LOCUS       NM_004415               9697 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens desmoplakin (DSP), transcript variant 1, mRNA.
ACCESSION   NM_004415
VERSION     NM_004415.4
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 9697)
  AUTHORS   D'Elia,S., Caputo,A., Natale,F., Pezzullo,E., Limongelli,G.,
            Golino,P., Cimmino,G. and Loffredo,F.S.
  TITLE     The Desmoplakin Phenotype Spectrum: Is the Inflammation the 'Fil
            Rouge' Linking Myocarditis, Arrhythmogenic Cardiomyopathy, and
            Uncommon Autoinflammatory Systemic Disease?
  JOURNAL   Genes (Basel) 15 (9), 1234 (2024)
   PUBMED   39336825
  REMARK    GeneRIF: The Desmoplakin Phenotype Spectrum: Is the Inflammation
            the 'Fil Rouge' Linking Myocarditis, Arrhythmogenic Cardiomyopathy,
            and Uncommon Autoinflammatory Systemic Disease?
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 9697)
  AUTHORS   Andrei,D., Bremer,J., Kramer,D., Nijenhuis,A.M., van der Molen,M.,
            Diercks,G.F.H., van den Akker,P.C., Vermeer,M.C.S.C., van der
            Meer,P. and Bolling,M.C.
  TITLE     Epidermal growth factor receptor inhibition leads to cellular
            phenotype correction of DSP-mutated keratinocytes
  JOURNAL   Exp Dermatol 33 (3), e15046 (2024)
   PUBMED   38509711
  REMARK    GeneRIF: Epidermal growth factor receptor inhibition leads to
            cellular phenotype correction of DSP-mutated keratinocytes.
REFERENCE   3  (bases 1 to 9697)
  AUTHORS   Hoorntje,E.T., Burns,C., Marsili,L., Corden,B., Parikh,V.N., Te
            Meerman,G.J., Gray,B., Adiyaman,A., Bagnall,R.D.,
            Barge-Schaapveld,D.Q.C.M., van den Berg,M.P., Bootsma,M.,
            Bosman,L.P., Correnti,G., Duflou,J., Eppinga,R.N., Fatkin,D.,
            Fietz,M., Haan,E., Jongbloed,J.D.H., Hauer,A.D., Lam,L., van
            Lint,F.H.M., Lota,A., Marcelis,C., McCarthy,H.J., van Mil,A.M.,
            Oldenburg,R.A., Pachter,N., Planken,R.N., Reuter,C., Semsarian,C.,
            van der Smagt,J.J., Thompson,T., Vohra,J., Volders,P.G.A., van
            Waning,J.I., Whiffin,N., van den Wijngaard,A., Amin,A.S.,
            Wilde,A.A.M., van Woerden,G., Yeates,L., Zentner,D., Ashley,E.A.,
            Wheeler,M.T., Ware,J.S., van Tintelen,J.P. and Ingles,J.
  TITLE     Variant Location Is a Novel Risk Factor for Individuals With
            Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating
            Variant
  JOURNAL   Circ Genom Precis Med 16 (1), e003672 (2023)
   PUBMED   36580316
  REMARK    GeneRIF: Variant Location Is a Novel Risk Factor for Individuals
            With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP)
            Truncating Variant.
            Review article
REFERENCE   4  (bases 1 to 9697)
  AUTHORS   Di Lorenzo,F., Marchionni,E., Ferradini,V., Latini,A., Pezzoli,L.,
            Martino,A., Romeo,F., Iorio,A., Bianchi,S., Iascone,M., Calo,L.,
            Novelli,G., Mango,R. and Sangiuolo,F.
  TITLE     DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging
            Evidence from an Italian Cohort
  JOURNAL   Int J Mol Sci 24 (3), 2490 (2023)
   PUBMED   36768812
  REMARK    GeneRIF: DSP-Related Cardiomyopathy as a Distinct Clinical Entity?
            Emerging Evidence from an Italian Cohort.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 9697)
  AUTHORS   Cabral,R.M., Wan,H., Cole,C.L., Abrams,D.J., Kelsell,D.P. and
            South,A.P.
  TITLE     Identification and characterization of DSPIa, a novel isoform of
            human desmoplakin
  JOURNAL   Cell Tissue Res 341 (1), 121-129 (2010)
   PUBMED   20524011
  REMARK    GeneRIF: A novel minor isoform of desmoplakin that is also produced
            by alternative splicing of the desmoplakin gene, is described.
REFERENCE   6  (bases 1 to 9697)
  AUTHORS   McNally,E., MacLeod,H. and Dellefave-Castillo,L.
  TITLE     Arrhythmogenic Right Ventricular Cardiomyopathy Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301310
REFERENCE   7  (bases 1 to 9697)
  AUTHORS   Virata,M.L., Wagner,R.M., Parry,D.A. and Green,K.J.
  TITLE     Molecular structure of the human desmoplakin I and II amino
            terminus
  JOURNAL   Proc Natl Acad Sci U S A 89 (2), 544-548 (1992)
   PUBMED   1731325
REFERENCE   8  (bases 1 to 9697)
  AUTHORS   Arnemann,J., Spurr,N.K., Wheeler,G.N., Parker,A.E. and Buxton,R.S.
  TITLE     Chromosomal assignment of the human genes coding for the major
            proteins of the desmosome junction, desmoglein DGI (DSG),
            desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and
            plakoglobin DPIII (JUP)
  JOURNAL   Genomics 10 (3), 640-645 (1991)
   PUBMED   1889810
REFERENCE   9  (bases 1 to 9697)
  AUTHORS   Anhalt,G.J., Kim,S.C., Stanley,J.R., Korman,N.J., Jabs,D.A.,
            Kory,M., Izumi,H., Ratrie,H. 3rd, Mutasim,D., Ariss-Abdo,L. et al.
  TITLE     Paraneoplastic pemphigus. An autoimmune mucocutaneous disease
            associated with neoplasia
  JOURNAL   N Engl J Med 323 (25), 1729-1735 (1990)
   PUBMED   2247105
REFERENCE   10 (bases 1 to 9697)
  AUTHORS   Green,K.J., Parry,D.A., Steinert,P.M., Virata,M.L., Wagner,R.M.,
            Angst,B.D. and Nilles,L.A.
  TITLE     Structure of the human desmoplakins. Implications for function in
            the desmosomal plaque
  JOURNAL   J Biol Chem 265 (5), 2603-2612 (1990)
   PUBMED   1689290
  REMARK    Erratum:[J Biol Chem 1990 Jul 5;265(19):11406-7]
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from M77830.3, AK296756.1,
            AL713610.1, AW890985.1, AL713599.1, CN282963.1, J05211.1,
            AI304615.1 and BF435232.1.
            
            On Nov 23, 2018 this sequence version replaced NM_004415.3.
            
            Summary: This gene encodes a protein that anchors intermediate
            filaments to desmosomal plaques and forms an obligate component of
            functional desmosomes. Mutations in this gene are the cause of
            several cardiomyopathies and keratodermas, including skin
            fragility-woolly hair syndrome. Alternative splicing results in
            multiple transcript variants. [provided by RefSeq, Jan 2016].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (I).
            
            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 :: M77830.3, SRR7346977.2872743.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000379802.8/ ENSP00000369129.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2335              M77830.3           35-2369
            2336-2336           AK296756.1         1634-1634
            2337-2875           M77830.3           2371-2909
            2876-2897           AL713610.1         312-333
            2898-2957           M77830.3           2932-2991
            2958-2958           AW890985.1         294-294
            2959-2974           AL713599.1         586-601
            2975-8305           M77830.3           3009-8339
            8306-8307           CN282963.1         565-566
            8308-8861           J05211.1           4706-5259
            8862-9554           M77830.3           8896-9588
            9555-9696           AI304615.1         1-142               c
            9697-9697           BF435232.1         10-10               c
FEATURES             Location/Qualifiers
     source          1..9697
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p24.3"
     gene            1..9697
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /note="desmoplakin"
                     /db_xref="GeneID:1832"
                     /db_xref="HGNC:HGNC:3052"
                     /db_xref="MIM:125647"
     exon            1..415
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     CDS             246..8861
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /note="isoform I is encoded by transcript variant 1;
                     250/210 kDa paraneoplastic pemphigus antigen"
                     /codon_start=1
                     /product="desmoplakin isoform I"
                     /protein_id="NP_004406.2"
                     /db_xref="CCDS:CCDS4501.1"
                     /db_xref="GeneID:1832"
                     /db_xref="HGNC:HGNC:3052"
                     /db_xref="MIM:125647"
                     /translation="MSCNGGSHPRINTLGRMIRAESGPDLRYEVTSGGGGTSRMYYSR
                     RGVITDQNSDGYCQTGTMSRHQNQNTIQELLQNCSDCLMRAELIVQPELKYGDGIQLT
                     RSRELDECFAQANDQMEILDSLIREMRQMGQPCDAYQKRLLQLQEQMRALYKAISVPR
                     VRRASSKGGGGYTCQSGSGWDEFTKHVTSECLGWMRQQRAEMDMVAWGVDLASVEQHI
                     NSHRGIHNSIGDYRWQLDKIKADLREKSAIYQLEEEYENLLKASFERMDHLRQLQNII
                     QATSREIMWINDCEEEELLYDWSDKNTNIAQKQEAFSIRMSQLEVKEKELNKLKQESD
                     QLVLNQHPASDKIEAYMDTLQTQWSWILQITKCIDVHLKENAAYFQFFEEAQSTEAYL
                     KGLQDSIRKKYPCDKNMPLQHLLEQIKELEKEREKILEYKRQVQNLVNKSKKIVQLKP
                     RNPDYRSNKPIILRALCDYKQDQKIVHKGDECILKDNNERSKWYVTGPGGVDMLVPSV
                     GLIIPPPNPLAVDLSCKIEQYYEAILALWNQLYINMKSLVSWHYCMIDIEKIRAMTIA
                     KLKTMRQEDYMKTIADLELHYQEFIRNSQGSEMFGDDDKRKIQSQFTDAQKHYQTLVI
                     QLPGYPQHQTVTTTEITHHGTCQDVNHNKVIETNRENDKQETWMLMELQKIRRQIEHC
                     EGRMTLKNLPLADQGSSHHITVKINELKSVQNDSQAIAEVLNQLKDMLANFRGSEKYC
                     YLQNEVFGLFQKLENINGVTDGYLNSLCTVRALLQAILQTEDMLKVYEARLTEEETVC
                     LDLDKVEAYRCGLKKIKNDLNLKKSLLATMKTELQKAQQIHSQTSQQYPLYDLDLGKF
                     GEKVTQLTDRWQRIDKQIDFRLWDLEKQIKQLRNYRDNYQAFCKWLYDAKRRQDSLES
                     MKFGDSNTVMRFLNEQKNLHSEISGKRDKSEEVQKIAELCANSIKDYELQLASYTSGL
                     ETLLNIPIKRTMIQSPSGVILQEAADVHARYIELLTRSGDYYRFLSEMLKSLEDLKLK
                     NTKIEVLEEELRLARDANSENCNKNKFLDQNLQKYQAECSQFKAKLASLEELKRQAEL
                     DGKSAKQNLDKCYGQIKELNEKITRLTYEIEDEKRRRKSVEDRFDQQKNDYDQLQKAR
                     QCEKENLGWQKLESEKAIKEKEYEIERLRVLLQEEGTRKREYENELAKVRNHYNEEMS
                     NLRNKYETEINITKTTIKEISMQKEDDSKNLRNQLDRLSRENRDLKDEIVRLNDSILQ
                     ATEQRRRAEENALQQKACGSEIMQKKQHLEIELKQVMQQRSEDNARHKQSLEEAAKTI
                     QDKNKEIERLKAEFQEEAKRRWEYENELSKVRNNYDEEIISLKNQFETEINITKTTIH
                     QLTMQKEEDTSGYRAQIDNLTRENRSLSEEIKRLKNTLTQTTENLRRVEEDIQQQKAT
                     GSEVSQRKQQLEVELRQVTQMRTEESVRYKQSLDDAAKTIQDKNKEIERLKQLIDKET
                     NDRKCLEDENARLQRVQYDLQKANSSATETINKLKVQEQELTRLRIDYERVSQERTVK
                     DQDITRFQNSLKELQLQKQKVEEELNRLKRTASEDSCKRKKLEEELEGMRRSLKEQAI
                     KITNLTQQLEQASIVKKRSEDDLRQQRDVLDGHLREKQRTQEELRRLSSEVEALRRQL
                     LQEQESVKQAHLRNEHFQKAIEDKSRSLNESKIEIERLQSLTENLTKEHLMLEEELRN
                     LRLEYDDLRRGRSEADSDKNATILELRSQLQISNNRTLELQGLINDLQRERENLRQEI
                     EKFQKQALEASNRIQESKNQCTQVVQERESLLVKIKVLEQDKARLQRLEDELNRAKST
                     LEAETRVKQRLECEKQQIQNDLNQWKTQYSRKEEAIRKIESEREKSEREKNSLRSEIE
                     RLQAEIKRIEERCRRKLEDSTRETQSQLETERSRYQREIDKLRQRPYGSHRETQTECE
                     WTVDTSKLVFDGLRKKVTAMQLYECQLIDKTTLDKLLKGKKSVEEVASEIQPFLRGAG
                     SIAGASASPKEKYSLVEAKRKKLISPESTVMLLEAQAATGGIIDPHRNEKLTVDSAIA
                     RDLIDFDDRQQIYAAEKAITGFDDPFSGKTVSVSEAIKKNLIDRETGMRLLEAQIASG
                     GVVDPVNSVFLPKDVALARGLIDRDLYRSLNDPRDSQKNFVDPVTKKKVSYVQLKERC
                     RIEPHTGLLLLSVQKRSMSFQGIRQPVTVTELVDSGILRPSTVNELESGQISYDEVGE
                     RIKDFLQGSSCIAGIYNETTKQKLGIYEAMKIGLVRPGTALELLEAQAATGFIVDPVS
                     NLRLPVEEAYKRGLVGIEFKEKLLSAERAVTGYNDPETGNIISLFQAMNKELIEKGHG
                     IRLLEAQIATGGIIDPKESHRLPVDIAYKRGYFNEELSEILSDPSDDTKGFFDPNTEE
                     NLTYLQLKERCIKDEETGLCLLPLKEKKKQVQTSQKNTLRKRRVVIVDPETNKEMSVQ
                     EAYKKGLIDYETFKELCEQECEWEEITITGSDGSTRVVLVDRKTGSQYDIQDAIDKGL
                     VDRKFFDQYRSGSLSLTQFADMISLKNGVGTSSSMGSGVSDDVFSSSRHESVSKISTI
                     SSVRNLTIRSSSFSDTLEESSPIAAIFDTENLEKISITEGIERGIVDSITGQRLLEAQ
                     ACTGGIIHPTTGQKLSLQDAVSQGVIDQDMATRLKPAQKAFIGFEGVKGKKKMSAAEA
                     VKEKWLPYEAGQRFLEFQYLTGGLVDPEVHGRISTEEAIRKGFIDGRAAQRLQDTSSY
                     AKILTCPKTKLKISYKDAINRSMVEDITGLRLLEAASVSSKGLPSPYNMSSAPGSRSG
                     SRSGSRSGSRSGSRSGSRRGSFDATGNSSYSYSYSFSSSSIGH"
     exon            416..518
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            519..667
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            668..842
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            843..971
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            972..1022
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1023..1184
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1185..1289
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1290..1385
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1386..1511
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1512..1664
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1665..1819
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1820..1946
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            1947..2148
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            2149..2375
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            2376..2542
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            2543..2681
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            2682..2875
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            2876..3038
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            3039..3122
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            3123..3230
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            3231..3329
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            3330..5624
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     exon            5625..9697
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9536..9541
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /note="hexamer: AATAAA"
     polyA_site      9557
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /note="major polyA site"
     regulatory      9665..9670
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
                     /note="hexamer: ATTAAA"
     polyA_site      9697
                     /gene="DSP"
                     /gene_synonym="DCWHKTA; DP"
ORIGIN      
        1 cctctgcgcc cttgccgccc tccgagccac agctttcctc ccgctcctgc ccccggcccg
       61 tcgccgtctc cgcgctcgca gcggcctcgg gagggcccag gtagcgagca gcgacctcgc
      121 gagccttccg cactcccgcc cggttccccg gccgtccgcc tatccttggc cccctccgct
      181 ttctccgcgc cggcccgcct cgcttatgcc tcggcgctga gccgctctcc cgattgcccg
      241 ccgacatgag ctgcaacgga ggctcccacc cgcggatcaa cactctgggc cgcatgatcc
      301 gcgccgagtc tggcccggac ctgcgctacg aggtgaccag cggcggcggg ggcaccagca
      361 ggatgtacta ttctcggcgc ggcgtgatca ccgaccagaa ctcggacggc tactgtcaaa
      421 ccggcacgat gtccaggcac cagaaccaga acaccatcca ggagctgctg cagaactgct
      481 ccgactgctt gatgcgagca gagctcatcg tgcagcctga attgaagtat ggagatggaa
      541 tacaactgac tcggagtcga gaattggatg agtgttttgc ccaggccaat gaccaaatgg
      601 aaatcctcga cagcttgatc agagagatgc ggcagatggg ccagccctgt gatgcttacc
      661 agaaaaggct tcttcagctc caagagcaaa tgcgagccct ttataaagcc atcagtgtcc
      721 ctcgagtccg cagggccagc tccaagggtg gtggaggcta cacttgtcag agtggctctg
      781 gctgggatga gttcaccaaa catgtcacca gtgaatgttt ggggtggatg aggcagcaaa
      841 gggcggagat ggacatggtg gcctggggtg tggacctggc ctcagtggag cagcacatta
      901 acagccaccg gggcatccac aactccatcg gcgactatcg ctggcagctg gacaaaatca
      961 aagccgacct gcgcgagaaa tctgcgatct accagttgga ggaggagtat gaaaacctgc
     1021 tgaaagcgtc ctttgagagg atggatcacc tgcgacagct gcagaacatc attcaggcca
     1081 cgtccaggga gatcatgtgg atcaatgact gcgaggagga ggagctgctg tacgactgga
     1141 gcgacaagaa caccaacatc gctcagaaac aggaggcctt ctccatacgc atgagtcaac
     1201 tggaagttaa agaaaaagag ctcaataagc tgaaacaaga aagtgaccaa cttgtcctca
     1261 atcagcatcc agcttcagac aaaattgagg cctatatgga cactctgcag acgcagtgga
     1321 gttggattct tcagatcacc aagtgcattg atgttcatct gaaagaaaat gctgcctact
     1381 ttcagttttt tgaagaggcg cagtctactg aagcatacct gaaggggctc caggactcca
     1441 tcaggaagaa gtacccctgc gacaagaaca tgcccctgca gcacctgctg gaacagatca
     1501 aggagctgga gaaagaacga gagaaaatcc ttgaatacaa gcgtcaggtg cagaacttgg
     1561 taaacaagtc taagaagatt gtacagctga agcctcgtaa cccagactac agaagcaata
     1621 aacccattat tctcagagct ctctgtgact acaaacaaga tcagaaaatc gtgcataagg
     1681 gggatgagtg tatcctgaag gacaacaacg agcgcagcaa gtggtacgtg acgggcccgg
     1741 gaggcgttga catgcttgtt ccctctgtgg ggctgatcat ccctcctccg aacccactgg
     1801 ccgtggacct ctcttgcaag attgagcagt actacgaagc catcttggct ctgtggaacc
     1861 agctctacat caacatgaag agcctggtgt cctggcacta ctgcatgatt gacatagaga
     1921 agatcagggc catgacaatc gccaagctga aaacaatgcg gcaggaagat tacatgaaga
     1981 cgatagccga ccttgagtta cattaccaag agttcatcag aaatagccaa ggctcagaga
     2041 tgtttggaga tgatgacaag cggaaaatac agtctcagtt caccgatgcc cagaagcatt
     2101 accagaccct ggtcattcag ctccctggct atccccagca ccagacagtg accacaactg
     2161 aaatcactca tcatggaacc tgccaagatg tcaaccataa taaagtaatt gaaaccaaca
     2221 gagaaaatga caagcaagaa acatggatgc tgatggagct gcagaagatt cgcaggcaga
     2281 tagagcactg cgagggcagg atgactctca aaaacctccc tctagcagac cagggatctt
     2341 ctcaccacat cacagtgaaa attaacgagc ttaagagtgt gcagaatgat tcacaagcaa
     2401 ttgctgaggt tctcaaccag cttaaagata tgcttgccaa cttcagaggt tctgaaaagt
     2461 actgctattt acagaatgaa gtatttggac tatttcagaa actggaaaat atcaatggtg
     2521 ttacagatgg ctacttaaat agcttatgca cagtaagggc actgctccag gctattctcc
     2581 aaacagaaga catgttaaag gtttatgaag ccaggctcac tgaggaggaa actgtctgcc
     2641 tggacctgga taaagtggaa gcttaccgct gtggactgaa gaaaataaaa aatgacttga
     2701 acttgaagaa gtcgttgttg gccactatga agacagaact acagaaagcc cagcagatcc
     2761 actctcagac ttcacagcag tatccacttt atgatctgga cttgggcaag ttcggtgaaa
     2821 aagtcacaca gctgacagac cgctggcaaa ggatagataa acagatcgac tttaggttat
     2881 gggacctgga gaaacaaatc aagcaattga ggaattatcg tgataactat caggctttct
     2941 gcaagtggct ctatgatgct aaacgccgcc aggattcctt agaatccatg aaatttggag
     3001 attccaacac agtcatgcgg tttttgaatg agcagaagaa cttgcacagt gaaatatctg
     3061 gcaaacgaga caaatcagag gaagtacaaa aaattgctga actttgcgcc aattcaatta
     3121 aggattatga gctccagctg gcctcataca cctcaggact ggaaactctg ctgaacatac
     3181 ctatcaagag gaccatgatt cagtcccctt ctggggtgat tctgcaagag gctgcagatg
     3241 ttcatgctcg gtacattgaa ctacttacaa gatctggaga ctattacagg ttcttaagtg
     3301 agatgctgaa gagtttggaa gatctgaagc tgaaaaatac caagatcgaa gttttggaag
     3361 aggagctcag actggcccga gatgccaact cggaaaactg taataagaac aaattcctgg
     3421 atcagaacct gcagaaatac caggcagagt gttcccagtt caaagcgaag cttgcgagcc
     3481 tggaggagct gaagagacag gctgagctgg atgggaagtc ggctaagcaa aatctagaca
     3541 agtgctacgg ccaaataaaa gaactcaatg agaagatcac ccgactgact tatgagattg
     3601 aagatgaaaa gagaagaaga aaatctgtgg aagacagatt tgaccaacag aagaatgact
     3661 atgaccaact gcagaaagca aggcaatgtg aaaaggagaa ccttggttgg cagaaattag
     3721 agtctgagaa agccatcaag gagaaggagt acgagattga aaggttgagg gttctactgc
     3781 aggaagaagg cacccggaag agagaatatg aaaatgagct ggcaaaggta agaaaccact
     3841 ataatgagga gatgagtaat ttaaggaaca agtatgaaac agagattaac attacgaaga
     3901 ccaccatcaa ggagatatcc atgcaaaaag aggatgattc caaaaatctt agaaaccagc
     3961 ttgatagact ttcaagggaa aatcgagatc tgaaggatga aattgtcagg ctcaatgaca
     4021 gcatcttgca ggccactgag cagcgaaggc gagctgaaga aaacgccctt cagcaaaagg
     4081 cctgtggctc tgagataatg cagaagaagc agcatctgga gatagaactg aagcaggtca
     4141 tgcagcagcg ctctgaggac aatgcccggc acaagcagtc cctggaggag gctgccaaga
     4201 ccattcagga caaaaataag gagatcgaga gactcaaagc tgagtttcag gaggaggcca
     4261 agcgccgctg ggaatatgaa aatgaactga gtaaggtaag aaacaattat gatgaggaga
     4321 tcattagctt aaaaaatcag tttgagaccg agatcaacat caccaagacc accatccacc
     4381 agctcaccat gcagaaggaa gaggatacca gtggctaccg ggctcagata gacaatctca
     4441 cccgagaaaa caggagctta tctgaagaaa taaagaggct gaagaacact ctaacccaga
     4501 ccacagagaa tctcaggagg gtggaagaag acatccaaca gcaaaaggcc actggctctg
     4561 aggtgtctca gaggaaacag cagctggagg ttgagctgag acaagtcact cagatgcgaa
     4621 cagaggagag cgtaagatat aagcaatctc ttgatgatgc tgccaaaacc atccaggata
     4681 aaaacaagga gatagaaagg ttaaaacaac tgatcgacaa agaaacaaat gaccggaaat
     4741 gcctggaaga tgaaaacgcg agattacaaa gggtccagta tgacctgcag aaagcaaaca
     4801 gtagtgcgac ggagacaata aacaaactga aggttcagga gcaagaactg acacgcctga
     4861 ggatcgacta tgaaagggtt tcccaggaga ggactgtgaa ggaccaggat atcacgcggt
     4921 tccagaactc tctgaaagag ctgcagctgc agaagcagaa ggtggaagag gagctgaatc
     4981 ggctgaagag gaccgcgtca gaagactcct gcaagaggaa gaagctggag gaagagctgg
     5041 aaggcatgag gaggtcgctg aaggagcaag ccatcaaaat caccaacctg acccagcagc
     5101 tggagcaggc atccattgtt aagaagagga gtgaggatga cctccggcag cagagggacg
     5161 tgctggatgg ccacctgagg gaaaagcaga ggacccagga agagctgagg aggctctctt
     5221 ctgaggtcga ggccctgagg cggcagttac tccaggaaca ggaaagtgtc aaacaagctc
     5281 acttgaggaa tgagcatttc cagaaggcga tagaagataa aagcagaagc ttaaatgaaa
     5341 gcaaaataga aattgagagg ctgcagtctc tcacagagaa cctgaccaag gagcacttga
     5401 tgttagaaga agaactgcgg aacctgaggc tggagtacga tgacctgagg agaggacgaa
     5461 gcgaagcgga cagtgataaa aatgcaacca tcttggaact aaggagccag ctgcagatca
     5521 gcaacaaccg gaccctggaa ctgcaggggc tgattaatga tttacagaga gagagggaaa
     5581 atttgagaca ggaaattgag aaattccaaa agcaggcttt agaggcatct aataggattc
     5641 aggaatcaaa gaatcagtgt actcaggtgg tacaggaaag agagagcctt ctggtgaaaa
     5701 tcaaagtcct ggagcaagac aaggcaaggc tgcagaggct ggaggatgag ctgaatcgtg
     5761 caaaatcaac tctagaggca gaaaccaggg tgaaacagcg cctggagtgt gagaaacagc
     5821 aaattcagaa tgacctgaat cagtggaaga ctcaatattc ccgcaaggag gaggctatta
     5881 ggaagataga atcggaaaga gaaaagagtg agagagagaa gaacagtctt aggagtgaga
     5941 tcgaaagact ccaagcagag atcaagagaa ttgaagagag gtgcaggcgt aagctggagg
     6001 attctaccag ggagacacag tcacagttag aaacagaacg ctcccgatat cagagggaga
     6061 ttgataaact cagacagcgc ccatatgggt cccatcgaga gacccagact gagtgtgagt
     6121 ggaccgttga cacctccaag ctggtgtttg atgggctgag gaagaaggtg acagcaatgc
     6181 agctctatga gtgtcagctg atcgacaaaa caaccttgga caaactattg aaggggaaga
     6241 agtcagtgga agaagttgct tctgaaatcc agccattcct tcggggtgca ggatctatcg
     6301 ctggagcatc tgcttctcct aaggaaaaat actctttggt agaggccaag agaaagaaat
     6361 taatcagccc agaatccaca gtcatgcttc tggaggccca ggcagctaca ggtggtataa
     6421 ttgatcccca tcggaatgag aagctgactg tcgacagtgc catagctcgg gacctcattg
     6481 acttcgatga ccgtcagcag atatatgcag cagaaaaagc tatcactggt tttgatgatc
     6541 cattttcagg caagacagta tctgtttcag aagccatcaa gaaaaatttg attgatagag
     6601 aaaccggaat gcgcctgctg gaagcccaga ttgcttcagg gggtgtagta gaccctgtga
     6661 acagtgtctt tttgccaaaa gatgtcgcct tggcccgggg gctgattgat agagatttgt
     6721 atcgatccct gaatgatccc cgagatagtc agaaaaactt tgtggatcca gtcaccaaaa
     6781 agaaggtcag ttacgtgcag ctgaaggaac ggtgcagaat cgaaccacat actggtctgc
     6841 tcttgctttc agtacagaag agaagcatgt ccttccaagg aatcagacaa cctgtgaccg
     6901 tcactgagct agtagattct ggtatattga gaccgtccac tgtcaatgaa ctggaatctg
     6961 gtcagatttc ttatgacgag gttggtgaga gaattaagga cttcctccag ggttcaagct
     7021 gcatagcagg catatacaat gagaccacaa aacagaagct tggcatttat gaggccatga
     7081 aaattggctt agtccgacct ggtactgctc tggagttgct ggaagcccaa gcagctactg
     7141 gctttatagt ggatcctgtt agcaacttga ggttaccagt ggaggaagcc tacaagagag
     7201 gtctggtggg cattgagttc aaagagaagc tcctgtctgc agaacgagct gtcactgggt
     7261 ataatgatcc tgaaacagga aacatcatct ctttgttcca agccatgaat aaggaactca
     7321 tcgaaaaggg ccacggtatt cgcttattag aagcacagat cgcaaccggg gggatcattg
     7381 acccaaagga gagccatcgt ttaccagttg acatagcata taagaggggc tatttcaatg
     7441 aggaactcag tgagattctc tcagatccaa gtgatgatac caaaggattt tttgacccca
     7501 acactgaaga aaatcttacc tatctgcaac taaaagaaag atgcattaag gatgaggaaa
     7561 cagggctctg tcttctgcct ctgaaagaaa agaagaaaca ggtgcagaca tcacaaaaga
     7621 ataccctcag gaagcgtaga gtggtcatag ttgacccaga aaccaataaa gaaatgtctg
     7681 ttcaggaggc ctacaagaag ggcctaattg attatgaaac cttcaaagaa ctgtgtgagc
     7741 aggaatgtga atgggaagaa ataaccatca cgggatcaga tggctccacc agggtggtcc
     7801 tggtagatag aaagacaggc agtcagtatg atattcaaga tgctattgac aagggccttg
     7861 ttgacaggaa gttctttgat cagtaccgat ccggcagcct cagcctcact caatttgctg
     7921 acatgatctc cttgaaaaat ggtgtcggca ccagcagcag catgggcagt ggtgtcagcg
     7981 atgatgtttt tagcagctcc cgacatgaat cagtaagtaa gatttccacc atatccagcg
     8041 tcaggaattt aaccataagg agcagctctt tttcagacac cctggaagaa tcgagcccca
     8101 ttgcagccat ctttgacaca gaaaacctgg agaaaatctc cattacagaa ggtatagagc
     8161 ggggcatcgt tgacagcatc acgggtcaga ggcttctgga ggctcaggcc tgcacaggtg
     8221 gcatcatcca cccaaccacg ggccagaagc tgtcacttca ggacgcagtc tcccagggtg
     8281 tgattgacca agacatggcc accaggctga agcctgctca gaaagccttc ataggcttcg
     8341 agggtgtgaa gggaaagaag aagatgtcag cagcagaggc agtgaaagaa aaatggctcc
     8401 cgtatgaggc tggccagcgc ttcctggagt tccagtacct cacgggaggt cttgttgacc
     8461 cggaagtgca tgggaggata agcaccgaag aagccatccg gaaggggttc atagatggcc
     8521 gcgccgcaca gaggctgcaa gacaccagca gctatgccaa aatcctgacc tgccccaaaa
     8581 ccaaattaaa aatatcctat aaggatgcca taaatcgctc catggtagaa gatatcactg
     8641 ggctgcgcct tctggaagcc gcctccgtgt cgtccaaggg cttacccagc ccttacaaca
     8701 tgtcttcggc tccggggtcc cgctccggct cccgctcggg atctcgctcc ggatctcgct
     8761 ccgggtcccg cagtgggtcc cggagaggaa gctttgacgc cacagggaat tcttcctact
     8821 cttattccta ctcatttagc agtagttcta ttgggcacta gtagtcagtt gggagtggtt
     8881 gctatacctt gacttcattt atatgaattt ccactttatt aaataataga aaagaaaatc
     8941 ccggtgcttg cagtagagtg ataggacatt ctatgcttac agaaaatata gccatgattg
     9001 aaatcaaata gtaaaggctg ttctggcttt ttatcttctt agctcatctt aaataagcag
     9061 tacacttgga tgcagtgcgt ctgaagtgct aatcagttgt aacaatagca caaatcgaac
     9121 ttaggatttg tttcttctct tctgtgtttc gatttttgat caattcttta attttggaag
     9181 cctataatac agttttctat tcttggagat aaaaattaaa tggatcactg atattttagt
     9241 cattctgctt ctcatctaaa tatttccata ttctgtatta ggagaaaatt accctcccag
     9301 caccagcccc cctctcaaac ccccaaccca aaaccaagca ttttggaatg agtctccttt
     9361 agtttcagag tgtggattgt ataacccata tactcttcga tgtacttgtt tggtttggta
     9421 ttaatttgac tgtgcatgac agcggcaatc ttttctttgg tcaaagtttt ctgtttattt
     9481 tgcttgtcat attcgatgta ctttaaggtg tctttatgaa gtttgctatt ctggcaataa
     9541 acttttagac ttttgaagtg tttgtgtttt aatttaatat gtttataagc atgtataaac
     9601 atttagcata tttttatcat aggtctaaaa atatttgttt actaaatacc tgtgaagaaa
     9661 taccattaaa aaactatttg gttctgaatt cttacta
//
