NONHSAT137541

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XIST is the master regulator of mammalian X-chromosome inactivation (XCI) and act a tumor suppressor or an oncogene in different tumors.

Annotated Information

Name

Approved symbol: XIST

Approved name: X inactive specific transcript

HGNC ID: HGNC:12810

Previous names: X (inactive)-specific transcript; X (inactive)-specific transcript (non-protein coding); X inactive specific transcript (non-protein coding)

Alias symbols: NCRNA00001; DXS1089; swd66; LINC00001

Alias names: long intergenic non-protein coding RNA 1

RefSeq ID: NR_001564

LncBook ID: HSALNT0289343

Characteristics

XIST is a six-exon transcript of 19296 bp long non-coding RNA that is found in the X-inactivation center (Xic) at human chromosome Xq13.2 (HGNC). It Contains repeated sequence motifs A-F that are critical for its function. XIST expression initiates the process of XCI in mammals.

Function

XIST and its mouse homologue are involved in X-chromosome inactivation[1].

XIST is required to initiate XCI in mammals and functions as oncogene and tumor supressor [2][3][4][5].

Ectopic XIST expression from an autosomal transgene causes long-range gene repression [6][7]. XIST operates by interacting with loops of nearby chromosome, which a tight correlation with twists and turns close to where the XIST gene was located [7].

Reaching out. To silence genes on the X chromosome, XIST produces lncRNAs, which diffuse to nearby loops of DNA.[7]

XIST and RepA RNAs bind to and recruit PRC2, which catalyzes the deposition of the repressive chromatin mark H3K27me3 on the Xi [8][9][10][11][12]. Small RNAs formed from XIST/TSIX duplexes may play a role in regulating XIST expression and XCI [13]. However, loss of Dicer has only a modest effect on XIST expression [14]. Contrary to what would be expected if RNAi is a major regulator of XCI. hnRNP U (also known as SP120 or SAF-A) binds XIST through its RGG domain while the SAF domain is also required for localisation to the Xi. hnRNP U is required for both XIST localisation to the Xi and the initation of X-inactivation [15].

XIST Repeat C sequences are required for Xist localization to the Xi [16][17]. YY1 can interact with several DNA binding sites within exon 1 of XIST, and also to the repeat C (and perhaps repeat B) RNA sequences of the XIST transcript. Thus YY1 tethers XIST RNAs to the Xi and nucleates the XIST cloud that coats the Xi [18]. XIST forms a transcriptionally silenced sub-nuclear domain and perinucleolar localisation of the silent XIST coated chromosome has been observed [19][20]. The A region repeats are essential for the recruitment of late inactivated X genes to the silencing compartment and for the recruitment of the silencing complex PRC2 [21]. After the initiation of XCI, XIST function is not absolutely required to maintain XCI in fibroblasts [22]. Nor is continued XIST expression required to maintain XCI-like repression around an autosomal XIST transgene in male, differentiated ES cells [23]. However, lack of XIST function in differentiated cells can lead to partial reactivation of select X-linked genes [24]. XIST RNA is methylated at specific cytosines within the A-region,Potential relationship between cytosine methylation and functional properties of XIST RNA [25].

. Regulatory role opf XIST in cancer progression. [5]

XIST is dysregulated and acts as an oncogene or a tumor suppressor in different human malignancies. XIST is implicated in many aspects of carcinogenesis including tumor initiation, invasion, metastasis, apoptosis, cell cycle, stemness, autophagy, and drug resistance [5].

XIST served as a ceRNA in cervical cancer progression through modulating miR-200a/Fus axis [4].

Expression

XIST is expressed in all somatic cells in female eutherian mammals, monoallelically from the inactive X-chromosome (Xi) [26]. XIST is not expressed in males. XIST is a nuclear RNA that coats the Xi in females [27][28].

In mouse, Xist expression is imprinted at specific times and places in development: Xist is transcribed exclusively from the paternally-inherited X (and thus the paternal X is always the Xi) only in the early pre-implantation blastocyst, and later in development only in extra-embryonic tissues such as the placenta. Imprinted XCI in humans has not been demonstrated and may not exist [29]. In somatic tissues in mouse and human, XCI is random, not imprinted: either the paternal or maternal X can express XIST and become the Xi. This decision is made in each cell of the epiblast in the mouse, and the same X is inactivated in subsequent generations of daughter cells. Thus expression of XIST (and of nearly all X-linked genes) is mosaic, in the sense that each of the two alleles is active in different populations of cells. Stage specific expression in different regions of developing mouse retina, with Tsix displaying a similar but weaker profile [30].

In female undifferentiated mouse ES (embryonic stem) and iPS (induced pluripotent stem) cells, Xist is not expressed and both X chromosomes are active. In mouse iPSCs and ESCs, Xist expression and XCI strictly correlate with the pluripotent state. Differentiation of mouse ES cells results in the onset of Xist expression and XCI, and thus these cells are an important model system for the study of XCI. In contrast, XIST expression and XCI are variable in female undifferentiated human ES cells [31][32][33][34]and iPS cells [35][36][37][38][39], which may reflect variability in the broader epigenetic states and developmental potential of these cells.

In XIST, methylation of a fraction of the molecules may serve to functionally distinguish the methylated species from the bulk XIST RNA(e.g., by their PRC2-binding abilities). It is also possible that only one of the two RNA species that are transcribed from the XIST locus may be subject to methylation [25].

XIST was extremely overexpressed in cervical cancer tissues and cell lines [4].

XIST expression is significantly upregulated in hepatocellular carcinoma (HCC) tissues and cell lines, gastric cancer (GC), colorectal cancer (CRC), bladder cancer, pancreatic cancer (PC) tissues, non-small cell lung cancer (NSCLC) [5].

Conservation

XIST is present in all eutherian (placental) mammals examined to date, but it is not present in marsupials or monotremes [40][41][42][43]. An unrelated ncRNA in marsupials, Rsx, is likely to play a role similar to that of XIST in XCI [44]. The most conserved XIST RNA region, the A region, contains eight or nine repeats separated by U-rich spacers.

Regulation

The ubiquitous autosomal transcription factor, Yin-Yang 1 (YY1), plays an essential role in transcriptional activation of Xist in both human and mouse [45].

Associated components

The compact Xi structure, Barr body, in human inactive X chromosome (Xi) is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). XIST preferentially colocalizes with H3K27me3 domains. The molecular network involving HBiX1 and SMCHD1 links the H3K9me3 and XIST-H3K27me3 domains to organize the compact Xi structure [46].

Diseases

Trisomy 21 rescue. [47]
  • Bladder cancer [48]
  • Breast cancer [49]
  • Cervical cancer [4]
  • Colorectal cancer (CRC) [5]
  • gastric cancer (GC) [5]
  • Hepatocellular carcinoma (HCC) [5]
  • Non-small cell lung cancer (NSCLC) [5]
  • Pancreatic cancer (PC) [5]
  • Trisomy 21

Jeanne Lawrence and her colleagues restored normal gene expression in trisomy 21 cells by silencing the extra chromosome using XIST [50]. Working with pluripotent human stem cells created from people with Down syndrome, Lawrence used proteins that target specific cDNA sequences to place XIST on one of the copies of chromosome 21 [50]. This offers hope that some deleterious effects of the trisomy could be reversed to improve this incurable disease [47], but the prospect of using XIST to treat Down syndrome in humans—either in utero or adulthood—is still extremely remote [51].

Labs working on this lncRNA

  • Howard Hughes Medical Institute, Boston, MA 02114 USA[17][18][20].
  • Mammalian Developmental Epigenetic Group, UMR 218, Curie Institute, 75248 Paris Cedex 05, France[19].
  • Faculté des Sciences et Techniques, AREMS, Nancy Université, UMR 7214 CNRS-UHP 1, Vandoeuvre-lès-Nancy, France[21].
  • Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA[23].
  • Department of Genetics, Stanford University School of Medicine, California 94305[26][34].
  • Department of Human Genetics, Geffen School of Medicine, and Departments of Pathology and Laboratory Medicine and Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA[31].
  • ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, The Australian National University, Canberra, ACT 2601, Australia. timothy.hore@anu.edu.au[42].
  • MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK[44].
  • Departments of Pathology and Medicine, University of Washington, Seattle WA98115, USA[47].
  • Department of Cell and Developmental Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA[50].
  • Section of Comparative Biology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK [2].
  • Department of Obstetrics and Gynecology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No.1665, KongJiang Road, YangPu District, Shanghai, 200092, China [4]..

References

  1. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named ref51
  2. ↑ 2.0 2.1 Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N. Requirement for Xist in X chromosome inactivation.Nature. 1996 Jan 11;379(6561):131-7.
  3. ↑ Marahrens Y, Panning B, Dausman J, Strauss W, Jaenisch R. Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev. 1997 Jan 15;11(2):156-66.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Zhu H, Zheng T, Yu J, Zhou L, & Wang L. LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a[J]. Biomedicine & Pharmacotherapy. 2018, 105:789-797
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Yang Z, Jiang X, Jiang X & Zhao H. X-inactive-specific transcript: A long noncoding RNA with complex roles in human cancers[J]. Gene. 2018
  6. ↑ Wutz A, Jaenisch R. A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell. 2000 Apr;5(4):695-705.
  7. ↑ 7.0 7.1 7.2 Pennisi, E. 2013. "Long noncoding RNAs may alter chromosome's 3D structure." Science 340(6135): 910.
  8. ↑ Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.Science. 2008 Oct 31;322(5902):750-6.
  9. ↑ Kaneko S, Li G, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA.Genes Dev. 2010 Dec 1;24(23):2615-20.
  10. ↑ Kanhere A, Viiri K, Araújo CC, Rasaiyaah J, Bouwman RD, Whyte WA, Pereira CF, Brookes E, Walker K, Bell GW, Pombo A, Fisher AG, Young RA, Jenner RG. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol Cell. 2010 Jun 11;38(5):675-88.
  11. ↑ Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT. Genome-wide identification of polycomb-associated RNAs by RIP-seq.Mol Cell. 2010 Dec 22;40(6):939-53.
  12. ↑ Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M. Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nat Struct Mol Biol. 2012 Jun 3;19(7):664-70.
  13. ↑ Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. 2008 Jun 6;320(5881):1336-41.
  14. ↑ Kanellopoulou C, Muljo SA, Dimitrov SD, Chen X, Colin C, Plath K, Livingston DM. X chromosome inactivation in the absence of Dicer.Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1122-7.
  15. ↑ Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S. The matrix protein hnRNP U is required for chromosomal localization of Xist RNA.Dev Cell. 2010 Sep 14;19(3):469-76.
  16. ↑ Beletskii A, Hong YK, Pehrson J, Egholm M, Strauss WM. PNA interference mapping demonstrates functional domains in the noncoding RNA Xist.Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9215-20.
  17. ↑ 17.0 17.1 Sarma K, Levasseur P, Aristarkhov A, Lee JT. Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome.Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22196-201.
  18. ↑ 18.0 18.1 Jeon Y, Lee JT. YY1 tethers Xist RNA to the inactive X nucleation center.Cell. 2011 Jul 8;146(1):119-33.
  19. ↑ 19.0 19.1 Chaumeil J, Le Baccon P, Wutz A, Heard E. A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced.Genes Dev. 2006 Aug 15;20(16):2223-37.
  20. ↑ 20.0 20.1 Zhang LF, Huynh KD, Lee JT. Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing.Cell. 2007 May 18;129(4):693-706.
  21. ↑ 21.0 21.1 Maenner S, Blaud M, Fouillen L, Savoye A, Marchand V, Dubois A, Sanglier-Cianférani S, Van Dorsselaer A, Clerc P, Avner P, Visvikis A, Branlant C. 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol. 2010 Jan;8(1):e1000276.
  22. ↑ Csankovszki G, Panning B, Bates B, Pehrson JR, Jaenisch R. Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation.Nat Genet. 1999 Aug;22(4):323-4.
  23. ↑ 23.0 23.1 Wutz A, Jaenisch R. A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell. 2000 Apr;5(4):695-705.
  24. ↑ Csankovszki G, Nagy A, Jaenisch R. Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol. 2001 May 14;153(4):773-84.
  25. ↑ 25.0 25.1 Amort T, Soulière MF, Wille A, Jia XY, Fiegl H, Wörle H, Micura R, Lusser A. Long non-coding RNAs as targets for cytosine methylation. RNA Biol. 2013 Jun;10(6):1003-8.
  26. ↑ 26.0 26.1 Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991 Jan 3;349(6304):38-44.
  27. ↑ Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, Willard HF. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus.Cell. 1992 Oct 30;71(3):527-42.
  28. ↑ Clemson CM, McNeil JA, Willard HF, Lawrence JB. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure.J Cell Biol. 1996 Feb;132(3):259-75.
  29. ↑ Moreira de Mello JC, de Araújo ES, Stabellini R, Fraga AM, de Souza JE, Sumita DR, Camargo AA, Pereira LV. Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome. PLoS One. 2010 Jun 4;5(6):e10947.
  30. ↑ Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, Weber G, Lee K, Fraioli RE, Cho SH, Yung R, Asch E, Ohno-Machado L, Wong WH, Cepko CL. Moreira de Mello JC, de Araújo ES, Stabellini R, Fraga AM, de Souza JE, Sumita DR, Camargo AA, Pereira LV. PLoS Biol. 2004 Sep;2(9):E247.
  31. ↑ 31.0 31.1 Shen Y, Matsuno Y, Fouse SD, Rao N, Root S, Xu R, Pellegrini M, Riggs AD, Fan G. X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4709-14.
  32. ↑ Silva SS, Rowntree RK, Mekhoubad S, Lee JT. X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells.Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4820-5.
  33. ↑ Hall LL, Byron M, Butler J, Becker KA, Nelson A, Amit M, Itskovitz-Eldor J, Stein J, Stein G, Ware C, Lawrence JB. X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines that initiate as expected. J Cell Physiol. 2008 Aug;216(2):445-52.
  34. ↑ 34.0 34.1 Lengner CJ, Gimelbrant AA, Erwin JA, Cheng AW, Guenther MG, Welstead GG, Alagappan R, Frampton GM, Xu P, Muffat J, Santagata S, Powers D, Barrett CB, Young RA, Lee JT, Jaenisch R, Mitalipova M. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell.2010 May 28;141(5):872-83.
  35. ↑ Bruck T, Benvenisty N. Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells. Stem Cell Res. 2011 Mar;6(2):187-93.
  36. ↑ Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R.Bruck T1, Benvenisty N. Nature. 2009 Dec 3;462(7273):595-601.
  37. ↑ Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, Willard HF.The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus.Cell. 1992 Oct 30;71(3):527-42.
  38. ↑ Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR. Hanna J1, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R. Cell. 2010 Nov 12;143(4):527-39.
  39. ↑ Tchieu J, Kuoy E, Chin MH, Trinh H, Patterson M, Sherman SP, Aimiuwu O, Lindgren A, Hakimian S, Zack JA, Clark AT, Pyle AD, Lowry WE, Plath K. Female human iPSCs retain an inactive X chromosome.Cell Stem Cell. 2010 Sep 3;7(3):329-42.
  40. ↑ Duret L, Chureau C, Samain S, Weissenbach J, Avner P. The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science. 2006 Jun 16;312(5780):1653-5.
  41. ↑ Davidow LS, Breen M, Duke SE, Samollow PB, McCarrey JR, Lee JT. The search for a marsupial XIC reveals a break with vertebrate synteny. Chromosome Res. 2007;15(2):137-46.
  42. ↑ 42.0 42.1 Hore TA, Koina E, Wakefield MJ, Marshall Graves JA. The region homologous to the X-chromosome inactivation centre has been disrupted in marsupial and monotreme mammals. Chromosome Res. 2007;15(2):147-61.
  43. ↑ Shevchenko AI, Zakharova IS, Elisaphenko EA, Kolesnikov NN, Whitehead S, Bird C, Ross M, Weidman JR, Jirtle RL, Karamysheva TV, Rubtsov NB, VandeBerg JL, Mazurok NA, Nesterova TB, Brockdorff N, Zakian SM. Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials. Chromosome Res. 2007;15(2):127-36.
  44. ↑ 44.0 44.1 Grant J, Mahadevaiah SK, Khil P, Sangrithi MN, Royo H, Duckworth J, McCarrey JR, VandeBerg JL, Renfree MB, Taylor W, Elgar G, Camerini-Otero RD, Gilchrist MJ, Turner JM. Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature. 2012 Jul 12;487(7406):254-8.
  45. ↑ Makhlouf M, Ouimette JF1, Oldfield A1, Navarro P2, Neuillet D1, Rougeulle C1. A prominent and conserved role for YY1 in Xist transcriptional activation. Nat Commun. 2014 Sep 11;5:4878.
  46. ↑ Nozawa, R. S., et al. 2013. "Human inactive X chromosome is compacted through a PRC2-independent SMCHD1-HBiX1 pathway." Nat Struct Mol Biol 20(5): 566-573.
  47. ↑ 47.0 47.1 47.2 Disteche CM. How to correct chromosomal trisomy. Cell Res. 2013 Dec;23(12):1345-6. doi: 10.1038/cr.2013.135.
  48. ↑ Wang F, Li X, Xie X, Zhao L, Chen W. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 2008;582:1919–1927
  49. ↑ Sirchia, S.M., et al., Misbehaviour of XIST RNA in breast cancer cells. (1932-6203 (Electronic))
  50. ↑ 50.0 50.1 50.2 Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, Carone DM, Carone BR, Shivak DA, Guschin DY, Pearl JR, Rebar EJ, Byron M, Gregory PD, Brown CJ, Urnov FD, Hall LL, Lawrence JB. Translating dosage compensation to trisomy 21. Nature. 2013 Aug 15;500(7462):296-300. doi: 10.1038/nature12394.
  51. ↑ Underwood E. Can Down syndrome be treated? .Science. 2014 Feb 28;343(6174):964-7.

Sequence

>gi|7503|ref|NR_001564.2| Homo sapiens X inactive specific transcript (XIST), long non-coding RNA

000001 CCTTCAGTTC TTAAAGCGCT GCAATTCGCT GCTGCAGCCA TATTTCTTAC TCTCTCGGGG CTGGAAGCTT CCTGACTGAA 000080
000081 GATCTCTCTG CACTTGGGGT TCTTTCTAGA ACATTTTCTA GTCCCCCAAC ACCCTTTATG GCGTATTTCT TTAAAAAAAT 000160
000161 CACCTAAATT CCATAAAATA TTTTTTTAAA TTCTATACTT TCTCCTAGTG TCTTCTTGAC ACGTCCTCCA TATTTTTTTA 000240
000241 AAGAAAGTAT TTGGAATATT TTGAGGCAAT TTTTAATATT TAAGGAATTT TTCTTTGGAA TCATTTTTGG TTGACATCTC 000320
000321 TGTTTTTTGT GGATCAGTTT TTTACTCTTC CACTCTCTTT TCTATATTTT GCCCATCGGG GCTGCGGATA CCTGGTTTTA 000400
000401 TTATTTTTTC TTTGCCCAAC GGGGCCGTGG ATACCTGCCT TTTAATTCTT TTTTATTCGC CCATCGGGGC CGCGGATACC 000480
000481 TGCTTTTTAT TTTTTTTTCC TTAGCCCATC GGGGTATCGG ATACCTGCTG ATTCCCTTCC CCTCTGAACC CCCAACACTC 000560
000561 TGGCCCATCG GGGTGACGGA TATCTGCTTT TTAAAAATTT TCTTTTTTTG GCCCATCGGG GCTTCGGATA CCTGCTTTTT 000640
000641 TTTTTTTTAT TTTTCCTTGC CCATCGGGGC CTCGGATACC TGCTTTAATT TTTGTTTTTC TGGCCCATCG GGGCCGCGGA 000720
000721 TACCTGCTTT GATTTTTTTT TTTCATCGCC CATCGGTGCT TTTTATGGAT GAAAAAATGT TGGTTTTGTG GGTTGTTGCA 000800
000801 CTCTCTGGAA TATCTACACT TTTTTTTGCT GCTGATCATT TGGTGGTGTG TGAGTGTACC TACCGCTTTG GCAGAGAATG 000880
000881 ACTCTGCAGT TAAGCTAAGG GCGTGTTCAG ATTGTGGAGG AAAAGTGGCC GCCATTTTAG ACTTGCCGCA TAACTCGGCT 000960
000961 TAGGGCTAGT CGTTTGTGCT AAGTTAAACT AGGGAGGCAA GATGGATGAT AGCAGGTCAG GCAGAGGAAG TCATGTGCAT 001040
001041 TGCATGAGCT AAACCTATCT GAATGAATTG ATTTGGGGCT TGTTAGGAGC TTTGCGTGAT TGTTGTATCG GGAGGCAGTA 001120
001121 AGAATCATCT TTTATCAGTA CAAGGGACTA GTTAAAAATG GAAGGTTAGG AAAGACTAAG GTGCAGGGCT TAAAATGGCG 001200
001201 ATTTTGACAT TGCGGCATTG CTCAGCATGG CGGGCTGTGC TTTGTTAGGT TGTCCAAAAT GGCGGATCCA GTTCTGTCGC 001280
001281 AGTGTTCAAG TGGCGGGAAG GCCACATCAT GATGGGCGAG GCTTTGTTAA GTGGTTAGCA TGGTGGTGGA CATGTGCGGT 001360
001361 CACACAGGAA AAGATGGCGG CTGAAGGTCT TGCCGCAGTG TAAAACATGG CGGGCCTCTT TGTCTTTGCT GTGTGCTTTT 001440
001441 CGTGTTGGGT TTTGCCGCAG GGACAATATG GCAGGCGTTG TCATATGTAT ATCATGGCTT TTGTCACGTG GACATCATGG 001520
001521 CGGGCTTGCC GCATTGTTAA AGATGGCGGG TTTTGCCGCC TAGTGCCACG CAGAGCGGGA GAAAAGGTGG GATGGACAGT 001600
001601 GCTGGATTGC TGCATAACCC AACCAATTAG AAATGGGGGT GGAATTGATC ACAGCCAATT AGAGCAGAAG ATGGAATTAG 001680
001681 ACTGATGACA CACTGTCCAG CTACTCAGCG AAGACCTGGG TGAATTAGCA TGGCACTTCG CAGCTGTCTT TAGCCAGTCA 001760
001761 GGAGAAAGAA GTGGAGGGGC CACGTGTATG TCTCCCAGTG GGCGGTACAC CAGGTGTTTT CAAGGTCTTT TCAAGGACAT 001840
001841 TTAGCCTTTC CACCTCTGTC CCCTCTTATT TGTCCCCTCC TGTCCAGTGC TGCCTCTTGC AGTGCTGGAT ATCTGGCTGT 001920
001921 GTGGTCTGAA CCTCCCTCCA TTCCTCTGTA TTGGTGCCTC ACCTAAGGCT AAGTATACCT CCCCCCCCAC CCCCCAACCC 002000
002001 CCCCAACTCC CCACCCCCAC CCCCCACCCC CCACCTCCCC ACCCCCCTAC CCCCCTACCC CCCTACCCCC CTCTGGTCTG 002080
002081 CCCTGCACTG CACTGTTGCC ATGGGCAGTG CTCCAGGCCT GCTTGGTGTG GACATGGTGG TGAGCCGTGG CAAGGACCAG 002160
002161 AATGGATCAC AGATGATCGT TGGCCAACAG GTGGCAGAAG AGGAATTCCT GCCTTCCTCA AGAGGAACAC CTACCCCTTG 002240
002241 GCTAATGCTG GGGTCGGATT TTGATTTATA TTTATCTTTT GGATGTCAGT CATACAGTCT GATTTTGTGG TTTGCTAGTG 002320
002321 TTTGAATTTA AGTCTTAAGT GACTATTATA GAAATGTATT AAGAGGCTTT ATTTGTAGAA TTCACTTTAA TTACATTTAA 002400
002401 TGAGTTTTTG TTTTGAGTTC CTTAAAATTC CTTAAAGTTT TTAGCTTCTC ATTACAAATT CCTTAACCTT TTTTTGGCAG 002480
002481 TAGATAGTCA AAGTCAAATC ATTTCTAATG TTTTAAAAAT GTGCTGGTCA TTTTCTTTGA AATTGACTTA ACTATTTTCC 002560
002561 TTTGAAGAGT CTGTAGCACA GAAACAGTAA AAAATTTAAC TTCATGACCT AATGTAAAAA AGAGTGTTTG AAGGTTTACA 002640
002641 CAGGTCCAGG CCTTGCTTTG TTCCCATCCT TGATGCTGCA CTAATTGACT AATCACCTAC TTATCAGACA GGAAACTTGA 002720
002721 ATTGCTGTGG TCTGGTGTCC TCTATTCAGA CTTATTATAT TGGAGTATTT CAATTTTTCG TTGTATCCTG CCTGCCTAGC 002800
002801 ATCCAGTTCC TCCCCAGCCC TGCTCCCAGC AAACCCCTAG TCTAGCCCCA GCCCTACTCC CACCCCGCCC CAGCCCTGCC 002880
002881 CCAGCCCCAG TCCCCTAACC CCCCAGCCCT AGCCCCAGTC CCAGTCCTAG TTCCTCAGTC CCGCCCAGCT TCTCTCGAAA 002960
002961 GTCACTCTAA TTTTCATTGA TTCAGTGCTC AAAATAAGTT GTCCATTGCT TATCCTATTA TACTGGGATA TTCCGTTTAC 003040
003041 CCTTGGCATT GCTGATCTTC AGTACTGACT CCTTGACCAT TTTCAGTTAA TGCATACAAT CCCATTTGTC TGTGATCTCA 003120
003121 GGACAAAGAA TTTCCTTACT CGGTACGTTG AAGTTAGGGA ATGTCAATTG AGAGCTTTCT ATCAGAGCAT TATTGCCCAC 003200
003201 AATTTGAGTT ACTTATCATT TTCTCGATCC CCTGCCCTTA AAGGAGAAAC CATTTCTCTG TCATTGCTTC TGTAGTCACA 003280
003281 GTCCCAATTT TGAGTAGTGA TCTTTTCTTG TGTACTGTGT TGGCCACCTA AAACTCTTTG CATTGAGTAA AATTCTAATT 003360
003361 GCCAATAATC CTACCCATTG GATTAGACAG CACTCTGAAC CCCATTTGCA TTCAGCAGGG GGTCGCAGAC AACCCGTCTT 003440
003441 TTGTTGGACA GTTAAAATGC TCAGTCCCAA TTGTCATAGC TTTGCCTATT AAACAAAGGC ACCCTACTGC GCTTTTTGCT 003520
003521 GTGCTTCTGG AGAATCCTGC TGTTCTTGGA CAATTAAAGA ACAAAGTAGT AATTGCTAAT TGTCTCACCC ATTAATCATG 003600
003601 AAGACTACCA GTCGCCCTTG CATTTGCCTT GAGGCAGCGC TGACTACCTG AGATTTAAGA GTTTCTTAAA TTATTGAGTA 003680
003681 AAATCCCAAT TATCCATAGT TCTGTTAGTT ACACTATGGC CTTTGCAAAC ATCTTTGCAT AACAGCAGTG GGACTGACTC 003760
003761 ATTCTTAGAG CCCCTTCCCT TGGAATATTA ATGGATACAA TAGTAATTAT TCATGGTTCT GCGTAACAGA GAAGACCCAC 003840
003841 TTATGTGTAT GCCTTTATCA TTGCTCCTAG ATAGTGTGAA CTACCTACCA CCTTGCATTA ATATGTAAAA CACTAATTGC 003920
003921 CCATAGTCCC ACTCATTAGT CTAGGATGTC CTCTTTGCCA TTGCTGCTGA GTTCTGACTA CCCAAGTTTC CTTCTCTTAA 004000
004001 ACAGTTGATA TGCATAATTG CATATATTCA TGGTTCTGTG CAATAAAAAT GGATTCTCAC CCCATCCCAC CTTCTGTGGG 004080
004081 ATGTTGCTAA CGAGTGCAGA TTATTCAATA ACAGCTCTTG AACAGTTAAT TTGCACAGTT GCAATTGTCC AGAGTCCTGT 004160
004161 CCATTAGAAA GGGACTCTGT ATCCTATTTG CACGCTACAA TGTGGGCTGA TCACCCAAGG ACTCTTCTTG TGCATTGATG 004240
004241 TTCATAATTG TATTTGTCCA CGATCTTGTG CACTAACCCT TCCACTCCCT TTGTATTCCA GCAGGGGACC CTTACTACTC 004320
004321 AAGACCTCTG TACTAGGACA GTTTATGTGC ACAATCCTAA TTGATTAGAA CTGAGTCTTT TATATCAAGG TCCCTGCATC 004400
004401 ATCTTTGCTT TACATCAAGA GGGTGCTGGT TACCTAATGC CCCTCCTCCA GAAATTATTG ATGTGCAAAA TGCAATTTCC 004480
004481 CTATCTGCTG TTAGTCTGGG GTCTCATCCC CTCATATTCC TTTTGTCTTA CAGCAGGGGG TACTTGGGAC TGTTAATGCG 004560
004561 CATAATTGCA ATTATGGTCT TTTCCATTAA ATTAAGATCC CAACTGCTCA CACCCTCTTA GCATTACAGT AGAGGGTGCT 004640
004641 AATCACAAGG ACATTTCTTT TGTACTGTTA ATGTGCTACT TGCATTTGTC CCTCTTCCTG TGCACTAAAG ACCCCACTCA 004720
004721 CTTCCCTAGT GTTCAGCAGT GGATGACCTC TAGTCAAGAC CTTTGCACTA GGATAGTTAA TGTGAACCAT GGCAACTGAT 004800
004801 CACAACAATG TCTTTCAGAT CAGATCCATT TTATCCTCCT TGTTTTACAG CAAGGGATAT TAATTACCTA TGTTACCTTT 004880
004881 CCCTGGGACT ATGAATGTGC AAAATTCCAA TGTTCATGGT CTCTCCCTTT AAACCTATAT TCTACCCCTT TTACATTATA 004960
004961 GAAAGGGATG CTGGAAACCC AGAGTCCTTC TCTTGGGACT CTTAATGTGT ATTTCTAATT ATCCATGACT CTTAATGTGC 005040
005041 ATATTTTCAA TTGCCTAATT GATTTCAATT GTCTAAGACA TTTCAAATGT CTAATTGATT AGAACTGAGT CTTTTATATC 005120
005121 AAGCTAATAT CTAGCTTTTA TATCAAGCTA ATATCTTGAC TTCTCAGCAT CATAGAAGGG GGTACTGATT TCCTAAAGTC 005200
005201 TTTCTTGAAT TTCTATTATG CAAAATTGCC CTGAGGCCGG GTGTGGTGGC TCACACCTGT AATCCCAGCA CTTTGGGAGG 005280
005281 CTGAGGTGGG AAGATCCCTT ACTGCCAGGA GTTTGAGACC AGCCTGGCCA ACATTAAAAA AAAAAAAAAG TAAGACAATT 005360
005361 GCCCTGGAAT CCCATCCCCC TCACACCTCC TTGGCAAAGC AGCAGGAGTG CTAACTAGCT AGTGCTTCTT CTCTTATACT 005440
005441 GCTTAAATGC GCATAATTAG CAGTAGTTGA TGTGCCCCTA TGTTAGAGTA GAATCCCGCT TCCTTGCTCC ATTTGCATTA 005520
005521 CTGCAGGAGC TTCTAACTAG CCTGAATTCA CTCTCTTGGA CTGTTAATGT GCATACTTAT ATTTGCTGCT GTACTTTTTT 005600
005601 ACCATGTAAG GACCCCACCC ACTGTATTTA CATCCCAGCT GGAAGTACCT ACTACTTAAG ACCCTTAGAC TAGTAAAGTT 005680
005681 AGCGTGCATA ATCTTAGGTG TTATATACAC ATTTTCAGTT GCATACAGTT GTGCCTTTTA TCAGGACTCC TGTACTTATC 005760
005761 AAAGCAGAGA GTGCTAATCA ATATTAAGCC CTTCTCTTCG AACTGTAGAT GGCATGTAAT TGCAGTTGTC AATGGTCCTT 005840
005841 CAATTAGACT TGGGTTTCTG ACCTATCACA CCCTCTTTGC TTTATTGCAT GGGGTACTAT TCACTTAAGG CCCCTTTCTC 005920
005921 AAACTGTTAA TGTGCCTAAT GACAATTACA TCAGTATCCT TCCTTTTGAA GGACAGCATG GTTGGTGACA CCTAAGGCCC 006000
006001 CATTTCTTGG CCTCCCAATA TGTGTGATTG TATTTGTCGA GGTTGCTATG CACTAGAGAA GGAAAGTGCT CCCCTCATCC 006080
006081 CCACTTTTCC CTTCCAGCAG GAAGTGCCCA CCCCATAAGA CCCTTTTATT TGGAGAGTCT AGGTGCACAA TTGTAAGTGA 006160
006161 CCACAAGCAT GCATCTTGGA CATTTATGTG CGTAATCGCA CACTGCTCAT TCCATGTGAA TAAGGTCCTA CTCTCCGACC 006240
006241 CCTTTTGCAA TACAGAAGGG TTGCTGATAA CGCAGTCCCC TTTTCTTGGC ATGTTGTGTG TGATTATAAT CGTCTGGGAT 006320
006321 CCTATGCACT AGAAAAGGAG GGTCCTCTCC ACATACCTCA GTCTCACCTT TCCCTTCCAG CAGGGAGTGC CCACTCCATA 006400
006401 AGACTCTCAC ATTTGGACAG TCAAGGTGCG TAATTGTTAA GTGAACACAA CCATGCACCT TAGACATGGA TTTGCATAAC 006480
006481 TACACACAGC TCAACCTATC TGAATAAAAT CCTACTCTCA GACCCCTTTT GCAGTACAGC AGGGGTGCTG ATCACCAAGG 006560
006561 CCCTTTTTCC TGGCCTGGTA TGCGTGTGAT TATGTTTGTC CCGGTTCCTG TGTATTAGAC ATGGAAGCCT CCCCTGCCAC 006640
006641 ACTCCACCCC CAATCTTCCT TTCCCTTCCG GCAGGGAGTG CCCTCTCCAT AAGACGCTTA CGTTTGGACA ATCAAGGTGC 006720
006721 ACAGTTGTAA GTGACCACAG GCATACACCT TGGACATTAA TGTGCATAAC CACTTTGCCC ATTCCATCTG AATAAGGTCC 006800
006801 TACTCTCAGA CCCCTTTTGC AGTACAGCAG GGGTGCTGAT CACCAAGGCC CCTTTTCTTG GCCTGTTATG TGCGTGATTA 006880
006881 TATTTGTCTG GGTTCCTGTG TATTAGACAA GGAAGCCTTC CCCCCGCCCC CACCCCCACT CCCAGTCTTC CTTTCCCTTC 006960
006961 CAGCAGGGAG TGCCCCCTCC ATAAGATCAT TACATTTGGA CAATCAAGGT GCACAATTAT AAGTGACCAC AGCCATGCAC 007040
007041 CTTGGACATT ATTGGACATT AATGTGCGTA ACTGCACATG GCCCATCCCA TCTGAATAAG GTCCTACTCT CAGATGCCCT 007120
007121 TTGCAGTACA GCAGGGGTAC TGAATCACCA AGGCCCTTTT TCTTGGCCTG TTATGTGTGT GATTATATTT ATCCCAGTTT 007200
007201 CTGTGTAATA GACATGAAAG CCTCCCCTGC CACACCCCAC CTCCAATCTT CCTTTCCCTT CCACCAGGGA GTGTCCACTC 007280
007281 CATATACCCT TACATTTGGA CAATCAAGGT GCACAATTGT AAGTGAGCAT AGGCACTCAC CTTGGACATG AATGTGCATA 007360
007361 ACTGCACATG GCCCATCCCA TCTGAATAAG GTCCTACTCT CAGACCCTTT TTGCAGTACA GCAGGGGTGC TGATCACCAA 007440
007441 GGCCCCTTTT CCTGGCCTGT TATGTGTGTG ATTATATTTG TTCCAGTTCC TGTGTAATAG ACATGGAAGC CTCCCCTGCC 007520
007521 ACACTCCACC CCCAATCTTC CTTTCCCTTC TGGCAGGAAG TACCCGCTCC ATAAGACCCT TACATTTGGA CAGTCAAGGT 007600
007601 GCACAATTGT ATGTGACCAC AACCATGCAC CTTGGACATA AATGTGTGTA ACTGCACATG GCCCATCCCA TCTGAATAAG 007680
007681 GTCCTACTCT CAGACCCCTT TTGCAGTACA GTAGGTGTGC TGATAACCAA GGCCCCTCTT CCTGGCCTGT TAACGTATGT 007760
007761 GATTATATTT GTCTGGGTTC CAGTGTATAA GACATGGAAG CCTCCCCTGC CCCACCCCAC CCTCAATCTT CCTTTCCCTT 007840
007841 CTGGCAGGGA GTGCCAGCTC CATAAGAACC TTACATTTGG ACAGTCAAGG TGCACAATTC TAAGTGACCG CAGCCATGCA 007920
007921 CCTTGGTCAA TAATGTGTGT AACTGCACAC GGCCTATCTC ATCTGAATAA GGCCTTACTC TCAGACCCCT TTTGCAGTAC 008000
008001 AGCAGGGGTG CTGATAACCA AGGCCCATTT TCCTGGCCTG TTATGTGTGT GATTATATTT GTCCAGGTTT CTGTGTACTA 008080
008081 GACAAGGAAG CCTCCTCTGC CCCATCCCAT CTACGCATAA TCTTTCTTTT CCTCCCAGCA GGGAGTGCTC ACTCCATAAG 008160
008161 ACCCTTACAT TTGGACAATC AAGGTGCACA ATTGTAAGTG ACCACAACCA TGCATCTTGG AAATTTATGT GCATAACTGC 008240
008241 ACATGGCTTA TCCTATTTGA ATAAAGTCCT ACTCTCAGAC CCCCTTTGCA GTATAGCTGG GGTGCTGATC ACTGAGGCCT 008320
008321 CTTTGCTTGG CTTGTCTATA TTCTTGTGTA CTAGATAAGG GCACCTTCTC ATGGACTCCC TTTGCTTTTC AACAAGGAGT 008400
008401 ACCCACTACT TTTTAAGATT CTTATATTTG TCCAAAGTAC ATGGTTTTAA TTGACCACAA CAATGTCCCT TGGACATTAA 008480
008481 TGTATGTAAT CACCACATGG TTCATCCTAA TTAAACAAAG TTCTACCTTC TCACCCTCCA TTTGCAGTAT ACCAGGGTTG 008560
008561 CTGACCCCCT AAGTCCCCTT TTCTTGGCTT GTTGACATGC ATAATTGCAT TTATGTTGGT TCTTGTGCCC TAGACAAGGA 008640
008641 TGCCCCACCT CTTTTCAATA GTGGGTGCCC ACTCCTTATG ATCTTTACAT TTGAACAGTT AATGTGAATA ATTGCAGTTG 008720
008721 TCCACAACCC TATCACTTCT AGGACCATTA TACCTCTTTT GCATTACTGT GGGGTATACT GTTTCCCTCC AAGGCCCCTT 008800
008801 CTGGTGGACT ATCAACATAT AATTGAAATT TTCTTTTGTC TTTGTCAGTA GATTAAGGTC ATACCCCATC ACCTTTCCTT 008880
008881 TGTAGTACAA CAGGGTGTCC TGATCAACCA AAGTCCTGTT GTTTTGGACT GTTAATATGT GCAATTACAT TTGCTCCTGA 008960
008961 TCTGTGCACT AGATAAGGAT CCTACCTACT TTCTTAGTGT TTTTAGCAGG TAGTGCCCAC TACTCAAGAC TGTCACTTGG 009040
009041 AATGTTCATG TGCACAAACT CAATTCTCTA AGCATGTTCC TGTACCACCT TTGCTTTAGA GCAGGGGGAT GATATTCACT 009120
009121 AAGTGCCCCT TCTTTTGGAC TTAATATGCA TTAATGCAAT TGTCCACCTC TTCTTTTAGA CTAAGAGTTG ATCTCCACAT 009200
009201 ATTCCCCTTG CATCAGGGGC ATGTTAATTA TGAATGAACC CTTTTCTTTT AATATTAATG TCATAATTGT ATTTGTGGAC 009280
009281 CTGTGTAGGA GAAAAAGACC CTATGTTCCT CCCATTACCC TTTGGATTGC TGCTGAGAAG TGTTAACTAC TCATAATCTC 009360
009361 AGCTCTTGGA CAATTAATAG CATTAATAAC AATTATCAAG GGCACTGATC ATTAGATAAG ACTCCTGCTT CCTCGTTGCT 009440
009441 TACATCGGGG GTACTGACCC ACTAAGGCCC CTTGTACTGT TAATGTGAAT ATTTGCAATT ATATATGTCT CCTTCTGGTA 009520
009521 GAGTGGGATA TTATGCCCTA GTATCCCCTT TGCATTACTG CAGGGGCTGC TGACTACTCA AAACTTCTCC TGGGACTGTT 009600
009601 AATAGGCACA ATGGCAGTTA TCAATGGTTT TCTCCCTCCC TGACCTTGTT AAGCAAGCGC CCCACCCCAC CCTTAGTTTC 009680
009681 CCATGGCATA ATAAAGTATA AGCATTGGAG TATTCCATGC ACTTGTCTAT CAAACAGTGG TCCATACTCC CAACCCTTTT 009760
009761 GCATTGCGCC AGTGTGTAAA ATCACAGGTA GCCATGGTGT CATGCTTTAT ATACGAAGTC TTCCCTCTCT CTGCCCCTTG 009840
009841 TGTGCCCTTG GCCCCTTTTT ACAGACTATT GCTCACAATC TCAGGTGTCC ATATTTGCAG CTATTAGGTA AGATTGTGCT 009920
009921 GTCTCCCTCT TCCCTTCCCT CTGCCCTGCC CCTTTTGCCT CTTTGCTGGG TAATGTTGAC CAGACAAGGC CCTTTCTCTT 010000
010001 GGACTTAAAC AATTCTCAGT TGCACTTTCC TTGGTCCCAC CCATTATACA TGAACCCCTC TACTTCCTTT CGCATTGCTT 010080
010081 CTGAGTATGC TGACTACCCA AAGCCCCTTC TGTGTTATTA ATAAACACAG TACTGATTGT CCCATTTTTC AGCCCATCAG 010160
010161 TCCAAGATCT CCCTACCACT TTGGTGTGTT GGTGCAGTGT TGACTATGAA AAGCAGGCCT GAACTAGGTG GATAAGCCTT 010240
010241 CACTCATTTT CTTTCATTTA TTAATGATCC TAGTTTCAAT TATTGTCAGA TTCTGGGGAC AAGAACCATT CTTGCCCACC 010320
010321 TGTGTTACTG CTTTACTGTG CAAAATACTG AAGGCAAGTC AGACCCAGGG AGCTGGATTG CCATCCTTTA TTTTGTGTTT 010400
010401 CCAGTGTACA CTATAAAATT GTCTCCCCAG GAAGGAAGGT TGGCACTTTC TCTGCATTCT TCTTTCCAGA GCAGATTGCC 010480
010481 TGGTTAAGAA TCTCTTGTTG TCCCCTTTGT ATATTGTTAT TGTAAAGTGC CAAATGCCAG GATACAGCCA GAAAAATTGC 010560
010561 TTATTATTAT TAAAAAAATT TTTTTAAGAA AGACATCTGG ATTGTAGGGT GGACTCGATA ACCTGGTCAT TATTTTTTTG 010640
010641 AAGCCAAAAT ATCCATTTAT ACTATGTACC TGGTGACCAG TGTCTCTCAT TTTAACTGAG GGTGGTGGGT CTGTGGATAG 010720
010721 AACACTGACT CTTGCTATTT TAATATCAAA GATATTCTAG AGTGGAACTC TTAAGACCAG TATCTTTGTG TGGGCTTTAC 010800
010801 CAGCATTCAC TTTTAGAAAA ACTACCTAAA TTTTATAATC CTTTAATTTC TTCATCTGGA GCACCTGCCC CTACTTATTT 010880
010881 CAAGAAGATT GCAGTAAAAC GATTAAATGA GGGAACATAT GCAGAGGTGC TTTTAAAAAG CATATGCCAC CTTTTTTATT 010960
010961 AATTATTATA TAAAATGAAG CATTTAATTA TAGTAATAAT TTGAAGTAGT TTGAAGTACC ACACTGAGGT GAGGACTTAA 011040
011041 AAATGATAAG ACGAGTTCCC TATTTTATAA GAAAAATAAG CCAAAATTAA ATATTCTTTT GGATATAAAT TTCAACAGTG 011120
011121 AGATAGCTGC CTAGTGGAAA TGAATAATAT CCCAGCCACT AGTGTACAGG GTGTTTTGTG GCACAGGATT ATGTAATATG 011200
011201 GAACTGCTCA AGCAAATAAC TAGTCATCAC AACAGCAGTT CTTTGTAATA ACTGAAAAAG AATATTGTTT CTCGGAGAAG 011280
011281 GATGTCAAAA GATCGGCCCA GCTCAGGGAG CAGTTTGCCC TACTAGCTCC TCGGACAGCT GTAAAGAAGA GTCTCTGGCT 011360
011361 CTTTAGAATA CTGATCCCAT TGAAGATACC ACGCTGCATG TGTCCTTAGT AGTCATGTCT CCTTAGGCTC CTCTTGGACA 011440
011441 TTCTGAGCAT GTGAGACCTG AGGACTGCAA ACAGCTATAA GAGGCTCCAA ATTAATCATA TCTTTCCCTT TGAGAATCTG 011520
011521 GCCAAGCTCC AGCTAATCTA CTTGGATGGG TTGCCAGCTA TCTGGAGAAA AAGATCTTCC TCAGAAGAAT AGGCTTGTTG 011600
011601 TTTTACAGTG TTAGTGATCC ATTCCCTTTG ACGATCCCTA GGTGGAGATG GGGCATGAGG ATCCTCCAGG GGAAAAGCTC 011680
011681 ACTACCACTG GGCAACAACC CTAGGTCAGG AGGTTCTGTC AAGATACTTT CCTGGTCCCA GATAGGAAGA TAAAGTCTCA 011760
011761 AAAACAACCA CCACACGTCA AGCTCTTCAT TGTTCCTATC TGCCAAATCA TTATACTTCC TACAAGCAGT GCAGAGAGCT 011840
011841 GAGTCTTCAG CAGGTCCAAG AAATTTGAAC ACACTGAAGG AAGTCAGCCT TCCCACCTGA AGATCAACAT GCCTGGCACT 011920
011921 CTAGCACTTG AGGATAGCTG AATGAATGTG TATTTCTTTG TCTCTTTCTT TCTTGTCTTT GCTCTTTGTT CTCTATCTAA 012000
012001 AGTGTGTCTT ACCCATTTCC ATGTTTCTCT TGCTAATTTC TTTCGTGTGT GCCTTTGCCT CATTTTCTCT TTTTGTTCAC 012080
012081 AAGAGTGGTC TGTGTCTTGT CTTAGACATA TCTCTCATTT TTCATTTTGT TGCTATTTCT CTTTGCTCTC CTAGATGTGG 012160
012161 CTCTTCTTTC ACGCTTTATT TCATGTCTCC TTTTTGGGTC ACATGCTGTG TGCTTTTTGT CCTTTTCTTG TTCTGTCTAC 012240
012241 CTCTCCTTTC TCTGCCTACC TCTCTTTTCT CTTTGTGAAC TGTGATTATT TGTTACCCCT TCCCCTTCTC GTTCGTTTTA 012320
012321 AATTTCACCT TTTTTCTGAG TCTGGCCTCC TTTCTGCTGT TTCTACTTTT TATCTCACAT TTCTCATTTC TGCATTTCCT 012400
012401 TTCTGCCTCT CTTGGGCTAT TCTCTCTCTC CTCCCCTGCG TGCCTCAGCA TCTCTTGCTG TTTGTGATTT TCTATTTCAG 012480
012481 TATTAATCTC TGTTGGCTTG TATTTGTTCT CTGCTTCTTC CCTTTCTACT CACCTTTGAG TATTTCAGCC TCTTCATGAA 012560
012561 TCTATCTCCC TCTCTTTGAT TTCATGTAAT CTCTCCTTAA ATATTTCTTT GCATATGTGG GCAAGTGTAC GTGTGTGTGT 012640
012641 GTCATGTGTG GCAGAGGGGC TTCCTAACCC CTGCCTGATA GGTGCAGAAC GTCGGCTATC AGAGCAAGCA TTGTGGAGCG 012720
012721 GTTCCTTATG CCAGGCTGCC ATGTGAGATG ATCCAAGACC AAAACAAGGC CCTAGACTGC AGTAAAACCC AGAACTCAAG 012800
012801 TAGGGCAGAA GGTGGAAGGC TCATATGGAT AGAAGGCCCA AAGTATAAGA CAGATGGTTT GAGACTTGAG ACCCGAGGAC 012880
012881 TAAGATGGAA AGCCCATGTT CCAAGATAGA TAGAAGCCTC AGGCCTGAAA CCAACAAAAG CCTCAAGAGC CAAGAAAACA 012960
012961 GAGGGTGGCC TGAATTGGAC CGAAGGCCTG AGTTGGATGG AAGTCTCAAG GCTTGAGTTA GAAGTCTTAA GACCTGGGAC 013040
013041 AGGACACATG GAAGGCCTAA GAACTGAGAC TTGTGACACA AGGCCAACGA CCTAAGATTA GCCCAGGGTT GTAGCTGGAA 013120
013121 GACCTACAAC CCAAGGATGG AAGGCCCCTG TCACAAAGCC TACCTAGATG GATAGAGGAC CCAAGCGAAA AAGGTATCTC 013200
013201 AAGACTAACG GCCGGAATCT GGAGGCCCAT GACCCAGAAC CCAGGAAGGA TAGAAGCTTG AAGACCTGGG GAAATCCCAA 013280
013281 GATGAGAACC CTAAACCCTA CCTCTTTTCT ATTGTTTACA CTTCTTACTC TTAGATATTT CCAGTTCTCC TGTTTATCTT 013360
013361 TAAGCCTGAT TCTTTTGAGA TGTACTTTTT GATGTTGCCG GTTACCTTTA GATTGACAGT ATTATGCCTG GGCCAGTCTT 013440
013441 GAGCCAGCTT TAAATCACAG CTTTTACCTA TTTGTTAGGC TATAGTGTTT TGTAAACTTC TGTTTCTATT CACATCTTCT 013520
013521 CCACTTGAGA GAGACACCAA AATCCAGTCA GTATCTAATC TGGCTTTTGT TAACTTCCCT CAGGAGCAGA CATTCATATA 013600
013601 GGTGATACTG TATTTCAGTC CTTTCTTTTG ACCCCAGAAG CCCTAGACTG AGAAGATAAA ATGGTCAGGT TGTTGGGGAA 013680
013681 AAAAAAGTGC CAGGCTCTCT AGAGAAAAAT GTGAAGAGAT GCTCCAGGCC AATGAGAAGA ATTAGACAAG AAATACACAG 013760
013761 ATGTGCCAGA CTTCTGAGAA GCACCTGCCA GCAACAGCTT CCTTCTTTGA GCTTAGGTGA GCAGGATTCT GGGGTTTGGG 013840
013841 ATTTCTAGTG ATGGTTATGG AAAGGGTGAC TGTGCCTGGG ACAAAGCGAG GTCCCAAGGG GACAGCCTGA ACTCCCTGCT 013920
013921 CATAGTAGTG GCCAAATAAT TTGGTGGACT GTGCCAACGC TACTCCTGGG TTTAATACCC ATCTCTAGGC TTAAAGATGA 014000
014001 GAGAACCTGG GACTGTTGAG CATGTTTAAT ACTTTCCTTG ATTTTTTTCT TCCTGTTTAT GTGGGAAGTT GATTTAAATG 014080
014081 ACTGATAATG TGTATGAAAG CACTGTAAAA CATAAGAGAA AAACCAATTA GTGTATTGGC AATCATGCAG TTAACATTTG 014160
014161 AAAGTGCAGT GTAAATTGTG AAGCATTATG TAAATCAGGG GTCCACAGTT TTTCTGTAAG GGGTCAAATC ATAAATACTT 014240
014241 TAGACTGTGG GCCATATGGT TTCTGTTACA TATTTGTTTT TTAAACAACG TTTTTATAAG GTCAAAATCA TTCTTAGTTT 014320
014321 TTGAGCCAAT TGGATTTGGC CTGCTGTTCA TAGCTTACCA CCCCCTGATG TATTATTTGT TATTCAGAGA AAATTTCTGA 014400
014401 ATACTACTAG TTTCCTTTTC TGTGCCTGTC CCTGTGCTAG GCACTAAAAA TGCAATGATT ATTGATATCT AGGTGACCTG 014480
014481 AAAAAAAATA GTGAATGTGC TTTGTAAACT GTAAAGCACT TGTATTCTAC TGTGATAAGC GTTGTGGATA CAAAGAAAGG 014560
014561 AGCAAGCATA AAAAAGTGCT CTTTCAAAAG GATATAGTAC TATGCAGACA CAAGGAATTG TTTGATAAAT GAATAAATTA 014640
014641 TATGTATATT TGAGGCCAAT TTGTGTTTGC TGCTCTGGTA ATTTTGAGTA AAAATGCAGT ATTCCAGGTA TCAGAAACGA 014720
014721 AAACACATGG AAACTGCTTT TAAACTTTAA AATATACTGA AAACATAAGG GACTAAGCTT GTTGTGGTCA CCTATAATGT 014800
014801 GCCAGATACC ATGCTGGGTG CTAGAGCTAC CAAAGGGGGA AAAGTATTCT CATAGAACAA AAAATTTCAG AAAGGTGCAT 014880
014881 ATTAAAGTGC TTTGTAAACT AAAGCATGAT ACAAATGTCA ATGGGCTACA TATTTATGAA TGAATGAATG GATGAATGAA 014960
014961 TATTAAGTGC CTCTTACATA CCAGCTATTT TGGGTACTGT AAAATACAAG ATTAATTCTC CTATGTAATA AGAGGAAAGT 015040
015041 TTATCCTCTA TACTATTCAG ATGTAAGGAA TGATATATTG CTTAATTTTA AACAATCAAG ACTTTACTGG TGAGGTTAAG 015120
015121 TTAAATTATT ACTGATACAT TTTTCCAGGT AACCAGGAAA GAGCTAGTAT GAGGAAATGA AGTAATAGAT GTGAGATCCA 015200
015201 GACCGAAAGT CACTTAATTC AGCTTGCGAA TGTGCTTTCT AAATTATAAA GCACTTGTAA ATGAAAAATT TGATGCTTTC 015280
015281 TGTATGAATA AAACTTTCTG TAAGCTAGGT ATTGTCTCTA CAAAATTCTC ATTGTATAGT TAAACCACAG TGAGAAGGGT 015360
015361 TCTATAAGTA GTTATACAAA CCAAGGGTTT AAATACCTGT TAAATAGATC AATTTTGATT GCCTACTATG TGAACTCACT 015440
015441 GTTAAAGGCA CTGAAAATTT ATCATATTTC ATTTAGCCAC AGCCAAAAAT AAGGCAATAC CTATGTTAGC ATTTTGTGAA 015520
015521 CTCTAAGGCA CCATATAAAT GTAACTGTTG ATTTTCTCAC TTGGTGCTGG GTACTAGGTT TATAAAATTG TATGATAGTT 015600
015601 ATTATATTGT GCAAATAAAG TAGGAAAATT TGAATAACAA TGATTATCTT TTGAATACGC ATACGCAAGG GATTGGTTGT 015680
015681 CTGAAGAATG CCACTATAGT AGTTATCTAT TGTGTGCCAA TCTCATTGCT AGGCATTGGG GATGCAAAGA TAAACCATCT 015760
015761 TTATTGTGTC TTGGGTAGCA GAAGAAAATA TGTGTAAAAT CAATTTATAA TTTGTAAACT GCCACCCATA TATAAGCTAT 015840
015841 ATCTGCTGAA TGATCATTGA TTACTCTTAT CCTTAGAGAT AACAACTGGG GGCACAAACA TTTATTATCA TTATTGAACC 015920
015921 TACAACAGAG ATCTATGTGT AGATTTACAA AGCCTACAGT TCTATACAGA TAGGAATGAA CTATTGGCTT ACTGAATGGT 016000
016001 GATTACTTTC TGTGGGGCTC GGAACTACAT GCCCTAGGAT ATAAAAATGA TGTTATCATT ATAGAGTGCT CACAGAAGGA 016080
016081 AATGAAGTAA TATAGGTGTG AGATCCAGAC CAAAAGTCAT TTAACAAGTT TATTCAGTGA TGAAAACATG GGACAAATGG 016160
016161 ACTAATATAA GGCAGTGTAC TAAGCTGAGT AGAGAGATAA AGTCCTGTCC AGAAGATACA TGCTTCCTGG CCTGATTGAG 016240
016241 GAGATGGAAA ATTTTTGCAA AAAACAAGGT GTTGTGGTCT TCCATCCAGT TTCTTAAGTG CTGATGATAA AAGTGAATTA 016320
016321 GACCCACCTT GACCTGGCCT ACAGAAGTAA AGGAGTAAAA ATAAATGCCT CAGGCGTGCT TTTTGATTCA TTTGATAAAC 016400
016401 AAAGCATCTT TTATGTGGAA TATACCATTC TGGGTCCTGA GGATAAGAGA GATGAGGGCA TTAGATCACT GACAGCTGAA 016480
016481 GATAGAAGAA CATCTTTGGT TTGATTGTTT AAATAATATT TCAATGCCTA TTCTCTGCAA GGTACTATGT TTCGTAAATT 016560
016561 AAATAGGTCT GGCCCAGAAG ACCCACTCAA TTGCCTTTGA GATTAAAAAA AAAAAAAAAA AGAAAGAAAA ATGCAAGTTT 016640
016641 CTTTCAAAAT AAAGAGACAT TTTTCCTAGT TTCAGGAATC CCCCAAATCA CTTCCTCATT GGCTTAGTTT AAAGCCAGGA 016720
016721 GACTGATAAA AGGGCTCAGG GTTTGTTCTT TAATTCATTA ACTAAACATT CTGCTTTTAT TACAGTTAAA TGGTTCAAGA 016800
016801 TGTAACAACT AGTTTTAAAG GTATTTGCTC ATTGGTCTGG CTTAGAGACA GGAAGACATA TGAGCAATAA AAAAAAGATT 016880
016881 CTTTTGCATT TACCAATTTA GTAAAAATTT ATTAAAACTG AATAAAGTGC TGTTCTTAAG TGCTTGAAAG ACGTAAACCA 016960
016961 AAGTGCACTT TATCTCATTT ATCTTATGGT GGAAACACAG GAACAAATTC TCTAAGAGAC TGTGTTTCTT TAGTTGAGAA 017040
017041 GAAACTTCAT TGAGTAGCTG TGATATGTTC GATACTAAGG AAAAACTAAA CAGATCACCT TTGACATGCG TTGTAGAGTG 017120
017121 GGAATAAGAG AGGGCTTTTT ATTTTTTCGT TCATACGAGT ATTGATGAAG ATGATACTAA ATGCTAAATG AAATATATCT 017200
017201 GCTCCAAAAG GCATTTATTC TGACTTGGAG ATGCAACAAA AACACAAAAA TGGAATGAAG TGATACTCTT CATCAAACAG 017280
017281 AAGTGACTGT TATCTCAACC ATTTTGTTAA ATCCTAAACA GAAAACAAAA AAAATCATGA CGAAAAGACA CTTGCTTATT 017360
017361 AATTGGCTTG GAAAGTAGAA TATAGGAGAA AGGTTACTGT TTATTTTTTT TCATGTATTC ATTCATTCTA CAAATATATT 017440
017441 CGGGTGCCAA TAGGTACTTG GTATAAGGTT TTTGGCCCCA GAGACATGGG AAAAAAATGC ATGCCTTCCC AGAGAATGCC 017520
017521 TAATACTTTC CTTTTGGCTT GTTTTCTTGT TAGGGGCATG GCTTAGTCCC TAAATAACAT TGTGTGGTTT AATTCCTACT 017600
017601 CCGTATCTCT TCTACCACTC TGGCCACTAC GATAAGCAGG TAGCTGGGTT TTGTAGTGAG CTTGCTCCTT AAGTTACAGG 017680
017681 AACTCTCCTT ATAATAGACA CTTCATTTTC CTAGTCCATC CCTCATGAAA AATGACTGAC CACTGCTGGG CAGCAGGAGG 017760
017761 GATGATGACC AACTAATTCC CAAACCCCAG TCTCATTGGT ACCAGCCTTG GGGAACCACC TACACTTGAG CCACAATTGG 017840
017841 TTTTGAAGTG CATTTACAAG GTTTGTCTAT TTTCAGTTCT TTACTTTTTA CATGCTGACA CATACATACA CTGCCTAAAT 017920
017921 AGATCTCTTT CAGAAACAAT CCTCAGATAA CGCATAGCAA AATG<