| Project/Area Number |
16H04821
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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 |
Evolutionary biology
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| Research Institution | The Graduate University for Advanced Studies |
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Principal Investigator |
SATTA Yoko 総合研究大学院大学, 先導科学研究科, 教授 (20222010)
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| Co-Investigator(Kenkyū-buntansha) |
早川 敏之 九州大学, 基幹教育院, 准教授 (80418681)
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| Research Collaborator |
Fujito T Naoko
Takahata Naoyuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | 統合失調症関連遺伝子群 / 脳機能 / 人類進化 / 正の自然選択 / 祖先型・派生型SNP / リスク型・非リスク型SNP / 環境適応 / 社会構造の変化 / 統合失調症 / リスク型と非リスク型 / 統合失調症関連遺伝子座 / DNA多型解析 / リスク型SNP / 祖先型及び派生型SNP / 出アフリカ / 自然選択 / 頻度分布 |
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| Outline of Final Research Achievements |
It is known that many disease-related SNPs (risk SNPs) in humans are ancestral, shared by non-human primates, implying that human-specific environmental or social changes would be a trigger of the onset of SNP-related diseases. To examine this hypothesis, we studied linkage disequilibrium (LD) surrounding target SNPs, a signal of positive selection on ancestral and derived SNPs and estimated the divergence time of a derived allele group. A recent large-scale association study has identified 128 schizophrenia-related SNPs. Of these, 66 derived SNPs in East Asia showed strong LD blocks. Our newly developed statistical test revealed significant signals of ongoing positive selection at 15 SNPs and the most recent common ancestor of a derived allele group at a half of the SNPs occurred no earlier than 50,000 years ago. This age of positively selected alleles at each target SNP coincides with the time of drastic changes in human brain activities that became evident in archaeological remains.
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| Academic Significance and Societal Importance of the Research Achievements |
現生人類は30万年ほど前にアフリカ大陸で誕生後、およそ5～8万年前に全世界へとその生息域を広げた。これに伴い、洞窟の壁画、遺跡から発掘される装飾品や石器などに見られるようにヒトは文化や技術の面で大きな発展を遂げた。この文化的・技術的な発展にはヒトの脳機能の亢進がともなっていることは想像に難くない。統合失調症は認知や思考の障害であり、その発症に関わる遺伝子は、そのようなヒトの脳機能の亢進に関わると考えられる。そこで本研究では、最近、大規模関連解析で同定された統合失調症に関連する128個のSNPを対象に、ヒトの脳機能の亢進に関与したと思われる遺伝子を検出し、その適応的役割を明らかにする。
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