Difference between revisions of "NONHSAT137541"
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+ | [[File:Disease.png|right|frame| Hopeful result. Jeanne Lawrence points to a cell in which her team has turned off a third copy of chromosome 21, leaving the two others untouched. ''<ref name="ref42" />'']] | ||
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Working with pluripotent human stem cells created from people with Down syndrome, Lawrence used proteins that target specifi c DNA sequences to place XIST on one of the copies of chromosome 21<ref name="ref42" />.This could provide a controlled model for testing drugs,The XIST strategy is already a powerful tool for studying what goes wrong in Down syndrome in humans. Some lab is also planning to test strategies to deliver the XIST gene directly into neural stem cells in mice hippocampi to see if the injected gene can correct fetal brain development and later function in vivo<ref name="ref42" />but the prospect of using XIST to treat Down syndrome in humans—either in utero or adulthood—is still extremely remote<ref name="ref42" />. | Working with pluripotent human stem cells created from people with Down syndrome, Lawrence used proteins that target specifi c DNA sequences to place XIST on one of the copies of chromosome 21<ref name="ref42" />.This could provide a controlled model for testing drugs,The XIST strategy is already a powerful tool for studying what goes wrong in Down syndrome in humans. Some lab is also planning to test strategies to deliver the XIST gene directly into neural stem cells in mice hippocampi to see if the injected gene can correct fetal brain development and later function in vivo<ref name="ref42" />but the prospect of using XIST to treat Down syndrome in humans—either in utero or adulthood—is still extremely remote<ref name="ref42" />. | ||
Revision as of 02:57, 14 October 2014
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Contents
Annotated Information
Name
Xist: X inactive-specific transcript
Characteristics
Spliced, polyadenylated, ~17kb in mice, ~19kb in humans. Contains repeated sequence motifs A-F that are critical for its function. Xist is located on the X chromosome in the X-inactivation center (Xic), an approximately 100-kb region in the mouse containing (as of June 2012) five other lncRNAs, many of which play crucial roles in X-chromosome inactivation (XCI). Xist expression initiates the process of XCI in mammals.
Function
Xist is the master regulator of mammalian XCI, the mechanism of dosage compensation that balances X-linked gene expression between males and females. Xist function is required to initiate XCI [1] [2] .Ectopic Xist expression from an autosomal transgene causes long-range gene repression in cis [3].Xist and RepA (see associated components below) RNAs bind to and recruit PRC2, which catalyzes the deposition of the repressive chromatin mark H3K27me3 on the Xi [4] [5][6] [7][8].Small RNAs formed from Xist/Tsix duplexes may play a role in regulating Xist expression and XCI [9]. However, loss of Dicer has only a modest effect on Xist expression [10]. 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 [11]. Xist Repeat C sequences are required for Xist localization to the Xi [12] [13]. 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 [14]. Xist forms a transcriptionally silenced sub-nuclear domain [15]and perinucleolar localisation of the silent Xist coated chromosome has been observed [16]. 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 [17]. After the initiation of XCI, Xist function is not absolutely required to maintain XCI in fibroblasts [18]. Nor is continued Xist expression required to maintain XCI-like repression around an autosomal Xist transgene in male, differentiated ES cells[19]. However, lack of Xist function in differentiated cells can lead to partial reactivation of select X-linked genes [20].XIST RNA is methylated at specific cytosines within the A-region,Potential relationship between cytosine methylation and functional properties of XIST RNA [21] .Dosage compensation for X-linked genes in female mammals relies on X-chromosome inactivation. This process involves monoallelic up-regulation of the non-coding Xist RNA which coats in cis the chromosome and triggers epigenetic reprogramming that will prevent chromosome-wide transcription[22]. Noncoding RNAs lncRNA Xist have been implicated in the regulation of epigenetic pathways in X chromosome inactivation [23].
Expression
Xist is expressed in all somatic cells in female eutherian mammals, monoallelically from the inactive X-chromosome (Xi) [24]. Xist is not expressed in males. Xist is a nuclear RNA that coats the Xi [25][26]. In the 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 [27].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 [28].In female undifferentiated mouse ES (embryonic stem) and iPS (induced pluripotent stem) cells, Xist is not expressed and both X chromosomes are active. 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 [29][30][31][32]and iPS cells [33] [34][35][36][37]. 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 [21].
Conservation
Xist is present in all eutherian (placental) mammals examined to date, but it is not present in marsupials or monotremes [38][39][40][41]. An unrelated ncRNA in marsupials, Rsx, is likely to play a role similar to that of Xist in XCI.[42] The most conserved Xist RNA region, the A region, contains eight or nine repeats separated by U-rich spacers.
Misc
Please input misc information here.
Transcriptomic Nomeclature
XIST normally resides on the X chromosome and serves to shut down one of the two X chromosomes in females—both men and women get along with one X. The gene produces a long strand of RNA, likely covers the chromosome in an RNA shroud, triggering proteins that block any genes from being transcribed.[23]
Regulation
Xist transcription is controlled, directly and/or indirectly, by several ncRNA (Tsix, Jpx, Ftx) and factors (Sox2, Oct4, Nanog, Rex1, Rnf12).[42] Specific YY1 play a prominent and conserved role in Xist transcriptional activation
Allelic Information and Variation
Please input allelic information and variation information here.
Evolution
Please input evolution information here.
Disease
Working with pluripotent human stem cells created from people with Down syndrome, Lawrence used proteins that target specifi c DNA sequences to place XIST on one of the copies of chromosome 21[23].This could provide a controlled model for testing drugs,The XIST strategy is already a powerful tool for studying what goes wrong in Down syndrome in humans. Some lab is also planning to test strategies to deliver the XIST gene directly into neural stem cells in mice hippocampi to see if the injected gene can correct fetal brain development and later function in vivo[23]but the prospect of using XIST to treat Down syndrome in humans—either in utero or adulthood—is still extremely remote[23].
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Labs working on this lncRNA
Department of Molecular Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.[13] Mammalian Developmental Epigenetic Group, UMR 218, Curie Institute, 75248 Paris Cedex 05, France.[15] Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.[14] Howard Hughes Medical Institute, Boston, MA 02114 USA.[16] Faculté des Sciences et Techniques, AREMS, Nancy Université, UMR 7214 CNRS-UHP 1, Vandoeuvre-lès-Nancy, France.[17] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.[19] Department of Genetics, Stanford University School of Medicine, California 94305.[24] 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.[29] Whitehead Institute for Biomedical Sciences, 9 Cambridge Center, Cambridge, MA 02142, USA.[32] ARC Centre for Kangaroo Genomics, Research School of Biological Sciences, The Australian National University, Canberra, ACT 2601, Australia. timothy.hore@anu.edu.au [40] MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK.[42]
References
- ↑ Penny GD1, Kay GF, Sheardown SA, Rastan S, Brockdorff N.(1996) Requirement for Xist in X chromosome inactivation.Nature. 1996 Jan 11;379(6561):131-7.
- ↑ Marahrens Y1, Panning B, Dausman J, Strauss W, Jaenisch R. (1997)Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev. 1997 Jan 15;11(2):156-66.
- ↑ Wutz A1, Jaenisch R. (2000) A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell. 2000 Apr;5(4):695-705.
- ↑ Zhao J1, Sun BK, Erwin JA, Song JJ, Lee JT. (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.Science. 2008 Oct 31;322(5902):750-6. doi: 10.1126/science.1163045.
- ↑ Kaneko S1, Li G, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D.(2010)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. doi: 10.1101/gad.1983810.
- ↑ Kanhere A1, 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.(2010) 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. doi: 10.1016/j.molcel.2010.03.019.
- ↑ Zhao J1, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT.(2010) Genome-wide identification of polycomb-associated RNAs by RIP-seq.Mol Cell. 2010 Dec 22;40(6):939-53. doi: 10.1016/j.molcel.2010.12.011.
- ↑ Guil S1, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M.(2012)Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nat Struct Mol Biol. 2012 Jun 3;19(7):664-70. doi: 10.1038/nsmb.2315.
- ↑ Ogawa Y1, Sun BK, Lee JT. (2008)Intersection of the RNA interference and X-inactivation pathways. Science. 2008 Jun 6;320(5881):1336-41. doi: 10.1126/science.1157676.
- ↑ Kanellopoulou C1, Muljo SA, Dimitrov SD, Chen X, Colin C, Plath K, Livingston DM.(2009) X chromosome inactivation in the absence of Dicer.Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1122-7. doi: 10.1073/pnas.0812210106. Epub 2009 Jan 21.
- ↑ Hasegawa Y1, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S.(2010)The matrix protein hnRNP U is required for chromosomal localization of Xist RNA.Dev Cell. 2010 Sep 14;19(3):469-76. doi: 10.1016/j.devcel.2010.08.006.
- ↑ Beletskii A1, Hong YK, Pehrson J, Egholm M, Strauss WM.(2001)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.
- ↑ 13.0 13.1 Sarma K1, Levasseur P, Aristarkhov A, Lee JT.(2010)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. doi: 10.1073/pnas.1009785107. Epub 2010 Dec 6.
- ↑ 14.0 14.1 Jeon Y1, Lee JT.(2011)YY1 tethers Xist RNA to the inactive X nucleation center.Cell. 2011 Jul 8;146(1):119-33. doi: 10.1016/j.cell.2011.06.026.
- ↑ 15.0 15.1 Chaumeil J1, Le Baccon P, Wutz A, Heard E.(2006) 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.
- ↑ 16.0 16.1 Zhang LF1, Huynh KD, Lee JT.(2007)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.
- ↑ 17.0 17.1 Maenner S1, Blaud M, Fouillen L, Savoye A, Marchand V, Dubois A, Sanglier-Cianférani S, Van Dorsselaer A, Clerc P, Avner P, Visvikis A, Branlant C.(2010) 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol. 2010 Jan;8(1):e1000276. doi: 10.1371/journal.pbio.1000276. Epub 2010 Jan 5.
- ↑ Csankovszki G, Panning B, Bates B, Pehrson JR, Jaenisch R.(1999) Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation.Nat Genet. 1999 Aug;22(4):323-4.
- ↑ 19.0 19.1 Wutz A1, Jaenisch R.(2000) A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell. 2000 Apr;5(4):695-705.
- ↑ Csankovszki G1, Nagy A, Jaenisch R.(2001) Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol. 2001 May 14;153(4):773-84.
- ↑ 21.0 21.1 Amort T1, Soulière MF, Wille A, Jia XY, Fiegl H, Wörle H, Micura R, Lusser A.(2013)Long non-coding RNAs as targets for cytosine methylation. RNA Biol. 2013 Jun;10(6):1003-8. doi: 10.4161/rna.24454. Epub 2013 Apr 1.
- ↑ Makhlouf M1, Ouimette JF1, Oldfield A1, Navarro P2, Neuillet D1, Rougeulle C1.(2014) A prominent and conserved role for YY1 in Xist transcriptional activation. Nat Commun. 2014 Sep 11;5:4878. doi: 10.1038/ncomms5878.
- ↑ 23.0 23.1 23.2 23.3 23.4 23.5 Underwood E.(2014)Can Down syndrome be treated? .Science. 2014 Feb 28;343(6174):964-7. doi: 10.1126/science.343.6174.964.
- ↑ 24.0 24.1 Brown CJ1, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF.(1991) 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.
- ↑ Brown CJ1, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, Willard HF.(1992)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.
- ↑ Clemson CM1, McNeil JA, Willard HF, Lawrence JB.(1996) 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.
- ↑ Moreira de Mello JC1, de Araújo ES, Stabellini R, Fraga AM, de Souza JE, Sumita DR, Camargo AA, Pereira LV.(2010) 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. doi: 10.1371/journal.pone.0010947.
- ↑ Blackshaw S1, 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.(2004)Moreira de Mello JC1, de Araújo ES, Stabellini R, Fraga AM, de Souza JE, Sumita DR, Camargo AA, Pereira LV. PLoS Biol. 2004 Sep;2(9):E247. Epub 2004 Jun 29.
- ↑ 29.0 29.1 Shen Y1, Matsuno Y, Fouse SD, Rao N, Root S, Xu R, Pellegrini M, Riggs AD, Fan G.(2008)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. doi: 10.1073/pnas.0712018105. Epub 2008 Mar 13.
- ↑ Silva SS1, Rowntree RK, Mekhoubad S, Lee JT.(2008) 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. doi: 10.1073/pnas.0712136105. Epub 2008 Mar 13.
- ↑ Hall LL1, Byron M, Butler J, Becker KA, Nelson A, Amit M, Itskovitz-Eldor J, Stein J, Stein G, Ware C, Lawrence JB.(2008)X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines that initiate as expected. J Cell Physiol. 2008 Aug;216(2):445-52. doi: 10.1002/jcp.21411.
- ↑ 32.0 32.1 Lengner CJ1, 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.(2010) Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell.2010 May 28;141(5):872-83. doi:10.1016/j.cell.2010.04.010. Epub 2010 May 13.
- ↑ Bruck T1, Benvenisty N.(2011) Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells. Stem Cell Res. 2011 Mar;6(2):187-93. doi: 10.1016/j.scr.2010.12.001. Epub 2010 Dec 13.
- ↑ Hanna J1, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R.(2009)Bruck T1, Benvenisty N. Nature. 2009 Dec 3;462(7273):595-601. doi: 10.1038/nature08592. Epub 2009 Nov 8.
- ↑ Brown CJ1, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, Willard HF.(1992)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.
- ↑ Marchetto MC1, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR.(2010) 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. doi: 10.1016/j.cell.2010.10.016.
- ↑ Tchieu J1, 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.(2010)Female human iPSCs retain an inactive X chromosome.Cell Stem Cell. 2010 Sep 3;7(3):329-42. doi: 10.1016/j.stem.2010.06.024. Epub 2010 Aug 19.
- ↑ Duret L1, Chureau C, Samain S, Weissenbach J, Avner P.(2006) The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science. 2006 Jun 16;312(5780):1653-5.
- ↑ Davidow LS1, Breen M, Duke SE, Samollow PB, McCarrey JR, Lee JT.(2007)The search for a marsupial XIC reveals a break with vertebrate synteny. Chromosome Res. 2007;15(2):137-46. Epub 2007 Mar 5.
- ↑ 40.0 40.1 Hore TA1, Koina E, Wakefield MJ, Marshall Graves JA.(2007)The region homologous to the X-chromosome inactivation centre has been disrupted in marsupial and monotreme mammals. Chromosome Res. 2007;15(2):147-61. Epub 2007 Mar 5.
- ↑ Shevchenko AI1, 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.(2007) Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials. Chromosome Res. 2007;15(2):127-36. Epub 2007 Mar 5.
- ↑ 42.0 42.1 42.2 Grant J1, 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.(2012) Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature. 2012 Jul 12;487(7406):254-8. doi: 10.1038/nature11171.
Basic Information
Transcript ID |
NONHSAT137541 |
Source |
NONCODE4.0 |
Same with |
, |
Classification |
intergenic |
Length |
19271 nt |
Genomic location |
chrX-:73040486..73072588 |
Exon number |
6 |
Exons |
73040486..73047819,73048903..73049066,73050901..73051109,73053073..73053209,73057275..73057338,73061217..73072588 |
Genome context |
|
Sequence |
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 AATGGAGATG GAGACATGAT TTCTCATGCA ACAGCTTCTC 018000 018001 TAATTATACC TTAGAAATGT TCTCCTTTTT ATCATCAAAT CTGCTCAAGA AGGGCTTTTT ATAGTAGAAT AATATCAGTG 018080 018081 GATGAAAACA GCTTAACATT TTACCATGCT TAAGTTTTAA GAATAAAATA AAAATTGGAA ATAATTGGCC AAAATTGAAA 018160 018161 GGAAAAATTT TTTTAAAATT TCTCTAAATG TAGGCCTGGC TGGGCTTTGA CCTTTTCCGT TTTTAAATCA CTCACAGAGG 018240 018241 GTGGGACAGG AGGAAGAGTG AAGGAAAAGG TCAAACCTGT TTTAAGGGCA ACCTGCCTTT GTTCTGAATT GGTCTTAAGA 018320 018321 ACATTACCAG CTCCAGGTTT AAATTGTTCA GTTTCATGCA GTTCCAATAG CTGATCATTG TTGAGATGAG GACAAAATCC 018400 018401 TTTGTCCTCA CTAGTTTGCT TTACATTTTT GAAAAGTATT ATTTTTGTCC AAGTGCTTAT CAACTAAACC TTGTGTTAGG 018480 018481 TAAGAATGGA ATTTATTAAG TGAATCAGTG TGACCCTTCT TGTCATAAGA TTATCTTAAA GCTGAAGCCA AAATATGCTT 018560 018561 CAAAAGAAGA GGACTTTATT GTTCATTGTA GTTCATACAT TCAAAGCATC TGAACTGTAG TTTCTATAGC AAGCCAATTA 018640 018641 CATCCATAAG TGGAGAAGGA AATAGATAAA TGTCAAAGTA TGATTGGTGG AGGGAGCAAG GTTGAAGATA ATCTGGGGTT 018720 018721 GAAATTTTCT AGTTTTCATT CTGTACATTT TTAGTTAGAC ATCAGATTTG AAATATTAAT GTTTACCTTT CAATGTGTGG 018800 018801 TATCAGCTGG ACTCAGTAAC ACCCCTTTCT TCAGCTGGGG ATGGGGAATG GATTATTGGA AAATGGAAAG AAGAAAGTAA 018880 018881 CTAAAAGCCT TCCTTTCACA GTTTCTGGCA TCACTACCAC TACTGATTAA ACAAGAATAA GAGAACATTT TATCATCATC 018960 018961 TGCTTTATTC ACATAAATGA AGTTGTGATG AATAAATCTG CTTTTATGCA GACACAAGGA ATTAAGTGGC TTCGTCATTG 019040 019041 TCCTTCTACC TCAAAGATAA TTTATTCCAA AAGCTAAGAT AAATGGAAGA CTCTTGAACT TGTGAACTGA TGTGAAATGC 019120 019121 AGAATCTCTT TTGAGTCTTT GCTGTTTGGA AGATTGAAAA ATATTGTTCA GCATGGGTGA CCACCAGAAA GTAATCTTAA 019200 019201 GCCATCTAGA TGTCACAATT GAAACAAACT GGGGAGTTGG TTGCTATTGT AAAATAAAAT ATACTGTTTT G |