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New Strategies for Elucidation of a Gene Defect in Huntington's Disease

Research Project

Project/Area Number 63440034
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionUniversity of Tsukuba

Principal Investigator

KANAZAWA Ichiro  Univ. of Tsukuba, Inst. of Clin. Med., Associate Prof., 臨床医学系, 助教授 (30110498)

Co-Investigator(Kenkyū-buntansha) MASAKI Tomoo  Univ. of Tsukuba, Inst. of Basic Med., Prof., 基礎医学系, 教授 (60009991)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 1989: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1988: ¥10,000,000 (Direct Cost: ¥10,000,000)
KeywordsHuntington's disease / 4th chromosome / linkage analysis / DNA probes / D4S10 / D4S43 / striatal mRNA / DNAマーカー / S4S43
Research Abstract

Huntington's disease is a dominantly inherited neurodegenerative disorder, characterized by choreic involuntary movements, dementia and psychiatric problems. The approximate gene locus of Huntington's disease is now assigned to the very terminal portion of the 4th chromosome through a linkage analysis performed mainly by Gusella et al. in U.S.A., providing new DNA probes in 4pl6 region. By collaborative studies with Gusella, we have found Japanese Huntington's disease to be genetically identical with that in western countries. The actual genetic defectin Huntington's disease, however, is not yet elucidated, in spite of the extensive efforts of Gusella and his group. Therefore, we planned to approach to this problem with the following strategies; 1) dissect the 4pl6 region using a "chromosome dissector with a laser knife", which was newly developed by Ikeda, providing a powerful source for new DNA probes. 2) prepare cDNA library from mRNA in the normal human striatal tissue. 3) select cDNA which hybridizes with one or more of the new probes., This may be a hopeful candidate of gene products related to the pathogenesis of Huntington's disease. We have succeeded in recovering the dissected fragment of the 4th chromosome. In addition, we have found the unexpectedly stable character of mRNA especially in rat brain. Based on these findings, we have successfully prepared the fresh mRNA from the neurologically normal human striatum. Therefore, we are hoping to combine these two procedures in near future.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] 金澤一郎: "精神神経疾患の遺伝学の最近の進歩-Huntington舞踏病-" 神経精神薬理. 10. 345-350 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 金澤一郎: "脳の変性疾患-その分子生物学的アプロ-チ-ハンチントン病" 日本医師会雑誌. 99. 2045-2050 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ichiro KANAZAWA: "Huntington's disease.A molecular biology approach" Asian Medical Journal. 32. 18-24 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Conneally,P.M.: "Huntington's disease:No evidence for locus heterogeneity" Genomics. 5. 304-308 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ikuko KONDO: "Exclusion mapping of the hereditary dentatorubropallidoluysian atrophy gene from Huntington's disease gene" Journal of Medical Genetics. inpress (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ichiro KANAZAWA: "Studies on DNA markers(D4S10 and D4S43/S127)genetically linked to Huntington's disease in Japanese families" Human Genetics. inpress (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 金澤一郎: "Huntinglon病。神経疾患の診かた-難しい症例をめぐる診断過程の着眼点-" 亀山政邦,荒木淑郎編、医学書院, 167-176 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kanazawa,I.: "Huntington's disease. A molecular biology approach." Asian Medical Journal. 32. 18-24 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] "Conneally,P.M., Haines,J.L., Tanzi,R.E., Wexler,N.S., Penchaszadeh,G.K., Harper,P.S., Folstein,S.E., Cassiman,J.J., Myers,R.H., Young,A.B., Hayden,M.R., Falek,A., Tolosa,E.S., Crespi,S., Dimaio,L., Holmgre,G., Anvret,M., Kanazawa,I. and Gusella,J.F." Genomics, 5 : 304-308, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kondo,I., Ohta,M., Yazaki,M., Ikeda,J.E., Gusella,J.F., and Kanazawa,I.: "Exclusion mapping of the hereditary dentatorubropallidoluysian atrophy gene from Huntington's disease gene" Journal of Medical Genetics.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kanazawa,I., Kondo,I., Ikeda,J.E., Ikeda,T., Shizu,Y., Yoshida,M., Narabayashi,H., Kuroda,S., Shinoda,H., Mizuta,E., Okuno,Y., Sugawara,K., Murata,M., Takahashi,M. and Gusella,J.F.: "Studies on DNA markers (D4S10 and D4S43/S127) genetically linked to Huntington's disease in Japanese families." Human Genetics.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ichiro KANAZAWA: "Huntington′s disease.A molecular biology approach" Asian Medical Journal. 32. 18-24 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 金澤一郎,近藤郁子: "ヒト細胞の芽化と保存ー遺伝性神経疾患の遺伝子の保存とその利用" 細胞工学. 8. s76-s80 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 金澤一郎: "ハンチントン病の分子遺伝学" 神経研究の進歩. 33. 583-587 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Conneally,P.M.: "Huntington′s disease:No evidence for locus heterogeneity" Genomics. 5. 304-308 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ikuko KONDO: "Exclusion mapping of the hereditary dentatorubropallidoluysian atrophy gene from Huntington′s disease gene" Journal of Medical Genetics. (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ichiro KANAZAWA: "Studies on DNA markers(D4S10 and D4S43/S127)genetically linked to Huntington′s,disease in Japanese families" Human Genetics. (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kanazawa,I.;Kwak,S.;Sasaki,H.;Muramoto,O.;Mizutani,T.;Hori,A.;Nukina,N.: Journal of Neurological Sciences. 83. 63-74 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 吉澤利弘,金澤一郎: 代謝. 25. 145-154 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 金澤一郎: 生体の科学. 39. 63-66 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 近藤郁子,金澤一郎: 蛋白質核酸酵素. 33. 1023-1025 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 金澤一郎: 神経精神薬理. 10. 345-350 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kanazawa,I.: Asian Medical Journal. 32. 18-24 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 金澤一郎: "「神経病学」第3版Lecture29 遺伝性疾患 臨床神経遺伝学" 田崎義昭,吉田充男(医学書院), 410-426 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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