfitting by reducing the complexity for prediction model building. Using SBS, a set of 220 marker regions (listed in
Results and Quality Filtering
[0573] Based on evaluation of mapping quality, duplication level, conversion, and coverage, 37 samples were deemed invalid for additional analysis and were excluded. This left 70 colorectal cancer samples, 81 advanced adenoma samples, 37 non-advanced adenoma samples, 14 gastrointestinal disease samples, and 142 colonoscopy negative samples for further analysis.
Colorectal Cancer Model
[0574] Read-wise methylation values were used to train a machine learning model on 68 ctDNA samples as presented in Table 4 below. Samples analyzed were from 18 early stage (I-II) and 16 late-stage (III-IV) CRC patients and 34 age, BMI, gender and country of origin matched neoplasia-free controls. The median age of subjects was 63 [50-74], the mean BMI was 27 [19.5-37], 50% of subjects were female, 50% of CRCs were distal cancers. Subjects were from either Ukraine or Spain.
TABLE-US-00017 TABLE 4 Training Subject Demographics. Controls CRC Characteristics (n = 34) (n = 34) Age (years, mean (IQR)) 63 (50-74) 63 (50-74) Gender (n (%)) Female 17 (50%) 17 (50%) Male 17 (50%) 17 (50%) Body mass index 27 (19.5-32) 27 (20-37) (kg/m.sup.2, mean (IQR)) Stage Stage I 10 Stage II 8 Stage III 11 Stage IV 5 Cancer Location Proximal colon 17 Distal colon 17
[0575] This model was then applied to an independent, validation set of subjects as presented in Table 5 below. The subjects were from Spain, Ukraine, and Germany. Subjects included 36 stage I-IV cancer patients (median age 61.5 [55-82], BMI 28 [16-39], female 47%, 42% of the tumors were distal) and 159 age and sex matched controls. 87 of the control subjects had a negative colonoscopy finding (cNEG), 19 had hyperplastic polyps (HP), 37 had small non-advanced adenomas (NAA), and 16 were diagnosed with other benign gastrointestinal diseases (GID).
TABLE-US-00018 TABLE 5 Validation Subject Demographics. Controls HP NAA GID CRC Characteristics (n = 87) (n = 19) (n = 37) (n = 16) (n = 36) Age (years, mean 63 (46-79) 62 (50-71) 61 (45-78) 58 (50-78) 62 (55-82) (IQR)) Gender (n (%)) Female 48 (55%) 6 (32%) 20 (54%) 9 (56%) 17 (47%) Male 39 (45%) 13 (68%) 17 (46%) 7 (44%) 19 (53%) Body mass index 27 (20-41.5) 28 (22-41) 29 (20-43) 27 (20-39) 29 (16-39) (kg/m.sup.2, mean (IQR)) Stage Stage I 6 Stage II 13 Stage III 12 Unknown 3 Cancer Location Proximal 21 Distal 15
[0576] Using a 203 marker panel as presented in
[0577]
[0578]
[0579] Further analysis was conducted on the 203 DMRs (
TABLE-US-00019 TABLE 6 KEGG Pathway Analysis Results. DAVID KEGG Pathways Term hsa05216: Thyroid cancer hsa04550: Signaling pathways regulating pluripotency hsa05200: Pathways in cancer hsa04015: Rap1 signaling pathway
[0580] Subset analysis of 203 DMRs showed that subsets of DMRs performed surprisingly well in distinguishing between CRC and control samples in the validation set. It was found that combinations of 2, 4, 9, and 24 DMRs performed well in identifying CRC subjects from control subjects. For example, a panel of only two DMRs showed an AUC of 78%. Though accuracy improves with increased numbers of DMRs, these smaller DMR panels may also be useful in identifying subjects suffering from CRC. Results of these subsets of DMR combinations are presented below in Table 7.
TABLE-US-00020 TABLE 7 CRC DMR panels statistics. Number of DMRs 2 4 9 24 203 AUC 0.78 0.83 0.87 0.92 0.97 Sensitivity 0.54 0.80 0.83 0.90 0.92 Specificity 0.89 0.72 0.64 0.72 0.97 Accuracy 0.82 0.74 0.68 0.76 0.93 Kappa 0.43 0.39 0.32 0.45 0.78
[0581] Tables 8, 9, 10, and 11 (presented below) correspond to the 2, 4, 9, and 24 DMR combinations, respectively, indicated in Table 7. DMRs listed in Tables 8, 9, 10, and 11 are also found in the 203 DMR panel shown in
TABLE-US-00021 TABLE 8 2-DMR Panel for CRC. chr start end SEQ. ID. NO. promoters 1to5 kb 5UTRs exons introns 3UTRs 7 96997902 96999222 SEQ ID NO.: 92 DLX6-AS1 8 96145538 96145718 SEQ ID NO.: 108 AP003465.2 GDF6
TABLE-US-00022 TABLE 9 4-DMR Panel for CRC. chr start end SEQ. ID. NO. promoters 1to5 kb 5UTRs exons introns 3UTRs 7 96997902 96999222 SEQ ID NO.: 92 DLX6-AS1 8 96145538 96145718 SEQ ID NO.: 108 AP003465.2 GDF6 2 100322218 100322818 SEQ ID NO.: 28 LONRF2 LONRF2 LONRF2 2 29115776 29116791 SEQ ID NO.: 17 CLIP4 CLIP4
TABLE-US-00023 TABLE 10 9-DMR Panel for CRC. SEQ. ID. chr start end NO. promoters 1to5 kb 5UTRs exons introns 3UTRs 7 96997902 96999222 SEQ ID DLX6- NO.: 92 AS1 8 96145538 96145718 SEQ ID AP003465.2 GDF6 NO.: 108 2 100322218 100322818 SEQ ID LONRF2 LONRF2 LONRF2 NO.: 28 2 29115776 29116791 SEQ ID CLIP4 CLIP4 NO.: 17 2 88765502 88766042 SEQ ID ANKRD36BP2 ANKRD36BP2 NO.: 25 4 153249541 153249721 SEQ ID TRIM2 NO.: 55 2 86790271 86790811 SEQ ID CD8A CD8A NO.: 24 2 176094518 176094878 SEQ ID HOXD12 HOXD13 HOXD13 NO.: 35 3 37453325 37453874 SEQ ID ITGA9 NO.: 41
TABLE-US-00024 TABLE 11 24 DMR Panel for CRC. chr start end SEQ. ID. NO. promoters 1to5 kb 5UTRs exons introns 3UTRs 7 96997902 96999222 SEQ ID NO.: 92 DLX6-AS1 8 96145538 96145718 SEQ ID NO.: 108 AP003465.2 GDF6 2 100322218 100322818 SEQ ID NO.: 28 LONRF2 LONRF2 LONRF2 2 29115776 29116791 SEQ ID NO.: 17 CLIP4 CLIP4 2 88765502 88766042 SEQ ID NO.: 25 ANKRD36BP2 ANKRD36BP2 4 153249541 153249721 SEQ ID NO.: 55 TRIM2 2 86790271 86790811 SEQ ID NO.: 24 CD8A CD8A 2 176094518 176094878 SEQ ID NO.: 35 HOXD12 HOXD13 HOXD13 3 37453325 37453874 SEQ ID NO.: 41 ITGA9 10 43105168 43105348 SEQ ID NO.: 124 RET RET 7 90596855 90597335 SEQ ID NO.: 90 AC002456.1 AC002456.1 AC002456.1 CDK14, AC002456.1 6 28988380 28988560 SEQ ID NO.: 69 AL662791.1 19 53254542 53254962 SEQ ID NO.: 190 ZNF677 ZNF677, VN1R2 ZNF677 ZNF677 ZNF677 7 141072108 141073057 SEQ ID NO.: 99 TMEM178B 14 104117671 104117851 SEQ ID NO.: 159 MIR203B 6 163413139 163413679 SEQ ID NO.: 80 QKI QKI CAHM 5 38555799 38556399 SEQ ID NO.: 60 LIFR-AS1 LIFR-AS1 LIFR LIFR LIFR 2 95025733 95026933 SEQ ID NO.: 26 MAL, MAL MAL, MAL, AC103563.7 AC103563.7 AC103563.7 7 35257235 35257535 SEQ ID NO.: 86 TBX20 1 2132912 2133092 SEQ ID NO.: 2 PRKCZ PRKCZ PRKCZ 3 128491607 128492807 SEQ ID NO.: 49 GATA2 GATA2 GATA2 GATA2 GATA2, GATA2- AS1 20 23049079 23049259 SEQ ID NO.: 193 THBD 1 243917149 243917569 SEQ ID NO.: 15 LINCO2774 LINCO2774 LINCO2774 1 38045915 38046095 SEQ ID NO.: 6 MIR3659HG POU3F1
[0582] In some embodiments, the present disclosure includes combinations of DMRs in which each of the DMRs is, includes all of, includes a portion of, or is present in a gene identified as being associated with a DMR of Table 8 (e.g., as shown in
Advanced Adenoma Model
[0583] Calculated read-wise methylation values corresponding to individual DMRs were used to build and cross-validate a machine learning model on 217 ctDNA samples from 81 patients with advanced adenomas and 136 age, BMI, gender and country of origin matched neoplasia-free controls. Statistics regarding the advanced adenomas subjects used in validation and training of the model are presented as follows: median age 63 [46-79], mean BMI 28 [19-48], female 51%. Subjects were from Spanish, Ukrainian, and German populations. The distribution of patients with different forms of advanced adenomas can be seen as listed below in Table 12.
TABLE-US-00025 TABLE 12 Validation and Training Subject Demographics. Advanced Controls Adenoma Sum 136 81 Advanced Adenoma Histology Tubular 30 Tubulo villous 29 Serrated 15 Carcinoma in situ 7 Dysplasia grade Tis 7 Characteristics High grade 25 >=1 cm 41 <1 cm (serrated with dysplasia 8 or tubulovillous low grade) Age (years, mean (IQR)) 63 (46-78) 63 (50-79) Gender (n (%)) Female 69 (51%) 42 (52%) Male 67 (49%) 39 (48%) Body mass index (kg/m.sup.2, 28 (19.5-42) 28 (19-48) mean (IQR))
[0584] The SBS feature filtering method was evaluated in combination with RF, PLS-DA and SVM classification models to identify DMRs of interest. A SVM classification model based SBS selected features (DMRs) showed the best performance in a cross-validation setting.
[0585] Statistical results regarding the sensitivity of the model to subjects diagnosed with various classifications and types of advanced adenomas are presented in
[0586] All 220 contributing regions were also further analyzed using a KEGG pathway analysis. The results of the KEGG pathway analysis are presented below in Table 13. The main contributing pathways were linked to cancer as well as signaling pathways, affected in cancer development.
TABLE-US-00026 TABLE 13 KEGG Pathway Analysis Results. DAVID KEGG pathways Term hsa05200: Pathways in cancer hsa04510: Focal adhesion hsa04810: Regulation of actin cytoskeleton hsa04015: Rapl signaling pathway hsa05214: Glioma hsa04010: MAPK signaling pathway hsa05218: Melanoma hsa04350: TGF-beta signaling pathway
[0587] Subset analysis of 220 DMRs (as shown in
TABLE-US-00027 TABLE 14 Advanced Adenoma (AA) DMR panels statistics. Number of DMRs 2 4 10 220 AUC 0.51 0.52 0.54 0.82 Sensitivity 0.21 0.26 0.31 0.54 Specificity 0.82 0.77 0.74 0.90 Accuracy 0.59 0.57 0.58 0.70 Kappa 0.03 0.03 0.06 0.27
[0588] Tables 15, 16, and 17 (presented below) correspond to the 2, 4, and 10 DMR combinations, respectively, indicated in Table 14. DMRs listed in Tables 15, 16, and 17 are also found in the 220 DMR panel shown in
[0589] The described 220-DMR panel shows increased sensitivity values by advanced adenoma progression group as shown in
[0590] In a hypothetical population of 1000 patients, 76 patients would be expected to have advanced adenoma, given an incidence rate of 7.6%. Using a 90% adherence rate for blood tests as opposed to 65% of the stool tests, 68 advanced adenoma patients (68/76) would take part of the blood test-based screening. In contrast, only 42 (42/76) would take part with a stool test. With 54% sensitivity, 37 patients (37/68) would be correctly identified as advanced adenoma patients using a blood based test (e.g., as described herein), as opposed to 18 patients with stool test (18/42). Accordingly, there would be a 2× increase in the actual detection rate for AA using blood-based tests described herein.
TABLE-US-00028 TABLE 15 2-DMR Panel for AA. chr start end SEQ ID NO. promoters 1to5 kb 5UTRs exons introns 7 100785927 100786167 SEQ ID NO.: 221 ZAN ZAN 14 97412990 97413410 SEQ ID NO.: 374
TABLE-US-00029 TABLE 16 4-DMR Panel for AA. chr start end SEQ ID NO. promoters 1to5 kb 5UTRs exons introns 7 100785927 100786167 SEQ ID NO.: 221 ZAN ZAN 14 97412990 97413410 SEQ ID NO.: 374 20 3083167 3083587 SEQ ID NO.: 411 AVP AVP 8 37797956 37798676 SEQ ID NO.: 329 ADGRA2
TABLE-US-00030 TABLE 17 10-DMR Panel for AA. chr start end SEQ ID NO. promoters 1to5 kb 5UTRs exons introns 7 100785927 100786167 SEQ ID NO.: 221 ZAN ZAN 14 97412990 97413410 SEQ ID NO.: 374 20 3083167 3083587 SEQ ID NO.: 411 AVP AVP 8 37797956 37798676 SEQ ID NO.: 329 ADGRA2 16 57091834 57092014 SEQ ID NO.: 387 CPNE2 AC009090.2 AC009090.2 4 7940020 7940200 SEQ ID NO.: 287 AFAP1 AC097381.1 19 40811045 40811585 SEQ ID NO.: 403 CYP2T1P CYP2T1P CYP2T1P, AC008537.1 1 154567391 154567691 SEQ ID NO.: 246 CHRNB2 CHRNB2 14 105364294 105364612 SEQ ID NO.: 376 PACS2 PACS2 9 61862430 61863030 SEQ ID NO.: 338 AL391987.1 AL391987.1 AL391987.1
[0591] In some embodiments, the present disclosure includes combinations of DMRs in which each of the DMRs is, includes all of, includes a portion of, or is present in a gene identified as being associated with a DMR of Table 15 (e.g., as shown in
Example 3: Bisulfite Conversion Vs Enzymatic Conversion
[0592] The purpose of this Example is to demonstrate the usefulness of both bisulfite and enzymatic conversion in identifying methylation sites using NGS assays. In particular, both methods are shown herein to be useful in determining the presence of colorectal cancer. In addition, this Example shows the effect of different processing steps, such as removal of duplicates (e.g., optical duplicates, PCR duplicates), on the amount of data obtained from NGS assays. Deduplication is shown to remove a significant number of reads from the bioinformatics analysis pipeline.
[0593]
[0594] In this example, a comparative analysis was performed for 16 sample pairs prepared with bisulfite and enzymatic conversion in order to compare the performance of the two conversion methods.
[0595] Then PCA (principle component analysis) was performed on the resulting data using a 203 CRC marker panel (
[0596] Further analysis using prediction algorithm developed previously on the 68 samples resulted in sample pairs being classified similarly with similar prediction scores as shown in Table 18 below.
TABLE-US-00031 TABLE 18 Paired samples prepared with enzymatic bisulfite conversion. Sample PredictionScore Prediction Reference Match UDX016525_Bis 0.43 CNT CNT TRUE UDX016525_EM 0.44 CNT CNT TRUE UDX016707_Bis 0.68 CRC CRC TRUE UDX016707_EM 0.69 CRC CRC TRUE UDX017209_Bis 0.46 CNT CNT TRUE UDX017209_EM 0.45 CNT CNT TRUE UDX017309_Bis 0.45 CNT CNT TRUE UDX017309_EM 0.47 CNT CNT TRUE UDX017397_Bis 0.42 CNT CNT TRUE UDX017397_EM 0.38 CNT CNT TRUE UDX017440_Bis 0.60 CRC CRC TRUE UDX017440_EM 0.57 CRC CRC TRUE UDX017732_Bis 0.64 CRC CRC TRUE UDX017732_EM 0.64 CRC CRC TRUE UDX018506_Bis 0.91 CRC CRC TRUE UDX018506_EM 0.91 CRC CRC TRUE UDX018688_Bis 0.80 CRC CRC TRUE UDX018688_EM 0.80 CRC CRC TRUE UDX018828_Bis 0.44 CNT CNT TRUE UDX018828_EM 0.46 CNT CNT TRUE UDX018948_Bis 0.39 CNT CNT TRUE UDX018948_EM 0.46 CNT CNT TRUE UDX019177_Bis 0.35 CNT CNT TRUE UDX019177_EM 0.34 CNT CNT TRUE UDX019715_Bis 0.40 CNT CRC FALSE UDX019715_EM 0.41 CNT CRC FALSE UDX019764_Bis 0.38 CNT CNT TRUE UDX019764_EM 0.44 CNT CNT TRUE
[0597] The sample name provides a unique sample ID, along with the method of preparation—enzymatic (_EM) conversion or bisulfite (_Bis) conversion. A prediction score for each sample was generated using a random forest (RF) prediction model. In this case, the RF prediction model is a colorectal cancer prediction model, which used the methylation status of the 203 markers of
Computer System and Network Environment
[0598] As shown in
[0599] The cloud computing environment 1600 may include a resource manager 1606. The resource manager 1606 may be connected to the resource providers 1602 and the computing devices 1604 over the computer network 1608. In some implementations, the resource manager 1606 may facilitate the provision of computing resources by one or more resource providers 1602 to one or more computing devices 1604. The resource manager 1606 may receive a request for a computing resource from a particular computing device 1604. The resource manager 1606 may identify one or more resource providers 1602 capable of providing the computing resource requested by the computing device 1604. The resource manager 1606 may select a resource provider 1602 to provide the computing resource. The resource manager 1606 may facilitate a connection between the resource provider 1602 and a particular computing device 1604. In some implementations, the resource manager 1606 may establish a connection between a particular resource provider 1602 and a particular computing device 1604. In some implementations, the resource manager 1606 may redirect a particular computing device 1604 to a particular resource provider 1602 with the requested computing resource.
[0600]
[0601] The computing device 1700 includes a processor 1702, a memory 1704, a storage device 1706, a high-speed interface 1708 connecting to the memory 1704 and multiple high-speed expansion ports 1710, and a low-speed interface 1712 connecting to a low-speed expansion port 1714 and the storage device 1706. Each of the processor 1702, the memory 1704, the storage device 1706, the high-speed interface 1708, the high-speed expansion ports 1710, and the low-speed interface 1712, are interconnected using various busses, and may be mounted on a common motherboard or in other manners as appropriate. The processor 1702 can process instructions for execution within the computing device 1700, including instructions stored in the memory 1704 or on the storage device 1706 to display graphical information for a GUI on an external input/output device, such as a display 1716 coupled to the high-speed interface 1708. In other implementations, multiple processors and/or multiple buses may be used, as appropriate, along with multiple memories and types of memory. Also, multiple computing devices may be connected, with each device providing portions of the necessary operations (e.g., as a server bank, a group of blade servers, or a multi-processor system). Thus, as the term is used herein, where a plurality of functions are described as being performed by “a processor”, this encompasses embodiments wherein the plurality of functions are performed by any number of processors (one or more) of any number of computing devices (one or more). Furthermore, where a function is described as being performed by “a processor”, this encompasses embodiments wherein the function is performed by any number of processors (one or more) of any number of computing devices (one or more) (e.g., in a distributed computing system).
[0602] The memory 1704 stores information within the computing device 1700. In some implementations, the memory 1704 is a volatile memory unit or units. In some implementations, the memory 1704 is a non-volatile memory unit or units. The memory 1704 may also be another form of computer-readable medium, such as a magnetic or optical disk.
[0603] The storage device 1706 is capable of providing mass storage for the computing device 1700. In some implementations, the storage device 1706 may be or contain a computer-readable medium, such as a floppy disk device, a hard disk device, an optical disk device, or a tape device, a flash memory or other similar solid state memory device, or an array of devices, including devices in a storage area network or other configurations. Instructions can be stored in an information carrier. The instructions, when executed by one or more processing devices (for example, processor 1702), perform one or more methods, such as those described above. The instructions can also be stored by one or more storage devices such as computer- or machine-readable mediums (for example, the memory 1704, the storage device 1706, or memory on the processor 1702).
[0604] The high-speed interface 1708 manages bandwidth-intensive operations for the computing device 1700, while the low-speed interface 1712 manages lower bandwidth-intensive operations. Such allocation of functions is an example only. In some implementations, the high-speed interface 1708 is coupled to the memory 1704, the display 1716 (e.g., through a graphics processor or accelerator), and to the high-speed expansion ports 1710, which may accept various expansion cards (not shown). In the implementation, the low-speed interface 1712 is coupled to the storage device 1706 and the low-speed expansion port 1714. The low-speed expansion port 1714, which may include various communication ports (e.g., USB, Bluetooth®, Ethernet, wireless Ethernet) may be coupled to one or more input/output devices, such as a keyboard, a pointing device, a scanner, or a networking device such as a switch or router, e.g., through a network adapter.
[0605] The computing device 1700 may be implemented in a number of different forms, as shown in the figure. For example, it may be implemented as a standard server 1720, or multiple times in a group of such servers. In addition, it may be implemented in a personal computer such as a laptop computer 1722. It may also be implemented as part of a rack server system 1717. Alternatively, components from the computing device 1700 may be combined with other components in a mobile device (not shown), such as a mobile computing device 1750. Each of such devices may contain one or more of the computing device 1700 and the mobile computing device 1750, and an entire system may be made up of multiple computing devices communicating with each other.
[0606] The mobile computing device 1750 includes a processor 1752, a memory 1764, an input/output device such as a display 1754, a communication interface 1766, and a transceiver 1768, among other components. The mobile computing device 1750 may also be provided with a storage device, such as a micro-drive or other device, to provide additional storage. Each of the processor 1752, the memory 1764, the display 1754, the communication interface 1766, and the transceiver 1768, are interconnected using various buses, and several of the components may be mounted on a common motherboard or in other manners as appropriate.
[0607] The processor 1752 can execute instructions within the mobile computing device 1750, including instructions stored in the memory 1764. The processor 1752 may be implemented as a chipset of chips that include separate and multiple analog and digital processors. The processor 1752 may provide, for example, for coordination of the other components of the mobile computing device 1750, such as control of user interfaces, applications run by the mobile computing device 1750, and wireless communication by the mobile computing device 1750.
[0608] The processor 1752 may communicate with a user through a control interface 1758 and a display interface 1756 coupled to the display 1754. The display 1754 may be, for example, a TFT (Thin-Film-Transistor Liquid Crystal Display) display or an OLED (Organic Light Emitting Diode) display, or other appropriate display technology. The display interface 1756 may comprise appropriate circuitry for driving the display 1754 to present graphical and other information to a user. The control interface 1758 may receive commands from a user and convert them for submission to the processor 1752. In addition, an external interface 1762 may provide communication with the processor 1752, so as to enable near area communication of the mobile computing device 1750 with other devices. The external interface 1762 may provide, for example, for wired communication in some implementations, or for wireless communication in other implementations, and multiple interfaces may also be used.
[0609] The memory 1764 stores information within the mobile computing device 1750. The memory 1764 can be implemented as one or more of a computer-readable medium or media, a volatile memory unit or units, or a non-volatile memory unit or units. An expansion memory 1774 may also be provided and connected to the mobile computing device 1750 through an expansion interface 1772, which may include, for example, a SIMM (Single In Line Memory Module) card interface. The expansion memory 1774 may provide extra storage space for the mobile computing device 1750, or may also store applications or other information for the mobile computing device 1750. Specifically, the expansion memory 1774 may include instructions to carry out or supplement the processes described above, and may include secure information also. Thus, for example, the expansion memory 1774 may be provide as a security module for the mobile computing device 1750, and may be programmed with instructions that permit secure use of the mobile computing device 1750. In addition, secure applications may be provided via the SIMM cards, along with additional information, such as placing identifying information on the SIMM card in a non-hackable manner.
[0610] The memory may include, for example, flash memory and/or NVRAM memory (non-volatile random access memory), as discussed below. In some implementations, instructions are stored in an information carrier such that the instructions, when executed by one or more processing devices (for example, processor 1752), perform one or more methods, such as those described above. The instructions can also be stored by one or more storage devices, such as one or more computer- or machine-readable mediums (for example, the memory 1764, the expansion memory 1774, or memory on the processor 1752). In some implementations, the instructions can be received in a propagated signal, for example, over the transceiver 1768 or the external interface 1762.
[0611] The mobile computing device 1750 may communicate wirelessly through the communication interface 1766, which may include digital signal processing circuitry where necessary. The communication interface 1766 may provide for communications under various modes or protocols, such as GSM voice calls (Global System for Mobile communications), SMS (Short Message Service), EMS (Enhanced Messaging Service), or MMS messaging (Multimedia Messaging Service), CDMA (code division multiple access), TDMA (time division multiple access), PDC (Personal Digital Cellular), WCDMA (Wideband Code Division Multiple Access), CDMA2000, or GPRS (General Packet Radio Service), among others. Such communication may occur, for example, through the transceiver 1768 using a radio-frequency. In addition, short-range communication may occur, such as using a Bluetooth®, Wi-Fi™, or other such transceiver (not shown). In addition, a GPS (Global Positioning System) receiver module 1770 may provide additional navigation- and location-related wireless data to the mobile computing device 1750, which may be used as appropriate by applications running on the mobile computing device 1750.
[0612] The mobile computing device 1750 may also communicate audibly using an audio codec 1760, which may receive spoken information from a user and convert it to usable digital information. The audio codec 1760 may likewise generate audible sound for a user, such as through a speaker, e.g., in a handset of the mobile computing device 1750. Such sound may include sound from voice telephone calls, may include recorded sound (e.g., voice messages, music files, etc.) and may also include sound generated by applications operating on the mobile computing device 1750.
[0613] The mobile computing device 1750 may be implemented in a number of different forms, as shown in the figure. For example, it may be implemented as a cellular telephone 1780. It may also be implemented as part of a smart-phone 1782, personal digital assistant, or other similar mobile device.
[0614] Various implementations of the systems and techniques described here can be realized in digital electronic circuitry, integrated circuitry, specially designed ASICs (application specific integrated circuits), computer hardware, firmware, software, and/or combinations thereof. These various implementations can include implementation in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which may be special or general purpose, coupled to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device.
[0615] These computer programs (also known as programs, software, software applications or code) include machine instructions for a programmable processor, and can be implemented in a high-level procedural and/or object-oriented programming language, and/or in assembly/machine language. As used herein, the terms machine-readable medium and computer-readable medium refer to any computer program product, apparatus and/or device (e.g., magnetic discs, optical disks, memory, Programmable Logic Devices (PLDs)) used to provide machine instructions and/or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term machine-readable signal refers to any signal used to provide machine instructions and/or data to a programmable processor.
[0616] To provide for interaction with a user, the systems and techniques described here can be implemented on a computer having a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying information to the user and a keyboard and a pointing device (e.g., a mouse or a trackball) by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well; for example, feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user can be received in any form, including acoustic, speech, or tactile input.
[0617] The systems and techniques described here can be implemented in a computing system that includes a back end component (e.g., as a data server), or that includes a middleware component (e.g., an application server), or that includes a front end component (e.g., a client computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the systems and techniques described here), or any combination of such back end, middleware, or front end components. The components of the system can be interconnected by any form or medium of digital data communication (e.g., a communication network). Examples of communication networks include a local area network (LAN), a wide area network (WAN), and the Internet.
[0618] The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other.
[0619] Elements of different implementations described herein may be combined to form other implementations not specifically set forth above. Elements may be left out of the processes, computer programs, databases, etc. described herein without adversely affecting their operation. In addition, the logic flows depicted in the figures do not require the particular order shown, or sequential order, to achieve desirable results. Various separate elements may be combined into one or more individual elements to perform the functions described herein.
[0620] Throughout the description, where apparatus and systems are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are apparatus, and systems of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.
[0621] It should be understood that the order of steps or order for performing certain action is immaterial so long as the invention remains operable. Moreover, two or more steps or actions may be conducted simultaneously.
[0622] While the invention has been particularly shown and described with reference to specific preferred embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
OTHER EMBODIMENTS
[0623] While we have described a number of embodiments, it is apparent that our basic disclosure and examples may provide other embodiments that utilize or are encompassed by the compositions and methods described herein. Therefore, it will be appreciated that the scope of is to be defined by that which may be understood from the disclosure and the appended claims rather than by the specific embodiments that have been represented by way of example.
[0624] All references cited herein are hereby incorporated by reference.
TABLE-US-00032 SEQUENCES FIG. 2 SEQUENCES >1:1062388-1062568 (SEQ ID NO.: 1) ACGGGGGGGCTGTTCACCAGGAAGGGGCAGGGCTGCAGCCTCAGCCTCCCCTCCAG ATGCCGGCAGCACCAGCCTCTGCCTGCATGGGGCCGCGAGGTTTGCAGTGACATCCC CCGAGCTTCCTGACCTGCCCCGGACACGGAGCACGGCTCCCAGGGGCCGCACAGGC ACCCGCTGGCCT >1:2132912-2133092 (SEQ ID NO.: 2) TGGAGGCGTGGGGACCCCATCTCCAAATACAGCCACATTGGGGGTTAGGGCTCCCC ACGTGAATTTAGGGGACACTTCAGTTCGTCCCGGCGGGGACTGGGGACGCCGGGCT GTGTGCTGTGTCCTGTGGGAGAGTTTGTTCACCCTGCTGGAGGCTCCCTGATGAGCC CTGGCGTCTGCT >1:3073311-3073791 (SEQ ID NO.: 3) GCAATTAGGGATCCTTGGGGGGCTTGGGCTGGTAATTAAGGTGATGTATAATTAGAG TTTCAACAAAAATTATCCGGGATTAAAAATCTTTTGAATAATTTCGTTTAAAATTTTC AAATAGCGTTAAATACAATTTATCAGGTTTTGAATCAAACCCGTGTAACGAGTCTTG GAAGCTGCAGCTCCCGTCGCCGGCGCGGGAGGACCAGGAGCAGCTCCGGCGACTTC CCCGTGCGGGAAGGAAACTTCGCGAGCGAAGCCAGCTGGCTGGGGCCTCGCCGCGG TGCAGCGGCGGCCGCGGGCTCAGAATCGAGCCACCGAGGGCTGCAGACGGCGTGGG CCGGGTCGGGGAGCGGGGCCTGGGGGACCCCGGGCCGGCCGGTAGTCTCGGCCGAC TTCCCACTCCCCGCGCACAAAGTCGCGGCCAACTACCGCGGAGCAGCGCCCGCGTC CACACCGCGCAGCCTGGCGCCCCGACCCT >1:32464123-32464603 (SEQ ID NO.: 4) GCAACCAAAAGGAGACATTTTGACATGGAGACATATACAGGGAATATGCCCTGTGA ACATGAAGATGGCCATATGCAAGCCCAGGAGAGAAGCCTGGAAGAGACCGTTTCCT CACAGCGCTCAGAAGGAAAGAACCCTGCCAACATCTTGCTTTCAGATGCCCCCAGG ATTGTCAGACAATAAGATCTGTTATTGACGCCACCGGGTTGGTGATACTTAGGTACA GCAGCCCTAGCAAACGAATACACCCCCATGAGAACTAAGCTCCCTGAGAGCGGTAA GCTGCCTTGTCTTGCTCACAGCTGACAAGAACACGCCTGTACGGTCACTTAGCACCT AGTACTGCCATTTAACCGTTTCACTAGTATGTATGAACCGGAGAGCCTGTCAAGGGA AGAGCTGAATCTTTTATCTTTTGTAACGACTACCCAGTGAAAGAAACCGCGGGTATG CAATAAAAACCTGTTGAATCGATTAAACC >1:32753865-32754105 (SEQ ID NO.: 5) CGGGAGGGGCGGAGCCGACGGGATGCGCGCCAGGCCCCGCCCCTCCTCCGGGCCCG CCCCCGGCCTGGCCATTGGCCGCAGAGCTCGGGGGCGTGGTCGAGCTGGGGCTGGG GGCGCCCGCGGTGCCCGCCCGCGAGTCTCGCTGCCTCCCTCCCGGGGCTGCGGGCCC GGCGGCCGGGCTGGCTGGGCCGCGCTTGGGTTCCCGCGCCGGCTCCCGCACCCGCA ATGGGGAACTCACACC >1:38045915-38046095 (SEQ ID NO.: 6) CCACGTCGGCCTGCGTAAAGCCCAGCTTGATGCGCCGCTGCTTGAACTGCTTGGCGA ACTGCTCCAGGTCGTCCGAGCTGGGCGCATCCTCGTCCGAGTGCTCGCCCACCGATG AGCCGCCGCCGCCCGCGCCCGGGTGCAGGTGCGCCGCCGCCGCGTGCAGGCCGCCC GCGTGTGCATG >1:50417741-50418443 (SEQ ID NO.: 7) TGCGCACCTTGACGGCTCCTTAGGGACAGACCAGCCGCAGGCAAGAGGGGCAGGTG GGCAGGATTCATCCCGAGTTTCCAATATATTTAATCTCTAAACCTGATAAGTACAAT GCGCGCATAGTCTAATTTTTTTCCATTTTGTCCCTTTTTTTGCTTGTTTTGAATGTTTTT CACGTTAATACCGAGGTCACCTACAGATTACAATTAATAACTTAGAATTCCATTTTA TAACATTATACACTGGCTTGTATATATATATGTATAGATTATATATAGATTTATACAT ATATAAAAACACACTGCACCAAGGAAACCCATGCTTATCGGCATAAGCAACAAAGA GAGCGACAAATACCGCAACGAGGAAAGTGCACCTTAAAACTTGTTTCCTTTTTTTTT TTTTACAATTGTATCGATATATATGTGTGTCCCAAAGACTCAGTGCCAAGAGATTTA TACATCCTAAATTTATATTTGTTAGAGCGAATATTTAAATTTTTTAAAAGTGAGGGCT GGGGAGACACAGAAAAGACTCTCGGATTATCCTGCCATCCACTGAGAGCCGGATGA GCACAGCTAAGGAGCCGCAGGAGCCTGCGCTGCTGTCGCAGCCTCTGAATTCTCATG AATTCCCAGCCTTTTGGAAAGGGGGCCGGGTGAGGCTGGAAGAGGGATCCGGAGGT AGGAGATGAGGACCCAGG >1:98053745-98054105 (SEQ ID NO.: 8) AACCACCACCTTGGATTTCAGATCGAGGAAAGGAAGCCAAAGCAAAGGTGTGGTTA CACAGGACATCCATAGACAAATCGTTGCCTCTCTAAGTGGGCCTGAGCTTTGCGGCT CCAGAAGCGCGAGGCGCGGTTGGTGCGGACGCGGGGGCGTGGGAGTCATCGCTCTC CCCGCAGCCCTGGCCGAGCTCTCTGCTGTCCTCCCGAGTTTGGGCCAGAGACCACGG CTCACTCCCTAACGCCCTCGCAAGGACGGCTGCCCGTCGGGCCAAGGGCGCCCCGG GCTGGAGGCCGGAGCAAGACGGCCCCGCGGGACTCGGGAGCCTTGGTAAGGCGGA GGCTCAGACCCCGTTCACGAAAAC >1:151721519-151721944 (SEQ ID NO.: 9) CTTGACGACCGCAGCAAGATGGAGACGCTGCCAGGCTTGCTGCAGCGGCCCGACCC CGGGGCGCTTAGCGCAGCGCAGCTGGAGCAGCTGCGAAAATTCAAGGTGGGTGCGC CCGCGCCCCCATCCAGCGTCCACCAAAGTGTAGCTGCCCCAGGACTGGGGCCCCAG ACTGGGAAGAGAGCCGCCGAGAGAAGGGGAGCGGGAGCCTGTTCCCTGATAAAGT GGGGAGGGCGCAGGGGAGACCCCCGGCGGACCTCTAGGCGTCTGATCCCAGCACAG AGCGCGACGGGCATCTGAGAGTGCAGGAAGAACTAACTCAGGGACTCGGCCAGAG AAATGGGCCGAAATTACTGCCAGACACATCCGACCTTAGTAAAGGCCCCTCATCCTG AACAAGCGGCAGAATGATATTTTATCTGTAAGAAG >1:158180920-158181460 (SEQ ID NO.: 10) GCGCCCTTCGGCAGAAGCAGCAAACCGCCGGCAAGCCCAGCGAGGAGGGCTGCCG GGGTCTGGGCTTGGGAATTGGCTGGCACCCAGCGGAAAGGGACGTGAGCTGAGCGG CGGGGGAGAAGAGTGCGCAGGTCAGAGGGCGGCGCGCAGCGGCGCTCCGCGAGGT CCCCACGCCGGGCGATATGGGGTGCCTGCTGTTTCTGCTGCTCTGGGCGCTCCTCCA GGCTTGGGGAAGCGCTGAAGGTGGGTGGAACGAGGGCGCTTGAGTGCACTCGCGGG AGGGCGGAGAGAGGGAGCTGGGTAGGGACGGGGAGGGCAACGCCTGATGGGGACT GGTGAGACCCGGGACGCACTGGCGCGATCTAGGTAGAAAACTCGCTGCTCCCTGGC TCCGGGGAGAGGCAGCGCGGCACAGAGTTCGCTGGCATCAGCCGCCTCCTGAAGCT CATCTCCTCTTGTTTCTTTCTTCCTTCTCTTTATGCTGGCTGCTCTCCCGGCCACTTGC TACACGCCTCCAATCTTCATTCTCTCCCAGTCCCGC >1:159200739-159201039 (SEQ ID NO.: 11) TGGGCAGGGTGGACTCAGAGGTTGGGAAGCTGCTCCTGAGAGGAGAAGCCTCTGTC TCTACACAGGAACCTACCTGACACATGAGGCAAAAGGCTCCGACGATGCTCCAGAC GCGGACACGGCCATCATCAATGCAGAAGGCGGGCAGTCAGGAGGGGACGACAAGA AGGAATATTTCATCTAGAGGCGCCTGCCCACTTCCTGCGCCCCCCAGGGGCCCTGTG GGGACTGCTGGGGCCGTCACCAACCCGGACTTGTACAGAGCAACCGCAGGGCCGCC CCTCCCGCTTGCTCCCCAGCC >1:160083804-160084524 (SEQ ID NO.: 12) GCCAGGCAACACGAAGGGACTCGCCCAGGGCCCCCCAGGGCTCGGTGCTGGCCCTG ATGCCCCGTGCCTCCCCATCTCCCGAGGGGCCACTCATTCGGCAAACCTTTATTAAG CCCCTCCAGGACCCCCGACGCCGCCTAGGCGCCCAGCGACGCGCGGCAGGTGGCAG CAGCTCGGGCCCCCGCCGCACTCCAGGCGCCCGCAGCGCTCGCCCTGACGCGGCCG CCATGGCGCAGGAGAACGCGGCCTTCTCGCCCGGGCAGGAGGAGCCGCCGCGGCGC CGCGGCCGCCAGCGCTACGTGGAGAAGGATGGCCGGTGCAACGTGCAGCAGGGCA ACGTGCGCGAGACATACCGCTACCTGACGGACCTGTTCACCACGCTGGTGGACCTGC AGTGGCGCCTCAGCCTGTTGTTCTTCGTCCTGGCCTACGCGCTCACCTGGCTCTTCTT CGGCGCCATCTGGTGGCTGATCGCCTACGGCCGCGGCGACCTGGAGCACCTGGAGG ACACCGCGTGGACGCCGTGCGTCAACAACCTCAACGGCTTCGTGGCCGCCTTCCTCT TCTCCATCGAGACCGAGACCACCATCGGCTACGGGCACCGCGTCATCACCGACCAG TGCCCCGAGGGCATCGTGCTGCTGCTGCTGCAGGCCATCCTGGGCTCCATGGTGAAC GCCTTCATGGTGGGCTGCATGTTCGTCAAGATCTCGCAGCCCAA >1:160401102-160401282 (SEQ ID NO.: 13) AGGGGCTCGTGGGGAGGGGGCGGAGCCCAGGCCTGGAGAGCCGGGGACTTTCCTGG GCCCGGGCGGGGGCCTTAATGATCCCAGGGGAGCCGGTTGAAGCCGGAGACGGGG AGCTTGTGTTGGAGGTGGGGGGAGAGGCGTGGAAGGATCGGAGTCTGGAGGTATTG GAAGCCAAGGGTGT >1:183185880-183186120 (SEQ ID NO.: 14) TTAGCGCTCTTAAGATTGGGCCTCCCAGTTTGAGGAAGGGGCGGGCTGCTGTCTACC TCTGTGAATCTGCCCTGGACCACCCCGGGAGAGAAGGAGGGCTCCGGGGAATCTCG CACATTCCAGGCAAAGGCTCCCGGGCCGCAGCCTCTGTGCCACACCCTTGGCCCGGG CCAGGTGTGCGCCCTCCTCGCTGCGAGGGGGAGCGGGCGGCTGCGGGGAGCGATTT TCCAGCCCGGTTTGT >1:243917149-243917569 (SEQ ID NO.: 15) CAAGAACAGGTGGGAAGAAAAACAGCAGCCTGATCCGTCTTGCTTTTCCCTTTTCTC CATGCAGCCAGCACTTTTCCTTCTCACTCTCCCCGCACGCCCACGCCCACCCGCTTCT GCACCGAGAACCTCGAGGCGCGCACGCACGTGGAGGTGACGCCAAGCCCAGCGGC GAGGTCGGGGCTGGGGGTGGGGGGAGCCGGCGTCCCGCGGGCCCCCGAGGCCGGG GAGCTCCGCCAGCGCATTGTGCGAGCGAGCTGAATGCAGCCGAGGGGCGAGCGCGC GGGCTCGCACGGATTAGCCGTGCTTTCCCATGAGCCACAAAAGAATGCCCGAATCT GGGACATCTGTCATCAAGGGGCAGGCTGCTCAGGATGCAAGGTAACCAGAGCTTTC CTCGGACTGCTTCAGTCTTTGGGGACGT >2:10080669-10080849 (SEQ ID NO.: 16) TGGAAACGCTCCCCAGACGACGCTCGCCGGGCCCGTGGGAGGCCGCGGGAGCTTGG GGGGACTTCCCAAAGCCTGAGCCCCCTAGCGATGCGCGGGGTGGGCGGGGGAAAGA CCCTGAGGGCTGCGCGCGCTGCGTTCGCGAGGTCCGGCCGTCAGTGCGCCCCGACCT TTCAGTGTCCGC >2:29115776-29116791 (SEQIDNO.: 17) GGTCGCGCAGAGGCGCTGGGGGCTGTGGAAGCCCCGCGGCCGCCTCCCGTGGGCAC CGGTGTCGCTGGCCGCGGGGAGGCCTTCTCGGGGCGGAGCGGCCCACCCGGCGGGG ATGGGGACTCCTCGTGGCGGCCGCTGACGGACGGCCCAACTTTAGGTTGAGGGGCG CGGGGTGTGCGGGACCCGGCGGCGGAGCTGGGCTCTGGGCCACGACCGCCAGCCGC GGCTGCCCCGAGAGTCCCCGCACGCGCAGTGGCTTTCCAACGCGGCCTCTTCCCATT TCTCACTTGACTCCCCTTGCGCATTAAATTGTCGAGAAACCTTTGGCCAGTGGGTCTT CAAAGCTAAACCAAATGGCTGTCCTTGCAGTCCTTGGCTACCTGAGATCCCTTAATT CTGAACCATCCGCACCTGGGAGGGGAAGTTGAAAGGAGCGCTGGAGCTGAGCCCGC ATCCTTAAGGATCCCATTCACTGCTTATGATGGTAGAGCTTTGAATTAGATGTCAGG CTGTTCACGTCATCCAGACTCTGGTTTTCAGCTCTGTGCTGAGACAGTGTTTTGATAC GTATCAGAGGATGATGTTCCTATGGGACAATAACTTGCTGTATGTTCTGAGATACTA GACTGCGTTCATATTGTAGCACCATCATCGTATAAAACGGGCGCCTTTGAAAGGTTT CAGTAAACACCTTCCTCAGGAACATCCGCCAGCACTTAAATTGTACTTCACTTTCAC TTTGACGTTTGTTGTTTGTGAATCTTGTGCACAATTTAAAGTGAGTCGTCTAAACAGC ACAGGATCACGTGGTGCGGGGCATTGAGCAACTGGGGAGGAAAGCAGAGACTTGA ACCTGCTGGAGTCTAGTTGGTCTGCGTTTTTATGTTGGAGAACCATCCTGGTTCCAGC TTATTTTGCTTTCGTAAATATGATGCATTTTTTAAATGCTTTCATTTGATACGGTCTAT CTGGACTGTAAGATTGAGTCTAGCCATGCATGGAATGTGTTTACTTCT >2:31136883-31138428 (SEQ ID NO.: 18) CTCTGTACTGTACTTAACTGGTGAGACGCCACCTCCCGCCCACATCTTCCTGTTTTTC AGTCTCCCATTTCCGACCATAAGCTCCTCCAAGGCTTTTGCCCAGACCCCTAGACGA CTGTTCTGGACCCAGTTTATAAAGACTGCCTGGCTGGCCAGGAAATCCCCCAGAGGC CTCCTTCCGTGTCCCCGGGCCAAATCTGTGAAGAGAAAACGGAAGGCTACCATGTC ACGAAAAACTATGATCAAATAAATTATTATGCCTTTTCTCCTATTGATCTGCCTTTTG TCAACTGATTTTCAGTGAACCTTCGGAGAGCCATGGGGAAGTTTTCCCTTTCCCCCTA CAGGGCTCTGAATCTGAAGGTAAGAGTGAGCCTATAGGGGGAACCTTCTGGCTCCCT CACAGGAACTGACTGAGCAGGAGTTGGAAAAGCCACTTGGATTCCCATTTCCTCAAC TCCCCGCCAATACCAAGGCGTCTGTTTTTACAGGCTCTTTCGTGGTGTTCTGGGCACA TTCAACTTCCAATGCAGCTGAGAGGGTCGGGAACAGTTAGAGAACAGGGGTGGCAG CCGCCCGGGAGGCTGCAAGGCGCTCGCCCGCAACGCACAGGCGCGCGCGGCGCACC CGGCCTCCGGCCTCCCCAGGTCGGGCCTGGCAGCTGCGGGAAGGAGGTCAGCGCAG CCGCCACACTTCGCCCGGGCGCTGGCCCGACCCGACCGCCGGCGACTCTCTGGCAGC GCCCGGAGACCGCCAGCCCCTGGGCCGCCCGTCCGCAGAGCCCCCTCCGCCCCGGG ACCCTCGCGCGCAGCTCAAGTTGGGAGCCCCGCTCCGCAGGCGAGCGCGCGCCCAC CACCCACACCCACTGCCACTCATGCACACCGCGGGTCCGGAGATGCCCCCGAGCGTT TTAAAATCCAGAAACATCACATGGTAGCCACATCCGGCGGCTGTTACCTGCTCGCAG CACCCAGACCCTCGCCCTGGTTTCCCGGGAGCCCGCAAACCCGGCACGCGGGCTGC GCGCCCTCCCGCAAGCCACCGCTCAGCGCCAGCGCGCCGGCAAGCCGCCTACCTTA GGGGTCTGCACTTCAGGTCCCGTCGGCACCTCCAACTTCCTCTTGGTTACCCAGAAG AACAGCAGCACCGTGATCCAGAGCACCCCGAAGACTGGCAGAACCAGCCGACGAGT CAGGCGCCGCATGGTCCCCTTTGCCGCTTCCTCTCCGCGGCGCTACGTCCCGGGGGC ACCCCCCGGCGGTCAGGGTTGGCGGGGCAGGAGTCCTGGCGAGCGCCTCGCTCTGG GGAGCTCTAGACCCAGGATCCGGTTGGAGGGGCGGCAGGATCCTGCAAGGCGCCCT TCCCGCTTCGAAGAGAAGCGAGCCTGGGTGGGGGGTGCAGGGCGACCCGAAACGTG GCAGGGAAGGACCGAGGGCAGCCAAGCTGGACGCCCGCTCCAGCGGGAGAAGCGC GGTGGCTGCCGAGATGTTCCCCACGCCGCCACCGCGGCTGCCGCCGCCGCCGCCGCC GCCTTGCCCGCTGCCGC >2:47369683-47369863 (SEQ ID NO.: 19) AGAGGCCGCGCTTTCCAGCGTGGAGACCGGACGGTGCGGCCGTGCTCCGGCTCAGG CCCTCCGCGCGGTAGGAAACGGCGAGGGCCGTCCCGGGGAGCAGCCTCACTTCGCA GCTTTGCTCGCCTTGGTAGGGAAATGGCCTTGGGCGGAGGCGGGGGACAGGCAGGG AACGGAGTGGCCA >2:47569537-47570197 (SEQ ID NO.: 20) GCGCCGAGGGTGGAGGGAGAAGGGGCTTTTGAGATCATCCTGGAGAGGAAACTGAG GCCTGGGGGTTGTGGGTGGAAAACAGGAAGGAACCGGTAGCCCTTGGCACGTATTC TTAGAGGAGAAAACGGAGGCTCACAAAGGTCAGATCACAGAGCCGGCCAGTGTTGG AGCACAGGCGGCCCGGGGTGAGCGCCAGAGGTGGGCTTTCTTCCCTCACTGAAAGC CGGGAGGGAGAGAGAGAGAGAGAACGGGGGCCGGCGGAGAAGAGGGCGAGACGA AAGTAAGCAAAGGGACATTAGAAGGGAAGGCAGAGCCGAGGGACGCGGACCGAGC GGCCGAGCAGTGGAAAGGGCGGCAGGTGAAAGGCACAGAGAGGAAAGATGCGCGG GGGACGCGCCGCTCACCTATGGTTGACACCACGGTGCCCACGAAGTAGAAGGCGCC GGGGAAGTCCCAGCGCGGGCGCAGCGCGTCGGCGCGGACGCCGGCGGCCAGCGCG GCCTCGTAGTGCCGGAGGAAGGCGCGCAGCTCTGGCTCGGCCACGCCGTGCGCAGC GCTGAAGTTGCGCAGCGTGGCGCCCCAGCGCGCCCGCGCCTCCGCCTCGCCGGGGC TCTCGAGCGCCGAGAAGACTGTGGCACCCGCCACCAGGTAGAGGCCGATG >2:61145001-61145181 (SEQ ID NO.: 21) GCCGATGGGGCGCGGCTCCTTGGAGCATGCGCACACAAACTTTCCGCTAGGAATCA AGCGAGCATGCGCACACAGATGTTAGGGTTCGGGCGAGCTATTTGGAGCCTGCGCA GTCAGATCCGAGGACATGTTGACGTCGTCCGAGAGTCTTAAAATCCTGCTCTGGCCG GATTCCAGACTC >2:64204147-64204447 (SEQ ID NO.: 22) CTGGGTTGGGAGCCTGGGCAGGGTGGGTGTCAAGTGGCTCTGGCAACTGGACCCCTT CGGGGTTGCCCTCAGGATCAGGATGAAAAGGGGGAAGTCAGGCTGGAGCAGCAGC GCGGTTCACGCAGAGAGCACCCCAGGCAGCCACGAACTGGCTTGCTCCGTTCAGAT TTCTCTTAAACAGCAGTTTTCCGTTTCTGTTCTATGGCCTCTGAGGGAATTTCCCAAA TTAACCTTCACTAAGCTTTCCTGAGGGACTGTTTTTGAGCGCTGATGGGGGAATTTCC CCCTTTTGACCACACTG >2:68319245-68319425 (SEQ ID NO.: 23) AATCTTCACCTCAACCTTGTAGGAGGAGCCGGTGAGCAGCTTGATGGTGCGGTTCTG GCCGAAGCGCTGCCCGTCCACCTTGTAAAAGACCGGGCCGTCATTAGGCTGGATGC GCAGCGCGATGGAGAGGCGCACGAGGCCCGGCAGGTCCCCCATGTCTGGGCGAGGG TCTGGCGCGGCG >2:86790271-86790811 (SEQ ID NO.: 24) AGGTTGAGGTGAACCCCAAGCCCCACGCGGAGAGGTGCCGCAACCCGGCGCGCGGA CCTGGCAGGAAGACCGGCACGAAGTGGCTGAAGTACATGATGGAGTTGCTCAGGGC CGAGCAGAAATAGTAGCCCTCGTTCTCTCGGCGGAAGTCGCTCAGGGTGAGGACGA AGGTGTCCCCCAACCTCTTGCCCGAGAACCGCTGGGTGTCCAGCCCCTCGGCCGCCT TGGGCTTGTTTTGGGAGAGGTATAGGAGGAAGGTGGGACTGGCGGCGGCGCCGCGC GGCTGGAAGAGCCACGAGCAGCCCGACGTCGGGTTGGACAGCAGCACCTGGCACTT CAGCTCCACTGTCTCGCCCAGGTTCCAGGTCCGATCCAGCGGCGACACCCGGAACTG GCTCGGCCTGGCGGCGTCTGCAGGCGGCAAGCAGCGAGGCTGAGCCCGCAGTCCCG CGCCCCCCGCCCCCCGCCCGCCCCATCCCCTGCCTTCCCGGGCGTCTCAAACTCACG GAGCAGCAAGGCCAGCGGCAGGAGCAAGGCGGTC >2:88765502-88766042 (SEQ ID NO.: 25) GGGGCGACGCAGTGGCGAAGTCGGGCTGTGGGCCCGGCGGCGGCACCAGGCGGAG AAGCGCCACTCAACCCCATCCCTGGGCTGCAGAGGGCCCAGCGCGGAGGGCTCCGC GCGTCGGGAGCCGGTGGAAGAGGAGAAGAGCGCGCGGGCGACAGTCATACAGGCC TTGGGGCAGGGCGCGCCTCGCGCTCCAGGGAGCCACGCCAGCCCGCTGCGCCTCCG CAGCAACCGCCGCCTGCACGTGGCGGGGCGAGAGAGCTGCTAGGGCGGTTTCTCCG CCTCGGGCCTGTTGGGCGGGGCCGGCTAAGGTGCGCGTGCTCGCTGGTCCTAACGGT TCTGTTGGGCGTTTCTGCTGAGAGGCGGGAGGGGCTGAGAGTCTGTGCGAAGGTAG GTGGACAGACTGCATTGCTTGTTGTTGCGCTTCGGAGGCGGCGATCCCCGAAGGCGA GCTGAAATACGGCTGGAGCGTTCCCAGGCTACAGTTTGTAGCCGACGATTGTGGAA GACTAGGAGCCGGAGAGGTGGCCCACCCTCAGGGAGC >2:95025733-95026933 (SEQ ID NO.: 26) GGTCTGCGCGGAGTCTGAGCGGCGCTCGTCCCGTCCCAAGGCCGACGCCAGCACGC CGTCATGGCCCCCGCAGCGGCGACGGGGGGCAGCACCCTGCCCAGTGGCTTCTCGG TCTTCACCACCTTGCCCGACTTGCTCTTCATCTTTGAGTTTGTGAGTGGCTCCTGGCC GGGGAAGGGACGGGGTGGGCTGAGCCGTGCGCTCTCTCGGGCGCCCAGCACAGCTG TCGGACGGGATCCGCTAGCTGCGCAGGTTCTGGGAGCATCGGGGCAGCAGGCGCAG GGCGGGGACTAAGCCAGGGAAGTCCCCTCCCACCTCCGGTCCTTTGTGCCCTTCTAG ACCAACAGAATGAGGGGAACAGTCTACAGGACTATGGAGGAAAAACTGGGTTCCCA ACTGGGGTCAGATGTAGGCAGCGGGGCAGGGGGGGACGGCTCTTGGTTCGCTGGTC CCAAAGCTGCGCGCGGGGCCCACTTGACGCGCGCAGCGCCACCGAAGCTCCCGCCG CGCTTTGCGCGGTTGGGTAGAAGTGCGCAGCTTTTACAAGGGAGAAGGTTTCGTTAA AAAAGAAAAAAAAATCAGCAAGAGAAACATTAGTATTACCAACCGAGATTTGGAG ATGAGAGGGAGCTGAATCCGGTTTATTTTCTTCTGGCCTTTTAAAGTTTCTGGCGAG GGAACGTATTTGCGACCAATTCGATCTGGAAATGAGGCCATCGTTTGCTTGGCCGCA GTCCTTCTGCCCCGTGTGCGGGGTGGGGGTGGAGGAGATGGGGGGTGGGGGGTGGG GGGTGGCGGCGAGAGCGATCCGCGCGCCTCGACTGACCTTGGGCAGGCCCGGGGCC TCTGCACCTGCGGTCGGTCCCGCCTTGCACGCACGGTCTCTGCCTGAGGCTGCAGGA AAGCGCTTCCTACTGAGAACTCCTGATAAGCGCTCACGGTGTCGCGAAGCCGAAGT GACCTCCCTCAGCCTCAACTCCCCGGGGGCCGCTGGCCTTCACCTGGGAGGGGTGTG CCCTGTATGTCCTGTGGGTGCGGTCCGTCACCGCCTGAGGGACACCTTTTCCGGCAC CCCACCCTCAGAAGTGTCAGCGTGGAGAGTTGGGCGGGAAAGAAAATGTCGGAGCC TGGCTGTTTAAAAATTGGACCCCAGGTTGTTATTGCCTGATTGGAGGGGGAGGGTGT GAATACCAAAGGGAGC >2:95074648-95075068 (SEQ ID NO.: 27) AATTCTGCTTGGTCTGTGGTAAATGCCCTTTCTGAGAAGCAACCATGACCTTCTCAA GAATACTTCAGAGGCACTTTTGCTCCTTCTCCACTAACCGACATCCTGTTTTGCTGGA ACACATGGGGCAGAGCGCACACAGCTTTGTTCCTGCACCCGCCCTCAGAGCTTTGCC ACCTGTTTTCAGGCTGCCTCTGCCTCCAAACCCTGCGGAGCCCTCCCTGCCCCGTGCT TTGAAGCAGTTTCTTTGGAAGCTGCTGCACAGGGGTTAACAACAAGCAACAACTCA GGTCGCATTCTTGTCAACGGAAGGGAGGGCCAGGTGGAACCGCCAAGGGGGCCATT TCTGGCTTTGCTGGAGGCTGTCAGCTTCTGGTGGGAGCCACAGCCTGAGGGCAGCCA GGATGGCTCTGCTGGGAGGGAC >2:100322218-100322818 (SEQ ID NO.: 28) GGCGGCGCGCTGCGAGCGGCTGAGACCGCGGGCGGGGGCGGGCGCCTGGCTTGGGC AGCGTCCTCAGCGCGGTGTGGGCGGCGAGCCCCGCAGGGCTGCAATCGTTCCGGGG TGGGGGCCGGGACAGGCACCGCGGGCGCAATCTGAGCCCCTGCCCACGCGCAGCGG CCTCTCAGTCCCGCCGGCTTAGGTAACCCAGGTCGCTGCGGTAACGCAGTGACCGCG CTCCAGGTCCGCGTCTCTTGCGATGCTTCCCCCACTCGCCTGAGGGCTCCTGCGCGA CTGCGCGCGCGTCCTCTGCCTGCCGCCTCCCCGCAGAGGTGCCGGGGCCCTGGGAGC AGGTGGCCTTGGCCGCGGGCTGCTGGCGCGCCGGCACCGCGGCACCTGCTCTTCCCC AGAGGCCTGGCCGCCCCCACAACCTGTGGCTCCGCTTAAGCAAGAACCCAGGAAAA GTCACCAAACGCATCACGCATCTCTAGCTTCGACTTAGGAAATTGTCCTAAATGACT GGGGAGGCTGAAGTGGGCACCCAGAGGCCCCGCCTCAGCGAGCTTCTTCTCTTAACT CTAGGCTGAGGCCTTTGAGAACTCATTTTAACAGA >2:117835956-117836256 (SEQ ID NO.: 29) TTTCTAGGACTTACCGGTTTCTCACACCCTCTCCCCACCATCAAAATCATGGTTTCAG AGGCATTAGGCCAAAAAACTGCAAAAGGGAGCCTCCTTCTGGGAAGTCTCCGGCCC TTCCGCGGCTCCCGGCGTCTCCAGCAGAGGGCTCTCGGCTGTGCCGACTCAGGACAG CTGCTGCGACGGGGCCGGCTACGCTTGTCAGAGCAGCAGCTGGTGATTTTGGACTTG CCTTTGCTGGCAGGGGAGCGCTATCGAGGGTTCATTTTATCCAGCTTGAGGAAAGAA AGGTCGGAGTGTAGGG >2:130287611-130287911 (SEQ ID NO.: 30) TGAGCCGAGAGGGCCACTGAGCCCCAGCCTCAGCGACACAGCTAGACCCTGTCAAG GAAAGGGGAAGGAAGGAAAGGGAAAGCAAAGAAAAGAAAACAAAAAAGCAGAAG CAAACGGGCAAGAGGCCAGCGTGTGGTCCCGGGCTGGCCTCAGTAGTAAAGATGCT CGGAGGATTGATTGATTTGCCGGATTCTGCGCGGTTTCCCAGCCTGTGCCTGGTTGC AGTGCCCTCCCTGTGGTCGCTGGCTGCCCGGACCCATACCCAGCCCCACGCCTGCCC TGCCCTCTTCCCAGCCAGAGT >2:130372760-130372940 (SEQ ID NO.: 31) GGCGCCCTCGGCTCTCCCCTTCGGGCCTCCGGGGAAGCGTCCCCGCTAGGGGTGGGG TCTTGGGACTCCCTGGGGCTTCCGGAGCTGACCCGTGGGGGGTCTGCTGCCCTCAGT TCCTGCTGACCAAAGTCCTGCCGGATCTGGCGCCTACGAGGACGTGGCGGGTGGAG CTCAGACCGGT >2:144516784-144516964 (SEQ ID NO.: 32) ACTTTAAGCCTCGCTGAGGCGCAGACCCGGTTCCCCTCTCCTGCCTTCGCAGTCTCTC TGCCACCCCCGCCCCCGCCCCGGGATCCTGCGCGATCCAGCGCCTGGGCCCCCGCCC TGCCCCAGGCGGACGCTCCCGAAGCCCGGCCGGAGACCCGGCGGGCCGGGCGCGAG CGGAGCGGGA >2:159904622-159904992 (SEQ ID NO.: 33) ACCAGAAGAGCAGCATGAGGAGCCCCGCCGGGCGGCGAGGGGTCGCCCAGCCTGTC CTCATCCTGAGCTGGCGCAAGCCTTCCGGCCGGGTCCTCGGGCGCACGCGGCTCCCG CCCCGCCTGCTGAGCGCGGCCTGCCCCGCCCGCACCTCTGTCTAGGCCTCTGGGGGC GCCCCGGCCCCGCCCCCGCCGCCCTCGGCCAATCAGACGTGCGTCTCCTCGGCCCCG GGGCGGAGCGGGCCAGGTGTGGGAAATGAACAGGGCTGGGCGCTAGATACCTGCGT GGGGTAGGACCCGCGAGGAAGAGGTACGTGCGGATCGGTGGGAGAGCCAGGCACC AGACAGGCTCCTGCACTGGAGGGTTCGGTCCCC >2:172736178-172736658 (SEQ ID NO.: 34) GGGGTTGAGGTCCTCGTCCGGGAGACAGGAGGACAAGGATCCCCGCCTCTCGTGGG GTGCCAGCGGCATGAGATTATTACACGTGGTGGAGAAAATGCAGCGCAGTAAGGGG AGAGAGCACCCACCTCTCCAACCCCCTGCCCTGCCGCGACTCCAGGCTCCGCTCCTG GGTGGGGGTTTATTTTCTCTTGGCATCACGGGACAGAAGAATCGATGCATACCCTTT CCGGCTATTCAGACCTTGCGGGGTATGAAGTTTTAAAGAGGGGTGGGGGCACCGGC AGGTGCAGAGTAACATTCTTTTTTTGTTCTTGAAAGCAAAGTGTGAGGGACCCGGTG GAGCTGTCGAATCCCTTGCTGAAATTCACAGCTCTCTGCCCCCGCAGTCGCTCGCTC AAGGTCTGTGTTAGAGAAGGTCATTTGGGAGGCTGCTTTCGTCTTAATACCTGCTTCT CGGGAAAAGATCTTTACGCTAAAAATA >2:176094518-176094878 (SEQ ID NO.: 35) CGAAGAGGGAGGAAGAAGAGAGTGCCTTACACCAAACTGCAGCTTAAAGAACTGG AGAACGAGTATGCCATTAACAAATTCATTAACAAGGACAAGCGGCGGCGTATCTCG GCTGCTACGAACCTATCTGAGAGACAAGTGACCATTTGGTTTCAGAACCGAAGAGT GAAGGACAAGAAAATTGTCTCCAAGCTCAAAGATACTGTCTCCTGATGTGGTCCAG GTTGGCCACAGACAGCTTAGAAGCCATTCGGTTGTCTCCAAAAGGCCTTTGGAAAGA CTTGAATATGTATTTAATTCCCCCCACCCCCTGCCAATGGTGGCAAATTTTGTGAATT GTTTTTCTCTCTTCCCCTTATCT >2:176638778-176638958 (SEQ ID NO.: 36) TGAAATAATCATGTCCAGAAATGTATCAAAGGCCAGAGGGATTATCCCACTTAATA GCTCCACAGATGCGCCCAGAAGAATGTGGACGCGCGACAGGACGGGCTGAAAGGCT GCAGGAGGAAGCAGGCAGCCCCGGCTCCTGGCTTTACCATTTCGGTTGCTTTCCTAA AAGGCTACATGC >2:216013535-216013835 (SEQ ID NO.: 37) TTTGGGGCGTGAGTTTTCTTCGGGCTTTTTTTCCCCTCTTTTAATTCCCCGAGCGCAAT TTGGGGCGCATGCGTCCACGAGACGCCCCGCTACCGCCCTCTAAGGGTGAAGCAGG GACTCCAGCCAGTCCTCAAAATCCCAGGGCACCGGAGGCTGGCAGCCGGGCTGGGG GAGGGCGGGGAGGGGAAAGCCCTGGAGCCACAGAGCACGAGGTTGGGCTGAATCT ATTCGTACCTTTTATTGGCTTCACTGCGCGAGGAAATTAAAGATCCTCCCCCACCCCT ACAGGCCTTCAAAGCAG >2:222424114-222424294 (SEQ ID NO.: 38) GGGAGGAAATCCGACTTCACCTTGGGCTCAGAGTTGCAAGGAAGGTCACTGTGGGA TCAGCCTGAGCCCAAAAGGATGGGCTAATGGGAGCGGCCGCAGGTGCACGCGCGCT CGGCCGCTCCCATTAGTGTTACGTCTGCCGGGGGAAGAAGGTGGGGTGGGGGGTTG GGGGCGCCGGGAG >2:238848026-238848686 (SEQ ID NO.: 39) GCCCAGCTAGAGTTTCCAAAAAAGTTAGAATAACTTCCTCTCCCGGAGACCTCGGTT TTGCACAAGCCGGCCTTGAAATCAGAGCCTTTCCAGCAACTCCGAGAGCGTGTGCTC GGCGACCGCGGGCTTGGCCAGCGGCGCGCGCTCGGCGCCCCGGCGCCCCCAGCCCC ACGCGCGCCGGGCGGGCGCCATGGAGGAGGGCTCCAGCTCGCCCGTGTCCCCCGTG GACAGCCTGGGCACCAGCGAGGAGGAGCTCGAGAGGCAGCCCAAGCGCTTCGGCC GGAAGCGGCGCTACAGCAAGAAGTCGAGCGAAGATGGCAGCCCGACCCCGGGCAA GCGCGGCAAGAAGGGCAGCCCCAGCGCGCAGTCCTTCGAGGAGCTGCAGAGCCAGC GCATCCTGGCCAACGTGCGCGAGCGCCAGCGCACCCAGTCGCTCAACGAGGCCTTC GCGGCGCTGCGCAAGATCATCCCCACGCTGCCCTCTGACAAGCTGAGCAAGATCCA GACGCTCAAGCTGGCCGCCAGGTACATAGACTTCCTCTACCAGGTCCTGCAGAGCG ACGAGATGGACAATAAGATGACCAGCTGCAGCTACGTGGCCCACGAGCGCCTCAGC TACGCCTTCTCCGTGTGGCGCATGGAGGGCGCGTGGTCCATGTCC >3:14880783-14881083 (SEQ ID NO.: 40) CATTTTAATTGTCCAAAACTAATTGCCCTTTTACAAGTCTGTGATATAAGAGGCAGG AAAGCAATGTGGAGACAGAGGTGATTTCCATTAACAGAGGCCTGGCAGCAGGCAGG CACTCACCGACGCTTTTCAGGGAAGTCCGTCTCCTGATTAATGTGCTTCCGGGGGCA GACAGCGGATGCGTCTCCTTGCTCAGGGATGGGGTGCATGGGGGCATGGTCTGAGG TTTTGTGCAGGTTGTTTGAGGTTTCCTTAGCCCTCTTGCTGAGAAAGGCAGGAAGAG GACAGTGGAGTGTTTCTG >3:37453325-37453874 (SEQ ID NO.: 41) TCTATAGTGGCCAAGGGGTCCAGTTGTCCCCTGAGTCCGGAGGGGTGGGCCTAAGA AGGGGGCAGCTCTCCCCCATTAAGCACCATAAGCCGAGTGGTACAGAGCTTGTGCC CAACCCCAGCAGAGAAGCACTAAGGGGGGGTTGGTGCCCTCCTTGGCCACATCCTC TGGACCAGAGGGTATAAACAGCCACACAGTGGTCACTTCTTGATAGGAGAGAGAGT TAGGCTGCGGGAAGTTCCCCCGTTCAAGGTCGTGCCTCATGGGGGCCCAGGTGACA GCCAGGCCGGGGTTGATTTTATTGTGTATTCACCAGCCTGAGCGTCCTTAGGGGTGG CAGGCAGGGAGGTCGAGGTCACTGATGCTGGTGCTCTCAGCATGTAGTTATGCAGG AGAGTCACTGCTCTGTATTGGACAGAGGCTGATGGAAAAGGGTGGTTTGTGGATCG CAGTACTCAAGCATTCCTGGAAAAGGGGACTCTGAGACCAGCCCACTAAGAATCAT GCTGTTCAGGAGATCAGCCTTCAAGAGAACCAGTTTTCAAAGCCC >3:38039106-38039524 (SEQ ID NO.: 42) GCTGAAGACACAAATGTTTACAATGACCACAGCGATGACGGGATCCGAGAGAAAGG CAAGGCGGAAGGGGTGAGGCCGGAAGCCGAAGTGCCGCAGGGAGTTAGCGGCGTC TCGGTTGCCATGGAGACCAGGAGCTCCAAAACGCGGAGGTCTTTAGCGTCCCGGAC CAACGAGTGCCAGGGGACAATGTGGGCGCCAACTTCGCCACCAGCCGGGTCCAGCA GCCCCAGCCAGCCCACCTGGAAGTCCTCCTTGTATTCCTCCCTCGCCTACTCTGAGG CCTTCCACTACAGCTTCGCAGCCCGGCCCCGCCGCCTCACGCAGCTTGCGCTGGCGC AGCGTCCCGAGCCTCAGCTGCTTCGTCTGCGCCCCTCCTCGCTGCGCACCCAAGATA TCTCGCACTTGCTCACCGGCGTCTT >3:43894073-43894613 (SEQ ID NO.: 43) ATAACGCGTAATGGAGTTAAGATGCAGATTCTGGAGCCAGACTGTCTGAGTTCAAA GGCTCCTAATAGCTGGGCTCCTTAACCTCTCTGTGCCTCACTTCCTCGTCCGGAAATT GAAGCTAATAAGAGCACTGACTTCCCTGGGCGGCGGTTGAAGGCTACCTGTGTGGA TCTGGGCACAGCGAAGAGCGGAGCCTTAACAGGGTGAGCACGCCGGTTGCGCGCTC TCCAGAGCAGCCCAGCATCTCCCGCCAGCCTCGCTGCCCGCTCCGCCCCGGCGCAGG GGCCCCAAGCCCACAGGCAACGCCAGCGCGCTCCCAACCGCTGGAGACAGAAACAA TGTGCGCGCGCACACGGCCCACGTGCACGCGCGCACGCCCACGCGGCATACAGGCG CGCACGTGCACACGCGCGCCTGCACAGCTCTGCGGCTCTGCTCCGGCCCCACAGGCC CATCTTAAAGTGTTTCGTGCTCTAACTTACCAAACACGTGGCAGCCGGCAGAACGAA AAGGAAAATAAATGAACTGCGACGAAATAAAG >3:43998051-43998471 (SEQ ID NO.: 44) AGTTTGAAAGAATCCAGTGTAGAAACAGACTTCTCCGTCCAATTTGGTTTTAATCAG TAATCATATAAGTATACCCACATAACCACCTAAGTGGAGAGCAGACGCCCAGATTC ACGGTCCCCACGTGTTGCTGGAGTTGGCGCAGACGCGTGTGCGGGCATAGCGGCGG ACGTGACACCGCATTTTCTCCGAATTCCTGCCATCTAGGGTGGTGCCGCCCCAAGAG GGGGCCGTGGGGAGGTGGGGTAATAGGCTGCGCAATCCACTTGCTCTGGGGGAGCT TAGGGTTCAGAGCAGAGCGCAACTCCGGGGGGCTGTCGCACAGCCCCATTCTCCCA CACCAGAAGAGCAATGCTCCTTATGGATGATTAATAGCCGGGCTTCTCCTGACCATG CGGCGCGTCCCTGCCGGCACCACTTA >3:44022250-44022430 (SEQ ID NO.: 45) CTGCGGGCTGAGCTCGCCCCCTCCCCCGACTTCTTTGCGGGGCATTTTCTCTTGCTGG TGTATTACGTGTCATTTCTCACGGGGCATTGCCGGCCGCTTTTCTGCAACTGTCCTTT CGGATTTGGTGATCTGGTCCGGCACAGAGGCTCTCCTAGGAGGTGGTGCCCATGCAT ATTCATTC >3:54121546-54121726 (SEQ ID NO.: 46) GGCGCCGGAGTGGGGAGCAGGCAATCCCCCAGGCTCGGAGAAATCTTTTATCCCGA AATCCAGGGTGTCCCCCGGTCAGGATCGACTCGGCGCCGCGTTGGCTTCCTCGCTCA ACCCTGACATCCCGGTCCCCACCAGTCACCGCAGCCGGGCGGACTCCGAAGGCAGC GGCCGCTGGGGA >3:113441338-113441758 (SEQ ID NO.: 47) AAGGCTATAACACTGGTCCAGCCTGAGAGAAGCCCAAGTGGGGTTCACTGCCCTCT GAGCCACAGATTTAAGGGGGAGGGTGTGGAAACTGCCGGCTGCTGAGGTCCAAACT CACCGAAGGTACTGACCGCCGCGGCTCCTCTCTTCACAGCGTCTGCCGGAGGCCTCC GTTTACTCCGGTTACCGAGACAACGCCACCCCTCTTCCAGGGAGGCGGAACCAGGG CGGGCCGTGGGGCGCATGCGCGGCCGGCGTCCAGCTCTCCGGGAACCCGGTACCTA TCCGCCCTTTGGTCGGGCCTTCTCCGCCTCATGACACTGGTTCAAAGCCAAACAGAA AAGCCCGACGAGTTTATTATCCCCTAAAGGACGTCATGTAGATAATTAAATGACATG AATACCGTCGAAGATACCTGCCTGAT >3:119322448-119322772 (SEQ ID NO.: 48) CCTTCCTCCTCCGGGCAGCTTCTCTCAGTGGCAGCTGTGTTCCCCATGGTTTGTCCTG GATGTCTCCCTTGTGCCATCCTTGCAAGCCCGCGGCCAGCGCCTCCACCCACGCTCC GGCCTTGCTCCCACTCCCACCGCTCTGCCACCTCCCACCTCAGCCTCCCACCTTGGTG TGGAGGGACCAGCGTCGAAGACAAAGGAATCTCTGACGAGAACCGGCCAGTCCGG GAGGGACGGCGGGGAAGGGGGTGCTGCTCTGGCGGAGCCCTCACTTCACTCGCTTC CCCTCGAGCGCCCCTCTAGGCTGGGGCCCGGCCGCTCTGGG >3:128491607-128492807 (SEQ ID NO.: 49) GTTCAATTCCAGCCCCTTAAAGCAGAAGGCTCCCTCCCTCGGCATCAGTGCAGGCTC TCCCACCTCATTACTGTTCTGTGTCTTTGGGAATCGTAGAGTCTGTGGCCCCCACGTC CTAGGTGTCTCGGCACCCTGGACCCAGGCGCCTCCGAGATTCTATATCGCTTCTGAC CCCTACCTTCAAGCCTGGCAGGCTCCCCGCGGAACCCTGCTGAGACCCGGAGACAA TCGGGCCGTGCTTCTCCCTCCTCCACGAACAGCCACGGTTTATTTGGAGCGGCCGGG GCCGGCGGCCTGACAACTGGTAAATCCGTTTCGTTAGGCACAATTTGTCTGCAATTT GTCAGCCCGGCTGGGAAACGCTCCCCAGACGCCTCGGCTGCCGCACGGGCCCTACC TGGTTCTCGAATCCTGCCTGCTCATAAACGAATCCTAGCACGGGGTGCCTGCGTAGA CCTGGAGCTCACCACCAGATGTTCCCGACCTCGGGAGAGGAGGCTTTTTCCAAAACA ACGAATTTCCTTCCTTGTTTTCCGGTAAAGGAGCGTTCGCCACACACGGGGTCCCTG AACGCGGGGCCTTTCCCCTCGTGGTTGGAGCAACGCGGAGTTCAAGCCTGGCCGCC ACAGAATAATTTTAAATGCCCCGTTTTCAGACAGATCCAGAACGCCGTCTACGCCTA CCGGCGGCAGATCTTCAAGCCCGCGGCGGCCCCATTCTTATTGAAATCCCACTAAAC GGATTCCGACTCCGGCTTGGGGCGGGGGGAGACTTCCAGACCCGGCGCTCTCCCCC ACACGCACCCCAGTCACACAGGATAAAGGGCTGCGGGGCGCAGCGCGCGGGGGCG CAAGCAGGAGCGAGCTGGGTTAAGCCGCGAAAAGCCGGCGCACGGGACCAGCCGG CAGGTGCAGCCGCCGCTCGGCGGCCCGGCTCGGACGCATCCGCCGCGGTGGCCTGG GGATTGGGGGCGGCCGAGACAAAGGCCCCAGTTCGGGGGCCGGGAGGCGGGGGTG CTTTGCGAGGCTCTGGGAATGCCAGGGTCTCGTGGCCTGTGGCTCCGAGAAATGGGA AGACAAGAGGCCCGAGGCGGGCCTGCTGTGCCCAGGTAACCAAATACTCCCTCTGG TTAAAGTCCCTATAACCAGGGTTTCCGGTCTCTGGCAGGGCCAAGGCGAGCCCCAA AGGTAGGGGCCACAGG >3:185363363-185363963 (SEQ ID NO.: 50) GTTGTTGTGAGTATTGCACTCTGTTTTTCCTGTTTCTTCAGTATTTATTTCACAAGGAC AGACAGAGAATGTGTGATTTGAGGTGATTAGAAAGCTGATATTATTGAGGGCGACA CCGTGAGAGAGACAGAGAGACAGAGGCGGAGAGAAACCCGAAACCCCGTTACAGC TAGGAGCCTCTGAAACTGACAGCTGGTTTTCCTTTGCTTGTCTGCCTGCTAGACGTGG ACATTTTTCATTTACGGTTCTGCACGTTACCTCGGATGCCTGCTTGGCTTTCCTTAAA GGGAGATTCATTTCTCTGAGAGATGATGTGGATGGTATTAGCAGAAAAGCCCAGAA CACCAGAAAGGTGCTGAGAAAAGCGGGGCCCGCAAGACAGAGCAGGTTCTATCCTG TGGGGCACTTGTCTTCCTTGCGACCGTCCTTTCTGCCGTTCCTCACCCTTCACCTTGC CTTTGTTTCATATTGTGTAACAGTCAGTATCTTGCGATTGCAATTTGGTGAAGATGAA TACTTGTTCAACCATTTTTCAAAAGCTCTTATGACGGGAGCCATAGTGGTGTATTTAT ATATATTCATAGCTCTTCTTTATGTCACT >4:41867059-41867539 (SEQ ID NO.: 51) TTTCCCTCCTCGGCCCAGCTGAACGAGGCTCAATGCCTCAAAGATGCAGAGCTGCCT CGGTGGACATGCTCTGTGGCTGATATTATAATTTTCATAATGCGCTTTTATGTCGCGC CAGACTCCTCCGGTGAGGAGCCCGCAGAGCTGCTGAAAGGGGCTTTGAGAGGCCCG GGCGCGCGGCTGCTGCGAGCTGCGCGCCCCCCGCCGGCCTGAGTGGCACCGCGTGC CCCTGCCGGGGCGCGGCTCCTGCACTGCGGGCGCGCAGGCGGCGGCGGGCTCTGCC GGCGCCCCTTATTAGCATGCACCCTGGGTGCGCCTGGCCTGCTCCCGCTGCTTCCGG GCCTCTCTGCGCCCCTCCGAGTCTCTGCCATCCGCCTGGGTGCGAGGTCCCTGGCCTT GCTCCTGGTCAAACTCCATTCCGCTCCAGCTCAGGCTTTAGGGAAGGTCAAGGTGTT AAAATGTGGGCAGAACATTCCGGAAG >4:42151203-42151863 (SEQ ID NO.: 52) AGAAGTGGAGAGAAGAAGAAACAAATGGAGGAAGAAGGAGAAAGGGAAAAAGCA GACGGAAAAAGTGAAGTAGTACGAGGGCGTCCCAGCGGGGCGGCCCGAGAAGCTC CAGCTTCTTCCCGAGCGGCCGCCGCTATCCCCCGGGGGGGCGTCTGGCCCCACTCCG GACCACGCCCGAGCGATCCTGGTCGCCGACTGCCACAGCCGTGCTTCCCGGCGCGG GATCCAAGCCGCGGAGCCACCTGTTAGGCGCGCGCCGTCGGAAGCCCAGGCGCGGC GGCGCTGGAGAATCCTCTCGAAGTTTCCGGGTGCGCGGGGAGGCCCCAGGTGCGCC CCGACATCCCGACACGGCCCAGCACGGGTAAGTGTCGGCGGCCCCCCGCTTCTCCTT CCTGGGTCCCCTCCCGCTGCCCCCGGCCGTGGCGGGAAGGAAAGTTGTGCGGAGAG TTGGTACCTGCGCTGAGCTCCAGGCTGGCGCTGTCGCTACCCGTGCCGCCGGTGCCG GCGGCCGCCGCCGCGCCTGGGCCATACCTGACGACAGCGGCGAACGAAGACGACGA GGAGGCGGCGGGGGACGCGGGCGGCGGCTGCGCCGGAGTCCTCAAGTGGCCCTGG GATGTGGCGGGCGTGCAGGACGGCGACGACGACGAAGCGGCGGCGG >4:143699914-143701174 (SEQ ID NO.: 53) GTGCTGATAGCGCACCCCAGCACGGAGGAAAGCCTCACAGTCTACGCCCTTGCCCCT GGGGAGAGGGGCCCCCACCGCGTCCACCAAGCGCCCGTACTTGGGCAGGGGGCCGT CCTCGTGAGGAAGTGGGGTAAGCCGGCACCTGCGGGTGGCCGTGGCTCCAGACTTC AGGGAGGCGAAGTCCAGCACTCTCCTGTCTATGGCGCGGCTCCAGCTTCGCAGCTTC TCCACTACCAAAGGCCTGTTACGCGTCACCAGCTCCAGCTGGGAGAAGACCAAGTC CACCGCCAGCGTGAAGGGCAGCACCAGAGTGTGAGTCGGGGCGTCGTAGCGCAGCT GCAGCAGCACCCGGGCGCGTCCGGGGCTGTGGGAGCCGAAGTGAGTGTACTGGACT TGGCGGGGCCCGAAGGTGCAGGGGAAGCGGCGCGGGGAGAGCGCGCCCTTGAGCC GCGGCAGGGCGTCCAGTACCGTGACTTCGCACCGGTCCCCCGGCTGCACTCCAATCA CCAGATCCCGGAGCGGGTCGAGCCAAAGGGAACGACCCAGGGGCACCCGGAGTCC AGGGTTGGCAATCAGCACGCTGGGGCCGTCGGGGCGAGTGCCGTCAAGCGCACCCC GGGCGGGCAGGTAAAGCGCCGGGTCGGGCTCGGTCCCAAGTGAGGATGCCCGTCCC TGCAGCGCGGGGCGACTCAAGAGCAGGCAGGCGAGCGCCACAAGGAGCTGCCGGG GCGTCCCAGTCGGGTGCCGAGAAGCCCCCGCCATGGCCACGGATGGCTCCTGGCGT TGGGATTCCCGGGGTGGGGTGCCCTGTGCAAAGAGGGATCTGCTGAGCGGCAGGTG CAGGCAGTGGAAGCAGTAGCTGCTGTCCAGTCGGTAGCCGACTTGCGGATCCAGCA AGAGCCAGCGGCTGCGCTTCGGCTGCTGCAGGTAACGGCAGCGGGGGAAGGGGCTC TGCCCACTTCCTGCTCAGCCCCGGTCGCAAGTCTCTCTCTGCTGGCTTCTGGGGACCC CAGATACGCGCCCAGCGCGGCGAGACTTAGCGAGGGTGCAGCGCTGTCCCCTCCGC TCCTGGGCGCTTCACCCAGCCTACCTTACACACCTTCTCGCCGGGAGCCGTGGCCGC CGCACTGCTGCCCGCGCTGCCAGACTCCGACCAGCTGTCTGGATACTCTCTTCCCCA GGTGCCACAAAGGGATTGTCCCTCAGGGTTGGGAGAGAGACGGTGACTGTACTCGG GTCAGTCCTGCGTCTGTGAGATTGA >4:145733372-145733552 (SEQ ID NO.: 54) AGGGACCGGGAGCGGCAGGGGCTGCACATGACCTGGGGCGCGGGAAGGAGCCCGC TGCCGTCTAGGCCCGCGAAGGGCCCCGGCAGCCGCCGACTTCTGAGGAAAAGCAGA ACGGTGTTTGGTTTACTAAAGTAGCCGCCTCCTACCACTCTTCCTCCCCAGCCCCGCT CTCTGCTCCCCA >4:153249541-153249721 (SEQ ID NO.: 55) AGCATGTGTGGAAGAGGCAGGCATTATTAGCAGCGCGTCCGCCTCGGCCACCTCCCT GCTCCCGCCTCGGCCACCTCCCTGCTCCCGCCCCGGCCCTGGGGGCCTCTGTTCAGC CTCCACCAGCTCAGTCGCCCACGGAGACTCCCGAACTCTTAAATCCCAGCCCTGTAG TCAAAACCAC >4:182448095-182448815 (SEQ ID NO.: 56) CTTGCACACATGCCTTCAGCCCCTGGTACCGTCTTCTCTCCCCGGGTCGCGACACTG ACTCGTCAACGTTAATGGGGGTCCGCGACTGCTGCGGGGACGAGGGCGCAGAGCAG CCCCCGCCACGGGCCGGTCCACGCAGGGGCCGAGAAAGTGGCGGAGAGGCGGTGG CCGAGGCCCAGGGGCGAGCGCGGGCTGAGCTGGTCCCTGCTGCGTTCACGAGCGAC ACCCACCCCTTCGCTGCGGACGCCCCGCGGGCGCCAGGCTGGGGGCCCTGCGACCG ACCCCTCCCGCCCCCGAGGTACCGCCGGGCCCGCCTGGCAGGCAGCGCGTCCCGCG AGCTGGAGGGCCGAGTTTCGCGGGGCCGTGGGGCGTGTGGGTGAAGGCGACACCTC GGATGCGGGACGCATGAATGGTGGCAGAGCAGGGGTCGGGATCCGTTCATGGGTTG GGAGAGAGATGCTTTTGTGAGCACGGGAAAGTAGCGCTGCCGGAGAACAGCTCTGA GGCGGGATCAAAAGCCGCCGGCGAAGCCCCGCCGAGGAACACGGCCGCTGCCCGG GGCGGCTCGCGAGCGTGCGTGTGTGGAGGGGAGGATGCCGCCCCGCGGGGTCTTCG GAGGGTGCCGGGAGCGGGTTCTCAGTGCAGTTCCCCCGTCTTCGCTGGGGGCACGG CTGCTCACAGGCCCCGGCCCGCGTGTGTGGAGCGGGGCGAGGGGGTGAGG >5:1875964-1876144 (SEQ ID NO.: 57) GCTATTACTGTCAAGTACCCTTGACTCTTTATTTTTGCCCTTTTATCTATTACAACTAA TTCGAGTTCTTTTGCCCTTTTCAGTCTAAGACGTGGGCTTTCTGCAAAGCCTCCCCCT GCCAGCGAGCTCTCGGAGCGCGGAGCCTTTAGAAATTGAGGGGTTTACTGTCAAAA TGAAAATT >5:31854956-31855556 (SEQ ID NO.: 58) GCCTTCGGGAAGTCCTGCAGGAGCCGCGTTCCAGGAGGGCAGCTGGCAGCCGCCCC AGGCCCCCGGGCCGCCTGCAGGTGATTAGGCTAATGAGCTGCCCCGGGGGCGCGGA GACCGGCCTGGCGAGCGGATTACCCGGCGCCCAGCTGCTGCCGGCGGAGACTCCCA GGAGCTCCGGAGAGGAACCCTCCGAAGGTGACTTCAGAACTGGAGGTAGGAAATCG GCTTCTCAGGCGAAAGCCTCAGGTTTTCTGATCTGATCCAGGTCGGGTGCAGACTGG GGCTGAATCCACAAATGTGGAGATTTAGCCACAGCCTCGGAGGCGCGGAGCGGCCA CCTAAGCGTCTGCCCTTCTCGTCTCCCGGATCACTGGGGTGTGTTGTTTTTAAAGTGG GGGATTTGCGTGTTGAGAGACGGTTTGTGTTCCTCGGGAGGAGTAAGTGACTTGGAG CTGGTTTGTCAATGGCTGGACGGAAGGAGGCGCCCCGGCTGTGTGTGACGGGCAGG GAAGGGGTGCCCAGAGGGGACAGGTAATAGGGGGTTCCGGAGCCACGGCGGTTTCA GAACCTTGGGGCCTGTGCCGTTGAAGCCCCGGTAGGG >5:32713356-32713716 (SEQ ID NO.: 59) CTCGAGGCTGAGGATGGTGGCTATGGCTTCGGGGAGCGGGGGGACGCGGACGTGTA ATCGCCAGTGTGGCCCATTTTACGGTAGGGTAGAATCTGAGGGAAGGCGGACTGAG ATGCCGGTATAGCGCCGATCCCTCCTCCCTCTAGTCAGGGATTAGGAGCACTGCGAT GAGGGAATCCCGTCTCTGCTCCCCCTTGGCGCTCACGCGCCTGGAATGTGAGTGGTG CAATCCCGGCAAAGCTCCCCGAGACCCCAGTGCCACGCGGATGAGACCGAAGGGGA GCGGAGTTGAGCCAGGCGCCGGGCTAGTCCACAACTTGGCATGGCCGAGCACCTGG GCGCTGGTCGTAGGGGACAGCGC >5:38555799-38556399 (SEQ ID NO.: 60) TCCTGAATCCAGCTTTGTGCTTTTACACAACATAACAGAAATGGCATCTTTCACAAA GCCTAACTTTGACCTCCAACACTTTAACTTTGGGTTTAACCAGTACACCACCTTCGGA AGTTAGCACATAAAAATACAGGTAAGTCAAATGCACTACGGATACAGAAAGGACGA GGAACAGGTTTAAAGGGGAGTTGAAGCAGAGGGGCACGAAATCACCTGGCAGGTC ACCTCTCCGAAGGAAAAACATTTCAAGCTCCCTCCCATCCCCCAGGTAACCTCTGGC CTCAGAACTCACTGCCCTGCGTGGGGCAGAAGTTCTGGGCGCTGGAGTCCGCGTCCC CCAGGACACGAGGGTGACCCAAGGGCGCGCGGAGAGCGGCGGGACCCGGAGCGGC GCTCTCCGGGGTCACTCCCCTAGGACGCTCCGCAGAGCTGGGAGCGCTGCCCCACCC CGCCCGGGCCGCCCCTGGGGACCCCGCTCGGGGCTCCGCGGCTCCCCTGCTCCGCGC CGCGCCCACCCGCCCCCAGGACTCACGGTACGCTCCCGCGCCGCTATCTTGCCATCC CCTGCCGCCGGCTCTGTAGCCTCGGCCGCCGCCCC >5:88683649-88683949 (SEQ ID NO.: 61) CCGACCTAACCACACTCCAGTCTCTTCTAGGTCGTCACCGCTCTGCACCAAACAAAT GAGTCCTGTTTCACCACTAGGGTGCCGAGGTGGATGGTGGATGCTGGCCCCCGCCCC TGGCAGCGCTCAGCCCTTAGAAACCAGAGCCAGCTGACAACACGCGAAACACACAG GCACAGCGAAAACGCCGAGCCGACGCTCATTCCCTCTGCCCCCTCCCTCTGCTCTCT GTAACAAGGAGGACACGTACACAGCCTTTACACACTTAAAAGCCCTTGCGACTCCCT CTGAATTCTTAGTTACT >5:93621604-93621784 (SEQ ID NO.: 62) TGGTTTCCCCTGCGTGCGGGATCGCACAGCGCCTGTTTCCTTGCTTCCCAAGGGGGT GGTGTGGAGGGGAAGGGGGAATGATTTTTCTTGCGTCTCCCGGAAGCTGTGCTGTTA GACACAATTACCTCAGCTAGGTCACTGAGACCAAATCATACGGGACGCTTAATGAA GGACCGCATTC >5:173236238-173237198 (SEQ ID NO.: 63) TGCGGCTCGGTCAGGCGCGTGGGGGAAGGGCAGGGCAAGTGGGGTGATCATGATCA TTTTTAGCCCAGGGTCAGTAGAGTAGGGCACAGAAGTCAGACAAATCTGCCAGAGT TTCAGGAGCGCCAGCTACATGGCCAGATCCTGCCCGGGTGGCCTCATTTCTCTGGGT CCCCGCACTCCTTGGGAGGTCTGATGAAAGCTTGGGGTCTTCTCCATTCCCCAGAAC ACTGCAGAGAGGAGTTTTATTTTGCTTACAATTCAGGAGTCCGGGCAGGCAGAGCG GGCCCAGGTTAAGGACGCCTTCTAGAGCTGGGGATGACAGGATTTGTCAGTGGAAA AGCGTTGGCTTCTCACGGCCCTAGCTGGTACAGGGAACCGCGGGCGGGAAGCTGGG CGGGACGCGTGGACTTGCTGAGAATGGGGATGTGGAGGGCTTGGCTCTTTGCGGAG TGCGGGTTGGCAAGAGGCGCTTGGAGTAGAATAAAGGCGGCGCAGGGCCAAAAACT ACCTAAAGACACAGCTCCCGCAGGCGCGCCCAAGGTGCGGAGGAAACGCTCCATGT ATGGGGACAAAATAGTGTCTGTCCAGAACGTACATCTTGGGTGCTCAAACCCGACA GTGTGCCGTCTGAGACGCCGACGCAAGTGAAGTCAAGCATTGGCCTGATGTTGGGA CTTTTCCTGTCCCTCATCAAAGCCACACTCCCAGGACCTGGGGCCTCCATGCTGGGG AGAGAGGTGAGCCCCGCAGGGCAGCCCAGGAGGCGCGCAACGCCCTGACCCCGGCT TCTAGGCGCCAGCCGTCAGTAACAGGCCTGGGCTGCCACGCCGAAATCACGCCTCG AGTTTCTGAGCCAGGGACTACTGGGGGTCTGGAATTGTTAGTCTAGTCTGTGGAGGA TGCCTTTTCTTAAATGTGGGGCGTTCAAGGCCCAGGAAACCTCGTCCCCCCACCTCT TCAC >5:175772822-175773002 (SEQ ID NO.: 64) CTCCAAGCCGACGCGCCCTGTTTTATGCCTTGAGTAGGCGGGAGCCTTGCAGGTCTG TGGGTTTCTTTCTCAAAGGAAAATTGCTGGGCTCGTGAGGAACAGCCTCGGGCACTT GCTCTACTTGGAAAGGGTGAAGAGCGCGGGCTTTGGAACCCTAGGCGCGCCCGCAA TCCCAGCTCTG >6:6004596-6005316 (SEQ ID NO.: 65) AAATAAGTCGTGAACATTTCTGTCTTTTAAAACTGTGACTCCTTGGACTCTAGCCTTC TCTGGGAGGCCGGGAGGCTGCGCGCGGGACGGATTTTGCAGGCGCACGCGTCCCAG CAGGTCGCAGCCCGTGGGTCCCTCGCTGTCCTTCCTGAACCCCGCTTAGGCGAGACT CTAGCGGGTGACCCTGGCTCCTTCCCTGTCCTCTCTGCCGTCCCCTTCTTGTGCGGTT TCCATCCGTTCATTCATTCGTTCGACCTCTCATTCATTCCGAACTTCCTCCTGCTGCGT CTTCTTTCGTGTTCACCACACTCTTCTACCTCCCCGCCCCTCCCAACCCCCACTTTTCT TGCCAAATGTCAATGATTTGGGACAGCTCCCAGCCGTGAATTAATAAAGACCGAGG TTCTGTTGCAGGAAAGGGCAGACATTAGGGAACAAATACGTTCAATTTCAATTCCAC AGTCAACAAATAGTCATTTTTGGACCGAGGTTAATGTGTTCAAAACGCGTCCCTCAG GCACGACCACCGTCTTTTTTTTCCCTCCAAACCTCTCAAAGTAAGGTTATTTCCTACC GGGAAAACAGAGTCCCAAATCTTGTCCGATTAAAATTTCTATCTCAAAAACAACTCT CTCTCCTGCTCTCTAAAAATTCAAAGGTTTATTGCAAAATGCCACATTCACTTATTTC CAACATTTAAGGAATTTGCTGCCATTAGAAA >6:10415249-10415489 (SEQ ID NO.: 66) GATCTCCCTCTAATGGTAGAAACTTTTCCCTTTTCCAGCTCTTTACCAACAGCCTAAT CGCCTCATTAGCATATCAACAATAGTCCAATTGCTCGCCAGTACCACAATCTGCCGC CGGCCGCTCCGACACAGGTATAAAGGCCTCTCTACGCCGCGAACTTGCTTCTAGAGC GCACTCCAGCCTGCGAACTGATAAAACCTTCCTCGAGCTCCGCCGCGAGGCCCTGCC CCAACACCCCCT >6:26550445-26550884 (SEQ ID NO.: 67) GAGATAGAGTGAGAACTCCGTCTCAAAAAAAAAAAAAAAAAATACCTCCTTCTTCT CTCAAAACTCTCCAATGGCTTCCACCCTGGGTCATCAACATGGCCTGGAAGAGCCGT ACTCTGGATACCCGAGGGCGCGGCCCCAGCGCCGCGACGCCCCGCCCCTCTGGCTG CTCCGCTCTGGGATGCACTTCCGACGCCCTCTAGGCTTGGGAGTTCCGCGCCTCTCG GTGTCGCCTGGGGGGCGTGCTCCGGTTGGCGCACTGATTCCCAGTTGGGTAGGGGAG GCTTGACTGAGCTCCCACCCGGAATTTCACCTTAGACCTTTAAAGACCTTGCTCCGG CCTCCCGCGCCAGCGCTAACACCTAGTCCTCTTTAGTGGAGTTCCGGCGGAAGGGGA TGGCGGGCACCCGACGGTGGTCTCCTCCCAGATGGCGAATTTC >6:26754333-26755053 (SEQ ID NO.: 68) AATAAGAAAGTTGAGGAGCAAAACGACGTGTCTAACGTCACACATTGAGCTAAAGA CAGATGGGATCTGACATGCATTGTCAGCACAAATACAGCGCTTTTAAAAATCATACG GATTTTGTGTCGTGAGGCACTCAGGACTCAGCTGATCTCGGCGTTCAGTCGTGCGTG ATTTTGGATTTGCACCTCGCCCTTGGGCAAGTGCAGAATCCTGGGGTTATACAAAGC ACATCACAGTTAACCCCTTTGTCCCAGTCCGCAGAATGAGAGCTCGGAGCCCGGCCA TGGGTGGCTCGGTTATATAGGCAGGAAAATCAAGGAACCCAGGTGTGAGCAGGGGC GTTTGTGGCGCGGAGAGAGCTCCTGTCCTTGCCGTCCACCTATTTCTCAGGCTTGGCC CCTGGCGTGTAGAAAACCGCATCTCCGGAAAACCCAGAAAGTTACGTCGCCCAGGT ACTCTCTTGTCATTCTCCGGGATGTAAAAGACTCAGGGTCTCTTCACGGATCACTGA AACCGCCTTCTCCGAGGCCTCCAGGGTGACTAAAGAGAGGGTGGGTGTTCTGTGTTC TCCCGCCGGTGTGTTCCTCTTCATGTCCAACCGCTTGTGTCTGTGCCCGCTAGGGTCT CGGGGGTTTTTATAGGCACAGGATGGGGGCGTGGCGGGCCAGGGTGGTCTTGGGAA ATGCAACATTTGGGCGCGGAGGAAGAAGTGCCCCTCCTC >6:28988380-28988560 (SEQ ID NO.: 69) TGCATTGCATTATACTATAGCAGCAACTATACTTTTAAATGATTCGAATCTTGAGGTT TCAAACTGAACCGTCTTGTGCCTTTTGCCCGGCGGGCATTTCTGCGGGGACCGCGGG TCACCTTCTGAATTTTTACCTTCATAAACAGCAAGGACTGCGCTCTTTCGCACGGCGC CCCGTTTT >6:31308135-31308735 (SEQ ID NO.: 70) CCCACCCCAGCTCCTTCCTCCCTCTGTCATTGGTCACAGAACAAGTCAGTCATGATC CAGATTGAAGGAGAAACCTGGAGCAAAATGGCCCCAGCGCTTCCCCACCTGAGAGG GATCAGCTGAGGCCCCGCCCCCCCATCCCTGGGAGAACCGGGCTGGTCACTCTGGG GTCGGGGCGGGGCACACCTGTGCCCGGAGTCTGAGGTCACTCACCGGCTGACCCTG GTGGTGGTGCGGGCCCAGGAACCTCAGGCCCCTCAGTAACACATTCCCTGCGGTCTT CGAGAACTTTCCTCAGGGCGCCCACAGCCCTGTGCCATCTTCTCCACCCGCGCTTCA CGCTCTGATTCTCGCCGCGGCTGTGGAAGCTCAGGAATCGCGTGTCGCCCACGAAGG CGCCGCGGAGGAACTCAGGGCCCACGTGGTGAAGGCGGAGCCCGGCGGCCTTCAAG TACCCGGGGTGCGGGCCTGGGCTCCGGGAACCCGCACATTGCGGGCGGGAGAGGCG CAGGGTGCCTGGGACGCCGCCCCGCTCGCCTCTCTCCTGGACGCCGTCGCCCTGCCT CCCCGCGGGGACACAGCCTCCCTCCCACGTCCCGCC >6:37570393-37570813 (SEQ ID NO.: 71) GAGTTCCTCTTTGACCAGACGGCCTATGCATTGGGCCAGCTGAGCCCTAGATCATTC CTCCTTTATCAAAGTTTTAATCCTCTCTGAGGTCCCGTGCACTCACCTCGCAGCTCTC TTGGGAGCCCTTCCTGACTGCTGCGTTTCCTCCCGTCTGCTGGGGCCAGCTCCGGGC CTTGGCGTATGCCGCCTGCTTCCCTTTTTATAGGCTCCACCTGCCTCACTAAACATCT TTAAGCCTCTGAAATCAGAGGCCGTGTCTTGTGCCTCTTAACCCTTTACTGAGCCCA GCACATTGTGAGTACTCTAAGAATGTCTACGGAGTGACTGACGAACCAGGAAGATG GAGGAGATGGGTTCCTGCACTCCCTGTGCTCGCCCCTGGAGAGCTCCTGTGATATGG AAGAGAATCCCAGGCTCCTGG >6:42726729-42727149 (SEQ ID NO.: 72) CGACGAGGAGGGCGGTGCTGAGCCCATAGCAAGTCTGTGGATGCCCCCTGGTGGCC CTAAATAGAATGGCTTCAATGGATGGAAATTTAACGTGCTCGCATCCCCAGCACGTT AAATTACCCAGAAAAGTAAGAGAAAAAGAACAGACACATCAGAAATGTCTCTGGCC AAACCTTTCAAGTACGAATCAAGGCAAGATATGGCGATGAACAAGCAGAGAAAAGT GGACTGCAAAGGAAGCAGTAATTAATCTGTCAGAGAAGGGAGGGCTCCTTCCTGCT TCCGGACCATGTTGGATGTGAGTCTAGATGCGAGACATCTATTATAGAGATAATAGA AGAGGTTAGCGGAACCAAGGATGGTTCACTTTTCTTCTTTAGAAATACCATTAATGC TGATCGTCTTCGCCGCCGCCTGCGTG >6:42771139-42771319 (SEQ ID NO.: 73) AGGACATGGAGCAAATTAGCATCACACAAATGACGATGCTGCAAATGAGCGGTGTA CAGGGTTGGCGGGTGTTGCAGGCAGGTTTCCTGTCGTTGGCGCCACGTGCTGCAGAA AGAGGACCCCTCCCCCTGCGGGCCGCCGCTGCGCCCGTGCATCCGTCACAGGTACA ATTCGCACCGGA >6:43174231-43174471 (SEQ ID NO.: 74) CGTCCTAGGGGACAGGTGTCCATCCTCACTTTCCTGATAGAAGACCGCCCCCCTAGA TAAGCGGGCGGCCTCCGTGCCCATATAAGGCCGGCTTGGGCTCCACGCCGGCCTCCC GCCCGCAGCCCGCCTGCCTGGCAGGGCCTTTGCATTCCTCCCGCCAGCTGTCTCCCC GCTAGGGGCGGGGGTGTAGTTTAGCCCGGCCCTCCGGGCTGGGTCGCCAGGGAGTA GAAAGGGAGCACTC >6:44002777-44003257 (SEQ ID NO.: 75) CGGCGGCGGCGGCGGCGGGAGGAGACGCAGGTCACGCCCCCTTCCCACCACCTCCC GCCGCCGACGGGGCGCGCGCGCCGAGGAGCCCGGGACAGGTGACTCCTAGAGGACT GCGTCTGCGCCTCCCCCGGCGGGAGTCCCTTCTTCGCGGCCTCTGCCGCCCCCTGCG TCCCCTCCTGGGCTTCCGAGAGTCTGACTCAGCCAAGCCGGCATCGCTTCGCCTCCT ACAACACACCCCGAGCGCGAGAAGAAATTACAGGATTGCAGGGGCACGGCTAATGC GCTCTAATTACCCACCGCCGCTGTCATCCGCGGCGCTCCGCGGCGCTGGGCCAACGC GCCGTAATTAAGACGCCGCTCCCCGGTCCCGGAACCCTCCCTTCGCCACCCTCCACC CACCCACCTCGCGGTCCCCAGGACCACTGGCTGCCAACTCCTGCCGCCCTCTGGGAC TGCCCCTCAGTCCCAGGAGAGCTATGAG >6:72622682-72623402 (SEQ ID NO.: 76) GCGCGTGCACACGTGGTGGCTTTTATTTCTTCGCACGTGTTCGTGGTCTTCCTTCTGG AGCCTCTCCCCTCCCCCAGCCCCACTTCTCTCATCTCTACAGCTTGAACCTTTTCCCC GAGGACACCCAATGAACTGCCCGGTAGCTTCAGGCTCCCGGGGCGAGAGCCAGGCA GACGCGGGACTTAGGCTGCGCGGATAATTGGGAGCAATTAGGTCCCAAGATACGTA AACTTCAACCGAACGGGGCGCCCGGGAGCTAGGGAATGCAAAGGGAGGACAGGCG CCCGTGTGAGGCTTGAGAGTATACTGGAGAGGTTAGGAGGTGATGGCGGGGTAGGA CGGGGAGAAGTGAGGGGGCATCGAGGGCTAGGTCCTCAGTCCTAGGGGCGGAGTAG GGGAAGCTGCTACTTGGAGAGAGCTGCTAGGTTTTAAGCGCGCCCGGAAACACGCC TCGCCACCACCCAGCCACCACCAACGGAAAATCTGTCAGTGCATGTAGCCCTTCCTG CCACGGAGAAGGTGGCCAAGGTCTAGAGGAGGCCAGCAGGCCAGGCGAAGCAACG CTCCCGCGCTGCAGGGGGCGGGGAGGCAGCGGGGAACCTGGGGCGCAGGAACGCG GGCGGAGGTGCGATAGCAGAAGCGCAAATGGGTCGCCTCTGACAGAGATCGGGCAG TGGGTTAAGTCCCCGTTTGTGGCGCGGAGTCAAAGAGTGTGTGTGTG >6:73309532-73310552 (SEQ ID NO.: 77) GGGCCCCTAAAGCCACTCACCTCGATTTCTGCGGATCCAAAGGTGGAAAGACACTG TCCCGATCAGGAGCATCGCAAGGGTCTGGAGAAAGGGCCATCCATAAATGAAGATC AGGACTCCGTATTCTGAGACTGTTTCAATCACAAATAAGACTCGGAACAGCCTCTGG AAGGCCGACAGCATTTCGCGTTTCTGGCCTGGGAAAGTAAGGGTGCGCTAAGGCAC GAGTAGTACAGCTCCTCCCGCCACCGCAGAGCCCGCCGGCGGGAAGAGACCAGACA CCGACGGAGAAGCGAAGTTCAGGACGCGAAGGAAAGGGCCACTTCGGGTCGGGGT CAACCCAGACTGGACCAATGCACAGTCTAGGTGGATTAACGCGCCACCGCGAGAAG TGGGCACGGGACCACATGCGGCTGGCAAGACGTCCCAGGGCTCAAGCTCCAGGCTC GGTCACCAAACAACGGTGATAACATCCACAACGCCACGTAAACCATCTTTGGGCCTT GATCGTTTTCCAATAACCGACTGAACTGAGGGCGTGACCAAACGACAAGAACCGGA GGAGAGGACCCGGAGAACGGAGCAGCATCCCGCCGCCCGCCTCCAGGAAAGCCCG AGGCACTGTAGCAGGAGGGTCTGGGCTCCGCGCCTTAATTACACCGCCCTGGACCC GCCTCTTCCGCCGCTCGCTCCTCTGACCGGCACCCGAAGGTGCTGTCCCGCCCACGG ACTCGCTCACACTCCGTTTCTTCGATCCTTTAGACGACTTTTTACCGTTCAGGGATGC TCTCCGTTACCGCCTCTGCCATTTGGTTGCCCTCCCTGCGGTCCAAGGGCCTGGAAC ACTCCCCAGGGCTGCCAGGCCAGCGCTTTCCAGGGGCTCCAGCCTACAGCGCCGCC ACCTGGGGCTGGAGCCAGAAACGCAGGGGCCGGGGGCTCACCGGCTGCCAAGTAG AGGGCGTCGAAAATGGGGCTGGGTGTGTAAGAATGCTTGTGATTTTTGCACACTGAT TTTGTATCC >6:79946660-79947835 (SEQ ID NO.: 78) GATGAAGGAGCTAGATAGAAGAAAAGATTAGCAGGGTTCTGTCAAAGCGACCAGG AGGCTGAAGAAACCTCCTGTACCTTCAGCTGCCCCTGAAGCCCTCCTTCCTCCCCAG CCCGCTCTCCATACAAAATAGGACTAAATGTTAAAAGGAATCCTGTGCACGGGGAA GAGGGAGGCGAGCTCGGGAGATGTGGGAGCACAGGGTGGGGCGGCTCCTGCGAGG AGCTCCTGGCTGCACAGGCTCCATCTGATATGTCAGCTCCCGCATCCGAGAGCTGAT GAGAGATGGAGGGAGCTCAGAAGAAAACCCTGCGAGTGTCGGGGGAGGGGAGGCC TTAACATTCGGATCAGATTAACCAGTGCTCAACCGCAGTGCCCGCGCCGGCCCCTCC GCTGATCCGCAGCATCCGAAAGCCGCAGGGCGCGGGGGCCTGTGGGGCCGGGCCCG GGAGCTGCGAGACCAGGGGCCGGTGACCCCCCGCGGGGGACCGAGCGAGGATGGG GAAGTCAGCGGCTTTACCTGCGATGGACCAGGTCCAGCGGTAGAACTCTACCGTGTC GTTGAGTGCCGTGGACACTACGTTTAGGACACTACCCGGCTCCGAGTCCAGGAGCCC CATCGCGGCGATGAGCGGGCGCTGGCGGCAGGAGAAAGCGGAGACCCAGAGAGAG GGCTGACCCCGGAGGCGGTGGCGGCCGACGGGGCGAGCGGCGGCCGGGAACCCCT CTAACGGCGGCGGCCCGGCTGCGTCTTCTCCTGCTCCTCAAGGCGCCGCGGCGGCGG GGATGCGGCAGAAGGCAGGGCCAAGCGGAAGGCGTCGTCAAGGTTCCCGGGAGAA AGACGAGGAGGTGGAGGAGGCCCAGCCGCCAGCACAGTGCGCTGCACCAGTCTGCA GCCTCGCGCAGCCGCCCCTCCAATCTCCTCAGCCGGCGTCACGTGGCCGCGCGCGGG GGCGGGGGGCCGGCCGCCCCTCCTCCCTCCCTCCCTCCCTAGTATTGGGACTCGCTG GCGTAGGGATGCTGCGCTCAAGGGTGCGACGCCAACTGGGCTCGCGCAGGCGCGCG CCGTCGAGCGGGAGCGGGACACCTGGGCTCCTCCTTGGCCCCTCCCCGCACAAGTCG CCTCATTAGCCTTCCCCGCCCCTGTCCCGGGCATCGGCCCCTGCGGAGGAGTTC >6:123803435-123804335 (SEQ ID NO.: 79) CAGCCCCTGCGGTCCTCAAAGTTGGCCCCCTGGGAGGGGGCGGCAGGGAGCAGGAT GAAGGATTTGTTGTAGGAGGAGGATTCACACATCTGGGCGAAGGGAGGGGCAGCGC CGCTGCTGGGACGCGGCGCGGACCCGCATCATTGCGCGCAGCAGCCGCTGCAGCAG CCGCCGGGGACCGCGGAGCCGGGACGCCCCCGCTCGGCCCGCGCCCCGCTCCCCGC CCCACCCCCGCCCGCCGGGCCCAGCAACGCAGGGTGCCTAGGAGCCGCGGGCTGCG CAGGGAGGCGGGCAGCGGCCCTCGCGCGCTTCTGCCGCCCCCGGAGCCGGCGCGCG GCGAGCGCAGGGCGAGCGCGCGTCGGGCGGCGGCCGCGCTGGGGGGCGTGAGGCG AGCGGCGCGGAGAGCGGCAGGGGCGAAACTTCGCGGGCCAGATGCCCGAGGGCGC GGCGGCGCTGCCAGGCTGCCGCTGCTGCCCCTGCGGGCCCCGAGCGCGCCTCCGCA GGCGGCACTGCCCGCGGCGCGGCGTGTGCACCGAGCGAGTGAAGGTATGTGTGGCG GGCGCGGCTGGAGCTGCCGCCGCCGCCGCCGCCGCGCCAGCAGGTCCTAATGCCTG TCACTTCCCAGGACGCTGGCAGCAGCAGCAGCCCGGAGCCCCCGAGCCCTCGGCAG GTTTGCGTGTCCTTCCCCGCGATCTGATTGGATAAAGTGGGGGCTCGACGGTGGCCG ACGTGGGACAGTCTGGCTGTGGCAGGGGTCTCGGAAACCATGGGTTATTGCAGTGG CAGGTGCACGCTTATCTTTATCTGTGGCATGCAACTGGTAAGTGACACTTGGGTCCC CTTATTCTGTAATGTGTCTTTGAGATAGTGGGCAGGGGAGTGCAGCAAAGGGTCTGC CATT >6:163413139-163413679 (SEQ ID NO.: 80) ACTGCCGACTTCTATAGATCAAGGACTTCATTGGTGCAGCTGAGGAAATTCTTCCAA ACAAGTCTAAATGTTGGAAATCCACCAAACTGCAGAGAAAGACCTCTTGCCTCCGTA TTCTTTCTTCATCTGTAAAAATGTTGACTTCTGCTTTTCAGACTACGCGCACAGCCTC TTTATTTCCTACTGCGGCTTCATTCCCTCACGGAACACTGACGCCATCGCGAAGGAA GCATTTCGAGCACGACTGACGCTCCCCTTATTATTTGCTAAGCCGCTGCGCTCGGGT CTGGCTACGATTTGCTTTCAGAATAACGGGAAGGTGCAACAAGATCGCTTCCCTAGA GGCGCGTCGCCCGCGTGGCCCGGACCCCCCACGCCCGCCCGCCGCCCCGTGGGTGC GCACGCGTGTCCGCGCAGGCTTCCCGCCTGGCGAGTGCAAGGCTCCTCTCCGCCGTG CTGCTTTCCAGCCTCTCAGCAAATCACGAACACCGAAAGAAGCCACGGCGGCGACG GGAGGGGCGTCGCGCGTGCTTCCCTCGGC >6:170736319-170736619 (SEQ ID NO.: 81) TGGCTCAAAATATTCAAAATTTTTTCCAGAGTTTGGCCTTTTCTTCAGCACTGGGAAT TGTGATCCAAAGCTTTTCCTGATGAGGCACAAAGTTGGAGAAACAAAACGCAAACT AAGCAACAATGAAACAGAACAGAGTGAATCTGCTGTAGCTCAAGAGAGGACGTAGC TGCCCCCACTCCGCATCCCCGGGCTCGGGTTTGCCTTGCTGACCTCTGCTGCCACCTG GTGCCGCACAGAGAAACTGAGGAGAAACCACATCAGTCTCCTTCAGCCTCAGCTTC ACATCTGTGGTGGGTCA >7:24284003-24284543 (SEQ ID NO.: 82) GGGCGGGAGGGTTGGGGTGTGGGTGGCTCCCTAAGTCGACACTCGTGCGGCTGCGG TTCCAGCCCCCTCCCCCCGCCACTCAGGGGCGGGAAGTGGCGGGTGGGAGTCACCC AAGCGTGACTGCCCGAGGCCCCTCCTGCCGCGGCGAGGAAGCTCCATAAAAGCCCT GTCGCGACCCGCTCTCTGCACCCCATCCGCTGGCTCTCACCCCTCGGAGACGCTCGC CCGACAGCATAGTACTTGCCGCCCAGCCACGCCCGCGCGCCAGCCACCGTGAGTGC TACGACCCGTCTGTCTAGGGGTGGGAGCGAACGGGGCGCCCGCGAACTTGCTAGAG ACGCAGCCTCCCGCTCTGTGGAGCCCTGGGGCCCTGGGATGATCGCGCTCCACTCCC CAGCGGACTATGCCGGCTCCGCGCCCCGACGCGGACCAGCCCTCTTGGCGGCTAAA TTCCACTTGTTCCTCTGCTCCCCTCTGATTGTCCACGGCCCTTCTCCCGGGCCCTTCCC GCTGGGCGGTTCTTCTGAGTTACCTTTTAGCA >7:26377180-26377360 (SEQ ID NO.: 83) GAGGACAGAAGGGGGCGCTGCCGGGCCAGTGCGGAGGCTGCAGCCGCCCACTGCA GAACGCGCCCTTGGTTGGGTCTGGCGAGCTGCCCGCGTAGTGGAGTGGTGTTAGGGC TCCCAAGTAGAAAGAACCTGTTCCCTACGTAGGTGTCGGTTGTACTTAAGAGCATCA TTTGGTCGCTCG >7:27174216-27174696 (SEQ ID NO.: 84) CCAAAAAAGAGTTCGCGGCGGGGCTCTCCGAGCATGACATTGTTGTGGGATAATTTG GCGAAGGGAGCAGATAGCCCTTTCTGGCTGACATTTCTTGTGCAAAACATGCTGAAT ACGATTAGCAATCCCCCCGCACCGCGGCGGGCGCCCGCAGCCAATCCCGAGCCAGA GTTTCCGCGCGACCACTCCCAGTTTGGTTTCGTAGGCGCGGGGCCGCTCTCCGAGGG CGCCCTCAGAGCCCGCGATTGATATAAATATGTAATCTGTATTGATGGGCCAGGAGA CGCACCCCGACACCTTGGCCCGAAGGCCGGGAGCTGTGGGGGCTGCCCCAACGTGG CTGGTGGGGGGCCTGGCCATTGGGCTCGCCCCGCCCCTACCCGGACGTGAGCCCCAT ACCGGGGTCCCTTAGAAGGGCCCTTGGGCCCCGCGCAGTTAACAAGTGGGGTGTTTA TGGTGCGCGCCCAGTCTGCCTTGGGTG >7:28957467-28957647 (SEQ ID NO.: 85) GAAAGCGGATCCGGTTGGACTCCAGATGTAGGTAGAGCAGGTTGCCCAAGGGAGCG AAGACCGCGTCCGGCAGCGCCCCCAGGGCGTTCCCGTCCAGCCGCAGCTTGACTAG ACTCTCCAGGCCCTCGAAGGAGCCGCGGCTTAGGCGGCTGATCTCGTTCCCGTTGGC GTAGAGGATGCG >7:35257235-35257535 (SEQ ID NO.: 86) CCACTCTTTCAAATTCTCATTTGTAGCTCCCGGAACTCAGAAGACAGTCGACCCCCA AAACTGTCCAGGAAGTAATCGGTTTCCGGCTTTTGGACAATGGTCCCTCGCTTAACG AATGCTAACGAATGCTCCCTTAGCTGGGAGCTGCAGGGACCGGTCCCGGCAGGTCT AACCAACCGTCCGCAGGCGCCGTGGTCGAGAGCAGAGCCGAGACGGCGGGGCAGG GTGCCAAGCGGAGGGCACAGCCTGGCAGCCACCGTTGGCGGCAGGAGAGAATGGG AGAAGGGAGACCCGCTTCTCA >7:35259057-35259357 (SEQ ID NO.: 87) CGGGACTATTAACCTGGAACCCCAAGAGGGGGAGAAAAGCGGACAAGGGACACGT TTCCTGCTTCGAGATGAAGGTCTTGTTGGCTGGGTGCCCTGGCCTGCCCGGGCGGAC GCGTGGGACCTGCGTGGATGGCGCACGCTGCAGCCAAACAGGCTGCCCGAGGGCTC TTCCTGAGCGCAGTTCCTCCGGTGTTTAAAAACAAACTCAAACTAAGTGAGAGTTTC TCTTTGGAATCGCTTCACTTGGGAAAATGATCCAGCCTTCCACCAGCAACTGTGCAC TGTCCCCTCTGGTGACTGC >7:50303675-50303855 (SEQ ID NO.: 88) TCCAGGGACGTGAAGCTGAGCGTACAGCGGGCGCTCCCAGACACTGGGGAAAGTGC TTTACGATGTCCCGAGTCCCTCCAGTCTCGCCAGCGGGGCGAGCGTGAGGGTGCCCC GACCGACCAGCGGCCCCGGGTGCAGGGTGGCGGGCCCGGCGGCGCGCGTCCCCCTC CCCCTCCTGGCG >7:64889447-64889627 (SEQ ID NO.: 89) CTCACCTTTCCTGGGGCTGCGTCCCCGCGGGACGCCAGGTTCCCGGTTTCTTCTAGGT CGCCCTGGTTCCTGGCAGCTCCTGGTGCCACGCGGTCCTCTACGGTCTCCTCTGACCT GAGAGGGACAGTGAGATGGGGCTGGCGGGGATGGGGGTCCCCGCGCTGTTGGAAA GCAGCGGGGC >7:90596855-90597335 (SEQ ID NO.: 90) GTGCTAGGGACCCGGGGGAGGGCAAGGACGTAAAGGAAAGAGACCCCTCTTCCTCA GGATCTGGGGGTTCATTTGTAGATTCTCTCAAGCCTACAATATGGGTTCTCCCCTCCT CCGCCACTAGTGCTCGCCCTTTCGCGCGCGTGGGGGACGGGCGAGGGGACCCCTCG GCCCCCACCGCGCAAGGGGCTGCGCGGCTGCTTGGGCCACTTGTTATTTTTTGCGCA CAGGCTTGGATATTGGGCGTTTAGTCAGTAATTTAGCTTTGGAAATTGGTGAAACGT TAGACTGTGCCCTGGTATTGTTTAACGTATCCAACCTAAAGGGAAGTGGGACAGTTA CCTTGGGACCTATTGTTCGGTACTTCGGGTCCTGGAAAGCGAGATTTGGGTGTTCAG TCTCGAGGTCTCTGAATCTTCCCGCTGCTGGAGAGAAATGCGCGCTGTGGAGTTGTC TGGACATTTAGGAATGTCTCTCGAAC >7:93890873-93891053 (SEQ ID NO.: 91) CTGCAAACTGTGTAAGAGGGAGAGGAATTCCCCGCCAAGTTGAAAAGTTGAACCTG CCTCCCAAACTTTCTCCTGTAGTCCAGACGGGGACGCCCTGAGGGAGCGTTTGTGTC AGTAATGGGAAATCTGCAAGCTAGACGGAAATGACCTGCTAGTGATTGCGCTGTAA AGAAGCCGGAAT >7:96997902-96999222 (SEQ ID NO.: 92) CTAGAACCCTAAAAACTCCTTTGGCCTCCAGAAAGACCCCGGTGCAGCTCTCTACCC TAACCCCTAAGCCCCTCTCAAGTGAGAGCCTCTCAGTTAGTACTCAGTTGCCACGTC TCGCAGGAACTTTGGAGCAAGTTTTCAGCTCCCAGGTGTCCAACCTTTAAAAGGAAA AGCATAATAATACTAACCTTTCTTTCACGACCACGCGAAACGCAAAGGATGTGGAGT GGGGAGGGGAGGAAAAAAAAAGGGGCGGCCAGCCAAATCAAAGCTTGGGAGACAT TTTGACAGTGCGCTTGAAATAATGCTCTTAATTTTTGGAAGGTTTTCAAGAAGGGGG TGGGGGGCACGTGGGAGAACCACAACTTTCTCCTGTCTGTCACTCAAGCGGCCAGA GAGGGCTCCAACCTCCAGCTCCCGCGGCAACACACAGTGGGAAATTGCTTCAAGAT ACAGTGGGGCTCTATTCTTTCTCTACCCCTGCCCCGCCTTTCCCGAGCAGTGAACTTC ACAGAGAGGGTGGTAAGGGAGGGTTATCCTGGGTGTCAAAAATCTGTGCATAGCCT GAGATCAGAAGAGTTAACCCCAGGCCCTAGACCCAGCCCAGCGGCCAAACTGGCAC CCCGTGCTGATCAGCCCCCGCATCCCCATATCTGCATCCCCATATCTACCTCCCCAGT CGGGGGTGGTGAGGTTTGGGGGAGGGGGGCGACACTACCATATGCATCCACCACCT AAGTCCAGCCCAGGCTGGCTTCAATGAAAGCTGGCAAATCCGGCGAATCTCGCAGA AATTTTCTTCGAACTTAATTCAATTTTAAAGTGGATTTTTACTATTAAAAACGCTGCC GAGCAACACATTGAATTAATCTGACTGTACGGTTTTAATTACAGTGAGGGTTTCTCT ACAAATCTGTACAAGACAGTGGCTGGTTCTTGGAGGATCTCTGCCTCCTGAATTCCA TTATCGGGCCCCTGGTTCCCTGCAGACGGCAGCTCGTGGGAGCCAGCTGCGGTGCGA GCGTTCAGTCGCCCTCTGCTTCTGCCGGGCCTCCTGGCTCCTGTCCCTCCTCCCTTCC TTCATCCCAGCCCCATGGAGAGCCCAGGATTCCTGCCTGTCATTTGAGACTGCTGAA CTGATATCCTGAAACGCTACCCTTGCTTTTTAAACTCTTGGGCCCCAGACTTTTGAGC CCCCTGAGCATCGTTCTTAAAGTGGCTCGTTTTGTCTGGGAGGGTGACCTCTTGTGTA GTGTTTTTTGAAGGGTTCTCCTGCTTCGACTTAGCAGCTGTTAGAGTGGGCAGCGTG ATGCCCAGTCTG >7:97020672-97021092 (SEQ ID NO.: 93) TATGATTTTCTAGAACAGCAAAACACAGTAGTCCCAAAAAAGAGAGTAAGAGAGAG CAGCCCATCTAATAGAGTGTCCCGGAGGCCAGCGCCAGCGGGTGCTGTAAGGAGCC CGGCGGCGGCAGGTGGGAATTGATTGAGCTGGCTGCACTTGTGTACCAGGATGCAG AGTTCTCCAGGTAGCTGGACGCTGGGGACTGGTTGGAGGTCGGAGGGTGGGCATGA GGGTGGTGGCTGAGCGAGCGGGACGAGCCCTGGGGCTCCCACACCGCTGGAGACTG CGGCGAGTTACACGCCATTGGGTCGCTGGAGCTGGGACTGTGCTCCGGGGGCATCTC CCCGTTTTTCATGATCTTCTTGATCTTGGATCTTTTGTTCTGAAACCAGATTTTCACCT GAGTTGGGGAACAAAGGCACACGTT >7:103988969-103989749 (SEQ ID NO.: 94) CTCCACTAACTTTATTCTCGCTCCCTGGACCAAGCGCATCGCTGGGGCCAGGGTTGT CATGGTTCTTGTTTCCAAGGCCCCTTGGAAGAAGGAAAGGGATGAGAAAGGTGCGC TGGCGGGCGCACCCGGCGGCGGCGAGCGCGGAGGTGCTGCGGTACCTACCATGGTA TTCTTGTCCCGGAACGTAGTAGGTGGGGTTGCCCGCAATATGCAGGGAAATGAGCA CCTCGCCCTGCTCCCCATCCCCTTCCAGCTCCCCGTGGTGGGTGCACAGGAAAAAGA AGGGCGAAAAGCGGGGGTAATAGCCAGCCGCCGCGCGCGCCCTCAGCGTCGCCCCC AGCAACAGCGCTAGGAGGAAAGTCTGCCGGGCCCAGCCACTGCGCTCCATGCCGCC GCCGCCGCCGCCGCCGCCGCGCGCCCTACGCGCCGCTCGCTCATTCAGTTTTGGAGA CGCCGGGACGGAGGAGCCACGCGGAGAGAAGGCGAGAAGAAGGCGGACGGGAGC GGAACGGGCTCGGGAGCGGGCCTGGGAGCGGGCCCCCGCCGAGAAGTTCCGCGGG AGACGGCGGCTCCCAAAGTTACTTTGGGCCGCGGGAGCGCGGGACCGGGGCTGCGG GCGCCGAGAGCGCGTCGTCTGCCGCCTCCGTGCGCCGCCGCCGCCTCTGCGCGACGC CCCTCGGCCAGGCCTGGGAAAGCGCCCGCCCCGCTCCACACCTTCTTAAAGCCCCGG GCGCCGCGTCCCCCCCGCCGCCGCCACACGTGTCCCGGCCGCTCCCCCGCC >7:107660513-107660693 (SEQ ID NO.: 95) GGGCTCTGCTCTTCTTTAAGGAGTCCCACAGGGCCTGGCCCGCCCCTGACCTCGCAA CCCTTGAGATTAGTAACGGGATGAGTGAGGATCCGGGTGGCCCCTGCGTGGCAGCC AGTAAGAGTCTCAGCCTTCCCGGTTCGGGAAAGGGGAAGAATGCAGGAGGGGTAGG ATTTCTTTCCTG >7:122300668-122301028 (SEQ ID NO.: 96) CTAATTACCCCTCTTAATTAAAGTCTTTAGCAGTTGTTTCATTGTTTTGGCAAGAAAA CAGGAGAGACGTGCAGTTAGAAACACCAGAGCCCGAGCTCACAGCGGAGCCGCTG ATTAACACTTGAAGCATTTCAAGGACCTGGCACCCGCCACAGTTTGGTTTTCATCCA TGTTTCCTCCTTGAATGGAAGTATATTCGTCTATAAACATACATACACATGTAAAAA CACGGAGGCTCCGTTTGCCAGCTGTGTACAAGTCAGTATGTGCCGTCAGGATGCAAA CAATAGATACCTGTCTATCTATGATTGTAATGCGTTTGAGGAGATGTACATTGCATA CAGCTACTGGATACGTTGTT >7:134458200-134459460 (SEQ ID NO.: 97) ATGTTTCATGTCCTATTGTCATTCTCATCCGGCTAGGCACTTCTCGGGGACGCTGTGT GGTGTTGAGGTTTTACAGGGAAAATGCTAACCTTGGCGCCTCCTGAATTATCAACTA GCTACGGGGTGCCCAGATTTTTCTCCCGAGTTCCAGACCCAGGGCACCCCGAGGCGG CGCCTGGCCGAGGAGCTCCGCACTGCGCCTTGTTAACAGCTGGGTCCGGGCAAACTC GCGCCACCTAATTCTCTGCCCTCTACCGGCTTGAGATGCTTATTCCTCAGGGAGGGC AAGAATCGAAACGATTGAGACCAACTATTTACAAGTGAGGCAACCGGGCTACAGGT GCCTCGAGGGAAAGGAGGCTGGGTCTGCGCTCCCACACCTTGCCGACGGCTCCACG TCCCTGTCTGCGCCCGAGGTCCACCGGTCTGTGAAGCCCACTTTCCCCGCCTCCCTCT CGCGTTGTGCCGCTTGGGGCGCCCGCTAGGACCCAAAATGCGGACTGGTGGGCCGC CCATCAAGGGTTGCCCGCGGTAGGGCGGGGGCTCCCGTGAGCTGCTCCCAAACCCC ACTCGCAGGATGCTGCCCTGACGCCCAGGGCCAACCCGGGGAGCCAAGGCCCCCGG TCTCTGCAAGGCCGACCCCAGCCCGCTGGGGACCCTGCAAGCCCGCGCGTGGCTCCC AGCACGCCGGGCGTCCGCGGGGCGAGCTGCTCAGGGTCACTCGGGGTCCCTCGCCA ATACAGGCCGCGCGGAGAGTGTGAGGCGAGCCCCGGGCCCGCGCCCCCACGAGCAC CTACCTTCCAGGTACCCAACCCCAGGATGGGCATCTTGGCGCCGTTGTTGAGCAGGA GACGGCTTGCCATGGCTGCTGCGCTCCCCAGACCCCCGCCCAGTACGGTGCGGCCTT GGCCGCGGCGCGTACCTTTAAATAGCCCGTGAGGTCGGCAGAAAGGGCGCCTGCGG TTGGCGCGCCGCTGCGCGAAGGAGCCTTCTGATTGGTTGCGCTGGGGGTGCCGCGGC GGCCTTCCCCAAGGGTCGGCGGGGATGCTTCTTCCGCCTGGTCCTAGTGGCAGCGGA TTCTTTCCGCCCCCAACGCTCGCCCGCGCCCCGCGTGGCAGAAAGGAGTTCCTCAGC TGCTGTATCTGGTGGGAAAGCGAATGCTTTAGCGAAAATAACAGGCATCCCATAAA TACATAGACTAGAAATAAGTTTTGGTTTCATTAAGAGCCCAGAAGAATGCCTTTGTT GTCCAACCCCAGTT >7:139434580-139434880 (SEQ ID NO.: 98) TTGCAGCCTGTTCCTGTTTTTTAAAAGTATTTATAAAAGCTGAATGTCAATTTTCTAC TTAGAGTTATAAATAGAAGCAGATGCTCTGGTTTGTTGATCAGCACGCTGTGTTCTT ACAGGGGAAGTCAAAGAATCCGAAGTGTGCTTGGAGCATAGAACTAGCGCAAGAG GGCGCTAGTGAGGCGGTGCGGCGCGGGCGGCCAGGAGCTAGGGTTTGAAAACAGAC TTCGGTTTGAGCCCTGAATCTGCCACTTAGAAGCTGTGTGCCCTTGGGAAGCGATAA TAATACATTTACCAAAGT >7:141072108-141073057 (SEQ ID NO.: 99) ACTCCGCAGCCGCTCTCAGCTCAGTCCTAGGTGGAAACGCCTGTAGCTTGCAAGGTA GCGCCTGTGGCTTTCTGGGGAAAAAAAGATCAAATGCCTCCCAAGACACCAGCGAC CCAAACCGGGGATGCAGGGAGCTCGCTTGGCCCCTTTGAAGGCCGACTCCGCAATA AGCAGTTTTTCCTTTAAATAACCGTAGTGGATTTGAGAGAATTTTCCATGGCTGAAA AGAGAAACAGGAGCTGTAGGCAACATCCCTAAATTTATAATAATGCATGTAAACAT GCTACATACCACATATATGTATATGTGCATAAATATGGATGTGGTTGGGCACATACC TATCTAGACACCATTGACTTGCCTGGTCAAAGAATAAGACTTAGACATTTCGTGCCT GGGAAATGGTGCAGTTTATCTTTAAGGAGACTAGAAAAATAAGAGATGAGGCTCAC GTTGCACGGATGACATCACTAGCTTTTGGCTGCGCGCTCGGTGTTCTCGTCTGTGGGT TTTAGCCAAGGCTGCAGCTACCCGCGCCGGACGAGAGAGCGCGGCAGCAGCTTCCT CCGGCGCCCGCACCCGGGCAATGCGATTTCCCCAGTCCCCTGGGCGCAGCCTGGGCT CTCGCGCCTCCCGGGCACCAGCCGAGCCTGCGAGGCCTCGGAGCCGCCGCGGCTAG AGGAGGAGGCGACGAGGGGAAGCCGAGTGACCCAGCCTCCCTCCCCCACCCTCTCC CCATTCATCTCGGCGACCACCGCGCGCCGGGAGCCGGATCGTGGGACGCCGAGGCC AGGACGGGATTCTCTGCACGCTGTCGAGTGAGCCGGCATCTCGGCGCCCGGGTGGG CTGCGAAGAAAATGGTGCAATCTGAGAGCGACTGAGCCCAGCTGGGCAGAGCAGAC GGGGTGCCAGAGTGCCAAGGGCTCAGGTGCCTGGAGAAAGGGGCGGA >7:143345452-143345795 (SEQ ID NO.: 100) GGAGTGCGGAGCGCGGTGGTGCGAGAGGGCTTGGAGGGGGCGCTCAGGCAGGGCG TGGGTTTCCCTCAGATTCAATGATCCTGCTGGGCTCGGTGGAGCGGTCGGAACTGCA GGCCCTCCTGCAGCGCCACCTGTGTCCTGAGCGCAGGCTGCGCGCAGCCCAAGAGA TGGCGCGGAAGTTGTCGGAGCTGCCTTACGACGGGAAGGCGCGGCTGGCTGGGGAG GGGCTCCCCGGCGCGCCTCCAGGCCGGCCCGAGTCCTTCGCCTTTGTGGATGAGGAT GAGGACGAAGACCTCTCTGGCAAGAGCGAGGTGACCGCGCCGGGAAGGGCTAGGG AGTGGGAT >7:157336263-157336683 (SEQ ID NO.: 101) GGGATGACCTAAAGTCCAGCTATCAAAATGCGCCGCGTTTTCAGAAAAACTACTGCC ACGATTTAACCTAAAAAGCTTCATCTGTATTTTCTGCCACAGTTTGCTTCCGTTTCCT TCAGTCACTATTCCCTGGCGAAGTCTCCACGCGCTCCCGTTCGCCGGGGAACTTAGG GTATCCGGGCTTCCCTAAATTGACAAGCGGGGGCCGGCGCCTTCGCCCGCCTTCGCT GGCCGCCGCTTGGTTTGTTCTTCTTCTCCTTCGGGGACTTCTCCGCCCGCGCCCGCGC CCGCGCCCCAGCTTTCGTCCCGCTGTGCGGAGATGCCACCCAGCTCCACCGCAGGAC CGCGGAGCGAGAGGCGGCAGACGCGCTCCGGGGGCCGCCGGTCAAGAGGAAGATG AAGGGCGCGACGACTTCGCGGT >8:23163898-23164198 (SEQ ID NO.: 102) CTCGAGGCGGTCGGGACGCTTTGTCCCCAAAGTCCCATGAGAAGGGAGGAGGGTGG ATCGAAAGCGCCAAAAATCAATCAGAAATCGTCCCCGTAGTTTGTGCGCGTGCAAA GGTTCTCGCAGCTACACTGCCAGAATAGAACGTGCTCCTCCGCTTTTATACCCCGGA AAAAAGGCGTGGTCAGTTGTACTCCCTTCCCGCAGTCACTTCCAGGCACTCAGGCTG GGTCTCCCCCAGCACCTCCAGGAGGGCCCAGGTTGTGTGGGTGGGTGCATGGACGG ACAGGAACTGGCTCTTTCC >8:39107409-39107589 (SEQ ID NO.: 103) GGTGCAGGAGAGCACACGCTGACTGTGAATAAGTGTGTCAGTTCTTAAGGTCCAGC AACACAAAGCGAAAAGTTAGTGGAGGACTACGAGCGCGATCTCGACAGAGGGCGCT GGGTGGTCAGTGGCTCCAGCAACCACGCGGCTGGGGTGCGCCGGGAAGGGAGCTGG ATGTTTTAGCCTC >8:41828830-41829010 (SEQ ID NO.: 104) GGGCCTGGGAGGCTGCGCCTTCTTCCCGCGAATCCCGAAAACTGCGCGGCAAAGGC GGGTTCCGCAGAAGTCGCGCGTGACCCGGGGCGCCGCCCTCCTCGGGGCCCATTCG GATCTGCCGCCCGTCCTCTCCAGAGCGCCCCCTGGCGCCCTCTAGGCCATCTTGATT CCACCGCCGCAG >8:52564305-52566225 (SEQ ID NO.: 105) CGTGTCCTGCCCTCCTCCCTCCAGCGCTGCCCCAAGTGCCCGGCCGCCCCCTCGGAC CTCCTTTTCCAGGGGCTTTTCCGTGTTCCCCGTATTCACACGACTTCTCTGCCTGTGG ATGTCTCATGACCCTCTAGAGCAGCGACTTTTTCCTCCCTCATTCCTTCCACTCCCCT CGGGCATCTAAGTAGCAGGAACCTGACTGTCCAAAGTTGATTTGGGAGCAGCCGGC TGCCCTTCTAAAATGATCTAGGAAAGGTGCCAGTAACATAAGCCGCCGCCTGCTGAA ACTGGCGCTTCCTCAGCCACTCGCTGCGGCCAGCGTGAAAGGGGAGGGGAAAGGGG CATTCCTGGCACGGTCAGGTGTCTACGGACAGCAATCTTAGTTAATTCTCAAAACCC CGGAAGATCCAGAAATGGGGTGCTGACAGGGACCTAACCTGTCCACCACCCCTCGG TCGGTGGGACTGAAACCCATGTCTTTGAGCTGCTTTACCAGTTTATTTCCAAAAAGT CCTCCTACACCTGGGAAGGGACATAGAAAGCTGATCCCATTGCCAGCCGGATTTCTT TACTTAACTCTCAACCGTGGTAAATCTAATTCGCTTACGACCTCTTTCCGAGAGCTGG GAATCTGCAGAGATGCTCTGTTTTCTGCTGTACTAATCTCAGGCTTCCCAAAGCGAG TGCCTCGCCCAGCTCCTAGGGGAATCCACGGAGCCCCAGGCGCAGGGCAAAGGATG GGGCGGGATGGGGACATCGTACCTGCGCTCCGGGAGCCGCTGGGAGTCCGGCCGGC CCCGGCCGCGGGGAGGAAAAGCAACGGCTTGGGCTCCTTATCCGTGACGCGCGCTC CCCTGCGCCCCCGGGGCCTCCCGTGGGCTCCGTGCGGGGACAAAGCCAGCGCCAGC AGGAAGAGTGCGGGCAAAGGGGCGCCGGGCTTAAGGGGCCGCATGTTCGCAAGCC GGGAGGAGAGAGCGGGAGACTCCGGGAGGATCCCGACGCAGGTCCGGAGGGTGCG CGGCCCAAGAGAAGGCCAGCGGGACCACAGCGCGGCTACGCGGCCGGCCGCAGTCT TCACCGCGCGCCTGCCCTTGTCTACGTCCCGGGGGTCGGCTGGAGCTGCACTGGGAC TCGGTCCTCAGTGTGCCGAAGCCTAAGCGCTGCGGGGCGCGGGGCGGGAACGGGAG GCGGTGCCTGGGGCCACGGGGTCGTCCCCCAGGATGAGGGCGTGTCCCAGCGCGCG GGACCCTCGGAAGTCCGCGCTGGGCCGGGCGGGCACCAGCCTCGGACTCAGCGGGT CTCAGGGCTCCCTGCGCAACGCCTGCCTCGGATCCGGACCCCGGGCTCGCTCTCTGG TCGCCGTCCCCGGGAGGACCCAGTAGGGTAACTGCCGCGTCGCCCCGGCGGTTCTCC CTGGGCTCTGTCTCCCGCCGCCTCCACCCCCCGAGCCTCGGGGTCCGTCACGGCTTC CCCTGGCTGGCGGGGTCAGTAGAACCCGCGGCGCCTAGGTCCGGACGGAAAAAAGC AGGGCCGGGGTGCGGCCTGGATGAGCGGAGATCTCCGCGCCTTGGGCTCAAAGGTG CGGGGTGCGCTCTGCTGCCGAGCCCCTGCTCGCTCAGGAACACTGGCCACGCCGTCA CGCCAGCCGCCCCTGCCCCAGGTCTGGAGGCCCGACCTGCTCTCCTAGGCGCAGCAC CGCGTTCTCTTCCGCGTGGGGGAGCGGCGGGCGGAAGAGGTCTGGGGCTGGGCACC GGGGACACGCGCCCAGCTCCCCTGGCCTCCCTGGGGGGAGTGGCCGGTTTCAGTGCT TCCCCAGGTGAAATCGCCAAGGTTGACCAGTGCGCCCAAAAAAGCAGCCGGCTGGA TTTTTCTTCAAATTAGGGAACTCTTATAAAGAGTTTTAGTGTTAACAACTTAAAAA >8:69994687-69995047 (SEQ ID NO.: 106) CCCTGTGTGAACCAACGGGCGGGCAAGGCGCTGCAGGGAGGGACTCCAAAGACAC ACGCGCGCAGCCCTCCTCCCGCCCGCAGCCCTTCAGCTGCTACAGTGGCCACAGCTA TTCCGAGGTCTATTCCGGCCTCGCCGCCGTGGCGAGGCTTGCGCATGCGCACTGGGC GCCTGAATAATGGCTCAGGCGCCGGCCCTGCCTGCGTTGCCCGCAGGCCGGAGTCCC CCACCCTGCTGCGGGTTTATCGCTCCAGCTCATGCTCATACTCCTTTGTACCATGGGA TTTTACTTACAAAACAAGTTCAACGATAAAATAATTAAGAATTTTAGGAGTGCAGGG GCCGGGCGCGGTGGCTCACG >8:72004794-72005334 (SEQ ID NO.: 107) ATACCCCATAAATACTGATTGGCTATTACGCGCATAACGTGAGATCAAAAGGAGTTC CTACAAAGACCCTTAAATCCTCCAGACTTCTTAAGCTTAGGAAAGATTTTTGCTTGG TTTTCGGTTTTCTTTTTCTTATTTTGAGCAGCAGACCAGCGTGACTCCACAGTTTCAA AGAGCAAGCGTCTATATTTGTGTGACCCGGGGCCGAGCTGGGGAAGGGGAAGCAGA GCAGCGCTGACGCAGTCAGGTCCCTGGTGCAGGTGCCAGCTCCCCACAGCGCGCCG AACTCCCCAGTATGAGCGAACCTCAAGTCACTGCCCTCGCGCTTGTCGAGCGAACTC TCAAGGCTTGCAGGTCGTCTCCAGGAGTCAGAGAGGTCCGGACTCCGGGGATTCCTG CTCCGCGGAGAACTGGGGAGCCCCCGTTCCTGTGCCACTCTCAGGTGGGGTGACTTT GGGCTCTGGGAAGGAGAGCTGTGTCCGTGTCACGAGGGGGCCCCGGCAGGTGGCGA GCAGCACCGAAGCGCGGGCCAGGACGCTCG >8:96145538-96145718 (SEQ ID NO.: 108) AATAATTACAGTCAGTTTCACTTAAGGGGGAGATCAGCCCGGTGCTCTTCGGCCGCC CCGGGAGGAAAAGGGCGGGGAGTGGGGGCAGGTCGGCCGGGCAGTCCAGCTTGCC CGGCCCAGGGCCTGACCACCCCGGCTCCCCATCTGGCTGGTGCATGGCGCGGGGAA GGGGGCGCGCCAG >8:98951181-98951931 (SEQ ID NO.: 109) GAATGTTGTTCCTTAAGAGAGGATTAGAGTTTTTCCTTCCCCCTTTTCCTGCCTATGA CATGGTGATGAAATGTGAAGAGCTGGAAATCACAAAGCCCACCGAGGTGGCTGCGG GTCTGCCTCCGAAGTTATCAGTGTAATCGGGCCTCTGTGTATGCCTGCACGTGTATTT TCATGATTGGAAGATTAGGAGCACGGATTTGTTCCTGCAAGTCTCCTCTTTTGTTGTC ATGAGAGTGTTATGTTAACGCTTGTGATAACGATAAGACAGAAACTATTGAAAAGG GTGCAGTGGTGGTGTGAAGGATTAATCCTTTGCTTGCTTCACATCTGAACAGGAATC TCCACACAAATGTCCCACATGTGGAAGAACCTTTAATCAGAGAAGTAATCTGAAAA CTCACCTTCTCACCCATACAGACATCAAGCCCTACAGCTGCGAGCAGTGCGGCAAA GTGTTCAGGCGAAACTGTGATCTGCGGCGGCACAGCCTGACTCACACCCCGCGGCA GGACTTCTAGAGAAGCCCAGGATCTGTCCCGTGCCGCCGCTGCTCCCCTCCCCAGAC ACCTCTCCACGTCTCCTACCCAGGGGGTCGCATCCCTAGCCCTTCACTGACCCCAGC TCTTCCCTTGCTGCAGCCGCACCTGCAGCTCCAGGGAGTTAACTCTTCTTCTGGGGG ACTGAGAACTGTAGAAAGCCACACACTACTACATCCCTTCACAAAGAGTATATGCTA GTTTCTTGTAGA >8:103371382-103371833 (SEQ ID NO.: 110) TGACAGGCCGAGCGACTGCAGTAGGAGGGGGCGGGCCCGGCTCTCGGTCCGCCCCC ACGCCGGGCTCGGGGTGGGGGCTCGGGGCCTATTACGGGATGGAAGCTCCGGGTGT CGCGGGGGCGGGAGGAATTAAGGGAGGGAGAGAGGCGCGCGGGTGAAAGGCGCAT TGATGCAGCCTGCGGCGGCCTCGGAGCGCGGCGGAGCCAGACGCTGACCACGTTCC TCTCCTCGGTCTCCTCCGCCTCCAGCTCCGCGCTGCCCGGCAGCCGGGAGCCATGCG ACCCCAGGGCCCCGCCGCCTCCCCGCAGCGGCTCCGCGGCCTCCTGCTGCTCCTGCT GCTGCAGCTGCCCGCGCCGTCGAGCGCCTCTGAGATCCCCAAGGGGAAGCAAAAGG CGCAGCTCCGGCAGAGGGAGGTGGTGGACCTGGTGAGTCCGAGGGAGCCGAGCCG GGAC >8:104367291-104367591 (SEQ ID NO.: 111) TCAGAGGATTGTAAACCACTTAAGAAAAGGAAACAGAACTTGGGGAGGCGGTGGCG GCGAGAGTAAACAACTCCCAGGGGGCCCGTCTGCAGCGCCTAGGGGAGGGGAGAG GCCGGGAGCCGCCTCCGGGGGTCTCGCGGGGCCGCCGCTGGGACAGATGAGTCGGA GACAGGCCAAGCCGGAACCTCGCTGGGTAAGGAACAGGACCGGAGCGCGCTCCGG GTGGGAGAGGCTTGCGCTCCTGCAGCCCCTTCCCAGGGCCTGCGCTGACTCATGGCG CGCACTGGAGCCCCTGCAGTCG >8:108082141-108082671 (SEQ ID NO.: 112) ATGAGCTACAGGGAAGATGGTTAGGAGGACAGAGAGAAGAACAACGACGACAAAA AAAAAATGCATGTCAGATAAGAAATACGTCCTAAAGAGACAAGTTTAGATGAGGAG GTGGGGCGGCGAACATGAGTGCGGACCGCACGACTTAGCCCTGAGCGCCCGATTGG CGCCCGGCTCGCCGAGCTCCCAGCGCGTCTCGCTCCGGCTCCCCGCGCCTCCAGGGT ACAGAAAACAGAGTGTTTTGTAGAGCTCCAGGGTCCTAAAGGTGGGGACTGGGGAC CCGCAAAAGCTGGGGTGGAGAGCACAGCCCTGACCATCTGAGCCCCCGGAGCCAGG GCGTGAGTGAGCGCCTCCACACGCCACCCCTGAAGCCCACCACGCACCTTTGGCAG AGAGGGACCCACCTCGCTTACTGCGTCTCCATCGGTTGCCTTGGCAGTGGCTGTAAT CCATGCAGTTCAGAATGATGAGGGCAAAGGAGAAAAGGCGAAACTGCATCTGGGCG GTCGGGCGGGGGAGAGACGCCTCTCA >8:126556342-126556522 (SEQ ID NO.: 113) GGAATCCCAGATGGGGCCCAGACAGTGGCAAAAGAGGGAGGAAGAGAGGGAGAAA GGGAGCAGCGGCTGCTACTGCAAACAGTTCCCCTTCGCAGCTCTGCGCTCAGCTCGC CCATCAGTGTGCCACTGCCTCTCCGTCCTCCTCCTCGGAGCTGGGCGCAGGGGGGCG CCCGGGAGGCGG >9:23824147-23824447 (SEQ ID NO.: 114) CGGTAATTACGAGAAAATACCCAGTCTCGCCATCAGTTTTGCTAACCGGTACTTGAA AATGGGAAACGGGGAACTTATCCAACCTCCAATTTGTCACAGTTGTATAGCTTTCGT ATTAATTCTGTACAGACGTGAAATAGGTGGGTACGTAGCAACGTGCTGGGCATAAA TTAAGCAACAATGGCCACGCGAGGTCTCGTCCGCCGCGGAGCTCCAGTGGTGGGCA CTGCCACCTTGCCATCCCTAGCCCCCACCGCCCTTCGCAGAGTCCAGTCCGGGAGGC TGACGGTGCGCTGGCTTT >9:109639950-109640490 (SEQ ID NO.: 115) CAGGACACCTGGATGACAACCAGGTCCCTGCTCTGGAAACCGTTAGGAGTAGAGGA TTCTCAGAGGGGGTGGAGGCAGGGTGTGCGTACTCCAGGTGGCTTATTACCGCGGG GCCGGGGCCGTGGTAATTTGGGAAACCATAGTCAATATAGCTATTGTTTTCAAATAG CAGACTAGGGAAACTGACCCTGGACAATGTCTTCCTGGCAGGCGGGAACACGCAGA ATTTGGAGTGAAACGGAAAGGGGCATGGGGTCGCCAAGGTGGTGAAACGCCGCATT AAGGCGCTTCAAGATAGCTGGAGTTTTGCTTGGGAAACTCAGAGGGATCTCGCCCG GCCGGCACAATGGCGTTTCTGAACCCATGCCCAGCCCACTGGGGGCAGTCCTTGCTG CTTGCAGAGGCCAGACGCTTCTTGCAACTTCTAAGCGGCGAGAGCTGCCACCTTGCC AATGACTCAACCGTTTGCCTATGCCCTCTGGGCTGTGCCACCAGCCGCAGCCGCCCT GCTCCCCCACCCACCCTTCTCCCCAGGCTCCGC >9:109640702-109641422 (SEQ ID NO.: 116) ATTCACTTTCAACCCTCCAGGGGAGGAGGGGGTGCGGGTGGGGAGGGGAGACGGCT CCCAGCTCCACCTCGCGCGCGGCGCGGCCAGTGCACTCGGCTCCGGGAGAGGCGAG CAGCGCCGGTGAGCCCCGCAGCAGCGCACCCGGCCGCGGAGCCCCGCGATGGAGTG AGTATCCCCGAGCCGCGCCGCCAGCTGCTCTCCTCTCGGCATGTTGCCATGGTGACC GCGGCGGCAGGCAGATCCCGCTCGGGTCCGCGTCCAGGATGGGTGTTTAATTTCAGC CCCGTGTGTACGCCTGGTGTTTCTATAGCAGCCGCCGCGGCGGCAGGAGGCAAGGG GTGGGAGCCCCGGGTGGCGTGGTTTTTGCGGCTGCCCCTTGGCTAGCAGGGCCTGGG GGGCGAGTGAGGGGAGTAGATGATGTTGCTAAGGACGGAGGCATATTCTAGGCTTT CCTATCTCTGCCCCAAGCTTCCGCTTATCGGGGAGTTGGCCGCAATAGCCATGACTT CCGATTCCTAACCATGTCAGCATTATTGGACTGCAGTTAAAAAAAGAGGGAGGGGG TCACTGCGGATCGGAAGCAAACGCGGTTCAGTGTGAAGCGTGTAATGGAAGGATGA GTTAGTGGGTAATATGAGCCAGGGCTGCAATGTCCTGGCTACTAGAAACCATCAGA AGACCCAAAAGAATTGATTTGTTCCTGGGGTATTGGAGAAATAAG >9:114387376-114388005 (SEQ ID NO.: 117) AAGAGCTGAGCTGGGTCTGCTGGTCCTCGGACTGTCCTTGGCTCCTCTCCTTGCTCTT ACGCAGCTGGCATAAGGGGCCACTCCTTCAATAGGGACCACCCCCCGGCGCCGTCG CTGCCTCCTGGCCTGCTGCCCATGCCTGCATCGTCTCTGAGACCCCTTAGCAACCAA GGACACTAACTCTCCAGGTGCAGACGACGACACCCCAGGCACAGAGATGGACCCGC CTACCCAAGTTCACAAGAGATCAGAATCAGAGCTAGGACTGGAATCTAGCATCCTG AGGCTTGACGAAATCCTCCTTAAATCCACCCTTGCCCTGGAGGCCGGGATCCCCTAA GCCAAGAGAAAAGCGGTGCAGCTCCAGCAGCTGCAACTTCCTGGCTGGGCTGGTCC GGCTGCCTGGACTGTCCCGGAGAGTCTGTGACTGGCCCGTCCAGAAGGAAAGCGGC CTCCCGGGCCCTCCTCCGTTCCAATCCCTTACCTCTCTCGGGCTCCACCACCGTCCTG CCGACCCAGTTTCAGGGGACCTGCCTGTGAATTCTTTGTTCCAAACCCAGGGAGCCC CCTGTCTCCATTGCGCCCTGGCCCACCTCCAGGCCGTTCTGCCAGCCCAAGCTGCTG CTCACA >9:120869156-120869336 (SEQ ID NO.: 118) CGGGGGGCCCTGACCCCCTGCCTTACTCTCCGGGCCCGCCGCAGTAGCAGTAGCATT GCTGCTGGTTGGTGCGATGGGGCGAGTCCCACTCGAGCTCCTCGGGCTGGTAGGACA GCACCATCTTCACGGCCTGCAGCGTCCTGGCGATGGCGCCCTTCTTCAGCGCGCCGC CTTTCTGGGG >9:124007671-124008151 (SEQ ID NO.: 119) GGAGGACAGAAGATGTTACACTTTACTCAGGGAACAGAGGCGGGCAACTGGCCCTG TGACTGCAGCCAACAGCTTTAAGAACACAGTCCTTTCTGCTTCAAGGTTAGGGAGAC GTTCTCGCCTCTTTCTTCTTTGCAGTTATTATTCAAGAGGCTTCCCCCGACCCCAGTC CCCAGCACCATCCTCAGAGCTTCAGACCATACATTGACAGTGAGCAAAGGGGGCCC CAGGCAGGCGGGTCTGGGGCCAAGGAGGGCGGCTCCCCTGCGCGGATCCTTCCCTG GTGGCTCCCAAATCCGGCGTTTTCTCTGCCGCCTCTCCCTCGGGGGAGACTCGGAAA GGCTGCAAAAATCTGGGCGCCCGTTCGCTCGCTTGTCAAGAAGCAAACTGTCTTCAC ATTCTCCAAGAGCAACATCCCTGCCTAGGAAGAGGAAGGAAGAGGCAAAATAAATA AAACCAGTTAATGTTGTAGTTAACTTGC >9:129258261-129258441 (SEQ ID NO.: 120) CTCAGTCACTTGCACAACGCATATCGCTAGTAAGCGTTGCTGGTGGGATCACACTCA GCACTTCATAGGCAAAGAAAATCCCAGGAGTGCCGAGGAAACGCTGTCAAGATGTC AAAAATACGCGGTAAGACGTCAGCCCGGTGAGCATCCTCCGCACTGCGGACCGCCC GGGGTCGGGGTC >9:133257345-133257645 (SEQ ID NO.: 121) CCTCAATGTCCACAGTCACTCGCCACTGCCTGGGTCTCTACCCTCGGCCACCTCACT GACTTACTTCTTGATGGCAAACACAGTTAACCCAATGGTGGTGTTCTGGAGCCTGAA CTGCTCGTTGAGGATGTCGATGTTGAATGTGCCCTCCCAGACAATGGGAGCCAGCCA AGGGGTACCACGAGGACATCCTTCCTACTGCACATGGAGAGAGGCGTGCGGTCACA TGGAGCTGGCAGGGTGCCACCCACATGCGCCTCTGGCACACGGCCGCCCCCACCTG GAAACTCCACTCAGCTTC >9:134407349-134407680 (SEQ ID NO.: 122) TACCGCCCTGCGCAGCCAGGCTGGCTGGCAGGCTGCAGCGGGAAGCGCCTGTGGGT CCTCGGCGCTGACTGCAGAGCTGGGTGGAGGCAGCGGAACCAAAACTGCTGTGTCA CTGCACGCTGCAGCTGTTGCCAGGGTGACCGGGTGAGTTTCCCACGCTTGCCCGGGC GGCAGCGTGCGGGCCGGCGGGTGGGGCGGAGGGGTGTGCAGAGAGGCCAGTGGTG TCGTGCCACCCGATGCCCGGGGGTGTCCACTCCCCTCTCCTGGGTCACGTGACCAGG GCCCCTGCCCTGCGGTGTTGTGGGGTGTATGTGTGGTTCTTGGGGGGGTCC >9:135926952-135927312 (SEQ ID NO.: 123) TGGCAACGCAGCCGCCTCAGGGCAGTGTGACTTCCTGATGGTGGTGACTCAGGACA ACAAAAGCGAGAGGCCCTGAGAGTCAGGCGGGCACCACAGGGCCTTGCTGAGGCA GCCGGGGACTCCCGCTCCCTCTGCTGACACCATTGGTGGCCAGTGAGTCAGAGGCA GAGGTGCCAGAGACCCCGCCCGAAGGGAGGAGATCTGAGAGCCTGCAGCCACAGG CTCCTCCAGGACTCGAGCACCGGGGCCGCACAGAGAGCCCTTTCTCTCCTGGGCAGG CCAGGCGGGGATCCCCCAGCGCCCTAACCTGCTCTGTGACCACGGCAATGTGGCCTT GGGGATGTGCCCTGCCTCTCTGGGT >10:43105168-43105348 (SEQ ID NO.: 124) CCGTGGTGGAGTTCAAGCGGAAGGAGGTGCTTGTCCGCGCGTGCTGTGGTCTACCCA GTGTCTGTCTCCGGCCACAGTTCGTTTCTCGGTCGGTTTAGTGTCCGTGTAGCCACCC AACCGTGTGGCCGACCATTCGCGCTTTCATTTGTCCTTCGCCTCCGTCTGCGCCGTCT GTCCTAGG >10:59817900-59818140 (SEQ ID NO.: 125) GTTCCGTCACACGCATTTAGAGCCAGAAGCAGCATGGCAAATCATCATTTTAAAGCT GAGGAAACCACTAGCCTGCAAGATGACATGACTCAGGCAGTCATGCCACCAAGATA GGAACGGATATCGGTCACCATGGCAGCCAAAATTGCTGGGTCCTGTCCAACCAGCA AGTACAGAGGAACTTGAGGGAAACATGGATTTAGGGCAAATCAAGCTGTGGTTTGT GGGCCTATCTCCTTTG >10:75408705-75408885 (SEQ ID NO.: 126) AGGGTGAGGTGCGGTGAATAGCCGTATCCGGAAACCGAGCGTGCCCCGGGCTTCTT TCCCGCCGCCAGACCCCGCACAGCCGCCCTGGGACGTTTTTCGAGGCTTGGGACCTA AGACGGGTCCCCGGACCCTGCTGGGAAACCAGGGGGCGTTTTTCGTCCCTCTCTGAG GCCATTATCCA >10:96044290-96044470 (SEQ ID NO.: 127) GGGAGGGGGCGCAGAGGGTCGCGGGGGAGCCGGCAGTGACCGCGCCTGGGGTGTG TCTTACAGACTCGAGTTGCCGCGTCGGGCTGGGCGCGCCGCCGGGTCCCATGGAGCT GGAGGGGCAGTGGTGGCGAGGACAGCTGGCCGCCGATATTCACCAAGCGCTTCGCT ACAAGGTAACTCC >10:98029739-98030219 (SEQ ID NO.: 128) CGGCCTGGCTGCCCCATCAAAGCCTCCAAGTGCCCCCACGGGGTCGAGGAGGACTC AGGGTTCCCCTGGAATGCCTGAAGCCGGCTTGCCTCAGGCAGCCTGAAGGGAAGAC CACACCTCGTCCAGCATAAGGCGGCTAGCAGCTACGCCGCGCGCGGGGCTGGCTCC CGGAGCTCTCTGCCACCCAGCGCTGTGCCCGGGAACTCGGCTTCCCAGGGGAGGAA GAGCCAGCCCGCGGGGCTCTTCCCCAGCCTGGAAGCGTAGGCACTCGGCCGAGGCC AGTGGCTTCCCAGGCCCGGGTCTCAGCCTGGCTGACTGGGAGACTCTCCCGATAGCC CGGCACATCCCTCCTCACCCGCTCCGCCCCCTCCAGGCCCCAGAGGCCCCCTCCCCT GACAGCTGACCTCCAGTGCGCCCCCAACACTTTCTCTGCCAGCTGCTGGCTGTCGCC CCCACACATCAGCTCCCACCTCTCCGCCAC >10:99329112-99330672 (SEQ ID NO.: 129) GAGGCCATGCTGCAAACCCAGACTTTTCAGGCTGCATCTCAGATATACCGAAGTGTG TACCCGCTACGCACAGTGCGGTGATGCCTGGCCACCTCCAGCCTCCAGCGGGGACCT CCTGCCCAGGTGGAGTCTGAATGCCCACCGCCACCAGCCCACGCGCGCAGTGGGCG TACACGTGGTGACCTGCCTGCGGCTGGGTTCCCAGCTCCGGCTCCTCCTCCCTCCAG CTCTCGCTCGGCTTCCTGCAGTATCACGTGCAGCTGCGCTGGGTGCAGGATGGCGGC GGCCGCGGCGGCGGCAGCAGCGGTGGGTGTCAGGCTCCGGGACTGCTGCAGCCGAG GCGCTGTGCTCCTGCTCTTCTTTTCCCTGTCTCCTCGGCCCCCGGCCGCCGCCGCCTG GCTGCTGGGCCTGCGGCCCGAGGACACTGCTGGAGGCCGCGTGTCCCTGGAGGGGG GCACCCTGCGCGCCGCCGAAGGCACCAGCTTCCTCCTGCGTGTCTATTTCCAGCCAG GACCGCCGGCCACCGCCGCACCGGTGCCCTCACCGACCCTCAACTCGGGGGAGAAT GGCACCGGCGACTGGGCTCCGCGGCTCGTGTTCATCGAGGAGCCCCCGGGCGGTGG CGGCGTGGCCCCCAGCGCGGTCCCCACTCGCCCCCCGGGACCGCAGCGCTGCAGGG AGCAGAGCGACTGGGCATCGGACGTGGAAGTCCTGGGGCCCTTGCGTCCCGGGGGC GTGGCAGGCTCGGCCCTGGTCCAGGTGCGAGTGCGGGAGCTGCGCAAGGGCGAAGC GGAGCGGGGCGGCGCGGGCGGTGGCGGGAAGCTCTTTTCACTCTGCGCCTGGGATG GGCGCGCGTGGCACCACCACGGCGCCGCCGGCGGCTTCCTGCTGCGCGTTCGCCCGC GGTTGTACGGCCCAGGCGGGGACCTGCTGCCCCCTGCGTGGCTGCGGGCGCTCGGG GCGCTCCTGCTGCTAGCCTTGTCGGCCCTGTTCAGCGGCCTGCGCCTGAGCCTGCTG TCGCTGGACCCGGTGGAGTTACGGGTGCTGCGGAACAGCGGCTCGGCCGCCGAGCA GGAGCAGGCGCGCCGCGTGCAGGCCGTTCGCGGCAGGGGGACCCATCTGCTCTGCA CCCTACTCCTGGGCCAAGCCGGAGCCAACGCGGCCCTGGCTGGCTGGCTGTACACCT CGCTGCCGCCGGGCTTCGGGGGCACCGGGGAAGACTACAGCGAAGAGGGGATCCAC TTCCCGTGGCTGCCGGCGCTCGTGTGCACCGGCGCGGTATTCCTGGGCGCCGAAATC TGCCCCTACTCAGTGTGTTCGCGGCACGGGCTGGCCATCGCCTCGCACAGCGTGTGC CTGACCCGGCTTCTGATGGCAGCCGCCTTCCCCGTGTGCTACCCGCTGGGCCGCCTG CTGGACTGGGCGCTGCGCCAGGAGATAAGCACCTTCTACACGCGGGAGAAGTTGCT GGAGACGTTGCGGGCCGCAGACCCCTACAGTGACCTGGTGAAGGAGGAGCTCAACA TCATACAGGGTGCCCTGGAGCTGCGCACCAAAGTTG >10:101134289-101134829 (SEQ ID NO.: 130) CGGCCGAGCGCGCCGCCCTGGCCAAGGCGCTCAAAATGACCGATGCGCAGGTCAAA ACCTGGTTCCAGAACCGGCGGACAAAGTGGAGGTGAGCAAGCGGGGCGGGCCGGC CGCCCGCGAGCGGCGCGGTCTCAGGCAGCTCTCGGTTCATTGGCCTCTCGTGGGGCG CACATACTTTTTCCGCTCGCGGTTTCTGATCCTTTCGGAGGAGCGAGCTCCCGCTAGG CTTGCGGGGAGCTGGAAGCAACCGAGGCCGATAGCTGGGATGGGGCTGAAGAGCCC TGGCTCTGTTTTACCGGAGGCTTCAGGGCTTTCTGGTTGGCACACTCTCTGCCGGTGT AGACGCGGCAGGTCTATTCCGCCGCTTGGGCAAACAGGCGGGTTAGTGCACTCCAC GCAGTCCAGGCTCCAGGGATCTGTGAGTCCTGGGGAGCTTTTTGTTTGCGCAAACTC TTGCTTATGGAATCCTGCTCTGTCCTGGAGACTGGATGCAGAACAGCCCGCACCTTG TTGCAGCGCTCCAGCCGGGCTCCCGGCAGAG >10:116272416-116272956 (SEQ ID NO.: 131) CATGTGCGTGTTTTCCAGGGGCCGCTGACACGGGGATGGAGGTGAGGGCTGGAGAG GTCTGAAGAGGGTTCCTAAAGTCCAAGGGGGTGTCTGTTGGGTTCAACCCGAGACG CTGAACGCAAGCAAATAAATAAATAAACGGTACTTTCCGAGCGTCGCGAGCGGAGC CTGCAGCTGCCTGGAGTCCGAGCCCTCGGTGGCGGCGGCGGCAGCTCCCTAGCCAG CCCTGGCGCCGAAAGAGCCCCTTCTCCCGGGAAGTTGGCCTCCCCCTCCTCGCGTCA GCCAGCGAGCTCGCTCAGCCGCCGGCCCTCCCCACTCCGATCGCCAATCCCTAGCCC CAGTCGCCGCCCTCCTTCTCCCCGGGACTCGTCTCCCTCCAGAGGCCGCCAAGCCAG GGGGAACCGATGTCCCGACTGGGGCTGAAACCCGGTTCCTGCGCCCCTACCCCCTAC CCGCCGCGCGTCCTCGGCTCCCTCCTGGGCGTCCGCTCCTCTCACACTCTCGCCCGGT GCCCAGGACTCGGGCGCTTCCGCACCCCAGC >10:132786883-132787292 (SEQ ID NO.: 132) GCCGGGAGAACAGAGACCAGGACGGCCTCAGCGCGGAAGCCCTGTCCAGGGCCCG AACGTGGGTGCGGGCTGGGGGCGCAGCGGCAGAAACGCGGCCTTAGACGCGCGCG GGGGGCCGGTGTCCCCCCCGCCCCCACGGCACCGGGAGCCGCTCGCTCATCCATCCC GCAGACCGGGCGGTGAGATGACTCCGAGCCCCGCGCACGGCGGCCGCGAGCAAAC GCTCCGACGTCTGTGGTGACGTCTCGTATTGATTTAGGGACACGGGGCGGCTGTGGC TGTGGCCCACGGCTCGTGGGGAGCCCGAGTCTGTGCGCAGGGAACGCCGCTGCGTG GCCTCTCTCGGGCCTGTGCCGCGGAGGAAGGCGGCGCCCGGGGTTCGGGGCCGGGG TCTCACGTCCGCCCCCTCG >11:639416-639956 (SEQ ID NO.: 133) GTGGTGTCGCCGCGCAGGTCCAGGGTGGCGCGTGGCTGCTGAGCCCCCGCCTGTGC GACGCCCTCATGGCCATGGACGTCATGCTGTGCACCGCCTCCATCTTCAACCTGTGC GCCATCAGCGTGGACAGGTGCGCCGCCCTCCCCGCCCGCGCCCCGGCGCCCCCGCG CCCCGCCCGCCGCCCTCACCGCGGCCTGTGCGCTGTCCGGCGCCCCCTCGGCGCTCC CCGCAGGTTCGTGGCCGTGGCCGTGCCGCTGCGCTACAACCGGCAGGGTGGGAGCC GCCGGCAGCTGCTGCTCATCGGCGCCACGTGGCTGCTGTCCGCGGCGGTGGCGGCG CCCGTACTGTGCGGCCTCAACGACGTGCGCGGCCGCGACCCCGCCGTGTGCCGCCTG GAGGACCGCGACTACGTGGTCTACTCGTCCGTGTGCTCCTTCTTCCTACCCTGCCCGC TCATGCTGCTGCTCTACTGGGCCACGTTCCGCGGCCTGCAGCGCTGGGAGGTGGCAC GTCGCGCCAAGCTGCACGGCCGCGCGCCCCG >11:8080670-8081150 (SEQ ID NO.: 134) AAATGTTCCCCTTCCCTTGACGCTATAGCTTAGATGGGAGGGAGCCACTGCTGAGGA AACACCTCCTTAACCCAAAGACAGAGGGTTCCCCAGGCGGGGGTGTGGGAACTCGG AGGTGGGGGTGAGGGAAGGCCAACCTCCACGCTTCGGCCCGGAGGTTCCCCCGCCT CTTCCTGCACGACTGGATTCCTTCTCCATCCGCGCCTCCGGCCCGGTCCCTGCCCCGC CAAATCCGCGCATCGGTTTCCCATCCCATAGCGCAGATAGGTAGGGCAGGTACACA GGGAGGTGTTCGAATGATCCCCGTTTCACAGAAGACGAAACTGAGGCTGGGAGGCC TGGGGACTGGCCCGGCTGCAGCGCCGCCGTTAGCCGAAGGTGGGAGCCGGCGCGGT CACGCGCATGGAGCGTGGATCGCGACGATTTCGGGGGAGGGGGCAAGGGCGCTCCG CAGGCCCTGAGCCGGCCGGGGGGTGGGGTC >11:17351464-17351704 (SEQ ID NO.: 135) TAAGTTTATCGCGCCAACGGTAAGATGTCGCTCTGGACGCGTGCACCTGCTCTCGCA ATCACCGACTGCGGTCAGCATCTTCCTTAGAGCAGCGCCCCGGGCCACTTGGATCCC GGTCTCAATTTACTAAGCGAACCCAGAGGATGCCCCGAGTCCTGGACCGCAGAGCC GCTCGCGAGAGGCACCGGGGCTGTAACCGCGCAACCTCGTGCCGCGGGCGGAGGCG AGGGAGGATTCCCCG >11:64060717-64061197 (SEQ ID NO.: 136) TCGAGGCTGAGCTCTGTGCCGAGCCCACTGTATTTTCACCGGAAAATGCGAGACTTT CATTTCTACCTCTCGAATGCCCAGTCTTTGAGTCCTGCAGCCCCCGGGTCGCCCGGG TCCCGGAGCCGGCGGGTGTGAACGGGGCCAAAGCCCTCCAGGCCGGGCGTGTCAGC CCCGCCCCCGAGGCTCTTTGCATATTCATGACCTTGGCGGGCATGCGCACCGCGGCG GCGGCGGCGGCGGGGCTCCCGGGCCGCCAGGCGACCGGGCGGGCCGGCGTCGACCT TCCCCGACCCAGGCATCCTCAACCGCGGCCTCCTCCTCCCTTGTCTTGATGGAAAGG GCTTGGCGTCCCCCCCACTCCCAACCACCTGAGAGCCTCGCGCTGGAAGGACTTTGG TAATTATTTGTTTCAGTTGAGCTGTTTTCAGTCTAGGCTAGGCTGAGTCTTGTAATGA GTATGGATTTGCCAGTAAATAAGTCC >11:67583928-67584405 (SEQ ID NO.: 137) CCGGCAGGGCTCCTCGCCCACCTCGAGACCCGGGACGGGGGCCTAGGGGACCCAGG ACGTCCCCAGTGCCGTTAGCGGCTTTCAGGGGGCCCGGAGCGCCTCGGGGAGGGAT GGGACCCCGGGGGCGGGGAGGGGGGGCAGACTGCGCTCACCGCGCCTTGGCATCCT CCCCCGGGCTCCAGCAAACTTTTCTTTGTTCGCTGCAGTGCCGCCCTACACCGTGGTC TATTTCCCAGTTCGAGGTAGGAGCATGTGTCTGGCAGGGAAGGGAGGCAGGGGCTG GGGCTGCAGCCCACAGCCCCTCGCCCACCCGGAGAGATCCGAACCCCCTTATCCCTC CGTCGTGTGGCTTTTACCCCGGGCCTCCTTCCTGTTCCCCGCCTCTCCCGCCATGCCT GCTCCCCGCCCCAGTGTTGTGTGAAATCTTCGGAGGAACCTGTTTCCCTGTTCCCTCC CTGCACTCCTGACCCCTCCCCGG >11:68855693-68855873 (SEQIDNO.: 138) CCAGCCCCGGCGGACCCGCCCCCGGCCCGGCCCAGCGTCCCCAGGGGCTCCCGGCC CACCCCGTCCGTTCTGGAGCGAGAGTTCACTCCCCGGGCTGACTGCTCCAAGCCCCC TTTATTAGAAGCATTCCTTGTGGAAAAACAGGAAACACTGACCTGTAAAACAAAAC GCTTATTAAAAT >11:69637540-69637720 (SEQ ID NO.: 139) CTCCCCACCACTTGGTCTGAGAGGGGCTGGGGCCGGAAGGCCAGGGAATCTCTGGT GGATTTGGGGGTTCATATTGCTCAGGGTACCAGCCGATGCGTTTTGAGGGGCGGGAG TCGAGGAATTAGAATCGCCTTTAACCCTCAAGAGTTGCGCCTTCAGCCTCGGGATCC CAGATGCGTCG >11:73309427-73309607 (SEQ ID NO.: 140) AGCCCAGAGTCCGGCCTACCACGGCGGCCACTCCTCGGGCAGTGACGACGACCGAG ACGGTGAGGGCGGCCACCGCTGGGGAGGGAGGCCCGGGCTCAGGCCTGGAAGCTCC CTATTGGATCAGGACTGCAGGCCTGACAGTGATGGGTTAAATCTAAGCAGCATGAA CTCAGCAGGGGTT >11:74311342-74311687 (SEQ ID NO.: 141) GTCACCCCACCCTGCGGCACAGTGTATCCCACTGAGGCCCCTCGGTCGCTCCCACTC GTCGTGCCCTCACCTAGTCAGGTCCCGCAGCCGCGCCTCCTCCCCGCGCAGGTACCG CCTCAGCAGCCCCAGCAGCCGGCGCTCGGGCGCCAGGGCGCGCGCCACGCTGGTCA GCGCCGAGAACGTGTCGCCCCGAGCCGCAGCCCTTTCTGGGTCTCCTGTCCCGAGCG CCAGCACCGCCAGCAGCGCCGCCAGCCGCGCCCCAGGACCCATAGCCAGCGCTCGC GAACTTCCCCTCAGACAGTCCTGGCCGCGCGGCGGCAGCCGCTCCCGCCCTCGCCTG CCCCGC >11:74467133-74467313 (SEQ ID NO.: 142) GCGCAAGTCCCCACGGTTTCCAGACGGGGCGCGCAGAGCCCAGCTCCCTACTCCCA CATGCTGCTCCACGATCACTGCGCTCGGGAGGATCGGGGAGGATCCGGGAGGACTA GCTTGGTATTTGCAGCGCCCACCCCTCCCCCACTCCCCCTCGGTTCCACAGTCTCACG GAGAGCGCGCC >11:104163936-104164116 (SEQ ID NO.: 143) AGCGACTAGAGACAGCGTCGCTCCAAGAAAAAGCCGGGTTCTGCTCCCGGGACCGA CGCCGCGCCGCCCTGCGCTCTCGCCGCCTGCGCTCGCCCTGCGCTGGCCCGGGTCGC TGTGCTAATCGCCGAGCTCTCCCCAAACTTCCTGCATGCTGAACTTTCCGAGCGCGT GTGGGTGCCGC >11:134332352-134332532 (SEQ ID NO.: 144) CGACACCCGGCGTGCCCTCGGGAGCCGGCGTCTGTGCCCCGAGCCGCCCACCCCGC CGCGCCTGTGACGCCGGGCTCTGCCCCCCGTGGACGCCCGCAGCCCTCCAGCCGTCA GAGCCCTCTCAGACGCACCCCATCGCGGCCCCGTCCCCACTGCTCCGCGGAGAGCTC CCTCTGCCCTT >12:3200277-3201237 (SEQ ID NO.: 145) GCAGGGGGCGGGGCCGAGGGCCCGGGGAGGGGGCTCCAGGCGATTTCAGAGTCGC GAGTCGGGGCCGGGATTTCGCAGGGAAAGCCCAGCGGTTGCAGCTGCGGCGGATCC CTCGGCACTGTCCGCCGCGCGCCGGGGCAGCCCAGGGCCGGCGGCAGCTCCGCAAA GTCGCGGAACGAGAGGAGGCGGAGCGCCGGCCAAGTGGTGGGGCTCAGCGCTGGG GCTGGGCTGGGCTGGGAGAGGTGTGCCCAGGGAGCCTGGATCCCGGTGCCCTTCTC CCTCGTGTGGAGCGGCCAGTGCGGCCAGAGGCGAGCTGACGGCCTGGAAAGAGAA ATCAAATTGCAGCCTCCCCAAAGACGCTGAGTTACGCGGGCGAGCCGGTTCCCGGG GATCGTTCGCGAGCGCGCAGAGAGCCGCGCCGCGCCGCAGAGCCCTCCCGGGGCCG CCGGCCAGAAGCGGGGCGCCGTCCGACAGGCAGCAGCCCCTGGGCGCGGGGTTCGG CCGCGAGTGAGCCCCTGTGCAGAGAGGGGGCGTGCAAGGCTCCGCCGGCCCCCCCG CAGCCCGCGCCCGACTTGGGCGCCCCCTCCGTCCCATTCTGGGAGCGATGCCCCCCG CTCCTCGCACCCCCCGGGAACGCCGCGAGCATGGAGAAGTCGAGTAGCGAGGATTC TTCGATCCATCGGAGTCCATCTTTGGACAGCAAGGACTCGGACTTTGCCAAGCCGTC CACCTCCGGCCGCCCGTTCGGCCGCGGCTTCACGGCCGGCGCCTTCTACGGCACCGC GGGCTCCCGGGGCCAGAGCCGCGCCGAGGCCGGCGTTAAGACCGACAAGTGCAATG CACCCAAAGGCAGCAAGTACGTGGTGTTTTACCTGGACCTGTCCTTTGTGTTCCTCCT AGAATTTAAGAAGTGCAACATGGCCAGGGGCTGCCTCTGCTGCTTGAAGTACATGAT GTTCCT >12:3493022-3493802 (SEQ ID NO.: 146) CCTACCCCACGGCGTAGGCAGCAAAGCTTTATAAATCCCCCTTCTCTGAGAGACTAG AAGCAGCATGCATCTGACAATTGTCAATTTCAAAACAAACACGCTCCGGGACTTGA ACGCAGCGGGGCATTCAGTAGCGAATGCTGTCTCCTTGAGTTAGGGCAAAGCCTGC GTGCCCGCCGTCCCCTCACCACTTCCTCTTCCCCAGCCCCCACCTGAGAGCAGACAT TCGGAATGATGTGTAGTGCGAGGCGGCTAGCCTCCCAGCAGAAAGCCATCCTTACC ATTCCCCTCACCCTCCGCCCTCTGATCGCCCACCCGCCGAAAGGGTTTCTAAAAATA GCCCAGGGCTTCAAGGCCGCGCTTCTGTGAAGTGTGGAGCGAGCGGGCACGTAGCG GTCTCTGCCAGGTGGCTGGAGCCCTGGAAGCGAGAAGGCGCTTCCTCCCTGCATTTC CACCTCACCCCACCCCCGGCTCATTTTTCTAAGAAAAAGTTTTTGCGGTTCCCTTTGC CTCCTACCCCCGCTGCCGCGCGGGGTCTGGGTGCAGACCCCTGCCAGGTTCCGCAGT GTGCAGCGGCGGCTGCTGCGCTCTCCCAGCCTCGGCGAGGGTTAAAGGCGTCCGGA GCAGGCAGAGCGCCGCGCGCCAGTCTATTTTTACTTGCTTCCCCCGCCGCTCCGCGC TCCCCCTTCTCAGCAGTTGCACATGCCAGCTCTGCTGAAGGCATCAATGAAAACAGC AGTAGGGGCGGCCGGGCTCCTGCGAACAACAACAAAACAAACAA >12:6540419-6540659 (SEQ ID NO.: 147) CCCACCCTCTGCCTCGCTGAGCTCCCTGCTGCGAGGGCCTCGGGTGCAAGGGGGAG GCAGGTCTCTATCTCATGGAGCTGTCAGATGAGACATCGCGATCGGAGTCCTCAGCC TCGCTTGGCGGCGGCGGCGGGTCGCTAAGCGGGACCGCAGTGAAAGCAGGAGACTT TCTAGAAAAAAACACCAGTTGTCAACCTTGGGGCAGGCAGGAATCCTGAAGACGGA CGGCACTCCTCCTCCT >12:40224354-40224954 (SEQ ID NO.: 148) GGGGCAGTTTTGATGGCTAACCCCTCTTTCCATCCTTTGGGGGAAAATTGCTCATCTC CCTATAGGTGGAACTCTAAAGACAATGTATTCCTAAAAGGGGCCATCTGGGCGGTGT CCTCTTTTCCCAGCGCCCTGATTTCTATTCTTAGATCTGGAGATAGGCGGCTTTCATT TTTCCTGCTCCCAGTTCCCAGACCTTCCGTGGGGCCGCAGGATCCCCGGCTGGCGGG TCGCGGAGGGTGGCCGGCCGGGCTGCGCACTGCGCGCCTCCGCTGCGGGGCTCCGG GCCTGTGGACTCAGCGGAGTCCGCTGAGTCAGTTTCTTCCCGCGCGACTCCCGGCCG CGCCGCCGCTGCGGTGGAATCTGGTCCCAGGAGGCGGCGTCCGCCCGGGGTCCGGT CTAGGCGTGCGTGGGGGCCACGGTCACGGTCATCCCAGCCAGGCCCGGCTCCAGCA GCCCCACGGCCGCCGCCAGAGTTCTGCGCGGCCCGTCGCCTCGGCGGAGCCTCTGGC AGGCCCCTGAGCTCGTTTTTGGGGCCTGAGTGGGGGAGGAGGAAGCCGAGCAGGAG GGCTCCGGAGAGGGAGGGCAACGCGGGGCGGGG >12:63150967-63151627 (SEQ ID NO.: 149) CTCTGCGATCCCTCCAGTGGGCGTCTCCCGGAGCAGCGTCCCGCCTGCCCACTGAGC AGCTCTCAGCAGGGTGAGCTGGCCCCTCTCCCTGCTCTGCCTTTTTTCAACTTCGGCG AGGTCGGGAAGGTGAGCTCCGAGCTTCCGGAAGCACTGGGTTCCCAACTCAAGTAT TTATGCGGTGCTTGTTTCCTTGGGACGCGCTCCCTCCCGCCCTATTGCCGGAAGACTG CTGGTTGCCTACTCCCCGCTCCCTGGAGTTTTATTTTTTCCTCTCCCTACGTCGGTGTT TGTCCTCTGCATCACTGTGGAGGGGGTGGAGCTGGGAGACTCGCAGATTCCTCCTCA CAGTAGGTGGGATCGTGGCGCTTTCCCGCTTTTCCCTTCCAAAAACTTGGACAACTG GACGAGTCATGCCTTTTCTGGGCTCGTAGCCGTTTCCACAAGCTTCCCTCACTAGCCT TCCTCGCTAGCCTCCTTAACCATGCATTTGACTTCAACAGGCACGCTAAGCGCGGTA CCTGGAAACCTCCAGTCCACGCACCGGCGTCCACGCATCTAGCTCCTGCACCTGAAC CTGGCTCTCGACCTCACCTCCTCCAGTCCGGGTTTCTTCCTTCTCACCGAGCTCACCC GTGCAGCAGTCTGGCAAATTTTATTCCCC >12:104456512-104457736 (SEQ ID NO.: 150) CTCGCTCCCTGGGGGTTTGGGGCAACTTCCCCGCTACGTCGCCCAGGGATTTTAAAT AATTGCCAGCCACCAGAAACCCCCTAACCCTTAATTCTTCCCTCCGAGACCCAGCCC GCTGCTTGCCACTTCCCTCTCCAAACGCTGGCGGGGGTGGGTGGCAGCACCGAGGC GATTTTCTTCGTCTTTTTTTCCTCCGGGTTTTGTCATGGAAACGCTGACACAACCTCC AGACGGCGGCCGAGCCCGGCCGGGGACTGAGGGCTTTTGGGACCCTGCGGGAGCGC GGCGCGCACACCGCACTCCCCGGGCAACAGCTGGACGCGACCATATCCCGGGTAGG GGCGGGGGGAGCGCGACGCTCCGCCCCGGCGCTAGGGTCCCTCCCTCCTCCCGGCTC TCCGCAGGCGCCCTCCCCTCGCCGGGGGCCGCGAGTTGCATTTGGTAAAACCCAGCC CCGGAATATATAGATCGTTGGAGCGCAATGAAGTAGCCTTTGGAGAGAAGGGAGAG GGCCCGTCGGACAGCCACAGCGGCCAGCGCAGCGGCAGCGGCGGCGGCACCACCAT CACCGCTCGCACCCCAGCCGCCCGGCCCGCGACCAGGCAGCGGCGGCCGCCGGCGG GATCGGAGGAGGCGGCGGAGCGGCGAGGAGGAGGAGCAGGAGCGCGCAGCCAGCG GGTCCACGCATCTCAGCACTTCCAGACCAACTCCGGCACCTTCCACACCCCTGCCCG GGCTGGGGGCTCCGAGAGCGGCCGCGAAGCGACTCCGATCCTCCCTCTGAGCCTTG CTCAGCTCTGCCCCGCGCCTCCCGGGCTCCGGTCCGCGCGGCGGGGTCCCTGCTCCT GCGCCCCGGGCGCGCTTCCCGGACACCCCGGTCCCCGCAGCCAGGACAAAGCCATG AAGCCAGCGCTGCTGGAAGTGATGAGGATGAACAGAATCTGCCGGATGGTGCTGGC CACTTGCTTGGGATCCTTTATCCTGGTCATCTTCTATTTCCAAAGTATGTTGCACCCA GGTAGGGGGCGCGTTAGCGTGGTTTTGTTGGATATTTTCTTCTCTCTCGCGCTCTAGC TCGCTCCGCCTGATTTCTGCCTCTTCCAACCCTACCTCTCCGCCTTCGGCCTCTTCGG GGCTCCTGGCTGCCCAGAGCTCCTGGCTGCCCAGATCTACCCGGGTCACCGCGTCGG GATGGGGAGGAGAAGGGAAGGTGTGCTTCGCCCTC >12:132904844-132905024 (SEQ ID NO.: 151) CTTCTCAGGAAGCCAAGCTCCCTCACCCTGTGGCGACGCCGCGGGCGGAATGCGCA TGCGCGCCACGAGCCACAATCGTAGGGTTGGGCGCGCCCTGCCGGCCACCAGGGGC AGCGCAGGAGCTGAGCGCACCCCATCAGCGAAAGAAGCGCGCCTCCCCGCTCTTTT CTGAACCGTATCT >13:24271993-24272173 (SEQ ID NO.: 152) TTTCTATATTGAGAACACAGACCACATGAGTGAGAGGGCTCGGTAATGCTAGCGAG ACGGCACTGGCAAGACCTGGGTGGAGGAAGCGGACGTGCGGGTGCTCCCTCCCAGG GTTCCTGCACCCATGGCCTTGAGCAGGGGCGTGTTCATTCCCACCGGGAGTGCAGCC AGCACGAACGGG >13:36297374-36297734 (SEQ ID NO.: 153) GGCAAAATACACGCCATATGATTGGATCCTTAAGGGCAGCACATCCTACCCGGAAA GCTGCCTACTTAACAATACCAAAGGCTTACTCAAAGAGGCACGTGAATCTTTCGCAT GGAATACTTTTGGAACCCAGACCGAAGTGCCCAGGGGTTAATCACGGCGCCGGTCTT ACAGCACCCTCAGCGGCTTCAGCCCTGAGACTCTGCAGGTGAAGGCTCGGGGGGTG TGGACGGGACCCCACACCGCGCCGCCCGCCGACTCACTTCTTGCGGACTTCTTCCAG CAACTGCTGTTTCAGGCGGTTGGTGCTCACACCGTCGAAGTTGTAGTTTCTCTCTTCC TTCATAGTGTCAGGCCAGAG >13:102394503-102394683 (SEQ ID NO.: 154) ATGGTTTCCATAGCAACAACAGCACAAGCTGCCGGGTCCCAGAGACGCCCTAGGGT CAGAGGTCATCTCCGTGGCAACGGAAACTTCCCGCGCTACGGCGGCTCCAACGGGC CGCTTCCGCCGCATTGCGTAGCGAAGCCCCCGGCGAGCCGAGGCTGGGAGCGCGGT GATGGCCGGTCCC >14:21068771-21069311 (SEQ ID NO.: 155) GCCATAGGTTCTTTTTTGACGCATGGAGCAGAGGCCTCTTCTTGCCTCTAAGAAGGA TGAACACTTGCTCTGTCCTTTTCCAGGCTCAGCGGAGCGGAGAAAAAGGTGGAGGTT AGCGTCCAGAGGAGGTGAGAGAAGAGCAAGTCACCTTGGCGGCACCCCCGCCTCCC CTCCCGCTGTTCCAACAACTGCCCAGAGGCTCCGGCCTCCGAGGAACTGCAGGCGA GGCCAGACGTTTTCTCATCATCGCCCTCCAGCTGCAGGGGCACACGCGTTCACGCCC CTCCGGGGACTATTCGGCTTTCCGATCTCCTCTCCTCTCCCTTCCGTCCACCCTTTAG AAGAGCTCACGGAGCTGCGGGGCTTCCCGGTGCCTGCTCAGAGGCCAGGCAGGGCA TCTCCCCGCCGTGCCCGTGCCTCCCCCCGGGCTCCTGGGAGACCCCCCATCTGGCCT TCCTTTCTCATTCAGACACTGTCGGGGGACGCTCGGGGTTTGATGAGGGAGTGAGGC TAGAACTTTCGTAACTAGCCCACCCTGCTT >14:53956625-53956805 (SEQ ID NO.: 156) AGGGCCGGGGACTGTGGCGCTGCAGGCTCGAGATAGCTTGGACGGGAATCCCATCG GGGAGACAAGCTAGATACTCAGCCGGAGCAGCAGCGGCGTCTCAGGCTCGCGTCCC TCAGCTCGGATGCCACACTCACCTAGCTTCCGGGCCGGGCTCCGCGCTCCTTCCCTC CCTCCCTCCTCC >14:97412990-97413410 (SEQ ID NO.: 157) CTTTCAAGTGTCCAGGCCATAAATTCTTCTCAATTCCCTCTCTCTCTCCTTGTCGGAA TTAATGAGATCAGATCTGATCAGGGCGCTGATGTGTTCAGCGCCAAATCACACAACA GCGCGCGCACCGTAATGGAATTTGCATCTAATGCATACATAAATCAAACATCTTTCT GGACATTTTCATATGCATAATGTCATTTCATCCAGTTCTCTCTGTGCAGAGGGGGAG ATTTTTCTCTCTGAGAGAATGACTTTCTTTAATGCTTTCATTTTATTTTCGCTGACTGC AGTCCGGGAGAATGCGCTCGGTCGGAGAATCTTTCGGGGCGCGGTTGACAGTTCTTT TTCCAAGAGGGGTCCTTCACATTTATCATGCCTCTTCCTCGGGGGCTTTGTTATGCAA ATGTGGCTGAAATTGATA >14:101561321-101561561 (SEQ ID NO.: 158) TCCGCCCTCCGCCCGCCTGCGCCCGCCCTCAGCCCAAGATTTCTAGGGCATTGGCCG CGCTGCTGGGTGATCCCTCCGGGCTCAAGTTGCAAGGGGGCGGGCCGGGCCGGAGG TGGAGTCTCCCGCCAATTGAAGCCTCCGCTATAAATTGAACTCCCTGCACTGCTGAA GCCCAGATGCCTCGCCAGGCCACGTCGCGGTTGGTGGTCGGAGAGGGCGAGGGGTC CCAGGGGGCTTCGGG >14:104117671-104117851 (SEQ ID NO.: 159) CAGGGAAGACCCTCGGCCGGAGAGCCAAGTGCTGCTGGGAGGTGGCCGGGCGTGGC CGGGCTGTGCTGTGGGAACCGCTGGGTGGGGGCGCGCTGGGTTGCCCACGCTCCTG GCGCGCTGCCGGCCTGGAGACGCCGCCGCCGCCCTCTTGCACCCCGAGGGCCCGCA CCTCGAAACTCCG >15:52789319-52790159 (SEQ ID NO.: 160) CTGCCCAGACCGGAGCTGGAGAGGGGCGAGAGGCTCTGGCCCATGCCGGCCACGTC CTTGTGGTAGGGGGTATAGAGGTTATTCATGGAGGCCAGCCCGCGCTCATCCCGCAT GAGCGTGAAGCTACCGCTCACGTTGCCCGCCAGGCGCTGGTGGTGGTGCGGGTGGT GGTGGTGATGGTGGTGGTGGTGATGGTGGGGGAACTTGTCCGAGACTGTGGAGATG GGAGGCAGCGGCTGCAGAGGGGTCAAGGTGGTGTAGGTGGTGGGCATGCTCATACC TGGGGGAGTCTCGCAGGCCATGGTCATGGTGGGATGCAGGGGGCCGGCCAGGCTGT GCTCAGGGGCCCGGTGGTGGTGGTGGTAATCTCCGCCGCCGCTGCCGCCGTCCAGCA GGGACGCCATGCCCATGGAGCGCGGGTGCGCGGGGGGCAGGTGGCTGCCGCGGTGC GCCACGGAGCTGCGCGCGTGGGGGCTGCCGCCCAGCAGGTCGGCAGGGGCGGGCAC CGGCTCATGGCTCACCCCGTGCAGCTCGCCGATCGCTTCCATGGTCAGCTGCGCGTT CATCGTGATCCGGGCGAGCAGGCGGCGGACACAACATCGATGTGGCCAGGCAGAGG CGGCGAGGGGCGCACGGAGTCCGGTCTTCACATCGGCTGCTGGCGACTGTTGCCTTC CTTCCTCTCACTGTGGGGCTCTGTCTCTCTCTCTCTCTCTCTCCGTGTGTGTGTGTCCG TGTGTGCGTGTGCGTGTGTGTGTGTGTGTGTGTCTCGCCTTCCCTCTTACCCCCCACC TTCCCCTCTGCGTCCTCGGCTTTTTTTTTTTTAATATTAATTTCCAAA >15:79089695-79090115 (SEQ ID NO.: 161) CGAGGAGCTAGCGCAGACCGCTCTCCGCCCTCAGCTGCGGCGAGGCAAGGGCTGGC AGCGCTCGGACGCCTCCGTCTTGCCCTTCCCATGCCTAAGCGCGGGGAATTACACGT TCCCGGTGTAGAACAGACGATCGGGGCTATTAGGGCTGGGCGGTGGGAGTGGGGGT TGGGAGCACCATTTTTGGCTGGACGTGTGTCCAGACTCATCGTCTCTGGTCCTTAGG ACCCCATCTTCCTCTGCATCTCCAGGTGTCGGCCCCTCTGTACCCGCCTCCCACGGGG CTCGTCCGGCGAAGGGCAGCCGCAGCCCACATCTACTCCCCGCCCTCAATCCCTGCC CCCTCTGCCCGCCGCAGTCACTCGCCTGGCTGGGAGCAAGCCTCCCCTCTCGCTGAG GGTGCAGAGAGCGCCTAGGGCGC >15:84079746-84080646 (SEQ ID NO.: 162) CACCAGCGTTATATCCCGTCGCTGCTTCACATATATTATTTACCTGGCCCGGGTGGCA TTTTACTTTGCATCCTTGATTGGGAGTCTCAGGGGCTACGAACAAACGTTTTATCCCC GGGTAGCCGGCGGGTGCGGAGCGAGTATTCGTGGGGCGGGATAAGTGCGGAAGTCG CTGCGCCCTCGTCCCTTCATCTCCGGGGGACGGCCACTCTCAGGGTTCCCGAGGAGC CCGCTCCGTGCACCTAGGCCCTAGGTCGGCTCCCAAGCCCTGGCCCGCCGCTACACC AGCGGTTTCTTACCCGCAAGTACAAATGTGACACAGACACCAGCTCCTCGTGCTCTT GGCTCCCAGGGTTTCTTTCACCGCGCCTCAGCACCTGCAGCTTCTCCACTCTTACAGC GCCCGCCGTCGTCAAGGCAACAGAGGGATGCCCGGTGACAGACTCGGCGCCGGCTT CCGGCGCCGTAAGAGAAGCGTCCGCGCGGGCGTTCTGGACCCGCAGAGTTCTCGGC GTTTCCGAAGCTCTTGGTGTGGCCGGGACCCGGGAGAAGGAGCAGGGCTGGTGGGG CTGCTGCAGCCGGTGAGTGTGTGCTGGCGCTGGGGGCTGGAACCTCCTAGGCCAGTC TCTGGGCGGTGCCGCAGGACCCTGCTCGCTGCGGCTCTGAGGCGGAAACAGGGGCT GGGGCCGAGCGCGGGCTGGAAGCTTTGGTCCCTGGAGTGTCGCTTCCAGTCTGGGGC CGAGGCGGTCGCCTGTGTAGACCCGGGATCCTCAAATAGAACGAATCCGGGACCCT GCAGAAATGAAGGGCATGTAGTGTAGAGGTTTTTCCTTTTTATTTAGAAAGGAATGA AAGACCGACAGTGCACCTGCTTGGATAGTAAGCACGTGACCCAAAACTT >15:88803502-88803862 (SEQ ID NO.: 163) CTCAAGGTCTCTCTCTCTCAGCACCCTCGCCGGCCGGCGTCTGACGCGGGTGCCAGG GTCTCCGGGCACCTTTCAGTGTCCATTCCCTCAGCCAGCCAGGACTCCGCAACCCAG CAGTTGCCGCTGCGGCCACAGCCCGAGGGGACCTGCGGACAGGACGCCGGCAGGAG GAGGGGTGCGCAGCGCCCGCGCAGAGCGTCTCCCTCGCTACGCAGCGAGACCCGGG CCTCCCGGCCCCAGGAGCCCCCAGCTGCCTCGCCAGGTGTGTGGGACTGAAGTTCTT GGAGAAGGGAGTCCAACTCTTCAAGGTAACTGTCTCCTTCCCTCCAGAGCGAGGCTC TCCCAGGGCGCCCGGCGAGCC >16:3151986-3152166 (SEQ ID NO.: 164) GCGCCTCTTGGGGTATCCTTCCACGGGGTGGGGTATCCTTCCACGGGGTGAAGGCTG CGGAGAGTCGCAGCTGCAGGCATGGCCTCCGGTCGGCGGACGCTGGTGACCTGGCG TCGTGCAGGGTGTCACTTTCTCCTTTAATTTTTTTTGATGTTTCAGTGGTTTACGAAG GTATTTGTTT >16:23182247-23182634 (SEQ ID NO.: 165) AGGTCAAAGGATGAGTGGCCTGGCTGAACAGCCCCTGCTGCCTACAGCCGGACGCT GGTGGGCACTGAAGCTGCAGGTCTGGAGGGAGTCCGAGGAGCGAGGCTGCGTGGGA TTACTGCTGGTGCTAGGGCAGGCACCTGCCATCTGGACGGGAGTGGAAGGAAGTCG CGGGGCAGTAATAGGGGGCAGCAGGCGCTTTGAGGCGCCTTGGGGTAAGTGCCGCA GAGACCCAGCGGGAATGCAGGATGGCAGGGCGGCCTCGGGGCGGCAGCAGGCACT GCGCGGTGGCCCAGGAAGACGCAGCGCGGCCGGGCTGGGGCGCAGGGCGGCTTCG GGGCGCCAGGGGGCGTTGTGAAGTCGTGGCCCGCTCCGGGCGGTCTCAGGTGCC >16:57091834-57092014 (SEQ ID NO.: 166) AGGCTTGAGCGCCCAGCGACAGACAAGTGTCCTAAGAATTGGTGCCTCTTCTAGGG AAAAGGAGGCCTGGGCTCCAAGGCCTTAAAGACTCGCCTAATTTTCCGCACGGATG AGTAGACCCAGGCCCAGTTCGGATCCGTCTTTATCTTATCGTCTGTGTCAGAGAAAT ATGTCATATTTC >16:57536947-57537307 (SEQ ID NO.: 167) TCACTGTTGTTACCTGCATTTTTCCCTGGGCCAGCTCTGCCACCGAGTGGAAGTGGG CCAACAAGTCTGTGCCCATCGGGCCTCAGTTTCTCTTTCTGTACAACAGAAGGGTTG ACGAAAGCAACCTTGCGCTTGTTAAGAGGTGGGGGGCGCGGGGAGCACTCGGCCCG GCGGGCGGAGACTTTTCTCTGCATTGCGATGGTGGTTGGCAGGCCCTGGGGAATTAC GGTACTTCGCCTTCGGGGACGCCCAGCTGTTTTGGGGCTTTCTCTCTATTGGGGGTAG GATGTTTGTGGTCTTGACTGGAAAGCCGGGACAGGCGTCTGGAGGACTCCCCACTAC ATCCTGTACCCTGGAAGGC >16:68448640-68449000 (SEQ ID NO.: 168) GCCCGCAGGTTCCTGGGTCTCTCCTTCAAGACCACATCCCCCAGAGACCGGCGGAGT TTCGCACAGCCTTCTGGGACTTATAGTTCTTTAAGGACGCGGAGTGGGCTCACGCCG CGGGTAGGCAAACAGAGCGGGACTGCATTTCCCAGAGTGCACTGAAGACACGGAGG CGCGGAGCAGGGCGGGAGGACCGTTTCCATAGCAAAGACGACCAGCCGAGGATGG CTGGCGGAGGCGTGGGGCAGGCCGCAGGACCCTCGAAGGATCGTGTGAGACCCCGG GCAGCCTCTTGGGAGGCCATTTCGAGGAGAAAACCTTGATTTCTGCCTCAGGACCCT GGGCCTCAGTTTTCCTATCTGAG >16:68737031-68737271 (SEQIDNO.: 169) AGTGAGCCACCGGCGGGGCTGGGATTCGAACCCAGTGGAATCAGAACCGTGCAGGT CCCATAACCCACCTAGACCCTAGCAACTCCAGGCTAGAGGGTCACCGCGTCTATGCG AGGCCGGGTGGGCGGGCCGTCAGCTCCGCCCTGGGGAGGGGTCCGCGCTGCTGATT GGCTGTGGCCGGCAGGTGAACCCTCAGCCAATCAGCGGTACGGGGGGCGGTGCCTC CGGGGCTCACCTGGCT >16:72787676-72787856 (SEQ ID NO.: 170) ACGCCAGGCAGTGGTACGAGCCGCCGCCGCCGCCGCCGCCGCCACCGCCGCCGCCG CCGCCACTGCCACCGCCGCCGCCGCCGGTGGGGACGTGAAGCACCATCTCTTGCAG GTTCACCACAGACTGGCCGAAGAAGCAGAGGGACTTCAGGTGGCTCCTCGCTGCCT CCTCGTCGCTGAA >17:5500469-5500649 (SEQ ID NO.: 171) GGAAAGAAACAAGCATCGAAAGCTACATGAAGGGGGTGCAGCGCTGTTCTAAAACA CAAAATGCCGAGCCCCGTTTTCCCTTTCCCTCCCCGCTCGGTCCTGCGCCCACCCCGT CCCGCGCTGGCCACTCAGGCAAGCTGTAAATGGATATAGGTAAAGATGCAGGAGGT GATGGAGAAGG >17:15966446-15966686 (SEQ ID NO.: 172) TTGAGAGCTGGGAATTGATTTCTAAGCCTGGTTTGAGCTGAGGGCCACAGAGCCAGT GCAGGAGGAGACCCTGCCCCAGAAATAGGCCAGTGCTTGTTATGCAGGCCTTGGCG GTTCCCCGTTTCCTTACGTAACCTCAGTGTTCACGCTGTTTCCTTTTGTTGATTCCCTC CGTGTGACTGTTTTTCTGTCAATCTCCTTAGCTAATGAGCTCCTTATAAGGAGAATGG ATGGATCAGAG >17:17757263-17758043 (SEQ ID NO.: 173) TGCAGAGTCAGGAAAGATTTCCTGAGCCTGGACTGAGAGGCCAAGGTGGGTTTGCG GAGGCAGGAGAGAGCTCCAGATCAGGAGGCAGTGTGGGCCAAGCCGGGGGGCGGC AGGATGTGAGCACAGAGAGGGCAGCAACCCTTCTACAGACCAGTTCAATTCCAGTA ACCCCAGCCTGCCGTAGGGGTGGGGGACAGCCTGGCTGCAGCGGGGCCCACCTGCC AGTGTGTGCCTTGCCTGCGCTCCACCTTCCCCCTCGGGCACTGCGGCTTTCTTGGGAC AGCAGGACCCCAGTTAAACAGCCCTGTTTCCTGCCCAGCCGTGGCTGCCGCCTCTTC TCGGAGGATTTTTTTTTCCCACAACTCAACAACCACTACCACTTGCAGCTAAGCAGA AGGGAAGTTAGGACTCGCATTTTGCCTCTGTAGCGCCTGTAATCAGCCCCACACAGC CCCCGCCGCAGGCGCCCATCAGTGCCACTTCCGGAGACTACTTGAGATACACCTGCT CACGCTAAAAGGAGAAGCAGTAATCCATCAAAACAACCCCAGGCGCCGGGGCGGG AGAGGCTGAGACTCAGTTTCCCCTCCCATGGAACAGGGCAGTGTTGGGCATCTGAA GTCCCCACGGGTCCTGGCATTCTGGAAGAACACGACTCAGTAGCTTTCCCCTTCTGG GCCTCGGTTTCCCTGTCTGCCAAAGGTGCAGGGAGATGAGCTCCCAGCTCATGCCTC TGGGCCTCCTACCTCGCCCCCACCCTCATCTCTCCCTTTCCAGAGAC >17:19744858-19745191 (SEQ ID NO.: 174) GCCCCAAGTCCTTCCTGAACCTCTCTGGGTCGCACTCTCCCCAGCCCCTCCCCCCACG CCCCATCGCATGGCCCCGACACTGGCAGAAGGCGGCCGCCCAGCCTGAGCACCTTG TGCAGGTCTGCGGCCAGCGCGCCCACCAGCTCCTGCTCCTGCTCCTGGATCAGGCGC TGCAGCGCCTCCAGCTGCTGGATCCGGAACTGCAGCGGACGGGTCCTGCCCGAGCT GAAGGCGGCGCGGGCGCGCTTCACGGCCTCGCTGATCTTGCTCATGGCGCCTGGGG ACAGAGAGCACCTGCAGCTGGCTGAGGGGCACGAGCGCGCCCTGCCTCCCA >17:19867961-19868141 (SEQ ID NO.: 175) GCCTTGAAGGCCGCAGCGCCAGCCGGCTCCCTCCGCCGGGGAAAGGAGTGCGGCCA GGGCTTGGCGCCCGCAGCTGGGCAGATCCTCGGCCGCTCCTGAGGCGGGGACGAAG GGCGCGACCCGCTGCGGCCACAGCGGGTTACGGGCTGCGGGCTCCGTTCTGGGCCT GGGGAGCAGATTC >17:29019967-29020267 (SEQ ID NO.: 176) CCATTTGCGATCGGCACCTGGAGGGGCGCGCCGTGCACAATGAGGGCGGGGCCGTG GGGCTCCGGGTGCGGGCGGCGGCCGAGTGCCCACGTGGGTGCAGGCTAGGCCGGGC TGATTTCCCTGGAACCCCGCGCCGCGTGCTTCCCTGTAATGAGCTCCCAGGGCCCGA GGTGAGCTTCCTCGGCTGCTCACACGGCAGCCGCGTGGCAGCAAAGAACACGGGGA CTTTTTTCTTCCGTGCCTGACAGCTCATTAGAAGAATTAATTTACTCTAGCGTTTGCA GTTTAAAGGACATTATTT >17:56834692-56835015 (SEQ ID NO.: 177) CGCCCGGTTTGGCCCCGGAAAGGCAGGAAGGGGGCGGGGAAGGGATGGCGAGCTC GGGGTGCACCGCCTGTTTCTTTTCTGGTTAGGTATCGTCCTTGGAGAAGATGGAAGC GGAGAGGCGGCCGGCGCCGGGCTCGCCCTCCGAGGGCCTGTTTGCGGACGGGCACC TGATCTTGTGGACGCTGTGCTCGGTCCTGCTGCCGGTGTTCATCACCTTCTGGTGTAG CCTCCAGCGGTCGCGCCGGCAGCTGCACCGCAGGGACATCTTCCGCAAGAGCAAGC ACGGGTGGCGCGACACGGACCTGTTCAGCCAGCCCACCTACT >18:46756320-46757040 (SEQ ID NO.: 178) CACCCGGGGGCTCGCCGGCCGGCTCCGCGCATCCCGCCCTCTCAATGGACTTTCTTA CCTCTTAATGTAGTTCCTGCCATACAGGATCTGTTGCAGCAAGGTCACCAAGGCAAA GGCGCAGATGAAGATGAAGAGCAAAGTTCGGCTCCCCAACAAATCCCGGTTGGCCG AGGGGTCCGCGTAGCGCATCCTGGCTACCGGGCGCCGCGGGCGCGGGGTACGGGGC GGCCAGGCAATGACTCGCGGGGTTCCGGGGCCCCGGGGGGCGCGCGGCCGACTTGG CGCCTCACGGTGCGGTCAGGCAGGCGGGGGACTTCGAGGGGCAAAGTTTCTGGTTG GCGCGGCCGGAGCTGGGGGCATCCAAGCGTCGCAGGCGCTGGGGCGGCAAGCAGG ACAGGGCCGGTGGCAGGGAGCTCTGCCGCGGCCAGGGGCCTTCCCCACCCCCGGGT ACCTTTACCTCCAGGCGCCGGTGCCGGGTAGCCGCCGATTTCCCCGCGGAGGGGAG ACGCCAGGTGCCACGAGCCGGAGGCGGCCCCTCCCGCCGAGGTGGCGGCCAATGGG GAGCAAGACCCGGGCTCCGTCCCCTGTGCGCCCCAGCGCGCCGCGCATCGACCCCTC CAGTCCGGCGCCGGATCGCGGTTGCCCAGCGCGCTGTGCCCTGCCGGGGGCGGGCC ACGTTTGATCTCCGGGCCCGCAGCAAGGGATCGCGAAGGTTGGCCTC >19:4328597-4329017 (SEQ ID NO.: 179) CTGCTTCTGACCACGCCCCCGCGCCCACCCTCTTCCCACCCTCCTCCCACCCAGGGCT CTCCAGACGCGCATGCGCACCCGTTGTGCATCTGCCGCGTGGTGACCGACACGCCGT CGGCGCCGTCCCCGCTGGGCCGCAGCAGCAGGTTCCCGCACTCGGGGTAGCGCTCC AGGAGCAGTTGTGCCTCCAGCCGGCTCACCTTCAGGAAGCACCTGTGGCGGGCCGC GTCACCCACTCGGGACCCCGGAGACCAAGTCCGCTCTTCTGCACGTAAACCCTGCCT CCTCTGAGACCCAGCCCCATCCCCATCCCCTAGGCCCAGGAGACCCTGCCCTGCTCT CCAGACCCAGGCCCCTCCCACGGAGACCCAGTCCGGCCTTCCAGGCTCCTAGTTTTT GTGGGGTTTTTTGTTTTTTTTTT >19:12867684-12868104 (SEQ ID NO.: 180) GGGTCGAAGGGGGCGTGTCTTCCATAACCACGCCCCCTCCATGCAGCAAGCGATTCT CCGCGTCCGAGGCCAGTTTCCTGGAGGGAGAGGCCAGTCCCCCTTTGGGCGCCCGCC GCCGTTTCTCGGCGCTGCTGGAGCCCAGCCGCTTCAGCGCCCCCCAAGAGGACGAG GATGAGGCCCGGCTGCGCAGGCCTCCCCGGCCCAGCTCCGACCCCGCGGGATCCCT GGATGCACGGGCCCCCAAAGAGGAGACTCAAGGGGAAGGCACCTCCAGCGCCGGG GACTCCGAGGCCAGTGAGTGCCCTATCGTGCTGCCTTCCCCAATCTTCCCCAATGTC CTACTGGTCATATAGTGAGCATCCCACGAGCCTGGTGCTGTTTATGAAAGATCTCAG GTCCTATTCACATTGCAATTTGGGAT >19:15551391-15551571 (SEQ ID NO.: 181) GTGCGGCGGAAGCCGGAGCTCATACTGCGCACGGAGAACGGGCTCTGGCTCAAGGT GGAGCCGCTGCCTCCGCGGGCCTGAGCGTGGGCGCGCCCCTGCGGCTCCCGAGGGT CCAGGCCCCGCCCCCAAAGGACCAGGACTCGCCCCAAAGATCCCGAGGGCATAGGC CACCCCCCTCGAA >19:18438234-18438414 (SEQ ID NO.: 182) TGGAGACCCGGTTCGAGGCCCGACAACCCAGAGCCACCGTGGCCATCGGGTCCCCG CCTGGCGGAAGTGGCCAGGCGTCCACGAGCGCGGCGCGTATAGGTTCACCTCGCTC GCTCCGCAGCCCCCAGGGGCTCATGGCTGCCTATCCCCCCTTTACAAGAGGACAATG AGGCTACACATG >19:19618353-19618696 (SEQ ID NO.: 183) CGTTCCGTTTGAACCCCATACATCCCTTCGTCCTCGGGACCCCCCTCCAGCCCTCCTC AAGCGCCCCTCGTCAGTCTGGCCTCCACGCCCCGTCCCCTCAGCCCGCCAACCTCAC TGCCACGACCCTGCGTGGCCCCTGCCGAGCCCGCGGGCAGCACCTGGCCTGTGCCTC GTCCAGGCTCTGGTCGGTGATGGCCATGATCTGCTGCAGGACGTCGCTCGTGTCGAG GCGCCGCGGGGCGGGGGGCGATGGCGCGGGGCGCGGCGGGGCGGCCATGAGCGGC AGGGCCGGGCGGGCGCTGTGAGGGTGCCGTCGAGCCTGGAGCACTACCACTGGCGC CGCA >19:20238353-20238533 (SEQ ID NO.: 184) GGGCCACAGAGGCTGGGCCTCCAGGAGAATAGGACACAGACCAGTGAAGACGAGA CCTGAAACGCCGGCTGCAGCTAGAGACAAAGGCCGCGCCAAAAGCGGAAAGCCGT CCTCGTCGCTCCAGCTGCGTGCCTGATTGGACGGTTTCCAGCCCAGCGTCTCTGATT GGATAATGCTTTAG >19:20424875-20425055 (SEQ ID NO.: 185) AGCAGAGAACACAGAGCAGTGAACAAGAGATCTGGAGCTCCAGCGGCAGCAAGAG ACAAAGGCCGCGCCATACCAGAAAGCCGTCCTCTTCGCTCCAGCTGCCTGCCTGATT GGAGGGTTTCCAGACCAGCCTCCCTGATTGGATTATGCTTAAGGCTCTGCCCCCTCA GTACCTGAGTGA >19:47243022-47243202 (SEQ ID NO.: 186) CTGCTTGTCTCTGGGACGGTGTGTGTGTGTGTGTGCGCGCCGCTGTGATTGTATGTCA GCGCGCTTCGCTGGGTGTCGGGGGAAGGTGCGCGTGTCTCCAGGCCTCCTGCCCGAG AACAGCGGCGCTGCTCTCTGATTGGCCGCGGCCGCGCCAGTGAGAAGCTCCCGAAT CCTGCGGTAA >19:47754579-47755119 (SEQ ID NO.: 187) AGAAGCTGGAGCGGCAGCTGGCCCTGCCCGCCACGGAGCAGGCCGCCACCCAGGTG AGCCCCGCACCTGCCCACTCCCTCCCCTCCCCGGGCCTCCTACCCACCCCTGACACT GCACCCCGCCTCCCCAGGAGTCCACATTCCAGGAGCTGTGCGAGGGGCTGCTGGAG GAGTCGGATGGTGAGGGGGAGCCAGGCCAGGGCGAGGGGCCGGAGGCTGGGGATG CCGAGGTCTGTCCCACGCCCGCCCGCCTGGCCACCACAGAGAAGAAGACGGAGCAG CAGCGGCGGCGGGAGAAGGCTGTGCACAGGCTGGTGAGCGCCTGGGCCAGCGGGG CCTGCCTCTGATGCCTCGCCCCCTTCCTTCCTTCCTCCCACCATGGGCTGCCCTGGGT GCTGCGGGCAGCCTGCACACCCCAAGCCCCGCATGTGGCCTGTGGTTTGGGCTGTTT GGGATCCTCACAGCTGAGACTCATTTCCCAGCCTCTTCCAGGCAGGGCTCGGGCTGG GGTGGGACAGGGTCCCTGGCGCTTCTGTTTGAGG >19:49142732-49143092 (SEQ ID NO.: 188) GTTCCCCCATCTCTCCGATTTTCTCCTCCTCTGTCCCTCTGTCCCCTCTGTCCCTCTGT CCCTCCGCTGCAGCTGTGGGTGGGCATGCCTGCCTGGTATGTGGCCGCCTGCCGGGC CAATGTCAAGAGCGGTGCCATCATGGCCAACCTGTCAGACACGGAGATCCAGCGCG AGATCGGCATCAGCAACCCGCTGCACCGACTCAAGCTACGCCTCGCCATCCAGGAG ATGGTCTCGCTCACCTCGCCCTCAGCCCCCGCCTCCTCCCGCACTGTGAGTGTCCGG CGGCCAATTCCAGCCTTCGCTTCCTCAGAGCCCCGCCTCTTGCCCTCAGTCTAGCCA ATCCTGGGCCTGCTCACTC >19:50050361-50050716 (SEQ ID NO.: 189) CCTCTCTGAGCCTCAGTTTCTTCAGTGGACTCAAGAATGATACTCAGTGTAAGGATT CTCAAAACGAGCATCAGCAGGTTCCGCCCACGCCGGCCTCCTGGGTTCAGTTCTCTA ATAACCACCTCCCTTCCCCGCCTACTCCAGCCAATCCTTGTGCTGACTCGGCTCCTGG CCACGCCCTAACCCCACCCCCGCTGCCTCTAAACCCGTCCCCACCCCTGCAGCCTCA CAGGCTGCCGTCAGATTCTCAAGCCCCTATTCCTCTCGGTGGCCTAAATCCCCAACT GCTCGGGGCCACTTTTCAGGCCAAAATGGGCCCAAAATGGGGAGGGCAAGTGATGA ATGTCACTAGACAG >19:53254542-53254962 (SEQ ID NO.: 190) CAGAGAAGAGTTTTAAGCAGAGAAACGACGCGGTGGGCGGTCGGTGTCCACACTGA CCTAAAGCAAAAAGGTCGGGGCCAGTACCCACTTCAGAACGATTTTAATCCGAAAT GGACGCAGATCTCTAGACCCTCTCGGAGCGACGGGACTGGGAACGTCTTAGGGCCA CGCCGCGAGAGGAATGAGCAGGTTCGGGGTTTTAACCTACAGGGCGACCCCAAAAC CCGACAGCGGAGCGTGGGAACCTGTGGCCCGCGAGGCGCAGGCTTGAACCCGAAAG ACGGAGACTCACCCGAGAGCGCCAGTAGCCCCGCGAGATCCGCTTCCGGGTCGGCA GGAACCTGCGCGTACGCGAGTGCACTGGGGCGGCGCAAGGGGCAAGGGCAGGGGC AGGGCGCGGACAACTGTGGGGATGGGCGGG >19:53866337-53866517 (SEQ ID NO.: 191) GCTGAGCATCCGCAGCCGCCACCAGGCCCCGCCCAGCGGCCGCAGCCAGCCAGGCC GCGCCCGGGACGACTGCAGAGCGCGGTGAGTGAACGCGGCCAGAGGGAGGGACTC AGGCGTCCCAGGTCCCCGCCCTGCCCCTCCCCGGGGGCCCGACATCCCGACCCTCAG CTCCCTCTTTTTC >19:53982150-53982330 (SEQ ID NO.: 192) CGAGGAGAAGAAAAACCACTACTCGTACGGCTGGTCCTTCTACTTCGGCGGGCTGTC GTTCATCCTGGCCGAGGTGATAGGCGTGCTGGCCGTCAACATCTACATCGAGCGCAG CCGCGAGGCGCACTGCCAGTCTCGCTCGGACCTGCTCAAGGCCGGCGGGGGCGCGG GCGGCAGTGGC >20:23049079-23049259 (SEQ ID NO.: 193) AGCGGAGACAGCGACGCACAACGGGCCGCAGAGGGGAGCCCCATTGAGGTCGAGC CGTGCCCACCTGCTATAGCTGGTGTTGTTGTCTCCCGTAACCCACTGGAAGCCGCGC AGGGGCCCGAGGCGCTTGGGGTCGCCGCAGCCGGGTGGCAGCTGCAGGCCGATCCA GAGGCGCCGGCGG >20:23049351-23051331 (SEQIDNO.: 194) AGATCTGACTGGCATTGAGGAAGGTCGCGGGGCCCGGGTAGAGCGCGAAGCAGTCG TGCTCGACGCACTGGCTGCCACCCGGCTGCGGCTCTGCGGGTGCGGGGAACCCCAG GCCGGCCAGGGCCAGCGCGCCAAGGACCAGGACCCCAAGCATGTTACCCAGGCGCG CCGCGTGCAGGCGCCGGGGAAAGCGCGGGCACTGCGACAGGGCCGTGCCGGAGCA GAGGGGCACAGGACGCCGATGGCGACAGCCTCTCCTGTCCGTCCCAGCCCAGACAC TTCTTGCCGCTGCGCGCAGCCCCTGCGAGGCAGCCTCTGACATGCGGATCGGCCAGG GCTCGAGTTTATAAGTGCCCGGCCCTCCCTCCCTGGACGTTCGGGAAAAGGAAGGA AGTGCCTGGTGGGAAGGGCTGATGCCGCATACTCGGATTGCTGGGTTCTCTGGCCGC CCTTGCGCCCGCCCTCGCGCATGGGATCACCTCGCCGGGATGAGTAAACCCTGCCCT GGCGCAGGGAGGTTCTCGGGCGGGGCCGACAGGGGCAGGCGCCAGGGAAGGCCAG CACCCCTGTAACAAGACGACTGTCCCCGCCCACCACTCGGGCCCCCACGCGTGCAGC CCTCTTTCATCTCTTGGTCCTCCTTTCTTTCTTTTCATACATGTTACAGCCACTTCCAA GGAAAGCCTGGATTGCAAGAGCTCTGGGAACCGGAGACTTCAGAGAAGAGGGCTTT GAATGGGGAGTGGGGGAGGTGGTGCACAGGACCTGCAAGACGCTGGGAGGGGTGA TCGGCACCAAGGGCACTTTGGGAGGACCTGCCTAGGACGTGGACTTCCCCGAAGAC AGGATCGCAAGGAGAGACAGCTGGATCCTGTCCGCGGCCAAGGTGCCTGGCTCAGG AAACCAGCGGAGCGCGCTTGGCCTCACAGGACAGTGGGTGTGGCTGGGGTGACGGG GCAGGGTGGGGAAGACTGGCCTAACACCAGCGCCCTCTGCCCCATGGCTGGCCAGG GACCCGCGAGTCCCTGGACACGCACTGGCCAACGCCAGACCCCATCTCATCGGGTG GGGAAGTCGCGGGGACACTGTCAGGGCGCCGAAGTCCGGACCCGGCTCAGAGGCG GTGGCAGGTGAATTGCTGCGGCGCCGGGTAGGGGCGGGCGCGTGGGAGCGAGTCAG CCTGGCCAGTTTCGGCCCAGCTTCCGAAGGATGGTGCTTCTTGCACCCCAACAGAGT GGCTGGCAACCCCCCAGGGGAGCGCGCAGGATCCCAGCTGATCCCACCCGGGTCGG CTAAGGAGGTTTCCATTTCGTCCAGAGTCCGAATTGATACCCACGTGCATAGAAACG CCACTTGCTCGGCAAAGGGCACTGAAGAGCCACCGTCCTGTGGATGGGCAGGGTGG GGGGGGGGCTGGAGGAGGACATGGGAATCCGTCACTTTCGACCTCTTCCGGTGGTTC ACTTACCGGGAATGCGGAAGAGTGGGTCTCCCCCTCGGGTCGCCCCCATAATGGTG AGAGGCAAACTGTTTAAAAACACCCTTGCCTCTCTCCTCTACTGTCCTCACAACGAG CGCCAGGGGGCGGCGCTGTCGAGCTCTAAACAAAGCCAAGGAAGTTGGAGAAGTTT CGGGCTAAAAAGGGTTAAGGTGTAGGAGCACAGAGTCCTCCTTCTGGGGTTGGAAG CTCCGTTCCCGGGCAGCTCAGCGTGGATTCCGCTGCGTTCACCTCTTGCCTCCAGGG CCCAGTAGATCCTGGGCTTTAAACAAGAACAGAGAGTATGGCGTCTGCCACGTGCG ACAGACACGCACCGGTGGGGTGGGCCGGGCTGGACTGGACTGACCTGCAGTGACCA AACGGGTGGGGCGTGGACACTCTGAAAGTGAAAAAGGCAAGCACGACTGTCCCGCC GCACACTCCCCAGCGCCTTGGGGCAGAGAGCCTCCAAACGTCCCGCTGAGTTGAGC TCTTCGCTGGGAA >20:43188826-43189486 (SEQ ID NO.: 195) CTCCAGCACCCGCCAACGTGCCTTTAGGAGCACGGCAGGCACCACCCCCCCGCCCCC GCTCCCCCTACTCTGGGGAACTACCTCTGCTCACCGCCTTCCCGTGGCCAAACCCAA ATATGAGTTCCCCGAACTTTTCAGGAGCGGACGCGCTCACGGGTCAAATCCACTCCC CTCCAAGGGCCTTAACACGGGCGCCCAGCTACCTCGGAGAAAAGCCAGCGGGTAGG GCGGAGGTATTGCTCTCGGTCATCAACGCAAACATCCCCTCGGGTGCCTACAGCGGC CTGCTTAGGGGAGCAGCGTGTTCAGAGCAAATGGAGAGCTTCCTGTATCTCCGAGG AAAAAAGAAAAGCCGCCGCCCCGGCAGCCTCGGCCTGCTGGGGACCTGTCCTCCCC ACTAAAAGCGCGCGCTGCCCGAGGAGCTGCCCGGGAGAGAACGCTCCACCCCGGGC GTCGGTGCCGCTCCTCGTCTCGCCGCCCCAAACACTCAAGTGGCAGATTCCGACAAG TGGGAGGCAGCAAGTGGAAATATTCGCAACAACCGCGGAAAGTTACTCCAGCCCGG GGGGCCGGCAGGAAACTGAAGCGGGGAACTTCGCCAAACGCGGGCTGCCGAGGGA CGCGAGGGGCCGGGCTCGCTGGCCGGGGCGCGCGGGGACAC >20:48828207-48828567 (SEQ ID NO.: 196) GTCGGAAGCTCGGGGGTCGGGCGGGAGCCTCCGGAAGGGCCCCGCGGAGCCGGGA GTCCGAGGCCGCGCGCACGCCGAACCGAGCGTACCAACTCCGCGCCCGGACGCGTG GCGCCCCCCCAACCCGCAGTCACCGCGGGCTACGCCACTCCCACCCGGCACACGCG ACACCCGCCGCGCGCAGGCTCCTGCTTGCAGGTCCGGCCGCTGCTCGGGCCAAGTA AACACCGGGCTGGGAAAGCTCGCTGCGGAGCCGCTCGGGGGCAAGCCAGCCCCGCC ACGCGCGCCTCCGCGGCCCCGGGAAGTCAGGGGCGACCGCTGCCTGGGCAGTGACG GCCCCTCTCTGGGCAGTGACGGCCCC >20:63829922-63830102 (SEQ ID NO.: 197) CTCGGCGCACAGGTGTCTGCGCCCAGGCCGCGCGCTAAACACGTTTCTAATTAGCAT TTCTTTAAACAATGCTGATCACAATCTTGCCACCGTAATCCACTCCAAATGCATCGTT GAGATTGCAGCACGGAAAGCGAGAGAGGAAATTCGCTGCGAATCTCAAACTTTCTT TTGTTTATAT >21:26843610-26845470 (SEQ ID NO.: 198) CCCGGGAAAGACCTCCCAAGCAGGTTCTGCGAAGGGGCCCCACCGCCTTCAGCCCG CCTGGGTCAGCCTTATAAGGGGGAAAGGGGACAGAAGTCTGCAGAACAGAGATCCT AGCGTAGCCGCTCAGGGTACCTTCCCAGGTCACCATTGCTCCTCTGCCCTCTCCACA TCCGCCCTCCCGTGAGCGCAGGATGCACGCACAGGCAGCGGTTACAAAACTCAGCG CAACGTTGCAACCCGCACAAAAGGCGCACACAAAATCATTAAAAAGAAATACACAG AGTGGAAAGAACTCGCACAAGCTCCAACTCGCTAAAGGTGGAAGGAGTCAGGTTAC AAACTCTCCCTCCCCGGCCTAAATGCTTTGCTTTAGTTTGCAGAAAATCGTTTGTCAG TTTTTTTCTTGGTTATTCATTATTCGGGCAAATGCAAGTATGTTTTCTAGCTGAGTTC ACCAATCCAAACCTCAAACCACATTCCTCCACTCCAGGCCTCCGTTCTGTCCGCGGA CTTATGATCCTGCCTGCCAGCAGGAGTCTACCCTGAAGTCGCGTGGGATAGATAAAG TGAGGAGAGGAGGATGAATGGACAGACAAACGAGAGCAATTCTTCTACCTGTGGGC TGTCCTACGCCTTGCAGTGCCGGGTCCTGCGGCGACCACTGAGCCCCTTCGTCCTCG CCCTCAGTCCCTTCGTCCTCGTCTTCGGTCTCCGCTTTCCCAGTCGGCCGGGGCTCGT CGTCCACGACCCCGCACGTGCCGCCGACGTCGCCCTGCCGATTCCGCCGCAGGAGGT GGAACTGTAGTGGTGCCGGCGGCTTCTCCCCTGGGGCGGCGGTGGCGAGGCGCTCG CTGGCGGCGGGCAGCGGCTGGATGAAATACGCCTCCCCCAGCAGGTAGAAGGCGCC GCGCACGCCCTCGCAGAGGCTGAGGGCGGCAGCCGAGCTGGGATCGCCATTCACGG TGCCGGAGTAGAAGCAGTGCGCCAGGTCGGTTTCCGGAAGCGGCGTCTCGGACCCG GATTTGCGCCCCACGTTCTGGAGCGTGAAGCCGGGCGCCAAAAAGCTGCTGTCGGG CCGCAGCTCCAGATCCAGCTGCTGGTCAAAGGCGTGCAGGCGGAGGCGCGTGGTCC CGTGTCCCGGGGCGCGCTCCAGCTCCGGCACCACTAGCTCCTCGTCCTCCTCGGAGG GGCGCCCGAGTGCGTCCGACACGGCCAGTAGCGCCGCGGCGAGCAGCAGCAGCGTG GGTACTGGCCCAAAGCTCCGAGACCCCGGAGCCCGCTCCGCGTTCCCCATGTCGCTG CCCAGCTTGCGCCTTCCGAACCCCTCGGGCACAGCTCGCTGCATTGGAGCCCCAGGA GACACCGCTCGTAGCAGCGCACGGAGCGAGGGACCTTTAGTTCGGGTCGGGAGAGC AAAGCCTCGTTGGCCTGCTCTGGATTGTTAAAATTAACAATTTCTATTATTCGTTGGA AGGGCGCGCAGAGCCGGCTACAGCCGAAGCTCCCGGAGTCACTAAAAGGAGGCGCT GCAGTTCTGCCGGCGCGCGGGAAGTTTTTCTTCCAGCGCAAAGTTGGAGACACTGAG AGGCAGGCGCAGGCAGAGTGGCTCTGCTGGGACAAGAAGCGCTCTGGGGCGCCTCC GGGGCTGAGGCAACGCGGAGATTGGTGCCTGGCGCCCCTCTTCGGCCTCCGCCTTGG CTGCGATGTTGCTCACTCTGCTCAGGGCTCTCCCCTCTCCGTCCGGTAGCGCACCCTG GCTTTGCAATAGCCCCTGGCTCGGAGCCGCTTTCCAGCGAGTGCAAGAACCGGGCA GCCGAGCGGTCCTTTTATAGTGGACCAGTGAAACCCCCACCCCCACCCC >21:33071136-33071916 (SEQ ID NO.: 199) GCGTCTGGGAGAGCGAGGCCGAGCAAGGAAAGCATTTCGAACCTTCCAGTCCAGAG GAAGGGACTGTCGGGCACCCCCTTCCCCGCCCCCACCCCTGGGACGTTAAAGTGACC AGAGCGGATGTTCGATGGCGCCTCGGGGCAGTTTGGGGTTCTGGGTCGGTTCCAGCG GCTTTAGGCAGAAAGTGCTCGCTCTCACCCAGCACATCTCTCTCCTTGTCCCTGGAG TTGCGCGCTTCGCGGGGCCGATGTAGAACTTAGGGCGCCTTGCCGTGGTTGGCGCGC CCCGGGTGCAGCGAGAGGCCATCCCCGAGCGCTACCTCCCCGGAGCGGAGCACGCC GGCTCCCAGTACTAGGGGCTGCGCTCGAGCAGTGGCGGGGGCGGAGGGGTGGTTCT TTTCCTTCTCCTCCGCCAGAGGCCACGGGCGCCCTTGTTCCCGCCGGCCAGGTCCTAT CAAAGGAGGCTGCCGGAACTCAAGAGGCAGAAAAAGACCAGTTAGGCGGTGCAGA CGGTCTGGGACGTGGCAGACGGACGGACCCTCGGCGGACAGGTGGTCGGCGTCGGG GTGCGGTGGGTAGGGGCGAGGACAACGCAGGGTGCGCTGGGTTGGGACGTGGGTCC ACTTTTGTAGACCAGCTGTTTGGAGAGCTGTATTTAAGACTCGCGTATCCAGTGTTTT GTCGCAGAGAGTTTTCGCTCTTAAATCCTGGGGGTTTCTTAGAAAGCAACTTAGAAC TCGAGATTCACCTTTCGTTTCCCTTTCCCCAAAAGTAGCGTAACC >22:24654234-24654594 (SEQ ID NO.: 200) GAGAGGGGCTTGTCACACGGGCCCCTGCCTGCAGTGTGACCCTTCTCAGCTTCTCTC AGCAGCCCTGCCTGCAGAGTGTCACCACCACCATGATCATTTCCCTGACACTGCGAG GGTCGGGGGACGTCCTGGGTAGAGACAGGGCCCGTGGCAGCAGCAGGCTCAGGGG CGCCCTACACTGGTGGGCTGGGGACCTGGTGGAGACCACGCCAAGGGCTGGACAAG GGGACGAGCCTCCACCCTGGCCTCTCCGCAGGCCTCAGCAGCCCCTCCCACAGGCA GAAGGGTTGACACTGGGTTCTGCCCTCACTGCAAGAGCTGCAAGTGCCACGTGCTGT TCTGCCCAATCTGGTGTCTGCAG >22:25282006-25282426 (SEQ ID NO.: 201) CAACACCCAAACTAAAACCTCTCACCTGAGTGTAAGGGCGTGCTGACCTTCTTAAGC AGAGAGCTCTTCCATCAGGGGGCTCCCTAAGGGCATCTCTGTTCCTAGCGGCGAAGC CCTCACCCCACTTTGCTCTGCTTAGCCTGAGACACGCAACTTTCTCCAGCCTTTACTC TTCGCTGAATTCTCACGGCGGGCTTGCGGGTACGTTCAGGAGCGAGGTTGGGGGCCC GGCCCGCTGGGCGCTGTTCACAGGTAGCTTGGACCAGAGCAGGGGCTTCATCATTAC CTGCGGGGACAGGTGGGACACATGCATTTCCGGGGTCATCCCAGACCTCCTGGAGG ATGCTGATTGATGCTGTCCCGTTTGAGAACTACTGTGTCCAGGTAGCAGAGGCCTCC CCGATGCCCCTTGAGTAGTGGG >X:108732499-108733039 (SEQ ID NO.: 202) CTAACACTGTAGACTGTAGCGCATCGAATCATTAGACAATGACCATTCACTTTAGGG AAATTAATTCTAAAATTACCGACCTCTTTTGGGAGAGTCGAACTGATTATCACGTCT GGCAAAATCCATTCTCACGTGAGTGTCGTCGTCGTTGTCAGAATCTTCTCTCTCCGGG GGTCTTGGCACCCGGCGACTGCGAGGTGGTGGTTCCGGAGCGGCAGCTGCAGCGGC AGCCCCGCCAGCCTGGTTATCACCTCTGGCAAGGTTTGCAGATGGGTTGTGGGCTCC AGGGTTCGAGCCACCGGCAACGTCTTGGGCTCCCCTTACTGCTTCGGCATCAGCAGC ATTAGCAACAGGTTGAAACCAGCGGGCAGAGGCGGAGTCAAATCCAGCAGCTGCGG CTGCTGCGCCGATGCCCGGGGCTGCGGCGAGCGCGGAGGCCGCAGCTACAACTTGG CTGAGGGCTAAAGTCGGCTCTGCAGCCGAAGCGACAGCCGGGGCTGAGGATGGGGA AAGGTCTCTCTCGAGGCTGTCTGTTGGAAAA >X:114582244-114582664 (SEQ ID NO.: 203) AAGGCAAGACTAAGCATTCCACATTCATAGAGTAAGGGGACACTTGGGGAGTTTTT AAAGATGAGTGCTTAATTATTTAAAGAGAAGACATACGTTTTCTCTTCCATATTTAT AAATTACTGTTCGCTACCAAAGCATTTCTAAAGATGCGAGCGTTGTGCAGTCGGTGG ACTTGGCAGCGCTGTCGCAGCCACCTGTGCGGCATCATACAGCAGCATTCAACAGAT GCTTCAAGAAAACTGCGATGGGTTTTTGCTTTTCGAAACAGAACTTGGGTGCCGACA GTATGTTCACTGCCAAATTAAATTTCAAAGCCTGAATTCAGTGGCGATGGAGGGAAT CAGAGGATTCCCAAAATGCCCCTTTTGGAATAGACTGGACAGCTCCTTTCACAAATA TGGAAACAGAGGCACAGAGAGAA FIGs. 3A-3G SEQUENCES >19:56507424-56508024 (SEQ ID NO.: 204) AATAAGCTTAACACAGAAAGATAATGACACTCCCACGGACTGGCACAGAAGGCCGC GCTCCGAATGACATCGCGATCACAGAGGCACAGACAGCGTCACAAAGCCCCACGCG TACTCACACCGAAGGCTCAGCCGTCGCGCGTTTCCCTCCCAGGCCCCAGGAACTAGT AACTAGGGACGCTTCTGGTCTCTAGGCGAGGAGAGGGGGAGAGCGCAATCTTTGCG CCTGCGCACACTCCTGCTCTTACCCGCCGGAACCCTGGGCCACGCCCGGCTCGCGTA ATCACGCACTGCGCAGGCACCGCCCGCTCTGCTCTAAGGTCCCTCTCACTCCTTCAG CAGCCCGAGGACAATCCCCTCAACACTAGGCCACGCCTTGTCTCCGCCCCTCTCGTC CGACCCCTGGAGAGAGGCTGGCGCCTGCGCGATGGGGGGTTCCAGCGTCGACTCAC GGAGTCCTTCGGATGAGAGCGTCTGGGTGCCAGACGAGGCCGGGGGTTTGTTTTGG GTGGTTTGGGAGTCCGAGCTCGAGGGCTGGGCCAGGAAGGGCAGGCGAGGCGGGC GGCTCCGACGCGGGTCGCGAAGGCCCAGCCGCGTCCTC >19:56508112-56508652 (SEQ ID NO.: 205) GGCGTTCGGGGCGGCTTGGGGCGGCGGGACCACTGGAGTGAGCTGTGGGAGAGATG GGGGTGTGCCTGTGTGTAAAAGATCTGTCAGAGTGTGAGGCTCCGTGAGAGGGTGT GGTTTCTGTGTGTGTGTGTGTGTGTGTGTGACAGACCGAGAGTCCAGTGTGAGACCA GGGTATGTTCGTGTGTGACAGAGCGAGACGGGCCAGTGTGAGAGACCAGTGAGTGT GAGAGAGATAGGGATGTGCCTGCATTTGAAAGAGAGCGTGTGAAGCTCAGTGAGAG GTTGCGAGGTGTGTGGGTGTGTAAGTGTGTAACAGACCAGGTGTCCAGAGCGTGAG ACCAGGATGTATTCGTGTGAGAGAGTGAGACGGGCTGGATGGAGTGTGAGAGACCA GTGAGTGTGAGAGATGGGCGTGTGCCTGTGTGTGAAAGGCCGGTCGGTCGGTGGGT GAGGCTCAATGAGAGGCCGGTGTGTGTTCGAGAGAGAGAAGAATCACCATGTATGC GAGACTAGACTGTGCAAGAACAGAGTGTGAGACTGT >19:36915828-36916968 (SEQ ID NO.: 206) CTCGTGATCCTCCTGCCTCGGCCTCCCAAACACAACCTCCACCTTTCAGGCCGCTCC GCCCGCAGGGGCCCAAGGCGCCAGCTCCCCATCGGTCTTCGGTATCCTCACCTAAGC CCTTTCCAGTCATCCCGGATGGGAACTTGCAGACCTGAGCCAGTTCTCCTGGGGACC AAAATATCTCACCTCCCAGATCTAAGGGTCCCGCCAGGAGTGACGAAACGTTCGAA TTCCTGCGAGAAAAGTGGCAGGCCACCAGGCCCTCTGGGAAATGTAGTCCAGAGCG GGACCCACGCCGATTCCTGTCAGCTCCTCGCCTGGGCCCACCCGAAACGGCTGCTCC CTCAACTCTCAACATCCAGCCGAGCCTCGGAGTTGCGGGTCGCCGTAGCGCTGCGCA ATGGAGATGAGCCTCCCGGGGAACCCGGCCCAAGCCTCACCCTCACACAGGAAAGC AGATGTGTTCTGGCCGGAAGTTGAGTGGGGCCGCGGGGCCTGCTGGGAGGTGTTGT CCTCGGAAACGTCGCTGGCGCGGAGGGATGGTTCGGCGCTTTAGGCGTCTGTCACAG ACCTATCTGCGGGTCGCCTTCACCCAGCATCTCAGAAACTGCGCGCGGGATGAACAT TCGGGTGTTTCCGGCAGGTGACGCTGCCGAGTCCCCGCAGCAGGGGGCGAGCAAGG GACTCGCGGTTGACGGGACACGGATCCTCTAAGGCCCAGAGTGTCCCGAGTAGCGG CAGTGGGGAGTGCTCAGGGTACGCTAATGGTGAGTGGTTGCAGTTGATGGGACAAA AAACTGTGATGGGAGTTAGTGTGGGTGTGTGGTTGTGTGTGTGAGTGTGACGGCACG AATAATCTGATGGGGTGATTGTGATATTTGGTTGCGCGGGATTATGATGAAATGTGT GATATGTGTGTGATTATGATTAAGGCTGTAGCGAGTGTGAACGTGGCGAAGTGTGCG TGATTGTAATATGTCTAGTAGTTCTTGTCTTGAGCTGGCTTTTCTGTAGCATTTGGCA CAGTTGGTAACGGCTTGAAAAACACTTATTTGTTTTCTACTGATCCTCCCTCCTTGTT GGCCACTCCTCTGTAGTCTTCTTTGCTGTCTTTTTTACCCTAGTAGCCCTTGGCCCTTT GTAA >3:151086591-151087491 (SEQ ID NO.: 207) CCCCCTGGAGACAAGGTAGGGGGGAGCAGAGGAGGCAGGCGCCGCGGAGGACCCT GGCCGACCTCTAGTCCCTCCGCCGCCGCCACCGGAGCGGTGCGTCCCGGGGCTCGA GCGCAGCCGAGTACCCGCCGAAGGCTGTCCCCATCAGTGCGTGTCTGCTGCCGGGC AGCGGCAGCATCCAACCTGCTTTATTCCTCCTGCCTGCAGCGCCACAGCGAGCGAGC GAGCGAGGAGGGGGAGAGAGGGAGTCTGTCTGCAAAGTGCTGCTCCCTGGTGCTCA GAGGCGGCTGCTCCAGCTCCAACTCTCATTCATTTCGCCGGTTAACATGAGAGATCA TGGCCGCCTTCGGGCTTCTCAGCTATGAGCAGAGACCGCTGAAGCGCCCCCGGCTCG GGCCGCCCGACGTCTACCCACAGGACCCCAAGCAGAAGGAGGTAAGGGCGCCGGC GGCCTCCCCGGCAACCGGGGCCGCGCTCTGCAGCACTGACCCGGGGCCAAGTTGGC CCAGCGGGCATCGCCGGCGCTGCGGTGGAAGAGGTCGGGGAGGGGGATTAGAGGC GGGGGCCAGGCTGGGGGTGCTGGGCGACCCCCCGGCGGCGGAGACCGAGCGGCTGT CAGTCCCCGCGCTCCACTGGGGCGCTCGCTTTCCATGTGCCGGTCGCTTTCCCGTTGC CGGGCCTTGCACGGCGCCGCCGGGCGCTTCTCGGGCTTCTTCCCTGCCGAAACCTTG CTCGCTCTCACCCGTTTCTGCCTGCTTTATTTTTCTTCTTGCCGCTTCGGTAAATCGTC GTAAACTTTTTGAAAAATGTTGGAATGCAGTGCATCCTACACTGAGGTCTTGCGTTT TGCTTTTGCTGGCCAGGGACGAAGGTGAGGGGGAAGCTTTTCAAATTTTCCAGT >4:141132059-141132899 (SEQ ID NO.: 208) AAAGTTAGCCCGCCACGTTGAACCCCTGTCCAAGCGGCGCTATGCCAAGCTCTCCGG CAGCCTCTCCCCTACCCAATACAGTTAATCTTCTCCTCTTTGTAAACCCCCCAAGTGA CGCGGAGCAAAACTTAATCGGTCCAGGGAACCCAGACACGTCTTCCGCGCCGCACG GACTTCCCAGAAGGAGCCTGGAGGCAGGCGCTGGATCCCTCTAGGCACCTCCGTCC CCGCCGGCTCCCCTCCCCCGCGCCCGCTGGGCCACTCACCCGCGTGGGGCATGGTGA TGGTCTCGTTGGTGTTGGAGCCCACGTTGAAGATGACCACGGCTGAGGCGTTCTGCA GGAACGCGTTCCGGATCTTATCCCTGTACGTGCAGTTGCCCTTGGGGATGAGGGCTA TCCAGTTCTTGCCGCGGGTCGGGGCGGCGAACTTGGTGTTGGGGTCGCAGGCCAGGC GGTCGTGGGCCGAGCTGGCCATGACCACCTCCCCGCGGGCGTCCTGCTTGGGCGAGT GCTCTCCGTAGCGCCCGCACTCCGTCTTCTCCGTGTGCAGCTCCGCGCCGCCGCCGC CCGCCGCCCCGGCCCCGGGGTCCGGCGCGGGCTCGGCGTAGGTGATGTTCACGAAG GCGGTGTACCATTCCTCCTTCTCGGCCACGGTAAAGTCCAGGCAGAGCAGATGCACG AAACAAAAGGAAAGCAGCCATGTTGAGAGAGCCAGACTGCAGCACGCTTGGATGA GAGACATTGCCATCTTTATCCGCCGGGGCCCCCTCCCCGCCCCCGCGCCCTCCCTCC GTCCCGTCCCTCCTCCCCAGCCCCGGCCAACCCCGGGCCGCTGCCTC >7:35185861-35186281 (SEQ ID NO.: 209) GCTTTTTCAGATTTGGGATCCTCCCCGGGGAGGACCTCCTGGCGCCCCCTGGCAGTT TCCCGCCGCCTAGGGCCGACTTTTCCACCTCCAGCTCCCGGGCGGGGGAGGCCCCGT ACGGCCGCTTAGACGGGCTGGGGCGGGAAGATTGCAGCGGCTTTGGGTTTACTCCTT GTTTCTTCATAATCCCTAGTGGAGCTGGGTCAATTTCAGGCACAGCCCATCCGAGTC AGGCGAGGTCCAGAAAGGCCTGACTCGCCTGGCAGCCTCAACGGACTTGTCCCCGC AGCCGTTGACTAGCCGTTGACGAGCGGACCTCCCGGTCGTCATGGCGACTGTGAAAT GTAGGGTGGAGCGCATGCGTTCGAAGCCATTCGCGCGGGCAGTCCCTGCGTGTCCCC CTGCGTGTCCCCCCACGTGCTCC >7:141072108-141073057 (SEQ ID NO.: 210) ACTCCGCAGCCGCTCTCAGCTCAGTCCTAGGTGGAAACGCCTGTAGCTTGCAAGGTA GCGCCTGTGGCTTTCTGGGGAAAAAAAGATCAAATGCCTCCCAAGACACCAGCGAC CCAAACCGGGGATGCAGGGAGCTCGCTTGGCCCCTTTGAAGGCCGACTCCGCAATA AGCAGTTTTTCCTTTAAATAACCGTAGTGGATTTGAGAGAATTTTCCATGGCTGAAA AGAGAAACAGGAGCTGTAGGCAACATCCCTAAATTTATAATAATGCATGTAAACAT GCTACATACCACATATATGTATATGTGCATAAATATGGATGTGGTTGGGCACATACC TATCTAGACACCATTGACTTGCCTGGTCAAAGAATAAGACTTAGACATTTCGTGCCT GGGAAATGGTGCAGTTTATCTTTAAGGAGACTAGAAAAATAAGAGATGAGGCTCAC GTTGCACGGATGACATCACTAGCTTTTGGCTGCGCGCTCGGTGTTCTCGTCTGTGGGT TTTAGCCAAGGCTGCAGCTACCCGCGCCGGACGAGAGAGCGCGGCAGCAGCTTCCT CCGGCGCCCGCACCCGGGCAATGCGATTTCCCCAGTCCCCTGGGCGCAGCCTGGGCT CTCGCGCCTCCCGGGCACCAGCCGAGCCTGCGAGGCCTCGGAGCCGCCGCGGCTAG AGGAGGAGGCGACGAGGGGAAGCCGAGTGACCCAGCCTCCCTCCCCCACCCTCTCC CCATTCATCTCGGCGACCACCGCGCGCCGGGAGCCGGATCGTGGGACGCCGAGGCC AGGACGGGATTCTCTGCACGCTGTCGAGTGAGCCGGCATCTCGGCGCCCGGGTGGG CTGCGAAGAAAATGGTGCAATCTGAGAGCGACTGAGCCCAGCTGGGCAGAGCAGAC GGGGTGCCAGAGTGCCAAGGGCTCAGGTGCCTGGAGAAAGGGGCGGA >9:21970722-21971382 (SEQ ID NO.: 211) CCCATTTGCCGCCCTGGCGGGGCAGGGCGATAGGGAGACTCAGGCCGTCCCACCGA TTGGCGCGTGAGCTGAGGCAAGACCGGAGACTGGTCTCCCGGGCTGAACTTTCTGTG CTGGAAAATGAATGCTCTGAGCTTTGGAAGCTCTCAGGGTACAAATTCTCAGATCAT CAGTCCTCACCTGAGGGACCTTCCGCGGCATCTATGCGGGCATGGTTACTGCCTCTG GTGCCCCCCGCAGCCGCGCGCAGGTACCGTGCGACATCGCGATGGCCCAGCTCCTC AGCCAGGTCCACGGGCAGACGGCCCCAGGCATCGCGCACGTCCAGCCGCGCCCCGG CCCGGTGCAGCACCACCAGCGTGTCCAGGAAGCCCTCCCGGGCAGCGTCGTGCACG GGTCGGGTGAGAGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAGCAGCAG CAGCTCCGCCACTCGGGCGCTGCCCATCATCATGACCTGCCAGAGAGAACAGAATG GTCAGAGCCAGGGTGGGGGCCGGCATGACGGAAAGGAAGCTTGTGTAGAGCCCCCT CACCGCCAAGCAGACCCCCACACAAGCCCCAGGTGTCTAATTACCCCTACATTTGCT TCCAGTTTCCAATTTCCTTCTTGAGTTCTCTATCCATTCTT >15:64823877-64824537 (SEQ ID NO.: 212) CACAGGGCTGATGGTGACGAAGTCGCGGGGCCGCGGGCCCAGCAGCTGCGCTCGGG CGGAGGCCGGCCCGGGACCCGGGGCCGCAGCCAGCTTGAGGCGCAATGTGCGCAGG AAGCGGCGCAGGCGGTCTGGGGGGCAGTCCGAGAGCAGCAGCTGCACTGCGCCGGC CCCGGGGGTGTCGTGGGCGGGGAGCCGCAGGGTGCTGCGCCCGGCCTCGGCGAAAC GCGTGAAGAGGCGCGCGGCGCGCAGAGGAAAGCAGCGCGGCCGCCCCGCGGGCCC TGGCGCTTGCAGCCGCAGCATCAACTCGCGGCGCTCGTTGCGACCCAGGCTCAGCTC CGCGGTGCGCAGGGCCTGGCGCCTTCGCGGCTGCCCGCCCGGGCTCAGCTCCTCCAC AGCCACGCGGCACCGCAGCTCCGAGTCCTCATATTCCCCTGCCGCCGCCTCTATGCC CGAGAGCATCGTCACCGCCTCTGCTGGTCTGCGAAGACACCGGAGCACAGGGGTCA TGAGGATTCATGAGACGTAATGGGTGCTATAGGGGACGTAATGGGTGCTATAAAGG ACGTGACAGGGAGCAGGGTCAAGGCTACACAAGATCACGAGGACTGTCACTGGTAA CACAAAGAGGTCACAAAGACGGAGAAAGGGCTTTGGGCTAACC >15:79089695-79090115 (SEQ ID NO.: 213) CGAGGAGCTAGCGCAGACCGCTCTCCGCCCTCAGCTGCGGCGAGGCAAGGGCTGGC AGCGCTCGGACGCCTCCGTCTTGCCCTTCCCATGCCTAAGCGCGGGGAATTACACGT TCCCGGTGTAGAACAGACGATCGGGGCTATTAGGGCTGGGCGGTGGGAGTGGGGGT TGGGAGCACCATTTTTGGCTGGACGTGTGTCCAGACTCATCGTCTCTGGTCCTTAGG ACCCCATCTTCCTCTGCATCTCCAGGTGTCGGCCCCTCTGTACCCGCCTCCCACGGGG CTCGTCCGGCGAAGGGCAGCCGCAGCCCACATCTACTCCCCGCCCTCAATCCCTGCC CCCTCTGCCCGCCGCAGTCACTCGCCTGGCTGGGAGCAAGCCTCCCCTCTCGCTGAG GGTGCAGAGAGCGCCTAGGGCGC >16:70737472-70738072 (SEQ ID NO.: 214) ATCCTGCAGAGGGCAGGAGCATGAGGGAGAGTGCCATCCCTCAGCTGAAGGCCACT GTGCCTTGTATTTCTGGTTTGGGCAAGTGAGGAGCCTGCCAGCCCCTGGCAGGAAGT GCACGTGACCGGCGGCTGGCCAGGGGCACAGAGACGCACTCCACACAGAAACCCA GGCTGGCGGGGTGGGCGGCCGGGGAGCCAGCCCTGCAGATGTTACTAAGTGAAACC TGATGTGGTGACATGAGAATCCACAGAACGTCTCACAAACAACCTGCCCCGGGATG TTTTGGATTGAGTTTTGTGGTTATGACGTGAAGAAACCTCACATGTCAGGATAAAAA TAACCCTGGCTTCAGTACATAACGCGAGTTACAGTTCAACAGAACCAGATGTGAAA ACGTCAGCCACCCAGTTCAGGCCCAGCAGGGTCCCTGCTCCACTCCGGCCTCCCTCC CTGCTGGGGTTGGGGTCCATGTGCCCGGACAGCCCGTTGTGGGCTCAAGATCTGCTG CCTGGAGGATACAAGGGAAGGGCCAGAGGCCGCTCAGGGGAGGCAGCACCACCTT CTCCGAGGCCAGCTCCTCTTCTGTGAACCAGGCAGGGCT >21:31343623-31344643 (SEQ ID NO.: 215) GGTCGGGAGCCACAGCTTCTGAATATTCCTTCGGAACTTTTTTCTCACTTGATTCCCA AGCCTGTCATGGGGTTCTTTTTCAATGGCACTGACCTGCAATTACCCAACGAGCAGC GGGACAGCCCCGGGCAGGACGCATCCTGGGTGGGTGACGTGATCCCGCAGTCTCCT CCCCGACCCCATATCCCATACAATGATCCTCGCTTACAGAAGTCAAGGGGGAAAGA TGACGCTTTCAAAGCCCGAATCTCTTTACCCTGGAGCCAGAACCAGCGTCGCCGCCG TCCCCTGCAGCTCAGCCGGCAACGCGCGCCGAGCCTCGGGGCGCAGCTTGGAGACG CGCTTGCTCGTTCTGGGAAGGGGCACGGGACGCACGGTTCCCCGGCCCCAGCTGCA CAGCTCAGCTCGGGGCTCTCACCTATCCTCGTTCAGAGCCACATTCGGCTGCCTCCC CTGACCACCCGACACAAAGAGATTCGCCGGTGGAAAGAATCGATTTCAAAATTCAA GCTCACCGCTGCTCAACAAGGCGCGCACGTTTCTCCCCGTCTGGCTTCACATGTCCC AAACTTCCAGTAACAGAAATGAGGAAGCAGCAGCCTTCCCCGGCTGCTGGCGGAGG CAGTGGGTGTAACTTGTGAAGTTTCGTGCTATGATGAATCTGGTCACTTGGGTGTGT TGGAGAGGGTTGGTCGCTCCTCCCTTCCTCCTCCCACCATCACCTCCCTCCTCTCCGC CTCCCTCTCCAATTTAATTCTTCCCTCTGGCATTCGCCGGCTGTCACTCAGAATCCCA GCACCCTCCCCACCACATCCTTGGGGGCAATGTATTTCGAAAAGGTCTTAACCATTT TACGGATGAACCTGGTCACCCTGCACAAAGCGTGAGTGCTTGTCAAATAATTTTCTA CAGCACGTGGCAAAAAAGCAGCGCCTCTTAAAAGATATAAAAGGCCAGCAATGTTA CATAAGCGCCCCCCACCAGCCCTTCAAGGACAGAAACGTGGGTAGTTCATTCAGTG >10:75407325-75407565 (SEQ ID NO.: 216) GCAAGAAACGGCTCCCGGCTCGCGTGTACGCCGACACCTCGGCCCAACGCAGGACT CGAGGTGGTTTCTAGTGCCCGGGTGGCTGCAAGTCTGCCCTCCGAGGGAGGCTGGAC AAGCGGCGCCCCCAGGTCGAGCGGCCTCTCGCTGCCTGGCAGTGCCTGGCAGCCCC CACCTCTGCCAGTGCTTCGGAAACCCGCCTGGCCAGGTTCGCCCGCGGTGAAAAATG AAAGCAAATTCCCCA >10:75407574-75408594 (SEQ ID NO.: 217) AGCCGGAACTTTCCTCGACGAAGGCTCCCTCCTGCGCCTGTGTCTGGAGAACCCCCA GAGCGCTGCAAGTTAGCAAGAGAGATTCGATGGCGGCTCTGGAAGGCGCACGAAGG GTGGGGCGGGGGAGCAAAGAGGCCACTGGGTGACCCAGCCTGGTCCGGGGTGAAA CGCTAGAGAAGGCGCCTCGCCTTCCTTATTTCAATGCAACTCCTCGGCCCCAGACGG TAAAAATAGTTTCCAAGCTGCCGCGGACGCCCAGGATGTGTTTGCAGAGATCAAACT GGGGAGGAGGCAGCTTTGTAAAAGTTGCAGAAAGATTAGCCGAGAAGCGTCCGCCC GGCGGGGCTCAAGAAAGCTTGGGGACAGCTCCATGTTCCTTGGGGCGGAATGGCCC AAGAATTGGCCTGGGTAACCCCCTGCCCAGTTCTCTGTCCTCACTTCGAGCCAGTGC TTAAATAACTTCCCGCCGCCTGCCCTGCAAACTTCCCGGCGCGGCGCCGTTGAGGCC AGGACACAGCAAAGGCTAGCAAAACCCCGCCGCGGCGCGCTCGGCCCCGGCCCTGA GAGGCTGCGCGGGTGGGAGGACCAGTGTGGTTTCTGCTCCCACTCGGCTGCCCAGA CCCTCAAGACCGATCCCCCAACTCCTGGGAGCGGGTGCTTCCCTCTGGGAGCCGAGA TCTTGCGGGGCCAGCGAGGGCGCAAAGTGCGCGCGCTGGCCCGCGCGGGGGCGGCC GCGCGTCTCTCCGCGGGGCCTGTCGCCAGGCCGGCCGCGGCGCGTGAGTGATGAGG GCAGAGAAGGGCGCCCATAAATCGCGGGTGTCAGGGCGAAAAACTCTCTTTATTGT CTGCGTGATGGATGGGCCCGGGGACGAGACACCAAATACTTCGTATCGCCTTTAAAT GGGAACACATTTTCCGCGGCCATAATTCATGTTTTTTAAATAGAAAGTTTGAAATGT TGCCTATATTTCACCAGCCCTGACATATTTATGAATCGCTCCCTGCATGCAAATATCA >10:75408705-75408885 (SEQ ID NO.: 218) AGGGTGAGGTGCGGTGAATAGCCGTATCCGGAAACCGAGCGTGCCCCGGGCTTCTT TCCCGCCGCCAGACCCCGCACAGCCGCCCTGGGACGTTTTTCGAGGCTTGGGACCTA AGACGGGTCCCCGGACCCTGCTGGGAAACCAGGGGGCGTTTTTCGTCCCTCTCTGAG GCCATTATCCA >1:159200739-159201039 (SEQ ID NO.: 219) TGGGCAGGGTGGACTCAGAGGTTGGGAAGCTGCTCCTGAGAGGAGAAGCCTCTGTC TCTACACAGGAACCTACCTGACACATGAGGCAAAAGGCTCCGACGATGCTCCAGAC GCGGACACGGCCATCATCAATGCAGAAGGCGGGCAGTCAGGAGGGGACGACAAGA AGGAATATTTCATCTAGAGGCGCCTGCCCACTTCCTGCGCCCCCCAGGGGCCCTGTG GGGACTGCTGGGGCCGTCACCAACCCGGACTTGTACAGAGCAACCGCAGGGCCGCC CCTCCCGCTTGCTCCCCAGCC >4:40198301-40198661 (SEQ ID NO.: 220) GGCGAGACTGACCTGGAGATGATAAGGCCAGTTGAAGAGACACTGGAGAAGAGAA GACAGTTTGTTTTACACATTGCAGGAAATCAGATTAGACAGTTAGGGTGTGGACACA AAAGCGAGGACCTTGCAGGCACTGGGGAGAAGTGACCCCATTCAATAGTCCTTGGT CTCCTTCTGCCCTGCGGCTGCGCTTCCTCGGCTCTCACGGCACCAGCAGAATTCCAT GTGAGAGGGAGCTTGTCGAGCGTGGCCTCTTCCCACTTGGGGCTGCTTTCTGCATCC CTGTGCCTGGCTGTGGGCCTCCATTTGCCCTCTACTGTCTTCCCTTAGGACATCATTT ATGCAGAGAAAGGTTCGTGTG >7:100785927-100786167 (SEQ ID NO.: 221) GGGATTACAGGCGTGAGCCGCCGCGCCCAGCCCCCTCCTCACTCTCTTTCTCTTCCTG TAACTTCTACAGCTGGGCAAGAGCTGGGTCTCCAGCGGTTGCACGGAGAAGTGTGTC TGCACGGGAGGAGCCATTCAGTGCGGGGACTTCCGATGCCCCTCTGGGTCCCACTGC CAGCTCACTTCCGACAACAGCAACAGCAATTGTGTCTCAGACAGTAAGGGGAGCGA CCGGGGAGGTTGG >8:98948170-98948530 (SEQ ID NO.: 222) TAGATGGGGCTGAGGGCAGAGGAAGGAAAAAGAAAACCTCCGAGGTCAGTGCGGG GCGAGGTGAGCCCCTCCCAGGGCCCTCTGGCCCAGGAGGATGAAGCGCGCCGGCTT CGCTCTTGCACGCCGGCTTGCCATCCGGGTAAGCGCGGGAAAGGCGGCCACAGGGC GCGGCGGCAGCGCAGCGCGTGGGATCTCACGACCCATCCGTTAACCCACCGTTCCC AGGAGCTCCGAGGCGCAGCGGCGACAGAGGTTCGCCCCGGCCTGCTAGCATTGGCA TTGCGGTTGACTGAGCTTCGCCTAACAGGCTTGGGGAGGGTGGGCTGGGCTGGGCTG GGCTGGGCTGGGTGCTGCCCGGCTG >15:96947637-96948417 (SEQ ID NO.: 223) CTGTCCTATCTTTTTTTTTTTTTTTTTTTTTTTTTTTTCAGAAAAGATAGCCTAAAAGG GTTAAGAATCCCAGCAAGACACAACATAGATGGGCTGAAAACTCGTGGCAGGATGG AAGGGTATAAAGACGCCGGGGAAGTGGCTGGGGAATAATAAAATAAGAGGGAAGC TAAACCAGTGACCCTTGTCGGCAGTGAAAAGCGGGAGATTAGAAAATGTTTCATGC TAATTTCCATGGAGATTTCTTTAATTTAGCGAAGACTGCTTCCCGGGCTCCGCCTGGC CCGCGCCGGCCCGCGTCCTCGGTGGTCTGGGCGCCCCGGCTGAGCCGCTAGCGGGTC ACTCGGGCGGCTCCGACGTCTCTATCAGCCGCGCCCGCGCCGCCCGCCTCCCCGCGC TGCTGCCCGGCTCTCGGGCTCTCGCTTTTTTTTTTTTTTTTTCTTTCCGCGGCAGTCTT AGGATTCTTGTCACATGATGGCTTCATCGGGCCCTTCTCCTCCTGATCCTTTCAAGCT CTTTCTCCTGCCTGGCATATCAAAGGAGATTTGTGGGTCACCGAGCCGGGACGCAGC ATATAAAGTCATCAGCCTGGCCGGCACCACCTCGATCATTTGCCGCATTGTTCTTGC AAGGAGCCCAGGATGGCTGTGGCTTTTTAATAACTAGCTTAGTAGTTAGCCGAAAAA TCTTAGTTTTTAAAAATACAAAAAAAAAAAAAAAAAAAAAAGAGACAGTCTGATAG TTTATTTGTTTTTCCATACACTCTTAATTGAAACTCAGT >17:15966446-15966686 (SEQ ID NO.: 224) TTGAGAGCTGGGAATTGATTTCTAAGCCTGGTTTGAGCTGAGGGCCACAGAGCCAGT GCAGGAGGAGACCCTGCCCCAGAAATAGGCCAGTGCTTGTTATGCAGGCCTTGGCG GTTCCCCGTTTCCTTACGTAACCTCAGTGTTCACGCTGTTTCCTTTTGTTGATTCCCTC CGTGTGACTGTTTTTCTGTCAATCTCCTTAGCTAATGAGCTCCTTATAAGGAGAATGG ATGGATCAGAG >19:48568628-48568928 (SEQ ID NO.: 225) CAGGGCGCCGGGACACTGCTTGGCGCGTCCTGGGAGTGAAGCGCATTGAACCCAGC TCAGGCTGGTGGTGGGGGAGTCTTGGCAATGCTCTCTCTCCAAAGGCGAGTTGATCA CAGACGCTGGCAGTGAGTCAGCGGCACCGCCAGGGCTGCTGAGAAATCCCTCCTGC TGTCCGATCGCATTCCTGGAAGGGTGGGCCGCTCAGGGCCCCCCAGCTCCAGTCCCA CTCAGGCCCCAGAATCCCAGCAGCCCACCACTCACTTCTTTGCGCTCACTCTTCCTTC TGGTCCCCACACACCGC >3:134364186-134364534 (SEQ ID NO.: 226) GGCAGCGCGCACGGGAGGGAGCGGCGGGGGGCGGGCCGGGAGCGGAACAGCTCGC GGCTCTGGAATGCCAGGCATCCAGGTCACCCGCGGCTGCAAGATTAATGGCTCCAG CGAGGAGCCAAGAACAGCTCGGCGCTCACTCGCTCCCCGGGGAGCGGAAACGCCTC CCGGCCGGCCCCCCTCTTCTCACCCACTAGCAAGCTCCCAGAAACCCGCCCCATGGC TTCCTTTCTTTGGCAGAGTCAGGCTCCAGAAGTCCGCCTTCCTCCACAGGCACCCTA ATCTGCCGTGCCCTTGCAGCTTCTCCTCCCCAGACTCCTCAGGGAAACCCCAGGGCT GCCCCCTCCCC >7:27169523-27169934 (SEQ ID NO.: 227) TGGATCCCAACAACAGGAAACTACCTAAATCACCGACCAGTTCTGGTGCTGCCCGC GAAGGGCTGCCTCGCCCGCCGCCGCCGCCGCCTCCGCCGCTGCCGCCGCCGCCAAG GAGAGAACCCTGCCATCGCGCCTGGCCCGGCCCAGCCCAGCCCCTAGGCAACCTGC GCCCGCCAGTGCAACAGAGTGCCCCAGGCGGCCGCAAATGCGTCAAGGAAGGGGA AGCCACAGGCCCCAGTAAGGTATTCCTGGGAGGGAGAGGGAGGAAAAGAGAGGGA GGAAAGGCAGGGAGAGAGGAATAAAGGCGGGGAGCAGGCGAGACGAGAGCAGCT CCGAGAAGCAGTGTGCGCGCCGCTTTCCCAAATCTTGCAGCCCAGCGAGCCGGCGC CAAGAGGCGGTAGCCGTGGAAGGC >1:2132912-2133092 (SEQ ID NO.: 228) TGGAGGCGTGGGGACCCCATCTCCAAATACAGCCACATTGGGGGTTAGGGCTCCCC ACGTGAATTTAGGGGACACTTCAGTTCGTCCCGGCGGGGACTGGGGACGCCGGGCT GTGTGCTGTGTCCTGTGGGAGAGTTTGTTCACCCTGCTGGAGGCTCCCTGATGAGCC CTGGCGTCTGCT >1:2133236-2133416 (SEQ ID NO.: 229) CCGCCCCCCAGCTGCGCGGCCGTCCCTCGGCTCCGCCCCACAGCTGTGTGACCGCCC TGCGGCTCCGCCCGCAGCTGCACGTTCGTCCCTCGGCTCCGCCCCCAGTTGCTCGTC GGTTCCCTCGGCTCCGCCCCCTCGGCTGTGCGTCTGGCCCTCAGCTCCACCCCCAGCT GCGCGTCCG >3:185363027-185363207 (SEQ ID NO.: 230) GCGGGCTCTGTTTATTCTGTGACCAGATTCCTTCTAAAAGAAGGAAGGCCATGTCTG CCTGAAGCCTATTGGCTGGGCCTACTCTGGACCCGCCCCTCTTTTTTTTTTCATGACA CACACCACAGCGAAGTCTGTGCGGAATCCTAAACCAGCCCAATTTACATCCATTCAT GAATCTGTG >3:185363363-185363963 (SEQ ID NO.: 231) GTTGTTGTGAGTATTGCACTCTGTTTTTCCTGTTTCTTCAGTATTTATTTCACAAGGAC AGACAGAGAATGTGTGATTTGAGGTGATTAGAAAGCTGATATTATTGAGGGCGACA CCGTGAGAGAGACAGAGAGACAGAGGCGGAGAGAAACCCGAAACCCCGTTACAGC TAGGAGCCTCTGAAACTGACAGCTGGTTTTCCTTTGCTTGTCTGCCTGCTAGACGTGG ACATTTTTCATTTACGGTTCTGCACGTTACCTCGGATGCCTGCTTGGCTTTCCTTAAA GGGAGATTCATTTCTCTGAGAGATGATGTGGATGGTATTAGCAGAAAAGCCCAGAA CACCAGAAAGGTGCTGAGAAAAGCGGGGCCCGCAAGACAGAGCAGGTTCTATCCTG TGGGGCACTTGTCTTCCTTGCGACCGTCCTTTCTGCCGTTCCTCACCCTTCACCTTGC CTTTGTTTCATATTGTGTAACAGTCAGTATCTTGCGATTGCAATTTGGTGAAGATGAA TACTTGTTCAACCATTTTTCAAAAGCTCTTATGACGGGAGCCATAGTGGTGTATTTAT ATATATTCATAGCTCTTCTTTATGTCACT >7:96993058-96993418 (SEQ ID NO.: 232) AAAAATGATGGCGAGGAATGCAGAGGGCCCTAAATGGACCCTAAGATGAAGTACG GGTGGTGGCTGGAGAGCTGGGACTGGAAGGTGGGGCTGGGGGAGACGGGTAAGCA GCTTGCTTTGGTGAGGAGCTCCCACGCTGAGAACGGTGGGAGGAGGGAATGATGGG GAAACCTTTGTTTAATGAGGAAACCTAATTATTGCGCATCTGGAAGTCTTAGTCCCT ACTACCAGACGAAGGCGGGTACCTGAGGGATGCAGTGCGCATGCCCGAGCCGTCGG ATTTGCATGATAAGGCTCGCACGTGAGCCAACTCCGGCGCAGCCCAGGCTGTGCCG CGGCCGGCCGCCAATGGAATCTTGCT >7:96997902-96999222 (SEQ ID NO.: 233) CTAGAACCCTAAAAACTCCTTTGGCCTCCAGAAAGACCCCGGTGCAGCTCTCTACCC TAACCCCTAAGCCCCTCTCAAGTGAGAGCCTCTCAGTTAGTACTCAGTTGCCACGTC TCGCAGGAACTTTGGAGCAAGTTTTCAGCTCCCAGGTGTCCAACCTTTAAAAGGAAA AGCATAATAATACTAACCTTTCTTTCACGACCACGCGAAACGCAAAGGATGTGGAGT GGGGAGGGGAGGAAAAAAAAAGGGGCGGCCAGCCAAATCAAAGCTTGGGAGACAT TTTGACAGTGCGCTTGAAATAATGCTCTTAATTTTTGGAAGGTTTTCAAGAAGGGGG TGGGGGGCACGTGGGAGAACCACAACTTTCTCCTGTCTGTCACTCAAGCGGCCAGA GAGGGCTCCAACCTCCAGCTCCCGCGGCAACACACAGTGGGAAATTGCTTCAAGAT ACAGTGGGGCTCTATTCTTTCTCTACCCCTGCCCCGCCTTTCCCGAGCAGTGAACTTC ACAGAGAGGGTGGTAAGGGAGGGTTATCCTGGGTGTCAAAAATCTGTGCATAGCCT GAGATCAGAAGAGTTAACCCCAGGCCCTAGACCCAGCCCAGCGGCCAAACTGGCAC CCCGTGCTGATCAGCCCCCGCATCCCCATATCTGCATCCCCATATCTACCTCCCCAGT CGGGGGTGGTGAGGTTTGGGGGAGGGGGGCGACACTACCATATGCATCCACCACCT AAGTCCAGCCCAGGCTGGCTTCAATGAAAGCTGGCAAATCCGGCGAATCTCGCAGA AATTTTCTTCGAACTTAATTCAATTTTAAAGTGGATTTTTACTATTAAAAACGCTGCC GAGCAACACATTGAATTAATCTGACTGTACGGTTTTAATTACAGTGAGGGTTTCTCT ACAAATCTGTACAAGACAGTGGCTGGTTCTTGGAGGATCTCTGCCTCCTGAATTCCA TTATCGGGCCCCTGGTTCCCTGCAGACGGCAGCTCGTGGGAGCCAGCTGCGGTGCGA GCGTTCAGTCGCCCTCTGCTTCTGCCGGGCCTCCTGGCTCCTGTCCCTCCTCCCTTCC TTCATCCCAGCCCCATGGAGAGCCCAGGATTCCTGCCTGTCATTTGAGACTGCTGAA CTGATATCCTGAAACGCTACCCTTGCTTTTTAAACTCTTGGGCCCCAGACTTTTGAGC CCCCTGAGCATCGTTCTTAAAGTGGCTCGTTTTGTCTGGGAGGGTGACCTCTTGTGTA GTGTTTTTTGAAGGGTTCTCCTGCTTCGACTTAGCAGCTGTTAGAGTGGGCAGCGTG ATGCCCAGTCTG >13:24270525-24270945 (SEQ ID NO.: 234) CCTACCTTCACTGAAGGCTCTCGGCAGCACCTGATGGCTTGTGAGTGTGTTTGTCTTT GGTGTATATAGGTTTTGCCTTAGTTTAGAATTCTCTCCTGAAGTCCCCCGCAATGTCA CTGTAGCCACTAACCCTTGGTCACACGGAGTGTGGAGCCAGCTGTCAGTTTCTGGGC AGGCTCTGGCCGGGAACGCATACAACGTCAAAGCAGTGAATAAGCGATTTCTGCAG TTCCCGTAGCTGCCAGCCTGTGCAGTCCTCTGTGATGCTTGGGGACCGGCTCCTCGG TCACACCCCAGTCCTGCTCTGAAGGTTGCCGTTTTCCAAACAGAAGGATGGTAGCTA GAGGGGAGATAGCAAGATTCTGGAGTCTGGAAAGCCTTCACTTGGGTATGTGTGCA AAGAATGGATTGTTGTACTGTG >13:24271993-24272173 (SEQ ID NO.: 235) TTTCTATATTGAGAACACAGACCACATGAGTGAGAGGGCTCGGTAATGCTAGCGAG ACGGCACTGGCAAGACCTGGGTGGAGGAAGCGGACGTGCGGGTGCTCCCTCCCAGG GTTCCTGCACCCATGGCCTTGAGCAGGGGCGTGTTCATTCCCACCGGGAGTGCAGCC AGCACGAACGGG >1:6447340-6447520 (SEQ ID NO.: 236) TGACCGGGGGCGGGAGCAGGGTCGTGGCGTCCGAACCTCCGGGCTGCAGGGGGCGC GGAGCGGGCGGGCTGGCCCAGAAAACAAATCCTGCGGTGTCGCATTTCCTGCAACG TGAGCCAGGTCGGGCGGGGTGAAGGGTCTGAGGCCACCGCAGGGACGCATGGGCTG GAGAGTGGGGCAG >1:19643753-19643933 (SEQ ID NO.: 237) CCAACAGCACGGACTTGAACCGGGTCGCATGCCGGAGCGGACGGGATGAGGTGCAC CGCAGAACTGGGGACTCCTGGTGCCGGGACGCGGCGGGCTGGGGCGCCCCACTCTC GGGGCAAGTCTGCAATGCCCGGTGCCCACAAAAAGGACACATCCATCTTTGTCACC CCGAGGCCTGGCA >1:26360410-26360890 (SEQ ID NO.: 238) AGGCCGGACAGGGAAAGTGGCCTGGGGCGAACAGAGGCGGGGAGGCGGGGCTGAG CGAGCGAGGGGGATCCCCCAGGAGCAGGAGGAGCTGGGCAAGGGGGGCGGTTGCG GGGAGGGGTGGATGGTTCGGAATGGGCGTGGTCTTGCCGAATGGGAGGGTCTAACG CGAGTGGTTGGCGTCCCGCGCGGGGCCCAAAGTGTGACACGGGTGGGCTTGGAACC GGGACCTTAGCTACTGGTGGGGCTGAAGCCCACCCTGCCATTGTTCTGCCACGGTCA GTGGGGCTTGCTCCTCCCTATGGGAAGCACTTACGGCCGGGAGCGGGAATCCCGTC ACCACCGCGGTGGGGAAGCCGCACGGAAATCCACGGGGTGCGGACGGTGCCATCTC CTGGAAGTTGGCCAGAGAACCCCACTCTGTCCGCAAATCGCTCTTATTTAATAACAA CTATCATCGATTGTGATCCTAACCTGGGCCTCC >1:31771901-31772621 (SEQ ID NO.: 239) GTGCCCTTACCCCTTACCCTCACAAAGGGCCCCACCGCCGGAAGCCGCCCGCGCTCC CACACCTTGTGCAGGTCTCCCCTGAAATGAATTTTAATTTCCGCTGAGGGCAGGCGG CGTCGTGAGTCCTGAGCCCGTGGCGGCGGCGGCGGCGCGGGTGTGGGGCCGCGCGG CCGGGAGCGGGCGGAAGAGAGCGCGAATTTGAATTTCAAAGGCATCTGGAACCCAA GTGCTTCTGCGTTGCCCGATTGTGTGTGTGGCGCTTTTGTGTGTCCGCGAATGCGCGC GTGCGTGTGTGGCGTGTGTCTGGGTGTTTTATGACTGTCCTCCGTGAGGCCGTGTGTG AGCCCTTGCGTGGGCCGTGAGTGCGGCAGGGAGCGCGGTGTCCGGGGGCCGCCTGT CGGTGTGTCTGTGCGTGCTTGTGCGCTAGCCTTTGCCTCTGCGAGTGCGTATTTTTAG GACCGAGTCTGTCTATATGAGCCTGTGTCTGTGTGTGTGCGCTCCCGGCCCTGCGTGT GTCTGTGAGCGTCTGCCGGGGCGCGTGTGTGCTCGGAACCCCGCGGTGGTGTGCGGG TGTGTCCGTGTGTCTGTGCACGTGCAGGCGAGCGTTCCCATCTGTGTGTGTGCATCTG AGTCTGGGCTATGTGTGACTCAGGGACCAGTCTATGAGCCTGCCTGTGCCTTTGAGC CGATACCTGTGTGTGACTCAGGGACGAGTCTATGA >1:32248455-32248635 (SEQ ID NO.: 240) GCCTGTCACCTGCACCAGGAGCTGCTGGATGAGGCCGAGCTGGAGCTGGAGCTGGA GCCCGGGGCCGGCCTAGCCCTGGCCCCGCTGCTGCGGCACCTGGGCCTCACGCGCAT GAACATCAGCGCCCGGCGCTTCACCCTCTGCTGAGGAACACCTGTGCCCCCCGACTC CCCGCCCCCTC >1:40317257-40317497 (SEQ ID NO.: 241) CTCCCGGCGCTCCTCCAGCGCTGGCTGTTCGCGGGCAGGGTGGGCTGGGGCTCCTGA ATATGCGGGGGGCGGGGCGGGGGCCGGCGTGAGCTGTCACCTGAGAGGACCGGCG GGGTTGCCGGGAGGGAGGCCGGCGCCAGGCATCCAGCTCCGCCCCGCTCGGTCCAG CCTCCTGCGCCCACCCTCTGTCCTCGAGGGGCGACCGGGGTGCGGGTCGGAGATGAT GGTCCAGTTTCTTTGT >1:92030047-92030410 (SEQ ID NO.: 242) AGGAAGGGCAGTGGGCCCCGCCGCCGCCTCCCAATGGCGAGGCTGCGGGATTGCCT GCCCCGCCTGATGCTCACGCTCCGGTCCCTGCTCTTCTGGTCCCTGGTCTACTGCTAC TGCGGGCTCTGCGCCTCCATCCACCTGCTCAAACTTTTGTGGAGCCTCGGCAAGGGG CCGGCGCAGACCTTCCGGCGGCCCGCCCGGGAGCACCCTCCCGCGTGCCTGAGCGA CCCCTCCTTGGGCACCCACTGCTACGTGCGGATCAAGGTGAAGGGCCGCGCGGGCC TGGCGGGAGCGGGAGGGAGCGTGACCGCCGCGAGGGTGGGGGGCTCCGGGCTTCTC CTTCCGAGACGCTGGCTCAGCGTCC >1:98045882-98046362 (SEQ ID NO.: 243) CCTCGCCCCCCGCCCCCTGCGCGAACCCATTTTCCAGTCCTGGTCACCAGAGGCGCA GCGCACAGCCTTTCCGGTGGAACCAGTGCGAAAACACCCGAGGAAATGAAAAGAAC AAGAAAGTGCTACCTTGGCAACCACGGGCGTTTAGTGGCCAGCTGGTGGGCTGGGG AGGGCGGCCGCTGCCCCCCTGCCGCTGGTACTCTCCTCGACTACGCGTATTCTTAAG CAATAACAACGTAATCCGTATTATCCACCCAAGAATACCCGTCACCGAAGAGAGTC AGAGGACCAAGCTGCCGCTGCCGCTGCTACCGCTGCCGCTGCTACCGCTGCCGCTGC TACTGCCGCCGCCGCCGCCACCAGAACTCTTGCTGCTCGCTGAGCCCGCCCCTGCCT GGGGATGGGCTGAGCTTGACCGGGACCATAAATCCATAACTCGATTTCCCTAAAGA AGGATCCAAAGCTGTGCTCGGCTGCTTCC >1:121008795-121009695 (SEQ ID NO.: 244) TTCTTCCGAACCCCTCTTGGGAATACTGAATGGAAAAGGGGGAGCGTGAGCAAGTG CTTGGTAGAGTGTAGACATTGTGGGATTTGACTGTGGTACCATCGCTTTGACGTCCT AGTGCTGATTTTTACACCTGCATTCTGCTTAGGGCACCGGCAACAGTTTTCCGTTTGT GCCTACTCCACCTGCTGTCTTTGTTGGGTCAGCGAACATCGCCTCCCTCTACCGCTCA ATCAGCAAAAGGGACCGCCCTTGAGGACCTCACCCGCCGCTCACTCCCCTCCCAAAT TCGCGGGCATCGCCTCCGGTCGCCTCTTCCGAAGGCCTAACGAGCATGTTAGCTGCG AACGGAGGTGAGGAGGCTCCGCTGACTGACCGGTGCCCATGTCCAGGGCACGCACA AACGCCATGACTTGGCTTGGCCTCTCTCTTAGTTATTCACAGCTCAGCCCGATAGGC ACCTCCGGGGCGGCGACGGCAAAGAGGGTGAGCTTATTAAGTGCAGCTCCACGGGG ACTGGCCTCTCTGCACGGCTGTGTACACCTGAGCGAGACGCTCAGTCGCTCTCTAAA GCCGCTTCTGCGGATGACAGACACGGAGATAAACGTGAGAGGTGGCCCACCACGAC TTGCCCTCCTTTGCCCGGGTTTGCCCCTCGCTGAGGAGGCTGTTCTACATCTGACCCT TGGAGCAGGCCGGCTGACAGCGTAGTAAAGGAAGATTTCTGCGGGAGGGCGGCCAG TGCAAAACAATTCCCTGACCGGGAATCGAACCCGGGCCGTGACGCTTTCAGCACCG AATCCTAGCCACTAGACAACCATGCAGATGCGGAAAGCTGCTTTCTCTCCCTTCTTC GACCTGAAGCGACACTTTCCTGTGCTCTAGGAGGACTTGGGTCTTGTGA >1:148302626-148302986 (SEQ ID NO.: 245) CCTTGGATTCCTCGCCAAGTTAGTAAGGTGTGAGGTCTCTTTTCCTTCCCCTGACGCG CCTGGTTGCGGGAGCAAAAGGGAAGAGCTGACAGCCTAGACTAACGACATTGCCGT GACTCGGATTCGAACCGAGGTTGCTGCGGCCACAACGCAGAGTACTAACCACTATA CGATCACGGCGAGCCACAGGCTAAGCCGCGATGGCGGAGCTTGCTCTAGCCCTTTTG ACGTCAATGGATTTCGATTATTAGGCGGATTCGTTCCCAGACAGCCACAGGGGACTC GCGCTTTTCTTTCATGCCCGCTCTGCTTTTCCCTCCCTTCCTCCCAATCTTCATACGTG ATGAGAACAATTCTCATC >1:154567391-154567691 (SEQ ID NO.: 246) AAACACATTTTCTCTGCTGTATCCTCAGCCTACCTGGGGAGCAGGACCATTTGGGTT TGGTAAGAGAAAAAAGGAGGGCGAAAACCCCGGACACTCCTCCTGTCTCCCGACGC TCGTTCTGGCCGTCTGGCCCTCAGTACTAAGCAGGCCCTGACCTACTTGTCTTACTCT TGCTGCTTCTTCCCGCCGGGCCTCTTGCCCCTTCTCCGACCATGCTGCAGGTCCTGCC CCAACTTTAGGACTTCAGAACTCCTCCACCGTGCCGTGGAGGAACAGCCCTTCTTCC ACCTCACGCACACCC >1:160083804-160084524 (SEQ ID NO.: 247) GCCAGGCAACACGAAGGGACTCGCCCAGGGCCCCCCAGGGCTCGGTGCTGGCCCTG ATGCCCCGTGCCTCCCCATCTCCCGAGGGGCCACTCATTCGGCAAACCTTTATTAAG CCCCTCCAGGACCCCCGACGCCGCCTAGGCGCCCAGCGACGCGCGGCAGGTGGCAG CAGCTCGGGCCCCCGCCGCACTCCAGGCGCCCGCAGCGCTCGCCCTGACGCGGCCG CCATGGCGCAGGAGAACGCGGCCTTCTCGCCCGGGCAGGAGGAGCCGCCGCGGCGC CGCGGCCGCCAGCGCTACGTGGAGAAGGATGGCCGGTGCAACGTGCAGCAGGGCA ACGTGCGCGAGACATACCGCTACCTGACGGACCTGTTCACCACGCTGGTGGACCTGC AGTGGCGCCTCAGCCTGTTGTTCTTCGTCCTGGCCTACGCGCTCACCTGGCTCTTCTT CGGCGCCATCTGGTGGCTGATCGCCTACGGCCGCGGCGACCTGGAGCACCTGGAGG ACACCGCGTGGACGCCGTGCGTCAACAACCTCAACGGCTTCGTGGCCGCCTTCCTCT TCTCCATCGAGACCGAGACCACCATCGGCTACGGGCACCGCGTCATCACCGACCAG TGCCCCGAGGGCATCGTGCTGCTGCTGCTGCAGGCCATCCTGGGCTCCATGGTGAAC GCCTTCATGGTGGGCTGCATGTTCGTCAAGATCTCGCAGCCCAA >1:160401102-160401282 (SEQ ID NO.: 248) AGGGGCTCGTGGGGAGGGGGCGGAGCCCAGGCCTGGAGAGCCGGGGACTTTCCTGG GCCCGGGCGGGGGCCTTAATGATCCCAGGGGAGCCGGTTGAAGCCGGAGACGGGG AGCTTGTGTTGGAGGTGGGGGGAGAGGCGTGGAAGGATCGGAGTCTGGAGGTATTG GAAGCCAAGGGTGT >1:166920601-166921261 (SEQ ID NO.: 249) CCTCCCGCCTCGCCACCTCCCCGGCCCCCAGACAGCGACACTGCTCGCCCTGCCTGG AGGCTCCCGCTCAGTCCCCTCGGAGGAGGGGAGGCAGACGCAGTCTCACGGTTTTCT TGGCGGGCTCCTTTTTCCTCTTCTTCTCCGAGTTGCTGTGGTAGGGCAGGTCGCGGCC GCGGTAGGACGGGCCGCGGGTCAGCTCCAGCTCGCTGTAGGGCGGCAGCGCGTCGT CGGACGCGTCCTCCTGGTCGTCCTGCGACGAGCCGGCCTTGTAGGTGCCGGGCGGCG ACCAAGCGTAGTAGGAGGCGCTGCGCGGGCCGAGCTGCGCGCTCCGCTTGGATGGC GTCTCCAGGCTGCCACCGCGGCTGGCGCCCTCGGGCCGCGCCTGGCGCTCCCGCGCG CTGCCCAGGTACGAGTGGTCGTATTTGGGTGCGGTGCCTGGCGTGCGGCTCACCAGC CGCGGCAGGTGCGCGTCCTCGGCGGGTCTGCGGCGCGCGGGGCTGAAGGCCCAGCC GCGGTCAGCATCGGTCAGGGGCTCGCGGCTGCGGCTGCGCTGACCGTAGTACTCCTC CAAGGAGTCGTCCTGGTAGAAGCCGCTGTGCGCCCGCGACTCCGAGCGCTCGAAGC GGCTCCCGCCCCGCGCCTCGTGACTGTTGCCGTCTGC >1:180232819-180233599 (SEQ ID NO.: 250) TGGCCTAAGAAGGGGGGAAGCTCGAGGGGTTGTGGGGCACACCCTTGGGCCTTCCG GGACAGTAGGCTCTTAAACCCTAGAGGAGGGGAGACAAAAGAAACGCTCTCCCACA GGGGTCCCTCCAGTCGCCAACTAGAAGGGTTTCCCTCTCAACACAGACATGTTTGCC TCTTCATCACATGGAGTCACCACGAATGGAGCACTTGGGGACGCAGGTCTAGGTGTC CCCAAGCTCGGTGCCTCTAGTGCCCTCCCCTCTAGGGGCATTTTAGAAGAAGTGATT TAAATCCAGCTTATTTCGGCGGCAGCTGGACTATTCCTTTGCTTATTTGGGGATGGGT GAGGGGCATACCCTTTAGGAAAACGTTTCCAAATGATGTAATAATTTCTCTCTCATC TCTGGTCTTGCTCCAGACTTGGCCTCTTCCTCGCCACTCTGTCCCGGCCTCCCGCCCC CGCAGGCTCCCGTGCGGACTTAGCAGTTCGCGCCGTAGCCCTCCTGGTTTTTTACCG CGCCTTGGTCGCGCGGCCCCCGGTGCGGGCCTCGTCGCTCCGACAGCCCTACAGCTG TCCCTACGGCCCGCACCGACAGCTCGTCCCCGCCACCTCCCTCCGGGCTGTAGGGAC GTCGAGATCCGAATCCTCACAGCGCCTGACCCGGGGCCGTGTTGGGTACGGGTACG GCGAGAGCCTTCCGAGCCGCCTCCAAAACTCTCCCCGCGGACCTCAGCAGTCCCTCC ACGCGTCGGGGCCCTGCTGGCCGGCCATGCCCTCTGAGGAG >1:183185880-183186120 (SEQ ID NO.: 251) TTAGCGCTCTTAAGATTGGGCCTCCCAGTTTGAGGAAGGGGCGGGCTGCTGTCTACC TCTGTGAATCTGCCCTGGACCACCCCGGGAGAGAAGGAGGGCTCCGGGGAATCTCG CACATTCCAGGCAAAGGCTCCCGGGCCGCAGCCTCTGTGCCACACCCTTGGCCCGGG CCAGGTGTGCGCCCTCCTCGCTGCGAGGGGGAGCGGGCGGCTGCGGGGAGCGATTT TCCAGCCCGGTTTGT >1:197913075-197913255 (SEQ ID NO.: 252) CCTTTATTTCTGCAGAGCTGAGGGCAGGCGGCGCAACAAATCTCAGGTAAAAGAGC ATCAGATTTCAGAAGAGCTGTATTCTAGACTTGGCGCAGGCCCCTTTGGGGAGAAGA GCCCAGGGGCTATAGAGAACAGAGGTTTGAAGGAAGCAAAAGCTGGCGAGAGGTTT TTTTTTTGTCGC >1:201539995-201540295 (SEQ ID NO.: 253) ATTGGGTGATCACGGGGAGCTCACCTGAGCGCTCCCGAGGCTTGGGCTCTGGTCCCT GCTAATCCCCAGAGCCGATAAAAACTGGTCATAGGATAAAGAAGCAGCTAAGTTTG CAGCGGGCAGAGGGGAGGCAGGAACTGGAGAGGACGCGAGTGGCGGGTGGCGGGG GCGGTGTGTAGGGGTGACGTCCACCCGGCAGAGAGGGTTCCTTGTCCCCTGGAGCC GAACACAGGAAAATCAGCTGGTGAGTCAATGGGACTTTGTTAGGATAGTCACAGGG CGCAGCTGGCGCCGGCTTAAG >1:203629355-203629535 (SEQ ID NO.: 254) CCGCTTTCGCCGCGGCCTCCCATCGTGGAGGCTCAGAGTGCAGCTATTCCTGCAGCC GGCCTTCCTATTTTCAGTAATCTGATTAGGGGTCGATGTTGGTGGGCTCGGGGACGG CTTCTCCGTGAGGTCGTTATTTAGCGCGCACCGGGTCGCCTGAGCCCGGGGTCGCGG CCAAAGGGGT >1:228818226-228818526 (SEQ ID NO.: 255) AAACCACGACTGCAGACCCAGGCCTCCTGCTCTGTGAGCAGGCAAAAGCCCTGCCC TCCTGAGCAGGGCTATAACTGCCCAAACTGCAGCTGTGCATCAGAGCCTCCCTGTGC TCTTGCGGGAGGGCTGGGAGCGGGCAGGATCTGCCTTCCCGGGTGCAGCTGCCCTCC CAGGTGCAGGACCCGGGTGTCTCTGCAGCCTGAACCCTTGGGTGCCCCAGGAAGGA CCCCCACACTTCTCCTGCAGAGCAGAGAGAAGCCAAGCAGCAGGAGCAGACACCCT GGAGCCTGGTCACGGTGGG >1:232805208-232805868 (SEQ ID NO.: 256) CATCAATTGTCTTAATACAAGGTTGGTGGCAAAAAACGGCTCACAAGTATGCATACA AAGGGGCCAAACACATTGAGCAGCAAAACCCCCAAAGCAGACACCGCCCGAGACC CGCTGGAGCGCTTCCGCAAATCTCGCGAGATAGCAGGCAGCGATGCCTTTTGCTCCG GTTTCTCGTGAGACCCCGGGGCTTCAGCTTCTCGTTTGCGGAGCCCGCGGCGGCGTT TCCTGGGGCAACAGCAATGGCGGCCTCGCTGTCCGAGCGGCTCTTCTCGCTGGAGCT GCTGGTGGACTGGGTGCGTTTGGAAGCCCGGCTGCTGCCGTCCCCCGCTGCCGCAGT GGAGCAGGAGGAGGAAGAGGAGGAAAAGGAGCAGGGGGAGGCCTCGTCGCCGCGC GGTCTGTGCCCCGCCGTGGCCTTCCGCCTGCTGGACTTCCCCACGCTGTTGGTTTACC CTCCTGACGGCCCCGGCGCTCCCGCCGCCGAACCGTGGCCCGGTGTCATCCGCTTCG GTCGCGGCAAGTCCTGCCTCTTCCGCCTGCAGCCTGCTACCCTGCACTGCCGGCTCC TGCGGACCCCGCTTGCCACCTTGCTGCTGCAGCTGCCCCCTGGGCGCCCGACGCCCA CCCCACAGCTCCTGGGGGCCTGCGACATTTCGCTGGC >2:3195914-3196214 (SEQ ID NO.: 257) CTTATTTGTTTGGTCTGTAACGTCAGTCTTTGAGTTTCTTGTTTTCAGATACTGAAATT CTTCACATCCTTCAAAAAACCATGCAGACAAAGGACACGATGACCACAGGACATGG AGAAATGGATTTCAGCAGGACGTTCATCACGGGCTGAGTCTGTGGTTTCCAGCTTCT GATTAGGAAACCAAACAAGCCCTCTGCACGGACGTGCACAAAGGAGGAAGTGGCA AGTGATTCTTTATTAGCCCCTGAGTTTTCAGAGGGGCCTTGGAACTAAACCTAAAGT TGTGCCCCCACCCTGGA >2:12719226-12719779 (SEQ ID NO.: 258) CTCCCCATCTCTAGACTTCCCTGTCTGCTCATCCCCTCTCTTCCGTGCCCCCCTGAAC AACACCTTTGCCTGTAAGGTTAAGAGGCTCCCGTTTGGAGCCCTAGGGATCCGCAGT GGTAATACCACTGCGATGGACACTTCGGTTTCCTTTTTTGTCTTTAACCCTGAACAGT GACTGGTTTATGTATATGTGTGTCTGTGTATCTTTGTGTGCACCCACCGGGCCCCAGA CAAGTGGATGAGGGGCGAAATAGTTGCGAAAAAGAAAATAACTATAATAGAGCAT ACTACTACCCAGAATTGGACCTAGATCAAGGATTCTTTGTCACTTAATTTTAGATTTG CTGACTGTTTTTTTTTTTTTTTGAGGGGGTAAGGGGAGAGTGGGGGACCCATTCTGCC TTTGAAATGGTCACTGGGCACGGTTGTGCTGCAAATAACACATCGCGCTTTTGCCAT TCACCACAGACTACTTTGCGGACTTGCCTTATTTCCTAGTGGACTGGAGTATTTCATT GCAAAATTTGGGTTTAGTGGAGATCTCCAGTCAGTTT >2:19350886-19351666 (SEQ ID NO.: 259) CCCAAGCAGAGAATTGTGTCTGAGGGACCCTAAGGGAGGGAGTGATGTTGGTTTGG GGTTCCGGGGAGGCAGCGGTCATTGTGTATTTGCACCCGAGTGTTGAGACCCGGGG AACGGGAAATATTACAGCTCTGAGGCTCTGTGAGGGCGGGTCCTTCCCACCCCAAA GCCAGAGGCCAGGAGGGAGGCCTTCGGTTAGGGTGGGGAAAGACATTCTCTTCTCT TCTTGCACCCTAAGCGATCTCAGCACCCAGAGACGCTGTCTCAGCACCCAGAGACTC TGGGATTTCTCACGGGCGGTTTTCTGCCTTCAGGCTTAGGTTCTTCGTAAACTCACAG CACTTTAGCGGTGAGGAGTGGGAAGGCTGAGACCCTATCCCTGAGGCGGAGGAGAA AAGTAGGAAAATCAATACATGGTGGGGCGGAGGCAGACCTAACCGGGAGAGAGGA CGTTGCTCCACACATCTCAGCCCTGTCATCCTAATAAGACGGGGTGGTAGGAGGGGG ACACGCTGGCGTCCAGCAGAGAAACCTGGTCCTCTCAAAGAGAGGACCCAACCGGT TTCCTGCGTTTAGGAGGGAAATTACCCATCCTGCAATGCCTGTAAAATAACCGTTTA TTTAATAGTTAAAAAAAAAAAAAACTCCAGTGATAAATGTCCGTTACCGATGGTCA GCATAAAGTGCCAATCGCAATATAACGCCCGGCTCTTGGCTGGCTGCTCCCTCGCAG TGTCGCGGCAGCGGAGGCCGGGCCCCCTGCAGACCCCAGGCCCGAGGT >2:20667295-20667775 (SEQ ID NO.: 260) CCCGCGACGGGCTGGAAGCGGCCGCCGTGCTGCGAGCGGCGGGGGCTGGGCCGGTC CGGAGCCCAGGGGGCGGCGGCGGCGGCGGCGGCGGCGGGCGGACTCTTGCCCAGG CTGCGGGCGCCGCGGCTGTCCCGGCCGCCGCGGTTCCCCGGGCCCGCGCCGCGCGC CGCGCCGCGGGCTCCGGCTTCAGGAACGGCTCGGTGGTGCCGCACCACTTCATGATG TCGCTTTACCGGAGCCTGGCCGGGAGGGCTCCGGCCGGGGCAGCCGCTGTCTCCGCC TCGGGCCATGGTCGCGCGGACACGATCACCGGCTTCACAGACCAGGCGACCCAAGG TACTTACGCCTCTTCTGTGCCCGCCCATCCCGTCAGGTCCTGGGCTGAGACCAGCCC CGGAGCCGTGCCGCAGCTCCGTTACATTTGGAGCCGCGGCCCCATGCGGCCCACCCT CAGGTGATAGAAAGAAACTTCGCCGAGGCC >2:45000833-45001613 (SEQ ID NO.: 261) TCAGGGTAGGCTGGGCCGCTGCTAGCTCTTGATTTAGTCTCATGTCCGCCTTTGTGCC GGCCTCTCCGATTTGTGGGTCCTTCCAAGAAAGAGTCCTCTAGGGCAGCTAGGGTCG TCTCTTGGGTCTGGCGAGGCGGCAGGCCTTCTTCGGACCTATCCCCAGAGGTGTAAC GGAGACTTTCTCCACTGCAGGGCGGCCTGGGGCGGGCATCTGCCAGGCGAGGGAGC TGCCCTGCCGCCGAGATTGTGGGGAAACGGCGTGGAAGACACCCCATCGGAGGGCA CCCAATCTGCCTCTGCACTCGATTCCATCCTGCAACCCAGGAGAAACCATTTCCGAG TTCCAGCCGCAGAGGCACCCGCGGAGTTGCCAAAAGAGACTCCCGCGAGGTCGCTC GGAACCTTGACCCTGACACCTGGACGCGAGGTCTTTCAGGACCAGTCTCGGCTCGGT AGCCTGGTCCCCGACCACCGCGACCAGGAGTTCCTTCTTCCCTTCCTGCTCACCAGC CGGCCGCCGGCAGCGGCTCCAGGAAGGAGCACCAACCCGCGCTGGGGGCGGAGGTT CAGGCGGCAGGAATGGAGAGGCTGATCCTCCTCTAGCCCCGGCGCATTCACTTAGG TGCGGGAGCCCTGAGGTTCAGCCTGACTTTCCCGACTCCGCCGGGCGCTTGGTGGGC TCCTGGGCTTCTGGGCTCACCCTTACACCTGTGTACTAAAGGGCTGCTACCCTCCCG AGGTGTACGTCCGCCGCCTCGGCGCTCATCGGGGTGTTTTTTCA >2:47569537-47570197 (SEQ ID NO.: 262) GCGCCGAGGGTGGAGGGAGAAGGGGCTTTTGAGATCATCCTGGAGAGGAAACTGAG GCCTGGGGGTTGTGGGTGGAAAACAGGAAGGAACCGGTAGCCCTTGGCACGTATTC TTAGAGGAGAAAACGGAGGCTCACAAAGGTCAGATCACAGAGCCGGCCAGTGTTGG AGCACAGGCGGCCCGGGGTGAGCGCCAGAGGTGGGCTTTCTTCCCTCACTGAAAGC CGGGAGGGAGAGAGAGAGAGAGAACGGGGGCCGGCGGAGAAGAGGGCGAGACGA AAGTAAGCAAAGGGACATTAGAAGGGAAGGCAGAGCCGAGGGACGCGGACCGAGC GGCCGAGCAGTGGAAAGGGCGGCAGGTGAAAGGCACAGAGAGGAAAGATGCGCGG GGGACGCGCCGCTCACCTATGGTTGACACCACGGTGCCCACGAAGTAGAAGGCGCC GGGGAAGTCCCAGCGCGGGCGCAGCGCGTCGGCGCGGACGCCGGCGGCCAGCGCG GCCTCGTAGTGCCGGAGGAAGGCGCGCAGCTCTGGCTCGGCCACGCCGTGCGCAGC GCTGAAGTTGCGCAGCGTGGCGCCCCAGCGCGCCCGCGCCTCCGCCTCGCCGGGGC TCTCGAGCGCCGAGAAGACTGTGGCACCCGCCACCAGGTAGAGGCCGATG >2:48530399-48530759 (SEQ ID NO.: 263) CCGCAGAGGGATGGCCTCCCGGCAGGGACTCCTCGGCTCCCCTCTGTTCTGAGACTG CTGCTGGGACCGGGGTCCGACTCTAAAGAGAAAACTCAAACAGCAAAAAAAGGAAT ATCGACTCAGTTCCGAGGGCGGGGGCCGGGGCTCGTTCTCACCCGCGCGCGGCCCCT CGACCTCTCGGACCCGGGCCACCAGCTCTGCGCCCCTCACGCCTCCCTCGGGGTCTC TGTGTCTCTCTCCCGCTCCCGGACTCCCTCCTCCTTCTGACTGCTGTTATTTGGGCTGT TGTCCCTCCCCGCTCCCTGGTACCTCAGCTCGGACCTTAGCCTGTGCCTGCAGCCCG GAGTCCCCTCCTGCCCTG >2:88765502-88766042 (SEQ ID NO.: 264) GGGGCGACGCAGTGGCGAAGTCGGGCTGTGGGCCCGGCGGCGGCACCAGGCGGAG AAGCGCCACTCAACCCCATCCCTGGGCTGCAGAGGGCCCAGCGCGGAGGGCTCCGC GCGTCGGGAGCCGGTGGAAGAGGAGAAGAGCGCGCGGGCGACAGTCATACAGGCC TTGGGGCAGGGCGCGCCTCGCGCTCCAGGGAGCCACGCCAGCCCGCTGCGCCTCCG CAGCAACCGCCGCCTGCACGTGGCGGGGCGAGAGAGCTGCTAGGGCGGTTTCTCCG CCTCGGGCCTGTTGGGCGGGGCCGGCTAAGGTGCGCGTGCTCGCTGGTCCTAACGGT TCTGTTGGGCGTTTCTGCTGAGAGGCGGGAGGGGCTGAGAGTCTGTGCGAAGGTAG GTGGACAGACTGCATTGCTTGTTGTTGCGCTTCGGAGGCGGCGATCCCCGAAGGCGA GCTGAAATACGGCTGGAGCGTTCCCAGGCTACAGTTTGTAGCCGACGATTGTGGAA GACTAGGAGCCGGAGAGGTGGCCCACCCTCAGGGAGC >2:95024998-95025598 (SEQ ID NO.: 265) CTGGTAACGTCCCTTCCTGTCGCATGGATTCAAGGCCGACCTGCCCCAGCACCACCA CCAGCAGCCTTCTGCTGGGGCCGGCACAGCTGGGAGCAACCTCCTACTCTCAGGCA GACGCGCAGCACCAAGCAGAGAGGCCCGGTGCAGGATCCCAGCGCCGAACCAGCG CCGGCTCAGTGGACGCGGAAGGGGCCGGCGGCCGCGGCCGGTCCCATCCCCCACTG CAGACCCCCAGCCTGTGGCGGTGGTCCAGTTCCGCCAGGAAACCGCCGCCTGGAGC TGTGGGTCGCGCACATTAACGCATCCAGCGGAAAAATGAAGGAGACCCAAATTCAA AGTTAAAGTAATGGTGACCCGAGAGGTGCCTTGATGAGAAGGTTTGGGGTCCCGGT TACTGATGGTTATCATTCTTACGAGATGCTGGTCACCTACGAAGGGAGAAAGGCACG AGGAGCGCCTGACCAAAGTGGTTTTGCCCTGCTTCCCGCAAGAGGTGGCACCCACG GCTGGAACGCAGGAGTCAGACCCACAGTCCCCAGCTCTGGACGCCCGCAGCGGGGC CTCGAAGAGGTTCAGGGCGGTGCCCGCGGCGCTCGGGCCG >2:95074648-95075068 (SEQ ID NO.: 266) AATTCTGCTTGGTCTGTGGTAAATGCCCTTTCTGAGAAGCAACCATGACCTTCTCAA GAATACTTCAGAGGCACTTTTGCTCCTTCTCCACTAACCGACATCCTGTTTTGCTGGA ACACATGGGGCAGAGCGCACACAGCTTTGTTCCTGCACCCGCCCTCAGAGCTTTGCC ACCTGTTTTCAGGCTGCCTCTGCCTCCAAACCCTGCGGAGCCCTCCCTGCCCCGTGCT TTGAAGCAGTTTCTTTGGAAGCTGCTGCACAGGGGTTAACAACAAGCAACAACTCA GGTCGCATTCTTGTCAACGGAAGGGAGGGCCAGGTGGAACCGCCAAGGGGGCCATT TCTGGCTTTGCTGGAGGCTGTCAGCTTCTGGTGGGAGCCACAGCCTGAGGGCAGCCA GGATGGCTCTGCTGGGAGGGAC >2:130372760-130372940 (SEQ ID NO.: 267) GGCGCCCTCGGCTCTCCCCTTCGGGCCTCCGGGGAAGCGTCCCCGCTAGGGGTGGGG TCTTGGGACTCCCTGGGGCTTCCGGAGCTGACCCGTGGGGGGTCTGCTGCCCTCAGT TCCTGCTGACCAAAGTCCTGCCGGATCTGGCGCCTACGAGGACGTGGCGGGTGGAG CTCAGACCGGT >2:134719120-134719540 (SEQ ID NO.: 268) CCGCTCGGCTCCGCGGCCGGTGGCGGAGGCTGGGGCCGCGTTGTTGCCGCCGCGCTC CGCCCCTGGGGGCAGGTGCGGGCGGCAGGGACCCGCCCCAAGGCCCGGGCGCGGG AGCCGGCGCACCGAGGCGGACGAGAGGGAGGAACCAGCGTGAGGACCCACAGGCG GCCCTGGCAGAGCTTGGCTAGGGCGTAGCGGGGACCCGCCCCACCTGCGCCGCGGG ATGGTGCCCAGAGGGGACCCCTCCCACTGGATTCCTCTGGGGTCCGCGAAGCCCGC GGCCGCGCGTGGGTAGCAGACAGCGCCCCTAATTTGGCATCTTTCTCTTCTGGAGCT GCACAGGCTTCAGAGGCTGTACAGGGTCTTCGCCTGGGCCTCCATTCTCACTGCTCA TCCAGGGAAAAAGGGTTCATCTGTCCCC >2:176638778-176638958 (SEQ ID NO.: 269) TGAAATAATCATGTCCAGAAATGTATCAAAGGCCAGAGGGATTATCCCACTTAATA GCTCCACAGATGCGCCCAGAAGAATGTGGACGCGCGACAGGACGGGCTGAAAGGCT GCAGGAGGAAGCAGGCAGCCCCGGCTCCTGGCTTTACCATTTCGGTTGCTTTCCTAA AAGGCTACATGC >2:197786407-197786887 (SEQ ID NO.: 270) GGGAGGAGAGAGCGAGCGGTCAGGCAAAGCTCCATGCACGCCTTCCCCTCTCCTCC ACTTGAGAAGAGTCGGCCTCTGGGACTGGTGGGTTTCGAGAGGTTGAGGTGACCTTA AGGCTTTACTGAGGTAGAAGAAGCCGGTTGACGGGCGACTTCCGAAGACTGGTGTA AAGCGAAGAAGGTTCTAGAGTCAAACTCTGACTCTCGGGGCCTGACTCGCAAAACT CGGGGGCTCCCGAGAAGCCGCGGACGCCGCTCTGCACCTGTTGCCGCCGTCACTCAT CCCGCCAGGCGGGCGGGGCCGCGCGGGTGGCTTGGTCAGGACCTGCCATTCAGCCC AGTCGGGCTCCGGTGCTCGCCCCGGACGGCGCCCCAAGCGGGTCCCGGCCCCGCTG AGCACCTCCAGCAGTGGCACAGCCTCTGGAGGGGTCCGGGACGAAGCCACCCGCGC GGTAGGGGGCGACTTAGCGGTTTCAGCCTCC >2:236507319-236507799 (SEQ ID NO.: 271) TCTCTGAAGGACGGTGGCAGCAGGGGTCAGGGCACTACCAGGAGCTACAGAGGATT TGGGTGGGGGGTCTTCTGGAGGGAGAAACCAGGACTGCGAGAATCTTCTGCTTCGG GCAGGAAAAGGTGAGGCCGGGTTTGCTTCGCAGGCACGGAGCGCGCAGGCGCAGA GAGGTGTTTCACTCCTTCCCGTCGCGACCCAGAGACTCGCGAACCTCACTTCGGCCA CTCAGGTGGGCGCGACGCGGCCCTAGCAACGGAAACGCCGCGCCTGCGCATTGCCT TCCGCCTGCCCCCTCCCCCCCCCCGCCCCCCGCATTCCGCGCCTGCGCCACCGCGGG AGGCCTGGGTGGGCGCAGCTGTGGGAGCCGGTCGGAGTCCGAGCGCTCCGTCGCGG GGCCCGGCCGCTTGGCGAGCCTGCTCCGGGCCCCAGCACTTAGCCTGTGGTCCTCCA GGCCGTCTTCCCGCTTTCCTGCTGGCCCCAT >3:14880783-14881083 (SEQ ID NO.: 272) CATTTTAATTGTCCAAAACTAATTGCCCTTTTACAAGTCTGTGATATAAGAGGCAGG AAAGCAATGTGGAGACAGAGGTGATTTCCATTAACAGAGGCCTGGCAGCAGGCAGG CACTCACCGACGCTTTTCAGGGAAGTCCGTCTCCTGATTAATGTGCTTCCGGGGGCA GACAGCGGATGCGTCTCCTTGCTCAGGGATGGGGTGCATGGGGGCATGGTCTGAGG TTTTGTGCAGGTTGTTTGAGGTTTCCTTAGCCCTCTTGCTGAGAAAGGCAGGAAGAG GACAGTGGAGTGTTTCTG >3:32026520-32026820 (SEQ ID NO.: 273) AAAGGAACCCTTAAAGGAACTATATGGTTCTAAAAAAACCCTAAATGTATATTGCA ACAGGATGCCTCCTACCACACACAGCAATGGCCGGGAGAGAAAGACGCAGAAAAC CCTACCGTTAATATCTGCATTACCTTTTGCCTAGTGAACCAAGAGAGATCTGGGGAA ATGACCGCCATACTAACGCTCTCTTTGTTTCAAAATAGCCCACACAGCTGCATTTTGC AGGTGGTGAACAGCTTTTACTACTTTTAGTTGAGACAGCTCTAAGCTGAGGAAACGG GCATGAACTGCAGTTCCC >3:37453325-37453874 (SEQ ID NO.: 274) TCTATAGTGGCCAAGGGGTCCAGTTGTCCCCTGAGTCCGGAGGGGTGGGCCTAAGA AGGGGGCAGCTCTCCCCCATTAAGCACCATAAGCCGAGTGGTACAGAGCTTGTGCC CAACCCCAGCAGAGAAGCACTAAGGGGGGGTTGGTGCCCTCCTTGGCCACATCCTC TGGACCAGAGGGTATAAACAGCCACACAGTGGTCACTTCTTGATAGGAGAGAGAGT TAGGCTGCGGGAAGTTCCCCCGTTCAAGGTCGTGCCTCATGGGGGCCCAGGTGACA GCCAGGCCGGGGTTGATTTTATTGTGTATTCACCAGCCTGAGCGTCCTTAGGGGTGG CAGGCAGGGAGGTCGAGGTCACTGATGCTGGTGCTCTCAGCATGTAGTTATGCAGG AGAGTCACTGCTCTGTATTGGACAGAGGCTGATGGAAAAGGGTGGTTTGTGGATCG CAGTACTCAAGCATTCCTGGAAAAGGGGACTCTGAGACCAGCCCACTAAGAATCAT GCTGTTCAGGAGATCAGCCTTCAAGAGAACCAGTTTTCAAAGCCC >3:49277016-49277327 (SEQ ID NO.: 275) TCTCGCGGAGGAACCCGCCATCTGCCAGAAGCCCCAAAGACGCCCCGCCCCACTTC CCACAGCTTCCTGGCCCGCCCCGCCGCTGCCTCCCGCCCCACCGCGGCTCCCAGGCC GCTGGCCCTACCGGCACCCCCCCTTTGGCGAGTCGGCAGCCACGTCCTTGTCCTCAC CCGCAGCGCAGTGACGCCGACCCATCCAACGGTCATCGCATGCGCGTGCCCCGCGC AGGCCCCAAACCCCCACGGATTAGGTTGAAGGTCAGACAAAAAATCCCGGACCCAT ACGTCCGGTTCCTTAAGGCCTTGCCCACAC >3:125357496-125357736 (SEQ ID NO.: 276) GCCCACTCGCCCAGCCACGGGCCAAGAGCGCACGGACCCAGGCGGGCGGCAGCCCA CCCGCCACCACGCAGCTCCACTTCGCTGTTCCACAGCCACCAACCGCACAGCCGGCA CAGTCCCGCCCGCGCAGCTGGCCCAATCGGGCCTGGGCTGCAAAAGCCCAGGGAAT ATGAGGGCTCCCTACTTCCAAGTTTCTTTAATAAAAATATTACATTTAATGATGCTTG TCAATATCCTCACC >3:126267526-126267946 (SEQ ID NO.: 277) CGCAAGCGAGGGGAGGAGACGCAAAGCCGGGGAGTGAGTGATTAAAGAAAAGAAA GAAGGGCTTCTTGCAGCTCCGGGCTGTGTTTTTTCCTGCGCGCCCTGGCGCAGTCCC CGGCTCGGAAAGGCAGGAGCACGTGAGCGGTTTGCAGAGCAGCCCGGCCCAGCCGC GCGCCCGTGGCCGGAGGCTCCATTTACCCTCCGCGGAGGGCGCTGTGCGGCGGCAC TTAAGCGGCAGCTTCCTCTCTCCCAGGCGGCCTTTGTGGCTGTGGCCGGGACAGGGA AAAGCTGCCCAGGCCAAGAGGGCGGGGGCGTCAGGGGCAGCCAGCGCCGCCTTTGC GCAACTGAAGCGGATGAAGCCGCCTGCTCTCAGGTCTTCTAAGGAGAAGGTCTTTTT ATCACTCCCATTTTACAGATGAGGAAA >3:128491607-128492807 (SEQ ID NO.: 278) GTTCAATTCCAGCCCCTTAAAGCAGAAGGCTCCCTCCCTCGGCATCAGTGCAGGCTC TCCCACCTCATTACTGTTCTGTGTCTTTGGGAATCGTAGAGTCTGTGGCCCCCACGTC CTAGGTGTCTCGGCACCCTGGACCCAGGCGCCTCCGAGATTCTATATCGCTTCTGAC CCCTACCTTCAAGCCTGGCAGGCTCCCCGCGGAACCCTGCTGAGACCCGGAGACAA TCGGGCCGTGCTTCTCCCTCCTCCACGAACAGCCACGGTTTATTTGGAGCGGCCGGG GCCGGCGGCCTGACAACTGGTAAATCCGTTTCGTTAGGCACAATTTGTCTGCAATTT GTCAGCCCGGCTGGGAAACGCTCCCCAGACGCCTCGGCTGCCGCACGGGCCCTACC TGGTTCTCGAATCCTGCCTGCTCATAAACGAATCCTAGCACGGGGTGCCTGCGTAGA CCTGGAGCTCACCACCAGATGTTCCCGACCTCGGGAGAGGAGGCTTTTTCCAAAACA ACGAATTTCCTTCCTTGTTTTCCGGTAAAGGAGCGTTCGCCACACACGGGGTCCCTG AACGCGGGGCCTTTCCCCTCGTGGTTGGAGCAACGCGGAGTTCAAGCCTGGCCGCC ACAGAATAATTTTAAATGCCCCGTTTTCAGACAGATCCAGAACGCCGTCTACGCCTA CCGGCGGCAGATCTTCAAGCCCGCGGCGGCCCCATTCTTATTGAAATCCCACTAAAC GGATTCCGACTCCGGCTTGGGGCGGGGGGAGACTTCCAGACCCGGCGCTCTCCCCC ACACGCACCCCAGTCACACAGGATAAAGGGCTGCGGGGCGCAGCGCGCGGGGGCG CAAGCAGGAGCGAGCTGGGTTAAGCCGCGAAAAGCCGGCGCACGGGACCAGCCGG CAGGTGCAGCCGCCGCTCGGCGGCCCGGCTCGGACGCATCCGCCGCGGTGGCCTGG GGATTGGGGGCGGCCGAGACAAAGGCCCCAGTTCGGGGGCCGGGAGGCGGGGGTG CTTTGCGAGGCTCTGGGAATGCCAGGGTCTCGTGGCCTGTGGCTCCGAGAAATGGGA AGACAAGAGGCCCGAGGCGGGCCTGCTGTGCCCAGGTAACCAAATACTCCCTCTGG TTAAAGTCCCTATAACCAGGGTTTCCGGTCTCTGGCAGGGCCAAGGCGAGCCCCAA AGGTAGGGGCCACAGG >3:134650612-134651272 (SEQ ID NO.: 279) TGGGGCAATCACGGGGCTGCGCGTTGCCACGGGACTGCGCGTTGCCACGGGACGCC GGTGCCACTGCGGGGAAGCGACGGCAGCCATGGGGGAGAGGGTCGGGTTCGCTGAC CTCGTTCGGGGGAGCAATGGGCGCCCCCCGGCGGGCAGGCCCTTGTGGCAAGGAGG CCAAGGTGCCGGGGGACCCGGGGACCCGGGTCGGGCGCGCGTTACCTCCTCCGCGC TGCAGCAGCGAGCTCGGGTTCGCCTGCTGGTCTGAGAGCGTACCCTGTGCGGCGCGC CGCTTCTCCGAGTGCACGATCAGCAGCATGTCGATAGATACAGCGTTGATGTCCTTC TTCAGCTCCATGATGCCGCCTCCTTTCCGACCTGGGCGCCGCGGCCGCACGCTAGGC TGCTTGCGCTGCAAATGGCCCCGTGCGCGCAGCTGCCCCACACGGGAGAGGGCGAG GGCGCGGAAGAGGGCGCTCCCCCGCCGCTGGAGCCGCAGGGCGCTGCTTTTCGCTG ACTCTGCCAAACACGCCATTAGGGCCCGCCTGGGAGGGCGCTACCCTAATGAAGCG GCTCTAAGTCACCTTTGAAAGGAAATCCCCGGGCCCAAGCCTTGACCTGCACCGGG GCCATAGTCAGCAGGGGCGGCCGGTCCAGAGCCTCCCTCCCT >3:147407874-147408234 (SEQ ID NO.: 280) CATTTTAATATATAGTCAATGGCTCTTTGTGGAAGGGACAAAAAGAAACTACGCGCA GTTGTTGAATAGACTTTGCGCTAGGCAAAGACAGGTTAATCGAGGGCCGCATCGCG AAAACAAGCGAGTGTTGTATGTTTGCACTGAATCCAAATGTCTGCATTTTCCTAACT AAATCAAAGGGAGTGTTATTTCTTTTTCTGCTCACTCATCTGAAGGTAAGTAAATTTT CTCTGGCGATCAAAAGCCTGGTCGGCAACAAAGACCGCGCCCGCTTTTTCCACCGTC CTGGTGTGGCGAGTTGCGGAATTTCAATAACTGTGACAAGGGTGACTGATTTGTGAA CTAGAAAAGGTTTGAATGT >3:160224533-160224833 (SEQ ID NO.: 281) CATGTTAACTGGGAGCGCAGAATTCCTTTAAAGTCAAACTTTGCGAACAAGAATAAT CTTGAAAAAGACCCTTTAGGCGCAAATCAACGCTCAAGAACGTTGCCAATCACTTGT AACCTCCTTAGGCATTTCACGGATGTGTTATTTATGCTCAAGGAGGGGTCTCCTTTCA GCCCGGCAACCCAAATCTTTGCTCTGTGCTTCGGACTCAGTGGGGGCTTGTCGGATG AGCCACTGGGAAAATATGCGTCCCCTCACTTCTCCTTAATCAACTAAGGTCACCTTG ACGGAGCGCTTCCCT >3:161105353-161105533 (SEQ ID NO.: 282) CCAGGGCCGCGGCCGGAAGCCCCTGGCTGCACGCGCGGGCCCAGGCGGCCCCCAGC CCTGTGAGCTCGCATGGCGCGCCCTCTGGGTCCTCGCGGTCACCTTGCATTCCGAGC ACGGCCGTGTTATGTATGCCTTTAGTTGATGCTGGCCAAAATTAGACAACTTAGTGG CAGACGTCGAG >3:173397661-173398081 (SEQ ID NO.: 283) CTCTCCTCGCCGCTCCTCCCCGCCTCCCCGCGGAGGGTTGACCCTTCAATTCGGAGTC CCGGCCTGTGGGCGGGCGGGGGAGCGCCGCGGCTGTAAGCCGAGGATCAGGCGGC GGCGCGGAGAGCGCGCCCGGGCGGCCAGCGCCGAGCGCGCGGAGCTGGCGTGGGG AGACACGGCAGGAAAGGCGAGTCGGAGTGGGTGATGAGAGGCCGGGAGAGCCCGT CCGAGCCGGAGAGACCGGAGAGAAGGGAGCGAGCGACTGTGCGGCGCTCACGCTG CCAGAGCCCGGGCGGAGTGCAGTCGCCTCCAAAGCCTTAGAGCGGCGCCCCAGTCA CTGCAGCTCTTCACCCTAGAGCTGTGCCCTGGGACCACAGAGACCAAGAGCATGGA AATCGGCTGAGAGGTACAAAAGAAATAAGGA >4:1404179-1404659 (SEQ ID NO.: 284) ATCGATCCGCAGGGCTGATACACACTTAATTAAACTCATTTTGTGTAGTGTACAAAC TAGTTAAGGCCATTTAATTTATTTCGGCGTATATTACCCCCCAATTACCGCCGGCGCA GGGCCAGCCAATTGCCGGGCATTTAATAACAGGCCCGGCGGTGGGGCCGGAGCCGG CCGAGAGAATGGGGCTTGGGGGACCCAAATCCTATGCCCTGGCCCCGACCCTACCT CAAGCCTCCAGGCCCTGAGCTTCGGTCGCGAGGGTCAGCCCCGGCTCCCCTGCCCGC GCCTCGGCCCCTGCGCAGAGTTGCCGCGGGTAGGGCCCTGCTCGGCCTCACCAGGA GGGCTGGGCGGGCGTGCAGGTCGGAGTGGCTCCCCGCGGCCTAAAGGCCCGGTCGG CCGAGTCTGAACAGCAGCTCCGCATCCTCCAAGCAGAGGCCCTGAAGTGACTGCAT TTTGAGTCTCTGAAATTTGGAAGAAAGCA >4:1683738-1683918 (SEQ ID NO.: 285) CTGCGCTCAGATTAACGGAAAAAGACACCCCTCTAGAGTCCGGCAGCAGCGGGCGG GCACCGGCGCCTTCTCCACACAGGAGAATCTCGGCGATTTACACCCCCAGGCTACGC AGAAAAAGCGGCTTCGGAATCCGCCGCAAGTCCCCTCCTCGGGTCGCCGGGGAAGT CTGGCCTCCCGC >4:7938762-7938942 (SEQ ID NO.: 286) AAGAAATCAAGAAGCTCCGGGCAGTAGGGCCCTGCTCCCTCCAATCAGAGCCCAGC CCGGGGCCAGAGCAGGAAGCGCGGCGGTGGGACGCGCGGTGACAGCCCCGCGCCC CCCGGGGCCCGCCGGCCAGGGGAGAGGACGGTGCGGCCGCTGCGCGACAGCTCCGG GCCCGCGCCTCTCG >4:7940020-7940200 (SEQ ID NO.: 287) GGGCTTGCGGGGTCCCGCGGGAGGACCCGCCTCAAAGAGCCGGCCCGATCATCGCC TCCTAGAATACCCAGCTCAACGTCTACCTGGAGTCGGCTCTACAGGACGCGCTCATC TCAAACCCAGAGCTCAGGCTTTTAGGGCAGAGAGCGAGAGAAAGGCTTGCTTTACA GAAAGGGAAACT >4:30720303-30721203 (SEQ ID NO.: 288) GAAAGGGAGGGAGGGAGGGGAGGGATCGAGAGAGAGCGGGGAGAGAGAGGCTGC AATCTCCTCCCTGAATCGCGCACAGCGCTGCAGATCCCACTGCTCCGACATGCGGGC CGAATGCAGGTGAGAAAAGGCACGGACTCTGCGGCTGCGAACCCAAACTTGGGCAC CGCACGGTGCGCACTGCTCAGCCTTCGCCCCCGTGGGCGAAAGGCTGCTGCGGTTTC AGGCGGCTGCTTCGTGACTAATGACCTTGCGCAGAGTTGTTAAGAAAAAAGAGAAA CCCGCGCTCTCCGGGGTGAGAAGGGACTGACTCTGGGCGTCTCTGAAGATGGCTCG GGCTTCTCTTTGGCGCGCCGGGGGGACCCTGACACTGACCGCTCTGTGACGCGAGTA GTCTCCCCTGCACCGTGCCCGAAGCGACGTGCCGGGGGATTTTTCATTCTCGATCTG TTGACTGGCTCCCCCGCTGCATGAGCAGAGTCGGAGTTGAGACTGGCTTGTTGCTGG CCCCAGCGCCTGGTGCAGGAAGCGACTCACGTTTGTCTGGGTGGCCGGAGCCGGAG CAGAGCCTGGGTTTGGAGTGAGTGCCTGGAACGTGAATTGGACTCAACTCGAGTAG CAGCAAAGACCAGCGGGCTGGCAGGCGGGGGAGGCTGCAGGCTCATTCCCCACCTC TTCCCAGCCCCACTGCCCGTCTGCCGGAGCGGTTCTGGCCCCTTCCGACAGAGCGGG GACTAGAGCCGGGGATTCTCCGCCCGCTGAGGGGATGACTCTGGGTTGGGGGAGCG CCGAACCCGCGGCGCGCAGTGTCCCGTGAACTGTGAGTACTGCGACTGAACGGCGG CAGGCGAGCGGGCGATTAGCACCCATTGCATGAATTATGAAACAATAACTTTCGGA A >4:41866325-41866745 (SEQ ID NO.: 289) CCAGCGTGCGAATTCCGCCCCGGGATGCGAAGGAGTTCGAACGCATGGAGTGGAAA ACAGGCAGGCGTGATGTGGCCATAGTGGGAGTCAAGACTGCGGAAATGGAGCGACC TGCAGGCTAGAGGAGAGATCCACGTGCGGGATCCACTTTGACCTCGGCTTCATCTCT GATGCTCTTACTGTGTTCGCTTCGGCTTTGGAGTCCAAGATATGTGCGGTCCCCACTA CGAAACCAGCTGCCTGCACCCGGATTCCAGAGCCTAGGCCCTTACCTATGGGAAATC CTATAGCTCCAGATGCTGGAATCCGAGCTCTGATAGGAAAACGCCCTAATGCTGGCA TCTCTCGCTTAGCACATAGGCAAGAAAATGGGGCACGACCCCCAAATCCACTCCCTT CCAGCCTCCGAAAAATGCACCCA >4:41878205-41878505 (SEQ ID NO.: 290) AGGCGAGAGAGAGAATCGCCCAGGCGGCTTAGGCAGCCAGTGGGCCAGTGGGCCT GCGCGCCGGGGTCAGGATGGCAGGGCAGTGTGTCCATCCTGGCGGGACAGTAATTG CCCCGGGTCTGACACGACGCCGGGGGCTCAGGGCGCCTCCATCCATCTCCATCCAGT TAGCGACGCGCCCCCCGACCGGGCGGGTGGCCGGGCTTGGGCCTCAGCTCCGAATA ATGAGAACAATTGTCTCCCCGCCTGGCATAGCCCTCCGCCGCTCCTCCGGGTTCGCT GCCCCTCTCATTTCTCTAGC >4:54231766-54232486 (SEQ ID NO.: 291) AAGAATGAACCCGTCGTTAGCCCCCGGTGCCCTGGCTCTTGTTTAAATCCTTAGATC GAGAAGGACTTGAAGGAGATCCCAGGCTCCCAGCTCTGCGCCCCTGGGCCAGTTTC CTCTCGGGACGCGGACTGAGGAGGGATGCAGGGGGAGGGGCATTGGGCCGGGCTTT CCAGCTGCAAACACGTCTGGCGCCGAGGCGGGCCCATTTTGTGCCTCCTGGGGACG GACCGTGGGCGGCGCGCAGCGGCGGGACGCGTTTTGGGGACGTGGTGGCCAGCGCC TTCCTGCAGACCCCACAGGGAAGTACTCCCTTTGACCTCCGGGGAGCTGCGACCAGG TTATACGTTGCTGGTGGAAAAGTGACAATTCTAGGAAAAGAGCTAAAAGCCGGATC GGTGACCGAAAGGTGTGGGTCTCAGGGTTCCCCGGGTCTAACTCGCCGGGTCCAAC CGCAGCATCAGCCTTGGGGCGGCAGATAATCTTTCGGTCTCGCCTGGGGCGCAAGAT GCAGGATCGGGGGCAAATGGCTTCTCCCAACTTCCCCCTAATTCGGGTTCTGCCAGA TGGTTGTCGTTTGCTGAAGTGGCTCGGCGGCATTTCCTTTTGTTTTAAACTGATCAAT GAGCGAACCTGGGATGGGCTGAAAAAGTAGATTGTAGGAGGGAATAATGGGAAAC CCGACTTGGGGCGCCTCCTTCCCTGCCTCCTACTGCAGTTTCTC >4:56530240-56530420 (SEQ ID NO.: 292) TTAGAAACTGACATGTTCTACCCCAGGGCCTCCGCGAACGACAGCAGGCGAGAATC CTTGCTCTGGACACGGGGAACAGGGTCAGCATCTCGTCTCCTATCTCCACCGACCTG TCTCTGGCTTTTCTTAGTCCCCAGATGCGCCCAGAAGGTCCTGGAGAGTGGTGCGTC CCCTTGGCAAC >4:165873652-165874192 (SEQ ID NO.: 293) TCCTTACCTGCCCTCCGCCCACCCGTGGGCCCCTAGCCAACTTCTCCCTGCGACTGG GGGTAACAGGCAGTGCTTGCCCTCTCTACTGTCCCGGCGGCATCCACATGTTTCCGG ACACCTGAGCACCCCGGTCCCGCCGAGGAGCCTCCGGGTGGGGAGAAGAGCACCGG TGCCCCTAGCCCCGCACATCAGCGCGGACCGCGGCTGCCTAACCTCTGGGTCCCGTC CCCTCCTTTTCCTCCGGGGGAGGAGGATGGGGTTGGGAACGCTTTCCCCGAGGATGC TCGTGTGGCTGGTGGCCTCGGGGATTGTTTTCTACGGGGAGCTATGGGTCTGCGCTG GCCTCGATTATGATTACACTTTTGATGGGAACGAAGAGGATAAAACAGAGACTATA GATTACAAGGACCCGTGTAAAGCCGGTAAGTGGCTCTCCAGGTTGGGACGGTGGCG CGCCGGGGGCCGCTGCGCTGGGTTTCCCATGGGTGGCGGTGGGAGCTCACCTGTTTC CTTCCCTCCCGCGTCAGCCCCTCCGCCGCCC >5:77210543-77210783 (SEQ ID NO.: 294) GGTGCGGGAGCCCGGCGAGGTCGAGCTGGGCGGCGGCGGGGGCCGCGCCGAGGGA GGAGGGGAAGGCGGAGGCGCGGGGAGCGTGTTTGGGGCGCCGCGGCGGGGAGGGT GGCGGCCGCTGGTGCGCGCGGGGCGCTGTGTATGCGCGCTCCCCCGCTCGGGGAGG AAGATGGCCCAAAAGGGAAAGTTGGGGTGACGCGCGCGGTCCCCGGAGGCTCGGC GGGGGGCACCGCGGCCAGCC >5:93579016-93579376 (SEQ ID NO.: 295) CTGGAGGCAGGGCTATGAGCACAAGTGGGGCGCCCTGTGGGTGTGCAACCGCGGTC GGGGAGCACAGGCTTCCGAAGAGAAACTGAGCTCTAAGTGCCACTCAGGCCGGACG AGTTCCAGAGGGGGACAGCGCCCTCCTCGAAAAGCCTTGGTTTCTCCCCGCCCCCTC TTGTGACAGAAAGTTGGCAAGGATGCCCCGTAGGAGTGCGAGCCGCTCCCCTCCTCC GAAAAGCCGCGGGCTTCCGCTGCTCCGGGCATCACCACCAACAGCTTCCCACTCCCA CCCCTGGGACTAGGACAGGGGACTTCACCCTCCTCCTTCCTTCCGGAGGAGCCCGCG GCTTCGCCTGAGGCCTCGCGG >5:93621604-93621784 (SEQ ID NO.: 296) TGGTTTCCCCTGCGTGCGGGATCGCACAGCGCCTGTTTCCTTGCTTCCCAAGGGGGT GGTGTGGAGGGGAAGGGGGAATGATTTTTCTTGCGTCTCCCGGAAGCTGTGCTGTTA GACACAATTACCTCAGCTAGGTCACTGAGACCAAATCATACGGGACGCTTAATGAA GGACCGCATTC >5:173236238-173237198 (SEQ ID NO.: 297) TGCGGCTCGGTCAGGCGCGTGGGGGAAGGGCAGGGCAAGTGGGGTGATCATGATCA TTTTTAGCCCAGGGTCAGTAGAGTAGGGCACAGAAGTCAGACAAATCTGCCAGAGT TTCAGGAGCGCCAGCTACATGGCCAGATCCTGCCCGGGTGGCCTCATTTCTCTGGGT CCCCGCACTCCTTGGGAGGTCTGATGAAAGCTTGGGGTCTTCTCCATTCCCCAGAAC ACTGCAGAGAGGAGTTTTATTTTGCTTACAATTCAGGAGTCCGGGCAGGCAGAGCG GGCCCAGGTTAAGGACGCCTTCTAGAGCTGGGGATGACAGGATTTGTCAGTGGAAA AGCGTTGGCTTCTCACGGCCCTAGCTGGTACAGGGAACCGCGGGCGGGAAGCTGGG CGGGACGCGTGGACTTGCTGAGAATGGGGATGTGGAGGGCTTGGCTCTTTGCGGAG TGCGGGTTGGCAAGAGGCGCTTGGAGTAGAATAAAGGCGGCGCAGGGCCAAAAACT ACCTAAAGACACAGCTCCCGCAGGCGCGCCCAAGGTGCGGAGGAAACGCTCCATGT ATGGGGACAAAATAGTGTCTGTCCAGAACGTACATCTTGGGTGCTCAAACCCGACA GTGTGCCGTCTGAGACGCCGACGCAAGTGAAGTCAAGCATTGGCCTGATGTTGGGA CTTTTCCTGTCCCTCATCAAAGCCACACTCCCAGGACCTGGGGCCTCCATGCTGGGG AGAGAGGTGAGCCCCGCAGGGCAGCCCAGGAGGCGCGCAACGCCCTGACCCCGGCT TCTAGGCGCCAGCCGTCAGTAACAGGCCTGGGCTGCCACGCCGAAATCACGCCTCG AGTTTCTGAGCCAGGGACTACTGGGGGTCTGGAATTGTTAGTCTAGTCTGTGGAGGA TGCCTTTTCTTAAATGTGGGGCGTTCAAGGCCCAGGAAACCTCGTCCCCCCACCTCT TCAC >5:173283672-173284272 (SEQ ID NO.: 298) GCACTCCAGGCGCGTCCAGCACGTTGCTTTTCTCATTTGCTGCTGCTCCGGGATCTTT GGCAGCAGCAAAACCCCATTCTTTTAAGGGCTGCGCAGAGTTGTGCCGCCCATGCCC GGCTGGTTTGAAGGTGCCCCATGGGCGGGCGCGGACGTGTGGTTGCTCCAGTGTTTC CTAGAGCACTCTCAGCCACGCCCCCGCCACCCCAGCGGCGCTGCAGGAACCAGCCC GCCGCCAGCGCGAAGGTGAGACCGGGCGCCACGTGCTTACCCGGCGGCCTCCGGAA CCAGCCCTGCCCGCCGGCTGTGCGCGGATGCCTGCAGACGCCGAGCTGCTGCCCCCG TGTGGCCTGGTGCGGGGGCTCCTCCTGCTCACTGGGGGCGCGTCCCGGTAAACCAGA ACCTCAGCCCATCAACTCACTCGTGGGGTTACTGAGGAGGAGAATCTTTGGTTCTCA CCGTCATGGCTCACCCAGTGGCTGAATCCCGCTCGCACGTGCCGCATCCAGGCAGCT GTGGAAACTGGTTGAAACCAGGATGGTCAGCTGCTACCCTGTGTTTGGGGGACTATG TGACAGTGCCTGCTGTGTCCCTATTCTGGTGC >5:175772822-175773002 (SEQ ID NO.: 299) CTCCAAGCCGACGCGCCCTGTTTTATGCCTTGAGTAGGCGGGAGCCTTGCAGGTCTG TGGGTTTCTTTCTCAAAGGAAAATTGCTGGGCTCGTGAGGAACAGCCTCGGGCACTT GCTCTACTTGGAAAGGGTGAAGAGCGCGGGCTTTGGAACCCTAGGCGCGCCCGCAA TCCCAGCTCTG >6:17102332-17102512 (SEQ ID NO.: 300) ATTCAAGGTAATAAACAAACAAACAAACAAACAAACAAACAGACAGAAAGCCTTTT GCCTGGGAGGTCTCGCGATTCCCACGCTTGGGGGCGACAAGAGTTGGCTGGAGCAG GGTCGGTCGAGGCTAGTTAACAGGTGGGAGCAACTTTATTCTGCCGGTGTTTAACTG CTGTCTTAACCG >6:25041894-25042434 (SEQ ID NO.: 301) TCTGATCCAGTGTAATCGCGAAGGTAACACCATGGTCCCAACAGAGCGGCCTAAAA CCTGCTCATGGCAAAGGAACAAAAGGGTCTTGCAGCTATCCTGGAAGTTAAGTCCA GACGTATAAAAATGAAAAAGAAAACTTAACCCCCCCCTTTTTGTTCTTTTCTTAAAA AAAAAAAAAAGAGTATTTGAGGCTTCCGTTGACTTCTTTTATCTTGTAACTTGCCTTG CCTTTCCTTCCCTTAACTTCCGACTGGCCCGAAGGCAGCTGCTGTGCTGGGCTGCCCT AGCCTCCTGTGCCATGTTTTATGCATGAAGATGATGGGGCGGTAATTTATTCAAGCA GAGACGATCACCGGGCTCCTGTGTCTGCCCTCGCGTCAGAGGAGCCGTGCAATGGC AGGGGGAGGGCAGGTGTGTCTGACTGCACGCAGGAATGGGCTGAAATGGGAATCCC TCTCTGTAGGCAGAAATGAAGAGCAGAGCTTTGCTGCTAGAGCTGAATCAGAGCAA CACCCCTTACCTTTTAGGGCGTATGATTTAT >6:28657067-28657555 (SEQ ID NO.: 302) CCAACGACTGTTTTTACTTAGGGAAACTACTGAACTGCCCCCCGATTCCTTACCGCA TCTCTGCATTGTCCCAAGTTGGAAGTTGAGACTAAAGCACCAAGATACAAGAGACG CGGCATCCCAAAAGGAGATTTTTGTGTATTCTGCGAAATACACAAAAGGGCTAGCC AAAGAAAGTCCTCACACACGTGCATGGTATAAAAGCACCAGCTTTAAAAAGAGAAG TGTTTTTGTTTTTTTGTTTGAGAAGCATAATTGAAGTGAGCAGTTTTAGAATCAGTGC AGCAAATTTAGAGATTTCAAAAGAGATCAATATAGAAGGGATCAAATCCACACAAT CATGGGAACGCTATGAACTCACTGGCAAAATGCAGTCACTGAAGGAAAAACGTCAG TGTCAAAATGCTACTATTTCACCTCTTTGTGTACGATTTCTGAGAGAACTGCCACGTT TGGAGATGCTAAATTTACCCAATGCCTTCGTAGCCT >6:29553847-29554027 (SEQ ID NO.: 303) CGTTTGCCGTCATCCTGGCCTCCTACGGTGCCGTGGCCCGAGCTGTCTGTTGCATGC GGTTCAGCGGAGGCCGGAGGAGGGCGGTGGGCACGTGTGGGTCCCACCTGACAGCC GTCTGCCTGTTCTACGGCTCGGCCATCTACACCTACCTGCAGCCCGCGCAGCGCTAC AACCAGGCACG >6:31308135-31308735 (SEQ ID NO.: 304) CCCACCCCAGCTCCTTCCTCCCTCTGTCATTGGTCACAGAACAAGTCAGTCATGATC CAGATTGAAGGAGAAACCTGGAGCAAAATGGCCCCAGCGCTTCCCCACCTGAGAGG GATCAGCTGAGGCCCCGCCCCCCCATCCCTGGGAGAACCGGGCTGGTCACTCTGGG GTCGGGGCGGGGCACACCTGTGCCCGGAGTCTGAGGTCACTCACCGGCTGACCCTG GTGGTGGTGCGGGCCCAGGAACCTCAGGCCCCTCAGTAACACATTCCCTGCGGTCTT CGAGAACTTTCCTCAGGGCGCCCACAGCCCTGTGCCATCTTCTCCACCCGCGCTTCA CGCTCTGATTCTCGCCGCGGCTGTGGAAGCTCAGGAATCGCGTGTCGCCCACGAAGG CGCCGCGGAGGAACTCAGGGCCCACGTGGTGAAGGCGGAGCCCGGCGGCCTTCAAG TACCCGGGGTGCGGGCCTGGGCTCCGGGAACCCGCACATTGCGGGCGGGAGAGGCG CAGGGTGCCTGGGACGCCGCCCCGCTCGCCTCTCTCCTGGACGCCGTCGCCCTGCCT CCCCGCGGGGACACAGCCTCCCTCCCACGTCCCGCC >6:42726729-42727149 (SEQ ID NO.: 305) CGACGAGGAGGGCGGTGCTGAGCCCATAGCAAGTCTGTGGATGCCCCCTGGTGGCC CTAAATAGAATGGCTTCAATGGATGGAAATTTAACGTGCTCGCATCCCCAGCACGTT AAATTACCCAGAAAAGTAAGAGAAAAAGAACAGACACATCAGAAATGTCTCTGGCC AAACCTTTCAAGTACGAATCAAGGCAAGATATGGCGATGAACAAGCAGAGAAAAGT GGACTGCAAAGGAAGCAGTAATTAATCTGTCAGAGAAGGGAGGGCTCCTTCCTGCT TCCGGACCATGTTGGATGTGAGTCTAGATGCGAGACATCTATTATAGAGATAATAGA AGAGGTTAGCGGAACCAAGGATGGTTCACTTTTCTTCTTTAGAAATACCATTAATGC TGATCGTCTTCGCCGCCGCCTGCGTG >6:43174231-43174471 (SEQ ID NO.: 306) CGTCCTAGGGGACAGGTGTCCATCCTCACTTTCCTGATAGAAGACCGCCCCCCTAGA TAAGCGGGCGGCCTCCGTGCCCATATAAGGCCGGCTTGGGCTCCACGCCGGCCTCCC GCCCGCAGCCCGCCTGCCTGGCAGGGCCTTTGCATTCCTCCCGCCAGCTGTCTCCCC GCTAGGGGCGGGGGTGTAGTTTAGCCCGGCCCTCCGGGCTGGGTCGCCAGGGAGTA GAAAGGGAGCACTC >6:46735424-46735814 (SEQ ID NO.: 307) CTGGTGATGCTGGAGGAGGTACCGGGGAGGAGCGTGTGTGGCCCCGGCCTCTCACT AGCAGCGGCGGCTCCCGACGCTAGCCTGCTCGAGCGCACCCAGCACCCTCCCCAAG ACCATGGCCCGCACCTGGACCCGCGGTTAACTTAGCCCGCCGCGGAGAGAGCCAGG CAATGCCTGGGTGGTGTCGTGCTCACCAGCTCCTTTCCGCAGACCTGATGCCGATCA GATTTACTCCCTGCTGAATTCACCCCCCAGTCAGGCCGGTTTTCCTTGTTTCACCGTG TTCTCTGAATACACTGAATTACTCCGAGCATCTATAGTTGGCAATGCCCTGCGCATTT TCCGCACTCCGATACACTTTACACTGAACACCAATTCGGAAGTTGTGTGG >6:56955981-56956161 (SEQ ID NO.: 308) GCTGCAGTGTGCCTTTCTGCGGACGGCCACGGCCACCTGGCCAGGAAGCGGCTGCT GCAGCAGTCATTCTGCGGCATCTTGCGGCCTTGGCGGGCGGTGCTGTGCCGCGTTCT GCTGCCCCCAAGGCAATGCTGGCTTTCCCTGTGTGGGGCTGGATTGTTTGTTTCATTT ACTCGCATAA >6:83708290-83708710 (SEQ ID NO.: 309) GGGTGCTGGACTAGCCACAACGTGCGTTGGGGTTATTCCCTGGGCGCCGCACCCACC GGTGCCCATCTCCCACCTCAGCAGACTTTCCTCCTAGCAGCCCGCAGGCTTCGGGGA ATGCATCGGATACCCAAGCCCTGGCTGCCTCCCTCCTCCTCCTCGCGCTGCTGCAGC AAAGGGCTCGTCCTCCCTCAGTCGCGAAGGAGATTATCCTAGCGTTGCGCCATGTTA TGCCCTCGCCTCCCCTTCCTTCCTCGCCGCCGGCTCCAAAGCCTCGCCGAGGCCCATC GCCCGGGCCCCTTCCCCCCGGTTCCAAATCCCTGCCGCAGGGGCCGCCCGGGAGCTC TGCGGAGGCGCCGGAGTCTTGGGGCGCCTCACCCTTCCTGGCTTTGGAGAGGAGCC GGGCTGACAGCGAAGCCCAGTC >6:98833379-98833919 (SEQ ID NO.: 310) GCCAAAGACATAGACTAACCCCACCCGCTAGCGCCCACCGAAGTTACTGATTAGGA AGGTTCCCCTGGCATCAGCCCATTTGCTTCACACACTCTTCCTCCTTCCCAAGGGGCT AACGGAAAAGTTGCACCTACCAGCGGTAGGAGCACGGGGAATCGCGCACGCAGGC CCTCCGCGCGGCTTCCCGGAGCGGCCTTTGGCGACTGCGCCGCCCCTACAAGGCCGC ACACCCCTCGCCAGCACTCCGGCAGCCTCGCACAAGACGGAGCCCACGCAGGCTTC TAGTTTTCTAAACCAAAAACTGCACGCGCCGGCGTGTGAATCTGACGGAGAGACTTT TAGAGTTTTGTTTGGTTTTCAGTTCAGACCGCTACGCTGTCAGAGCAAGCAACTCCG AGCCTTGATGGGAATGACTTACAAGCCGCGGTGCGGGCTGAGCCTGCCTCTCTCGGG GTTCTTTCCCCAAGGGAGTGGGAGACAATTGGGCCTGGAACCTAAAAGGAAGAGAG CCTGTGCTAGCCGCGGGGTAGAGGGGAAGGAG >6:167351042-167351222 (SEQ ID NO.: 311) CTGCCACACACCGCAGGCAGCGCTGACAGACTCGGCCTTCCGGGAGCGCAGGCGGG TGGGGGGCGCCGCCCTTGTCGCTGTCCGGAGCCCCGCAGGCCCGTGGCCCCCTGCCT GGTTCTCCCGCCTCTGCAAGCCTAGCCTTCAGGACTCCGCCTCGCCCCCCTCTTTTCT GTTCGGAGAC >6:170736319-170736619 (SEQ ID NO.: 312) TGGCTCAAAATATTCAAAATTTTTTCCAGAGTTTGGCCTTTTCTTCAGCACTGGGAAT TGTGATCCAAAGCTTTTCCTGATGAGGCACAAAGTTGGAGAAACAAAACGCAAACT AAGCAACAATGAAACAGAACAGAGTGAATCTGCTGTAGCTCAAGAGAGGACGTAGC TGCCCCCACTCCGCATCCCCGGGCTCGGGTTTGCCTTGCTGACCTCTGCTGCCACCTG GTGCCGCACAGAGAAACTGAGGAGAAACCACATCAGTCTCCTTCAGCCTCAGCTTC ACATCTGTGGTGGGTCA >7:351113-351413 (SEQ ID NO.: 313) ACAACTGCACACAGTCCAAAACTCACGCTCACACACATCAAAACACAACTTCGCAC GTCCAAAACTCACACACACACACGACACAACTTCACACAACGTCCAAAACTCACGC TCACACACATCAAAACACAACTTCACACAGCGTCCAAAACTCACGCTCACACACAT CAAAACACAATGTCCAAAGCTCACGCTCACACGCGCGTTGAAAGCAGCCGGAACAA CACAATTTCCTCCAAGGGGAAATGCCGATTCGAATGACAGCGAATTTCTCATCGGAA ACCATGCAGGCCAGAAGGAA >7:19118914-19119214 (SEQ ID NO.: 314) CTTTTTGAAATGAATTGAGGTAAAATAACCGTTTCAGGTCCATCCCTTACATGGCAA AGTAAAAAGCTGGAGTCAGTACACAGTGTTGGGGTGGGGGCAGCGTTTGGGGGCGA CGAGTTTTGTGCACCGCGCTGGAGTACCCTGCACATAAGGTCCGCTCATGGGCTTCT CAGTACGGACTCGCCGGCGGGAACAATTAATTGAGCAAAGCGCCCCTTTCTGGGCT GGAGCAAGGTTCGCGGCTGCAGATATCTCAAGCTGAAGGCAAGAGCCCAGGCGAGG CGCAGGCAGGCCACGTGGC >7:28957779-28957959 (SEQ ID NO.: 315) GGTCCAGCCGTCTGAGCTGCCCCAGACGGTGGAAGTCGAAGGCCGTGATGTTGGTT ATGAAGTTGCCGCCGAGGCTGTAGGTGAGCACGTCGTGGGGGCTCGGCAGCGAGCT GGTCTTGGGCACTACGCGGAGCCCCCTGTTGGTGCACAGGAGATGCTGGGGATGCT GGCAGTCGCAGCG >7:35254531-35255011 (SEQ ID NO.: 316) AAGAAAGTAGGGAAGCGCTCAGTAGAATCCGGCGCCTCTGAGCCGGCGCCAACTGG CCAGGTCCATACTCGGGGCAGATCCCAGGGCTGGGACTCTCATTCGATGGTCCCAAA TTTGATCTCTTTGACAGTGGGGCTGAGCAAATGCAGCCCTGAAAAAGATAAGCTTAG CGAGAGCTGCGGGCATTTGGCAAAGGATGCTGCTCTCAGAACCGTGGCTTCTGCTCC TCACCAGTGCGTCTCTAGCCTGGGGCTCCTATTTTCCCTAGAGGGACCCTGGAAAAT GGGACGGCTGCCGAAGAGAAGGCGAAGGTCAGGGCGCGGAGCTCTACGGTAACCA CGCGACGCGTAGTGGGAGAGTGCGAACCTTATGGTAGCGCCCGGACTAAGCGGACA CAGACCCCTCTGGTTTTACAAAGGCGGCTGTGACGAGGACTTCCCACGGCCTTGTTG GAGGGCGTCCTGTTAGCCCTGCTCAGCCT >7:54933072-54933372 (SEQ ID NO.: 317) ACATACATACATATATATATAATTAGAATGAATAAGACAGAATTTGATAGCTCAACA GGGTGACTATAGTCAATAATACTTTAATTGTACATTAAAAATTAACTTAGGTCAGCG CGAGGGAGCCCGGGTGGCCGCCATTACTGAGCCTGGCGCTGCGGCTGGCGCTGGGA GAGCGGGGAGGGACGGGGCCGCAGCTGGTGGCAGAGAGGGAGGGAGGGTGGGTGA GCAGGCTGCGGGGGCCGTGGGGCTCAGGGTTTCCGGGCGTGTGTGTCGGGGAGGGC GGAGGGAGGTGCCTGAAGGG >7:69599017-69599197 (SEQ ID NO.: 318) TCCCCTGGCTGCATTTCTTAAAAATTTGGGAGCCTGGGAGTGAGTTTTCTCCGAGGC GTGTGTGAGAGGCGGCGGGGGTGTTTTCCTGCGCGAGGGGCGGGTGAAGTTCATTG CCCCCACTTTTCCCGCGACCTTTTTCGGACCCGATTTTGGATCGAGTTGAGGGGGGC GCGGGCGTTTT >7:76511041-76511341 (SEQ ID NO.: 319) CCTTCAGCAATGGTACGGGGACTGCTGTGGGGCCTGGGTGAGGGTGACGGCTGAGG AGAGTGGTGGGCCCTAGGAGCCCCTCACCAGCAAGCGCCTTCAATGATTGAGCCCC TGTGGGGGCCTTTGGGAGAGTAGGTGTGGATGAATTGGGCTTTATCTAAAGGGGTA ATATGTGTATTGAAAAATACACACGTAGTGAACACCAAATCCCGGGAGTAGTGCTA GTGGTGGGTTTGTCAGCTGTCAAGGGCTCTGCAACCCTTTCTCTGAATCCAAGTAGT TCTTCCTTTGGACAGGGAAC >7:88219317-88219497 (SEQ ID NO.: 320) AACGATGGAAGGCTGGAGTTGGTAACATTCTGAGACGGGTGTAGCCTAGGGAAGAG TAAGGTGTCCGGCCGGGCTGTATCTCGTGGGTGGCGAGGGAACATTGCCTGTCTCGG AAACAGTTCCCAAGACAACGCGCATCCCAGACGCCCGGCGAGGCTGCCTTCCTACA GGTCTTTTACTT >7:91881001-91881181 (SEQ ID NO.: 321) GGCCGACGACACGTGGTGGAAAAGTAGCTATTATTTACATGCGTGTTGCAGTTTTTG ATAATGCGATTGCTGCTGCTAATGTGACTAACGCGATGCCGATGAACATCTCGGCGT TTTTTGGTGCAGGATAAGCGGGTGTAGACTCTGTCTGTTTAGTCCCAGATTCTCCTCC TTTAATGAA >7:108456902-108457082 (SEQ ID NO.: 322) AAATTCATCAGTTGGGGTGGTTGAGATTGGGTGAGTGGTTTTGGGGGTTTTGTTTTGT TTTTGCAACCGTTCTTTCCAAACACTCCCCGCCGCCCCCCACCACCGCAGAAAAAAG AGCTTTTAGCATAAGGCGGATGCTATCTATCCGCGGTAGAAACTGGGTCTTCTGGTC CCAAGGAAT >7:122300668-122301028 (SEQ ID NO.: 323) CTAATTACCCCTCTTAATTAAAGTCTTTAGCAGTTGTTTCATTGTTTTGGCAAGAAAA CAGGAGAGACGTGCAGTTAGAAACACCAGAGCCCGAGCTCACAGCGGAGCCGCTG ATTAACACTTGAAGCATTTCAAGGACCTGGCACCCGCCACAGTTTGGTTTTCATCCA TGTTTCCTCCTTGAATGGAAGTATATTCGTCTATAAACATACATACACATGTAAAAA CACGGAGGCTCCGTTTGCCAGCTGTGTACAAGTCAGTATGTGCCGTCAGGATGCAAA CAATAGATACCTGTCTATCTATGATTGTAATGCGTTTGAGGAGATGTACATTGCATA CAGCTACTGGATACGTTGTT >7:139483469-139483891 (SEQ ID NO.: 324) CGCCGCCTTCTCCACGGCCCCGGCCGGACTTGGGCTGCTTTCGGGACCTTCAGGTTG TCGCACCTTCGCGGGCACCTGCGGCTGCTCCAGCGTGGGGACCAGGCTTCCCACGGG CTCCATTGGGAGCTCTGCCCCGGCTTGGCCTCCGGGCGCAGCCTCCCAAGACTCCTC CATCCCGCGCGCCCCGCCACCCGGAGACGCTGAGGAGCGCACCTGGGCCCAGTGCA GAGGAGCTTCGCTCTCCTCCGTCCGGATTGGTCCAGCCGCGTCGCCGAAGTTGTCAG GCCACGCCCCTCCCCGAAGGACCCCGCTGTGATTGGCTGTGGCTGAGGTTCTGCTGC CCCGACCCCCTTCGGGACACAGCCCCGGCCTCCACCAGGCACTGGGAGGGAGCTGA GAACGGCAGCGGGGCCAGGCGAGGGT >7:143345452-143345795 (SEQ ID NO.: 325) GGAGTGCGGAGCGCGGTGGTGCGAGAGGGCTTGGAGGGGGCGCTCAGGCAGGGCG TGGGTTTCCCTCAGATTCAATGATCCTGCTGGGCTCGGTGGAGCGGTCGGAACTGCA GGCCCTCCTGCAGCGCCACCTGTGTCCTGAGCGCAGGCTGCGCGCAGCCCAAGAGA TGGCGCGGAAGTTGTCGGAGCTGCCTTACGACGGGAAGGCGCGGCTGGCTGGGGAG GGGCTCCCCGGCGCGCCTCCAGGCCGGCCCGAGTCCTTCGCCTTTGTGGATGAGGAT GAGGACGAAGACCTCTCTGGCAAGAGCGAGGTGACCGCGCCGGGAAGGGCTAGGG AGTGGGAT >7:155803569-155804049 (SEQ ID NO.: 326) AGTGAGGAAGTCGCTGTAGAGCAGCCGGCCCTGGTCGTCCGCCGCCAGCACGCGGT CCCCGGGGCTCAGGTCCTTCACCAGCTTGGTGCCGCCCTGCTCCAGGTGCACCGTGG CCGAGCCCGGGAAGCAGCCTCCCGATTTGGCCGCCACCGAGTTCTCTGCGGGTGAG GAGAAGGGAAAGAAGAGAGGACAGGGCATTGAGTTCCGAGAGGGAGGCGCGTCTC GGGGAGGAGGGCGCACGCTTGGTGCCCGCGCTCCTAGGCCAGGGGTGCGCAAGGCG CGGGGCGGGGCGATTGATTCCAGGCGGGTCCCGCACACACCTCCCTCCCCCAACCCC ACTGCCCCAGGGACAGGATTCCGACACATTCCTTAACGACTCTCTAAGTCTGGGCTG GCGGTCACAGAGGTTGGCTGGCGTTTCCTGCAGAGGCCGGTGACACTCTTTCCTTCC GCCTTCCTCCAACCCCACCCCCAGCTCCGC >7:157336263-157336683 (SEQ ID NO.: 327) GGGATGACCTAAAGTCCAGCTATCAAAATGCGCCGCGTTTTCAGAAAAACTACTGCC ACGATTTAACCTAAAAAGCTTCATCTGTATTTTCTGCCACAGTTTGCTTCCGTTTCCT TCAGTCACTATTCCCTGGCGAAGTCTCCACGCGCTCCCGTTCGCCGGGGAACTTAGG GTATCCGGGCTTCCCTAAATTGACAAGCGGGGGCCGGCGCCTTCGCCCGCCTTCGCT GGCCGCCGCTTGGTTTGTTCTTCTTCTCCTTCGGGGACTTCTCCGCCCGCGCCCGCGC CCGCGCCCCAGCTTTCGTCCCGCTGTGCGGAGATGCCACCCAGCTCCACCGCAGGAC CGCGGAGCGAGAGGCGGCAGACGCGCTCCGGGGGCCGCCGGTCAAGAGGAAGATG AAGGGCGCGACGACTTCGCGGT >8:544064-544544 (SEQ ID NO.: 328) AAGGACTTCTGCCGGCTTCCTTCAGAAAAATCAAGAATTTAAGAAAATACTTGTTAT GCAAACAAACATTTAGCCCACTTAACATTGAGCTACGGTCGTCCAAAGCTGCTTAGT GTCCGCGAGGAGGCCGTCCGGATGCGCGATGATTCAGGCCTTCTCCGCCAGCTCCAC CCGGGACGCGAGCACCCGGCGTGGACCTCTGCGTCCCGGGCCCACGACGCCCGCGC CGCGGGGTGCGCGCACTGCGTCCCCGCTCTCCTGGGACTGCGCCCCGAGTAACACGT GCAGGGGGCACTGGGTCCCCTGCAAGCGGCGAGAACGCCGGCAGCCCTGGCCAGTT AAGCGGGGAGTGGGTCCACGCGGACCACAGCGGCAACTCAGCCCAGGACGAGCCTC GGGTCAAGTTCTCCGACTCCGCACTCGGGCACCTAGCGGGCCGCGCCCCGGAGCTA CGCGGCCCCAACCTCACCTGCCCGCCCAA >8:37797956-37798676 (SEQ ID NO.: 329) CGCGTCCCGGACTGGGCTGGAGGAGTCTCCGGATTTACCTGGCTGGCCTTGTCCCTT CAATTGGGGTCATCCCATCCTTGCCCCCTGGCCTGCCAGCGCCGCTTCCAGCCGGTC TCCTTAGGGCAAGGGGAGGCTGGGCTCAGAAAAGTCGGCCCTTGGAATACCGGCGC TCCTGGGCTGCAGGAGACCCTGGCGTCCCCATCCCTCTAGAGGCCCCTCTCCCACGG CGCCGTTTGTGCAGTGAGCTCTGTGCTGGGTCCCGCGTCCTTGCCTCTCCTTTGCCTC TCCTGGAAGTAACTCGAGCTTTGGCTGTTTCTCCATTGACTTCGCGCAAAGATTGCG AAGAAAGAAACGCGGCTGGGGAAGCGGGGTTCCCTCACCGCAGCCCACCCGGGCCT CCTTCCGCGACTTCCCTCTTAGTCAGGGCCTCAGTACGCCTTTGCTTTGCTGGCAGCG AGCGCTGCAGCGCCGCAGCCCGACCCCAAGCCTCCTACAAGGGGGTCGCAAGTCCC AGCAGCCGCGCGAGCATTGGCGACCCCTCCCCACCGCAGAGATTTCCTGCGCCGAC CACGTGCTCGCAGCTCCACGCACGCCGTGGATTTGAGGGTCGGGCCCCCGCGGCCG CCGCTTCCTTTCCTGTCCCAAATCCAGCCTAAGAGCCGCTTCCCTTTCCCTGTCCTCC TGACCCCAGTGGCAACCGTTTCTCCACCGCCCCTTGCCC >8:39107409-39107589 (SEQ ID NO.: 330) GGTGCAGGAGAGCACACGCTGACTGTGAATAAGTGTGTCAGTTCTTAAGGTCCAGC AACACAAAGCGAAAAGTTAGTGGAGGACTACGAGCGCGATCTCGACAGAGGGCGCT GGGTGGTCAGTGGCTCCAGCAACCACGCGGCTGGGGTGCGCCGGGAAGGGAGCTGG ATGTTTTAGCCTC >8:71843830-71844010 (SEQ ID NO.: 331) GCTCACGGGCGTTGGCCGCGTTCCGCTGCGACTGCTTGCACTCTGCGGCTGAGCCCT TGGCCGGGAGGGGCTTCTTGCCACCACCGCCCGCGCTACCACCTGCGCCGCCGCCCC CAGCCACACGGGGCCGCTTCCTCTTGCAGCCTTCCGCGCTGCCGGCTGTGCCCAGAG CGCAGCGCTC >8:104367291-104367591 (SEQ ID NO.: 332) TCAGAGGATTGTAAACCACTTAAGAAAAGGAAACAGAACTTGGGGAGGCGGTGGCG GCGAGAGTAAACAACTCCCAGGGGGCCCGTCTGCAGCGCCTAGGGGAGGGGAGAG GCCGGGAGCCGCCTCCGGGGGTCTCGCGGGGCCGCCGCTGGGACAGATGAGTCGGA GACAGGCCAAGCCGGAACCTCGCTGGGTAAGGAACAGGACCGGAGCGCGCTCCGG GTGGGAGAGGCTTGCGCTCCTGCAGCCCCTTCCCAGGGCCTGCGCTGACTCATGGCG CGCACTGGAGCCCCTGCAGTCG >8:123073280-123073580 (SEQ ID NO.: 333) ATCCATCCTTAAATCCTTGGATGTGTTTAGACGCACAAGCATTCATCAACTATTTGTT GAGCTCCTACTGTGTGCCAAGCACGCCTCTAAGCGCTGGGGACGGCGATGGAACAA AACACACTTCCGGTTCTCTGGAGTTTACATATCGGCGTGTATGTAGGGGCTGGGGCG TTCATTATGCATTGCTGGGGGGCTTCTAGTACGGCCAGCGCTGCTTTTCATTCTGTTC CCAGTTACCTGTCCTGTTTGAGGCTCAGCCTGTCTTGTTTCCCTGGAAGCCTTTGCTA CAAAGCGGTGCCAT >8:143355090-143355270 (SEQ ID NO.: 334) AGCTCACAGCCGGGATGGCAGGAGAGTGCGGAAGCGGCACATGGCAGACACAACC GGGGATGACCCAGCTCCTCACCAGAGGGCAGGTACCGGAAACCAGCAAACACGATT TGACAGGACGCAGAGCAAACACCGCATTAAACAGCTCCTGCGTTCCAAGGCCAGGT GCTTAGTTCATCTA >8:143740045-143740225 (SEQ ID NO.: 335) TTGCGTGTCATGTACACATGTGCTTGTGCGCGCACGTGTGGGAGTGCGCGTGTACGC GCACCTGTGAGCGCTCGGCGCAGGCCCGCGACACGCCCGAGCCCCTCCCGCCGCGC CCCGCTCTCGCCCACCTCCTGGTGCTCCACCTCCCCGCCGCCCGGGTGCGTGGCCTCT CGGGAAGACC >9:23824147-23824447 (SEQ ID NO.: 336) CGGTAATTACGAGAAAATACCCAGTCTCGCCATCAGTTTTGCTAACCGGTACTTGAA AATGGGAAACGGGGAACTTATCCAACCTCCAATTTGTCACAGTTGTATAGCTTTCGT ATTAATTCTGTACAGACGTGAAATAGGTGGGTACGTAGCAACGTGCTGGGCATAAA TTAAGCAACAATGGCCACGCGAGGTCTCGTCCGCCGCGGAGCTCCAGTGGTGGGCA CTGCCACCTTGCCATCCCTAGCCCCCACCGCCCTTCGCAGAGTCCAGTCCGGGAGGC TGACGGTGCGCTGGCTTT >9:27528212-27528524 (SEQ ID NO.: 337) TGCCCTCCCGCCCTTGGAAACTTGTGGACCCCAGAATCTCAGCTTTCCGCCTACCAA AGGTGCCCCGATCCCCTCCCACTGCCCTAGCAGCGGCCCAGCCCCAACGCCTTTGGC TAGAGATTGAAATCCTCTGGAACCAACCACTGGACGCTCTGGATTGGGGCGGAACG CGCTTCCACTGTCTCGAAAGCAGCACCTTCTCGGATTTGAGCCTTTGCGGCGCGCCT GGGCTGAGATCTGAGAAATGCGCCCTGGGCCACAGGCAGCAGCGGAGGCGGGGAA GGAACAACTTTCCCTCCGCCCTCTAACCACA >9:61862430-61863030 (SEQ ID NO.: 338) GGGCACGCAGGCCGTCCTGTCCTCGAGATCACCGCGTCACGACTTTTGGGGAGACTC ACCCCCACCAACACCGTCCAGAGAGGCCTGAGGGAGGGATTCCATGCTGCCTTCTCC GGACTCTGCGTCGGGTTTCCTCACCCTGTTCGGCCCTTTGTGACTCTTGGCATCCGGA GACTTTCCCCTCGACCCAGTGGAGCCGTCAGGCCGGAGCCTCAGAGCCTTGACACCC AAGCACTGCCACGGAAGTCTCCCCCTTTGCCAAGCCTCGGGGACTGGTTTCTAAGAC AACCGTGGGAACCACTGTGACGGGAGAAACCGCTTGTGCTTCGCGCATGCGCATTG GCTGGGCCGACTCGTTCTCCCCTCCTGGCAGTCAGGCTGCGTCCCCTTTAAAGAACG CCACCGCTGAGAACTGACCCTCACATCTCCCTTCCTGAATTTCTTTAGGGAAAGCAA CAACCATCCCTGTAAGCCATGGGTTTTCATGCGGAGGAAGGAGAGGGCTAGTTGTCT GAGAGGGTAACTGCTTAAGGCTGCAGACTAGGAAATGGGATTCCAGGTTTAAGATA GCTCCTTTCTGGACCTCAGTCCTTCACCTAGT >9:77648213-77648393 (SEQ ID NO.: 339) TCCCCAGGCGGGAGGTAGGCGCGGAGTGGGTTGGAGGCAAAGGACCTGGCTGGCCT TTGCCTGGAAAGTTCTGAAAACCTCAGCAGTGACCGCAGACTAAGACTGAGTGGAA AGGTTCCCGCTAGCGTTTGTGGCTCTAAGTGGCAGGAGGAGGCGGAGCATCTTGAA CCTGCAGCCCTGG >9:87148272-87148872 (SEQ ID NO.: 340) CCAAGGCGGCCCTCCTTCCAGTGCTGCCAGGAGAGGGAAAAGGCACTCAGGGAGTT TTTGCTGGAGATAAGAGCAATTTTTGAAAAAAAGGTAGTAAGGCAGGAGGTGGAGT CTGCCACGGGTCTCTTTCAAACTTGCTACTTTCCATCCCGTTAATACAATCCCGGCCC TGTTTCCCGGCCCCGCGGCCATTGCAGAGTCATGAAGTCATCGCAGCTGCGCCTGCA GCCAGGCGGGAACGGGAACGGGAACTGGCTGGCCGCGGTCCCTTCTGTCCCCCGCC AGCCGGAAATGTCCGCGCGCTGAAAAGCAGACGCTGCCTGCCCGGGGAACGGCGAG AGAGAGCGAGAAAAAAAAAAGCCTGAAGGCGGCGCGGCAGCCAGCGAGAGGGGA GAAACAGATTCACACCCAGGGGCCTCCGGGCAGGGCCCACGGGACTCAGGCCGTGT CCCGCTTGGAATGTGGAGCAGGCGCGGCCTCGGCGTCAGCAGAGCTCCCCTGCATCT CCTCCTGGGGGTGTGGGGGCCGAGTGGGAGAACTGGCGGACAGAGGAAAGGGGCC TCGCTCGCAAGGCCCGGGCGGGGAGGCCTGGCCTCCTGCT >9:93184774-93184954 (SEQ ID NO.: 341) CTTTCCCAGGGCCCCCAGAGACGGCCCCCGCAGGCTCTCTCCGCGGCCGGGGCTGG GCAGGTTGCGGGCTTAGGGCGGCGTTGTCTCATCCGGCGGCCTGGGCAGGTGCGGC AGGGCCGGCGCTCACGCGGGCCTGTGTGTCCTTGGCCCACAGAGATGGACGGCGAT GGCGGCCGCCGAG >9:98709159-98709819 (SEQ ID NO.: 342) GAAACGCGGGAGGCGAAGGCGAGGCTGCTCAGGGGCGGCTCGGGCCGCCTCCAGG GACGGGGACGAGCCGTGCGCGCCGGGGGAGGGGGAGGCGCTGGCGCTGCGGCGGC CGCGGGGAGGGCCACCTTCCCAGCACACGCACACACGCGCCCCCGGCCCTCCGCTG CGCCAGCTGCCGCTGCCCGCCGACCGCTGACCTCCAGGCACCAGAGCGCCCGGGGA CAGCGATCTGGGAACCGGGACCGCGCGCTGGCACACGCAGTGGCCGCCGCCGCTCC GCCGAGCGCTGCCTGTAGCACCTGCACGGTGGTTTGGAACCGCTTCTCGGAGGTCTG GCCGGGAAGGTCTGGGCAGGAGAATGTTCCACGAAGGCGTCCCAGAGGCATCTGCA GCCTACGCTCTCCCGTTCTTTTCTGGCGCCCACGAGCCCCTGACCGAGTCCCGGGGG TCGCTGAAGACGCCCACGGGTGCTCGAACGCCCGTTGGTGCCAGGCTGCCCGGCCTT TAGGGCCTTGGCTGAGGACACCCCTTTCCTCCCCACCAGACGGAGCGACCGCCCTTT GCCAACCCCAAGCAAAGCTGGGGTCCCAACCTTACGTGCGCTACCGCCCCCTCCAG GCATTTGACCTCCCCGCGTCCCCATTCTTGATGGGCCCCGCCC >9:109640702-109641422 (SEQ ID NO.: 343) ATTCACTTTCAACCCTCCAGGGGAGGAGGGGGTGCGGGTGGGGAGGGGAGACGGCT CCCAGCTCCACCTCGCGCGCGGCGCGGCCAGTGCACTCGGCTCCGGGAGAGGCGAG CAGCGCCGGTGAGCCCCGCAGCAGCGCACCCGGCCGCGGAGCCCCGCGATGGAGTG AGTATCCCCGAGCCGCGCCGCCAGCTGCTCTCCTCTCGGCATGTTGCCATGGTGACC GCGGCGGCAGGCAGATCCCGCTCGGGTCCGCGTCCAGGATGGGTGTTTAATTTCAGC CCCGTGTGTACGCCTGGTGTTTCTATAGCAGCCGCCGCGGCGGCAGGAGGCAAGGG GTGGGAGCCCCGGGTGGCGTGGTTTTTGCGGCTGCCCCTTGGCTAGCAGGGCCTGGG GGGCGAGTGAGGGGAGTAGATGATGTTGCTAAGGACGGAGGCATATTCTAGGCTTT CCTATCTCTGCCCCAAGCTTCCGCTTATCGGGGAGTTGGCCGCAATAGCCATGACTT CCGATTCCTAACCATGTCAGCATTATTGGACTGCAGTTAAAAAAAGAGGGAGGGGG TCACTGCGGATCGGAAGCAAACGCGGTTCAGTGTGAAGCGTGTAATGGAAGGATGA GTTAGTGGGTAATATGAGCCAGGGCTGCAATGTCCTGGCTACTAGAAACCATCAGA AGACCCAAAAGAATTGATTTGTTCCTGGGGTATTGGAGAAATAAG >9:122218898-122219198 (SEQ ID NO.: 344) TGCACCGCTCTCTCAGCGCTGACCACACTGGTTTGTAAATGTTTCGTTTCTGGCTCTT CTCTTCCACCCCTTCCACCTTCCCAGAGTTGGGGTCCCGGGGTTGGGTGTGGGGGAC CAAGAAGATTTGCCTCTGCGTCCCCAGGGCGGGCACCCCTCCACCCGGGGGAGCAT TCGGAATCGCTTGTGTGTGCACGGAGGAAACAGTCCGGCAAAAAGGCTCTGGTTAC AGCCTGCCTGCCTTGGCAAATTCAAGCAACTGTCAGTTGAAAAAAACAGCGTTGGGT TGGACTGAGTGCAGGAG >10:7410763-7411078 (SEQ ID NO.: 345) TGGAAAAAGCCCCTGACCAGCGCACTCAACCTGCGGGCCGAAGGGCTGCTCTCCGG CCAGCCTGGGCGCCGGGGACAGCAGCCGGCGCGGCGTCCTACCTGGTGAAGTTCGT CCTGCCCTCGGCGTGGACCCAGGCCCCGGTCGCCGCCCGGGAGGGCACCGGCCTCG CTCGCTTGCTCGCTCGCCCGCCCTTGCCCGCTCGCTCCCCGCCCGCCGCCTCCCTCGC GCGCCCGCTCCGGTCCTCCGGCTCCCACTACAGCTCATTCCAATATGGCATCCTCTCT GTGCGCATGCTCGGCGCTCTTTTTTTTTTTTT >10:25174989-25175169 (SEQ ID NO.: 346) GCGGGTGAGACTATGGAGCAGCGTCTTCGGCGGCCGCGGCGGCAGCAGCAGCAGCA GCTTCTGAACGCGCCTCAATGAGAGCGGCGGTGGCGGCAGCCGGGCCGAGAGACGG ACTCGGGCTGACTCCAGCCGCTGGGAGCGCGAGGCCATGTAACCCGCTCGGCTCCA GGCTGCGAGGTGC >10:43105168-43105348 (SEQ ID NO.: 347) CCGTGGTGGAGTTCAAGCGGAAGGAGGTGCTTGTCCGCGCGTGCTGTGGTCTACCCA GTGTCTGTCTCCGGCCACAGTTCGTTTCTCGGTCGGTTTAGTGTCCGTGTAGCCACCC AACCGTGTGGCCGACCATTCGCGCTTTCATTTGTCCTTCGCCTCCGTCTGCGCCGTCT GTCCTAGG >10:86959058-86959298 (SEQ ID NO.: 348) CCTGTCTGTGCACGCACACACACATTCCCAAGCATACCAGCCTCCCCTGAGCCTGGA GCCCCTGAAGCCATGAGCAGCCTGTGCTCAGGTGGCCCCCACCCTCTCCACACGGGA GCGGCTACAGCCAGGTCACGGATCCCCTCCCTCCCCAGAGAGAAGGGGCAGGCTGG GGGATGAAACCTAGGCTCAGTGTTCCCTCCCCCGCATCCTCTCCTGGCACTCTCCAG AGGAGGAAGGGGAG >10:99329112-99330672 (SEQ ID NO.: 349) GAGGCCATGCTGCAAACCCAGACTTTTCAGGCTGCATCTCAGATATACCGAAGTGTG TACCCGCTACGCACAGTGCGGTGATGCCTGGCCACCTCCAGCCTCCAGCGGGGACCT CCTGCCCAGGTGGAGTCTGAATGCCCACCGCCACCAGCCCACGCGCGCAGTGGGCG TACACGTGGTGACCTGCCTGCGGCTGGGTTCCCAGCTCCGGCTCCTCCTCCCTCCAG CTCTCGCTCGGCTTCCTGCAGTATCACGTGCAGCTGCGCTGGGTGCAGGATGGCGGC GGCCGCGGCGGCGGCAGCAGCGGTGGGTGTCAGGCTCCGGGACTGCTGCAGCCGAG GCGCTGTGCTCCTGCTCTTCTTTTCCCTGTCTCCTCGGCCCCCGGCCGCCGCCGCCTG GCTGCTGGGCCTGCGGCCCGAGGACACTGCTGGAGGCCGCGTGTCCCTGGAGGGGG GCACCCTGCGCGCCGCCGAAGGCACCAGCTTCCTCCTGCGTGTCTATTTCCAGCCAG GACCGCCGGCCACCGCCGCACCGGTGCCCTCACCGACCCTCAACTCGGGGGAGAAT GGCACCGGCGACTGGGCTCCGCGGCTCGTGTTCATCGAGGAGCCCCCGGGCGGTGG CGGCGTGGCCCCCAGCGCGGTCCCCACTCGCCCCCCGGGACCGCAGCGCTGCAGGG AGCAGAGCGACTGGGCATCGGACGTGGAAGTCCTGGGGCCCTTGCGTCCCGGGGGC GTGGCAGGCTCGGCCCTGGTCCAGGTGCGAGTGCGGGAGCTGCGCAAGGGCGAAGC GGAGCGGGGCGGCGCGGGCGGTGGCGGGAAGCTCTTTTCACTCTGCGCCTGGGATG GGCGCGCGTGGCACCACCACGGCGCCGCCGGCGGCTTCCTGCTGCGCGTTCGCCCGC GGTTGTACGGCCCAGGCGGGGACCTGCTGCCCCCTGCGTGGCTGCGGGCGCTCGGG GCGCTCCTGCTGCTAGCCTTGTCGGCCCTGTTCAGCGGCCTGCGCCTGAGCCTGCTG TCGCTGGACCCGGTGGAGTTACGGGTGCTGCGGAACAGCGGCTCGGCCGCCGAGCA GGAGCAGGCGCGCCGCGTGCAGGCCGTTCGCGGCAGGGGGACCCATCTGCTCTGCA CCCTACTCCTGGGCCAAGCCGGAGCCAACGCGGCCCTGGCTGGCTGGCTGTACACCT CGCTGCCGCCGGGCTTCGGGGGCACCGGGGAAGACTACAGCGAAGAGGGGATCCAC TTCCCGTGGCTGCCGGCGCTCGTGTGCACCGGCGCGGTATTCCTGGGCGCCGAAATC TGCCCCTACTCAGTGTGTTCGCGGCACGGGCTGGCCATCGCCTCGCACAGCGTGTGC CTGACCCGGCTTCTGATGGCAGCCGCCTTCCCCGTGTGCTACCCGCTGGGCCGCCTG CTGGACTGGGCGCTGCGCCAGGAGATAAGCACCTTCTACACGCGGGAGAAGTTGCT GGAGACGTTGCGGGCCGCAGACCCCTACAGTGACCTGGTGAAGGAGGAGCTCAACA TCATACAGGGTGCCCTGGAGCTGCGCACCAAAGTTG >10:103693303-103693603 (SEQ ID NO.: 350) GCCCCAGCCCGCCCCGCTAACTGGGGCTCACCTTCCCTAAGCCTTGGCGGGGAAGG GCGAGGCAGGTTCTCCTCACTTCCCAAACTGGGAAACTGACGCTCCGGGATGGCGCT CGCCGGAACCCGGCCCCTACCCAGCGCTGGGAGCCCGCTCTCCCCGCCACCGGAGC GGTTCACCTCCCAATTCTTTGCATGGCTTGCCCTAGCGATGCAAAGAATTGGGAGGT GAACCCAGCCTACTCAGCCCGTAAGTCACTACTGAAATGTCACCTCCTCAACGTGTC TTCCTCAAAACCACCCGC >10:117534766-117535426 (SEQ ID NO.: 351) CCAGGGGTGGGAGGACACTTCGGGCCCAGCGTAGAGGAGGCCTCCGAGGCCCAAGC GGGCTTCGGCTGCTGCGAGTCCCCAGAGGCTCCCTCGGGCCTCACTCGCGGTGTCTC CTCCAGACGCCAGGGGCAGGCCACGAAGCCGAGGGCTCCGCGTGGCCGTGGGAGA AGCGGGGTGCACGGAGCCTTCCCGCGCCCAGACGCCGAGGGGATGCAAACAGGGG AGCCGGGCCTGGTATGGCCAACCTCCAGGATCGAGGGGCCCCAGAATGTGCGTGTG GCCGGGGGCGGGGGCAGCTGCGGGGGCCAGAACTAGAGTATTCCTTCGCTCTCCCC TGGGGGCCGGGCCCCCACGAGTTGCAGCAGAGCCCGTCTGTAATTAGGGCCTCCTG GTCCGGCAAAGCTGCGGCTGCTCCCAGAGAGAGTTGGGGTCTTCTCAGGGCCCGCG ATGGGGGAGTGGTCGTGGTCAGACCCCCGTGAGCCCCTTCGGAAGGTCCCAGTCCCT GTCCATTCTTCTGTCCCGCAGCTCTCTCCGCGCAGGCGGGGCAGAGCCGGGGAAGA AGACGCTGGACGAGGGGTCTTGGGGCCGCCTCGCTGGCTGCGGTTGGAAGCACCCG TTTTCCCGCCCGCCCGCGCAGGCGCTGCTCTGTGGCCACCAGCAG >10:127196238-127196538 (SEQ ID NO.: 352) GCTCGCGTCGCTCGCGTCCCTCCGGCCCCGCTTAGCGACGCGCGCGGGGAGGCAGC GGCTGGGCCAGCTCCGGGGACGCCCGCGCGCTCGCTTGCTCGCGACGCGGCGGAGC CAGCCACAGCCACCCGGCTTCGCGCTCCTCCGATGTCCTCATTTACTGCAATTGTCTT CGGCGAGATCTCAGAGCCAGGGCCAGGAGGCGGGGGCGGGGCAGAGGAGGGAGCA GGAGGGAAGTCCTTTCCGCTGCTCCAGGTCCCAGCTACTCCGCGGAGCCGGGCGGC CAGAGGCGAGGGCGCCCCAA >10:132786224-132786524 (SEQ ID NO.: 353) CGCGGTCCGGCCATTGGCCGGCGCCCCCCCCCCGCCCGCGCGCCCCCGCCGGCCGCG CACTCCATGAAGGGCCCATTAGCGCGGCAGGTGCCTCCCGGGCTGTAAATTCGCCCC GATTTATCTCCCCGGGGACGAAATAAATCCAGCTTGGATGGGAGTGTAGTTAGGCA AAGGTTTTCATGCGAAATCAGGAAAAAATACGAGAACGTATTTTATTAACGGAAAG AATGCAGATTTGAGGACCCGCCCGCGCGCTCGGAGCGCCCCACTCGGGGAAGAGTC CCGGCCCGCGTCCCAGTCG >11:313954-314134 (SEQ ID NO.: 354) CACACCTCATTGGTCCCTGGCTAATTCACCAATTTACAAACAGCAGGAAATAGAAAC TTAAGAGAAATACACACTTCTGAGAAACTGAAACGACAGGGGAAAGGAGGTCTCAC TGAGCACCGTCCCAGCATCCGGACACCACAGCGGCCCTTCGCTCCACGCAGAAAAC CACACTTCTCAA >11:639416-639956 (SEQ ID NO.: 355) GTGGTGTCGCCGCGCAGGTCCAGGGTGGCGCGTGGCTGCTGAGCCCCCGCCTGTGC GACGCCCTCATGGCCATGGACGTCATGCTGTGCACCGCCTCCATCTTCAACCTGTGC GCCATCAGCGTGGACAGGTGCGCCGCCCTCCCCGCCCGCGCCCCGGCGCCCCCGCG CCCCGCCCGCCGCCCTCACCGCGGCCTGTGCGCTGTCCGGCGCCCCCTCGGCGCTCC CCGCAGGTTCGTGGCCGTGGCCGTGCCGCTGCGCTACAACCGGCAGGGTGGGAGCC GCCGGCAGCTGCTGCTCATCGGCGCCACGTGGCTGCTGTCCGCGGCGGTGGCGGCG CCCGTACTGTGCGGCCTCAACGACGTGCGCGGCCGCGACCCCGCCGTGTGCCGCCTG GAGGACCGCGACTACGTGGTCTACTCGTCCGTGTGCTCCTTCTTCCTACCCTGCCCGC TCATGCTGCTGCTCTACTGGGCCACGTTCCGCGGCCTGCAGCGCTGGGAGGTGGCAC GTCGCGCCAAGCTGCACGGCCGCGCGCCCCG >11:640311-640791 (SEQ ID NO.: 356) GTTCCTGTCCTGAGGGGCGGGGAGGAGAGGAGGGGGGGGGTACGAGGCCGGCTGG GCGGGGGGCGCTAACGCGGCTCTCGGCGCCCCCAGGGGCCTTCCTGCTGTGCTGGA CGCCCTTCTTCGTGGTGCACATCACGCAGGCGCTGTGTCCTGCCTGCTCCGTGCCCCC GCGGCTGGTCAGCGCCGTCACCTGGCTGGGCTACGTCAACAGCGCCCTCAACCCCGT CATCTACACTGTCTTCAACGCCGAGTTCCGCAACGTCTTCCGCAAGGCCCTGCGTGC CTGCTGCTGAGCCGGGCACCCCCGGACGCCCCCCGGCCTGATGGCCAGGCCTCAGG GACCAAGGAGATGGGGAGGGCGCTTTTGTACGTTAATTAAACAAATTCCTTCCCAAA CTCAGCTGTGAAGGCTCCTGGGGGCTGATGGGGAGTGGGGAAGAGGGGTTTCTGCC TCAGTGGCCCCAGGCCCCCCAGCCAGTTA >11:9004093-9004273 (SEQ ID NO.: 357) GTCCACGCCCCGCGCGGCTCCCTCGCGTCCCGCGTCCCGCGTCCCGCGTCCCCTGCT CACCCGGTGGCAAAGCCGGCGAGGAGGCGGCGGCGCTGGTGGGGACTGACCCGGC AGTCCGAGAATCCACCGCGGCCTTTTCACCCAACCGCCCCCTCCTGCGTGGGGGCCC CGCATCCCCTGG >11:9091769-9091949 (SEQ ID NO.: 358) GGGCGCGGCCGCGGTGGCCCGAGCGCGGCTGTCAGCCTGGCGGGGCGGCAGCACCG TGCCTCGCGCCCCGCGCAGCCCTGGCACCCAGCCCGCTGCCCCCCGCATCCCCGCTC CGCTCCAACGCTCGGAGCCCTCGGTGCCGCGCCTGTTCCAGTGTGTTACAACTCGAC CCAGGCCCTCA >11:12009476-12009656 (SEQ ID NO.: 359) CACGCCCTCCTCTTCTGCCTCAGCGACCAGCTCTACCGAAGGCAGCCATCTCCTTCA CTGCCTGCCCCTGCGCCCGCGGCATCCCAGGCCCGTCTTCTCTGGCCTCCAGGCTTG CAACAGCCCACCGAGGTTGGGGGTAGGGGGAATGTTCCTCAGTCCCACCTTGGTCTT TCCAAGCCAA >11:19713295-19713895 (SEQ ID NO.: 360) CTTCCAAAGGGGCCTCCTCACTTCGGAGATGCAGTGACAAGTTAATATGGGCGTCCA AGCCTCTGTTTCCCAGGAGGAAATTTGCAAGAGGCGGCAGCCCCTGAGCGCCCAGA GCTCTTGAAAGGCCACCCAGGAGAGGTGTGAGACCCGGCGGCAGCATCCGTCCAGG TGGGACCCGCTGAGCGCCGTGGCCAGTCCCCCATTCCCATCCCGGCACCCCAAAGGC GCGCTCGCCCGATTGCTTCGAGTTCCCCGACCTGGGGATTTTTTTTTTAGCCGCTGGT GGTGGGCGCCTCGTGGGCTAAGGCCCGGCGCCTGCTCTGCTACCCGCGCTGCCTTTA GCGGTCGCCCCCGCCGCCGCTGCCAGGGACGTGCTGGGAAAGCCCAAGCCCCGGGA GAAGATGCCGGCCATCCTGGTCGCCTCCAAAATGAAGTCGGGACTGCCCAAACCCG TGCACAGCGCCGCGCCCATCCTGCACGTGCCCCCGGCCCGGGCGGGCCCCCAGCCCT GCTACCTGAAGTTGGGAAGCAAGGTGGAGGTGAGCAAGACCACCTATCCTAGCCAG ATCCCCCTGAAATCGCAGGTGCTGCAGGGGCTGCA >11:35418738-35420778 (SEQ ID NO.: 361) CCTCCACCTCTCGCATTTTCAAAGGATTAAGCAGCAATCTCCAGGAAAGAAAATCAA TCCCCTCCCCACCATCCCATCCCCAGCCAAGCTACGGCTCCGCCACCACCTCCGAGG CCCGCCGCCGCCGCCTCTCTATCCGCATCCCGGATAGGGGCGCCACCACCCCGCGCG TGACCCCGCTTTCCCGCGGGTACAGATAAAAATCCCCTCACCCTTCCGTAGATGCCA TGGTCTGGGGAACGCCCCCTCCTCTTCAGCACTATCCGGCAGCTGTGGGCGAGGGAG AAAGCGGACGCCGGGGTGAGCGCGAAGTGCGGCCGGGAGCGGTATTTAAGAGGAG CCTCTGCCCGCCCTTCCACCCGCCTCCGGGGTAAGCCCTTTAGCGCCTCAACGGGCG CAGGAGGCTCCTGCGGGCGCTAATCCGCGTCCCGGCTCTCCACGGCGCGCGACCCG CGCTCCCCTCCGCCCGCGGGGATGGCGCTTGGCGGGGAGCTCCGGGGGCTCCGAGG GTGGCTTCCCCGAGAGAGCGATGCGCCCAGGGCTGCAGGAGGGCGCACGCCGGCGA TGCGCCCCTGCAGCCGCTGCCACCTGTGCTTTGCTGCGGGGCTCGCGGGCGCGGCGA GTGGCGGGAGCAGAGAGTGGTGGCAGAGGACGGTGAGCGTGCGTGCGCGTGTGCG GGTGTGTGCGCGCCTGGGGAGGCGGTGGAGGCCGCTGCGCTCTGGCTCGGCGCCGG CCAGGGAGGGATTGCAAGGTTTAGCCCCGCCGGAGCTGGGGATTTGCAGGCGATCC CTCTCTATTTTCGTCGAGAGCTGACATCACCCGCGCCGCCGCCTCGGGCAACTCCTTT AACCGCCGCCCCCCGCCCCCATCTCCAGTCGCGGTCCCTCCTCTGCCATCCCTCCCCC CAGCCTCTCGCCATAAATTAGCCAAATAAGAAAAGAGGCCCCGCCGCTCGTCCGGG AAGGCTTGGGCAGCCGGTGGCAGGAGCCCAGGATCTAAGGAGTAGCTATTGTTTCC CCTGAAGCCCGCGTGGCCCCAGGTCACCCCGTGCGGGGTGAAGCGCAGGCGACCGC GCGGAGACCCGGGATGCCCCTCCGTCTCCGCCTCCCTGGAGCAGCCCCTGGCGCTCC CTCCTCACTCCCCGGAGCACCCGCTTCAGCTCACACTCACCCCCAAACTCACAGGCA GGCACACCCACCCCATCCTCCCACGTCTGGGGGTCCCAGGTCCAGCGGAGTCGAGC GGCTGAAACACGCGGGTGGTGCAGCCTAAACGCGGCCCAGCTGCGCTCCCTCCCCC GCCGAAGCTCGAATAAATCTCTGGCCTTCAATTATTCAGCGAGATTAATATTAATGC AGCTCCCTGGGGGCGGCGGGCGGGGTGCAGGGGAGGCCGGGATTTTTTTTTTTTTTT TTTAGGCCGAGAGAGGTCGGCCTCGTGGGTGCCGGCTGAGAAGGCGCGGAGAGTTG GCCGAGGGGTGAGTGGCGGGGGACGGTTCTCCACCCACTCGGCGCTGCTCGCCGCC TGCTTCCGTGTCCCGGGGGCGGCGCACAGAGACAGATGGGCTTGTGCAAGGGAGAG TTCGAGCCTTCCGGACGCCTTTGCATAAAAATGACGAGACCTGTGCAGCTTTGATTA TCTCTGGAATACTGCAGGAACCTAGGGTCCCACTACTTGCCGACCCTGTGAGCGCAG AGCAGGCAAAGCCTCACTTTCCTCGTCTAGGCAATGGAACCCAAAAGAACTCACTT GGAGGGCCACAGGAGAATTAAACAGACTCTCTTTTTCCCCGGGGTAGACGATCTTCG GATTTGCGCTGTGCTGGACCTTGTTAGACGATGGAACGCGACCGGCCACGTGCAAAC TCTCTGAGTAGGTCCCGGGGATGGTGCCAGAGGAGCCGGAGTCCCAGCAGGACCGA TTGGTAGTTAAATGCCAGGCGCTGATATCCGAAGGCTTGAGTTCTTCACCACCTTCT AGCTGAGTAACCTGGGGCAAATTCCTCCATCTCTCTCTTCATCCCACCTGTAAAATG GGACTA >11:62926056-62926596 (SEQ ID NO.: 362) TGCGGAGAAGCAGCTCCACTCCCCAGCCCCAAGTCTTGCGGGCAGTTCCCGAAGAA AAGATGGGTTTGGGGCGGTCGCGAAAGCGGCGCCTCGCGTGTTTTCCTGCCGTTCCC GGGTCCTTATAGCCCGGCCGGAGACTCCGCTGAGTTGACTCGGCGCCCGGGGTCCTG CCAGGGGTAGTGAATGCTGGGAACTGAGATAACGCAACGTGGCGTTTCGGACTCCC CGCTGGACCGGGCCGTGGAGAGGAGCTGCGTTCCCACAGGGCATCCCTAAGCGTCC TCTGTCCCCGCCTATGAGGACACAACCTGGAAGTCCAGGCCACTGGTTGCCGCCTTG GAGTTGGATGTACCGTGAAAGTGCGGCCCCGACGCAGGAAGCAGGCACCTTCCCCC GCACTATGGAAGCTCGCGCCCCTCGCTTCTCGAAACACCTGATTCACGGCGTCGACC CTGCTTCGCTGGGTCTGCGGACATTGGGCTCCTCAGCTTTCCGCCACAGGGTGTACG CGCCCGGGCCCAGGCGGGTGTAGGTCCCACGT >11:67583928-67584405 (SEQ ID NO.: 363) CCGGCAGGGCTCCTCGCCCACCTCGAGACCCGGGACGGGGGCCTAGGGGACCCAGG ACGTCCCCAGTGCCGTTAGCGGCTTTCAGGGGGCCCGGAGCGCCTCGGGGAGGGAT GGGACCCCGGGGGCGGGGAGGGGGGGCAGACTGCGCTCACCGCGCCTTGGCATCCT CCCCCGGGCTCCAGCAAACTTTTCTTTGTTCGCTGCAGTGCCGCCCTACACCGTGGTC TATTTCCCAGTTCGAGGTAGGAGCATGTGTCTGGCAGGGAAGGGAGGCAGGGGCTG GGGCTGCAGCCCACAGCCCCTCGCCCACCCGGAGAGATCCGAACCCCCTTATCCCTC CGTCGTGTGGCTTTTACCCCGGGCCTCCTTCCTGTTCCCCGCCTCTCCCGCCATGCCT GCTCCCCGCCCCAGTGTTGTGTGAAATCTTCGGAGGAACCTGTTTCCCTGTTCCCTCC CTGCACTCCTGACCCCTCCCCGG >11:74311342-74311687 (SEQ ID NO.: 364) GTCACCCCACCCTGCGGCACAGTGTATCCCACTGAGGCCCCTCGGTCGCTCCCACTC GTCGTGCCCTCACCTAGTCAGGTCCCGCAGCCGCGCCTCCTCCCCGCGCAGGTACCG CCTCAGCAGCCCCAGCAGCCGGCGCTCGGGCGCCAGGGCGCGCGCCACGCTGGTCA GCGCCGAGAACGTGTCGCCCCGAGCCGCAGCCCTTTCTGGGTCTCCTGTCCCGAGCG CCAGCACCGCCAGCAGCGCCGCCAGCCGCGCCCCAGGACCCATAGCCAGCGCTCGC GAACTTCCCCTCAGACAGTCCTGGCCGCGCGGCGGCAGCCGCTCCCGCCCTCGCCTG CCCCGC >12:6548902-6549202 (SEQ ID NO.: 365) GGCAGAGAGGGTGGGAATGGGGGAGAAGCATGAACCAGTAGGAAGGGGGGGCAGA CAGAGAGAAAAGTCACAGTTACAATGACAGGAACAGAAACACGGACAGTCACCAA GGGCCAGACACACAGCGGGGGTCAGGGCTGCAAACCGAGAAGGCAGAACAAGAAG AAATCGAGAAGAAGAGCAGTCAGACAAGGAAGGAAGGGCTCGCTGGGGCTGCAGT CAGATGTGCATGATGGCTCAAGAGGAAATTTTTTTCTAAAAAAAGTCTTTTTGATTA AATGACTCAACTAAAAAAAAAAAA >12:48198272-48198932 (SEQ ID NO.: 366) AGGCTGATTCGTCACAGGCCGTCAGCGCGGGCCACGCCTATTTCCTCTCCAGGTTCT AATTAGGTCAGGGGCCCTACAGCCTCTTGGGTAGTTTGCAAGTGCGTCGCGGAGCCG GCCTCGGAAATATGGCGACAGCTTCAGCTTTCAGTGTGAGGGAGCCGAGGGCCCAG CCAAACCCTGCGGGAGGCAATTCCTGGGTACCCTTCCCATATTTTCGGTCTTTGGGCT GCGCCGTGGTAACCTCAGAGCCTGGTTGCGTGCTCACCAGCGACAAGTGTCTTTCAT TGGGACATGAAAGGGGACTGGGAAGTGCCGTGCAGTTTCAGGGTGGTTTCTGGTTA ATTACATTTTCATGGGTTTTCGCAGAGTCTGGGGGCAATTTGTGTCCTCCAGAGACC AGGGACCAGGGCCGAAGCTACGGCAGGGGAGACGCGGCCAGGGCCGTGGCTTCTA GTGCGAGCTCGGTTCGCGTCCGTTCCCGTCTGGCGCCCGGGCCTCCGGGAGCCCAGG GCCTTGAATGAGACAGTGCTCGTCCTTGAAAAAGCAGTTCTAGGTCACTCGGCCTGC TTTGCCAGCATTCCGGGCCCCAGCTCACCTTCCGCCATCCATGTTGACAACACCAGT TCTACGACGAAGCGGGCGATTCCTCTTGCCTGGAATT >12:54053346-54053526 (SEQ ID NO.: 367) CCTCCTCGGCTCAGCCTGGGCCCCTCCCCATCCAACATCCACTCCAGTCCTCATTCAA CTTCCTCTTCCTGCGAAAGAGGGGCGCTGCCCCGTGACCTACACAGACTGAGACACG ATCGCCATGAATGGAGACCTCTGGAAAAGCTCAGGAGCCGAGGCCCACGGGGCCCA GCAGAGGCCT >12:104456512-104457736 (SEQ ID NO.: 368) CTCGCTCCCTGGGGGTTTGGGGCAACTTCCCCGCTACGTCGCCCAGGGATTTTAAAT AATTGCCAGCCACCAGAAACCCCCTAACCCTTAATTCTTCCCTCCGAGACCCAGCCC GCTGCTTGCCACTTCCCTCTCCAAACGCTGGCGGGGGTGGGTGGCAGCACCGAGGC GATTTTCTTCGTCTTTTTTTCCTCCGGGTTTTGTCATGGAAACGCTGACACAACCTCC AGACGGCGGCCGAGCCCGGCCGGGGACTGAGGGCTTTTGGGACCCTGCGGGAGCGC GGCGCGCACACCGCACTCCCCGGGCAACAGCTGGACGCGACCATATCCCGGGTAGG GGCGGGGGGAGCGCGACGCTCCGCCCCGGCGCTAGGGTCCCTCCCTCCTCCCGGCTC TCCGCAGGCGCCCTCCCCTCGCCGGGGGCCGCGAGTTGCATTTGGTAAAACCCAGCC CCGGAATATATAGATCGTTGGAGCGCAATGAAGTAGCCTTTGGAGAGAAGGGAGAG GGCCCGTCGGACAGCCACAGCGGCCAGCGCAGCGGCAGCGGCGGCGGCACCACCAT CACCGCTCGCACCCCAGCCGCCCGGCCCGCGACCAGGCAGCGGCGGCCGCCGGCGG GATCGGAGGAGGCGGCGGAGCGGCGAGGAGGAGGAGCAGGAGCGCGCAGCCAGCG GGTCCACGCATCTCAGCACTTCCAGACCAACTCCGGCACCTTCCACACCCCTGCCCG GGCTGGGGGCTCCGAGAGCGGCCGCGAAGCGACTCCGATCCTCCCTCTGAGCCTTG CTCAGCTCTGCCCCGCGCCTCCCGGGCTCCGGTCCGCGCGGCGGGGTCCCTGCTCCT GCGCCCCGGGCGCGCTTCCCGGACACCCCGGTCCCCGCAGCCAGGACAAAGCCATG AAGCCAGCGCTGCTGGAAGTGATGAGGATGAACAGAATCTGCCGGATGGTGCTGGC CACTTGCTTGGGATCCTTTATCCTGGTCATCTTCTATTTCCAAAGTATGTTGCACCCA GGTAGGGGGCGCGTTAGCGTGGTTTTGTTGGATATTTTCTTCTCTCTCGCGCTCTAGC TCGCTCCGCCTGATTTCTGCCTCTTCCAACCCTACCTCTCCGCCTTCGGCCTCTTCGG GGCTCCTGGCTGCCCAGAGCTCCTGGCTGCCCAGATCTACCCGGGTCACCGCGTCGG GATGGGGAGGAGAAGGGAAGGTGTGCTTCGCCCTC >12:114408286-114409006 (SEQ ID NO.: 369) GTGATGAACATAAGACACAAATAGAGCCAAGATCGACTTTCTTAGGAAGGGGGAGA GGAGGGAACTCTTCACGAAGGGAGGTGGGAGTCCACCTCAGACCTCTATTGGAAGG AAATCGAGTTGTTCCGGGGGACTGAGGTCTCTTGCATAAGGCATGGGATCCTTATTA TTATTATTATTATTTTTAAATCCCCCGCGGAGGAGCTCTGGGCAAATGAATACCGAG GCGCCGCTCTAGCTGGTTAGGCTTGGGATGCGATAACTCAGTGCCCTCTTGCAGACT TGCATAGAAATAATTACTGGGTTGTCGTGGAGGGGACACGAGACAGAGGGAGTTCT CCGTAATGTGCCTTGCGGAGAGAAAGGTCCAAGAATGCAATTCGTCCCAGAGTGGC CCGGCAGGGGCGGGGTGCGAGTGGGTGGTGGAGTAGGGGTGGGAGTGGAGAGAGG TGGTTTCTGTAGAGAATAATTATTGTACCAGGGCCCGCCGAGGCACGAGGCACTCTA TTTTGTTTTGTAATCACGACGACTATTATTTTTAGTCTGATCAATGGGCACAATTTCT AAGCAGCGCAGTGGTGGATGCTCGCAAACTTTTGCGCACCGCTGGAAACCCACTAG GTTGAGTTGCAAAACGTACCGCGTAGACGCCCCTGGTGGCGCCGAGAGAAGAGCTA GGCCTGCCCAGCACAGAGCCGGAGAGCGTCGGGCCTTCCGGAAG >14:36512000-36512700 (SEQ ID NO.: 370) AATTTATGTTGAAGGGTCCTGCAAATAACAAAAATAGATAAAACAGGAAAATGAAT TTAAATCTCACCCTTTCCAAAACTTTGCTACAACTCATAATAACAAGGGTAATAAAT GCTTACGAAGCAGAGGTCAAACGGGAAACATTAGCAAACGAGGAGAGGCGCAGGA GCCCAGGATCATGCCTCGATGCCCACCAAGTTGGGCATTAGGTCACTATCAGAGAG AAATGCAGCCAGCCACTTCAGCTATGGCTTCAGCTGAGGCAAAAGCTGTGCTGCCA AGTTGCTGAACCTGCTCTTTCTCCGTTCCTTTGAGATTCATTAAAGAAAGTTCAGAAA CACAACTACATGAGGTGAGGATAAGGGCATATGCAGACCCCCTTCAATAAAACTTA CTTTCATCTACTCCCATCCATATCCAAATCCCTCAGCTTGGGTGGACAAACTTTCCAG AGAGGGTGACTGAAAATAAGATACTCCTTCTAGAAACAACTGGCCGAAGGGGCACC AGAAAACTTTCTATGCTCCAAGTTGAGGTAAGCTACCAAATTGGGCCCCACAGAGG GTGGCCTGAAGTCTCAGAAACACAGCTGCACAAGGAGGAACGCGTCAGCCAGAAG GCAGGGAGAGCCAGAGGAACATGGTGTCCAGCGTCTCCTAACCAGGATCTAGCCGA GCAGAGAAAACATTCAGCCTCCTCCC >14:41606363-41607263 (SEQ ID NO.: 371) ATTAGTAAGCAAATCACCACCCACAACTAAGGGGACAGCGGAAGCCAGCCTCAGAT GACTGAAACCCCCAAGTCAGTAGCTCTCCTCAAAATTTCCGGCGGGTTATTATAGAT AATGACTTTTCCCACCGCCCTAAGCAGCCGAAGCTTGACTCAGTGATGATTCTCTCT ATCCCGTAACTGCGAGGAAGTGGGCGATCAGCAAATTGCCCTTTTGCAGGAGGCTG GGGACGCCCCTGGAAGTTCGCTTTCATTCTCCAGGTTTTCTGCCTTTTCCCTTCCCCC TTCCTGCAACGCCCCCGCGCCTCCTCAGCCTGGGGATTTCCTGGCGCTTCGCCGGCC CTCTCCGCAACCCCCTGATAAATCGGTTCAGAACCAGTCTGGCTGGGAGGCCCGAG GGCTGACAGCAGCGGAGCGGCCCCGGCCGGGGTCTCACGGACTCTCGGGGTCTGGC CGACACGGCCGCTCCCGTCACTGCAGCGCGGGCTGAGCTCACGGCCGCGCGCCCGC CGCCGCCGCCGCCGCCGCCTTCATGCTGCAGCGCAGGGCTCAGTTCCACGCGGCCAG GAGGCCGCCGTTGCCCACACGCGACGCTTTGGGAAGCCCAGCTCCCGGGTCCGCCC CGGCCGCGGCCGCAGCCCCGGACCTCGGCTGCTTGCCTCGCGCCTGAACTGCGGACT CGCCCCAGCGCGGTGGCCAGCGGGCGGGGCGCTGTGTTCCGCGGCGCGCAGGGAGG CGGTGAGCGTGTGCAGAGCTGCCCGAACGGAGGACTATGTATGTGTGTGCGCGTGTT TGCGTGTGTTTGAGCGTGTTTTTCCTTCTTCCCTTGAGGATGTGAATTGTTTAGCAGC TGGCTGCTCCCTTAGGATCCTTGACTTTGGGGAGCTCTGGCTGTGAACACA >14:55129115-55129355 (SEQ ID NO.: 372) GGTGTCTGGCCGGCGCGGGGCTCGCCCAGCCTGGTCCGGGGAGAGGACTGGCTGGG CAGGGGCGCCGCCCCGCCTCGGGAGAGGCGGGCCGGGCGGGGCTGGGAGTATTTGA GGCTCGGAGCCACCGCCCCGCCGGCGCCCGCAGCACCTCCTCGCCAGCAGCCGTCC GGAGCCAGCCAACGAGCGGTGAGCTGCGCGGGGCGCGGGGGACGCGGCTCCGGCC GGGCAGGGGAGAGGGCGC >14:64540512-64540932 (SEQ ID NO.: 373) AGTCAGGGAGGAACCTCATTTACATAACGGCCGCCCCTCTGTCTCCTGGCGGGGGCC GGAGTCCCGCCCCTCGTCCAACTTGAAATCTGTTGGGTCACGGGCCAGTCACTCCGA CCTAGGCAAGCCTGTGGTGGAGCTGGAAGAGTTTGTGAGGGCGGTCCCGGGAGCGG ATTGGGTCTGGGAGTTCCCAGAGGCGGCTATAAGAACCGGGAACTGGGCGCGGGGA GCTGAGTTGCTGGTAGTGCCCGTGGTGCTTGGTTCGAGGTGGCCGTTAGTTGACTCC GCGGAGTTCATCTCCCTGGTTTTCCCGTCCTAACGTCGCTCGCCTTTCAGTCAGGATG TCTGCCCGTGGCCCGGCTATCGGCATCGACCTGGGCACCACCTATTCGTGCGTCGGG GTCTTCCAACATGGCAAGGTGGA >14:97412990-97413410 (SEQ ID NO.: 374) CTTTCAAGTGTCCAGGCCATAAATTCTTCTCAATTCCCTCTCTCTCTCCTTGTCGGAA TTAATGAGATCAGATCTGATCAGGGCGCTGATGTGTTCAGCGCCAAATCACACAACA GCGCGCGCACCGTAATGGAATTTGCATCTAATGCATACATAAATCAAACATCTTTCT GGACATTTTCATATGCATAATGTCATTTCATCCAGTTCTCTCTGTGCAGAGGGGGAG ATTTTTCTCTCTGAGAGAATGACTTTCTTTAATGCTTTCATTTTATTTTCGCTGACTGC AGTCCGGGAGAATGCGCTCGGTCGGAGAATCTTTCGGGGCGCGGTTGACAGTTCTTT TTCCAAGAGGGGTCCTTCACATTTATCATGCCTCTTCCTCGGGGGCTTTGTTATGCAA ATGTGGCTGAAATTGATA >14:104117671-104117851 (SEQ ID NO.: 375) CAGGGAAGACCCTCGGCCGGAGAGCCAAGTGCTGCTGGGAGGTGGCCGGGCGTGGC CGGGCTGTGCTGTGGGAACCGCTGGGTGGGGGCGCGCTGGGTTGCCCACGCTCCTG GCGCGCTGCCGGCCTGGAGACGCCGCCGCCGCCCTCTTGCACCCCGAGGGCCCGCA CCTCGAAACTCCG >14:105364294-105364612 (SEQ ID NO.: 376) CGGGTGTGGTGGGCGTCCCGGGTGCGCGGTGGGCGGCGGCCCGGGGGTGTGGTGGG CGGTGTCCCGGGTGCACGGTGGGCGTCCCGGGTGCGCGGTGGGCGGTGTCCCGGGT GCGCGGTGGGCGGTGTCCCGGGTGCGCGGTGGGCGGCGTCCCGGGTGCGCGGTGGG CGGCGTCCCGGGTGCGCGGTGGGTGGCGGCCCGGGTGCGCGGTGGGCGGTGGCCTG GGTGCGCGGTGGGCGGCACCATCCAGGCTTGCTGCGATGTTGGCAAGAGGACGAGG TCTCCTCACCATGCATGTCTCAGAACATACCTCTGTCGT >15:52789319-52790159 (SEQ ID NO.: 377) CTGCCCAGACCGGAGCTGGAGAGGGGCGAGAGGCTCTGGCCCATGCCGGCCACGTC CTTGTGGTAGGGGGTATAGAGGTTATTCATGGAGGCCAGCCCGCGCTCATCCCGCAT GAGCGTGAAGCTACCGCTCACGTTGCCCGCCAGGCGCTGGTGGTGGTGCGGGTGGT GGTGGTGATGGTGGTGGTGGTGATGGTGGGGGAACTTGTCCGAGACTGTGGAGATG GGAGGCAGCGGCTGCAGAGGGGTCAAGGTGGTGTAGGTGGTGGGCATGCTCATACC TGGGGGAGTCTCGCAGGCCATGGTCATGGTGGGATGCAGGGGGCCGGCCAGGCTGT GCTCAGGGGCCCGGTGGTGGTGGTGGTAATCTCCGCCGCCGCTGCCGCCGTCCAGCA GGGACGCCATGCCCATGGAGCGCGGGTGCGCGGGGGGCAGGTGGCTGCCGCGGTGC GCCACGGAGCTGCGCGCGTGGGGGCTGCCGCCCAGCAGGTCGGCAGGGGCGGGCAC CGGCTCATGGCTCACCCCGTGCAGCTCGCCGATCGCTTCCATGGTCAGCTGCGCGTT CATCGTGATCCGGGCGAGCAGGCGGCGGACACAACATCGATGTGGCCAGGCAGAGG CGGCGAGGGGCGCACGGAGTCCGGTCTTCACATCGGCTGCTGGCGACTGTTGCCTTC CTTCCTCTCACTGTGGGGCTCTGTCTCTCTCTCTCTCTCTCTCCGTGTGTGTGTGTCCG TGTGTGCGTGTGCGTGTGTGTGTGTGTGTGTGTCTCGCCTTCCCTCTTACCCCCCACC TTCCCCTCTGCGTCCTCGGCTTTTTTTTTTTTAATATTAATTTCCAAA >15:62165240-62165420 (SEQ ID NO.: 378) GCCAGTGGCCTCTAGCCCGCTGCCGAGGCGCCACCTTCAGTACTGCGGCCAGGAGA GTGGCGCTCCCCTCTTATACCGTAGGCTGAGTCCCGCCCAGCCGCCAGCGGCCCAAC CCGGAGGTGCTGCACAGCCCGCCTTCCCGCCACCCTCTCCCACGACGCCGGGAGGTC TGCATGCACTG >15:67968089-67968329 (SEQ ID NO.: 379) CAAGGTCAGACCCTTTGGCTGCAACACGTCCGTCAAGAAGCCAGGCAAATCTAGCA TGCAAACTAGGATCATTTTCGGGCGTTGGGGCCCCCCCGCTTGAAATCTGGTTTCCA TGTTCACAAAACGCAGCCCGACTGGTGGAACTCGCGACTCCAGACGCAGAGAAGCT GTGGGCAGAGGCGGAGGCAGAGGGTGGGAATGCAGCCTGGCGTTGGAGTGGGGAG AAAGGGGAGGGAGGAAC >15:69031565-69031745 (SEQ ID NO.: 380) GCAGGCCCGCACTGGGCTTCATCCCCACTCGGGACAGGCAGTGGCTCCATTGACCCG GATGAGCTGCGCACTGTGCTGCAGTCGTGTCTGCGCGAGAGCGCCATCTCGCTGCCT GACGAGAAGCTGGACCAGCTGACGCTGGCGCTCTTCGAATCGGCCGACGCGGACGG CAACGGGGCCA >15:72319682-72319982 (SEQ ID NO.: 381) GCGGCTTGAGGTCCTGCTCGTCCAAGCCCCGCGGGATCTGCCCCACGAAGAGCTTGA TGGCGTCGTGGTCCTTCATGGGTACGGCGGGACCGGGGTTTAGCCCGCTCATGCCGA CGCCGCTGTCCGCGGTGCTGAAACCCAGGCGCGGGCCGGGGCCAGCGGGCTGCGCT GACCCTCCCGGCGCCGCGGCCATGTCCCCGCCCTGTCAGCCCTCCCGCCGGTCCCAC TGGTCCCGCCTGTCCCGCCGTCCCCTCCCTGGACCGGTGGCGAGGGCCAGGGGGAG GGGGCGGAGCCCGGGCGG >15:78264397-78264697 (SEQ ID NO.: 382) AGCGGCTGGGCCGCGCCGGACGGGCGTCGGGGGTCTGGGCCGCGAACCCGCCGCGG GGCCGCCGGAACCTCCGCGAAGGTTCTAGGCCTTTGTGGCGTCACCGTCTCCTTGCG GAAGCTTCCGCCGGCGCCGAATAAAACCCGCCGCGGAGGAGCCGGTGGCTCTAGTG CGGTGGAGCCAGGCGTGGAAGTCGGTCCGGCGCGGGGCGGGGGGCGGGCGGGAGC TACAAGCGGCGGCGGCGGCGGCGACCGTGACCGTGACGCGCGAGCGGGCGGCGGG GGCGCGGGCCAGGGGCGCGGGC >15:89486695-89486875 (SEQ ID NO.: 383) CAAGCCCGGGTCCCGCCGATGGGCACGCCCTCCTCCCTCAGGCTCACCTGCCCAGCC CCATCCCTCCCAGTCCGCCACGCCCCCGGGGCCCGCCCTGCGCTCACTTCTCCACGC CCACGACGATGTAGCGGTCTTGTAAGAAGTGGAACCAGCCCTGCATGAGCAGCGCC CACTGGATGCC >15:98651103-98651343 (SEQ ID NO.: 384) TATGCAGGTGGTGCCGATTAACTTTGAAAAAATCACGACTGAGCCTTCACGAGTGAG GCGGGGAAGGAGGAGGCAGCGGAGGTTGTATGGCCCCATCACCGGGGCAATTCAGA AAGGCTGTTTCTATAAACAAATCCTTAAACGTCTGGTAAGAAATGAGTCCGCGACGG AACGAGAGCAGATCGTGGTTCGCGTGTTTACTGCCGAGTGGGACGCGGACTGGGGC CGGACCTTCCACAGA >16:1272246-1272546 (SEQ ID NO.: 385) CTGATCTCCCCCCGCACCCCACTGTCTGAATACAGAGGCCCCCTCCTCTCTACTGGG GAGCCCAGACATCTAGCCCTTGCCCTGTGTGGTTCTCTCCGGGTGAGGTGGGAGGGA CCTGCCGGGAGAGACAACATCCCTGCTGCTTCACTCACGGTGTGAAGCCGGAAGGG ACCAGACTCAGACCCCCTCCCGGGCCAGCCTCTCCGTGAAGCCCCTTTCTCCAGCAG GAGAGTGTAGCTGCCCCTCTGGGTGCTCAGGGGCCTTCTCAGCCTCACCTGACCCTC ACCTTGGGGGTGGGGGG >16:50841053-50841413 (SEQ ID NO.: 386) GGACCTCCAAGGAGGCCAGAGCTGTTTCTCCCGTTTGGAGAGGGAGATCCTAGCCTT TCTCAATACTTTTTGATTTCTGGGAAAGGAGAAGTTGGAAGGCCGCCTCGCCTCCTG TCTCGGTGGCGTTCAAGGTTATCCAGACAGCGGTCTGCGGGTTTCATTTGCAAGTCA CTGCGCGGCGCATGCAGAAGCAGCCGCGGGCCGGCGGGGCGCGCAGATAAGGTCTG GGGGCGTGGGTTTCGGGCTGTACCTGCATTATCGCGGCTTCCTTAAGCTCGGATGAA TATGTAAATCTCTCGCTGCAGCCTTCCGGTGCCGCAGTCGCAGCCGTGGGGGCCGCC TCCGCTGTAGCAATTCCGAG >16:57091834-57092014 (SEQ ID NO.: 387) AGGCTTGAGCGCCCAGCGACAGACAAGTGTCCTAAGAATTGGTGCCTCTTCTAGGG AAAAGGAGGCCTGGGCTCCAAGGCCTTAAAGACTCGCCTAATTTTCCGCACGGATG AGTAGACCCAGGCCCAGTTCGGATCCGTCTTTATCTTATCGTCTGTGTCAGAGAAAT ATGTCATATTTC >16:57536947-57537307 (SEQ ID NO.: 388) TCACTGTTGTTACCTGCATTTTTCCCTGGGCCAGCTCTGCCACCGAGTGGAAGTGGG CCAACAAGTCTGTGCCCATCGGGCCTCAGTTTCTCTTTCTGTACAACAGAAGGGTTG ACGAAAGCAACCTTGCGCTTGTTAAGAGGTGGGGGGCGCGGGGAGCACTCGGCCCG GCGGGCGGAGACTTTTCTCTGCATTGCGATGGTGGTTGGCAGGCCCTGGGGAATTAC GGTACTTCGCCTTCGGGGACGCCCAGCTGTTTTGGGGCTTTCTCTCTATTGGGGGTAG GATGTTTGTGGTCTTGACTGGAAAGCCGGGACAGGCGTCTGGAGGACTCCCCACTAC ATCCTGTACCCTGGAAGGC >16:68737031-68737271 (SEQ ID NO.: 389) AGTGAGCCACCGGCGGGGCTGGGATTCGAACCCAGTGGAATCAGAACCGTGCAGGT CCCATAACCCACCTAGACCCTAGCAACTCCAGGCTAGAGGGTCACCGCGTCTATGCG AGGCCGGGTGGGCGGGCCGTCAGCTCCGCCCTGGGGAGGGGTCCGCGCTGCTGATT GGCTGTGGCCGGCAGGTGAACCCTCAGCCAATCAGCGGTACGGGGGGCGGTGCCTC CGGGGCTCACCTGGCT >16:87571366-87571666 (SEQ ID NO.: 390) TACCAGGAGTTTAACAAATATTTATCGAATGAATGAATTCATTCATTTACTTATTCAA TCAAGAAGATTGAAATCTTACAGTCAGAAGCTGCAGCCACAGAGGCAGCCCAAAGC TCGTTTATTAAATGCCGGCTGTGGTGGCCGTGTCCTGCCAGCATAGTCTGGTGTGGC CTCTATGGCGCCCTCGGGAGGGTGGTGACAATATAGCACAAGGTGCTCAAGCTCCTG GGATGGCTTCACCTGGAGGCTGGGGAGGCAGGGTGGGAAAGGTGAGCACCGTCATT ACATGAGGGTGACTCCT >17:19744858-19745191 (SEQ ID NO.: 391) GCCCCAAGTCCTTCCTGAACCTCTCTGGGTCGCACTCTCCCCAGCCCCTCCCCCCACG CCCCATCGCATGGCCCCGACACTGGCAGAAGGCGGCCGCCCAGCCTGAGCACCTTG TGCAGGTCTGCGGCCAGCGCGCCCACCAGCTCCTGCTCCTGCTCCTGGATCAGGCGC TGCAGCGCCTCCAGCTGCTGGATCCGGAACTGCAGCGGACGGGTCCTGCCCGAGCT GAAGGCGGCGCGGGCGCGCTTCACGGCCTCGCTGATCTTGCTCATGGCGCCTGGGG ACAGAGAGCACCTGCAGCTGGCTGAGGGGCACGAGCGCGCCCTGCCTCCCA >17:20320942-20321122 (SEQ ID NO.: 392) GGCCAAGAAGTCTTTTTCTGGGAGGCTGGAGCTGCAGCGCCACCTGCAGGCCAAGG AGTCTTTTTCTGGGAGGCTGGAGCTGCAGCGCGACGTGCAGGCCAAGGAGTCTTTTT CTGGGAGGCTGGAGCTGCAGTTGCAGTGAAGTCACAGGTTCCGTGACGTCACAGGT GGGCAGGCGCAC >17:29761193-29761373 (SEQ ID NO.: 393) AGTAAGGAATCATGTCGGGGCCACCGAGGCTGCAGGTGCAAGCGAGGGGCGCCTTC CTCTTGCGGGCCAACGTGCTCAGGGTCATGGGGCCGGCTCAAAGTGCACAACTCCG CATCCTGGCCTCTGCTCTGCTCCGGCACGAGGCGCAGGCTGCGCGTGCACCCGGCGG CGGAGGCGGGCC >17:40218777-40218957 (SEQ ID NO.: 394) AAGATGACGTAAATGATGACTTGTGAGCAGTGGCCTGCCTCTGTTGCCATGACAACC GGAGCTTGACTACTTGGCCTTTGCAAGGTTGGCCGAGGCGGGTTCTTCGTTAACTCG AGATTAAGGAAGGATATTTAGGGGGGAGGGTGTGTGTGTGTGCGGCGGATTAAAGA CGAAAGGAGTA >17:42421656-42421836 (SEQ ID NO.: 395) CCAAAAGCTACATTTTTATCCAAGTGTGAAGAATGGGGAGAGCTGCAAAGAAAGCA ACAAGTGGCCCCGGGCGGAGCCGGGGGGTGGGGGCGCCAGCCTCCTCCCGCCGGCT GCGCTGCTGCGCCTGGCCCCCGCCCCCGCAGGCATGCGGGGTGATTCACCTCGCCCA GACTGCGCCCAG >17:43211642-43211882 (SEQ ID NO.: 396) CATAACCACCTAAAGAATGGTGAAATAAATGTTCTTGGAAATTCCTACCCGGACTGG CTAGTCCTTGCGGAAGCAGCGTCCGGGCCCTCGGGTAACGTTTGAAGAGCTGGCAG CGTCTCAGGCTGCTGCGTGGCGAAGGGGCGGACCGGGGGACGGGGGGGTGGGCCCT TAGGGGCTGGGGCGGGACTTCCCTGGGCACTGAGTCAAAGCTTGAGGGGAGTGTTC GCTCCCGCATTTTCGA >18:9707922-9708102 (SEQ ID NO.: 397) GCAAACGGCCTCGGCCGAGAGCATTCGCTTTCCAGATGAGAATGGCATCTTCAGGG ACCCGCTGGTAGTGGGGCCAGGTCTCCACAGGGCCGGTCCAGTCCTTCCTACCCACC CGGGCCCTGCGGCCAGGCGGGGCCGGGAGGGGCGGATGCCGGAGGGCGCTGGGGG AGGCCGACCCGCG >18:24139209-24139559 (SEQ ID NO.: 398) CAGGCGGAGGGTCCTCAGAGTCGGGGGTGGGGGGCCTGTGGGGCGGCCCCGGCCCA CACCGGGGAGTGCGGCGACCAGACGGCCAGCTGCCGAATCTGAGGCCTCGGTGGGT CCGTCGCCCGCCTCTCTTGGACAAGTCCAGGCGATGTGAGCACGCCCAGCCTCCTAC ATTTCACTCCCGTCTCTCCCAAACAGACCTAGCGCAAAACGAGCACTGACACAGCG GGGGCCCACATCCCGGAGGTTCTTTAGGGAGAGGTCGGGGAGTGCGGTTACCTATG GCTCCGAAGTCCCCGCTGGCATCCTGAAAGGCATCGTATTTCTCGCTTAAGGCGTTA CCCTTGTGGTAGT >19:2263624-2263924 (SEQ ID NO.: 399) GGAGACTCTGTCTGAAAGAAAAAAAAAAGAAATATAAGTACGGTAAAGGGAAAAA CAACAACTTGCTCGAGATAAGCCCTGTTTACTTGGGGGCCTCGCTTTTCCATGTGTGT TTGCCCAGCTCATCCTGAGGCTGCCCACACGGCTGTGGGTCCTGCTTTATCACCCAG CAGCAGATGCCTCTGCGGCTTTGTGGCCAAACCCTGGCCCTGCACAGCCTCCTTGTG GCCTGAGCTTATTGCAGGCTGCACGGTGCACATTACAAATGGTCAGTTGGAGGCCAG GCGCGGTGGCTCACGCC >19:20167000-20167360 (SEQ ID NO.: 400) TCAGCTCAGGGAGGAAGCCCTGCCTGAAAAGGCTGCAGCTTAGGCTGTTACTCTTTC ATCACTCAGCCCAGCATCTGATCACATCCTCTGTCACTCAGGGACTGAGTGGGCGGG GCCTTAAGCATTATCCAATCAGAGACGCTGGGCTGGAAACCGTCCAATCAGGCAGG CAGCTGGAGCAAAGAGGACGGCTTCCGGGTTTGGCGCGGCCTTTGTCTCTCGCTGCA TCTGGAGCTCTAGGTCGCCTCTTCGCTACTCTGTGTCCTCTGCTCCTAGAGGCCCACC CTCTGTGGCCCTGTGTCCTGTAGGTATTGGGAGATCCACAGCCAAGATGCCGGGACC CCTTAGAAGCCTAGAAATG >19:20424875-20425055 (SEQ ID NO.: 401) AGCAGAGAACACAGAGCAGTGAACAAGAGATCTGGAGCTCCAGCGGCAGCAAGAG ACAAAGGCCGCGCCATACCAGAAAGCCGTCCTCTTCGCTCCAGCTGCCTGCCTGATT GGAGGGTTTCCAGACCAGCCTCCCTGATTGGATTATGCTTAAGGCTCTGCCCCCTCA GTACCTGAGTGA >19:40613725-40614145 (SEQ ID NO.: 402) TTTGGACCGTGATTGTAAAGAAGCTGTTCTAAACCCGTCGGGGGGCGGTGTTTGCAG GGAGGGAAGTAGCGTGAGGCAGGTTGGGGAAGGCGTGAGAGGCCTAGGAGAGCCG AGGGGCGGTGGAGGGGTGTGGCCTAGAATGTTAGGCGGAGCGGGAGGTGGGCCGG GCCTTCGGACGCCCTGTCCCGCAGACGTTGACGAGTGCAGCGAGGAGGACCTTTGC CAGAGCGGCATCTGTACCAACACCGACGGCTCCTTCGAGTGCATCTGTCCTCCGGGA CACCGCGCTGGCCCGGACCTCGCCTCCTGCCTCGGTGAGAGGCCCCGCCCCGGCCTG ATCCCTCCTCCCTTCGACTCCCCGACTCGCCGATTGGCCTCCCACCTCTGTCTTTCCT CCTCCGCTTCTCCCCTCCCCTTACCT >19:40811045-40811585 (SEQ ID NO.: 403) CTGTTGGCTGCAGGATGAACCTCCATTCTAACCTTACGCTTTAGCGCCGCCCCGCCC TCTCTCGGCCGTTTGCACCTCATTAGCTGGAGTCTCTATTAGGCCCCGCCCCCATTTG CCCGCCTCTACCATTTACCCGCCCAGCCTGGAGCGTCCGGGCCGGCAAGTCCAGCGC CGGGGCCTCACTGTTTCCGCGTGTGAAGCGTTCGAAGACTGCCATGGACCCGCGGCC AGAGACCGCATCCGCCTGTAGCACTAACGCGTCCCGCAGCGCTGCGTAGCCGCACA GCCCCACCGCAGGGCGCGGGCCCAGCCGCACTGTGAACACCCGGCCCCAGCGGCCG GAGAGCTACGGGTAGCCGGTGCTCAGCGGGTGCCCATAGGGTTCCTCATCGGAGCC ATTGCCCCCAGCTCCCTCTTCCTTCAGACCCAGGAGTCCTCGTCTCAGACCCTCATTC CTCAGGCCCAGGAATTCAAATCCCCAGCTCCTTCCTCCCTGAGATCCAGGAGTCCAG GCCCCCACTTCCTTCTTCCCTTAGGACCT >19:49142732-49143092 (SEQ ID NO.: 404) GTTCCCCCATCTCTCCGATTTTCTCCTCCTCTGTCCCTCTGTCCCCTCTGTCCCTCTGT CCCTCCGCTGCAGCTGTGGGTGGGCATGCCTGCCTGGTATGTGGCCGCCTGCCGGGC CAATGTCAAGAGCGGTGCCATCATGGCCAACCTGTCAGACACGGAGATCCAGCGCG AGATCGGCATCAGCAACCCGCTGCACCGACTCAAGCTACGCCTCGCCATCCAGGAG ATGGTCTCGCTCACCTCGCCCTCAGCCCCCGCCTCCTCCCGCACTGTGAGTGTCCGG CGGCCAATTCCAGCCTTCGCTTCCTCAGAGCCCCGCCTCTTGCCCTCAGTCTAGCCA ATCCTGGGCCTGCTCACTC >19:50050361-50050716 (SEQ ID NO.: 405) CCTCTCTGAGCCTCAGTTTCTTCAGTGGACTCAAGAATGATACTCAGTGTAAGGATT CTCAAAACGAGCATCAGCAGGTTCCGCCCACGCCGGCCTCCTGGGTTCAGTTCTCTA ATAACCACCTCCCTTCCCCGCCTACTCCAGCCAATCCTTGTGCTGACTCGGCTCCTGG CCACGCCCTAACCCCACCCCCGCTGCCTCTAAACCCGTCCCCACCCCTGCAGCCTCA CAGGCTGCCGTCAGATTCTCAAGCCCCTATTCCTCTCGGTGGCCTAAATCCCCAACT GCTCGGGGCCACTTTTCAGGCCAAAATGGGCCCAAAATGGGGAGGGCAAGTGATGA ATGTCACTAGACAG >19:53159277-53159457 (SEQ ID NO.: 406) GAATAGACTTACGTGGACCACTTATGATAGAAACCAAAATGATTTCCTCTTACCAAG TTGAAAACGGTTTATGTTAAAATTGTTTGCCGGCGGGTTGGACCCAGTCCTGCTAGG GAGTCTGCTGCAGCTCAGGAACGGGGATCTGGGAATCGGGGATCTCGGTCTGGGAA CTGGGATCTTA >19:56538908-56539088 (SEQ ID NO.: 407) GCCATGGGGGAGCGCGCGCGGGGCTGTTCGCTGGGCGTGGCGGGCGGGTGTGGCCA GGGGTGTGGGTCTGTGAGGGACCGGTCGGAAGGGCGTCGCGCGGCCTCGGGTGACA TGCGGGGGGCGGCGAGCGCGAGTGTCCGCGAGCCGACGCCGCTCCCGGGTAGAGGC GCCCCCCGCACAA >19:57888509-57888689 (SEQ ID NO.: 408) TGCTCCCAACAGGCACCTGTGGACCCCAGATTCCATCCTTCTGGCTCAGTTCACTTCC AGGCCTTTGCCCGCGCCAGTCCCTGTACCTGCCGGTCTCCCCACCGCATCCCACGGG TGTCAGAAATGGGGCCCCTCCCGCAAGCGCCTCAGTGTCCCAACGCCGGCGTCCGG GCTGCAGAGC >19:58347014-58347734 (SEQ ID NO.: 409) CGGCTGCATCAGCTTTCTAGACAACGGGAGAAAAGAGAAATGGTGGAGGAGGGGA AATCCTATGCCCTCCTCCTCGCGGAAATCAAGGCCGACCTCCCTGACGCCCCCCCGG AAGGAAGCGCGTGGTCGGCTGCCAGCCGAGACCCCCATCTGCGCCTCCAGCTGCAG GGCCTTTGCTGGGCGGTTCCTCGCCCGCAATTCCCCCACGAGCCCTGGGGAGACCCA GCGCTAACCAGGGGTGCCCAAGGGAGGAGCCGGGAGAGGCCCTCCTGGAGGTGGG CACAGCCCAGGCAAACATCAGCAGACGGAACCAGCACCCGGGACCCAGGGAAACG TCACCTGCCACCAGGAGCTCCACAGGGTCGCTGAGCTCCGATTCGAAGGTGTGGGG CACCCAGGAGCGGTAGCGGCACCTGTAGTTGCCGGCGTGCTGGGGCCCCACGAAGA TCAGCTCGAGGTTCGCCGCGGCCCCGGGGGTGCGGACCGTCTTCACGGCCTTCGTCT CGCCCTCGCGCAGCAGCTCGAAGGTGACGTCGGGGATGGGTCCCTCGCAGCGCAGG ACGGCATCTCGGCCCGCCAGGACCGCCCCACTCCACGTCGCCCGGAGCTGAGGCCT GGGAGGGGGTCCTGGGCGGAGCGGGCGGGTGGTCGGGCCAGGCCACGCCCCAGGC CACGCCCCAGGCCACACCCCAGGCCACACCCCAGGCCGCGCCCGCGCCTG >19:58562845-58563445 (SEQ ID NO.: 410) CACCAGGAGGGGCCGGGGGCTTAGCGCCAGGGCCCGGGGGATCGCCGTGGATGCGC TGGTGCTGCAGCAGATTGGAGCGCTGCCGGAAGCTCTGGCCGCACTCAGCGCAACG GAAAGGCTGTTCGCCCGTGTGCACTCTCCGATGCTCTTCCAGGCGCGCGCTGCGCAC GAAGCCCTGGCCACAGTCGCCGCACACGAACGGCCGCTCCTCGGTGTGCGTAAGCT GGTGGCGCAGCAGGTGCGAGCTGCGGCTGAAGCTGCGGCCGCACTCGCTGCACACG AATGGTCGCTCACCCGTGTGGATCTTCTGGTGCCTCAGCAGGTTGCTGCGTTGGCTG AACACCTTGCCACATACATCGCAACGGCCGCCCCTAACCACCCCGCCCCCAGTGCTG GGGCGGCCCCGGCTCCGGCCCCTGGGGGAGCGCCAGCGGGTGGTGATCAGAGCAGG GCCCACACCCCGGCAGGGATCCTCGTCCGTGGGGTCCTGTTCACTCCTCAGATCGCT GGGGAGCAGAAGCGCATGCGCAAAGCCACCTTCGCGGGAGGGTGATTGGATCTGGC CAGAAAGGCCAGCCATGCCGAGGTCCCAGGGGACGTG >20:3083167-3083587 (SEQ ID NO.: 411) GCAGGGGAGGCACTGCGGGGACGGGCGGGGTGAGCGGGAGGAGGGGAGCCGGGAG TCGAGGGGTTGGAGGGGAACGCAGCGAGGCGGGGATGCTGGGGTCCAGGGCTCGG AGTGCGGGCGGGACACCGGGGCTGCGGCTGCAGGCACGCTCGGGCGCCACTGGGCC TCGACCGCGGTCACGGGCGGGGCGTCCAGATCTGCTCGGCACCTTGGTTTCTTGGAT GACCTCTCGGTGACAGCCCTCAGCGTCCTCACCCTCAGCTAGGGACGGGTCTCCCGT GGACTACAGCGTGGGGAACCCTTCCTCGAGCCTCGGGGTCATCGCTGGTGGGCGCC ACTGTTGCAGCTGCCCCACCCTCCACCACTCCAGACCCTTCCTCCTTCCTCCTCGCCC TGCTGCGGCTTGAGCCCGGGCCCACCC >20:5504527-5504827 (SEQ ID NO.: 412) ACTCCCCGAGACAGGGACCCGGAGACGTGGGCTTTGTCAGTTTAACAGATTCTGCCT CCGGGAACCAACTGCCGGGAGATTCTGATTGGCTCAGCCGCGTGCCCACGTGACCG ACCAAAACCGGCCACCAGGGTCTCCCAACTGCCTGTCAAACGCACAGCCCTGTTGG GCCCCCGGAGAGGAAGAGCCGAGAAGGAGGCCAGGCCGGGGGTCAGGTGGCTTCC TCTATGGGCCCTTTAATCCACCTCACTTTTTTATCTTCTTTTTTTTCCCAGCAGCTTTA TTAAGTTATAATTCACAC >20:45469465-45469765 (SEQ ID NO.: 413) CCAGGAGCCCTGAGCCTTGGCCCTCAGGCCCCAGGAGGGAGGTCAGGAGGGAGGCG TGGACAAGGGTCCGGCCGTAGCTGGTCCCGTCCTGGAAGCTGCTTAAGTTCCTGGTT CCCACCGGGGCCAAGAGTGATACCTGATCCTGGGGGATTGTGAAATGACCTCATGT GGCAGCCCGCCCGCGGTGCCCGCAAAGCCCTCCACCCTCCCCTTCCCCGCTCGGCTC CACCCCTACCCCACGCCCCCTCCCGCGCGCGCGGTTAAATCCCCGCACCTGAGCATC GGCTCACACCTGCACCCC >20:52103731-52104151 (SEQ ID NO.: 414) GCCCCTCGACCCAGGGGACGGGATCCTGTAAGTCTCACCTGCCTATCTCCATCCCAG GCCTCGGGCACGAGGGTGGTTGTACTATCCTGGTTATGGTAGCTCCACTCGAGCAAG CTTTATTTTAACATATAAGCTATTCGTTTAGTGGAGGCTTCATTAAACTACTCCCCTC CACCACCACCTCGGGAAGTTGTGGTCAAAACCCACCAGACCGACTGTGGTGGAAGT TGATGCGGAAGCTGGAGAGCCCGCGGCTCTGGAGGGGTGAGCCGCCCCGGAGAGG GGACCCATCCTCCTTTCCGCGCCCGGAAAGAGCGGGGGAGAAGAGGAAGTCCAGTT ACAACTCCTTTCCTCAGCCCCTTAAAGGAAAGGTATCAGCTAACCACGGGGAGCTG GCAGCCTAAGAGAAAGTAGGAACCTA >20:60087400-60088000 (SEQ ID NO.: 415) CATCGGGCCTTGCAGCAGCGCCGCAGATATTCTGCCTCCCATTTTGCCCGCGGGGAC GCCGAGGCCCGGCGCCGCATCCTGCCGCCCGTTTTGCCCGCGGGGAAGCCGAGGCC CGATGCCGTACCCTGCCGCCCGTTTTGCCCGCGGGGAAGCCGAGGCCCGGCGCCGC ATCCTGCCGCCCGTTTTGCCCGCGGGGAAGCCGAGGCCCGGCGCCGTATCCTGCCGC CCGTTTTACCCGCGAGGAAGCCGAGGCCCGGCGCCGTATCGTGCCGCCCGTTTTGCC CGCGGGGAAGCCGAGGCCCGGCGCCGTATCCTGTGGCCGTTTTACCCGCGGGAAAG TCGAGGCCCGGCGCCGTATCCTGCCGCCCGTTTTACCCGCGAGGAAGCCGAGGCCC GGCGCCGTATCCTGCCGCCCGTTTTACCCGCGGAGACGCCGAGGCCCGATGCCGTAT CCTGCCGCCCGTTTTACCCGCGGGAAAGCCGAGGCCCGGTGCTGTATTCTGCCGCCC ATTTTACCCGCGGGGAAGCTGAGGCCCAGTGCTGTTTAATATCTTACTCATGTTCACT TGATGAGAAAGTGACAGATCTGAGACAAACCCAG >21:31558435-31558795 (SEQ ID NO.: 416) ACGCGTCGCCGAAAAGCCAGGCCCGGAGGTGCCTAAGTCAGGGACCGAGACGCAA ACATAGACACAAGGATGCACAAGCACGCCCTCCCCGAAGTTGACAAAAATCAGCCG ATAAAATACAAAGTGCCGCGGCCGCCGCAGGTCAGCGCTGACCTCCTGCTGCCGAG AGGACCGAATGCCGACGTCCGGACGCTGTCATTTCCATCCAGCGAAGGCACCTGGG CTGCACGGTCTCGTCTCCCTCCTTCGCGCGAGGGATGCCTCCTCCTGCCTCTCCTCCC CGCATCTCCCCACCTCCCAAGTGTGTGAACACGAAAACAATACGTGGAAAGCCCGA TCGGGGGGAGCTAGGACCCGCCGG >22:23751549-23751729 (SEQ ID NO.: 417) AGGATCCCCCTCCCCCAACCTGCTTCAAGGGTAGCCCTGTTCCTGTCTGCCCTCCCCG CCCCCACAGAAATAGAGATGAGAAGGGGCAGGCGAAGAACTAGGAGTGTCTGCGA GACCATCCCAGGACCCTGAGCCCCCCAACTCTCTGCATCCCAGGGCTGACTTCGACA TGAAGCGCCTC >22:37335098-37335278 (SEQ ID NO.: 418) GCCCCCACCCCAGCCTTGGATAGGGTAGTATACGATAGGGGGCGTAAAGAAGGGTC ATGGGCTCCGGTGGTCGCAGGTCCCACCGGCAACCGCCAGGGCGGGGGCAGCAGGA GCAGGAACCTGCTCGCCTCCGCATCTCGTCGGCTCCCCTCTCCCGCCAGACTCCTGT CTCTGCGCCAGG >22:42432029-42432209 (SEQ ID NO.: 419) CCTCCCCTTCAAAAGCCACCTTGGCAAGGCATTAGCTAAACATCTTCTCGGTCCCAG AAGGCTTCCCCTGTGAAGTCTGCAGCGTTCAAACGACAACCAGCAAATCCCCAGAG ACAGGTCCCTGGGAATTAGCTGCGCCGGGCGGGATGAAAGCCGCTCTGATGTTCTG GAGCGAGAGAGT >22:44752220-44752460 (SEQ ID NO.: 420) CCGTCTCAAAATAAATAAATAAATACATACATACATAAAGTAAAATAATGAATAAA TAAAATAAGAAATGGGGAAATGGATCAGCAAGAAAGTGCCCGCCCCAGGCATGGGT GCCGTGCGGGACGGGGACGCGGCCCAGCCGGGAATCGGGGTGCCCAGGGTGCGAT GTGCGAGGGGCTCCTGAGCGCGTGTGCTCCGCCCGACCCCGCCCTGTCCCCCCGACA CACAGGTGGACCCAGGG >22:45867691-45867871 (SEQ ID NO.: 421) AGCGCGCCCCTATCCTGCACGCATCCGCGGCCCCGGGCCCTTTCCGCAGCCCCACGC GGTCTCCTCCCGGGTTAAATCTATCCACTCGCGCGTTCCTTGGCAGCCGTGATCACA GGCGTGACCACGGTCCCCAAGCCCTCGCGCCTCCGTCCACGCTATTGCGGCCGCCCC TGCGCGCCTG >22:50085187-50085994 (SEQ ID NO.: 422) TGATCCATCTGGGCCCTCCAGGTGCAACACCTGACAACATCCATCGGCAACTTCGTC CATGAACACATCACGCCGGGGACTCAAGCACGTTAAACTGCTCCAATTGGTAGCTA AACGAGAGATTGCAAAACATGCCTCTACTCAACGGCTTAATGTCTGAGCACTTACCT CCCCCGCTGCTCTGCCGTTGGGAGCACTGGTCTCTGGGTGAGGGACTTCCAGCAAGA AGTATTCACAAATGAAACAAAAGCTCAGCAAACTTGAGCTGAAGGCAGGGGAAGG AGAGCTGCTTCCTGAATATCAATGAGGGGAGGAATCGGGTGGATCGTAGAAATGTT TCGTGTTGGTTGTGTAAACCACTGCCTCGGAGCTGTCAGAACCCAACTAGGAAAGGA AGGGGCCCTGCCTGTGCCACTCGCCACAGAGCTCGGGTCTCTCAGAAGAAAGAAGC GTCCCTAAGAATAGAATCCCACCAAGTACACATTCTGAGCAGGCTCTGTTTCTGAAA CGTAACTGTTTACTCGAAGGTCTTCTACATCTTTCCAAGTAGCCTTTTTCCATCCCCC ACAGCCACACGGTGGGAACCTCCTTCACACGGTCACATAAGCATTCACGCACTCGG CTTAGCTGTGTGGCCTTGGGCGGCTCCGGATTCGGCCCTGTGGTTTGCGTGGGCAGC CCGGATGGCTGGTGGGCCCGGTCCTGCTGCCCCCTTTATCTCTGCTCACCAAGCAGA GAAAAACCACAGTAATGTGTGTCGCCCAGAGACACTGGCACCCTGACAACTACAGC AACGGGTTCTTTGTGC >X:781309-781729 (SEQ ID NO.: 423) AGTCAGGAGCGGGCGAGCTGTATTTTTATGCTAAAATTTACACAAAGGGACGGCCC CAGGCTCTCCCTCCTTTACAAGCTGTGGTCAGTCACGCCGTCTGGCCGAGGAATCCG GCTTTCACAGGGGGAAGCAAATAATAGGACGGGGAAACCGCAGGGTCCTTGGGCAC TCAGAGCTGTCACTCATCACAAATCCATAAAACAATTCGTGTGGAAGTAATGATATT GTTTAACCACTGTATTTTTGATTAATGTATAAATAATTTAACTGAGTATTTCTTGAGT TTTCAGCGTGTCTGCCATTATTTACCGGCCCTGTCATGACGGCTGCTGGTGCTCTGCC ATATAAAACATCCTCAAGTCCGTCCGAGGAGGCTGGTGGGTTGTTAATGGTCTTAGG GGGAAACGGCATTGCAGCTATT FIG. 4 SEQUENCES MUTATION MARKERS (DNA SEQUENCE) >1:114709462-114709702 (SEQ ID NO.: 424) AATGAAAAAAATGCATAACAACAAAGAATATGAATATGGATCACATCTCTACCAGA GTTAATCAACTGATGCAAACTCTTGCACAAATGCTGAAAGCTGTACCATACCTGTCT GGTCTTGGCTGAGGTTTCAATGAATGGAATCCCGTAACTCTTGGCCAGTTCGTGGGC TTGTTTTGTATCAACTGTCCTTGTTGGCAAATCACACTTGTTTCCCACTAGCACCATA GGTACATCATCCG >1:114713788-114714028 (SEQ ID NO.: 425) TGCTCCTAGTACCTGTAGAGGTTAATATCCGCAAATGACTTGCTATTATTGATGGCA AATACACAGAGGAAGCCTTCGCCTGTCCTCATGTATTGGTCTCTCATGGCACTGTAC TCTTCTTGTCCAGCTGTATCCAGTATGTCCAACAAACAGGTTTCACCATCTATAACCA CTTGTTTTCTGTAAGAATCCTGGGGGTGTGGAGGGTAAGGGGGCAGGGAGGGAGGG AAGTTCAATTTTT >1:114716004-114716244 (SEQ ID NO.: 426) CAAGTGAGAGACAGGATCAGGTCAGCGGGCTACCACTGGGCCTCACCTCTATGGTG GGATCATATTCATCTACAAAGTGGTTCTGGATTAGCTGGATTGTCAGTGCGCTTTTCC CAACACCACCTGCTCCAACCACCACCAGTTTGTACTCAGTCATTTCACACCAGCAAG AACCTGTTGGAAACCAGTAATCAGGGTTAATTGGCGAGCCACATCTACAGTACTTTA AAGCTTTCTATAA >1:114716004-114716244 (SEQ ID NO.: 427) CAAGTGAGAGACAGGATCAGGTCAGCGGGCTACCACTGGGCCTCACCTCTATGGTG GGATCATATTCATCTACAAAGTGGTTCTGGATTAGCTGGATTGTCAGTGCGCTTTTCC CAACACCACCTGCTCCAACCACCACCAGTTTGTACTCAGTCATTTCACACCAGCAAG AACCTGTTGGAAACCAGTAATCAGGGTTAATTGGCGAGCCACATCTACAGTACTTTA AAGCTTTCTATAA >10:87933115-87933355 (SEQ ID NO.: 428) TTGCAGCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCA TATTTATTACATCGGGGCAAATTTTTAAAGGCACAAGAGGCCCTAGATTTCTATGGG GAAGTAAGGACCAGAGACAAAAAGGTAAGTTATTTTTTGATGTTTTTCCTTTCCTCTT CCTGGATCTGAGAATTTATTGGAAAACAGATTTTGGGTTTCTTTTTTTCCTTCAGTTT TATTGAGGTGTA >12:25225520-25225820 (SEQ ID NO.: 429) TATAGCATAATTGAGAGAAAAACTGATATATTAAATGACATAACAGTTATGATTTTG CAGAAAACAGATCTGTATTTATTTCAGTGTTACTTACCTGTCTTGTCTTTGCTGATGT TTCAATAAAAGGAATTCCATAACTTCTTGCTAAGTCCTGAGCCTGTTTTGTGTCTACT GTTCTAGAAGGCAAATCACATTTATTTCCTACTAGGACCATAGGTACATCTTCAGAG TCCTTAACTCTTTTAATTTGTTCTCTGGGAAAGAAAAAAAAGTTATAGCACAGTCAT TAGTAACACAAATA >12:25225520-25225820 (SEQ ID NO.: 430) TATAGCATAATTGAGAGAAAAACTGATATATTAAATGACATAACAGTTATGATTTTG CAGAAAACAGATCTGTATTTATTTCAGTGTTACTTACCTGTCTTGTCTTTGCTGATGT TTCAATAAAAGGAATTCCATAACTTCTTGCTAAGTCCTGAGCCTGTTTTGTGTCTACT GTTCTAGAAGGCAAATCACATTTATTTCCTACTAGGACCATAGGTACATCTTCAGAG TCCTTAACTCTTTTAATTTGTTCTCTGGGAAAGAAAAAAAAGTTATAGCACAGTCAT TAGTAACACAAATA >12:25227222-25227462 (SEQ ID NO.: 431) ATTTAAACCCACCTATAATGGTGAATATCTTCAAATGATTTAGTATTATTTATGGCAA ATACACAAAGAAAGCCCTCCCCAGTCCTCATGTACTGGTCCCTCATTGCACTGTACT CCTCTTGACCTGCTGTGTCGAGAATATCCAAGAGACAGGTTTCTCCATCAATTACTA CTTGCTTCCTGTAGGAATCCTGAGAAGGGAGAAACACAGTCTGGATTATTACAGTGC ACCTTTTACTTC >12:25245228-25245468 (SEQ ID NO.: 432) AAGAATGGTCCTGCACCAGTAATATGCATATTAAAACAAGATTTACCTCTATTGTTG GATCATATTCGTCCACAAAATGATTCTGAATTAGCTGTATCGTCAAGGCACTCTTGC CTACGCCACCAGCTCCAACTACCACAAGTTTATATTCAGTCATTTTCAGCAGGCCTT ATAATAAAAATAATGAAAATGTGACTATATTAGAACATGTCACACATAAGGTTAAT ACACTATCAAATAC >12:25245228-25245468 (SEQ ID NO.: 433) AAGAATGGTCCTGCACCAGTAATATGCATATTAAAACAAGATTTACCTCTATTGTTG GATCATATTCGTCCACAAAATGATTCTGAATTAGCTGTATCGTCAAGGCACTCTTGC CTACGCCACCAGCTCCAACTACCACAAGTTTATATTCAGTCATTTTCAGCAGGCCTT ATAATAAAAATAATGAAAATGTGACTATATTAGAACATGTCACACATAAGGTTAAT ACACTATCAAATAC >3:179218185-179218425 (SEQ ID NO.: 434) TATAAGATATTATTTTATTTTACAGAGTAACAGACTAGCTAGAGACAATGAATTAAG GGAAAATGACAAAGAACAGCTCAAAGCAATTTCTACACGAGATCCTCTCTCTGAAA TCACTGAGCAGGAGAAAGATTTTCTATGGAGTCACAGGTAAGTGCTAAAATGGAGA TTCTCTGTTTCTTTTTCTTTATTACAGAAAAAATAACTGAATTTGGCTGATCTCAGCA TGTTTTTACCATAC >3:179218185-179218425 (SEQ ID NO.: 435) TATAAGATATTATTTTATTTTACAGAGTAACAGACTAGCTAGAGACAATGAATTAAG GGAAAATGACAAAGAACAGCTCAAAGCAATTTCTACACGAGATCCTCTCTCTGAAA TCACTGAGCAGGAGAAAGATTTTCTATGGAGTCACAGGTAAGTGCTAAAATGGAGA TTCTCTGTTTCTTTTTCTTTATTACAGAAAAAATAACTGAATTTGGCTGATCTCAGCA TGTTTTTACCATAC >3:179234177-179234417 (SEQ ID NO.: 436) GCTCTGGAATGCCAGAACTACAATCTTTTGATGACATTGCATACATTCGAAAGACCC TAGCCTTAGATAAAACTGAGCAAGAGGCTTTGGAGTATTTCATGAAACAAATGAAT GATGCACATCATGGTGGCTGGACAACAAAAATGGATTGGATCTTCCACACAATTAA ACAGCATGCATTGAACTGAAAAGATAACTGAGAAAATGAAAGCTCACTCTGGATTC CACACTGCACTGTTAA >7:55160195-55160435 (SEQ ID NO.: 437) CCCTCAAGGAGATAAGTGATGGAGATGTGATAATTTCAGGAAACAAAAATTTGTGC TATGCAAATACAATAAACTGGAAAAAACTGTTTGGGACCTCCGGTCAGAAAACCAA AATTATAAGCAACAGAGGTGAAAACAGCTGCAGTAAGTCACCGCTTTCTGTTTAGTT TATGGAGTTGGTTCTAATGGGTCCTTTATTTGTATTTAGAATATTGAAGGGCTATTCC CATTTAAATTACTT >7:140753216-140753456 (SEQ ID NO.: 438) ACTCAGCAGCATCTCAGGGCCAAAAATTTAATCAGTGGAAAAATAGCCTCAATTCTT ACCATCCACAAAATGGATCCAGACAACTGTTCAAACTGATGGGACCCACTCCATCG AGATTTCACTGTAGCTAGACCAAAATCACCTATTTTTACTGTGAGGTCTTCATGAAG AAATATATCTGAGGTGTAGTAAGTAAAGGAAAACAGTAGATCTCATTTTCCTATCAG AGCAAGCATTATGA >19:1223005-1223245 (SEQ ID NO.: 439) CTCCGGCTGAAGCACCAGTGCCCATCCCACCGAGCCCAGACACCAAGGACCGGTGG CGCAGCATGACTGTGGTGCCGTACTTGGAGGACCTGCACGGCGCGGACGAGGACGA GGACCTCTTCGACATCGAGGATGACATCATCTACACTCAGGACTTCACGGTGCCCGG TGAGTCTGGCGGGGGCCCCTGCCCGGCTCTGCTGACTCGGCCAGGATGTCCCACGGG AGCAGGGTGCCTGCC >7:7673682-7673922 (SEQ ID NO.: 440) AATGTGTAAAATCACTTCTTTTTCCCCCCCTTTTTTTTTTTAACTGTGGAAAATCTAA AGTCTTCAAGAATCCTTGATGAATTCAAGTTCTGTCTTATAAATAGTACTAACCTTGT TTCATAAATTAGCATCTGAAATTAAATTAGGCATCCAATAAATATTTGCTGAATGAA GTAGACTTTAAAATCTAAATATGTTAAATAGTGTTTCCTGTTTAAGACTATTTTCTAT TATAAAATTA >4:54727179-54727419 (SEQ ID NO.: 441) TGCCAAAGTTTGTGATTCCACATTTCTCTTCCATTGTAGAGCAAATCCATCCCCACAC CCTGTTCACTCCTTTGCTGATTGGTTTCGTAATCGTAGCTGGCATGATGTGCATTATT GTGATGATTCTGACCTACAAATATTTACAGGTAACCATTTATTTGTTCTCTCTCCAGA GTGCTCTAATGACTGAGACAATAATTATTAAAAGGTGATCTATTTTTCCCTTTCTCCC CACAGAAAC >7:116700088-116700328 (SEQ ID NO.: 442) CCAGCCTGAATGATGACATTCTTTTCGGGGTGTTCGCACAAAGCAAGCCAGATTCTG CCGAACCAATGGATCGATCTGCCATGTGTGCATTCCCTATCAAATATGTCAACGACT TCTTCAACAAGATCGTCAACAAAAACAATGTGAGATGTCTCCAGCATTTTTACGGAC CCAATCATGAGCACTGCTTTAATAGGGTAAGTCACATCAGTTCCCCACTTATAAACT GTGAGGTATAAAT MUTATED AMINO ACID SEQUENCES (mutAA) SEQ ID NO.: 443 P SEQ ID NO.: 444 KPLRHH SEQ ID NO.: 445 CRAY SEQ ID NO.: 446 CRAV SEQ ID NO.: 447 S SEQ ID NO.: 448 P SEQ ID NO.: 449 NN SEQ ID NO.: 450 KPLRHH SEQ ID NO.: 451 CRAV SEQ ID NO.: 452 CRAV SEQ ID NO.: 453 QAGV SEQ ID NO.: 454 EKLPR SEQ ID NO.: 455 LR SEQ ID NO.: 456 R SEQ ID NO.: 457 EGA SEQ ID NO.: 458 L SEQ ID NO.: 459 GL SEQ ID NO.: 460 L SEQ ID NO.: 461 S MUTATION CODON (DNA SEQUENCE: chr:i.start-i.end) chr1:114709581-114709583 (SEQ ID NO.: 462) GGC chr1:114713907-114713909 (SEQ ID NO.: 463) TTG chr1:114716122-114716124 (SEQ ID NO.: 464) ACC chr1:114716125-114716127 (SEQ ID NO.: 465) ACC chr10:87933234-87933236 (SEQ ID NO.: 466) AGG chr12:25225626-25225628 (SEQ ID NO.: 467) TGC chr12:25225713-25225715 (SEQ ID NO.: 468) TTT chr12:25227341-25227343 (SEQ ID NO.: 469) TTG chr12:25245346-25245348 (SEQ ID NO.: 470) GCC chr12:25245349-25245351 (SEQ ID NO.: 471) ACC chr3:179218303-179218305 (SEQ ID NO.: 472) GAG chr3:179218306-179218308 (SEQ ID NO.: 473) CAG chr3:179234296-179234298 (SEQ ID NO.: 474) CAT chr7:55160314-55160316 (SEQ ID NO.: 475) AGC chr7:140753335-140753337 (SEQ ID NO.: 476) CAC chr19:1223124-1223126 (SEQ ID NO.: 477) TTC chr7:7673801-7673803 (SEQ ID NO.: 478) ACG chr4:54727298-54727300 (SEQ ID NO.: 479) ATG chr7:116700207-116700209 (SEQ ID NO.: 480) AAC UNMUTATED AMINO ACID SEQUENCE (AA) SEQ ID NO.: 481 A SEQ ID NO.: 482 Q SEQ ID NO.: 483 G SEQ ID NO.: 484 G SEQ ID NO.: 485 R SEQ ID NO.: 486 A SEQ ID NO.: 487 K SEQ ID NO.: 488 Q SEQ ID NO.: 489 G SEQ ID NO.: 490 G SEQ ID NO.: 491 E SEQ ID NO.: 492 Q SEQ ID NO.: 493 H SEQ ID NO.: 494 S SEQ ID NO.: 495 V SEQ ID NO.: 496 F SEQ ID NO.: 497 R SEQ ID NO.: 498 M SEQ ID NO.: 499 N seq_plus_30 bp_padding (DNA Sequence) SEQ ID NO.: 500 ctgaaagctgtaccatacctgtctggtcttGGCtgaggtttcaatgaatggaatcccgtaact SEQ ID NO.: 501 gtattggtctctcatggcactgtactcttcTTGtccagctgtatccagtatgtccaacaaaca SEQ ID NO.: 502 tagctggattgtcagtgcgcttttcccaacACCacctgctccaaccaccaccagtttgtactc SEQ ID NO.: 503 ctggattgtcagtgcgcttttcccaacaccACCtgctccaaccaccaccagtttgtactcagt SEQ ID NO.: 504 caagaggccctagatttctatggggaagtaAGGaccagagacaaaaaggtaagttattttttg SEQ ID NO.: 505 tatttcagtgttacttacctgtcttgtcttTGCtgatgtttcaataaaaggaattccataact SEQ ID NO.: 506 tgtgtctactgttctagaaggcaaatcacaTTTatttcctactaggaccataggtacatcttc SEQ ID NO.: 507 gtactggtccctcattgcactgtactcctcTTGacctgctgtgtcgagaatatccaagagaca SEQ ID NO.: 508 tagctgtatcgtcaaggcactcttgcctacGCCaccagctccaactaccacaagtttatattc SEQ ID NO.: 509 ctgtatcgtcaaggcactcttgcctacgccACCagctccaactaccacaagtttatattcagt SEQ ID NO.: 510 tctacacgagatcctctctctgaaatcactGAGcaggagaaagattttctatggagtcacagg SEQ ID NO.: 511 acacgagatcctctctctgaaatcactgagCAGgagaaagattttctatggagtcacaggtaa SEQ ID NO.: 512 gagtatttcatgaaacaaatgaatgatgcaCATcatggtggctggacaacaaaaatggattgg SEQ ID NO.: 513 gggacctccggtcagaaaaccaaaattataAGCaacagaggtgaaaacagctgcagtaagtca SEQ ID NO.: 514 aaactgatgggacccactccatcgagatttCACtgtagctagaccaaaatcacctatttttac SEQ ID NO.: 515 ctgcacggcgcggacgaggacgaggacctcTTCgacatcgaggatgacatcatctacactcag SEQ ID NO.: 516 gcgccggtctctcccaggacaggcacaaacACGcacctcaaagctgttccgtcccagtagatt SEQ ID NO.: 517 atcgtagctggcatgatgtgcattattgtgATGattctgacctacaaatatttacaggtaacc SEQ ID NO.: 518 ttccctatcaaatatgtcaacgacttcttcAACaagatcgtcaacaaaaacaatgtgagatgt