Analysis of de novo germline mutations by using environmental genome stress-sensitive mice
| 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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Report
(4 results)
Research Products
(20 results)
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[Journal Article] PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus Accumbens.2015
Author(s)
Ohnishi YH, Ohnishi YN, Nakamura T, Ohno M, Kennedy PJ, Yasuyuki O, Nishi A, Neve R, Tsuzuki T, Nestler EJ.
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Journal Title
PLoS One
Volume: 10(5)
Issue: 5
Pages: e0126710-e0126710
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Role of the oxidative DNA damage repair system in somatic and germline mutations in mice2015
Author(s)
Mizuki Ohno, Noriko Takano, Kunihiko Sakumi, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Yusaku Nakabeppu,Yoshimichi Nakatsu, Teruhisa Tsuzuki
Organizer
Zing conference Genomic integlity
Place of Presentation
Cairns, Australia
Year and Date
2015-08-01 – 2015-08-05
Related Report
Invited
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[Presentation] Role of the oxidative DNA damage repair system in somatic and germline mutations in mice2015
Author(s)
Mizuki Ohno, Noriko Takano, Kunihiko Sakumi, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Yusaku Nakabeppu, Yoshimichi Nakatsu, Teruhisa Tsuzuki
Organizer
Zing conference "Genome Integrity"
Place of Presentation
Cairns, Australia
Year and Date
2015-07-31
Related Report
Int'l Joint Research / Invited
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[Presentation] Influence of oxidative DNA damage on the rate of somatic and germline mutation2015
Author(s)
Mizuki Ohno, Noriko Takano, Kunihiko Sakumi, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Yusaku Nakabeppu,Yoshimichi Nakatsu, Teruhisa Tsuzuki
Organizer
15th International Congress of Radiation Research
Place of Presentation
Kyoto, Japan
Year and Date
2015-05-25 – 2015-05-29
Related Report
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