LOCUS       NM_001170629            8467 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens chromodomain helicase DNA binding protein 8 (CHD8),
            transcript variant 1, mRNA.
ACCESSION   NM_001170629
VERSION     NM_001170629.2
KEYWORDS    RefSeq; MANE Select.
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 8467)
  AUTHORS   Niu,X., Huang,F., Lyu,H., Liu,J., Zhang,X., Bian,J., Gao,Z. and
            Liu,B.
  TITLE     The Deficiency of the ASD-Related Gene CHD8 Disrupts Behavioral
            Patterns and Inhibits Hippocampal Neurogenesis in Mice
  JOURNAL   J Mol Neurosci 74 (4), 103 (2024)
   PUBMED   39480606
  REMARK    GeneRIF: The Deficiency of the ASD-Related Gene CHD8 Disrupts
            Behavioral Patterns and Inhibits Hippocampal Neurogenesis in Mice.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 8467)
  AUTHORS   Sorrentino,U., Boesch,S., Doummar,D., Ravelli,C., Serranova,T.,
            Indelicato,E., Winkelmann,J., Burglen,L., Jech,R. and Zech,M.
  TITLE     CHD8-related disorders redefined: an expanding spectrum of dystonic
            phenotypes
  JOURNAL   J Neurol 271 (5), 2859-2865 (2024)
   PUBMED   38441608
  REMARK    GeneRIF: CHD8-related disorders redefined: an expanding spectrum of
            dystonic phenotypes.
REFERENCE   3  (bases 1 to 8467)
  AUTHORS   Neuhaus,E., Rea,H., Jones,E., Benavidez,H., Miles,C., Whiting,A.,
            Johansson,M., Eayrs,C., Kurtz-Nelson,E.C., Earl,R., Bernier,R.A.
            and Eichler,E.E.
  TITLE     Shared and divergent mental health characteristics of ADNP-, CHD8-
            and DYRK1A-related neurodevelopmental conditions
  JOURNAL   J Neurodev Disord 16 (1), 15 (2024)
   PUBMED   38622540
  REMARK    GeneRIF: Shared and divergent mental health characteristics of
            ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 8467)
  AUTHORS   Shi,X., Lu,C., Corman,A., Nikish,A., Zhou,Y., Platt,R.J.,
            Iossifov,I., Zhang,F., Pan,J.Q. and Sanjana,N.E.
  TITLE     Heterozygous deletion of the autism-associated gene CHD8 impairs
            synaptic function through widespread changes in gene expression and
            chromatin compaction
  JOURNAL   Am J Hum Genet 110 (10), 1750-1768 (2023)
   PUBMED   37802044
  REMARK    GeneRIF: Heterozygous deletion of the autism-associated gene CHD8
            impairs synaptic function through widespread changes in gene
            expression and chromatin compaction.
REFERENCE   5  (bases 1 to 8467)
  AUTHORS   Bernier,R., Golzio,C., Xiong,B., Stessman,H.A., Coe,B.P., Penn,O.,
            Witherspoon,K., Gerdts,J., Baker,C., Vulto-van Silfhout,A.T.,
            Schuurs-Hoeijmakers,J.H., Fichera,M., Bosco,P., Buono,S.,
            Alberti,A., Failla,P., Peeters,H., Steyaert,J., Vissers,L.E.L.M.,
            Francescatto,L., Mefford,H.C., Rosenfeld,J.A., Bakken,T.,
            O'Roak,B.J., Pawlus,M., Moon,R., Shendure,J., Amaral,D.G., Lein,E.,
            Rankin,J., Romano,C., de Vries,B.B.A., Katsanis,N. and Eichler,E.E.
  TITLE     Disruptive CHD8 mutations define a subtype of autism early in
            development
  JOURNAL   Cell 158 (2), 263-276 (2014)
   PUBMED   24998929
  REMARK    GeneRIF: indings suggest that CHD8 disruptions represent a specific
            pathway in the development of Autism spectrum disorder (ASD) and
            define a distinct ASD subtype. Common phenotypic features include
            increased head size; a facial phenotype marked by prominent
            forehead, wide-set eyes, and pointed chin; as well as increased
            rates of GI complaints and marked sleep dysfunction.
REFERENCE   6  (bases 1 to 8467)
  AUTHORS   Nishiyama,M., Skoultchi,A.I. and Nakayama,K.I.
  TITLE     Histone H1 recruitment by CHD8 is essential for suppression of the
            Wnt-beta-catenin signaling pathway
  JOURNAL   Mol Cell Biol 32 (2), 501-512 (2012)
   PUBMED   22083958
  REMARK    GeneRIF: CHD8 promotes the association of beta-catenin and histone
            H1, with formation of the trimeric complex on chromatin being
            required for inhibition of beta-catenin-dependent transactivation.
REFERENCE   7  (bases 1 to 8467)
  AUTHORS   Kobayashi,M. and Hanai,R.
  TITLE     M phase-specific association of human topoisomerase IIIbeta with
            chromosomes
  JOURNAL   Biochem Biophys Res Commun 287 (1), 282-287 (2001)
   PUBMED   11549288
REFERENCE   8  (bases 1 to 8467)
  AUTHORS   Sakamoto,I., Kishida,S., Fukui,A., Kishida,M., Yamamoto,H.,
            Hino,S., Michiue,T., Takada,S., Asashima,M. and Kikuchi,A.
  TITLE     A novel beta-catenin-binding protein inhibits
            beta-catenin-dependent Tcf activation and axis formation
  JOURNAL   J Biol Chem 275 (42), 32871-32878 (2000)
   PUBMED   10921920
REFERENCE   9  (bases 1 to 8467)
  AUTHORS   Epplen,C. and Epplen,J.T.
  TITLE     Expression of (cac)n/(gtg)n simple repetitive sequences in mRNA of
            human lymphocytes
  JOURNAL   Hum Genet 93 (1), 35-41 (1994)
   PUBMED   7505766
REFERENCE   10 (bases 1 to 8467)
  AUTHORS   Mitchel,M.W., Myers,S.M., Heidlebaugh,A.R., Taylor,C.M., Rea,H.,
            Neuhaus,E., Kurtz-Nelson,E.C., Earl,R., Bernier,R., Ledbetter,D.H.,
            Martin,C.L. and Eichler,E.E.
  TITLE     CHD8-Related Neurodevelopmental Disorder with Overgrowth
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   36302072
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL161747.5, AB046784.3,
            AK122910.1 and BC036920.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 1, 2019 this sequence version replaced NM_001170629.1.
            
            Summary: This gene encodes a member of the
            chromodomain-helicase-DNA binding protein family, which is
            characterized by a SNF2-like domain and two chromatin organization
            modifier domains. The encoded protein also contains brahma and
            kismet domains, which are common to the subfamily of
            chromodomain-helicase-DNA binding proteins to which this protein
            belongs. This gene has been shown to function in several processes
            that include transcriptional regulation, epigenetic remodeling,
            promotion of cell proliferation, and regulation of RNA synthesis.
            Allelic variants of this gene are associated with autism spectrum
            disorder. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Dec 2016].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript and protein alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR18074969.1595906.1,
                                           SRR11853566.8075.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000646647.2/ ENSP00000495240.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-92                AL161747.5         72269-72360         c
            93-754              AL161747.5         47434-48095         c
            755-3783            AB046784.3         1-3029
            3784-3825           AK122910.1         2735-2776
            3826-8180           AB046784.3         3072-7426
            8181-8467           BC036920.1         1176-1462
FEATURES             Location/Qualifiers
     source          1..8467
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q11.2"
     gene            1..8467
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /note="chromodomain helicase DNA binding protein 8"
                     /db_xref="GeneID:57680"
                     /db_xref="HGNC:HGNC:20153"
                     /db_xref="MIM:610528"
     exon            1..92
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            93..1150
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     CDS             308..8053
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /EC_number="3.6.4.12"
                     /note="isoform 1 is encoded by transcript variant 1;
                     helicase with SNF2 domain 1; axis duplication inhibitor;
                     duplin; ATP-dependent helicase CHD8"
                     /codon_start=1
                     /product="chromodomain-helicase-DNA-binding protein 8
                     isoform 1"
                     /protein_id="NP_001164100.1"
                     /db_xref="CCDS:CCDS53885.1"
                     /db_xref="GeneID:57680"
                     /db_xref="HGNC:HGNC:20153"
                     /db_xref="MIM:610528"
                     /translation="MADPIMDLFDDPNLFGLDSLTDDSFNQVTQDPIEEALGLPSSLD
                     SLDQMNQDGGGGDVGNSSASELVPPPEETAPTELSKESTAPAPESITLHDYTTQPASQ
                     EQPAQPVLQTSTPTSGLLQVSKSQEILSQGNPFMGVSATAVSSSSAGGQPPQSAPKIV
                     ILKAPPSSSVTGAHVAQIQAQGITSTAQPLVAGTANGGKVTFTKVLTGTPLRPGVSIV
                     SGNTVLAAKVPGNQAAVQRIVQPSRPVKQLVLQPVKGSAPAGNPGATGPPLKPAVTLT
                     STPTQGESKRITLVLQQPQSGGPQGHRHVVLGSLPGKIVLQGNQLAALTQAKNAQGQP
                     AKVVTIQLQVQQPQQKIQIVPQPPSSQPQPQQPPSTQPVTLSSVQQAQIMGPGQSPGQ
                     RLSVPVKVVLQPQAGSSQGASSGLSVVKVLSASEVAALSSPASSAPHSGGKTGMEENR
                     RLEHQKKQEKANRIVAEAIARARARGEQNIPRVLNEDELPSVRPEEEGEKKRRKKSAG
                     ERLKEEKPKKSKTSGASKTKGKSKLNTITPVVGKKRKRNTSSDNSDVEVMPAQSPRED
                     EESSIQKRRSNRQVKRKKYTEDLDIKITDDEEEEEVDVTGPIKPEPILPEPVQEPDGE
                     TLPSMQFFVENPSEEDAAIVDKVLSMRIVKKELPSGQYTEAEEFFVKYKNYSYLHCEW
                     ATISQLEKDKRIHQKLKRFKTKMAQMRHFFHEDEEPFNPDYVEVDRILDESHSIDKDN
                     GEPVIYYLVKWCSLPYEDSTWELKEDVDEGKIREFKRIQSRHPELKRVNRPQASAWKK
                     LELSHEYKNRNQLREYQLEGVNWLLFNWYNRQNCILADEMGLGKTIQSIAFLQEVYNV
                     GIHGPFLVIAPLSTITNWEREFNTWTEMNTIVYHGSLASRQMIQQYEMYCKDSRGRLI
                     PGAYKFDALITTFEMILSDCPELREIEWRCVIIDEAHRLKNRNCKLLDSLKHMDLEHK
                     VLLTGTPLQNTVEELFSLLHFLEPSQFPSESEFLKDFGDLKTEEQVQKLQAILKPMML
                     RRLKEDVEKNLAPKQETIIEVELTNIQKKYYRAILEKNFSFLSKGAGHTNMPNLLNTM
                     MELRKCCNHPYLINGAEEKILTEFREACHIIPHDFHLQAMVRSAGKLVLIDKLLPKLK
                     AGGHKVLIFSQMVRCLDILEDYLIQRRYLYERIDGRVRGNLRQAAIDRFSKPDSDRFV
                     FLLCTRAGGLGINLTAADTCIIFDSDWNPQNDLQAQARCHRIGQSKAVKVYRLITRNS
                     YEREMFDKASLKLGLDKAVLQSMSGRDGNITGIQQFSKKEIEDLLRKGAYAAIMEEDD
                     EGSKFCEEDIDQILLRRTTTITIESEGKGSTFAKASFVASENRTDISLDDPNFWQKWA
                     KKADLDMDLLNSKNNLVIDTPRVRKQTRHFSTLKDDDLVEFSDLESEDDERPRSRRHD
                     RHHAYGRTDCFRVEKHLLVYGWGRWRDILSHGRFKRRMTERDVETICRAILVYCLLHY
                     RGDENIKGFIWDLISPAENGKTKELQNHSGLSIPVPRGRKGKKVKSQSTFDIHKADWI
                     RKYNPDTLFQDESYKKHLKHQCNKVLLRVRMLYYLRQEVIGDQAEKVLGGAIASEIDI
                     WFPVVDQLEVPTTWWDSEADKSLLIGVFKHGYEKYNTMRADPALCFLEKAGRPDDKAI
                     AAEHRVLDNFSDIVEGVDFDKDCEDPEYKPLQGPPKDQDDEGDPLMMMDEEISVIDGD
                     EAQVTQQPGHLFWPPGSALTARLRRLVTAYQRSYKREQMKIEAAERGDRRRRRCEAAF
                     KLKEIARREKQQRWTRREQTDFYRVVSTFGVEYDPDTMQFHWDRFRTFARLDKKTDES
                     LTKYFHGFVAMCRQVCRLPPAAGDEPPDPNLFIEPITEERASRTLYRIELLRRLREQV
                     LCHPLLEDRLALCQPPGPELPKWWEPVRHDGELLRGAARHGVSQTDCNIMQDPDFSFL
                     AARMNYMQNHQAGAPAPSLSRCSTPLLHQQYTSRTASPLPLRPDAPVEKSPEETATQV
                     PSLESLTLKLEHEVVARSRPTPQDYEMRVSPSDTTPLVSRSVPPVKLEDEDDSDSELD
                     LSKLSPSSSSSSSSSSSSSSTDESEDEKEEKLTDQSRSKLYDEESLLSLTMSQDGFPN
                     EDGEQMTPELLLLQERQRASEWPKDRVLINRIDLVCQAVLSGKWPSSRRSQEMVTGGI
                     LGPGNHLLDSPSLTPGEYGDSPVPTPRSSSAASMAEEEASAVSTAAAQFTKLRRGMDE
                     KEFTVQIKDEEGLKLTFQKHKLMANGVMGDGHPLFHKKKGNRKKLVELEVECMEEPNH
                     LDVDLETRIPVINKVDGTLLVGEDAPRRAELEMWLQGHPEFAVDPRFLAYMEDRRKQK
                     WQRCKKNNKAELNCLGMEPVQTANSRNGKKGHHTETVFNRVLPGPIAPESSKKRARRM
                     RPDLSKMMALMQGGSTGSLSLHNTFQHSSSGLQSVSSLGHSSATSASLPFMPFVMGGA
                     PSSPHVDSSTMLHHHHHHPHPHHHHHHHPGLRAPGYPSSPVTTASGTTLRLPPLQPEE
                     DDDEDEEDDDDLSQGYDSSERDFSLIDDPMMPANSDSSEDADD"
     exon            1151..1522
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            1523..1908
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            1909..2023
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2024..2206
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2207..2275
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2276..2331
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2332..2449
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2450..2533
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2534..2671
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2672..2793
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            2794..3037
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            3038..3214
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            3215..3358
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            3359..3614
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            3615..3825
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            3826..4021
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            4022..4189
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            4190..4369
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            4370..4480
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            4481..4677
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            4678..4877
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            4878..5034
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5035..5124
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5125..5228
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5229..5358
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5359..5434
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5435..5489
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5490..5697
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5698..5906
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            5907..6626
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            6627..6775
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            6776..7078
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            7079..7192
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            7193..7372
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            7373..7489
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     exon            7490..8467
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8447..8452
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /note="hexamer: AATAAA"
     polyA_site      8467
                     /gene="CHD8"
                     /gene_synonym="AUTS18; HELSNF1; IDDAM"
                     /note="major polyA site"
ORIGIN      
        1 gagggctggc catgctccgc cggaaggcgc cttgttctcg gagagggtga gttgaaacgc
       61 tgcctggaaa ggaagtacca ggacttgcac aggagttcca ccatcttcct ctgaagacgt
      121 agccatcttg ctccatgaag gtcaggacaa tctgacatgc acttgtttct tgcctctata
      181 cttgaagagt agtcctctta cattgtgtac atttttttct taatagggga ggggagggga
      241 gagccagtac cccccctccc cttccctccc tagaccttgg agaagtaccc tccattactt
      301 tcccaagatg gcagacccca tcatggatct gttcgatgac ccaaatttat ttggcctgga
      361 ctctctgact gatgacagct ttaaccaggt cacacaagac cccattgagg aagcccttgg
      421 actgccaagc tctctggact ccttggatca gatgaaccag gatggtggag gtggtgatgt
      481 ggggaattca tcagcaagtg aactggtccc tccaccagag gaaacagctc ccacagaact
      541 ttccaaagaa tccacagctc cagctccaga atccataacc ttgcatgatt ataccactca
      601 gcctgccagc caggagcagc cagcccaacc tgtcttacag acatcgacgc caacatcagg
      661 acttttgcaa gtctccaaga gccaggagat cctgagccaa gggaatcctt tcatgggtgt
      721 ctctgccaca gctgtctcct ccagtagtgc tggagggcag ccacctcagt cagcccctaa
      781 gattgttatc cttaaggccc caccaagctc ctcagtcact ggtgcccatg tggcacaaat
      841 tcaggcccaa ggtatcacca gcacagctca gcccctggtg gcaggcacag ccaatggtgg
      901 aaaagtcact tttaccaaag tgctaaccgg cacacccctt cgaccaggtg tttccattgt
      961 ctctggtaat acagtgttgg ccgccaaggt ccctgggaac caggctgctg ttcagcgcat
     1021 tgtccagccc agccgaccag taaagcagct ggtcctccag ccagttaagg gttcagctcc
     1081 tgctggaaac cctggggcca cagggccccc actgaagcct gcagttacac tgacctctac
     1141 acctacccag ggtgaatcga aacgcatcac cctggtcctc cagcagccac agtctggagg
     1201 tccccaagga catcggcatg ttgtgctagg gagtctacca ggcaagatag tgttacaggg
     1261 caaccagctg gcagccctga ctcaagccaa gaatgcccaa gggcagcctg ccaaggtagt
     1321 aactatccag ctgcaggtgc agcagccaca gcaaaaaatc cagattgtac cacaaccacc
     1381 atcatcgcag ccacagcccc agcagccacc ctccacccag ccagtgactc tgtcctctgt
     1441 acagcaggct cagataatgg gaccaggaca aagcccagga caaagacttt cagtaccagt
     1501 caaggtggta ctgcagccac aggctggctc ttcccaaggg gcctcttctg ggctctctgt
     1561 agttaaagtt ctgagtgcca gtgaagtggc agctttgtca tcaccagcaa gctctgctcc
     1621 tcattcgggg ggaaagacag gaatggagga aaaccgcaga ttggaacacc agaagaagca
     1681 agagaaagca aatcggattg tagcagaggc cattgcgaga gcccgtgccc gcggtgagca
     1741 gaacatacct cgagtcttaa atgaggacga gttgcccagc gttcggccag aggaggaagg
     1801 cgagaagaaa cgcaggaaga agagtgctgg ggagaggctg aaagaggaga agccaaagaa
     1861 gagtaaaaca tctggtgcct ccaaaacaaa gggcaagagc aagctcaaca ccatcactcc
     1921 tgtagtgggt aagaagagaa aacgtaatac ctcatctgat aattcagatg tggaagtcat
     1981 gcctgcacag tcacctcgag aagatgaaga aagcagcatt cagaagagac gctcaaaccg
     2041 ccaagttaag cgaaaaaaat atacagagga cctggatata aagatcacag atgatgaaga
     2101 agaagaagag gtggatgtaa ctggtccaat aaaacctgag cctatcctcc ctgaaccagt
     2161 gcaagaacca gatggcgaga ctttgccttc catgcagttc tttgtggaga atcccagtga
     2221 agaagatgca gccattgtag acaaagtgct ttctatgcgg attgtgaaga aggagctccc
     2281 ttctggacaa tatactgaag cagaagaatt ctttgtcaag tacaagaact actcctatct
     2341 gcattgtgaa tgggctacta tctcccaact agagaaggat aagaggatac atcaaaaatt
     2401 aaagcgcttc aaaaccaaaa tggctcagat gagacacttc ttccatgagg atgaagagcc
     2461 ctttaatcca gactacgtag aggtggatag gatattggat gagtctcaca gtattgacaa
     2521 ggacaatggg gagcccgtta tttactacct ggtgaaatgg tgctctctgc cctatgagga
     2581 tagcacatgg gagctaaaag aagatgttga tgagggcaag attcgagaat ttaaacggat
     2641 tcagtcaagg cacccagaac tcaaaagggt gaatcgtccg caggcaagtg cctggaagaa
     2701 attggagcta tcacatgaat ataaaaacag aaaccagcta cgggaatatc agttggaagg
     2761 ggttaattgg ctgctcttta attggtataa caggcagaac tgcatcctgg ctgatgagat
     2821 gggattgggc aaaactattc agtccattgc cttcttgcag gaagtatata atgtgggcat
     2881 ccatggtccc ttcttggtca ttgccccact gtccacaatt actaactggg agcgagaatt
     2941 taatacatgg acagaaatga acactattgt gtaccatggc agtctggcca gcaggcagat
     3001 gattcaacag tatgaaatgt actgcaaaga ttcacgggga cgcctcatcc caggcgcata
     3061 caagtttgac gctctgatca ccacttttga gatgattttg tcagattgtc ctgagcttcg
     3121 tgaaattgaa tggcgttgtg ttatcattga tgaagcccat cgactgaaaa accgtaattg
     3181 caagctgctt gatagtctca agcacatgga cctggaacac aaggtgctac tcacaggaac
     3241 accattgcaa aatactgtag aagaactgtt tagcttgctt catttcttgg aaccgtcaca
     3301 atttccctca gaatcagagt ttctcaagga ctttggggat ctcaagacag aggaacaggt
     3361 tcaaaagcta caggccattc ttaagccaat gatgctgaga agactcaaag aggatgttga
     3421 aaaaaacttg gcacccaaac aggaaacaat tattgaagta gagctgacta atatccagaa
     3481 gaaatactat cgggctattt tggagaagaa tttctccttc ctttccaaag gggcaggtca
     3541 taccaacatg cctaatctac ttaacacaat gatggagttg cgcaagtgct gcaaccaccc
     3601 atatctcatc aatggtgctg aagaaaaaat cctaacagaa ttccgtgaag cttgccatat
     3661 tatacctcat gactttcacc tgcaggccat ggttcgttca gccggcaaac tggttcttat
     3721 tgacaagttg cttccaaagc ttaaagctgg tggccataaa gttctgatct tctctcagat
     3781 ggtgcgctgc ctagacatcc tagaggatta tttaatccag aggaggtact tatatgaacg
     3841 tattgatggg cgagttagag gcaaccttcg acaggctgcc attgaccgct tcagcaagcc
     3901 tgactcagac cgctttgtct tcttactgtg tacccgggct ggtggacttg gtattaatct
     3961 tacagctgct gatacctgca tcatctttga ttcagactgg aatccacaaa atgacctgca
     4021 ggcccaggca cgatgtcatc gaattgggca gagcaaagct gtgaaggtgt accgcctcat
     4081 cactcgtaat tcctacgaga gagagatgtt tgataaggcc agcctcaagt tggggttgga
     4141 taaggctgtg cttcaatcca tgagtggtcg ggatggcaac attactggaa tccaacagtt
     4201 ctctaagaag gagattgaag atcttttaag aaaaggagca tatgcagcca tcatggagga
     4261 agatgatgaa ggctccaagt tttgtgaaga ggacattgac cagatcttgt taagacgaac
     4321 tacaaccatc accattgaat ctgaaggaaa aggttccacc tttgctaagg caagctttgt
     4381 tgcttctgaa aacaggacag atatttcttt ggatgacccc aacttttggc aaaagtgggc
     4441 caaaaaggct gacctagaca tggatctgct caacagcaag aataatttgg taattgacac
     4501 acctagagta cgaaaacaaa cgcgccactt tagcactctg aaagatgatg acctggtgga
     4561 attctctgat ttggaaagtg aggatgatga gcggccacgc tcccgcagac atgaccgtca
     4621 tcatgcctat gggcgcactg actgctttcg ggtggaaaag catctcctgg tatatggttg
     4681 gggacgatgg cgagatattt tatctcatgg acgcttcaag cgacgtatga ctgaacgaga
     4741 tgtggagacc atttgtcggg ccattctcgt gtactgtctt ctacactacc gtggggatga
     4801 aaatattaaa ggcttcatct gggacttgat tagcccagct gaaaatggca agacaaaaga
     4861 attgcagaat cattcaggtc tatctatccc tgtgcctcgt ggacgcaaag gaaaaaaagt
     4921 aaagtcacaa agcacttttg atatccataa ggcagattgg atccggaaat ataaccctga
     4981 cactttgttc caagatgaaa gttataagaa gcacttgaaa catcagtgta acaaggtact
     5041 gttgcgggta cgaatgctat actacctgag gcaggaggtt attggagacc aagcagaaaa
     5101 ggtgttaggg ggtgcgattg ccagtgagat tgacatatgg ttcccagtag tggatcaact
     5161 ggaggttcca acaacttggt gggacagtga ggctgacaag tcgctgctca ttggagtctt
     5221 taaacatggc tatgagaaat ataataccat gagggcagac ccagccttat gtttcctaga
     5281 aaaggctggc cgaccagatg acaaagcaat tgcagcagaa catcgagtgt tggataactt
     5341 ctctgacata gtagaagggg ttgactttga taaagattgt gaagatcctg aatataaacc
     5401 actccaaggt cccccaaagg accaagatga tgagggtgat cccttgatga tgatggatga
     5461 ggagatctca gtgattgatg gagatgaagc ccaggtgacc caacagccag gccatttatt
     5521 ctggcctccg ggctctgccc taacagctag gcttcggcgt ctagtaacag cgtatcagcg
     5581 cagctacaag agagaacaaa tgaagataga ggctgcagaa cgtggggacc ggcgaaggcg
     5641 gcgttgtgaa gcagccttca agctgaaaga aattgcacgg cgggagaaac aacaacgatg
     5701 gacaaggcgt gaacaaactg atttttatcg agtggtgtct acgtttggtg tggaatatga
     5761 ccctgacacc atgcagttcc attgggatcg cttccgcact tttgctcgac tagacaaaaa
     5821 gacagatgaa agccttacca agtacttcca tggctttgtg gccatgtgcc gccaagtatg
     5881 ccgccttccc ccagcagctg gagatgaacc ccccgaccct aacctgttca ttgagcccat
     5941 cactgaggag agagcctcac ggactctcta ccgtatagaa ttgcttcggc gcttacggga
     6001 acaagtttta tgccaccccc ttttggaaga tcggctggca ttgtgtcagc ctcctggtcc
     6061 tgaattgccc aaatggtggg agcctgttcg gcatgatggg gagcttctaa gaggggcagc
     6121 ccgccatggg gtgagccaaa cagactgcaa catcatgcag gacccagact tctcttttct
     6181 ggctgcccgt atgaattata tgcagaacca tcaagcagga gcaccagctc catccttgtc
     6241 acgctgctct actccactgc tgcaccagca gtatacctca cgcactgcct caccactgcc
     6301 cctgcgccca gatgctcctg ttgaaaagtc acccgaggag acagctaccc aggtccccag
     6361 tctggagagt ctgactttaa agctagagca cgaggtggtg gccaggagcc gaccaacccc
     6421 acaagactat gagatgcgag tatccccctc tgatactacc cctctggttt cccggagtgt
     6481 tccaccagtc aaactggagg atgaggatga ttcggactct gagctggact tgagcaagct
     6541 gtcaccatct tcttcttctt cctcatcctc atccagctcc agctccagca ctgatgagag
     6601 tgaggatgag aaggaagaga agctaactga ccagtcccgc tcaaagctct atgatgaaga
     6661 gagtctcctg tccctcacta tgtcccaaga tggattccca aatgaagatg gagaacaaat
     6721 gacccctgag cttctgctac tgcaggaaag acaaagagcc tctgagtggc ccaaggatcg
     6781 tgtcctgata aaccgtattg acctcgtctg ccaggctgta ctctcaggga agtggccttc
     6841 tagccgtagg agccaggaaa tggtaacagg aggaattttg gggccaggca accacttgct
     6901 agacagtccc tcattgactc ctggagaata tggtgactct ccagtcccca caccacgaag
     6961 tagtagtgca gcttccatgg cagaggagga agcatctgca gtcagcacag cggcagccca
     7021 gttcaccaaa cttcgccgag gcatggatga aaaggagttt acagttcaaa tcaaagatga
     7081 ggaaggattg aagttaacat tccagaagca caagttgatg gcgaatggag taatgggaga
     7141 tggacatcca ctgtttcata agaagaaggg gaacagaaag aagctagtag agctggaggt
     7201 ggagtgcatg gaagagccta atcaccttga tgtggacctg gagacccgga tccctgtcat
     7261 caataaggtg gatggtactt tgctggtggg tgaggatgcc cctcgccggg ctgaactgga
     7321 gatgtggtta cagggtcatc cagagtttgc tgttgatccc cgatttctag cgtatatgga
     7381 ggatcgcaga aaacagaagt ggcaaagatg taaaaaaaat aataaggcag aattgaactg
     7441 tttgggaatg gaaccagtac agacagctaa ctctagaaat gggaaaaagg gtcatcacac
     7501 tgaaacggtg ttcaaccggg ttttgccagg gcctattgca ccagagagca gcaagaagcg
     7561 ggcccgtagg atgcgaccag acctttctaa gatgatggcc ctcatgcagg gtggaagcac
     7621 tgggtctcta tctctgcata acacgttcca acacagcagt agtggcctac agtctgtgtc
     7681 atctttgggt cacagcagtg ccacttctgc atctttgcct tttatgccat ttgtgatggg
     7741 tggtgcacca tcatcccctc atgtagactc cagcaccatg cttcatcacc accaccacca
     7801 cccccacccc caccatcacc accatcacca tccaggcttg agagcccctg gctacccctc
     7861 ttcaccagtg actaccgcct ctggtactac cttgcggttg ccaccactgc aacctgagga
     7921 ggatgacgat gaggatgaag aagatgatga tgacttatct cagggctatg atagctcaga
     7981 aagggacttc tcactcattg atgatcctat gatgccagct aactcagact ccagtgaaga
     8041 tgctgatgac tgaagcccca gcatgggccc cattgcttgg gcggctgctg tattttcatt
     8101 tactctggcc cttggactat ggaaacgtgg gaggggcagg ggagatgtgg ggaagtccag
     8161 gactccagga ggtgaaaagg aaaaaaaaaa aaaaatgtac ctgattgctc ccaattatga
     8221 gaggattggg tgggcagggg aactcctaaa ataatacatg accacttcct catttctggg
     8281 gaaggaaagg agactagagc agctggtgtg ctcacccctc cctagtcacc tccattaacc
     8341 acagactatg tagcgctggc cctagcctct ggcagagcct gttcctggcc gaactgtgga
     8401 tacagctgga gggtcaggaa ctgttacctt ctttcccctt ggcattaata aatttaagtt
     8461 aatcctt
//
