LOCUS       NM_000690               9561 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens aldehyde dehydrogenase 2 family member (ALDH2),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_000690
VERSION     NM_000690.4
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 9561)
  AUTHORS   Yokoyama,A., Yokoyama,T., Yumoto,Y., Takimura,T., Toyama,T.,
            Yoneda,J., Nishimura,K., Minobe,R., Matsuzaki,T., Kimura,M. and
            Matsushita,S.
  TITLE     Associations of ADH1B and ALDH2 genotypes and alcohol flushing with
            drinking history, withdrawal symptoms, and ICD-10 criteria in
            Japanese alcohol-dependent men
  JOURNAL   Pharmacogenet Genomics 34 (5), 139-148 (2024)
   PUBMED   38465575
  REMARK    GeneRIF: Associations of ADH1B and ALDH2 genotypes and alcohol
            flushing with drinking history, withdrawal symptoms, and ICD-10
            criteria in Japanese alcohol-dependent men.
REFERENCE   2  (bases 1 to 9561)
  AUTHORS   Liu,Z.Y., Lin,X.H., Guo,H.Y., Shi,X., Zhang,D.Y., Sun,J.L.,
            Zhang,G.C., Xu,R.C., Wang,F., Yu,X.N., Wang,D., Weng,S.Q.,
            Shen,X.Z., Liu,T.T., Dong,L. and Zhu,J.M.
  TITLE     Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a
            critical mediator in the crosstalk between Treg-mediated
            immunosuppression microenvironment and hepatocellular carcinoma
  JOURNAL   Int J Biol Sci 20 (7), 2763-2778 (2024)
   PUBMED   38725845
  REMARK    GeneRIF: Multi-Omics profiling identifies aldehyde dehydrogenase 2
            as a critical mediator in the crosstalk between Treg-mediated
            immunosuppression microenvironment and hepatocellular carcinoma.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 9561)
  AUTHORS   Wang,X., Wang,J., Chen,Y., Qian,X., Luo,S., Wang,X., Ma,C. and
            Ge,W.
  TITLE     The aldehyde dehydrogenase 2 rs671 variant enhances amyloid beta
            pathology
  JOURNAL   Nat Commun 15 (1), 2594 (2024)
   PUBMED   38519490
  REMARK    GeneRIF: The aldehyde dehydrogenase 2 rs671 variant enhances
            amyloid beta pathology.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 9561)
  AUTHORS   Liu,R., Peng,M., Zhang,J., Qiu,K., Zeng,T. and Chen,L.
  TITLE     The ALDH2 gene rs671 polymorphism is associated with
            cardiometabolic risk factors in East Asian population: an updated
            meta-analysis
  JOURNAL   Front Endocrinol (Lausanne) 15, 1333595 (2024)
   PUBMED   38567307
  REMARK    GeneRIF: The ALDH2 gene rs671 polymorphism is associated with
            cardiometabolic risk factors in East Asian population: an updated
            meta-analysis.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 9561)
  AUTHORS   Tokiya,M., Hashimoto,M., Fukuda,K., Kawamoto,K., Akao,C., Tsuji,M.,
            Yakushiji,Y., Koike,H. and Matsumoto,A.
  TITLE     Asian flush gene variant increases mild cognitive impairment risk:
            a cross-sectional study of the Yoshinogari Brain MRI Checkup Cohort
  JOURNAL   Environ Health Prev Med 29, 55 (2024)
   PUBMED   39401906
  REMARK    GeneRIF: Asian flush gene variant increases mild cognitive
            impairment risk: a cross-sectional study of the Yoshinogari Brain
            MRI Checkup Cohort.
REFERENCE   6  (bases 1 to 9561)
  AUTHORS   Yoshida,A.
  TITLE     Molecular genetics of human aldehyde dehydrogenase
  JOURNAL   Pharmacogenetics 2 (4), 139-147 (1992)
   PUBMED   1306115
  REMARK    Review article
REFERENCE   7  (bases 1 to 9561)
  AUTHORS   Crabb,D.W., Edenberg,H.J., Bosron,W.F. and Li,T.K.
  TITLE     Genotypes for aldehyde dehydrogenase deficiency and alcohol
            sensitivity. The inactive ALDH2(2) allele is dominant
  JOURNAL   J Clin Invest 83 (1), 314-316 (1989)
   PUBMED   2562960
REFERENCE   8  (bases 1 to 9561)
  AUTHORS   Hsu,L.C., Bendel,R.E. and Yoshida,A.
  TITLE     Genomic structure of the human mitochondrial aldehyde dehydrogenase
            gene
  JOURNAL   Genomics 2 (1), 57-65 (1988)
   PUBMED   2838413
REFERENCE   9  (bases 1 to 9561)
  AUTHORS   Hsu,L.C., Tani,K., Fujiyoshi,T., Kurachi,K. and Yoshida,A.
  TITLE     Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2
  JOURNAL   Proc Natl Acad Sci U S A 82 (11), 3771-3775 (1985)
   PUBMED   2987944
REFERENCE   10 (bases 1 to 9561)
  AUTHORS   Greenfield,N.J. and Pietruszko,R.
  TITLE     Two aldehyde dehydrogenases from human liver. Isolation via
            affinity chromatography and characterization of the isozymes
  JOURNAL   Biochim Biophys Acta 483 (1), 35-45 (1977)
   PUBMED   18196
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC353712.1, BC002967.1,
            CB851683.1 and AC003029.5.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000690.3.
            
            Summary: This protein belongs to the aldehyde dehydrogenase family
            of proteins. Aldehyde dehydrogenase is the second enzyme of the
            major oxidative pathway of alcohol metabolism. Two major liver
            isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial,
            can be distinguished by their electrophoretic mobilities, kinetic
            properties, and subcellular localizations. Most Caucasians have two
            major isozymes, while approximately 50% of East Asians have the
            cytosolic isozyme but not the mitochondrial isozyme. A remarkably
            higher frequency of acute alcohol intoxication among East Asians
            than among Caucasians could be related to the absence of a
            catalytically active form of the mitochondrial isozyme. The
            increased exposure to acetaldehyde in individuals with the
            catalytically inactive form may also confer greater susceptibility
            to many types of cancer. This gene encodes a mitochondrial isoform,
            which has a low Km for acetaldehydes, and is localized in
            mitochondrial matrix. Alternative splicing results in multiple
            transcript variants encoding distinct isoforms.[provided by RefSeq,
            Nov 2016].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: SRR1803611.169202.1,
                                           SRR1803612.222503.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000261733.7/
                                                  ENSP00000261733.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-6                 DC353712.1         47-52
            7-1938              BC002967.1         3-1934
            1939-2014           CB851683.1         17-92               c
            2015-9561           AC003029.5         18768-26314
FEATURES             Location/Qualifiers
     source          1..9561
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.12"
     gene            1..9561
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /note="aldehyde dehydrogenase 2 family member"
                     /db_xref="GeneID:217"
                     /db_xref="HGNC:HGNC:404"
                     /db_xref="MIM:100650"
     exon            1..164
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     CDS             51..1604
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /EC_number="1.2.1.3"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; acetaldehyde dehydrogenase 2; nucleus-encoded
                     mitochondrial aldehyde dehydrogenase 2; liver
                     mitochondrial ALDH; ALDH class 2; aldehyde dehydrogenase 2
                     family (mitochondrial); epididymis secretory sperm binding
                     protein"
                     /codon_start=1
                     /product="aldehyde dehydrogenase, mitochondrial isoform 1
                     precursor"
                     /protein_id="NP_000681.2"
                     /db_xref="CCDS:CCDS9155.1"
                     /db_xref="GeneID:217"
                     /db_xref="HGNC:HGNC:404"
                     /db_xref="MIM:100650"
                     /translation="MLRAAARFGPRLGRRLLSAAATQAVPAPNQQPEVFCNQIFINNE
                     WHDAVSRKTFPTVNPSTGEVICQVAEGDKEDVDKAVKAARAAFQLGSPWRRMDASHRG
                     RLLNRLADLIERDRTYLAALETLDNGKPYVISYLVDLDMVLKCLRYYAGWADKYHGKT
                     IPIDGDFFSYTRHEPVGVCGQIIPWNFPLLMQAWKLGPALATGNVVVMKVAEQTPLTA
                     LYVANLIKEAGFPPGVVNIVPGFGPTAGAAIASHEDVDKVAFTGSTEIGRVIQVAAGS
                     SNLKRVTLELGGKSPNIIMSDADMDWAVEQAHFALFFNQGQCCCAGSRTFVQEDIYDE
                     FVERSVARAKSRVVGNPFDSKTEQGPQVDETQFKKILGYINTGKQEGAKLLCGGGIAA
                     DRGYFIQPTVFGDVQDGMTIAKEEIFGPVMQILKFKTIEEVVGRANNSTYGLAAAVFT
                     KDLDKANYLSQALQAGTVWVNCYDVFGAQSPFGGYKMSGSGRELGEYGLQAYTEVKTV
                     TVKVPQKNS"
     exon            165..269
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            270..410
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            411..490
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            491..602
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            603..731
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            732..845
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            846..948
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            949..1133
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            1134..1298
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            1299..1456
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            1457..1571
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     exon            1572..9561
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1988..1993
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /note="hexamer: ATTAAA"
     polyA_site      2009
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /note="major polyA site"
     regulatory      9541..9546
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
                     /note="hexamer: ATTAAA"
     polyA_site      9561
                     /gene="ALDH2"
                     /gene_synonym="ALDH-E2; ALDHI; ALDM"
ORIGIN      
        1 gagaccctag ctctgctctc ggtccgctcg ctgtccgcta gcccgctgcg atgttgcgcg
       61 ctgccgcccg cttcgggccc cgcctgggcc gccgcctctt gtcagccgcc gccacccagg
      121 ccgtgcctgc ccccaaccag cagcccgagg tcttctgcaa ccagattttc ataaacaatg
      181 aatggcacga tgccgtcagc aggaaaacat tccccaccgt caatccgtcc actggagagg
      241 tcatctgtca ggtagctgaa ggggacaagg aagatgtgga caaggcagtg aaggccgccc
      301 gggccgcctt ccagctgggc tcaccttggc gccgcatgga cgcatcacac aggggccggc
      361 tgctgaaccg cctggccgat ctgatcgagc gggaccggac ctacctggcg gccttggaga
      421 ccctggacaa tggcaagccc tatgtcatct cctacctggt ggatttggac atggtcctca
      481 aatgtctccg gtattatgcc ggctgggctg ataagtacca cgggaaaacc atccccattg
      541 acggagactt cttcagctac acacgccatg aacctgtggg ggtgtgcggg cagatcattc
      601 cgtggaattt cccgctcctg atgcaagcat ggaagctggg cccagccttg gcaactggaa
      661 acgtggttgt gatgaaggta gctgagcaga cacccctcac cgccctctat gtggccaacc
      721 tgatcaagga ggctggcttt ccccctggtg tggtcaacat tgtgcctgga tttggcccca
      781 cggctggggc cgccattgcc tcccatgagg atgtggacaa agtggcattc acaggctcca
      841 ctgagattgg ccgcgtaatc caggttgctg ctgggagcag caacctcaag agagtgacct
      901 tggagctggg ggggaagagc cccaacatca tcatgtcaga tgccgatatg gattgggccg
      961 tggaacaggc ccacttcgcc ctgttcttca accagggcca gtgctgctgt gccggctccc
     1021 ggaccttcgt gcaggaggac atctatgatg agtttgtgga gcggagcgtt gcccgggcca
     1081 agtctcgggt ggtcgggaac ccctttgata gcaagaccga gcaggggccg caggtggatg
     1141 aaactcagtt taagaagatc ctcggctaca tcaacacggg gaagcaagag ggggcgaagc
     1201 tgctgtgtgg tgggggcatt gctgctgacc gtggttactt catccagccc actgtgtttg
     1261 gagatgtgca ggatggcatg accatcgcca aggaggagat cttcgggcca gtgatgcaga
     1321 tcctgaagtt caagaccata gaggaggttg ttgggagagc caacaattcc acgtacgggc
     1381 tggccgcagc tgtcttcaca aaggatttgg acaaggccaa ttacctgtcc caggccctcc
     1441 aggcgggcac tgtgtgggtc aactgctatg atgtgtttgg agcccagtca ccctttggtg
     1501 gctacaagat gtcggggagt ggccgggagt tgggcgagta cgggctgcag gcatacactg
     1561 aagtgaaaac tgtcacagtc aaagtgcctc agaagaactc ataagaatca tgcaagcttc
     1621 ctccctcagc cattgatgga aagttcagca agatcagcaa caaaaccaag aaaaatgatc
     1681 cttgcgtgct gaatatctga aaagagaaat ttttcctaca aaatctcttg ggtcaagaaa
     1741 gttctagaat ttgaattgat aaacatggtg ggttggctga gggtaagagt atatgaggaa
     1801 ccttttaaac gacaacaata ctgctagctt tcaggatgat ttttaaaaaa tagattcaaa
     1861 tgtgttatcc tctctctgaa acgcttccta taactcgagt ttatagggga agaaaaagct
     1921 attgtttaca attatatcac cattaaggca actgctacac cctgctttgt attctgggct
     1981 aagattcatt aaaaactagc tgctcttaac ttactgggta actctttgtc catctcaata
     2041 accaaaggaa ggtgggcatg gtggctcacg cctgtaatcc cagcactttg ggaagccgag
     2101 gcgggtggat cactcgaggt caggagtttg agaccagcct ggccaacgta gtgaaaccct
     2161 gtctctcact aaaaatacac aaattaggca gtcatggtgg ctggcacctg taatcccagc
     2221 tacttgggag gctgaggcag gaaaattggt tgaacctggg aggtggaggt tgcagtgagt
     2281 ggagatcatg ccactgcact ccagcctggg agtcagagcg agactccatc tcaaaaaaag
     2341 taaataaatg aaatagccta aggaaatgct ggcaggcagt aatgatatgg cacactggat
     2401 atgatttctg cccctcctct gctgtgggta aacagcttct gtttcatgca tttacttttt
     2461 tattttaatt acaccaataa gaatgtgctt gaatgtttca tgcatttaat ttgtttcatg
     2521 catttaactt ctggcctgtt tacctgtagc aggctctgag atgtgctcta gagacagaac
     2581 ctaaacatga tgcccaagag aggggagaga tactgaatgt ccaatgttct caaatttttt
     2641 tttttttttt ttttgagaca gggtcttgct ctgccatcca ggctggagtg cagtggcacg
     2701 atcatagctc actgctgcct cgacctcctg ggctcaaatg atcctcctgc ttcagcttcc
     2761 tgggctaatg tttgtatttt ttgtggagat gggactttgt tatgttgccc aggctgtttt
     2821 caaactcctg gactcaagtg atcctcccgc cttagcctcc taaggtgctg ggattacagg
     2881 tgtgagccac tgtgcccaat tcagttctca gtaaaaactt gatcaggcca aatgaaagtg
     2941 acatgggcca atttcataat agattgattt ggaaaccaga tgtcaattta cttactttaa
     3001 gtgagatctg tatcttcagt aaccagacct cttgagtctc ccacccagaa cactatcttc
     3061 ctctagtcaa gatacctggc aaaggccggg cacagtggct cacgcctata attccagcac
     3121 tttgggaggc caaggtgggt gggtcacctg aggttgggag ttcgagacca gcctgaccaa
     3181 cagggagaaa ccccatctct actgaaaata caaaaaaaaa aaaaaaaact agccgggcat
     3241 ggtggctcat gcctgtaatc ccagctactc aggaggctga ggcaggagaa ttgcttgaac
     3301 ctgggaggca gaggttgcag tgagccaaga ttgctccatt gtactccagc ctgggcaaca
     3361 agagagaaac tccgtctcaa aatataaata aataagaaaa agaagaaatg gaagctgggt
     3421 tcaagagggc aatcagcagt ctctaccatc atgtgaaaca ccactctgtg atttgagtct
     3481 tgacaatgta ttttcttttt ttttttcttc tttttttttt gagactgagt ctcggtctgt
     3541 cgcccaggct ggagtgcagt gacgtgatct tggctcactg caacctctgc ctcctgggtt
     3601 ggagcaattc tcctgcctca gcctcctgag tagctgggat tacaggtgtg cgccaccatg
     3661 cctggctaat ttttgtattt ttagtagaga cggggttttg ccatgttggc caggctggtg
     3721 ttgaaggcct gacctcaggt aatccaccca cctctgcctc ccagagtact gggattacaa
     3781 gtgtgagcca ccgtgcccgg ccaactgtag ggaccagccc cacagggtcg gtgggttttt
     3841 ctccccatgt gcggagacga gagattgtag aaataaagac acaagacaaa gaggtaaaag
     3901 aaaagacagc tgggcttggg ggaccactac caccaagagg cggagaccgg tagaggcccc
     3961 gaatgtctgg ctgcactgtt atttattgga tacaaagcaa aaggggcagg gtaaagagtg
     4021 tgagtcatct ccaatgacag gtaaggtcac gtgggtcacg tgtccactgg acagggggcc
     4081 cttccctgcc tggcagccaa ggcagagata gacagggaga gagagagaca gcttacgcca
     4141 ttatttctgc gtatcagaga cttttagtac tttcactaat tttgctactg ttatctaaaa
     4201 ggcagagcca ggtgtacagg atggaacatg aaggcagact aggagcgtga ccactgaagc
     4261 acagcaccac agggagacgg ttaggcctcc ggataactaa tgattaatga tattcatata
     4321 taatcatgtc tgtgatctag atctagtata actcttgttg ttttatatat tttattatac
     4381 tggaacagct cgtgccctcg gtctcttgcc tcagcacctg gatggcttgc cgcccacagc
     4441 caacaatgtg ttttcaatat gctccccaaa ctacagcaaa ctcctcttaa ctcgggattt
     4501 agggtgatgc cctacttatg cctaacttta tcaccagctt aaccctcatc tcattatata
     4561 ggatgatatt acttctagga agattttcta tgtatggagg gtgcatcatt taagagtatt
     4621 ttaggccagg cactgtggct catgcctgta atcccagcat tttgggaagc tgaggtgggt
     4681 gatttgcttc agcccacgag ttcaagatca gcctggccaa tatggtgaaa ccccatctct
     4741 acaaaaaaat acaaaaatta gctgagcgtg gtgatgtgtg cctgtggtcc cagttactct
     4801 ggaggctgat gtgggaggat cacttgagcc caggaggtca aggctgcagt gagctgtgat
     4861 tgcaccactt cactccagcc cagagtgaga ccccatctct gaaaaaaaca caaaaaacaa
     4921 gaaaagaata ctgcaaagaa ccttggtagg ggtgaattgg aaaaagtaga gaaatgtaat
     4981 atttctttcc tgctgtactc actgtaactg tgagaggatc ggctctttta accaacagat
     5041 aagaaaggaa atattagcta tgaagaaatg tctatcaagt tgattttgac aacctagaca
     5101 cattaatctc cttgcacttt tagtgacagg aacccattag aaccttaagc agctgtctga
     5161 agtaaaaaca aagctctcag gtgatgaacc acctaatctc cctgggtatt cggatgtggg
     5221 tcagtcacag gagtattagg tgtaaagccg ctgcttctgg gtagagcctc cacttgtggc
     5281 tgcacagagg gcacagagag cttttccttc agcccggaga agcttcctaa gtgtgggcgc
     5341 caccttgtgg gacatacatt gaactacgac gctatttctc caagaattaa caggacagcc
     5401 cctcccaccg gtgtccttcc aacgatgttg catacaattt ggctgtacat ttggcaggca
     5461 gtgtaatgag ggaatcaaag accaggatca catactggaa agaattgaaa acagagactc
     5521 ccaacaaaaa cttgtacacg gacgttcaca gcagcactat tcacgacagc tcagagatgg
     5581 aatcaaccca aatatcagtc aatagatgaa tggacagaca aaatgtgaca tatccatgca
     5641 gtggaatatt atttagccat aaaaaggaag gaagtgctga tgcatgttgc gatgtggatg
     5701 aaccttgaaa acatgatgct gagtgaaaga agccagacac aaaaggagaa ggactgtatg
     5761 atttcactta taggaaatat ccagaacagg caaatctata tagagagaag gtcgattgct
     5821 gggggccctg ggaagggacc aagggggagt gacttctaat ggtggggtgc ccttttgggg
     5881 tgatgaaaat gttttggaac cagatacagg tggtggttgt acaacattgt gaatttacta
     5941 aatgcaacca aattgctcac ttaaaaacaa caaattcagg ccaggtgcag tggctcacac
     6001 ccgtaatccc agcactttgg gaggccgagg tgggcggatc acatgaggtc aagagttcga
     6061 gactagcctg gccaacatgg tgaaatccca tctcggccgg gcgcggtggc tcacgcctgt
     6121 aatcccagca ctttgggagg ctgaggcggg tggatcacga ggtcaggaga tcgagaccat
     6181 cctggctaac acggtgaaac cccgtctcta ctaaaaatac aaaaaattag ccaggcgtgg
     6241 tggtgggcgc ctgtagtccc agctgatcgg gaggctaagg caggagaatg gtgtgaaccc
     6301 aggaggcgga gcttgcagtg agccgagatc gcgccactgc actctatcct gggtgacaga
     6361 gtgagactct gtctccaaaa aaaaaaaaag aaaccccatc tctacccaaa atacaaaaat
     6421 tagctgggca tggtggctgg cacctgtaat cccagctact caggaggctg aggcaggaga
     6481 attggttgaa cctgggaggc agaggttgca gtgagctaag atcgcaccac tgcactccag
     6541 cctgggtgac agaacgagac tgtctcaaaa aaaaaaaaaa aaaaaagtgg ccaggtggtg
     6601 ccatggctca tgcctgtaat ctcagcattt tgggatactg aggcgggtgg attacctgag
     6661 gccaggagtt cgagatcagc ctggccaaca tgatgaaaac ccatctctgc taaaaataca
     6721 aaaaattggc tgggcttggt agcatgtgcc cagctacttg ggaggctgag acaggagaat
     6781 cgcttgaacc tgggaggcag aggttgcggt tagccaagat tgtgccactg cactccatgg
     6841 gtgacacaga gagactctgt ctcaaaaaaa aaaaaaaaaa agtaaatgct atgttatgtg
     6901 aatttcacct caactgaaaa aaacagggtc ccagagctgg tcaggggaac ttggacaaac
     6961 cacacaactt ctgagcttcc atttcctcac aatctctgca gtcacttcca actctcattt
     7021 ggcttattct gtgaaggata aaacagagct gacatttgtt catttgtatt gattttattt
     7081 acatttttca aaaggaaata gatgcagatg gtatagaaag tttcagtgaa atgtaaatct
     7141 gatgcccaat cctgtggccc caagaagtat taactgtgca cccactacat gccaggaact
     7201 gtacttggag ccttctcaag agcttcttaa caatattttc attttttata ttttttaatg
     7261 acagggtcta actccgtcgt ccaggctgga gtgcagtggt gcgatcatag ctcactgcag
     7321 cctctacctc ctaggctcag gtgattcttc tgcctcagcc tcccaaatag ctggtactac
     7381 aagcatgtgc caccacagtc agctaattat ttttggagag tcagggtttc actatgtagc
     7441 tcaggctggt cttcagctcc tggcttgaag tgatcctcct gccttggcac atagaagggg
     7501 ttacaatata catatattag agtgagagca tagatgtgat gcctggcgat atggcttact
     7561 tatgagacag cacctgacct acagccatct atgactccta ctgtatcttc catgccagga
     7621 gtaagggtga ggatacctgg caataataaa aataataacc tgagagtcta atggcttatt
     7681 ttttgtagag atggggtctc actgtgttgt ttaggctggt cttgaacttc tgggctcaag
     7741 tgatcctccc acctcagcct cctgagtagc tgggattata ggcgtgcact accatgcata
     7801 tatatatata tttttttttt tttttgagag agagagagag agatggagtc ttgctatgtt
     7861 gctcaggctg gtctcgaact cctggcctca agtcatcctg ctggcttggc ctctcaagtg
     7921 ctaggattac aggcatgaga cactgggcac agccctaata gcttattttt aaagctatat
     7981 caaaatgtca tgcacctgaa catttgaagt aacctctctg atagtacgga tatttatccc
     8041 ctcaaaatct catgttaaaa tgtaatcttc agtgttggag gtggggcaag gtgtgaggtg
     8101 ttaggatcat gggggtggat ccctcatgaa tggcttggtg tcctccccca tggtaatgag
     8161 ttcactcaag agctggttgt ttaaaaggtg acgtggacct aatccctgtt ggactgaaca
     8221 aaaggggacg aacacagcaa taaagataaa gaccaaagag tatatttgga agaaggggtc
     8281 agggggctcc ttgcttctag tgaaaaaggg ccctgagctt tagtgccctt tgtatttatt
     8341 gggtaaagga gatagggaga agggggggtg gttgtcggtc agcagcttga ttcacagcag
     8401 gctcacaaga ttgcattctt tgaacagtag gctctagatg tctcagtaga taacctcaaa
     8461 gagcatggcg ccagggagtg attgccctca gcgaaccttc tggcggctga agcagaagtg
     8521 agtttgccca cattctgcat ttatgataaa cagtttgctg tttgatcata tagcctcagt
     8581 ggaatgctga gttggtcaca acccatgggc attcagctct ctacatttcc ccctttctgt
     8641 ttatgaatta attgaaagaa tgtaaggcca ggctgggcag ctctcatttt ctgattggca
     8701 gtccatccaa ttttacagac tatgaacaga agacagagac aaaacaacat tattccaagg
     8761 actacatata agatgttaat gtggtgcttt agacaggtcc aagggttgag gctctccagg
     8821 ccttgctgga atttggtcta gtcttctaaa gaaggctgaa actcttgagt ttgtttattt
     8881 aaatcaagaa ttttgttttg taattcaccg atatcaaagg tgatgttgga tgtgcaagct
     8941 ccctgcaaat gggctttcac aaggtcccat ggatactcac tttggttata ttctaagttg
     9001 gttacacaaa tatgagtgtg attaaaatga tggtgcaatt gctgttgcaa ttgcaagctt
     9061 tgtacttgtt ctcctaactg tagagccgtg gatttcaaca atgccacttc agtttgtaac
     9121 tcagtgttaa ttttattctg aagtggccat gcttggttgg ctatacgcat ccagttttcc
     9181 atgtactgag ttgtttgaat agaactatgc aaagctacag aggacatcac aacggaagtt
     9241 attaatgtga ccaaggaaac aatagcaaaa attatcatgc ctaaggctct atgggcacaa
     9301 tgagtaagtt gagttagaag atgtttcatg aagtgcaaag caggtgtggt agcccaaggc
     9361 tgggacagat taacaggaat ccatagccca gggatgcgac ccaaaattat caaagtagag
     9421 acattatgtg tttgcaatgt gctatgatta atgcagtgac ataactggca agatttacag
     9481 gtcaattgga tattgtttac ctggagctgg tccttcttag ttgccaaaaa agacataagg
     9541 attaaaaaga caaaccataa a
//
