LOCUS       NM_001134232           12351 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens transmembrane protein 106B (TMEM106B), transcript
            variant 2, mRNA.
ACCESSION   NM_001134232
VERSION     NM_001134232.2
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 12351)
  AUTHORS   Rodney,A., Karanjeet,K., Benzow,K. and Koob,M.D.
  TITLE     A common Alu insertion in the 3'UTR of TMEM106B is associated with
            risk of dementia
  JOURNAL   Alzheimers Dement 20 (7), 5071-5077 (2024)
   PUBMED   38924247
  REMARK    GeneRIF: A common Alu insertion in the 3'UTR of TMEM106B is
            associated with risk of dementia.
REFERENCE   2  (bases 1 to 12351)
  AUTHORS   Zhu,M., Zhang,G., Meng,L., Xiao,T., Fang,X. and Zhang,Z.
  TITLE     Physiological and pathological functions of TMEM106B in
            neurodegenerative diseases
  JOURNAL   Cell Mol Life Sci 81 (1), 209 (2024)
   PUBMED   38710967
  REMARK    GeneRIF: Physiological and pathological functions of TMEM106B in
            neurodegenerative diseases.
            Review article
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 12351)
  AUTHORS   Picard,C., Miron,J. and Poirier,J.
  TITLE     Association of TMEM106B with Cortical APOE Gene Expression in
            Neurodegenerative Conditions
  JOURNAL   Genes (Basel) 15 (4), 416 (2024)
   PUBMED   38674351
  REMARK    GeneRIF: Association of TMEM106B with Cortical APOE Gene Expression
            in Neurodegenerative Conditions.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 12351)
  AUTHORS   Marks,J.D., Ayuso,V.E., Carlomagno,Y., Yue,M., Todd,T.W., Hao,Y.,
            Li,Z., McEachin,Z.T., Shantaraman,A., Duong,D.M., Daughrity,L.M.,
            Jansen-West,K., Shao,W., Calliari,A., Bejarano,J.G., DeTure,M.,
            Rawlinson,B., Casey,M.C., Lilley,M.T., Donahue,M.H., Jawahar,V.M.,
            Boeve,B.F., Petersen,R.C., Knopman,D.S., Oskarsson,B.,
            Graff-Radford,N.R., Wszolek,Z.K., Dickson,D.W., Josephs,K.A.,
            Qi,Y.A., Seyfried,N.T., Ward,M.E., Zhang,Y.J., Prudencio,M.,
            Petrucelli,L. and Cook,C.N.
  TITLE     TMEM106B core deposition associates with TDP-43 pathology and is
            increased in risk SNP carriers for frontotemporal dementia
  JOURNAL   Sci Transl Med 16 (730), eadf9735 (2024)
   PUBMED   38232138
  REMARK    GeneRIF: TMEM106B core deposition associates with TDP-43 pathology
            and is increased in risk SNP carriers for frontotemporal dementia.
REFERENCE   5  (bases 1 to 12351)
  AUTHORS   Lee,J.Y., Harney,D.J., Teo,J.D., Kwok,J.B., Sutherland,G.T.,
            Larance,M. and Don,A.S.
  TITLE     The major TMEM106B dementia risk allele affects TMEM106B protein
            levels, fibril formation, and myelin lipid homeostasis in the
            ageing human hippocampus
  JOURNAL   Mol Neurodegener 18 (1), 63 (2023)
   PUBMED   37726834
  REMARK    GeneRIF: The major TMEM106B dementia risk allele affects TMEM106B
            protein levels, fibril formation, and myelin lipid homeostasis in
            the ageing human hippocampus.
            Erratum:[Mol Neurodegener. 2024 Feb 27;19(1):21. doi:
            10.1186/s13024-024-00709-9.. PMID: 38409051]
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 12351)
  AUTHORS   Cruchaga,C., Graff,C., Chiang,H.H., Wang,J., Hinrichs,A.L.,
            Spiegel,N., Bertelsen,S., Mayo,K., Norton,J.B., Morris,J.C. and
            Goate,A.
  TITLE     Association of TMEM106B gene polymorphism with age at onset in
            granulin mutation carriers and plasma granulin protein levels
  JOURNAL   Arch Neurol 68 (5), 581-586 (2011)
   PUBMED   21220649
  REMARK    GeneRIF: Our results suggest that genetic variation in TMEM106B
            (rs1990622) may influence risk for frontotemporal lobar
            degeneration with TAR DNA-binding protein inclusions (FTLD-TDP) by
            modulating secreted levels of GRN.
REFERENCE   7  (bases 1 to 12351)
  AUTHORS   van der Zee,J., Van Langenhove,T., Kleinberger,G., Sleegers,K.,
            Engelborghs,S., Vandenberghe,R., Santens,P., Van den Broeck,M.,
            Joris,G., Brys,J., Mattheijssens,M., Peeters,K., Cras,P., De
            Deyn,P.P., Cruts,M. and Van Broeckhoven,C.
  TITLE     TMEM106B is associated with frontotemporal lobar degeneration in a
            clinically diagnosed patient cohort
  JOURNAL   Brain 134 (Pt 3), 808-815 (2011)
   PUBMED   21354975
  REMARK    GeneRIF: This study strongly supported TMEM106B as a risk gene for
            frontotemporal lobar degeneration.
REFERENCE   8  (bases 1 to 12351)
  AUTHORS   Vass,R., Ashbridge,E., Geser,F., Hu,W.T., Grossman,M.,
            Clay-Falcone,D., Elman,L., McCluskey,L., Lee,V.M., Van
            Deerlin,V.M., Trojanowski,J.Q. and Chen-Plotkin,A.S.
  TITLE     Risk genotypes at TMEM106B are associated with cognitive impairment
            in amyotrophic lateral sclerosis
  JOURNAL   Acta Neuropathol 121 (3), 373-380 (2011)
   PUBMED   21104415
  REMARK    GeneRIF: FTLD-TDP risk gene TMEM106B is involved in the development
            of cognitive impairment in amyotrophic lateral sclerosis.
REFERENCE   9  (bases 1 to 12351)
  AUTHORS   Wood,H.B.
  TITLE     TMEM106B is a susceptibility locus for Ftld
  JOURNAL   Nat Rev Neurol 6 (4), 184 (2010)
   PUBMED   20383883
  REMARK    GeneRIF: The genome-wide association study revealed a strong
            association between FTLD-TDP and several single nucleotide
            polymorphisms (SNPs) that mapped in the region of the TMEM106B gene
REFERENCE   10 (bases 1 to 12351)
  AUTHORS   Van Deerlin,V.M., Sleiman,P.M., Martinez-Lage,M., Chen-Plotkin,A.,
            Wang,L.S., Graff-Radford,N.R., Dickson,D.W., Rademakers,R.,
            Boeve,B.F., Grossman,M., Arnold,S.E., Mann,D.M.,
            Pickering-Brown,S.M., Seelaar,H., Heutink,P., van Swieten,J.C.,
            Murrell,J.R., Ghetti,B., Spina,S., Grafman,J., Hodges,J.,
            Spillantini,M.G., Gilman,S., Lieberman,A.P., Kaye,J.A.,
            Woltjer,R.L., Bigio,E.H., Mesulam,M., Al-Sarraj,S., Troakes,C.,
            Rosenberg,R.N., White,C.L. 3rd, Ferrer,I., Llado,A., Neumann,M.,
            Kretzschmar,H.A., Hulette,C.M., Welsh-Bohmer,K.A., Miller,B.L.,
            Alzualde,A., Lopez de Munain,A., McKee,A.C., Gearing,M.,
            Levey,A.I., Lah,J.J., Hardy,J., Rohrer,J.D., Lashley,T.,
            Mackenzie,I.R., Feldman,H.H., Hamilton,R.L., Dekosky,S.T., van der
            Zee,J., Kumar-Singh,S., Van Broeckhoven,C., Mayeux,R.,
            Vonsattel,J.P., Troncoso,J.C., Kril,J.J., Kwok,J.B., Halliday,G.M.,
            Bird,T.D., Ince,P.G., Shaw,P.J., Cairns,N.J., Morris,J.C.,
            McLean,C.A., DeCarli,C., Ellis,W.G., Freeman,S.H., Frosch,M.P.,
            Growdon,J.H., Perl,D.P., Sano,M., Bennett,D.A., Schneider,J.A.,
            Beach,T.G., Reiman,E.M., Woodruff,B.K., Cummings,J., Vinters,H.V.,
            Miller,C.A., Chui,H.C., Alafuzoff,I., Hartikainen,P., Seilhean,D.,
            Galasko,D., Masliah,E., Cotman,C.W., Tunon,M.T., Martinez,M.C.,
            Munoz,D.G., Carroll,S.L., Marson,D., Riederer,P.F., Bogdanovic,N.,
            Schellenberg,G.D., Hakonarson,H., Trojanowski,J.Q. and Lee,V.M.
  TITLE     Common variants at 7p21 are associated with frontotemporal lobar
            degeneration with TDP-43 inclusions
  JOURNAL   Nat Genet 42 (3), 234-239 (2010)
   PUBMED   20154673
  REMARK    GeneRIF: Variants in TMEM106B are strong risk factors for
            frontotemporal lobar degeneration with TDP-43 inculsions.
            GeneRIF: Observational study and genome-wide association study of
            gene-disease association. (HuGE Navigator)
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DA452299.1, BC033901.2 and AC007321.2.
            
            On Nov 23, 2018 this sequence version replaced NM_001134232.1.
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Variants 1 and 2 both encode the same protein.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript was available
            for the full length of the gene. The extent of this transcript is
            supported by 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 :: SRR11853560.25783.1,
                                           SRR1803616.277442.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000396668.8/ ENSP00000379902.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-530               DA452299.1         73-602
            531-1563            BC033901.2         719-1751
            1564-6248           AC007321.2         115407-120091       c
            6249-12351          AC007321.2         109304-115406       c
FEATURES             Location/Qualifiers
     source          1..12351
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7p21.3"
     gene            1..12351
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /note="transmembrane protein 106B"
                     /db_xref="GeneID:54664"
                     /db_xref="HGNC:HGNC:22407"
                     /db_xref="MIM:613413"
     exon            1..132
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     exon            133..351
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     CDS             135..959
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /codon_start=1
                     /product="transmembrane protein 106B"
                     /protein_id="NP_001127704.1"
                     /db_xref="CCDS:CCDS5358.1"
                     /db_xref="GeneID:54664"
                     /db_xref="HGNC:HGNC:22407"
                     /db_xref="MIM:613413"
                     /translation="MGKSLSHLPLHSSKEDAYDGVTSENMRNGLVNSEVHNEDGRNGD
                     VSQFPYVEFTGRDSVTCPTCQGTGRIPRGQENQLVALIPYSDQRLRPRRTKLYVMASV
                     FVCLLLSGLAVFFLFPRSIDVKYIGVKSAYVSYDVQKRTIYLNITNTLNITNNNYYSV
                     EVENITAQVQFSKTVIGKARLNNITIIGPLDMKQIDYTVPTVIAEEMSYMYDFCTLIS
                     IKVHNIVLMMQVTVTTTYFGHSEQISQERYQYVDCGRNTTYQLGQSEYLNVLQPQQ"
     exon            352..415
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     exon            416..575
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     exon            576..716
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     exon            717..766
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     exon            767..820
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     exon            821..12351
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2050..2055
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /note="hexamer: AATAAA"
     polyA_site      2073
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
     regulatory      6225..6230
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /note="hexamer: AATAAA"
     polyA_site      6248
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /note="major polyA site"
     regulatory      12329..12334
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
                     /note="hexamer: AATAAA"
     polyA_site      12351
                     /gene="TMEM106B"
                     /gene_synonym="HLD16"
ORIGIN      
        1 agctctacgg cggccgcgcg ctccaggccg gtcgctccac cccccggctc ccgggactgt
       61 ggactccacg accctgtcct cggccctgtc cgcgccgaag cagcccggga ctgcgcagcg
      121 ccccgcgtgc cgacatggga aagtctcttt ctcatttgcc tttgcattca agcaaagaag
      181 atgcttatga tggagtcaca tctgaaaaca tgaggaatgg actggttaat agtgaagtcc
      241 ataatgaaga tggaagaaat ggagatgtct ctcagtttcc atatgtggaa tttacaggaa
      301 gagatagtgt cacctgccct acttgtcagg gaacaggaag aattcctagg gggcaagaaa
      361 accaactggt ggcattgatt ccatatagtg atcagagatt aaggccaaga agaacaaagc
      421 tgtatgtgat ggcttctgtg tttgtctgtc tactcctttc tggattggct gtgtttttcc
      481 ttttccctcg ctctatcgac gtgaaataca ttggtgtaaa atcagcctat gtcagttatg
      541 atgttcagaa gcgtacaatt tatttaaata tcacaaacac actaaatata acaaacaata
      601 actattactc tgtcgaagtt gaaaacatca ctgcccaagt tcaattttca aaaacagtta
      661 ttggaaaggc acgcttaaac aacataacca ttattggtcc acttgatatg aaacaaattg
      721 attacacagt acctaccgtt atagcagagg aaatgagtta tatgtatgat ttctgtactc
      781 tgatatccat caaagtgcat aacatagtac tcatgatgca agttactgtg acaacaacat
      841 actttggcca ctctgaacag atatcccagg agaggtatca gtatgtcgac tgtggaagaa
      901 acacaactta tcagttgggg cagtctgaat atttaaatgt acttcagcca caacagtaaa
      961 aactggaaga gatggattta aagaagaaat atctattgat atttcctata ctctcaatga
     1021 agaggtattt cctaatagga gaccttaaat tgaacaaacc taaagtttac acttctaaga
     1081 gtacagttaa aagtatgtgg acctgcagtt cttgtaactc tccactctgt gttaatgata
     1141 tatttgtact aggatctttt acttgaatct aaatttactg gttgatttcc ttctccagcc
     1201 tatcccctac agggaaaagc tgatacttcc cctatagtac aataaataat tatttaaaag
     1261 tcatagctcc agtcactact gaaaacataa ttttggtgat aaacataatt tgagaaactt
     1321 aatttctgaa tgtttttata gaaaattact gaaagtctat tactcatgga agacttttaa
     1381 agaataacct tttttcctgt tttataaatt cccattgtta tatggtagta tttcagctac
     1441 acaatatttt agcttttagc tagacattta tagcttttca tttgttgaaa tggtaatcat
     1501 ctgcatgttt ttgtcactta tttcaggtta gtgattgcct aacacttata agccaaaata
     1561 atctttgcaa aattccatac ctaaaatttt gaaagcccct aatgttttca cacatctttc
     1621 tgtattagtt atagttttgt gaaatctttg tgtgatcttc aaacattatc atttaatgta
     1681 caatactgta aataaactgt gcatggcttt tatacagctt tagtaaatgt caaataaagt
     1741 ggtacagact cattacaaca agtttctcat aaaaatacaa taaataggaa aatgaaattc
     1801 agaaacccat agactgggaa taggttccag ttacagcttg gatctggcat aaaataaatt
     1861 tgaaataaaa tattttgatg ctccattttt ttatgttgct tttcatacta aagaatggtg
     1921 tagacatgtt ttgcaactgt taggtaccca gttatcaatt ttatcaatgt tttagaggag
     1981 gaaattattt ttttggtaga aattgttcaa gaaatcctta attgaatgtc attaaatgat
     2041 ggtggccaaa ataaaaccta tttagaaatt taatcacttt gcacatcact tggaatatga
     2101 tgcctctagt agttactttt ttatagtttt ctacttttgg ttttatttaa aattgttttc
     2161 aaatatagat tattgactta ttcaactttg ctgttttata ttttcagtat catttttcat
     2221 tttttttttt ttttgtcttt tcacttacca agttctaggg acatttaaaa tatgtactaa
     2281 gtgtaggagt ggttatgata ccaaaaaatg tagctgggtt gagattaatt tcgttctgtt
     2341 ttctcatgac agaaatcagg tttccctttc cccaccccta agtgcctaac ttaggtctga
     2401 aacagcctgt ttattagtct gactctctca accataaaac ataagcttta tttaattctg
     2461 cctttaaaca cactcaggtt tccccttaat tttcatatta ttttctgcaa gttttcttga
     2521 gtatcttcaa ttcgttgaat gtggtttttg gttttttttt gttttaacac tagtcttccc
     2581 ttaattcatt gctaactcaa gccatcctta ctattaaacc caaatcagtc ctttaagttc
     2641 attatggcct ttctagtatt taaaaaaaaa aaaatcattt tcatttttct tctgctacgt
     2701 ttcctgacta ctactgcata cttctctgat acaggttctg tttgtatttt ttatatcatt
     2761 ctcattttct catttgacat gatctatgtc tatatatgat ataggtcccc ttttgtctca
     2821 aaatttttaa ttatgtgact tcaaaaatca cctgtatctg tagtagggct tccaaatctg
     2881 cttctccata tgtgaccagt cacctgtctg ctttcacatt tagctagtga actacacatt
     2941 tactaaaatg tgtaaatttt acacatttag tgactgtgta aaataaaaaa aaagttattt
     3001 tatcatatcc tttctattat gttcccatcc tgtcctcatg tcccatttac tttattatca
     3061 ccattcattt cttcaaaatt atcttttaga tacgctcata caaaaatcaa tccttgtttt
     3121 cttgcttgtg tcttttaacc ttggaaaatt acatcgtgta aattaaacag atttttctga
     3181 tgatctgtgc ttcttatata ctattagagt gcatgatagt atctcctgaa aaggatggaa
     3241 agtagaagca tttgctttta gtcacttaat tttgaatctt ttttcttcat cttttgaatt
     3301 aatttttttt attatatcta cttttagtgg agtttgagtc agaaaaaaac aagaatttga
     3361 aacaagtaaa aagatagaag agaaataaag atggtatgtg actactttca gagagagtta
     3421 agtaactgtc agaataagcc tggaacaaaa caggctgtaa attaataaaa ctacaaacac
     3481 acattcaggt gaagcagaag tatagccata aaacatctag aaagagtgaa tgaggctttt
     3541 agcttttctt aggtcaatgt ccagtgtgct tttttccatg ggaataggat aggtattaat
     3601 acgcttttct aaactgctct cagaccttat ccagaggaca tggtaaagat atgttacaga
     3661 aatttttctg atacttcctg gaataacttt aagttacacc ctagtagact ggtcattcta
     3721 ataaaatcca gtactataac aaacctctgt atgttgatag cacattggcc ctttttagag
     3781 ttctttccta tgtttttctt acgtgatttc ccacagttcc atgagtccaa caaaggagag
     3841 tgataggctc cttatctttt agaagaggaa ggaaaggcat gaagaagttg agggactggc
     3901 tgaagatcac gtacttacta agtagtacaa ctggagcaag atcaagtatc tctgtctccc
     3961 atatctgtgt tctatcattt aaaatatata ttggaaatcc ctgctgactc agattggtat
     4021 gattaaaaat gagaggaaag ttcaaatagt tagtagtgac aaactaatac tgctggacta
     4081 agattttggt agcattgttt tctaaaatat tttaaatgga gaatgaacac ttataaaatg
     4141 ctttggaaca taatctttag cttaattttc tgttaaaatt tagtacccct tcatcattcc
     4201 aataaagata agactgatcc attgtctaag gaaattattt ataaataata gagattaatt
     4261 tatttgagat ttgaaataag aatagtatga aaatattaga taccacataa attgtttgaa
     4321 attactgaat aaccatctta agtatggaac atttaaatgg ctatatttta tttgtgtaca
     4381 gtttttctgt gccttgttag gccagtgaag caattatttt ctctaagaaa atgacaataa
     4441 aatataacac acttcagatt gtctgattta cagtttggaa aggacaccgc aatgttcaaa
     4501 taggtaggag accatcaaaa acacaattaa agtaacatat taggagactt gaaacttcag
     4561 cctaataaat ccttcatggt tcttagcctt attattgtga tataattcta gatattttct
     4621 tggagggcat gtgcccaact ctcccgcacc ccattttgtt tgtcttttaa agttcttaga
     4681 ataaacagtt ctttatataa taattatatt ttatttaaga aaatagtttg ttaggtactt
     4741 tttaaaagat gtaaattttt aaatttacaa atacatatgg gtctttgata agcaatagga
     4801 attgaattac aagttactag ggttataagc aaaaggttgc ttaccataat gtcattaggt
     4861 cacgattttt agctcacatc tggaagcagc aactacttgg ctcaagtaca tataagagta
     4921 attagtttta ttctctcttt tttataaaat cgggtttcag atgagatgtt tatcttagac
     4981 tattttaggg aaaaatttta catgtttgag atggtggagt aaaaagactg ttaaacattt
     5041 cttttaaaaa attattttta cattacaaca atatatttat gatgtgttca gatcaaaaat
     5101 ttaacttctg tgtcccagat ctactttcaa agtgagattt tcacttgtca gcttaaattt
     5161 ctgactagaa ctaacatttg tgtatttttg tgcttagtcg gaatacaaat ttcacagtgg
     5221 atttttgaag tttgtcctta aattggataa aatcaagtga ttaaagttac taaagagata
     5281 aaaatggtaa tttccatttt taaaagtaat ttggttgtgt ttatagttat ttgtacaagt
     5341 atttatcaca gactctaaat tgaaaaatgt agtatgatct atatttgacc ctaaaaatgt
     5401 tggattaatt taacaaatat ggcagatttt tcataactaa gtcttaagtc ttctaaaagg
     5461 aagctgttac ccttctgttt ttaattacat taattgaaat gtgttttaag agatacaatt
     5521 tcagcatatt ttatatatta aaaaacaaaa aaggattagt attgagccag tggccaaaag
     5581 gtaatattac taccatgtag actgttatag ttcaaattgt cccacttcac ccagaatttt
     5641 agaaactaga agtctgggag gtactatatc agctgtagtt gggtaattcc aagtgctgat
     5701 agtactattc atctttttta ttattgtgtc agatgaaaca aatgccaagt tgcaaaatat
     5761 gcagattttt attatataat ggttttaggc ataaattatt aacaagccat gccttatgtg
     5821 tttcatctta tatttttctt tagaactaaa ctataacaga ttttggaaaa tgatttgacg
     5881 tgcttgctca cttgattgac ttggtcagat atttgaatga tggtattacc tagattctaa
     5941 tccttgattc tagttatata ataaataata tagaatatga aaatatgttt gggcatttac
     6001 tgtttatatt atgtagtagc ctccatcatg acacacttac tacatttatg aattgagcag
     6061 ttctgtaatt gtaattatta ttgctgttca tgtaacaaaa catgcttata atagcaaaca
     6121 aatagaaatg cccccaaaat gctatttttt taattcagtt ataactgtta ctcttgtagt
     6181 tgtgtatgac gcaataaaat ttgtaaaaaa atttcagcat gaaaaataaa atttgtatca
     6241 cttatgtatt ttggctatgc ttttgaaatt tccttaacat aaacaaatca gtgtagatat
     6301 tcaaaatctt ttacctttaa tccttttcat ccttatagtc cttacctgaa ctctacttta
     6361 gcattatctt tgatttcttt ttttcattca cttaacttcc aatcagtact caagctttat
     6421 ccattctacc tctgtaatgt ctctggaatt tatctcatac gtgaaatttc ccttgatatt
     6481 atagacatac cttggatata ttgcaggttt ggttccacac catatcgata aagtgatata
     6541 atcaagcaag ttacacacct ttttttggtt tcccagtgca tatgaaagtt atgtttacat
     6601 catactgtag tctattaagt gtgcaatagc attatgtcga aaaacacaat atatatgcct
     6661 taataaaaaa taggctgtgt gcagtggctc acacctgtaa tcccagcact ttcggaggcc
     6721 aaggtgggag gatcacctga gcccagaagt tcaagaccaa attggtcaac atggcgagac
     6781 cccatataaa atatatacat acacacacac acacacacac acacacacac acacacacac
     6841 tattgctaaa aaatgttaac gatcatctga atgttcagaa gtttatactc cttttgccgg
     6901 cacaggatct tgtctggatg ttgtttgctg atagatccat gtagtggtta ctaaagttgg
     6961 ggtggctatg gcaatttctt aagacaacaa tgaagtttat cacatctatt gccttgtcct
     7021 ttcatgaaag atgtctctag catgtgatgc tgttttgata gcattttacc aatggtaggt
     7081 cttttttcaa aattggagcc agtcctctca aaccctgcct ctgctttatc gaccatgttt
     7141 aaataatttt ctaaattctt tattgtcatt tcagcagtgg tctcagcatc ttcaccagga
     7201 gtagattcca actcaagaaa ccactttctt agctcattca taagaaacaa ttcctcatct
     7261 gttcaagttt tggcatcaag ttgtagcaat tcagtcacat ctacagactc cattgctaaa
     7321 ttttagttct cttgctattt ccacatctgc tgtgacttcc ttcactgaag tcatgaaccc
     7381 ctcaaaatta tccatgagag ttgaaatcaa tttctttcaa actcctgtta atgttcatat
     7441 ttagacctct tcccctgaat cacaaatgtt gttaatggca tctagaatgg caaatccttt
     7501 ctggaaggtt tcaatttact ttgcccagat ccatcagagg aatcactacc tatgacagct
     7561 atggtcttac aaaatgtatt tcttatatag taagattcaa aagtcaaatt tactccctga
     7621 tccatggctg cagaatgcac gttgtgttaa gaggcatgaa aacaacatta atctatttgt
     7681 acatcatcag agctgttggg tgaccaggta cattgtcaat gagtagtaat actttgaaag
     7741 gaattttttt ttccaagcag gtctcaacaa tgggcttaaa atattcagtg aaccgtgttg
     7801 taaacagatg tcatattatc cagactgttc catttattga acacaggcag agtaggtaaa
     7861 agttttaagg gtcctaggat tttcaggatg gcaaatgagc attggcttca acttaaagtc
     7921 accagctaca ttcaccacta aagagagtca gcctgtcctt taaagcttta aaggcaagca
     7981 ttgacttctc tttagctatg aaagttttag atggcacctt tttgtaaaag aaggttgttt
     8041 tatctacatt gaaaatatat tgttcattgt aaccactttc atcaatgatc ttagctagat
     8101 attctgggta acttactgca ggttctccat cagcacttac tgcttcacct tgcactttta
     8161 tattatggaa acaacttatc tccttaaaca tcattaacca acctcttggt agcttccaac
     8221 ttttcttcaa tagcttcctc atctctctca gccttcatag aattgaagcg tgttagggct
     8281 ttgttcagga ttaggctttc acttaaggca atgttgtggc tggtttgatc tattgaaacc
     8341 actaaaacat tcccatatcg gcaataaggc tgtttgattt tcttatcatt catgttttct
     8401 ggaacacttt tcaattactt acagtaagga aatagcactt ttaatttcct tcaagaactt
     8461 ttcctttgcc ttcacaactt gtgcaagaga cctagctttc agcctatctt gactttccaa
     8521 gattgtcctt ggtgagaaat gcttgattac taggtgtaat tatttctagc ttttgattga
     8581 aagtgagaga tatgtgactc ttccttttac ttgaacagtt agaggctatt gtaggattat
     8641 taattggcct aatttcaatg ttattttgtc tcaaggagag agggatgtgg gaacagctgg
     8701 ttaggagagc agtccgaaca cacacttttt tttattactt tcactgcctt acatgggtat
     8761 ggttcatgct gcctccaaat acttacaaaa acatcaaaga tcactgatta cagatcatta
     8821 aaataggttt aataataatg gaaacatttg aaatattgca aaaattacca aaatgcgaca
     8881 gagacatgaa atgagaacat gctgttgaaa aaaatggcac tcatagactt gttggacaca
     8941 ggattgaaag aaaccaattc atcaaaacca caatatctgc aaaacgcaat aaggtgatgc
     9001 acaataaaag gaagtatatc tgcacttcct tcttttttac tgaaaaagcc caagttctta
     9061 ctctggtgtt gagaaccttt cattagctgg ctacaatctc agttcacaat catttcttat
     9121 tgcccttcaa caatgtcctg accaaatcga gttctttctc attgggaaca gttcattcct
     9181 ttatcccttc gctcattctg ttcctttttt cttagaaaaa ttatttgccc atgtttttta
     9241 tcccccaatt ctatcttttt caatgcccac ttcgtgtcca acccctctct actttccctc
     9301 taaacttact caaacacttg gtgaactttt tctgaatgtt ttttctgaat gtttactttt
     9361 aaaggagttg cccagtcaca aagtttgagc caagtttttt tgttttaaac ttgttttaaa
     9421 cttttgtttt catcaacttt tttcaaacaa tttttgtcag cttagaggtt gtgttttaat
     9481 tactattttt aaaatcttgt atgaggtagt atgatttgaa attagatgga atgtgcccaa
     9541 aattatctct gtagaataat atggaaaaac gaaaatgaaa agatgtatta cctgaatgtg
     9601 ctcctcctag ccagtttctc aagggagaag aatcattaat aagtttgtga ggcttttttt
     9661 ttttttctgg tagatttctg tttccttgat cagtggtttt tcagaatttt ttaaagcttg
     9721 tgaaatactt atttgtaaat agcatcttat gaggaacctt gatatgtgac aaaacagatg
     9781 ctttgatttg agagcagaag acctgcagcc cctgactgct cacctttcca gggacccctg
     9841 aacattggcc tagagggtag tgtacagtca cttcttcagt gataacttac tgagtgtgat
     9901 tcaacaaaac tgctttggtt tatgggtgaa acataattta taactaggca aatgtcagct
     9961 taaatttata ttttctaaat agcactgaaa atgacaatag acaaatgtaa tttctgattt
    10021 ttaagaaatg attttccatt ttaacataca ttttaaatgt tttgtcttca aagggaatcc
    10081 ttaaaaatga tatattggaa accactgatt tcttattttc atttcatgaa tttcagattc
    10141 atgaatggaa tatattgata atagcatttt ttaagttgcc ccaaaaagat gaaatacaaa
    10201 taattttaat cccaaatcta tttcagacac ctaacttttt ttttattttt tatactttaa
    10261 gttctaggat acatgtgcag aacgtgcagg tttgttacat aggtatacac gtgccatgtt
    10321 ggtttgctgc acccatcaac ccgtcatcta cattagatat ttctactaat gctatccctc
    10381 ccctagcccc ctaccccaca aaaggcccca gtgtgtgatg ttcccctccc tgtgtccatc
    10441 tgttctcatt gttcaactcc cacttatgag tggcaacatg tgctgtttgg ttttctgttc
    10501 ctgtgtgtgt ttgctgagaa tgatggtttc cagcttcatc catatccctg aaaaggacat
    10561 gaactcatcc ttttttatgg ctgcatagta ttccatggtg tatatatgcc acattttctt
    10621 tatccagtct atcattgatg gacatttggg ttggttccaa gtctttacta ttgtgaacag
    10681 tgctgcaata aacatatgtg tgtatgtgtc tttacagtaa aatgatttat aatcttttgg
    10741 gtatacaccc agtaatggga ttgctgggtc aaatggtatt tctggttcta gatccttgag
    10801 gaatcaccac actgtcttcc acaatggttg caatttacac tcccaccaac agtgtgtaaa
    10861 agcttcctat ttctctacat tctctccagc atctgttgtt tcctgactta atgattgcca
    10921 ttctaactgg cgtgagatgg tttctcactg tggttttgat ttgcatttct gtaatgaccc
    10981 gtgatgatga gctttttttc atgtttgttg gctgcataaa tgtcttcttt tgagaagtgt
    11041 aaggtactta attcttaaat taaaaaaaaa tacccggccg ggcacggtgg ctcacgcctg
    11101 taatcccagc actttgggag gccgaggcgg gtggatcatg aggtcaagag atcgagacca
    11161 tcctggctaa caaggtgaaa ccccgtctct actaaaaata caaaaaatta gccgggcgcg
    11221 gtggcgggcg cctgtagtcc cagctactcg ggaggctgag gcaggagaat ggcgtgaacc
    11281 cgggaagcgg ggcttgcagc gagccgagat tgcgccactg cagtccgcag tccggcctgg
    11341 gcgacagagc gagactccgt ctcaaaaaaa aaaaaaaaaa aaaaaaaaaa atacccttct
    11401 ttaacaaaat caagtttcaa gttttctgcc ttgttgataa cttgttaaca tttttttatt
    11461 ttagaataaa tctaaacaga gaccacactg atatctgtaa caacctatgt aaagttaaga
    11521 ttaaggttaa atcacatttt tcacagagag tgttttactg aaatataaac ttttatgcat
    11581 ctgatattat ctaattgtgt ccttactggg taacttgtgt atttttcaag ttaaaggatt
    11641 tcctaaaaat gcttatttga atatttatgt catttgtcac acatactttc aaaacataac
    11701 cttcttcaac gagtatcttc ttttccttcc taaaatactg ttaatagctg gctattttgt
    11761 aagcctgtat ctggtttaaa aaaaagaagt gaatattttc aatacttatg aaccatagaa
    11821 ttctgtattc ttttcataac ttttaacttt tccataggac ctatcactat gtaaaatatt
    11881 atacatatct actgatttat ttattgccta tgtacctata ctagaacata gtaaacatga
    11941 gaacagggaa tcttggttat taattcctgc aggactcaac tacttatcac tcaaacattt
    12001 gttcttgaaa agaacttcgt ataacatcat tagattttta cagaatcttt aaaaaagctt
    12061 taatattttc aaggtttttt atttatataa atattgttac tttaccacta gtgatttcaa
    12121 tagtggcatt gtcacatgat tcaagaagag gaggccatta cattactgtt gtattaaaaa
    12181 gtcagttcag gcttaatata tatgactact ataagtcaac ctcacatttt aatgtatgaa
    12241 gaagattgta tgaacgatca cattaattca tttaaatagt atgtattttg atactaattt
    12301 ttaagaagaa atgtatcatt ctcatggaaa taaaagataa tttgaaaagc a
//
