LOCUS       NM_007113               6985 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens trichohyalin (TCHH), mRNA.
ACCESSION   NM_007113 XM_005245468
VERSION     NM_007113.4
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 6985)
  AUTHORS   Lv,J., Li,W., Wang,X., Guo,L., Wang,D., Zhang,Y., Yu,J., Chen,T.,
            Niu,B., Wang,X. and Liu,Z.
  TITLE     Identification of MKI67, TPR, and TCHH Mutations as Prognostic
            Biomarkers for Patients With Defective Mismatch Repair Colon Cancer
            Stage II/III
  JOURNAL   Dis Colon Rectum 66 (11), 1481-1491 (2023)
   PUBMED   37643197
  REMARK    GeneRIF: Identification of MKI67, TPR , and TCHH Mutations as
            Prognostic Biomarkers for Patients With Defective Mismatch Repair
            Colon Cancer Stage II/III.
REFERENCE   2  (bases 1 to 6985)
  AUTHORS   Chen,S., Liu,T., Bu,D., Zhu,J., Wang,X., Pan,Y., Liu,Y., Lu,Z.J.
            and Wang,P.
  TITLE     Methylome profiling identifies TCHH methylation in CfDNA as a
            noninvasive marker of liver metastasis in colorectal cancer
  JOURNAL   FASEB J 35 (7), e21720 (2021)
   PUBMED   34110642
  REMARK    GeneRIF: Methylome profiling identifies TCHH methylation in CfDNA
            as a noninvasive marker of liver metastasis in colorectal cancer.
REFERENCE   3  (bases 1 to 6985)
  AUTHORS   U Basmanav,F.B., Cau,L., Tafazzoli,A., Mechin,M.C., Wolf,S.,
            Romano,M.T., Valentin,F., Wiegmann,H., Huchenq,A., Kandil,R.,
            Garcia Bartels,N., Kilic,A., George,S., Ralser,D.J., Bergner,S.,
            Ferguson,D.J.P., Oprisoreanu,A.M., Wehner,M., Thiele,H.,
            Altmuller,J., Nurnberg,P., Swan,D., Houniet,D., Buchner,A.,
            Weibel,L., Wagner,N., Grimalt,R., Bygum,A., Serre,G.,
            Blume-Peytavi,U., Sprecher,E., Schoch,S., Oji,V., Hamm,H.,
            Farrant,P., Simon,M. and Betz,R.C.
  TITLE     Mutations in Three Genes Encoding Proteins Involved in Hair Shaft
            Formation Cause Uncombable Hair Syndrome
  JOURNAL   Am J Hum Genet 99 (6), 1292-1304 (2016)
   PUBMED   27866708
  REMARK    GeneRIF: The two enzymes PADI3 and TGM3, responsible for
            posttranslational protein modifications, and their target
            structural protein TCHH are all involved in hair shaft formation.
REFERENCE   4  (bases 1 to 6985)
  AUTHORS   Wu,S., Tan,J., Yang,Y., Peng,Q., Zhang,M., Li,J., Lu,D., Liu,Y.,
            Lou,H., Feng,Q., Lu,Y., Guan,Y., Zhang,Z., Jiao,Y., Sabeti,P.,
            Krutmann,J., Tang,K., Jin,L., Xu,S. and Wang,S.
  TITLE     Genome-wide scans reveal variants at EDAR predominantly affecting
            hair straightness in Han Chinese and Uyghur populations
  JOURNAL   Hum Genet 135 (11), 1279-1286 (2016)
   PUBMED   27487801
  REMARK    GeneRIF: To evaluate the relative contribution of these variants,
            we performed a second genome-wide scan in 709 samples from the
            Uyghur, an admixed population with both eastern and western
            Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 x
            10(-12)) and TCHH (rs11803731: P = 1.46 x 10(-3)) are associated
            with hair straightness, but EDAR (OR 0.415) has a greater effect
            than TCHH (OR 0.575).
REFERENCE   5  (bases 1 to 6985)
  AUTHORS   Petrova,A., Capalbo,A., Jacquet,L., Hazelwood-Smith,S., Dafou,D.,
            Hobbs,C., Arno,M., Farcomeni,A., Devito,L., Badraiq,H., Simpson,M.,
            McGrath,J.A., Di,W.L., Cheng,J.B., Mauro,T.M. and Ilic,D.
  TITLE     Induced Pluripotent Stem Cell Differentiation and Three-Dimensional
            Tissue Formation Attenuate Clonal Epigenetic Differences in
            Trichohyalin
  JOURNAL   Stem Cells Dev 25 (18), 1366-1375 (2016)
   PUBMED   27460132
  REMARK    GeneRIF: The difference between the twoinduced pluripotent stem
            cell(IPSC) clones in TCHH methylation did not have an obvious
            effect on its expression in 3D human epidermal equivalent,
            suggesting that differentiation and tissue formation may mitigate
            variations in the iPSC methylome.
REFERENCE   6  (bases 1 to 6985)
  AUTHORS   Steinert,P.M., Parry,D.A. and Marekov,L.N.
  TITLE     Trichohyalin mechanically strengthens the hair follicle: multiple
            cross-bridging roles in the inner root shealth
  JOURNAL   J Biol Chem 278 (42), 41409-41419 (2003)
   PUBMED   12853460
REFERENCE   7  (bases 1 to 6985)
  AUTHORS   O'Keefe,E.J., Hamilton,E.H., Lee,S.C. and Steinert,P.
  TITLE     Trichohyalin: a structural protein of hair, tongue, nail, and
            epidermis
  JOURNAL   J Invest Dermatol 101 (1 Suppl), 65S-71S (1993)
   PUBMED   7686953
REFERENCE   8  (bases 1 to 6985)
  AUTHORS   Lee,S.C., Kim,I.G., Marekov,L.N., O'Keefe,E.J., Parry,D.A. and
            Steinert,P.M.
  TITLE     The structure of human trichohyalin. Potential multiple roles as a
            functional EF-hand-like calcium-binding protein, a cornified cell
            envelope precursor, and an intermediate filament-associated
            (cross-linking) protein
  JOURNAL   J Biol Chem 268 (16), 12164-12176 (1993)
   PUBMED   7685034
REFERENCE   9  (bases 1 to 6985)
  AUTHORS   Lee,S.C., Wang,M., McBride,O.W., O'Keefe,E.J., Kim,I.G. and
            Steinert,P.M.
  TITLE     Human trichohyalin gene is clustered with the genes for other
            epidermal structural proteins and calcium-binding proteins at
            chromosomal locus 1q21
  JOURNAL   J Invest Dermatol 100 (1), 65-68 (1993)
   PUBMED   8423399
REFERENCE   10 (bases 1 to 6985)
  AUTHORS   Fietz,M.J., Rogers,G.E., Eyre,H.J., Baker,E., Callen,D.F. and
            Sutherland,G.R.
  TITLE     Mapping of the trichohyalin gene: co-localization with the
            profilaggrin, involucrin, and loricrin genes
  JOURNAL   J Invest Dermatol 99 (5), 542-544 (1992)
   PUBMED   1431214
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL589986.15.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 14, 2020 this sequence version replaced NM_007113.3.
            
            Summary: The protein encoded by this gene forms crosslinked
            complexes with itself and keratin intermediate filaments to provide
            mechanical strength to the hair follicle inner root sheath. The
            encoded protein also is important for structural integrity of the
            filiform papillae of the tongue. Defects in this gene are a cause
            of uncombable hair syndrome. [provided by RefSeq, Feb 2017].
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on 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.
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000614923.2/ ENSP00000480484.1
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-54                AL589986.15        19649-19702         c
            55-223              AL589986.15        18201-18369         c
            224-6985            AL589986.15        10575-17336         c
FEATURES             Location/Qualifiers
     source          1..6985
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q21.3"
     gene            1..6985
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /note="trichohyalin"
                     /db_xref="GeneID:7062"
                     /db_xref="HGNC:HGNC:11791"
                     /db_xref="MIM:190370"
     exon            1..54
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /inference="alignment:Splign:2.1.0"
     exon            55..223
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /inference="alignment:Splign:2.1.0"
     CDS             86..5917
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /codon_start=1
                     /product="trichohyalin"
                     /protein_id="NP_009044.2"
                     /db_xref="CCDS:CCDS41396.1"
                     /db_xref="GeneID:7062"
                     /db_xref="HGNC:HGNC:11791"
                     /db_xref="MIM:190370"
                     /translation="MSPLLRSICDITEIFNQYVSHDCDGAALTKKDLKNLLEREFGAV
                     LRRPHDPKTVDLILELLDLDSNGRVDFNEFLLFIFKVAQACYYALGQATGLDEEKRAR
                     CDGKESLLQDRRQEEDQRRFEPRDRQLEEEPGQRRRQKRQEQERELAEGEEQSEKQER
                     LEQRDRQRRDEELWRQRQEWQEREERRAEEEQLQSCKGHETEEFPDEEQLRRRELLEL
                     RRKGREEKQQQRRERQDRVFQEEEEKEWRKRETVLRKEEEKLQEEEPQRQRELQEEEE
                     QLRKLERQELRRERQEEEQQQQRLRREQQLRRKQEEERREQQEERREQQERREQQEER
                     REQQLRREQEERREQQLRREQEEERREQQLRREQEEERREQQLRREQQLRREQQLRRE
                     QQLRREQQLRREQQLRREQQLRREQQLRREQQLRREQEEERHEQKHEQERREQRLKRE
                     QEERRDWLKREEETERHEQERRKQQLKRDQEEERRERWLKLEEEERREQQERREQQLR
                     REQEERREQRLKRQEEEERLQQRLRSEQQLRREQEERREQLLKREEEKRLEQERREQR
                     LKREQEERRDQLLKREEERRQQRLKREQEERLEQRLKREEVERLEQEERREQRLKREE
                     PEEERRQQLLKSEEQEERRQQQLRREQQERREQRLKREEEEERLEQRLKREHEEERRE
                     QELAEEEQEQARERIKSRIPKWQWQLESEADARQSKVYSRPRKQEGQRRRQEQEEKRR
                     RRESELQWQEEERAHRQQQEEEQRRDFTWQWQAEEKSERGRQRLSARPPLREQRERQL
                     RAEERQQREQRFLPEEEEKEQRRRQRREREKELQFLEEEEQLQRRERAQQLQEEEDGL
                     QEDQERRRSQEQRRDQKWRWQLEEERKRRRHTLYAKPALQEQLRKEQQLLQEEEEELQ
                     REEREKRRRQEQERQYREEEQLQQEEEQLLREEREKRRRQERERQYRKDKKLQQKEEQ
                     LLGEEPEKRRRQEREKKYREEEELQQEEEQLLREEREKRRRQEWERQYRKKDELQQEE
                     EQLLREEREKRRLQERERQYREEEELQQEEEQLLGEERETRRRQELERQYRKEEELQQ
                     EEEQLLREEPEKRRRQERERQCREEEELQQEEEQLLREEREKRRRQELERQYREEEEV
                     QQEEEQLLREEPEKRRRQELERQYREEEELQQEEEQLLREEQEKRRQERERQYREEEE
                     LQRQKRKQRYRDEDQRSDLKWQWEPEKENAVRDNKVYCKGRENEQFRQLEDSQLRDRQ
                     SQQDLQHLLGEQQERDREQERRRWQQRDRHFPEEEQLEREEQKEAKRRDRKSQEEKQL
                     LREEREEKRRRQETDRKFREEEQLLQEREEQPLRRQERDRKFREEELRHQEQGRKFLE
                     EEQRLRRQERERKFLKEEQQLRCQEREQQLRQDRDRKFREEEQQLSRQERDRKFREEE
                     QQVRRQERERKFLEEEQQLRQERHRKFREEEQLLQEREEQQLHRQERDRKFLEEEQQL
                     RRQERDRKFREQELRSQEPERKFLEEEQQLHRQQRQRKFLQEEQQLRRQERGQQRRQD
                     RDRKFREEEQLRQEREEQQLSRQERDRKFRLEEQKVRRQEQERKFMEDEQQLRRQEGQ
                     QQLRQERDRKFREDEQLLQEREEQQLHRQERDRKFLEEEPQLRRQEREQQLRHDRDRK
                     FREEEQLLQEGEEQQLRRQERDRKFREEEQQLRRQERERKFLQEEQQLRRQELERKFR
                     EEEQLRQETEQEQLRRQERYRKILEEEQLRPEREEQQLRRQERDRKFREEEQLRQERE
                     EQQLRSQESDRKFREEEQLRQEREEQQLRPQQRDGKYRWEEEQLQLEEQEQRLRQERD
                     RQYRAEEQFATQEKSRREEQELWQEEEQKRRQERERKLREEHIRRQQKEEQRHRQVGE
                     IKSQEGKGHGRLLEPGTHQFASVPVRSSPLYEYIQEQRSQYRP"
     exon            224..6985
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6966..6971
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /note="hexamer: AATAAA"
     polyA_site      6985
                     /gene="TCHH"
                     /gene_synonym="THH; THL; TRHY; UHS3"
                     /note="major polyA site"
ORIGIN      
        1 acacttgcct gtggtgtcag caagcactgt cgacttcttc ctctggtgaa gtgggtttac
       61 ttgaacttga aggaaagaaa aaaaaatgtc tccacttctg agaagcatct gtgacatcac
      121 tgaaattttc aatcagtatg tctctcatga ttgtgatgga gcagcattaa ctaagaaaga
      181 cctgaagaac ctccttgaaa gggaatttgg agctgtgctt cggagaccac atgaccctaa
      241 gacggtagat ctgatcctgg aacttctgga tcttgacagt aatgggcgtg tcgatttcaa
      301 cgaattcctc ctatttattt tcaaagtggc tcaagcttgt tactatgctc tcggccaggc
      361 cacgggactg gatgaggaga agcgagcccg gtgtgacgga aaggagagcc tgttacaaga
      421 tcgcaggcaa gaagaagacc aaaggagatt cgagccccgg gacagacaac tggaagaaga
      481 acctgggcaa cgacgcaggc agaagaggca ggaacaggag agggagctag ctgagggaga
      541 ggagcaaagt gagaaacaag agcgacttga acagcgcgac aggcagcgcc gcgacgagga
      601 gctgtggcgg caaaggcaag aatggcaaga acgggaagag cgccgtgcag aggaagagca
      661 gctgcagagt tgcaaaggtc acgaaactga ggagtttcca gacgaagagc aactgcgaag
      721 gcgggagctg ctggagctga ggaggaaggg ccgcgaggag aaacagcagc aaaggcgaga
      781 gcggcaagac agagtgttcc aggaggaaga agagaaagag tggaggaagc gcgagacagt
      841 gctccggaag gaagaagaga agttgcagga agaggagccg cagcggcaaa gagagctcca
      901 ggaggaagaa gagcagctac ggaagctgga gcggcaagag ctgaggaggg agcgccagga
      961 ggaagagcag cagcagcaaa ggctgaggcg cgagcagcaa ctaaggcgca agcaggagga
     1021 ggagaggcgc gagcagcagg aggagaggcg cgagcagcag gagaggcgcg agcagcagga
     1081 ggagaggcgc gagcagcagc tgaggcgcga gcaggaggag aggcgcgagc agcagctgag
     1141 gcgcgagcag gaggaggaga ggcgcgagca gcagctgagg cgcgagcagg aggaggagag
     1201 gcgcgagcag cagctgaggc gcgagcagca gctgaggcgc gagcagcagc tgaggcgcga
     1261 gcagcagctg aggcgcgagc agcagctgag gcgcgagcag cagctgaggc gcgagcagca
     1321 gctgaggcgc gagcagcagc tgaggcgcga gcagcagctg aggcgcgagc aggaggagga
     1381 gaggcacgag cagaagcacg agcaggagag gcgcgagcag cggctgaagc gcgagcagga
     1441 ggagaggcgc gattggctga agcgcgagga ggagacggag aggcacgagc aggagaggcg
     1501 caagcagcag ctgaagcgcg accaggagga ggagaggcgc gaacgttggc tgaagctcga
     1561 ggaggaggag aggcgcgagc agcaggagag gcgcgagcag caactaaggc gggagcaaga
     1621 ggagaggcgc gagcagcggc tgaagcgcca ggaggaggaa gagaggctcc agcagcggtt
     1681 gaggagcgag caacaactaa gacgcgagca ggaggagagg cgcgagcagc tgctgaagcg
     1741 cgaggaggag aagaggctcg agcaggagag gcgagagcag cggctgaagc gcgagcagga
     1801 ggagaggcgc gatcagctgc tgaagcgcga ggaggagagg cgccagcagc ggctgaagcg
     1861 cgagcaggaa gagaggctcg agcagcgact gaagcgcgag gaggtggaga gactcgagca
     1921 ggaggagagg cgcgagcagc ggctgaagcg cgaggagccg gaggaagaga ggcgccagca
     1981 gctgctgaag agcgaggagc aggaggagag gcgccagcag caactaaggc gcgagcagca
     2041 ggaaaggcgc gagcagcggc tgaagcgcga ggaggaggaa gagaggctcg agcagcggct
     2101 gaagcgcgag catgaggaag agaggcgcga gcaggagcta gctgaggagg agcaggaaca
     2161 ggcccgggag cggattaaga gccgcatccc gaagtggcag tggcagctag aaagcgaggc
     2221 cgacgcacgg caaagcaaag tctactcgag gccccgcaag caggaagggc agaggcgccg
     2281 ccaagagcag gaggaaaaga ggcggcgccg ggagagtgag ctgcaatggc aggaggagga
     2341 acgggctcac cggcagcagc aggaagagga gcagcgccgg gacttcacat ggcagtggca
     2401 ggcggaggaa aagagcgaga ggggccgtca gaggctgtcg gccaggcccc cattgcggga
     2461 gcagcgggag aggcagctga gggccgagga gcgccagcag cgggaacaac ggtttctccc
     2521 ggaggaggag gagaaggagc agcggcgccg ccagcgacgc gagagggaga aagagctgca
     2581 gttcctggag gaagaggagc agctccagcg gcgggagcgt gcccaacagc tccaggagga
     2641 ggaggacggc ctccaggagg atcaggagag gaggcgaagc caggagcagc gccgcgacca
     2701 aaaatggagg tggcaactag aagaagaaag gaagagacgc cgccacacgc tgtacgccaa
     2761 gccagcccta caagagcagc tgaggaagga acagcagctg ctgcaggagg aggaggagga
     2821 gctacagaga gaggagcgcg agaagagaag gcgccaagaa caggagagac aataccgcga
     2881 ggaagagcag ctgcagcagg aggaagagca gctgctgaga gaggaacggg agaaaagaag
     2941 acgccaggag cgggaaaggc aatatcggaa ggataagaag ctgcagcaga aggaagagca
     3001 gctgctggga gaggaaccgg agaagagaag gcgccaggag cgggagaaaa aataccgcga
     3061 ggaagaggag ttgcagcagg aggaagagca gctgctgaga gaggaacggg agaagagaag
     3121 gcgccaggag tgggagaggc agtaccgcaa aaaagacgag ctgcagcagg aagaagagca
     3181 gctgctgaga gaggaacggg agaaaagaag actccaggag cgggagaggc aatatcggga
     3241 ggaagaggag ctgcagcagg aggaagagca gctgctggga gaggaacggg agacgagaag
     3301 gcgccaggag ctggagaggc aatatcggaa ggaagaggag ctgcagcagg aggaagagca
     3361 gctgctgaga gaggaaccgg agaagagaag gcgccaggag cgggagaggc aatgtcggga
     3421 ggaagaggag ctgcagcagg aggaagagca gctgctgaga gaggaacggg agaagagaag
     3481 gcgccaggag ctggagaggc aatatcggga ggaagaggag gtgcagcagg aggaagagca
     3541 gctgctgaga gaggaaccgg agaagagaag gcgccaggag ctggagaggc aataccgcga
     3601 ggaagaggag ctgcagcagg aggaagagca gctgctgaga gaggaacagg agaaaaggcg
     3661 ccaggagcgg gagaggcagt atcgggagga ggaagagctt cagcgccaga aaaggaagca
     3721 gcgataccgg gatgaggatc agcgcagtga tctgaaatgg cagtgggaac cagaaaaaga
     3781 aaatgcagtt cgtgataaca aggtttactg caaaggcaga gagaatgaac agttccggca
     3841 gttggaagat tcccagctgc gcgacagaca atcccagcaa gatctgcagc acctgctggg
     3901 tgaacagcaa gagcgagatc gtgagcaaga gaggaggcgc tggcagcagc gcgacaggca
     3961 tttcccagag gaagaacagc tggagcgaga agagcaaaag gaagccaaaa ggcgcgacag
     4021 gaagtcccaa gaggaaaagc agttgctgag agaggaaaga gaagagaaga gacgccgtca
     4081 agagacagac agaaaattcc gcgaggagga acagctgctc caggaaaggg aggaacagcc
     4141 gctgcgccgc caagagcgtg acagaaaatt ccgcgaagag gaactgcgcc atcaggaaca
     4201 agggagaaaa ttcctcgagg aggaacagcg gctgcgccgc caggaacggg agagaaaatt
     4261 ccttaaggag gaacagcagc tgcgctgcca ggagcgcgag caacagctgc gtcaggaccg
     4321 cgacagaaaa ttccgcgagg aggaacagca gctgagccgc caagagcgtg acagaaaatt
     4381 ccgtgaagag gaacagcagg tgcgccgcca ggaacgagag agaaaattcc tggaggagga
     4441 acagcagctg cgccaggagc gtcacagaaa attccgcgaa gaggaacagc tgctccagga
     4501 aagggaagaa cagcagctgc accgccaaga gcgtgacaga aaattcctgg aggaggaaca
     4561 acagctgcgc cgccaagagc gtgacagaaa attccgcgaa caggaactgc gcagtcagga
     4621 accagagaga aaattcctcg aggaggaaca gcagctgcac cgccagcaac ggcagagaaa
     4681 attcctccag gaggaacagc agctgcgccg ccaggagcgc gggcaacagc ggcgtcagga
     4741 ccgtgacaga aaattccgcg aggaggaaca gctgcgccag gagagggagg aacagcagct
     4801 gagccgccaa gagcgtgaca gaaaattccg tttagaggaa cagaaagtgc gccgccagga
     4861 acaagagaga aaattcatgg aggacgaaca gcagctgcgc cgccaggagg gccaacaaca
     4921 gctgcgccag gagcgcgaca gaaaattccg cgaagacgaa cagctgctcc aggaaaggga
     4981 agaacagcag ctgcaccgcc aagagcgtga cagaaaattc ctcgaggagg aaccgcagct
     5041 gcgccgccag gagcgcgaac aacagctgcg tcacgaccgc gacagaaaat tccgtgaaga
     5101 ggaacagctg ctccaggaag gggaggaaca gcagctgcgc cgccaagagc gtgacagaaa
     5161 attccgcgaa gaggaacagc agctccgccg tcaggaacga gagagaaaat tcctccagga
     5221 ggaacagcag ctgcgccgcc aggaactgga gagaaaattc cgtgaggagg aacagctgcg
     5281 ccaagaaacg gagcaagagc agctgcgccg ccaagaacgc tacagaaaaa tcctagagga
     5341 agagcagctc cgtccggaaa gggaagaaca gcagctgcgc cgccaggagc gcgacagaaa
     5401 attccgcgag gaggaacagc tccgccagga gagggaggaa cagcagctgc gcagccaaga
     5461 gtctgacaga aaattccgcg aggaggaaca gctacgccag gagagggaag aacagcagct
     5521 gcgcccccaa cagcgtgacg gaaagtatcg ctgggaagaa gagcagctcc aacttgagga
     5581 acaagagcag aggctgcggc aggagcgaga ccggcagtac cgggcggagg agcagtttgc
     5641 cacgcaggag aagagtcgtc gtgaggaaca agaactatgg caagaagagg agcagaaacg
     5701 tcgccaggaa cgggaaagga aattacggga agaacacatc cgccgccagc agaaggagga
     5761 acagaggcac cgccaagtcg gggagataaa atcccaagaa gggaagggcc atgggcggct
     5821 tctggagccc ggcactcatc agtttgccag tgtcccagtg cgctccagcc ctctctatga
     5881 gtacatccaa gagcagagat ctcaataccg cccttaagtg atgttgccaa tatcttgaca
     5941 cctgccaaag cttcgagcac gggaaaatga gaaacactgg gtaccaagtg ataactcaga
     6001 tgtttctggt tgtgggaaaa ctctctgata ttagaatgtc ttttcttcca aaatcttaaa
     6061 ctacgctcat tttacgcact ttgtacttct gctttttatt cttcctcaag tagttcttta
     6121 ctgcaagatg tctttctttt gctctttgat gcagatgtgg tgtgcattta aaaaaaatat
     6181 aaatcattta atttgtttaa gaaattttgt ttgaggaaca tgttcattta ttgctttcag
     6241 aagtaacaag agtaatagga tgatttgaga ttctaaacaa tgggtcggtt tgtttaatga
     6301 ctgacccatc ttgtggaaag tgcagatact tttaatgttc aagttgctat ttcttcttga
     6361 acctaaattg atcattgcct ccaaacagca tttcatcttt tgtggcatag ttagcacaaa
     6421 ttccaggtaa ctaaattttt ataacccttg aatagtgcag ggggagtgac ctctgcataa
     6481 aaacttcctg taaaatcagc ccattactgg aagaaatatc tgttaagaat aggtttagct
     6541 ttgaagattt agaatttaaa ttagattttt tttaaactca actccactta aacacataat
     6601 ctcatgaaga aataatgagg tgtttctcaa cttcagagtt caaattttaa aactgtgtct
     6661 gttgtagtct atagtgttca ttctacttcc ccaagttttg atgagtttca gaatattatg
     6721 aacctttgtt aattttagct tgttagaagg aagctgctca gaatcccata aacatctgtc
     6781 ttactctagg gccaataaga gatcacatag agcatgttgg gggtgtaaaa gggaaaaatg
     6841 tgtgaacata ggggcaaatt tctagaggcc ctttgacaag acccatttgc ccacaatcat
     6901 ttgaggccta ttgataatac cttagatata ttcttgttga aataattgga ctgtgaaaaa
     6961 ttaataataa atgtttggca agtaa
//
