1997 年度実績報告書

ヒトゲノム構造解析

研究課題

研究課題/領域番号	08283108
研究機関	国立がんセンター
研究代表者	大木操国立がんセンター研究所, 放射線研究部, 部長 (00158792)
研究分担者	林健志九州大学, 遺伝子情報実験施設, 教授 (00019671) 戸田達史東京大学, 医科学研究所, 助教授 (30262025) 清水信義慶應義塾大学, 医学部, 教授 (50162706) 猪子英俊東海大学, 医学部, 教授 (10101932) 榊佳之東京大学, 医科学研究所, 教授 (10112327)
キーワード	11q13領域 / 21番染色体 / シークエンス地図 / MHCクラスI領域 / 自己免疫疾患APECED / 福山型先天性ジストロフィー / 変異検出法 / 高速大規模プラスミド調整機
研究概要	11番染色体長腕全域のNotI制限酵素地図を基に、IDDM4,SCA5等の遺伝病がマップされている11q13領域の一部、約6MbのコンティグマップをP1,PAC,BACクローンを用いて作製し完成させた。その他、T細胞レセプターα/γ鎖遺伝子(1Mb)、14番染色体q32.1領域(約2Mb)、21番染色体21qcen-D21S190約2Mb領域等のコンティグ化を行った。ヒト21番染色体のシークエンス地図の作成を目指し、昨年度のダウン症必須領域(1.5Mb)に加え、本年度はSOD-1からAML-1に至る3.3Mbのシークエンス地図を完成させた。ヒト抗体VH遺伝子座の全塩基配列957kbを決定し、123個のV遺伝子断片、26個のD遺伝子断片を同定した。ヒトMHCクラスI領域1.3Mbについて塩基配列の決定を行い、34個の遺伝子を同定し、ベーチェット病の原因遺伝子を約100kb領域内に絞りこんだ。ゲノムシーケンシングを基盤として自己免疫疾患APECEDの原因遺伝子AIREを発見した。ポジショナルクローニング法により、9q31に存在する福山型先天性ジストロフィー原因遺伝子本体を単離し、ほとんどの患者は福山型新規遺伝子へのレトロトランスポゾンの挿入変異を持つことを明らかにした。t(2;8;3)を持つてんかん・自閉症患者の転座点の解析を行い、3番染色体上の転座点より遺伝子を単離した。この遺伝子はカルシウムイオンチャンネルと相同性を持つ。 21番染色体セロトロメアα21-1領域由来YACをヒト培養細胞へ導入して形成された人工染色体の解析から、α21-1がセントロメア機能配列であることが判明した。高度に自動化された変異検出法として、キャピリ-電気泳動装置を用いたPLACE-SSCP法を確立した。1枚のプレートでバキューム操作のみで、プラスミドDNAを調整できる原理を開発し、それを応用して高速かつ大量にプラスミドを処理することができる高速大規模プラスミド調整機を作製した。DNAfiberFISH法で広範囲に分布する融合遺伝子の切断点を簡便、迅速なmappingを可能にした。

研究成果

(45件)

すべてその他

すべて文献書誌 (45件)

[文献書誌] Hosoda,F.: "A complete Notl restriction map covering the entire long arm of human chromosome 11." Genes to Cells. 2. 345-357 (1997)
[文献書誌] Kitamura,E: "A 3-Mb sequence-ready contig map encompassing the multiple disease gene cluster on chromosome 11q13.1-13.3." DNA Res.4. 281-289 (1997)
[文献書誌] Kitabayashi,I: "The AMLI,MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR)family,MTGRI." Mol.Cell.Biol.18. 846-858 (1998)
[文献書誌] Ohira,M.: "Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21." Genome Res.7. 47-58 (1997)
[文献書誌] Arai,Y.: "The inv(II)(p15q22)chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene,NUP98with the putative RNA helicase gene,DDX10." Blood. 89. 3936-3944 (1997)
[文献書誌] Hattori,M.: "A novel method for making nested deletins and its application for sequencing of a 300 kb region of human APP locus." Nucleic Acids Res.25. 1802-1808 (1997)
[文献書誌] Nakamura,A.: "Isolation of a novel human gene from the Down syndrome critical region of chromosome 21q22.2." J.Biochem.122. 872-877 (1997)
[文献書誌] Hsgiwama,Y.: "Screening for imprinted genes by allelic messge display:identification of a paternally expressed gene Impact on Mouse chromosome 18." Proc.Natl.Acad.Sci.USA. 96. 9249-9254 (1997)
[文献書誌] Tei,H.: "Circadian oscillation of a mammalian homorogue of the Drosophila period gene" Nature. 389. 512-516 (1997)
[文献書誌] Mizuki,N.: "Triplet repeat polymorphism in the transmembrane region of the MICA gene:A strong association of six GCT repetitions with Behcet's disease." Proc.Natl.Acad.Sci.USA. 94. 1298-1303 (1997)
[文献書誌] Mizuki,N.: "Nucleotide sequene analysis of the HLA class I region spanning the 237kb segment around the HLA-B and C gene." Genomics. 42. 55-66 (1997)
[文献書誌] Kikuti,Y.: "Physical mapping 220kb centromeric of the human MHC and DNA sequencing analysis of the 43-kb segment including the RING1,HKE6,and HKE4 genes." Genomics. 42. 422-435 (1997)
[文献書誌] Tanzen,T.: "Precise switching of DNA replication timing in the GC content transition area in the human MHC." Mol.Cell.Biol.17. 4043-4050 (1997)
[文献書誌] Endo,T.: "Evolutionary significance of intra-genome duplications on human chromosomes." Gene. 205. 19-27 (1997)
[文献書誌] Iwahara,J.: "A helix-turn-helix structure unit in human centromere protein B(CENP-B)." EMBO J.17. 827-837 (1998)
[文献書誌] Oyake,M.: "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy(DRPLA)cDNA:Strong conservation of a polymorphic CAG repeat in the murine gene." Genomics. 40. 205-207 (1997)
[文献書誌] Illarioshkin,S.: "Refined genetic location of the chromosome 2p-linked progressive muscular dystrophy gene." Genomics. 42. 345-348 (1997)
[文献書誌] Igarashi,S.: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch." Nature Genet.18. 111-117 (1998)
[文献書誌] Kawasaki,K: "One megabase sequence analysis of the human immunoglobulin γ gene locus." Genome Res.7. 250-261 (1997)
[文献書誌] Imamura,Y.: "Human retina-specific amine oxidase(RAO):cDNA cloning,tissue expression and chromosomal mapping." Genomics. 40. 277-283 (1997)
[文献書誌] Chrast,R.: "Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region." Genome Res.7. 615-624 (1997)
[文献書誌] Nagamine,K.: "Positional cloning of the APECED gene." Nature Genet.17. 393-398 (1997)
[文献書誌] Miyake,M.: "YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy(FCMD)candidate region on 9q31." Genomics. 40. 284-293 (1997)
[文献書誌] Kondo-Iida,E.: "Molecular genetic evidence of clinical heterogeneity in Fukuyama type congenital muscular dystrophy." Hum.Genet.99. 427-432 (1997)
[文献書誌] Saito,K.: "Prental diagnosis in eight Fukuyama type congenital muscular dystrophy families by haplotype analysis using the new markers closest to the gene." Am.J.Med.Genet.(in press).
[文献書誌] Matsumoto,N.: "A 1.2-megabase BAC/PAC contig spanning the 14q13 breakpoint of t(2;14)in a minor-image polydactyly patient." Genomics. 45. 11-16 (1997)
[文献書誌] Fujimoto,M.: "The gene for mesomelic dysplasia Kantaputra type is mapped to 2q24-q32." J.Hum.Genet.(in press).
[文献書誌] Matsumoto,S.: "Detailed deletion mapping of chromosome arm 3p in breast cancrers:A 2-cM region on 3p14.3-21.1 and a 5-cM region on 3p24.3-25.1 commonly deleted in tumors." Genes,Chrom.Cancer. 20. 268-274 (1997)
[文献書誌] Iida,A.: "Mapping of a new target region of allelicloss to a 2-cM interval at 22q13.1 in primary breast cancer." Genes,Chrom.Cancer. 21. 108-112 (1998)
[文献書誌] Imai,T.: "The structure and organization of the human NPAT gene." Genomics. 42. 388-392 (1997)
[文献書誌] Hori,T.: "A distamycin A-inducible fragile sote,FRA8E,is located in the hereditary multiple exostoses gene and not involved in HPV16 DNA integration and amplification." Cancer Genet.Cytogenet.99. 1-11 (1997)
[文献書誌] Yamagishi,F.: "Molecular analysis of chromosome 14q32 abnormalities in esophageal and gastric carcinoma." Annals of Cancer Res. and Therapy. (in press).
[文献書誌] Sakashita,A.: "Amplificatin of the TCL1 franking region af 14q32.1 with no TCL1 gene transcription in a patient with peripheral T-cell lymphoma." Leukemia. (in press).
[文献書誌] Kimura,M.: "Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer." Cancer Res.(in press).
[文献書誌] Kong,D.: "PTENI is frequently mutated in primary endometrial carcinomas." Nature Genet.17. 143-144 (1997)
[文献書誌] Yamane,Y.: "Allelic frequencies of twelve dinucleotide repeat marker loci o n chromosome 13 in the normal Japanese population." Jpn.J.Hum.Genet.42. 533-537 (1997)
[文献書誌] Chinene,K.: "Isolation of 45 ex on-like fragments from 8p21.3-p22,a region that is commonly deleted in hepatocellular,colorectal,and non-small cell lung carcinomas." Cytogenet.and Cell Genet.190-196 (1997)
[文献書誌] Ito,M.: "Simple and rapid preparation of plasmid template by a filtration method using microtiterfilter plates." Nucleic Acids.Res.25. 1315-1316 (1997)
[文献書誌] Yoshkawa,H.: "Chromosome assignment of abrrant Natl restriction DNA fragments in primary hepatocellular carcinoma." Gene. 197. 129-135 (1997)
[文献書誌] Iha,H.: "Identification and characterization of a novel trans-membrane protein gene,pdh1,from Schizosaccharomyces pombe." DNA Res.4. 393-396 (1997)
[文献書誌] Kimura,T.: "The brain finger protein gene(znf179),a memter of the RING finger family,maps within the Smith-Magenis syndrome region at 17q1.2." Am.J.Med.Genet.69. 320-324 (1997)
[文献書誌] Hiroike,S.: "Tandem duplications of the FLT3 Receptor gene are closely associated with leukemic transformation of myelodysplasia." Leukemia. 11. 1442-1446 (1997)
[文献書誌] Ueda,Y.: "Interphase detection of BCL6/IgH fusion gene in non-hodgkin lymphoma by fluoredsence in situ hybridization." Cancer Genet.Cytogenet.99. 102-107 (1997)
[文献書誌] Kukita,Y.: "SSCP analysis of long DNA fragments in low PH gel." Hum an Mutation. 10. 400-407 (1997)
[文献書誌] Inazuka,M.: "A stream-lined mutation detection system:Multi-color post-PCR fluorescence-labeling and SSCP analysis by calillary electrophoresis." Genome Res.7. 1094-1103 (1997)

1997 年度 実績報告書

ヒトゲノム構造解析

研究代表者

大木 操 国立がんセンター研究所, 放射線研究部, 部長 (00158792)

研究成果

[文献書誌] Hosoda,F.: "A complete Notl restriction map covering the entire long arm of human chromosome 11." Genes to Cells. 2. 345-357 (1997)

[文献書誌] Kitamura,E: "A 3-Mb sequence-ready contig map encompassing the multiple disease gene cluster on chromosome 11q13.1-13.3." DNA Res.4. 281-289 (1997)

[文献書誌] Kitabayashi,I: "The AMLI,MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR)family,MTGRI." Mol.Cell.Biol.18. 846-858 (1998)

[文献書誌] Ohira,M.: "Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21." Genome Res.7. 47-58 (1997)

[文献書誌] Arai,Y.: "The inv(II)(p15q22)chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene,NUP98with the putative RNA helicase gene,DDX10." Blood. 89. 3936-3944 (1997)

[文献書誌] Hattori,M.: "A novel method for making nested deletins and its application for sequencing of a 300 kb region of human APP locus." Nucleic Acids Res.25. 1802-1808 (1997)

[文献書誌] Nakamura,A.: "Isolation of a novel human gene from the Down syndrome critical region of chromosome 21q22.2." J.Biochem.122. 872-877 (1997)

[文献書誌] Hsgiwama,Y.: "Screening for imprinted genes by allelic messge display:identification of a paternally expressed gene Impact on Mouse chromosome 18." Proc.Natl.Acad.Sci.USA. 96. 9249-9254 (1997)

[文献書誌] Tei,H.: "Circadian oscillation of a mammalian homorogue of the Drosophila period gene" Nature. 389. 512-516 (1997)

[文献書誌] Mizuki,N.: "Triplet repeat polymorphism in the transmembrane region of the MICA gene:A strong association of six GCT repetitions with Behcet's disease." Proc.Natl.Acad.Sci.USA. 94. 1298-1303 (1997)

[文献書誌] Mizuki,N.: "Nucleotide sequene analysis of the HLA class I region spanning the 237kb segment around the HLA-B and C gene." Genomics. 42. 55-66 (1997)

[文献書誌] Kikuti,Y.: "Physical mapping 220kb centromeric of the human MHC and DNA sequencing analysis of the 43-kb segment including the RING1,HKE6,and HKE4 genes." Genomics. 42. 422-435 (1997)

[文献書誌] Tanzen,T.: "Precise switching of DNA replication timing in the GC content transition area in the human MHC." Mol.Cell.Biol.17. 4043-4050 (1997)

[文献書誌] Endo,T.: "Evolutionary significance of intra-genome duplications on human chromosomes." Gene. 205. 19-27 (1997)

[文献書誌] Iwahara,J.: "A helix-turn-helix structure unit in human centromere protein B(CENP-B)." EMBO J.17. 827-837 (1998)

[文献書誌] Oyake,M.: "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy(DRPLA)cDNA:Strong conservation of a polymorphic CAG repeat in the murine gene." Genomics. 40. 205-207 (1997)

[文献書誌] Illarioshkin,S.: "Refined genetic location of the chromosome 2p-linked progressive muscular dystrophy gene." Genomics. 42. 345-348 (1997)

[文献書誌] Igarashi,S.: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch." Nature Genet.18. 111-117 (1998)

[文献書誌] Kawasaki,K: "One megabase sequence analysis of the human immunoglobulin γ gene locus." Genome Res.7. 250-261 (1997)

[文献書誌] Imamura,Y.: "Human retina-specific amine oxidase(RAO):cDNA cloning,tissue expression and chromosomal mapping." Genomics. 40. 277-283 (1997)

[文献書誌] Chrast,R.: "Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region." Genome Res.7. 615-624 (1997)

[文献書誌] Nagamine,K.: "Positional cloning of the APECED gene." Nature Genet.17. 393-398 (1997)

[文献書誌] Miyake,M.: "YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy(FCMD)candidate region on 9q31." Genomics. 40. 284-293 (1997)

[文献書誌] Kondo-Iida,E.: "Molecular genetic evidence of clinical heterogeneity in Fukuyama type congenital muscular dystrophy." Hum.Genet.99. 427-432 (1997)

[文献書誌] Saito,K.: "Prental diagnosis in eight Fukuyama type congenital muscular dystrophy families by haplotype analysis using the new markers closest to the gene." Am.J.Med.Genet.(in press).

[文献書誌] Matsumoto,N.: "A 1.2-megabase BAC/PAC contig spanning the 14q13 breakpoint of t(2;14)in a minor-image polydactyly patient." Genomics. 45. 11-16 (1997)

[文献書誌] Fujimoto,M.: "The gene for mesomelic dysplasia Kantaputra type is mapped to 2q24-q32." J.Hum.Genet.(in press).

[文献書誌] Matsumoto,S.: "Detailed deletion mapping of chromosome arm 3p in breast cancrers:A 2-cM region on 3p14.3-21.1 and a 5-cM region on 3p24.3-25.1 commonly deleted in tumors." Genes,Chrom.Cancer. 20. 268-274 (1997)

[文献書誌] Iida,A.: "Mapping of a new target region of allelicloss to a 2-cM interval at 22q13.1 in primary breast cancer." Genes,Chrom.Cancer. 21. 108-112 (1998)

[文献書誌] Imai,T.: "The structure and organization of the human NPAT gene." Genomics. 42. 388-392 (1997)

[文献書誌] Hori,T.: "A distamycin A-inducible fragile sote,FRA8E,is located in the hereditary multiple exostoses gene and not involved in HPV16 DNA integration and amplification." Cancer Genet.Cytogenet.99. 1-11 (1997)

[文献書誌] Yamagishi,F.: "Molecular analysis of chromosome 14q32 abnormalities in esophageal and gastric carcinoma." Annals of Cancer Res. and Therapy. (in press).

[文献書誌] Sakashita,A.: "Amplificatin of the TCL1 franking region af 14q32.1 with no TCL1 gene transcription in a patient with peripheral T-cell lymphoma." Leukemia. (in press).

[文献書誌] Kimura,M.: "Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer." Cancer Res.(in press).

[文献書誌] Kong,D.: "PTENI is frequently mutated in primary endometrial carcinomas." Nature Genet.17. 143-144 (1997)

[文献書誌] Yamane,Y.: "Allelic frequencies of twelve dinucleotide repeat marker loci o n chromosome 13 in the normal Japanese population." Jpn.J.Hum.Genet.42. 533-537 (1997)

[文献書誌] Chinene,K.: "Isolation of 45 ex on-like fragments from 8p21.3-p22,a region that is commonly deleted in hepatocellular,colorectal,and non-small cell lung carcinomas." Cytogenet.and Cell Genet.190-196 (1997)

[文献書誌] Ito,M.: "Simple and rapid preparation of plasmid template by a filtration method using microtiterfilter plates." Nucleic Acids.Res.25. 1315-1316 (1997)

[文献書誌] Yoshkawa,H.: "Chromosome assignment of abrrant Natl restriction DNA fragments in primary hepatocellular carcinoma." Gene. 197. 129-135 (1997)

[文献書誌] Iha,H.: "Identification and characterization of a novel trans-membrane protein gene,pdh1,from Schizosaccharomyces pombe." DNA Res.4. 393-396 (1997)

[文献書誌] Kimura,T.: "The brain finger protein gene(znf179),a memter of the RING finger family,maps within the Smith-Magenis syndrome region at 17q1.2." Am.J.Med.Genet.69. 320-324 (1997)

[文献書誌] Hiroike,S.: "Tandem duplications of the FLT3 Receptor gene are closely associated with leukemic transformation of myelodysplasia." Leukemia. 11. 1442-1446 (1997)

[文献書誌] Ueda,Y.: "Interphase detection of BCL6/IgH fusion gene in non-hodgkin lymphoma by fluoredsence in situ hybridization." Cancer Genet.Cytogenet.99. 102-107 (1997)

[文献書誌] Kukita,Y.: "SSCP analysis of long DNA fragments in low PH gel." Hum an Mutation. 10. 400-407 (1997)

[文献書誌] Inazuka,M.: "A stream-lined mutation detection system:Multi-color post-PCR fluorescence-labeling and SSCP analysis by calillary electrophoresis." Genome Res.7. 1094-1103 (1997)

1997 年度実績報告書

大木操国立がんセンター研究所, 放射線研究部, 部長 (00158792)