LOCUS       NM_173495              12883 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens patched domain containing 1 (PTCHD1), mRNA.
ACCESSION   NM_173495
VERSION     NM_173495.3
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 12883)
  AUTHORS   Xie,C.T.Y., Pastore,S.F., Vincent,J.B., Frankland,P.W. and
            Hamel,P.A.
  TITLE     Nonsynonymous Mutations in Intellectual Disability and Autism
            Spectrum Disorder Gene PTCHD1 Disrupt N-Glycosylation and Reduce
            Protein Stability
  JOURNAL   Cells 13 (2), 199 (2024)
   PUBMED   38275824
  REMARK    GeneRIF: Nonsynonymous Mutations in Intellectual Disability and
            Autism Spectrum Disorder Gene PTCHD1 Disrupt N-Glycosylation and
            Reduce Protein Stability.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 12883)
  AUTHORS   Farley,K.O., Forbes,C.A., Shaw,N.C., Kuzminski,E., Ward,M.,
            Baynam,G., Lassmann,T. and Fear,V.S.
  TITLE     CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate
            patient phenotype when undergoing neural induction
  JOURNAL   HGG Adv 5 (1), 100257 (2024)
   PUBMED   38007613
  REMARK    GeneRIF: CRISPR-Cas9-generated PTCHD1 2489T>G stem cells
            recapitulate patient phenotype when undergoing neural induction.
REFERENCE   3  (bases 1 to 12883)
  AUTHORS   Halewa,J., Marouillat,S., Dixneuf,M., Thepault,R.A., Ung,D.C.,
            Chatron,N., Gerard,B., Ghoumid,J., Lesca,G., Till,M., Smol,T.,
            Couque,N., Ruaud,L., Chune,V., Grotto,S., Verloes,A.,
            Vuillaume,M.L., Toutain,A., Raynaud,M. and Laumonnier,F.
  TITLE     Novel missense mutations in PTCHD1 alter its plasma membrane
            subcellular localization and cause intellectual disability and
            autism spectrum disorder
  JOURNAL   Hum Mutat 42 (7), 848-861 (2021)
   PUBMED   33856728
  REMARK    GeneRIF: Novel missense mutations in PTCHD1 alter its plasma
            membrane subcellular localization and cause intellectual disability
            and autism spectrum disorder.
REFERENCE   4  (bases 1 to 12883)
  AUTHORS   Ross,P.J., Zhang,W.B., Mok,R.S.F., Zaslavsky,K., Deneault,E.,
            D'Abate,L., Rodrigues,D.C., Yuen,R.K.C., Faheem,M., Mufteev,M.,
            Piekna,A., Wei,W., Pasceri,P., Landa,R.J., Nagy,A., Varga,B.,
            Salter,M.W., Scherer,S.W. and Ellis,J.
  TITLE     Synaptic Dysfunction in Human Neurons With Autism-Associated
            Deletions in PTCHD1-AS
  JOURNAL   Biol Psychiatry 87 (2), 139-149 (2020)
   PUBMED   31540669
  REMARK    GeneRIF: Synaptic Dysfunction in Human Neurons With
            Autism-Associated Deletions in PTCHD1-AS.
REFERENCE   5  (bases 1 to 12883)
  AUTHORS   Torrico,B., Fernandez-Castillo,N., Hervas,A., Mila,M., Salgado,M.,
            Rueda,I., Buitelaar,J.K., Rommelse,N., Oerlemans,A.M., Bralten,J.,
            Freitag,C.M., Reif,A., Battaglia,A., Mazzone,L., Maestrini,E.,
            Cormand,B. and Toma,C.
  TITLE     Contribution of common and rare variants of the PTCHD1 gene to
            autism spectrum disorders and intellectual disability
  JOURNAL   Eur J Hum Genet 23 (12), 1694-1701 (2015)
   PUBMED   25782667
  REMARK    GeneRIF: both common and rare PTCHD1 variants contribute to autism
            spectrum disorder.
REFERENCE   6  (bases 1 to 12883)
  AUTHORS   Corominas,R., Yang,X., Lin,G.N., Kang,S., Shen,Y., Ghamsari,L.,
            Broly,M., Rodriguez,M., Tam,S., Wanamaker,S.A., Fan,C., Yi,S.,
            Tasan,M., Lemmens,I., Kuang,X., Zhao,N., Malhotra,D.,
            Michaelson,J.J., Vacic,V., Calderwood,M.A., Roth,F.P.,
            Tavernier,J., Horvath,S., Salehi-Ashtiani,K., Korkin,D., Sebat,J.,
            Hill,D.E., Hao,T., Vidal,M. and Iakoucheva,L.M.
  TITLE     Protein interaction network of alternatively spliced isoforms from
            brain links genetic risk factors for autism
  JOURNAL   Nat Commun 5, 3650 (2014)
   PUBMED   24722188
  REMARK    Erratum:[Nat Commun. 2023 Feb 2;14(1):569. doi:
            10.1038/s41467-023-36264-y.. PMID: 36732511]
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 12883)
  AUTHORS   Kennedy,R.B., Ovsyannikova,I.G., Pankratz,V.S., Haralambieva,I.H.,
            Vierkant,R.A. and Poland,G.A.
  TITLE     Genome-wide analysis of polymorphisms associated with cytokine
            responses in smallpox vaccine recipients
  JOURNAL   Hum Genet 131 (9), 1403-1421 (2012)
   PUBMED   22610502
REFERENCE   8  (bases 1 to 12883)
  AUTHORS   Filges,I., Rothlisberger,B., Blattner,A., Boesch,N., Demougin,P.,
            Wenzel,F., Huber,A.R., Heinimann,K., Weber,P. and Miny,P.
  TITLE     Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked
            intellectual disability with or without autism
  JOURNAL   Clin Genet 79 (1), 79-85 (2011)
   PUBMED   21091464
  REMARK    GeneRIF: Deletion in Xp22.11: PTCHD1 is a candidate gene for
            X-linked intellectual disability with or without autism.
REFERENCE   9  (bases 1 to 12883)
  AUTHORS   Noor,A., Whibley,A., Marshall,C.R., Gianakopoulos,P.J., Piton,A.,
            Carson,A.R., Orlic-Milacic,M., Lionel,A.C., Sato,D., Pinto,D.,
            Drmic,I., Noakes,C., Senman,L., Zhang,X., Mo,R., Gauthier,J.,
            Crosbie,J., Pagnamenta,A.T., Munson,J., Estes,A.M., Fiebig,A.,
            Franke,A., Schreiber,S., Stewart,A.F., Roberts,R., McPherson,R.,
            Guter,S.J., Cook,E.H. Jr., Dawson,G., Schellenberg,G.D.,
            Battaglia,A., Maestrini,E., Jeng,L., Hutchison,T.,
            Rajcan-Separovic,E., Chudley,A.E., Lewis,S.M., Liu,X., Holden,J.J.,
            Fernandez,B., Zwaigenbaum,L., Bryson,S.E., Roberts,W., Szatmari,P.,
            Gallagher,L., Stratton,M.R., Gecz,J., Brady,A.F., Schwartz,C.E.,
            Schachar,R.J., Monaco,A.P., Rouleau,G.A., Hui,C.C., Lucy
            Raymond,F., Scherer,S.W. and Vincent,J.B.
  CONSRTM   Autism Genome Project Consortium
  TITLE     Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum
            disorder and intellectual disability
  JOURNAL   Sci Transl Med 2 (49), 49ra68 (2010)
   PUBMED   20844286
  REMARK    GeneRIF: Systematic screen of PTCHD1 and its 5' flanking regions
            suggests that this locus is involved in ~1% of individuals with
            autism spectrum disorder and intellectual disability.
REFERENCE   10 (bases 1 to 12883)
  AUTHORS   Pinto,D., Pagnamenta,A.T., Klei,L., Anney,R., Merico,D., Regan,R.,
            Conroy,J., Magalhaes,T.R., Correia,C., Abrahams,B.S., Almeida,J.,
            Bacchelli,E., Bader,G.D., Bailey,A.J., Baird,G., Battaglia,A.,
            Berney,T., Bolshakova,N., Bolte,S., Bolton,P.F., Bourgeron,T.,
            Brennan,S., Brian,J., Bryson,S.E., Carson,A.R., Casallo,G.,
            Casey,J., Chung,B.H., Cochrane,L., Corsello,C., Crawford,E.L.,
            Crossett,A., Cytrynbaum,C., Dawson,G., de Jonge,M., Delorme,R.,
            Drmic,I., Duketis,E., Duque,F., Estes,A., Farrar,P.,
            Fernandez,B.A., Folstein,S.E., Fombonne,E., Freitag,C.M.,
            Gilbert,J., Gillberg,C., Glessner,J.T., Goldberg,J., Green,A.,
            Green,J., Guter,S.J., Hakonarson,H., Heron,E.A., Hill,M., Holt,R.,
            Howe,J.L., Hughes,G., Hus,V., Igliozzi,R., Kim,C., Klauck,S.M.,
            Kolevzon,A., Korvatska,O., Kustanovich,V., Lajonchere,C.M.,
            Lamb,J.A., Laskawiec,M., Leboyer,M., Le Couteur,A., Leventhal,B.L.,
            Lionel,A.C., Liu,X.Q., Lord,C., Lotspeich,L., Lund,S.C.,
            Maestrini,E., Mahoney,W., Mantoulan,C., Marshall,C.R.,
            McConachie,H., McDougle,C.J., McGrath,J., McMahon,W.M.,
            Merikangas,A., Migita,O., Minshew,N.J., Mirza,G.K., Munson,J.,
            Nelson,S.F., Noakes,C., Noor,A., Nygren,G., Oliveira,G.,
            Papanikolaou,K., Parr,J.R., Parrini,B., Paton,T., Pickles,A.,
            Pilorge,M., Piven,J., Ponting,C.P., Posey,D.J., Poustka,A.,
            Poustka,F., Prasad,A., Ragoussis,J., Renshaw,K., Rickaby,J.,
            Roberts,W., Roeder,K., Roge,B., Rutter,M.L., Bierut,L.J.,
            Rice,J.P., Salt,J., Sansom,K., Sato,D., Segurado,R., Sequeira,A.F.,
            Senman,L., Shah,N., Sheffield,V.C., Soorya,L., Sousa,I., Stein,O.,
            Sykes,N., Stoppioni,V., Strawbridge,C., Tancredi,R., Tansey,K.,
            Thiruvahindrapduram,B., Thompson,A.P., Thomson,S., Tryfon,A.,
            Tsiantis,J., Van Engeland,H., Vincent,J.B., Volkmar,F., Wallace,S.,
            Wang,K., Wang,Z., Wassink,T.H., Webber,C., Weksberg,R., Wing,K.,
            Wittemeyer,K., Wood,S., Wu,J., Yaspan,B.L., Zurawiecki,D.,
            Zwaigenbaum,L., Buxbaum,J.D., Cantor,R.M., Cook,E.H., Coon,H.,
            Cuccaro,M.L., Devlin,B., Ennis,S., Gallagher,L., Geschwind,D.H.,
            Gill,M., Haines,J.L., Hallmayer,J., Miller,J., Monaco,A.P.,
            Nurnberger,J.I. Jr., Paterson,A.D., Pericak-Vance,M.A.,
            Schellenberg,G.D., Szatmari,P., Vicente,A.M., Vieland,V.J.,
            Wijsman,E.M., Scherer,S.W., Sutcliffe,J.S. and Betancur,C.
  TITLE     Functional impact of global rare copy number variation in autism
            spectrum disorders
  JOURNAL   Nature 466 (7304), 368-372 (2010)
   PUBMED   20531469
  REMARK    GeneRIF: Observational study and genome-wide association study of
            gene-disease association. (HuGE Navigator)
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC073910.20, DC365753.1, DC351268.1, BC121061.2 and BX107899.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_173495.2.
            
            Summary: This gene encodes a membrane protein with a patched
            domain. The encoded protein is similar to Drosophila proteins which
            act as receptors for the morphogen sonic hedgehog. Deletions in
            this gene, which is located on the X chromosome, are associated
            with intellectual disability and autism (PMID: 21091464, PMID:
            20844286). [provided by RefSeq, Aug 2011].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript was available
            for the full length of the gene. The extent of this transcript is
            supported by transcript 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 :: SRR3476690.837819.1,
                                           SRR1660809.24632.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968832
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000379361.5/ ENSP00000368666.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-19                AC073910.20        128180-128198       c
            20-40               DC365753.1         1-21
            41-64               DC351268.1         17-40
            65-172              DC365753.1         46-153
            173-2720            BC121061.2         1-2548
            2721-4653           AC073910.20        66903-68835         c
            4654-5310           BX107899.1         1-657
            5311-12883          AC073910.20        58673-66245         c
FEATURES             Location/Qualifiers
     source          1..12883
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.11"
     gene            1..12883
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /note="patched domain containing 1"
                     /db_xref="GeneID:139411"
                     /db_xref="HGNC:HGNC:26392"
                     /db_xref="MIM:300828"
     exon            1..378
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /inference="alignment:Splign:2.1.0"
     CDS             28..2694
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /codon_start=1
                     /product="patched domain-containing protein 1"
                     /protein_id="NP_775766.2"
                     /db_xref="CCDS:CCDS35215.2"
                     /db_xref="GeneID:139411"
                     /db_xref="HGNC:HGNC:26392"
                     /db_xref="MIM:300828"
                     /translation="MLRQVLHRGLRTCFSRLGHFIASHPVFFASAPVLISILLGASFS
                     RYQVEESVEHLLAPQHSLAKIERNLVNSLFPVNRSKHRLYSDLQTPGRYGRVIVTSFQ
                     KANMLDQHHTDLILKLHAAVTKIQVPRPGFNYTFAHICILNNDKTCIVDDIVHVLEEL
                     KNARATNRTNFAITYPITHLKDGRAVYNGHQLGGVTVHSKDRVKSAEAIQLTYYLQSI
                     NSLNDMVAERWESSFCDTVRLFQKSNSKVKMYPYTSSSLREDFQKTSRVSERYLVTSL
                     ILVVTMAILCCSMQDCVRSKPWLGLLGLVTISLATLTAAGIINLTGGKYNSTFLGVPF
                     VMLGHGLYGTFEMLSSWRKTREDQHVKERTAAVYADSMLSFSLTTAMYLVTFGIGASP
                     FTNIEAARIFCCNSCIAIFFNYLYVLSFYGSSLVFTGYIENNYQHSIFCRKVPKPEAL
                     QEKPAWYRFLLTARFSEDTAEGEEANTYESHLLVCFLKRYYCDWITNTYVKPFVVLFY
                     LIYISFALMGYLQVSEGSDLSNIVATATQTIEYTTAQQKYFSNYSPVIGFYIYESIEY
                     WNTSVQEDVLEYTKGFVRISWFESYLNYLRKLNVSTGLPKKNFTDMLRNSFLKAPQFS
                     HFQEDIIFSKKYNDEVDVVASRMFLVAKTMETNREELYDLLETLRRLSVTSKVKFIVF
                     NPSFVYMDRYASSLGAPLHNSCISALFLLFFSAFLVADSLINVWITLTVVSVEFGVIG
                     FMTLWKVELDCISVLCLIYGINYTIDNCAPMLSTFVLGKDFTRTKWVKNALEVHGVAI
                     LQSYLCYIVGLIPLAAVPSNLTCTLFRCLFLIAFVTFFHCFAILPVILTFLPPSKKKR
                     KEKKNPENREEIECVEMVDIDSTRVVDQITTV"
     exon            379..1039
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /inference="alignment:Splign:2.1.0"
     exon            1040..12883
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5500..5505
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /note="hexamer: TATAAA"
     polyA_site      5529
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
     regulatory      12861..12866
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /note="hexamer: ATTAAA"
     polyA_site      12883
                     /gene="PTCHD1"
                     /gene_synonym="AUTSX4; CXDELp22.11; DELXP22.11; SLC65C1"
                     /note="major polyA site"
ORIGIN      
        1 ctcctcccgc gcccgctctg ctctaggatg ctgcggcagg ttctgcacag gggcttgagg
       61 acgtgtttct cccggctcgg ccacttcatt gccagtcacc ctgtcttctt cgcctcggcg
      121 ccggtgctca tctccatcct gctcggcgcc agcttcagcc gctaccaggt cgaggagagc
      181 gtggagcacc tgctggcgcc ccagcacagc ctggccaaga tcgagcgcaa cctcgttaac
      241 agcctcttcc cggtcaaccg ctccaagcac cgtctctact cggacctgca gacccccggg
      301 cgctacggcc gggtcatcgt cacctccttc cagaaagcca acatgctgga ccagcatcac
      361 accgacctga tcttaaagtt gcatgctgct gtcaccaaga tccaggttcc aaggcctggt
      421 tttaattaca cgtttgccca tatatgtatc ctgaataatg ataagacttg catcgtggat
      481 gacatagtgc acgtcctgga agagctaaag aatgctcggg ccaccaatcg gaccaatttt
      541 gctatcacat acccaatcac tcacttaaag gacgggaggg ctgtgtacaa tgggcaccag
      601 cttgggggcg tcactgtgca cagcaaagac cgggtgaaat ctgcagaggc catccagctc
      661 acctactacc tgcagtcaat caacagtctc aatgacatgg tggctgagag gtgggagtcc
      721 agcttctgcg acactgtcag actgtttcag aaatccaaca gcaaagtcaa aatgtaccct
      781 tacacgtcct cctcactgag ggaagatttc cagaagacca gccgcgtatc agaacgttac
      841 ctggtcacca gcctgattct ggtggttacc atggccatcc tgtgttgctc tatgcaggac
      901 tgcgtccgca gcaaaccctg gctaggcctg ctcggattgg tgaccataag cctggccact
      961 ctcactgcag ccgggatcat caatcttact ggtgggaaat ataattccac cttcctggga
     1021 gtccctttcg tcatgctagg tcatggatta tatgggactt ttgaaatgtt atcctcctgg
     1081 aggaaaacta gagaagacca acatgttaaa gagagaactg cagcagtcta tgcagactcc
     1141 atgctctcct tttctctcac cactgccatg tacctggtca cctttggcat aggggccagc
     1201 cctttcacga acattgaggc agccaggatt ttctgctgca attcctgtat tgcaatcttc
     1261 ttcaactacc tctatgtact ctcgttttat ggttccagcc tagtgttcac tggctacata
     1321 gaaaacaatt accagcatag tatcttctgt agaaaagtcc caaagcctga ggcattgcag
     1381 gagaagccgg catggtacag gtttctcctg acggccagat tcagtgagga cacagctgaa
     1441 ggcgaggaag cgaacactta cgagagtcac ctattggtat gtttcctcaa acgctattac
     1501 tgtgactgga taaccaacac ctatgtcaag ccttttgtag ttctctttta ccttatttat
     1561 atttcctttg ccttaatggg ctatctgcag gtcagtgaag ggtcagacct tagtaacatt
     1621 gtagcaaccg cgacacaaac cattgagtac actactgccc agcaaaagta cttcagcaac
     1681 tacagtcctg tgattgggtt ttacatatat gagtctatag aatactggaa cactagtgtc
     1741 caagaagatg ttctagaata caccaagggg tttgtgcgga tatcctggtt tgagagctat
     1801 ttaaattacc ttcggaaact caatgtatcc actggcttgc ctaagaaaaa tttcacagac
     1861 atgttgagga attcctttct gaaagcccct caattttcac attttcaaga ggacatcatc
     1921 ttctctaaaa aatacaatga tgaggtcgat gtagtggcct ccagaatgtt tttggtggcc
     1981 aagaccatgg aaacaaacag agaagaactc tatgatctct tggaaaccct gaggagactt
     2041 tctgtcacct ccaaggtgaa gttcatcgtc ttcaatccgt cctttgtata catggatcga
     2101 tatgcctcct ctctgggagc ccccctgcac aactcctgca tcagtgcttt gttcctgctc
     2161 ttcttctcgg cattcctggt ggcagattca ctgattaacg tctggatcac tctcacagtt
     2221 gtgtccgtgg agtttggagt gataggtttc atgacattat ggaaagtaga actggactgc
     2281 atttctgtgc tatgcttaat ttatggaatt aattacacaa ttgacaattg tgctccaatg
     2341 ttatccacat ttgttctggg caaggatttc acaagaacta aatgggtaaa aaatgccctg
     2401 gaagtgcatg gggtagctat tttacagagt tacctctgct atattgttgg tctgattcct
     2461 cttgcagctg tgccttcaaa tctgacctgt acactgttca ggtgcttgtt tttaatagca
     2521 tttgtcacct tctttcactg ctttgccatt ttacctgtga tactgacttt cctgccaccc
     2581 tctaagaaaa aaaggaaaga gaagaaaaat cctgagaacc gggaggaaat tgagtgtgta
     2641 gaaatggtag atatcgatag tacccgtgtg gttgaccaaa ttacaacagt gtgataatgt
     2701 ctgcttggca tattttcacc ttaggtctta tcaagaccaa agagattatg ttaatgaaac
     2761 aattaaattc aaagttcttc ccttttttaa agataggaaa caggcattgc caaaaaaaaa
     2821 aaaaaaaaaa aaaggaaagg acagtgggga gaaatgggcc tggcatattt tcagtcttta
     2881 aaacaaagga gttgttatga gaattcacac acacatagac acacacacac acacacacac
     2941 acacacacac acacacacac cctgggagac ctatagtctc ttaaactaag atcaagtaga
     3001 agaaagctta ttaacaagca ggatcctgcc ttatccaaac tgcagatgtt gctggcattg
     3061 tgacaaaacc cactgattga aaggtcaact gccaaggcag aaacaccttt aagcattgtt
     3121 caaacaataa ggcttccaga acttctgtag agcagtagct ccagtcatgg tctgtggttt
     3181 gaggttttag ctgtctcacc tagctcccta acactgaagg agatacttgt gaaagttctg
     3241 accagcaaaa gcaagccaga gccttggaaa ctgatatgtg gtagagtggc catcactcat
     3301 ggactaaaat tgattcaccg ctaaatttac ccaggtgaag cagtttcgtt gtctagaatg
     3361 aaattatcat attccgccat tggtatgcct ttaacatttg tatagtttgg tttgcttaaa
     3421 acaccttaaa accaatgaca gctccagcac tgcagaattg gtgtgattct actttggaat
     3481 agcttgtcac ttgtcaccaa atgggtctgc tttattagtt acagctcttg gcaggaggat
     3541 ccagggaccc aaaaccacag ggccaaaccc aaatacctgg catgatggag caaaagcagg
     3601 tgtctacttg gacccagata tagtgtctcc attttaacaa caacaacaaa atagccagct
     3661 ggtacagctg tttgcattgg ccctacatgc attttttgca tggatatcca gaaacatctg
     3721 cccacacaaa actgcgggga aaaaaaatga acactgaaat agttatttgc tgttgcttcc
     3781 aacttgtagt gccagtctgc ctttgctgtg aaacacacct gctcagagac agagagggga
     3841 agaagatctt tggtaagtct aagtcctgac gctgagaagc tttgtaaaag tgcagggaga
     3901 taaagggcca aaagggagat agatggaaaa cactggaaaa agtattcact gatacaaatc
     3961 tatcaatgat ggcagtccaa ttctcttgct aaagtggctg cacctcacct tgctggtccc
     4021 ccccacacct tttttgatgt ccttctgcgt catcatagca aggcccttct gtaaattaac
     4081 aagcctagat atttatactc ttgacttcca gtatctacag aagaatggtt catagatcta
     4141 aacagaaatg gtttagatct aaaaaggctg tatacgttgc ccaggcccct gcatttcttt
     4201 aaatttataa aaatgaagct aaaacctggt tacatttgaa gcaaatatct acagtatttt
     4261 tcccttttag agatgtagct tccttagaca tctgtagtgg taagcatttc ccaaaagcat
     4321 cttacctttc tgaaccttag cagacatact gtgcagctta cctatcttct gcagaggagg
     4381 aaactgagac ctaggagaat aaagtgactc actcaggtca caccactaaa gggttttcat
     4441 catttcagca tacctaagac agggcagtcc aattttcagt attctcataa gatggctatt
     4501 actcctctca aaatgcattt ccaaagtagg aacataggac ttcgttggcc acagggcaga
     4561 cattttttta gtgtctggaa ttaaaatgtt tgaggtttag gtttgccatt gtctttccaa
     4621 aaggccaaat aattcagatg taaccacacc aagtgcaaac ctgtgctttc tatttcacgt
     4681 actgttgtcc atacagttct aaatacatgt gcaggggatt gtagctaatg cattacacag
     4741 tcgttcagtc ttctctgcag acacactaag tgatcatacc aacgtgttat acactcaact
     4801 agaagataat aagctttaat ctgagggcaa gtacagtcct gacaaaaggg caagtttgca
     4861 taatagatct tcgatcaatt ctctctccaa ggggcccgca actaggctat tattcataaa
     4921 acacaactga agaggggatt ggttttactg ttaaatcatg tgttgctaaa tcattttctg
     4981 aacagtgtgt tctaaatcag tcattgattt agtgtcagcc acgtggagca cctcggctta
     5041 aagcagctcc acaaaacctg acacaacaca cacaccaatt aaatggattt tgttgagaat
     5101 ttaatcattc aatttggtca accagaatga cttcctgtgg aactctgttt tatgacagat
     5161 aatagttttc caacttgatt gagtctctgt ataccctggg atattgtatt ttttaatgaa
     5221 gggcattttc aaacttgtca acttctcttt tcagcacttg aaatgaaggc ttatggaatt
     5281 ctgactgtga aatgaatttt tctattggga gattatgcat gccaagattt attatttatt
     5341 gttagataat tattatttat ttgttaatac tgattattga ttattgctct gctgcattgg
     5401 tttagccccg ctatggagaa gacactttag aagtaactca gaatcacatc cccataaaat
     5461 ctaagtcttt acttcatcaa gttttacttt ttgaattgct ataaagacgg aaaaattgat
     5521 ccctgcaaac acttgaagaa gctgtgtttt ttttctttca attaattcca accaagacat
     5581 taacgtccac tttaccaaag aaacttactt ggttggtttt tagttggtgt ttgttgtttg
     5641 tttaccaaag aaaatattcg attcatcaaa aatattgctc ctggtcaact aaaaaactgt
     5701 gatactggga cttttttggc cattcataag gaaaattttt aaaagtcaag gtaagggtga
     5761 tattctctca tttagtggaa gaagaagatg tcaattcaca gggaatgtgg tgttcgcaag
     5821 aaagaaaatg atacttgaaa tagggcatta ttgtttagcc tacagcaaca tttcaacaag
     5881 cagcatcagg gctcctcagg ttaaaagaag tacagtttgt ttcagagaaa aaggaagaca
     5941 aaccctcgtg aaatgtttct ccattgttcc agctcataag ttttactttg ttttgggttt
     6001 tggagttttt agtttctttg atgtttgttt tgctttaatt tggtttgtgg tttgtgtttg
     6061 cttgtgtttg cttctgcctt tcctaccttc tgccttttac tccctcagtt ttcagtcaga
     6121 agtgtgataa tcagatgcca tcctccatgg ccacgcttat gtatgcaata taccgctcca
     6181 aatgaggacc ttggtaaccc ttgacccttt aattctaact aaccatcacc caatcgtaag
     6241 tggcattatg ggaccatgat accacttttc tccagtgtca atgacagagc tcagctgtgt
     6301 ccatcacaag aaaaggtgga atgggcagct gtcttggggg tgtggcaaga ggcagaacct
     6361 cttggacaca aatgttatct tcctcataat ggctttattc ttttggatcc tattaaagta
     6421 cccctgtagc ttatagtagt gtttgacctc tgtgactctg ttttctcatc tgtaaaatgg
     6481 ggataatatc agtaaatgtc tttaaattca gcaaatactt atcgagtgcc aaatatcgcc
     6541 cagatactgt tcgagaggct ggggacacaa cagtcaacaa atcagatttt ttaaaatctg
     6601 ctcttgtaga gtctaccttt gagtgacatt gcaggtatat tgtggggatt gaatgagatg
     6661 agagatgaca tttggaaagc actcttggaa aggcctggca aagaaaagag actcaagaca
     6721 ttatttgtaa ttcagcaatc tcgcacagta gcattagggc tcgggatgta aagctactga
     6781 gaagtagatt tgagcctgag aattagggct acaaatacaa tgagttgcca cagaaggtag
     6841 ttaattacca gtcattttag gacatcaaaa tgaagctgat caccacatag tggggccact
     6901 gtaaaggggc tgcaagtcct ggatgttggc atcatactat gatctttgaa aaaaacagat
     6961 acaggcactt gcttttgggg atggggaagg gacaccactg attactgaat aactgtggct
     7021 ggcttgtctg agggaatgta aacattccct tgaggtaatt tgcttttaat tttgtgtaaa
     7081 aagcaccagg tatttagaga cataaagttc ccgtttttta aaagaatagt aaatctgcaa
     7141 tacaaagaaa aatattaagt tagtggattc gctggcaaag aactaagaat ggctgcagcc
     7201 aacacactgc agagttcctc cctgtggtgg ttacaactgt tatttctgtt tcatgccagt
     7261 ccaggagaaa gcaaagagga aagtggatga gctataatcc gttcacctga ataggcagtg
     7321 ccaggatgtc ccccccagct tgcctctcac ccgccccgct gctgcccagc tgatttgttt
     7381 gaagtcctct ttgatatcta tgagagcacc gtggaaggaa gaagaaggga ggcgaccgga
     7441 gagctatggc ctctgtgcag atttttgagt tagattaaaa ttagtaccac ctgattagga
     7501 gcctacctgg tgaggaaaaa agccttcttt tcaaagtaca aaaaaaagcg atgtgtacca
     7561 aggagaaaac cagcagagaa agcttggtgg aagaagtgat gttcttgtgg aatgtgccag
     7621 cagcttctcc ttccagaatg ctgacaccag atgaatcttt ggttagaatt aagcctaccc
     7681 ctttgttttt cacatgagaa aactgaaccc tcgagtaatg aaattatatt cacagagcta
     7741 attagaaaca ggagactata attgaaatct agtttttagc ctcaattctt tctccatttt
     7801 gccactttac tgccaaattc tattcatcta aattattggg gtcttaacct gggggccaaa
     7861 tgagttcatg ggaggggtct ctgagtttcc tacaattaag ttacatgcaa aaatgtgtgt
     7921 atatgttcaa catgtgcatt ttcctaaact gagggctcag attccaaaag aggtctatga
     7981 ccgaaaaagg gtgaagaacc actgtcctaa attaatacag acctcattgg gagtgtgatc
     8041 ctggtgtcct cattttggct aatgagcaat caagaacttt tgaactatct tttctctaag
     8101 gatccaaaaa tgcttcaaaa tattggtttc ttcatcccaa gccaagtgcc tacttctatt
     8161 catttattct tcattcattc tttcattcat tcatttcttt attctgcaaa tgtattttca
     8221 gtgccaattc atgttctagc agcagctaaa tatgccctcc acagcaggac caggaaagga
     8281 gccctctgta ctgtgctctt gttggcaaga ggaacaccag gttgctacca cattctcact
     8341 gttgcaacaa attatatata gcctcaaatt ttcagtaacc atcccacaca cacatacaca
     8401 cataaaggca gcagccaaca aagccaacat atagaagtgt gccctgtcaa agaaccagga
     8461 agagcagcct atttccaggt tatatacagt gatatgctgt ttacaactgc ataccacatc
     8521 cttagaaggc ctgctcccaa atgagcccta ctctgagatg tctacaccag gcatgctttc
     8581 acacacgtgc agtaccctac tctcaaaaca agtatggaga gaataagtct cattcatctc
     8641 gttaatattt ttagtgggca aagaagcaac cgtggccatg gacagatggg tgcatttaag
     8701 gacaggtgtg gccgggcaca gtggctcaag cctgtaatcc cagcactttg ggaggcggag
     8761 gcgggcagat cacgaggtta agagattgag accatcctgg ccagcatggt gaaaccccgc
     8821 ctctactaaa aaatacaaaa aaattagctg ggcgtggtgg cacgtgcctg tagtcccagc
     8881 tactcaggag gcaggagaat cccttgaacc cgggaggtag aagttgcagt gagccgagat
     8941 ttcaccactg ccctccagac tggcaacaga gtgagacttc gtctcaaaaa aataaaggac
     9001 aagtgtgttt tatacacaaa tatgcagaag cccagttctc ttgactccaa gtcagaagct
     9061 agataaaata gaggttgctg ggggaagttg gaaaataaat gactatactg tacttgttgg
     9121 ctctgctgct gctgatataa cttcaggcac aacggaagcc gcctcggttg gcctatggga
     9181 agggctgggt gaatcactgc ttggccttgc atgaagcaca aaggacacac caatggctga
     9241 tcagtggccc ttccatcatc ttctgcccag ccatgataag gaaagccttc tattgagatg
     9301 gaggaatatt agctcaactt tgtagcatct gatgtaaagt ttgaggggtt tgtctttttt
     9361 gtttgtttgt ttgttttttt ttgagatgga gtctcactct gtcacccagg ctggagtgca
     9421 gtggcgccat ctcagctcac tgcaagctcc acctcccagg ttcacgacat tctcctgcct
     9481 cagcctcctg agtagctggg actacaggtg cccgccaccg cgcccggcta attgtgtgtg
     9541 tgtgtgtgtg tgtgtgtgtg tgtgtgttta gtagagatgg ggtttcaccg tgttacccat
     9601 gatagtctcg atctcctaac ctcgtgatcc acccgcctcg gcctcccaaa gtgctgggat
     9661 tacaggcgtg agccaccgtg cccggcaagg gctttgttca ttaggatcaa caaagtgctt
     9721 tgtctaattc ctgcaaaatg gcaaagaccc agcccatttc cattactcat tccaggctca
     9781 tgctcaggaa aactaataac gttctctttg acaaaacaat ttccttaatt ttctaggatg
     9841 aatcttgaac atgtttagct cagcctttca gatatttatt ctttaaatta ccatcctgtc
     9901 aaaattgcct ttacgcactg atccagaatc accaaggcag ttgccacgat gcctcccagg
     9961 actgtgggtg actgggcaaa ctggtaatga cccgttggct ctgcttcaca cacacacata
    10021 cacattgaca cacataaatg tacacatgca tatatgtgtg tacaacacaa ctataaaaca
    10081 tagaaacata tacctgtaca tatgcacatg cttacataca cacatatcac agatgtgcat
    10141 gcacacatac acatgcacac caccttttac aatatgcctg acacatttga ggcacattaa
    10201 aatgccttgg caggcccagc cctatagttc tgtaaggttt ggcaggccaa aggcttcgga
    10261 tgtctgcagg ataccattga aaaaatgtta tcttcccctt ctatatgttt cttatgcacg
    10321 agcacagcta agagcagcca aatagtaagc tttaaagaaa agaaacctgg aaaagtgaat
    10381 gtgccttgca atttaaaaat tgctaacagt ttcacagtgg gaaaattgca tttgttggaa
    10441 ttttccaagt cataagcaag aagaatagca tagacccaaa acgacagaga tctcttccaa
    10501 ggtatggaat tgtggaaatt tatttagaat atttgcttgg tgatccagag aagggggaaa
    10561 gaagtggtga ggaagaatat atggggtgat ccctccaaat tgccaactcc tcgtcttagg
    10621 aagaagtggg cagtttccat tgatccctag catcagtttg acgggaaaac cggtgcattt
    10681 catcaacctc aaggaaagga agtgccatgc atggaggcct ggtgataggc aacatccatt
    10741 tagaagaaca gtcacacaag caacagaaga actatccaag actagaagct tagaagctta
    10801 taccaaactc tctgtctctc tctctctctc tcacacacac acacacagag tggatgggag
    10861 gggacattaa gaggaaccct agtgcagttc ccccaaaaaa ccttggcata gagtataaca
    10921 gggaaaaagt aattactggg aagctgaaaa caatcaaata tgtgaggaat gactgaatat
    10981 gagctgagga taatgtaaat tgttctggat tgtctataag ataaagatac agagcctgaa
    11041 tctatgtttt tctgaataaa gagaccccat attctctttt gaattattga cctataattc
    11101 ctcttcagca gctttgaata cactcaagtt ctcttcctat tgtttatgat cccataatac
    11161 aaccacccac tatttgttgt ggtttacaat ccagcttaga acccttgagc aaaattattg
    11221 aattattgaa tgctaggccc aaacaaaaga aatttcagct tggttttagt aatttcttga
    11281 tcaaacttct ctcattcctc taaatgtaca aaggtttcaa agttgtaaaa aatatgtcta
    11341 catagccaat gctcttagta tttttaacag caaagataat ctctgccaat aattattaat
    11401 gacaaaatag tgataactgt tcaatgttgc tttaacagtc caattgtagt aggtgagaaa
    11461 acaaaaaaga agagaagcta tgttgaatat ttagtaatgt tggaaaagat cctcacccta
    11521 gacataaaat agtttaaaca tttaaacatg gcccctctct tattgtcatt gctagtgaaa
    11581 gaagttcctg aaattgcata ttacattgta aagttttggg ctaaatcaca atacattttt
    11641 aagttgcttc catggcaata gatcgtaaga ccacagcttg tcaaagtaac cactaattca
    11701 gtattcagaa accttatcat ctgttcctcc aaaaagaccc catagttaat gttgtgtttc
    11761 ccagtatttt agttgggttt cttcacactt aggcaagtgg gtgattctgg tcataataaa
    11821 ctattttcaa actaggaaaa agtatccaaa tgctagagca cataatgagt tcagcttggt
    11881 cagttttgag acagataagc ataaaaccct actagaaaaa aataatagtc aaacctaaag
    11941 ctttaaaaaa tgtgagtcac atcacttttc tccaggaaag gcagaacgtg ctcagggtgg
    12001 aatttaatca aaaatgtacc cagaacaatt tcccacaaag agctgtaata ctttgcagca
    12061 aggggcatta ataaactcta atttttaccg aaagtcaaga gacacacaga tcttttttgg
    12121 taccctctac atcatcatag caaggccctt ctgaacatta acaagcctag atgtttctac
    12181 tgcttatttg cagtatctac aggggaatgg ttcgtggata taaacagaaa tgttttatct
    12241 gaagaggctg tgtatgccac cccagacccc tgcatttctt aatatctata aaaatatgac
    12301 taaacttgtt acatttgagg caaatatgta cagtattttt cccttttaaa gatagtttaa
    12361 aaaatcaagg taataaaaaa cggccaactc tttcaggaaa aaaaaaatcc ggtattttgt
    12421 actacttgag tttctctaat gcctaaaata tgcatttaaa tcatcccaca cctacacaga
    12481 aacaaaatca gcagggaaaa ccatcccact gatgattggc aattccaccg ttcctctcca
    12541 tctgaccagc tttcaccaga gggcgatctt tcatgcttgc acatcgagtt tatacaatgt
    12601 agaagccccc aagtcacctg ggaaatggct catgccaaat acatggagtc cttagttgac
    12661 tatcttttca tattaaaatc ccatcttcca atgaagcatc ctgttttcaa tactgatatc
    12721 aaatttcgaa tgtaaaggag atttcaaatg tattgctttc accttttctt ttttattcat
    12781 ttatttttaa ttgacataaa aattgtatat atttatggga tacaatgtga tgttttgata
    12841 tatgtatgca ttgtggaatg attaaatcaa gctaattaac ata
//
