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ヒト・ゲノム解析研究

Research Project

Project/Area Number 05NP0401
Research Category

Grant-in-Aid for Creative Basic Research

Allocation TypeSingle-year Grants
Research InstitutionOsaka University

Principal Investigator

松原 謙一  大阪大学, 細胞生体工学センター, 教授 (20037394)

Co-Investigator(Kenkyū-buntansha) 大木 操  国立がんセンター研究所, 部長 (00158792)
中村 祐輔  (財)癌研究会癌研究所, 部長 (70217909)
吉田 光昭  東京大学, 医科学研究所, 教授 (80012607)
吉川 寛  奈良先端科学技術大学院大学, 教授 (70019876)
榊 佳之  東京大学, 医科学研究所, 教授 (10112327)
Project Period (FY) 1991 – 1995
Project Status Completed (Fiscal Year 1993)
Keywordsヒト・ゲノム / ゲノム構造解析 / ゲノム機能解析 / cDNA / DNA解析技術 / モデル生物 / 生物情報科学 / 塩基配列決定
Research Abstract

生命の設計図であるゲノムの構造と機能を解析研究しそこに包含される遺伝情報を理解する。この目的で、総括班ならびに3つの研究班を組織して研究の推進を図り次の成果を得た。
1.総括班。全体としての活動を円滑に進めるため各種会合の企画立案調整、機器の計画的購入と配分、情報交流、調査などを積極的に進めた。また、社会との接点の問題研究の展開を図った。さらに、評価委員会を設置して全班員の業績評価を行い、その結果に基き平成5年度に向けて班員の入れ替えを行い、先鋭的なゲノム研究の活性化を図った。
2.ヒト・ゲノム構造解析班。ヒト染色体21番につき物理地図を作製したほか、国際協力によるYACコンティグマップ作りに貢献した。また、染色体3,6,8,11,X,Yにつき高密度のコスミドマップ作製を進め、ゲノムデータベース作成において国際貢献を果たした。これらの研究作業を通して大量の資料を扱いつつそれらを処理、分析し、データ化して整理する方法論の開発と実行が軌道に乗った。また、これらの成果を活用して、がん抑制遺伝子や先天性発育遅滞に関する遺伝子の単離、または位置づけに成功した。これと並んで、特定領域として免疫グロブリン遺伝子H鎖V領域とHLA遺伝子群を選び、詳細なマップ作りと遺伝子の同定を実行した。これは、来るべきシーケンシング時代のモデルとなる先導的研究である。
3.cDNA解析班。ヒトの各種臓器や細胞の中で発現している全遺伝子をカタログ化し、その発現頻度を解析し情報化する「3'特異的cDNAライブラリー解析」を進め、約25000クローンの解析を終えた。これは、世界に先駆けてゲノム研究を構造解析と機能解析の両面から行おうという新しい方向性を与えるものであり、追随する仕事が多く現われた。良質なcDNAライブラリーの作成やその迅速な分類、カタログ化の手法がほぼ完成した。また、大容量のデータ整理などにおける新しい手法が種々開発されると共に、5'特異的cDNAライブラリーの作成や、cDNAの全長解析、cDNAのゲノムへのマッピングなどを可能にするいろいろな技術開発が行われ、一部でデータ生産活動が始まった。
4.DNA解析技術開発班。DNAの取り扱い技術とマーカーDNAの染色体上へのマッピングに関わる技術開発を進めた。特に、色素プローブを用いる染色体上への位置決め技術に大幅な進歩を見た。また、ゲノムスキャンニング法の確立と応用、T3ファージによるDNA欠失セットの作成技術、超高分子DNAの電場による分離技術の確立など、本班の業績が次々と出された。これと並んで、枯草菌、分裂酵母、線虫をモデル生物として選び、国際協力によってゲノムデータベースを作りつつ技術開発とデータベース間の相互連携をつくるシステム作りが長足の進歩を遂げた。全体として、近々に具体的にシーケンスデータを大量に生産するゲノム研究第二期が近づいたと思われる。

Report

(1 results)
  • 1993 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Virgilio,L.(Isobe,M.): "Chromosome walking on the tcl-llocus involved in T-cell neoplasia" Proc.Natl.Acad.Sci.90. 9275-9279 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugimura,K.(Inoko,H.): "Analysis of genes within the HLA region affecting susceptibility to Ulcerative Colitis" Hum.Immunol.36. 112-118 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akao,Y.(Imai,T): "Long-range mapping of the 11q23 region involved in chromosome aberrations in human tumors by pulsed-field gel electrophoresis with a yeast artificial chromosome" Genes,Chromosomes & Cancer. 8. 167-171 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ichikawa,H.(Ohki,M.): "A NotI restriction map of the entire long arm of human chromosome 21" Nature Genet.4. 361-366 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeda,O.(Kaneko,Y.): "There may be two tumor suppressor genes on chromosome arm 1p closely associated with biologically distinct subtypes of neuroblastoma" Genes Chrom.Cancer,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Harada,H.(Kimura,A.): "A missense mutation of cardiac beta-myosin heavy chain gene linked to familial hypertrophic cardiomyopathy in affected Japanese families" Biochem.Biophys.Res.Commun.194. 791-798 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nagafuchi,S.(Kondo,I.): "Dentatorubral-pallidoluysian atropy expansion of an unstable CAG trinucleotide on chromosome 12p" Nature Genet.6. 14-18 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hattori,M.(Sakaki,Y.): "Sequence-tagged NotI sites of human chromosome 21 : Sequence analysis and mapping" Genomics. 17. 39-44 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayasaka,K.(Shimizu,N.): "Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P gene" Nature Genet.5. 31-34 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Koide,R.(Tsuji,S.): "Unstable expansion of CAG repeat in hereditary dentatorubral-pallidolusian atrophy(DRPLA)" Nature Genet.6(1). 9-13 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fukutani,K.(Nakagome,Y.): "Detection of the testis determining factor in as XX man" The Journal of Urology. 149. 126-128 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Toda,T.(Nakamura,Y): "Localization of a gene responsible for Fukuyama type congenital muscular dystrophy (FCMD)to chromosome 9q31-33 by linkage analysis" Nature Genetics. 5. 283-286 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jinno,Y.(Niikawa,N.): "Imprinting polymorphism of the human WT1 gene" Nature Genet.,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Sekiya,T.(Hayashi,K.): "Detection of DNA aberrations in human cancers by single-strand conformation polymorphism analysis of the polymerase chain reaction" Int.J.Pancreatology. 13. 69 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshikawa,H.(Fujiyama,A.): "Two-dementional gel electrophoretograms of human chromosome specific DNA fragments" Biochem.Biophys.Res.Commun.196. 1566-1572 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masumoto,H.: "Properties of CENP-B and its target sequence in satellite DNA" NAT ASI Series : Chromosome Segregataion and Aneuploidy. 72. 31-43 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Haire,R.(Matsuda,F.): "Diversification,not utilization,of the immunoglobulin V_H gene repertoire is restricted in DiGeorge syndrome" J.Exp.Med.178. 825-834 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nagkura,J.(Miki,T): "Close linkage of the gene for Werner's syndrome to ANKI and D8S87 on the short arm of chromosome 8" Gerontol. 39. 11-15 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sasaki,Y.(Ayusawa,D.,Oishi,M.): "Construction of normalized cDNA library by introduction of a semi-solid mRNA-cDNA hybridization system" Nucl.Acid.Res.,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsubara,K.and Okubo,K.: "Identification of new genes by systematic analysis of cDNA and data base construction approach" Current Opinion in Biotechnology. 4. 672-677 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sekine,S.(Kato,S.): "Synthesis of full-length cDNA using DNA-capped mRNA" Nucl.Acids.Res.Symp.Ser. 29. 143-144 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tabara,H.(Kohara,Y.): "In situ hybridization on embryos -- Analysis of candidate clones for differentially expressed genes" The Worm Breeder's Gazette. 13. 22 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Maruyama,K.and Sugano,S.: "Oligo-capping: a simple method to replace the cap structure of eukaryotic on RNA with oligoribonucleotide" Gene,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Seo,Y.(Nakayama,T.): "Immunoaffinity purification and characterization of a liver-specific antigen" Jpn.J.Legal Med.47. 1-5 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nomura,N.: "Prediction of the coding sequences of unidentified human genes" DNA Research,in press. 1. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Inazawa,J.(Abe,T.): "High-resolution ordering of DNA markers by multi color fluorescent in situ hybridization of prophase chromosomes" Cytogenet.Cell Genet. 65. 130-135 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugaya,K.(Ikemura,T.): Three genes(receptor gene for AGE,homeobox-containing gene PBX,and int-3 related Notch-family gene)found in the HLA class III region near the border to the class II on 6p21.3. Cytogenet.Cell Genet,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] 河野 享子 (今本 文男): "YACクローンの安定化" 蛋白質核酸酵素「ゲノム解析研究」. 38. 607-612 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yokota,H.(Oishi,M.): "A differential cloning procedure of complex genomic DNA fragment" Analytical Biochem,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogasawara,N.: "Systematic sequencing of the Bacillus subtilis chromosome containing the replication origin" DNA research. 1. 1-14 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Okumura,K.: "Detection by fluorescence in situ hybridization of the erythropoietin gene introduced into animal cells" Animal Cell Technology : Basic & Applied Aspects. 5. 107-113 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 陶山 明: "オリゴヌクレオチドを用いたシーケンシング法" 蛋白質核酸酵素. 38. 647-657 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahashi,E.: "A high-resolution cytogenetic map of human chromosome 12 : localization of 195 new cosmid markers by direct R-banding fluorescence in situ" Hum.Genet.92. 405-409 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masubuchi,Y.(Doi,M.): "Periodic behavior of DNA molecules during steady field gel electrophoresis" Macromolecules. 26. 5269-5270 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mizukami,T.(Niwa,O.): "A 13kb resolution cosmid map of the 14Mb fission yeast genome by nonrandom sequence-tagged site mapping" Cell. 73. 121-132 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Baba,Y.: "Separation of DNA fragments by high-performance liquid chromatograpy and capillary electrophoresis" J.Liq.Chromatogr.16. 955-965 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayashizaki,Y.: "Restriction Landmark Genomic Scanning and its various application,"Changing Direction in DNA"" Electrophoresis. 14. 251 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirai,M.: "A method gor simultaneous detection of flourescent G-bands and in situ hybridization signals" Cytogenet.Cell Genetics,in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] 加藤 尚子 (藤澤 久雄): "T3ファージを用いた巨大DNAのクローニングと構造解析" 蛋白質核酸酵素「ゲノム解析研究」. 38. 618-625 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kagiyama,N.(Yoshida,M.C): "A novel fluorescent method for in situ hybridization" Acta Histochem.Cytochem.26. 441-445 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1995-03-23   Modified: 2018-06-07  

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