| Co-Investigator(Kenkyū-buntansha) |
OHNO Shigeaki Hokkaido University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (50002382)
NISHIDA Tomomi Yokohama City University, School of Medicine, Assistant, 医学部, 助手 (90336561)
ITHO Norihiko Yokohama City University, School of Medicine, Assistant, 医学部, 助手 (80264654)
SAKAKI Yoshiyuki Tokyo University, School of Medicine, Professor, 医学研究科・理化学研究所, 教授 (10112327)
INOKO Hidetoshi Tokai University, School of Medicine, Professor, 医学部, 教授 (10101932)
矢吹 和朗 横浜市立大学, 医学部附属市民総合医療センター, 助手 (30347348)
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| Budget Amount *help |
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2002: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Research Abstract |
The completion of the human genome project has led to worldwide interest in screening for genomic polymorphisms associated with disease susceptibility. For this to be accomplished, it is necessary to adopt efficient methods that probe the entire genome systematically, rapidly and accurately by polymorphic markers to identify specific genes with disease associated polymorphisms. Microsatellite (MS) is a repeated sequence consisting of generally two to six nucleotides (repeated unit), scattering throughout the human genome. MS characterized by a high degree of genetic polymorphisms in its number of repeated unit is expected to be an excellent marker in association analysis for evaluating disease susceptibility. The average number of alleles in MS is 10 (much more than that of SNP) and the average length of linkage disequilibrium of MS is 100kb (much longer than that of SNP). The best way to map the disease susceptibility gene, therefore, is first to narrow down candidate disease gene reg
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ions to 100 kb by genome-wide association mapping with MS, and then next to identify disease gene from these 100 kb candidate regions by conventional SNP analysis. We have collected and localized more than 30,000 MS markers in the human genome at 100 kb intervals and started pan genomic (genomewide) MS screening for identification of pathogenic genes of several diseases including hypertension, diabetes mellitus, open angle glaucoma (OAG), steroid glaucoma (steroid susceptibility gene), Behcet's diabetes mellitus, open angle glaucoma (OAG), steroid glaucoma (steroid susceptibility gene), Behcet's disease, high myopia, retinal lattice degeneration, age related macular degeneration (AMD), keratoconus, cataract, and sarcoidosis. Accordingly, we have so far found fifty to a hundred foci that may have hypertension susceptible genes. SNP analyses are under way to finally reach single disease genes. We are continuing MS screening, mapping and identification for the other diseases, demonstrating that our MS based strategy is quite efficient for genomewide mapping of diseases, especially complex or common diseases with multi-factorial basis. Less
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