| Project/Area Number |
26281022
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kyushu University |
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Principal Investigator |
Ohno Mizuki 九州大学, 医学(系)研究科(研究院), 助教 (70380524)
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| Co-Investigator(Kenkyū-buntansha) |
續 輝久 九州大学, 医学(系)研究科(研究院), 教授 (40155429)
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| Co-Investigator(Renkei-kenkyūsha) |
SAKUMI KUNIHIKO 九州大学, 生体防御研究所, 准教授 (50211933)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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| Keywords | 生殖細胞変異 / ミスマッチ修復 / 次世代影響 / DNA修復 / 環境ストレス / ゲノム変異 / 生殖細胞 / 生物影響 / DNA損傷 |
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| Outline of Final Research Achievements |
To clarify underlining mechanisms for spontaneous germline mutations, we attempted to analyze de novo germline mutations by whole exome sequencing using parents-offspring sample sets derived from mismatch repair (MMR)-deficient mice. We observed an increased mutation rate in MMR-deficient mice. DNM rate per generation was approximately 20-fold higher for base substitutions, and at least several hundred-fold higher rate for INDELs, compared with that of wild-type mice. Most of INDELs were found at dinucleotide-repeat sequences, namely minisatellite or microsatellite. The mutation pattern of DNMs detected in these mice is consistent with the pattern of somatic mutation of MMR-deficient human tumor, indicating that MMR plays a crucial role in the maintenance of germline genome integrity. Our experimental system for the detection of DNMs by using MMR-deficient mice family can be used for the assessment of the genetic effects of environmental mutagens.
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