| Project/Area Number |
07458253
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | National Children's Medical Research Center |
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Principal Investigator |
YAMADA Masao Director, Department of Genetics, National Children's Medical Research Center, 小児医療研究センター・先天異常研究部, 部長 (40124218)
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| Co-Investigator(Kenkyū-buntansha) |
TADOKORO Keiko Staff, Department of Genetics , National Children's Medical Research Center, 先天異常研究部, 研究員 (00236564)
OKUYAMA Torayuki Head of Teratology laboratory, National Children's Medical Research Center, 先天異常研究部・奇形研究室, 室長 (40177192)
MIYASHITA Toshiyuki Head of Genetics laboratory, National Children's Medical Research Center, 先天異常研究部・遺伝染色体研究室, 室長 (60174182)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Triplet repeat / repetitive sequence / genetic disease / neurodegenerative disorder / DNA synthesis / DNA repair / dentatorubral-pallidoluysian atrophy / DRPLA / 歯状核赤核淡蒼球ルイ体萎縮症 |
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| Research Abstract |
The remarkable expansion of short stretches of trinucleotide repeats associated with serious neurodegenerative disorders, including Huntington's disease (HD), has emerged as one of the most fascinating phenomena in human genetics. Dentatorubral-pallidoluysian atrophy (DRPLA), almost unheard of in Western countries but a little more common in Japan, has been identified by our group as the seventh member of diseases caused by triplet repeat expansion. To define the molecular basis for the geographic variation in prevalence, we have analyzed haplotypes around the DRPLA repeats in several different ethnic groups. Two intragenic biallelic polymorphisms distinguished three haplotypes, each of which formed a predominant haplotype found in the three major racial populations. All the expanded repeats of Japanese and Caucasian DRPLA patients studied shared a particular haplotype, which otherwise was associated with longer repeats commonly found in Asians. These results support a multi-step model for repeat expansion and suggest that expanded DRPLA repeats may have evolved from an ancient chromosomal haplotype of Asian origin. Chromosomes of the HRS patients, however, were associated with a different haplotype from those in Japanese and Caucasian DRPLA patients. This indicates that a second predisposing haplotype is present in the African population. We also conducted studies for reveal molecular mechanism of neuron death by CAG repeat expansion.
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