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|
LOCUS NM_014491 2472 bp mRNA linear PRI 28-MAY-2006
DEFINITION Homo sapiens forkhead box P2 (FOXP2), transcript variant 1, mRNA.
ACCESSION NM_014491
VERSION NM_014491.1 GI:17017962
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1 to 2472)
AUTHORS Sanjuan,J., Tolosa,A., Gonzalez,J.C., Aguilar,E.J., Perez-Tur,J.,
Najera,C., Molto,M.D. and de Frutos,R.
TITLE Association between FOXP2 polymorphisms and schizophrenia with
auditory hallucinations
JOURNAL Psychiatr. Genet. 16 (2), 67-72 (2006)
PUBMED 16538183
REMARK GeneRIF: The single nucleotide polymorphism rs2396753 appears to
confer vulnerability to schizophrenia with auditory hallucinations.
REFERENCE 2 (bases 1 to 2472)
AUTHORS Stroud,J.C., Wu,Y., Bates,D.L., Han,A., Nowick,K., Paabo,S.,
Tong,H. and Chen,L.
TITLE Structure of the forkhead domain of FOXP2 bound to DNA
JOURNAL Structure 14 (1), 159-166 (2006)
PUBMED 16407075
REMARK GeneRIF: Disease-causing mutations in FOXP2 map either to the DNA
binding surface or the domain-swapping dimer interface,
functionally corroborating the crystal structure.
REFERENCE 3 (bases 1 to 2472)
AUTHORS Benitez-Burraco,A.
TITLE [FOXP2: from the specific disorder to the molecular biology of
language. I. Aetiological, neuroanatomical, neurophysiological and
molecular aspects]
JOURNAL Rev Neurol 40 (11), 671-682 (2005)
PUBMED 15948071
REMARK Review article
GeneRIF: Review. FOXP2 codes for a CNS transcriptional repressor,
expressed in the basal ganglia, cortex, cerebellum & the thalamus,
involved in thalamic-cortical-striatal circuits for motor planning
& learning. Its loss causes specific language impairment.
REFERENCE 4 (bases 1 to 2472)
AUTHORS MacDermot,K.D., Bonora,E., Sykes,N., Coupe,A.M., Lai,C.S.,
Vernes,S.C., Vargha-Khadem,F., McKenzie,F., Smith,R.L., Monaco,A.P.
and Fisher,S.E.
TITLE Identification of FOXP2 truncation as a novel cause of
developmental speech and language deficits
JOURNAL Am. J. Hum. Genet. 76 (6), 1074-1080 (2005)
PUBMED 15877281
REMARK GeneRIF: Truncation of FOXP2 is the cause of developmental speech
and language deficits.
REFERENCE 5 (bases 1 to 2472)
AUTHORS Vargha-Khadem,F., Gadian,D.G., Copp,A. and Mishkin,M.
TITLE FOXP2 and the neuroanatomy of speech and language
JOURNAL Nat. Rev. Neurosci. 6 (2), 131-138 (2005)
PUBMED 15685218
REMARK Review article
GeneRIF: a mutation in FOXP2 had been found in a family with a
speech and language disorder.
REFERENCE 6 (bases 1 to 2472)
AUTHORS Gong,X., Jia,M., Ruan,Y., Shuang,M., Liu,J., Wu,S., Guo,Y.,
Yang,J., Ling,Y., Yang,X. and Zhang,D.
TITLE Association between the FOXP2 gene and autistic disorder in Chinese
population
JOURNAL Am. J. Med. Genet. B Neuropsychiatr. Genet. 127 (1), 113-116 (2004)
PUBMED 15108192
REMARK GeneRIF: Findings suggest that the FOXP2 gene may be involved in
the pathogenesis of autism in Chinese population.
REFERENCE 7 (bases 1 to 2472)
AUTHORS Teramitsu,I., Kudo,L.C., London,S.E., Geschwind,D.H. and White,S.A.
TITLE Parallel FoxP1 and FoxP2 expression in songbird and human brain
predicts functional interaction
JOURNAL J. Neurosci. 24 (13), 3152-3163 (2004)
PUBMED 15056695
REMARK GeneRIF: FOXP1 and FOXP2 expression patterns in human fetal brain
are strikingly similar to those in the songbird, including
localization to subcortical structures that function in
sensorimotor integration and the control of skilled, coordinated
movement
REFERENCE 8 (bases 1 to 2472)
AUTHORS Banerjee-Basu,S. and Baxevanis,A.D.
TITLE Structural analysis of disease-causing mutations in the P-subfamily
of forkhead transcription factors
JOURNAL Proteins 54 (4), 639-647 (2004)
PUBMED 14997560
REMARK GeneRIF: impact of disease-causing missense mutations on the
three-dimensional structure, stability, and surface electrostatic
charge distribution of the forkhead domains is examined
REFERENCE 9 (bases 1 to 2472)
AUTHORS Li,S., Weidenfeld,J. and Morrisey,E.E.
TITLE Transcriptional and DNA binding activity of the Foxp1/2/4 family is
modulated by heterotypic and homotypic protein interactions
JOURNAL Mol. Cell. Biol. 24 (2), 809-822 (2004)
PUBMED 14701752
REMARK GeneRIF: complex regulatory mechanism underlying Foxp1, Foxp2, and
Foxp4 activity, demonstrating that Foxp1, Foxp2, and Foxp4 are the
first Fox proteins reported whose activity is regulated by homo-
and heterodimerization
REFERENCE 10 (bases 1 to 2472)
AUTHORS Liegeois,F., Baldeweg,T., Connelly,A., Gadian,D.G., Mishkin,M. and
Vargha-Khadem,F.
TITLE Language fMRI abnormalities associated with FOXP2 gene mutation
JOURNAL Nat. Neurosci. 6 (11), 1230-1237 (2003)
PUBMED 14555953
REMARK GeneRIF: This experiment findings suggest that the FOXP2 gene is
critically involved in the development of the neural systems that
mediate speech and language.
REFERENCE 11 (bases 1 to 2472)
AUTHORS Lai,C.S., Gerrelli,D., Monaco,A.P., Fisher,S.E. and Copp,A.J.
TITLE FOXP2 expression during brain development coincides with adult
sites of pathology in a severe speech and language disorder
JOURNAL Brain 126 (PT 11), 2455-2462 (2003)
PUBMED 12876151
REMARK GeneRIF: FOXP2/foxp2 is expressed in several structures in
developing human/mouse brain including cortical plate, basal
ganglia, thalamus, inferior olives and cerebellum. These data
suggest a conserved mammalian role in development of motor-related
neural circuits
REFERENCE 12 (bases 1 to 2472)
AUTHORS Hillier,L.W., Fulton,R.S., Fulton,L.A., Graves,T.A., Pepin,K.H.,
Wagner-McPherson,C., Layman,D., Maas,J., Jaeger,S., Walker,R.,
Wylie,K., Sekhon,M., Becker,M.C., O'Laughlin,M.D., Schaller,M.E.,
Fewell,G.A., Delehaunty,K.D., Miner,T.L., Nash,W.E., Cordes,M.,
Du,H., Sun,H., Edwards,J., Bradshaw-Cordum,H., Ali,J., Andrews,S.,
Isak,A., Vanbrunt,A., Nguyen,C., Du,F., Lamar,B., Courtney,L.,
Kalicki,J., Ozersky,P., Bielicki,L., Scott,K., Holmes,A.,
Harkins,R., Harris,A., Strong,C.M., Hou,S., Tomlinson,C.,
Dauphin-Kohlberg,S., Kozlowicz-Reilly,A., Leonard,S., Rohlfing,T.,
Rock,S.M., Tin-Wollam,A.M., Abbott,A., Minx,P., Maupin,R.,
Strowmatt,C., Latreille,P., Miller,N., Johnson,D., Murray,J.,
Woessner,J.P., Wendl,M.C., Yang,S.P., Schultz,B.R., Wallis,J.W.,
Spieth,J., Bieri,T.A., Nelson,J.O., Berkowicz,N., Wohldmann,P.E.,
Cook,L.L., Hickenbotham,M.T., Eldred,J., Williams,D., Bedell,J.A.,
Mardis,E.R., Clifton,S.W., Chissoe,S.L., Marra,M.A., Raymond,C.,
Haugen,E., Gillett,W., Zhou,Y., James,R., Phelps,K., Iadanoto,S.,
Bubb,K., Simms,E., Levy,R., Clendenning,J., Kaul,R., Kent,W.J.,
Furey,T.S., Baertsch,R.A., Brent,M.R., Keibler,E., Flicek,P.,
Bork,P., Suyama,M., Bailey,J.A., Portnoy,M.E., Torrents,D.,
Chinwalla,A.T., Gish,W.R., Eddy,S.R., McPherson,J.D., Olson,M.V.,
Eichler,E.E., Green,E.D., Waterston,R.H. and Wilson,R.K.
TITLE The DNA sequence of human chromosome 7
JOURNAL Nature 424 (6945), 157-164 (2003)
PUBMED 12853948
REFERENCE 13 (bases 1 to 2472)
AUTHORS O'Brien,E.K., Zhang,X., Nishimura,C., Tomblin,J.B. and Murray,J.C.
TITLE Association of specific language impairment (SLI) to the region of
7q31
JOURNAL Am. J. Hum. Genet. 72 (6), 1536-1543 (2003)
PUBMED 12721956
REMARK GeneRIF: Genetic factors for regulation of common language
impairment appear to reside in the vicinity of FOXP2.
REFERENCE 14 (bases 1 to 2472)
AUTHORS Scherer,S.W., Cheung,J., MacDonald,J.R., Osborne,L.R.,
Nakabayashi,K., Herbrick,J.A., Carson,A.R., Parker-Katiraee,L.,
Skaug,J., Khaja,R., Zhang,J., Hudek,A.K., Li,M., Haddad,M.,
Duggan,G.E., Fernandez,B.A., Kanematsu,E., Gentles,S.,
Christopoulos,C.C., Choufani,S., Kwasnicka,D., Zheng,X.H., Lai,Z.,
Nusskern,D., Zhang,Q., Gu,Z., Lu,F., Zeesman,S., Nowaczyk,M.J.,
Teshima,I., Chitayat,D., Shuman,C., Weksberg,R., Zackai,E.H.,
Grebe,T.A., Cox,S.R., Kirkpatrick,S.J., Rahman,N., Friedman,J.M.,
Heng,H.H., Pelicci,P.G., Lo-Coco,F., Belloni,E., Shaffer,L.G.,
Pober,B., Morton,C.C., Gusella,J.F., Bruns,G.A., Korf,B.R.,
Quade,B.J., Ligon,A.H., Ferguson,H., Higgins,A.W., Leach,N.T.,
Herrick,S.R., Lemyre,E., Farra,C.G., Kim,H.G., Summers,A.M.,
Gripp,K.W., Roberts,W., Szatmari,P., Winsor,E.J., Grzeschik,K.H.,
Teebi,A., Minassian,B.A., Kere,J., Armengol,L., Pujana,M.A.,
Estivill,X., Wilson,M.D., Koop,B.F., Tosi,S., Moore,G.E.,
Boright,A.P., Zlotorynski,E., Kerem,B., Kroisel,P.M., Petek,E.,
Oscier,D.G., Mould,S.J., Dohner,H., Dohner,K., Rommens,J.M.,
Vincent,J.B., Venter,J.C., Li,P.W., Mural,R.J., Adams,M.D. and
Tsui,L.C.
TITLE Human chromosome 7: DNA sequence and biology
JOURNAL Science 300 (5620), 767-772 (2003)
PUBMED 12690205
REFERENCE 15 (bases 1 to 2472)
AUTHORS Zhang,J., Webb,D.M. and Podlaha,O.
TITLE Accelerated protein evolution and origins of human-specific
features: Foxp2 as an example
JOURNAL Genetics 162 (4), 1825-1835 (2002)
PUBMED 12524352
REMARK GeneRIF: A survey of a diverse group of placental mammals reveals
the uniqueness of the human FOXP2 sequence and a population genetic
analysis indicates possible adaptive selection behind the
accelerated evolution.
REFERENCE 16 (bases 1 to 2472)
AUTHORS Enard,W., Przeworski,M., Fisher,S.E., Lai,C.S., Wiebe,V.,
Kitano,T., Monaco,A.P. and Paabo,S.
TITLE Molecular evolution of FOXP2, a gene involved in speech and
language
JOURNAL Nature 418 (6900), 869-872 (2002)
PUBMED 12192408
REMARK GeneRIF: Human FOXP2 contains changes in amino-acid coding and a
pattern of nucleotide polymorphism, which strongly suggest that
this gene has been the target of selection during recent human
evolution.
REFERENCE 17 (bases 1 to 2472)
AUTHORS Bruce,H.A. and Margolis,R.L.
TITLE FOXP2: novel exons, splice variants, and CAG repeat length
stability
JOURNAL Hum. Genet. 111 (2), 136-144 (2002)
PUBMED 12189486
REFERENCE 18 (bases 1 to 2472)
AUTHORS Newbury,D.F., Bonora,E., Lamb,J.A., Fisher,S.E., Lai,C.S.,
Baird,G., Jannoun,L., Slonims,V., Stott,C.M., Merricks,M.J.,
Bolton,P.F., Bailey,A.J. and Monaco,A.P.
CONSRTM International Molecular Genetic Study of Autism Consortium
TITLE FOXP2 is not a major susceptibility gene for autism or specific
language impairment
JOURNAL Am. J. Hum. Genet. 70 (5), 1318-1327 (2002)
PUBMED 11894222
REMARK GeneRIF: FOXP2 is not a major susceptibility gene for autism or
specific language impairment
REFERENCE 19 (bases 1 to 2472)
AUTHORS Lai,C.S., Fisher,S.E., Hurst,J.A., Vargha-Khadem,F. and Monaco,A.P.
TITLE A forkhead-domain gene is mutated in a severe speech and language
disorder
JOURNAL Nature 413 (6855), 519-523 (2001)
PUBMED 11586359
REMARK GeneRIF: FOXP2 is disrupted by a translocation in CS, a child with
severe speech/language disorder. Moreover, a point mutation,
altering a critical residue of the forkhead domain, segregates with
speech/language deficits in all 15 affected members of family KE.
REFERENCE 20 (bases 1 to 2472)
AUTHORS Lai,C.S., Fisher,S.E., Hurst,J.A., Levy,E.R., Hodgson,S., Fox,M.,
Jeremiah,S., Povey,S., Jamison,D.C., Green,E.D., Vargha-Khadem,F.
and Monaco,A.P.
TITLE The SPCH1 region on human 7q31: genomic characterization of the
critical interval and localization of translocations associated
with speech and language disorder
JOURNAL Am. J. Hum. Genet. 67 (2), 357-368 (2000)
PUBMED 10880297
REFERENCE 21 (bases 1 to 2472)
AUTHORS Margolis,R.L., Abraham,M.R., Gatchell,S.B., Li,S.H., Kidwai,A.S.,
Breschel,T.S., Stine,O.C., Callahan,C., McInnis,M.G. and Ross,C.A.
TITLE cDNAs with long CAG trinucleotide repeats from human brain
JOURNAL Hum. Genet. 100 (1), 114-122 (1997)
PUBMED 9225980
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from AF337817.
Summary: This gene encodes an evolutionarily conserved
transcription factor expressed in fetal and adult brain. This
transcription factor is a member of the forkhead/winged-helix (FOX)
family of transcription factors, and contains a FOX DNA-binding
domain and a large polyglutamine tract. Members of the FOX family
of transcription factors are regulators of embryogenesis. The
product of this gene is thought to be required for proper
development of speech and language regions of the brain during
embryogenesis. Although a point mutation in this gene has been
associated with the KE pedigree segregating developmental verbal
dyspraxia, no association between mutations in this gene and
another speech disorder, autism, has been found. Four alternative
transcripts encoding three different isoforms have been identified.
Transcript Variant: This variant (1) encodes the predominant
isoform.
FEATURES Location/Qualifiers
source 1..2472
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
/chromosome="7"
/map="7q31"
gene 1..2472
/gene="FOXP2"
/note="synonyms: SPCH1, CAGH44, TNRC10, DKFZp686H1726"
/db_xref="GeneID:93986"
/db_xref="HGNC:13875"
/db_xref="HPRD:HPRD_05611"
/db_xref="MIM:605317"
CDS 151..2298
/gene="FOXP2"
/go_component="nucleus [goid 0005634] [evidence IEA]"
/go_function="zinc ion binding [goid 0008270] [evidence
IEA]"
/go_function="metal ion binding [goid 0046872] [evidence
IEA]"
/go_function="nucleic acid binding [goid 0003676]
[evidence IEA]"
/go_function="sequence-specific DNA binding [goid 0043565]
[evidence IEA]"
/go_function="transcription factor activity [goid 0003700]
[evidence IEA]"
/go_process="transcription [goid 0006350] [evidence IEA]"
/go_process="regulation of transcription, DNA-dependent
[goid 0006355] [evidence IEA]"
/note="isoform I is encoded by transcript variant 1;
trinucleotide repeat containing 10; forkhead/winged-helix
transcription factor; speech and language disorder 1; CAG
repeat protein 44"
/codon_start=1
/product="forkhead box P2 isoform I"
/protein_id="NP_055306.1"
/db_xref="GI:17017963"
/db_xref="CCDS:CCDS5760.1"
/db_xref="GeneID:93986"
/db_xref="HGNC:13875"
/db_xref="HPRD:HPRD_05611"
/db_xref="MIM:605317"
/translation="MMQESATETISNSSMNQNGMSTLSSQLDAGSRDGRSSGDTSSEV
STVELLHLQQQQALQAARQLLLQQQTSGLKSPKSSDKQRPLQVPVSVAMMTPQVITPQ
QMQQILQQQVLSPQQLQALLQQQQAVMLQQQQLQEFYKKQQEQLHLQLLQQQQQQQQQ
QQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQHPGKQAKEQQQQQQQQQQLAAQQLVFQ
QQLLQMQQLQQQQHLLSLQRQGLISIPPGQAALPVQSLPQAGLSPAEIQQLWKEVTGV
HSMEDNGIKHGGLDLTTNNSSSTTSSNTSKASPPITHHSIVNGQSSVLSARRDSSSHE
ETGASHTLYGHGVCKWPGCESICEDFGQFLKHLNNEHALDDRSTAQCRVQMQVVQQLE
IQLSKERERLQAMMTHLHMRPSEPKPSPKPLNLVSSVTMSKNMLETSPQSLPQTPTTP
TAPVTPITQGPSVITPASVPNVGAIRRRHSDKYNIPMSSEIAPNYEFYKNADVRPPFT
YATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVE
NVKGAVWTVDEVEYQKRRSQKITGSPTLVKNIPTSLGYGAALNASLQAALAESSLPLL
SNPGLINNASSGLLQAVHEDLNGSLDHIDSNGNSSPGCSPQPHIHSIHVKEEPVIAED
EDCPMSLVTTANHSPELEDDREIEEEPLSEDLE"
misc_feature 604..723
/gene="FOXP2"
/note="Region: polyglutamine tract"
misc_feature 1660..1878
/gene="FOXP2"
/note="Forkhead (FH), also known as a 'winged helix';
Region: FH"
/db_xref="CDD:28941"
misc_feature 408^409
/gene="FOXP2"
/note="Region: location of alternate exons 3a and 3b"
ORIGIN
1 agtgagctag cttctgagtt ttcccttctt tttatactgt tttctgtgct ggcttttttg
61 aatcttccta atttttcatc tctttaacaa actcctatga agttgaaacc gggaagtttg
121 ctctaacatt tccagagaag gtattaagtc atgatgcagg aatctgcgac agagacaata
181 agcaacagtt caatgaatca aaatggaatg agcactctaa gcagccaatt agatgctggc
241 agcagagatg gaagatcaag tggtgacacc agctctgaag taagcacagt agaactgctg
301 catctgcaac aacagcaggc tctccaggca gcaagacaac ttcttttaca gcagcaaaca
361 agtggattga aatctcctaa gagcagtgat aaacagagac cactgcaggt gcctgtgtca
421 gtggccatga tgactcccca ggtgatcacc cctcagcaaa tgcagcagat ccttcagcaa
481 caagtcctgt ctcctcagca gctacaagcc cttctccaac aacagcaggc tgtcatgctg
541 cagcagcaac aactacaaga gttttacaag aaacagcaag agcagttaca tcttcagctt
601 ttgcagcagc agcagcaaca gcagcagcag caacaacagc agcaacaaca gcagcagcaa
661 caacaacaac aacagcagca acaacagcag cagcagcagc aacagcagca gcagcagcaa
721 cagcatcctg gaaagcaagc gaaagagcag cagcagcagc agcagcagca acagcaattg
781 gcagcccagc agcttgtctt ccagcagcag cttctccaga tgcaacaact ccagcagcag
841 cagcatctgc tcagccttca gcgtcaggga ctcatctcca ttccacctgg ccaggcagca
901 cttcctgtcc aatcgctgcc tcaagctggc ttaagtcctg ctgagattca gcagttatgg
961 aaagaagtga ctggagttca cagtatggaa gacaatggca ttaaacatgg agggctagac
1021 ctcactacta acaattcctc ctcgactacc tcctccaaca cttccaaagc atcaccacca
1081 ataactcatc attccatagt gaatggacag tcttcagttc taagtgcaag acgagacagc
1141 tcgtcacatg aggagactgg ggcctctcac actctctatg gccatggagt ttgcaaatgg
1201 ccaggctgtg aaagcatttg tgaagatttt ggacagtttt taaagcacct taacaatgaa
1261 cacgcattgg atgaccgaag cactgctcag tgtcgagtgc aaatgcaggt ggtgcaacag
1321 ttagaaatac agctttctaa agaacgcgaa cgtcttcaag caatgatgac ccacttgcac
1381 atgcgaccct cagagcccaa accatctccc aaacctctaa atctggtgtc tagtgtcacc
1441 atgtcgaaga atatgttgga gacatcccca cagagcttac ctcaaacccc taccacacca
1501 acggccccag tcaccccgat tacccaggga ccctcagtaa tcaccccagc cagtgtgccc
1561 aatgtgggag ccatacgaag gcgacattca gacaaataca acattcccat gtcatcagaa
1621 attgccccaa actatgaatt ttataaaaat gcagatgtca gacctccatt tacttatgca
1681 actctcataa ggcaggctat catggagtca tctgacaggc agttaacact taatgaaatt
1741 tacagctggt ttacacggac atttgcttac ttcaggcgta atgcagcaac ttggaagaat
1801 gcagtacgtc ataatcttag cctgcacaag tgttttgttc gagtagaaaa tgttaaagga
1861 gcagtatgga ctgtggatga agtagaatac cagaagcgaa ggtcacaaaa gataacagga
1921 agtccaacct tagtaaaaaa tatacctacc agtttaggct atggagcagc tcttaatgcc
1981 agtttgcagg ctgccttggc agagagcagt ttacctttgc taagtaatcc tggactgata
2041 aataatgcat ccagtggcct actgcaggcc gtccacgaag acctcaatgg ttctctggat
2101 cacattgaca gcaatggaaa cagtagtccg ggctgctcac ctcagccgca catacattca
2161 atccacgtca aggaagagcc agtgattgca gaggatgaag actgcccaat gtccttagtg
2221 acaacagcta atcacagtcc agaattagaa gacgacagag agattgaaga agagccttta
2281 tctgaagatc tggaatgaga actgacttgt gaaacctcag cgtgaaggga catatcactg
2341 accttcataa ccactccaca accatgaata tttgacaaat ttttactgtg actatttatt
2401 aagcatggat aaaggagaca gccctaaagg aacttactaa gccagccctt tgggattcag
2461 taccaacagg ca
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