LOCUS       NM_001354712            7576 bp    mRNA    linear   PRI 08-JUN-2024
DEFINITION  Homo sapiens thyroid hormone receptor beta (THRB), transcript
            variant 9, mRNA.
ACCESSION   NM_001354712 XM_006713317
VERSION     NM_001354712.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 7576)
  AUTHORS   Salas-Lucia,F., Stan,M.N., James,H., Rajwani,A., Liao,X.H.,
            Dumitrescu,A.M. and Refetoff,S.
  TITLE     Effect of the Fetal THRB Genotype on the Placenta
  JOURNAL   J Clin Endocrinol Metab 108 (10), e944-e948 (2023)
   PUBMED   37149816
  REMARK    GeneRIF: Effect of the Fetal THRB Genotype on the Placenta.
REFERENCE   2  (bases 1 to 7576)
  AUTHORS   Copur,S., Yavuz,F. and Kanbay,M.
  TITLE     Thyroid hormone Beta receptor agonists for treatment of kidney
            disease: A promising agent?
  JOURNAL   Eur J Clin Invest 53 (5), e13939 (2023)
   PUBMED   36537819
  REMARK    GeneRIF: Thyroid hormone Beta receptor agonists for treatment of
            kidney disease: A promising agent?
            Review article
REFERENCE   3  (bases 1 to 7576)
  AUTHORS   Ng,L., Liu,H., Liu,Y. and Forrest,D.
  TITLE     Biphasic expression of thyroid hormone receptor TRbeta1 in
            mammalian retina and anterior ocular tissues
  JOURNAL   Front Endocrinol (Lausanne) 14, 1174600 (2023)
   PUBMED   37033230
  REMARK    Publication Status: Online-Only
REFERENCE   4  (bases 1 to 7576)
  AUTHORS   Lai,H.P. and Chen,M.H.
  TITLE     Atrial Fibrillation with Heart Failure in a Case with Resistance to
            Thyroid Hormone Due to a Rare Thyroid Hormone Receptor beta Gene
            Mutation
  JOURNAL   Int J Mol Sci 23 (23), 15241 (2022)
   PUBMED   36499571
  REMARK    GeneRIF: Atrial Fibrillation with Heart Failure in a Case with
            Resistance to Thyroid Hormone Due to a Rare Thyroid Hormone
            Receptor beta Gene Mutation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 7576)
  AUTHORS   Cui,B., Xiao,X., Wang,J., Wang,H., Wu,C., Yan,Y., Zheng,J.,
            Wang,J., Zong,Y., Zhang,Y., Hui,R., Gerdes,A.M. and Wang,Y.
  TITLE     Low THRB (thyroid hormone receptor beta) Promoter Methylation
            Levels in Peripheral Blood Leukocytes Induced By Systematic
            Inflammation Are Involved in Low Thyroid Hormone Function in
            Metabolic Syndrome
  JOURNAL   Hypertension 78 (4), 1005-1015 (2021)
   PUBMED   34397273
  REMARK    GeneRIF: Low THRB (thyroid hormone receptor beta) Promoter
            Methylation Levels in Peripheral Blood Leukocytes Induced By
            Systematic Inflammation Are Involved in Low Thyroid Hormone
            Function in Metabolic Syndrome.
REFERENCE   6  (bases 1 to 7576)
  AUTHORS   Falcone,M., Miyamoto,T., Fierro-Renoy,F., Macchia,E. and
            DeGroot,L.J.
  TITLE     Antipeptide polyclonal antibodies specifically recognize each human
            thyroid hormone receptor isoform
  JOURNAL   Endocrinology 131 (5), 2419-2429 (1992)
   PUBMED   1425440
REFERENCE   7  (bases 1 to 7576)
  AUTHORS   Behr,M. and Loos,U.
  TITLE     A point mutation (Ala229 to Thr) in the hinge domain of the c-erbA
            beta thyroid hormone receptor gene in a family with generalized
            thyroid hormone resistance
  JOURNAL   Mol Endocrinol 6 (7), 1119-1126 (1992)
   PUBMED   1324420
REFERENCE   8  (bases 1 to 7576)
  AUTHORS   Cugini,C.D. Jr., Leidy,J.W. Jr., Chertow,B.S., Berard,J.,
            Bradley,W.E., Menke,J.B., Hao,E.H. and Usala,S.J.
  TITLE     An arginine to histidine mutation in codon 315 of the c-erbA beta
            thyroid hormone receptor in a kindred with generalized resistance
            to thyroid hormones results in a receptor with significant
            3,5,3'-triiodothyronine binding activity
  JOURNAL   J Clin Endocrinol Metab 74 (5), 1164-1170 (1992)
   PUBMED   1314846
REFERENCE   9  (bases 1 to 7576)
  AUTHORS   Schmidt,E.D., Schmidt,E.D., van der Gaag,R., Ganpat,R.,
            Broersma,L., de Boer,P.A., Moorman,A.F., Lamers,W.H.,
            Wiersinga,W.M. and Koornneef,L.
  TITLE     Distribution of the nuclear thyroid-hormone receptor in extraocular
            and skeletal muscles
  JOURNAL   J Endocrinol 133 (1), 67-74 (1992)
   PUBMED   1517709
REFERENCE   10 (bases 1 to 7576)
  AUTHORS   Adams,M., Nagaya,T., Tone,Y., Jameson,J.L. and Chatterjee,V.K.
  TITLE     Functional properties of a novel mutant thyroid hormone receptor in
            a family with generalized thyroid hormone resistance syndrome
  JOURNAL   Clin Endocrinol (Oxf) 36 (3), 281-289 (1992)
   PUBMED   1563081
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC012087.10, AC099054.2,
            AC093927.3 and AC098971.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_001354712.1.
            
            Summary: The protein encoded by this gene is a nuclear hormone
            receptor for triiodothyronine. It is one of the several receptors
            for thyroid hormone, and has been shown to mediate the biological
            activities of thyroid hormone. Knockout studies in mice suggest
            that the different receptors, while having certain extent of
            redundancy, may mediate different functions of thyroid hormone.
            Mutations in this gene are known to be a cause of generalized
            thyroid hormone resistance (GTHR), a syndrome characterized by
            goiter and high levels of circulating thyroid hormone (T3-T4), with
            normal or slightly elevated thyroid stimulating hormone (TSH).
            Several alternatively spliced transcript variants encoding the same
            protein have been observed for this gene. [provided by RefSeq, Jul
            2008].
            
            Transcript Variant: This variant (9) differs in the 5' UTR compared
            to variant 1. Variants 1-10 all encode the same isoform (a).
            
            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.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803612.195109.1,
                                           SRR1803617.129543.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000646209.2/ ENSP00000496686.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-199               AC012087.10        124144-124342
            200-271             AC099054.2         46606-46677
            272-417             AC093927.3         2351-2496
            418-481             AC093927.3         70721-70784
            482-742             AC093927.3         109388-109648
            743-843             AC093927.3         147232-147332
            844-991             AC098971.2         171345-171492       c
            992-1197            AC098971.2         168171-168376       c
            1198-1344           AC098971.2         157986-158132       c
            1345-1603           AC098971.2         152169-152427       c
            1604-7576           AC098971.2         141823-147795       c
FEATURES             Location/Qualifiers
     source          1..7576
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p24.2"
     gene            1..7576
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /note="thyroid hormone receptor beta"
                     /db_xref="GeneID:7068"
                     /db_xref="HGNC:HGNC:11799"
                     /db_xref="MIM:190160"
     exon            1..199
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            200..271
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            272..417
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            418..481
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     CDS             460..1845
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /note="isoform a is encoded by transcript variant 9;
                     oncogene ERBA2; nuclear receptor subfamily 1 group A
                     member 2; thyroid hormone receptor, beta (erythroblastic
                     leukemia viral (v-erb-a) oncogene homolog 2, avian)"
                     /codon_start=1
                     /product="thyroid hormone receptor beta isoform a"
                     /protein_id="NP_001341641.1"
                     /db_xref="CCDS:CCDS2641.1"
                     /db_xref="GeneID:7068"
                     /db_xref="HGNC:HGNC:11799"
                     /db_xref="MIM:190160"
                     /translation="MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSE
                     RRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKCKGYIPSYLD
                     KDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQ
                     CQECRFKKCIYVGMATDLVLDDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEE
                     WELIKTVTEAHVATNAQGSHWKQKRKFLPEDIGQAPIVNAPEGGKVDLEAFSHFTKII
                     TPAITRVVDFAKKLPMFCELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLNGEM
                     AVTRGQLKNGGLGVVSDAIFDLGMSLSSFNLDDTEVALLQAVLLMSSDRPGLACVERI
                     EKYQDSFLLAFEHYINYRKHHVTHFWPKLLMKVTDLRMIGACHASRFLHMKVECPTEL
                     FPPLFLEVFED"
     exon            482..742
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            743..843
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            844..991
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            992..1197
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            1198..1344
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            1345..1603
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     exon            1604..7576
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6496..6501
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /note="hexamer: AAGAAA"
     polyA_site      6515
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /note="major polyA site"
     regulatory      6639..6644
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /note="hexamer: AATAAA"
     polyA_site      6664
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
     regulatory      7556..7561
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
                     /note="hexamer: AATAAA"
     polyA_site      7576
                     /gene="THRB"
                     /gene_synonym="C-ERBA-2; C-ERBA-BETA; ERBA2; GRTH; NR1A2;
                     PRTH; THR1; THRB1; THRB2; THRbeta; THRbeta1; Thrbeta2;
                     TRb; TRbeta; TRbeta1"
ORIGIN      
        1 gcacatcctc gggcgggcgg ccgtgacgcg gcggggatta actttgcatg aataatgtga
       61 gtgcgcttgg aaaagagacc tcctgctccg cgggctcggg gcaagagccc gcaggctacc
      121 ttccccgggc aggggcgctc aacccaaccg gctccagggc actggtaatt tggctagagg
      181 accgcgcgga ggcagcggga tctgcgattt ccttctggtt ggctgtcctg cgtgggtgcc
      241 aagttccaca catgatttaa tgaataagaa gctcgccaga gaggcaaact ccagcatttt
      301 atatttcatc tgcccccagt gacttcactg taggaagagg aaatgcagaa aaacaaacgt
      361 cttgaagact gaaagcctgt tattcaaaga ggttagcagt agactgttgg aagtaaggag
      421 atgtcagtga aaaaagggat ccagaatgat tactaaccta tgactcccaa cagtatgaca
      481 gaaaatggcc ttacagcctg ggacaaaccg aagcactgtc cagaccgaga acacgactgg
      541 aagctagtag gaatgtctga agcctgccta cataggaaga gccattcaga gaggcgcagc
      601 acgttgaaaa atgaacagtc gtcgccacat ctcatccaga ccacttggac tagctcaata
      661 ttccatctgg accatgatga tgtgaacgac cagagtgtct caagtgccca gaccttccaa
      721 acggaggaga agaaatgtaa agggtacatc cccagttact tagacaagga cgagctctgt
      781 gtagtgtgtg gtgacaaagc caccgggtat cactaccgct gtatcacgtg tgaaggctgc
      841 aagggtttct ttagaagaac cattcagaaa aatctccatc catcctattc ctgtaaatat
      901 gaaggaaaat gtgtcataga caaagtcacg cgaaatcagt gccaggaatg tcgctttaag
      961 aaatgcatct atgttggcat ggcaacagat ttggtgctgg atgacagcaa gaggctggcc
     1021 aagaggaagc tgatagagga gaaccgggag aaaagacggc gggaagagct gcagaagtcc
     1081 atcgggcaca agccagagcc cacagacgag gaatgggagc tcatcaaaac tgtcaccgaa
     1141 gcccatgtgg cgaccaacgc ccaaggcagc cactggaagc aaaaacggaa attcctgcca
     1201 gaagacattg gacaagcacc aatagtcaat gccccagaag gtggaaaggt tgacttggaa
     1261 gccttcagcc attttacaaa aatcatcaca ccagcaatta ccagagtggt ggattttgcc
     1321 aaaaagttgc ctatgttttg tgagctgcca tgtgaagacc agatcatcct cctcaaaggc
     1381 tgctgcatgg agatcatgtc ccttcgcgct gctgtgcgct atgacccaga aagtgagact
     1441 ttaaccttga atggggaaat ggcagtgaca cggggccagc tgaaaaatgg gggtcttggg
     1501 gtggtgtcag acgccatctt tgacctgggc atgtctctgt cttctttcaa cctggatgac
     1561 actgaagtag ccctccttca ggccgtcctg ctgatgtctt cagatcgccc ggggcttgcc
     1621 tgtgttgaga gaatagaaaa gtaccaagat agtttcctgc tggcctttga acactatatc
     1681 aattaccgaa aacaccacgt gacacacttt tggccaaaac tcctgatgaa ggtgacagat
     1741 ctgcggatga taggagcctg ccatgccagc cgcttcctgc acatgaaggt ggaatgcccc
     1801 acagaactct tccccccttt gttcttggaa gtgttcgagg attagactga ctggattcat
     1861 tctcataatt cctacagcac tactgggtgt catttcattc cattgcctag ctcttttttg
     1921 tttgtttctt tgtgttggga gggattattt gggagggaaa agggaagtag tccttggcat
     1981 agacatggat gaaattgccc cttgaatgcg ggtacttgaa actattgcat ttcgttctcc
     2041 ggtcctgtga tgtgaatgct ctgaaggttt tatggttgtg gaggtggggt gggggacaat
     2101 cattaactca ccagcaccaa gcatcaccag ctcccacccg tccctggtcc aagacttgag
     2161 tcagcaaaat ggcgccacag gacactaaag aagccttaaa accaagataa tacgaccacc
     2221 tccacccaat cctgatgttc gcagggctga agttaacaga gcacagacca cctttagtta
     2281 gatgtggctt tcagcctttt agggaaagac tcgaacaaat tttcatctat tcaagagcat
     2341 gctgtttgca gcactcttta tggtctccta ggagcataac ttggaatgta caggaatatt
     2401 tgtgtcctaa aaaaatcagc tgcccttcca atatcatttt tataacgtta tggtttaatt
     2461 caagttatac aaaggtgtga ctcaaggatg tgcaggtatt gactgatgga ggccaacaag
     2521 gaaaatattt tttttcagtg agcccagaga aattagaaat cttcaccaat gtcagtgact
     2581 gcatggtttc caaaaattca catagtatta cctcacagta ggaaggcttc tttcccattt
     2641 aggctcagag aacactttta cagaaatcaa acctatttac agggtggcac cccttttctg
     2701 tggcatctga tctgtcatct cccaagctcc tgaagttctt tatccaggtt gtatctttgc
     2761 tgagctgaca acagatttct ctatggatca aatattctaa tcaaggaaag atacggtgaa
     2821 acttcagtct tcttctggag aaatgctgag gcgagattag tgcagctaca ttctgagttg
     2881 aaggaaatgc agtgttctga gggccccttt gtgtcctgat ggctggagga cgcttcctcc
     2941 tggttagatc ctcaagctcc ttgcctcatt gacaaatgtc tcctagtccc ctttttccct
     3001 ctgactctga ggaactaaat agcttgacta tctctaaaca gagactggcc ctgccactga
     3061 ccctcctgtc cctctcatag cataccctga cagatactca atagaaaaca cctgcagacc
     3121 atgtgcacac ttaactttcc tgcccaacct gcctccccaa cggcccatgc tagaatagct
     3181 tgtgcccaga aaacaaacag tgacacttca tctcttcagc gtcagaaaat gggcatagaa
     3241 tgtacccatg caattgaatg tatctcattc tccactggca tagtagatat aaactattcc
     3301 tttgcctacc ttttactgcc ttatcctgga aatattgggg aaaataagcc atatcagtga
     3361 gatttaccta aaaacaaagg aaggaaagtc actatggaaa ccaagtagat gctttttgta
     3421 agtttggtgg agcataactg gcccagaagt ctgggtgcct gagttctagt tcgtgctctg
     3481 tcaactggta gatttgtaat tctaggtctt ggttttctta cctggtgaat aagtcatgat
     3541 ctctaaaacc cttcctgccc ttaatattgt ctgaatttca aggggaaaaa aaaaatctgg
     3601 ttcctttaat tatttttttt taacacttaa attcctaact ttattagaca agaagtatgg
     3661 cccacttaac agttaaggaa cgtaaatttg ttattggctc gaaataataa tttgacacaa
     3721 tactagtcaa ccatttagag gccttggaaa aagaagagga acagcactga aaattccaag
     3781 tatgattgga aattatctgg gagcggggaa ttaaatattc aatgcatgaa agcaattgta
     3841 ctggcttctg ggaaaaagga aacaagaaca ttgctatgga acttgttacc cagagaaagg
     3901 aagtgaaaag atttacaatt ataagcacga aattcattgg cagattacct gctttatcta
     3961 cagacagatt gttttggggt ttggttttgt ctaggcagcc tctggccagg ctccttaatt
     4021 gcttgctctg ctaatatttc agcttcctct cttgactcct tgaggaacca accgctcttt
     4081 ggaagacaaa cacttagcca cctctgtgct ccagggtaac cctgagaagc tctgctgtct
     4141 ggggcaagct ttctttccaa agggaatgag aggaaggcaa gcaggcaggg tcctgcagcg
     4201 tcaggccttc tggggaaagt ttcctcattt tgtttgacag ggtcctcagt acatcagaca
     4261 cccagatttg aatataagtt cagagcctga tctcaagcta aatcagaatg ctttggggac
     4321 taaccatgat cgagaattgg ccaaatagta tggcatataa acagccatcc agccagccgc
     4381 aagtaaagga acgtttgatc cttggcacct taaatgattg attgccttca ataggcaaac
     4441 tgctggtctg gaaatctcgt tgaaggctga atacttcatg cggagtagga caagccttag
     4501 cccaccttca ggttgaaagg aaaggccata ggactcaaaa gataatgact ctgaaactaa
     4561 actccttcct tctgaagctg acagaggtac ttagtgcatc tcaagactcc atctcataaa
     4621 actcatttgt gagggatttg ctctagattt ttctaaacat tttttcatct attgtccaga
     4681 cttgcaaatc cagtgtggac ctgatggaga tacccttcac acctgcgctc ccaccccctc
     4741 ggcagggaga cgtctcagta gaggagaaca cacccattat gctgggattt gtatttataa
     4801 atcacttccc ttttagggat gagcggtgtg gggcgtgtgt gcgtgtgagt gtatgcgcgt
     4861 gcgtgtgtga ccctcaagtg tactttgctc aatttagacg tgcagtattt ccagaaacaa
     4921 tgaaaaaagt aagatgtttt cttctttatg attctgctca aaacaccacg tgccgcctca
     4981 gagctttttc tagagcctcg gtcctcaatg acgcgcttga cctgttgatg cctcagccca
     5041 gcgaagcccc tcacctgtgc cccgggcgac agctcttcag tgtgcagtgc aggcctgggg
     5101 tggactgcca ggccttcgct ctgtgccagc aacgccgttc ttgttgctcc tccatgaaca
     5161 ggggtacaag ccctggcccc tcctcgacac taagcccccc acagactcag cctccaagga
     5221 accgctgagc acccttgaag catgtcattg tcagtgatac ctttttattc tatggaactc
     5281 taacctattc gtgtcatatt gaccttttgc tgcatgagtc ataaattatg aaatcagtct
     5341 tacagttttt gaaatgtagc cagcatttgt aaggctaaac ctttttcatg aactgaattt
     5401 aagtgaataa ccaagccaca gttcctcctc aaatggagag tgatgatcga catttgaatc
     5461 tctttgccct ttccaacggc tatggcatca ggttctaaaa taagctcgta atttttcctg
     5521 ttattttaat aatatggaaa tattagcata gtgtttcttt tgatagtgat agactataat
     5581 ccatatttaa attttataga gaagaaattt tattgtactg tgatgtagat atttattatc
     5641 caggtaagga tttgcccggt gtgtattttt tacaattgag acattttact ttaatcttta
     5701 aaaaaaatgc attaaaaaca cactcaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaccaga
     5761 ctgggggaaa aaaggtttgg ccttatcaca gaatttttac tgtgctgtat aaatgtttgc
     5821 aaatgcgaaa agtgtgcatt tatagtgtgt ttccacatta attaatgccg ccttcaagag
     5881 caatattgtg caggtaaaac gctgtttgtg gctttctgtt gcacagttaa agctgaccca
     5941 ccctatgcac aagacaatca aatataaatc tgtcctcctc aggatgcaga taatactcat
     6001 gtaaattatg gagcacaatg taagacaaaa ggagacactt tacatatgta ttgttgatac
     6061 agaaattatc agggcatgaa tgagctgatg tgacattatg ccacttcttt cttttggttc
     6121 tcccttatta acttggcatt tttaatttga ccatagagcc aaattagttc tccatgcttt
     6181 cttcgtagaa aatccttttt tttcccataa tgttttcatg ccctgagaat cagaaaaata
     6241 ctacagaata gaaaaagatt tacagtcatt ggaagatttg tgttttgcaa acagtgttaa
     6301 gtgatattgc tagatggtga tatttttttc agcctaaaac tctgttgaaa tctgtgatca
     6361 aaatgtttta aactatccaa aaaaaatttg tatatttggg aaaaatggat ttttacatag
     6421 cttttgtatg cagatataaa actgtaatta tgaatatagt gggcgtagat aaactcataa
     6481 gcttaaattc taaaaaagaa aaagcttata acagatatat tttcctgtct ctttctttaa
     6541 atattattat tttctacata ggcaaagagt tgcctgctct tctcacttca gctgctgcca
     6601 aaagacggaa ccacggatgt aaggacattt atttcataaa taaacatcta ctagaataag
     6661 caaatttact tgagaagaaa ctatggaggg agagaagaaa ctaagtaaaa tgctgatggg
     6721 gggttacctc tttggaaggg gccacaaaga tgaagggagg agagaggtga agttttgcag
     6781 ctcaaggaca acattcatct tctcatctca aattattcag gaatattact aatggaatta
     6841 tgttaacatc agctgccaac atatatctca atctctgttg ccctgaacac atgttaattg
     6901 agattctttc tatgacaagt aacaaaaagc taactcaaac tggcttaagc agaaagctaa
     6961 ttattgactt taatatctgg gatctagggt attgcatacc aaagcttcag gcatggctgg
     7021 atctgggtgc acttactcag tattctcagg aagctccttt ttttgtcatt catgtagact
     7081 taacattcac atggcctttc accttacggt ggcctccaat agctccagga tgagctttac
     7141 agctccaaat atagtgaaag gagaatttct tttctccaac aattctaatg aaaattctgg
     7201 cctaattctc actggcccaa gttcagtcat gtgcccattc ctgagccaat cactgtggtg
     7261 aggaaaacag atgcataacc aaccttatcc tcaggaatcc tggaactggg tgaggggaaa
     7321 gagggacagt cagcttcatc taaactatgg actgagagtt gaggcaagat gattcctgaa
     7381 agaaaattct aagtcttgct gctataagtg gaagagaatg gtgggcaagc aaaagcaacc
     7441 agtgcccaca ccaaaggtaa atctaaaaca acatcccatt tcagtacagc aagcggttct
     7501 ccttcacaca gaggaagctc atctccaagt ttttatttgg ccaggacatg aaccaaataa
     7561 acaccttcca aagaaa
//
