LOCUS       NM_198721               7713 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens collagen type XXV alpha 1 chain (COL25A1), transcript
            variant 1, mRNA.
ACCESSION   NM_198721
VERSION     NM_198721.4
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 7713)
  AUTHORS   Natera-de Benito,D., Jurgens,J.A., Yeung,A., Zaharieva,I.T.,
            Manzur,A., DiTroia,S.P., Di Gioia,S.A., Pais,L., Pini,V.,
            Barry,B.J., Chan,W.M., Elder,J.E., Christodoulou,J., Hay,E.,
            England,E.M., Munot,P., Hunter,D.G., Feng,L., Ledoux,D.,
            O'Donnell-Luria,A., Phadke,R., Engle,E.C., Sarkozy,A. and
            Muntoni,F.
  TITLE     Recessive variants in COL25A1 gene as novel cause of arthrogryposis
            multiplex congenita with ocular congenital cranial dysinnervation
            disorder
  JOURNAL   Hum Mutat 43 (4), 487-498 (2022)
   PUBMED   35077597
  REMARK    GeneRIF: Recessive variants in COL25A1 gene as novel cause of
            arthrogryposis multiplex congenita with ocular congenital cranial
            dysinnervation disorder.
REFERENCE   2  (bases 1 to 7713)
  AUTHORS   Hashimoto,T., Fujii,D., Naka,Y., Kashiwagi-Hakozaki,M., Matsuo,Y.,
            Matsuura,Y., Wakabayashi,T. and Iwatsubo,T.
  TITLE     Collagenous Alzheimer amyloid plaque component impacts on the
            compaction of amyloid-beta plaques
  JOURNAL   Acta Neuropathol Commun 8 (1), 212 (2020)
   PUBMED   33287899
  REMARK    GeneRIF: Collagenous Alzheimer amyloid plaque component impacts on
            the compaction of amyloid-beta plaques.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 7713)
  AUTHORS   Khan,A.O. and Al-Mesfer,S.
  TITLE     Recessive COL25A1 mutations cause isolated congenital ptosis or
            exotropic Duane syndrome with synergistic divergence
  JOURNAL   J AAPOS 19 (5), 463-465 (2015)
   PUBMED   26486031
  REMARK    GeneRIF: We highlight phenotypes of the 4 affected children from
            the 2 reported families: isolated congenital ptosis (one
            unilateral, one bilateral) and Duane syndrome (one unilateral, one
            bilateral) with synergistic divergence.
REFERENCE   4  (bases 1 to 7713)
  AUTHORS   Shinwari,J.M., Khan,A., Awad,S., Shinwari,Z., Alaiya,A.,
            Alanazi,M., Tahir,A., Poizat,C. and Al Tassan,N.
  TITLE     Recessive mutations in COL25A1 are a cause of congenital cranial
            dysinnervation disorder
  JOURNAL   Am J Hum Genet 96 (1), 147-152 (2015)
   PUBMED   25500261
  REMARK    GeneRIF: We identified COL25A1 mutations as a cause of
            autosomal-recessive congenital cranial dysinnervation disorder.
REFERENCE   5  (bases 1 to 7713)
  AUTHORS   Tong,Y., Xu,Y., Scearce-Levie,K., Ptacek,L.J. and Fu,Y.H.
  TITLE     COL25A1 triggers and promotes Alzheimer's disease-like pathology in
            vivo
  JOURNAL   Neurogenetics 11 (1), 41-52 (2010)
   PUBMED   19548013
  REMARK    GeneRIF: COL25A1 leads to Alzheimer's disease-like pathology in
            vivo
REFERENCE   6  (bases 1 to 7713)
  AUTHORS   Kakuyama,H., Soderberg,L., Horigome,K., Winblad,B., Dahlqvist,C.,
            Naslund,J. and Tjernberg,L.O.
  TITLE     CLAC binds to aggregated Abeta and Abeta fragments, and attenuates
            fibril elongation
  JOURNAL   Biochemistry 44 (47), 15602-15609 (2005)
   PUBMED   16300410
  REMARK    GeneRIF: suggest that CLAC becomes involved at an intermediate
            stage in the pathogenesis of Alzheimer's disease by binding to
            Abeta fibrils, including fibrils formed from peptides with
            truncated N- or C-termini, and thereby slows their growth
REFERENCE   7  (bases 1 to 7713)
  AUTHORS   Soderberg,L., Kakuyama,H., Moller,A., Ito,A., Winblad,B.,
            Tjernberg,L.O. and Naslund,J.
  TITLE     Characterization of the Alzheimer's disease-associated CLAC protein
            and identification of an amyloid beta-peptide-binding site
  JOURNAL   J Biol Chem 280 (2), 1007-1015 (2005)
   PUBMED   15522881
  REMARK    GeneRIF: CLAC displays features characteristic of a collagen
            protein, ie. it forms a partly protease-resistant triple-helical
            structure, exhibits an intermediate affinity for heparin, and is
            glycosylated; binding domain between CLAC and amyloid beta-peptide
REFERENCE   8  (bases 1 to 7713)
  AUTHORS   Kowa,H., Sakakura,T., Matsuura,Y., Wakabayashi,T., Mann,D.M.,
            Duff,K., Tsuji,S., Hashimoto,T. and Iwatsubo,T.
  TITLE     Mostly separate distributions of CLAC- versus Abeta40- or
            thioflavin S-reactivities in senile plaques reveal two distinct
            subpopulations of beta-amyloid deposits
  JOURNAL   Am J Pathol 165 (1), 273-281 (2004)
   PUBMED   15215182
REFERENCE   9  (bases 1 to 7713)
  AUTHORS   Soderberg,L., Zhukareva,V., Bogdanovic,N., Hashimoto,T.,
            Winblad,B., Iwatsubo,T., Lee,V.M., Trojanowski,J.Q. and Naslund,J.
  TITLE     Molecular identification of AMY, an Alzheimer disease
            amyloid-associated protein
  JOURNAL   J Neuropathol Exp Neurol 62 (11), 1108-1117 (2003)
   PUBMED   14656069
REFERENCE   10 (bases 1 to 7713)
  AUTHORS   Hashimoto,T., Wakabayashi,T., Watanabe,A., Kowa,H., Hosoda,R.,
            Nakamura,A., Kanazawa,I., Arai,T., Takio,K., Mann,D.M. and
            Iwatsubo,T.
  TITLE     CLAC: a novel Alzheimer amyloid plaque component derived from a
            transmembrane precursor, CLAC-P/collagen type XXV
  JOURNAL   EMBO J 21 (7), 1524-1534 (2002)
   PUBMED   11927537
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC004051.1, AF293341.1,
            BC030649.1, AF293340.1, AC097473.3 and KF457803.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_198721.3.
            
            Summary: This gene encodes a brain-specific membrane associated
            collagen. A product of proteolytic processing of the encoded
            protein, CLAC (collagenous Alzheimer amyloid plaque component),
            binds to amyloid beta-peptides found in Alzheimer amyloid plaques
            but CLAC inhibits rather than facilitates amyloid fibril elongation
            (PMID: 16300410). A study of over-expression of this collagen in
            mice, however, found changes in pathology and behavior suggesting
            that the encoded protein may promote amyloid plaque formation
            (PMID: 19548013). Multiple transcript variants encoding different
            isoforms have been found for this gene. [provided by RefSeq, Dec
            2011].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest 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 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 :: AF293340.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1966682,
                                           SAMEA1968189 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000399132.6/ ENSP00000382083.1
            RefSeq Select criteria :: based on conservation
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-15                AC004051.1         109152-109166
            16-627              AF293341.1         1-612
            628-765             BC030649.1         435-572
            766-1824            AF293341.1         751-1809
            1825-1866           BC030649.1         1576-1617
            1867-2622           AF293340.1         1852-2607
            2623-3587           AC097473.3         76429-77393         c
            3588-3980           KF457803.1         1-393               c
            3981-7713           AC097473.3         72303-76035         c
FEATURES             Location/Qualifiers
     source          1..7713
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q25"
     gene            1..7713
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /note="collagen type XXV alpha 1 chain"
                     /db_xref="GeneID:84570"
                     /db_xref="HGNC:HGNC:18603"
                     /db_xref="MIM:610004"
     exon            1..490
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            491..843
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     CDS             547..2511
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /note="isoform 1 is encoded by transcript variant 1;
                     collagenous Alzheimer amyloid plaque component; collagen
                     alpha-1(XXV) chain; collagen-like Alzheimer amyloid plaque
                     component; alzheimer disease amyloid-associated protein"
                     /codon_start=1
                     /product="collagen alpha-1(XXV) chain isoform 1"
                     /protein_id="NP_942014.1"
                     /db_xref="CCDS:CCDS43258.1"
                     /db_xref="GeneID:84570"
                     /db_xref="HGNC:HGNC:18603"
                     /db_xref="MIM:610004"
                     /translation="MLLKKHAGKGGGREPRSEDPTPAEQHCARTMPPCAVLAALLSVV
                     AVVSCLYLGVKTNDLQARIAALESAKGAPSIHLLPDTLDHLKTMVQEKVERLLAQKSY
                     EHMAKIRIAREAPSECNCPAGPPGKRGKRGRRGESGPPGQPGPQGPPGPKGDKGEQGD
                     QGPRMVFPKINHGFLSADQQLIKRRLIKGDQGQAGPPGPPGPPGPRGPPGDTGKDGPR
                     GMPGVPGEPGKPGEQGLMGPLGPPGQKGSIGAPGIPGMNGQKGEPGLPGAVGQNGIPG
                     PKGEPGEQGEKGDAGENGPKGDTGEKGDPGSSAAGIKGEPGESGRPGQKGEPGLPGLP
                     GLPGIKGEPGFIGPQGEPGLPGLPGTKGERGEAGPPGRGERGEPGAPGPKGKQGESGT
                     RGPKGSKGDRGEKGDSGAQGPRGPPGQKGDQGATEIIDYNGNLHEALQRITTLTVTGP
                     PGPPGPQGLQGPKGEQGSPGIPGMDGEQGLKGSKGDMGDPGMTGEKGGIGLPGLPGAN
                     GMKGEKGDSGMPGPQGPSIIGPPGPPGPHGPPGPMGPHGLPGPKGTDGPMGPHGPAGP
                     KGERGEKGAMGEPGPRGPYGLPGKDGEPGLDGFPGPRGEKGDLGEKGEKGFRGVKGEK
                     GEPGQPGLDGLDAPCQLGPDGLPMPGCWQK"
     exon            844..913
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            914..958
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            959..966
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            967..984
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            985..1011
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1012..1038
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1039..1110
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1111..1218
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1219..1254
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1255..1281
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1282..1326
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1327..1380
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1381..1407
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1408..1452
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1453..1485
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1486..1521
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1522..1566
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1567..1629
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1630..1698
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1699..1743
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1744..1788
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1789..1866
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1867..1890
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1891..1935
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1936..1980
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            1981..2061
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2062..2124
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2125..2175
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2176..2202
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2203..2256
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2257..2310
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2311..2337
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2338..2391
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2392..2469
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2470..2508
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     exon            2509..7713
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7686..7691
                     /regulatory_class="polyA_signal_sequence"
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /note="hexamer: TATAAA"
     polyA_site      7713
                     /gene="COL25A1"
                     /gene_synonym="AMY; CFEOM5; CLAC; CLAC-P; CLACP"
                     /note="major polyA site"
ORIGIN      
        1 agatccttcg ggcagccgcg acttcggctt cgcgagtagc attggttcct tgggtttatt
       61 tcgttttcct ctctcttctc caccttagtc gcccctttcg cgctgcgctg tagcgtgctc
      121 tcacagcctt tttgccttga actgaatgca ggtgggaaac aggtcggcgt gccgaaagac
      181 accgagtagg tagaaataag gcaaactcac agaggcgcaa caggtccggt cctccgtggc
      241 cagggcgagc cgcggccccg cgtggcgcct cggccgttgc cctcggaccc tgagcggcca
      301 ctgttggggc cctcgaaaga ggtgtcggtc ctctgggagt cggaagagct gtctgggtgg
      361 gtttcgtctt gctttttacc ccaccgccac ccagtccccg gacggagggt gcttttcact
      421 tccagctggg aggagagaag aaagcgggga tggtgcacgc ctgcgggtct ggacgctgag
      481 caaggcaggg gattatttga ggtgtagagg gtgggaagcg aagccgagac ggccgacccc
      541 gccacgatgc tgctgaagaa gcacgcaggg aaaggagggg gccgggagcc cagatccgag
      601 gacccgaccc ctgccgaaca gcattgtgcc cggaccatgc ccccgtgtgc cgtcctggcg
      661 gccctcctgt cagtggtggc cgtggtgtct tgcctgtacc tgggtgtgaa aaccaacgac
      721 ctccaggcga ggatcgccgc tctcgaatcc gccaaagggg ccccttccat tcatctgctg
      781 cctgataccc tggatcacct caagactatg gtgcaagaga aagtggagcg acttctggct
      841 cagaaatcct atgaacatat ggctaaaata agaatcgcaa gagaagcacc ttcagaatgt
      901 aactgcccag caggccctcc agggaaacga ggtaagagag gccgaagagg agaatctggt
      961 cctcctggac agcctggtcc tcagggccct cctggtccaa aaggcgataa gggagaacaa
     1021 ggtgatcagg gacctaggat ggtgtttcct aaaatcaatc atgggtttct ctctgctgat
     1081 cagcagctca ttaaacgccg cctgattaag ggtgaccaag gacaggcagg gcctccagga
     1141 ccccctggcc ctccaggccc aagagggcca cctggggaca cagggaaaga tggcccccgt
     1201 ggaatgccag gagtacccgg tgaaccagga aagccaggag aacaaggctt gatgggtcct
     1261 ctagggcctc cgggacaaaa gggttctatt ggagcacctg gaattccagg gatgaatggg
     1321 caaaagggtg agcccgggtt gcctggagca gtaggacaga atggaatacc aggacctaag
     1381 ggagaacctg gagaacaagg tgaaaaggga gacgctggag agaacggccc caagggtgac
     1441 acaggcgaaa agggtgaccc tggatcatct gctgcaggaa ttaagggaga acctggggaa
     1501 tctggtcgtc cagggcaaaa gggtgaacca gggcttcctg ggcttcctgg acttccgggg
     1561 ataaagggag aaccaggttt cattggtcct caaggagaac caggcttacc aggtttacca
     1621 ggaacaaaag gtgaacgggg ggaagcaggg cctcctggaa gaggtgagcg aggggaacct
     1681 ggagcccccg gaccaaaggg gaaacaaggt gaatcaggaa ctagaggccc aaaggggtca
     1741 aagggggatc gtggagaaaa aggggactct ggagctcagg gaccaagggg tccacctggt
     1801 caaaaagggg atcaaggagc cactgagatc atagactaca acggcaacct ccacgaagcc
     1861 ttacagagga ttaccacctt aactgtcacg ggtccccctg gacctcctgg acctcaagga
     1921 ctacaagggc caaagggaga gcagggatct ccaggaatcc caggaatgga tggagagcag
     1981 ggactcaaag gctcaaaggg agacatgggg gacccaggta tgacaggtga aaaaggagga
     2041 attggacttc ctggattacc gggagccaat ggaatgaaag gagaaaaagg agattctgga
     2101 atgccgggtc cacagggtcc ttctatcata ggcccaccag gcccaccagg tccccatggc
     2161 ccacctggcc ccatgggacc tcatggactt cctggaccaa agggtacaga tggtcctatg
     2221 ggaccccatg gccctgcagg tcccaaagga gaaagaggtg aaaaaggagc tatgggagag
     2281 cctggaccaa gagggcccta tgggctgcct gggaaagatg gagagcctgg tcttgatggc
     2341 ttccctggtc cacggggtga gaagggtgat ctaggagaaa agggagaaaa gggattccgt
     2401 ggcgttaagg gggaaaaagg ggagccaggc cagcctggcc tggatgggct ggatgcccct
     2461 tgccaattgg ggccagatgg cttacccatg cctggctgtt ggcaaaagtg atgaatctaa
     2521 cctttcaagc atgaagttgt gtatataagg gtccattttt aatatttata gttgaaaact
     2581 gaattgcaga ttttacaagt ctgagatatg tttacatagg gctgcttctt cctgctggca
     2641 gtagtataca tgtccatttt tactccactt acatctgaaa ttgggcaatt tgtgaaacca
     2701 gtgagaatcc tgcaaaaaat atagatcagt atctccttat cttatgtgaa gatacgtatt
     2761 tatatggaca aatcagtggt agagaatgat tgattgtact agctattttc cttcttttgg
     2821 cttgctaatt gcatggacaa aaagtgccat gaaatagttt acatgaaatg gtgaccaaat
     2881 atggactcaa agctatgaaa atgtactata ctgactgatt ttagagctga ttatcacatt
     2941 cccattcacc tttcatgtcg gcgttgactc atacctacac cacccattga aactaactaa
     3001 aaaagcatga ctgtgtgcca aacctgcttg ctgtgcaact tcagatgcta gcatgttgat
     3061 caggagtcct ttgattacat ctgaaccttt attccttttg tcatctcaag ggggttacac
     3121 catggcttat tgccaaaaag agataaggtg gcggagagca cacacacaat ttgtcttgta
     3181 ttttgaggga gttgcagtcc tgactgcaga tctacagctt ccagtattgt gggctcatgt
     3241 ggccactttg gttgaaatac gaaggggttg agcctgttgc tgccaccagt tttccttggg
     3301 ctgcccttgg cagtgaagac atgggaagag gaccgattca gcctccagca ctgcctctca
     3361 tgtgaccaag taggaaagag gtttacaaat gcaaacatgc agaaccacag actttaaaaa
     3421 tatgtataaa taaactgaat ttcagcaagt gttaatatag gtgcttttaa aaatgacaga
     3481 ggcacagcac ttcttttgga ataggagatt cttggaatgg gagatcctgt ccctgaggga
     3541 aaagggatgt ccatcccacc aaaacttggg ttgctgaaga aataacatgt tctgagaagg
     3601 gatcagccaa aatcgcctct cccgatgata taggagagct tactgggaca atctgtgcca
     3661 aagttgttgt gagagctttc cttcctccta cgatccaacc atgtcaaaca tttcctacaa
     3721 agtttgagaa acaggtattt ttcattcttt ttaatgcttt tttctttttc tttctttagt
     3781 cccaagaata ttgaaaaaat attagtttca gtttttgtca catatgtttt gaacaatttt
     3841 tttaagaagt cttcaaatca taataatttg gctccagtag tcaaaatgac cttttactaa
     3901 cttctctctt gttttggata attggataga atataaaaga agctccactt tcagtctaat
     3961 cattgtaaag catgaaagtt atgcattttt aagtagtttt gacttttttt acatgatgaa
     4021 tgtaacgtac atggagatta tcagttaata taaagccaag attttgtcac atttggtaat
     4081 attaactaat ttctattttt atggttttaa gttttgtcta tatttagatt tctttctctt
     4141 tttaacattt ctaaatgttt gtctcatcct catatccaca gaccaaatct aagatctcag
     4201 aaagctgtga aatatagttg ccataaagaa aatatttttc atctacttgc tcaaacttta
     4261 cctaaccata ttagatggaa catttctttg cacagtaaag agttggtagc gtgttttgaa
     4321 atggcttatt ctaagtggaa gtgttacatt gaaagaaaca ttatcaatga ggagtaggca
     4381 ccctttcagc ccattagaga atttaatttc tctcctgact caatgccatc ttctgggaag
     4441 atttctagtt tcatgcatag gtgtcaccac cagaagggaa attaactcat ccttggctta
     4501 tagttaagat ataaccataa gacaaggaac ctaaaatcct catgatctca tttatgttat
     4561 gtaaccaaat gacagtcata caaaatggca tcttcttttt tttctattaa atttttaagg
     4621 ttgaaagatg tttaaactat tagatcagtc taattggtaa catttctggt aacattccac
     4681 acccctaagc cagtttagca ttttgaaaat aatggaggac attttctaac aatttcttgt
     4741 atggcatggt gttaggataa cgtattgctc aatgtctgac acaatttgtc ttaaatggtt
     4801 tggaaaaatg aactgaagtg ggtggaacta cattctcttc aggaaaacaa actacagtgt
     4861 ccagtggcta tatttttttc ccttctatct ttttttctgc tcctctagta gaaagaggtg
     4921 gattgaaatg gatcactatt taaaacttgc acagcttcag gagacgatac ctcaacatca
     4981 aaagaaaaac actttatgta taaaaaaatt ttttgaaata cagcccttca aagaatacta
     5041 ttctgtcctg tgtgtatatt gagtttttgc tctataactg atttgacaac atcaacttat
     5101 ttcatgatta aatgaggttg taaactttca ttacatttat ttccttggga aaaacaaagg
     5161 gatggaaata ctcctccttg ttcagtggaa ttgctaggtc ttaaccatga tggataatct
     5221 ttaacttttg gttactacaa tgttttcaag catccatttt gtcatataga gaattcttaa
     5281 ataatttcta agtgaatgaa agaattgtgt ttgttgatat gtgttgatag ataatatact
     5341 ttccttaaag atttctttaa tgtgtgttat tggatagagg gttgagaaaa tatacatgaa
     5401 agacacattg gaaataaggc aaggtcagtt tctatttcta ataaaacatt gaaggatagc
     5461 aaattgatat gtgttttaga tttaaaattg tttttcattt atgttggttg gtgctaatgt
     5521 atctcttttc ctttttctct atggacaata caactactat ggataatttt atttccctgt
     5581 ttaatagcat tcctaaatca ttagtgtgtt attttatttt taaagttcat gaatttgcta
     5641 taattatggt ccaatgacca ggctttctta atgtaaaaca aaacagtgta ccaatagatg
     5701 atgtgtgttt actcggatca tggatcctcc tatttcatat tcatttcata catcatatgc
     5761 ctttatctac tttcatgtgt ctcatctttt tcattcactc gtcttttagt ttatatgatt
     5821 tgatgaaaca tgacaaaact agcatcagag aagtctgcac acaccgtata gagtacctag
     5881 tgcacaaata tacctaattt tttctttcag tttttgtttt tcattagcaa aagcagtctt
     5941 ggaggatttt tttttctcat gtgattttat agaggacatt agaatatctt taattcctac
     6001 cagaagaaag gtcttgtttt tgaatttaca ttctgtgcat acgatgttct gatgggacag
     6061 caagaactta cacatcaact agtttatact acatgtcctt tgtctaacta tctatctata
     6121 tagacatatg tgctagttta gaaaattgtc aaatcagcat gtcagtacca atggaaaaat
     6181 tgtctttgat atgttatatt tttctcactt aggaaatgtg cttaatttcc aagggttttt
     6241 ttttttaatg ttactattga agcatgaaaa gttaacatca tttgttatcc tttctttccc
     6301 cactatatat tgtcttaccc agagtagggc tatactttgg tggtgtttta acatcttcta
     6361 ataagtgatc ataagcaaca tacagatgct aatatttgaa atcttgtttt ttcttacttc
     6421 ctaataatca aattatatta atatttcaca ctacaaaaaa ataggatttt ctaatttgta
     6481 aaaacaagag ctcctgctat ctcttggaag ttaagtcctt aggaacccta tcttatcttt
     6541 ctaaaaataa taagtaagaa caatcacatg tgattctggc tattaaaatc atacatccct
     6601 agtggaatta acaagcttga ccaattatga ttatgctaaa ttgttttagg ctaggaggac
     6661 tgtcagtccc tacttcttcc catttttctt gggatatctt tatattggct agatttgttg
     6721 ccaatataaa attgacacag cagagacact cctctaactt aaatttttag tggagtttgg
     6781 tttttgctaa ccccgtacta ataaacactt taatgacttt tttcatttca aaatatttaa
     6841 atgtataaaa ttgcctatgc tgcttattga aagaaccgtc cttttgggca taagaagact
     6901 ttttcaacct aaaccgttat gtgtgattta ttaacaactt aacaaagaaa gtaccaacat
     6961 ctctcaaaat gtagttgata ttcttaccta tctcagaaat attaacgaat tggattcaca
     7021 aaagaatgtc ttacatactg ttgacattta tgtgaatatt ctttatactg ttgtaaatgt
     7081 ttcattcaac ttaataacat tttaaaagat gtatgtatct gatttttctt tagaaaatat
     7141 tatattttta tttgtatttt ttacatttta aagttcatct ctatgtgcag ctatttttat
     7201 attgccaaaa actcacataa atacaaaata agtgaaatat gcaaaaaaaa atattttggc
     7261 aagcattaca ctgcatattt ttttaaatgt ttgtgggcca gtctcataca attgattatt
     7321 ctaagaatgt gttgtgtctt atcactgtaa atatggcaca aacctgttta tctcagtagt
     7381 gtaaataatt gaaagattga attctccctg ttcaattttt attttaattt ccttgtaatt
     7441 tctccagctg acattactgt atcaaaagat gcataagatt tttgatttgc ggtttggaga
     7501 taattgcatt gtgttcagtt tccagtttgt ttttatttgc tttttaaatt tgttttcagg
     7561 gttcctagtt tgtgagaagt tgatcttcag aattattttt acactattta tgacttattt
     7621 tcataatgta aaaagtgtgt aattattaca atattaatcc aaacaatgat aatgaattgt
     7681 attgttataa agctttattg atgttcatga aaa
//
