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)
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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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