| Project/Area Number |
12204009
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyushu University |
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Principal Investigator |
FUKUMAKI Yasuyuki Kyushu Universty, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (90128083)
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| Co-Investigator(Kenkyū-buntansha) |
KUSUHARA Koichi Kyushu University, Graduate School of Medical Sciences, Associate Prof., 医学研究院, 助教授 (20243941)
田代 信維 九州大学, 医学研究院, 教授 (80037407)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥71,300,000 (Direct Cost: ¥71,300,000)
Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥18,400,000 (Direct Cost: ¥18,400,000)
Fiscal Year 2002: ¥18,400,000 (Direct Cost: ¥18,400,000)
Fiscal Year 2001: ¥19,500,000 (Direct Cost: ¥19,500,000)
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| Keywords | schizophrenia / affected sib-pair analysis / association study / polymorphism / qlutamate receptor / tuberculosis / host qenetic factor / susceptibility / 連鎖不平衡 / インターフェロン受容体 / DNAマイクロアレイ / 精神分裂病 / 連鎖不平衡解析 / メタンフェタミン / 相関解析 / 逆耐性現象 |
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| Research Abstract |
1. Study on schizophrenia susceptibility
The first genome-wide scan using 417 STR markers in 130 families with affected sib-pairs revealed that ten chromosomes (1, 2, 3, 4, 5, 8, 9, 14, 17, and 20) had at least one region with a nominal p value < 0.05. The second genome-wide scan using 5,861 SNPs in 236 Japanese families including 122 ones used in the first scan revealed that significant evidence of linkage of schizophrenia to 1p21.1-1p13.1 and suggestive evidence of linkage to 14q11.2, 4q11.2-q13.2 and 20p12.1-p11.2.
Based on the glutamatergic dysfunction hypothesis for the pathogenesis of schizophrenia, we conducted a systematic study of associations between glutamate receptor genes and schizophrenia. We selected SNPs evenly distributed across the relevant gene region for typing and did single marker and haplotype association studies. We found significant associations of halotypes of GRIN2D, GRIA4, GRM3 and GRM8 with schizophrenia. Genome- wide association study using 27,000 STR markers is on the way. The second set of screening showed significant associations of 720 markers with schizophrenia. The third and fourth sets of screening followed by dense SNP typing will elucidate the susceptibility loci for schizophrenia.
2. Study on tuberculosis susceptibility
We performed a gene-based association analysis of 21 candidate genes on 87 TB patients and 265 controls using 118 marker single nucleotide polymorphisms (SNPs). Subsequently, we analyzed the association between TB and coding SNPs (cSNPs) adjacent to positive marker SNPs. Three cSNPs of 1L.12RB1 were significantly associated with the development of TB, suggesting that 1L_12RB1 confers genetic susceptibility to TB in Japanese. We also collected blood samples from 56 patients who showed susceptibility to mycobacterial infection, and identified partial dominant IFN-y receptor 1 deficiency in 3 unrelated patients with BCG osteomyelitis and in one of their fathers. This is the first report of this disorder in Japanese.
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