1989 Fiscal Year Final Research Report Summary
New Strategies for Elucidation of a Gene Defect in Huntington's Disease
Project/Area Number |
63440034
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Research Category |
Grant-in-Aid for General Scientific Research (A)
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Allocation Type | Single-year Grants |
Research Field |
Neurology
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Research Institution | University of Tsukuba |
Principal Investigator |
KANAZAWA Ichiro Univ. of Tsukuba, Inst. of Clin. Med., Associate Prof., 臨床医学系, 助教授 (30110498)
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Co-Investigator(Kenkyū-buntansha) |
MASAKI Tomoo Univ. of Tsukuba, Inst. of Basic Med., Prof., 基礎医学系, 教授 (60009991)
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Project Period (FY) |
1988 – 1989
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Keywords | Huntington's disease / 4th chromosome / linkage analysis / DNA probes / D4S10 / D4S43 / striatal mRNA |
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.
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Research Products
(11 results)
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[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
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[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
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[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