2021 Fiscal Year Final Research Report
Development of comprehensive identification of spontaneous mutations based on whole genome sequencing applicable for the assessment of low-dose mutagens.
| Project/Area Number |
17H00789
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental impact assessment
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| Research Institution | Tokai University |
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Principal Investigator |
Gondo Yoichi 東海大学, 医学部, 客員教授 (40225678)
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| Co-Investigator(Kenkyū-buntansha) |
木村 穣 東海大学, 総合医学研究所, 特任教授 (10146706)
福村 龍太郎 国立研究開発法人理化学研究所, バイオリソースセンター, 開発研究員 (90392240)
牧野 茂 国立研究開発法人理化学研究所, バイオリソースセンター, 開発研究員 (30462732)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Keywords | 遺伝学 / 環境変異原 / ミュータジェネシス / ゲノム機能解析 / 実験分子進化学 / 全ゲノム解読 / 生物多様性 |
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| Outline of Final Research Achievements |
A hypersensitive mutation detection system was established from the mouse genome by original complete outbreeding mating and whole genome sequencing. To further develop into a system that can be easily analyzed in parallel for multiple groups, brother-sister mating method and the expanded trio method were compared. At the same time, the effects of the next generation on different genetic backgrounds and long-term exposure to low-dose gamma rays were also tested. As a result, it was found that the natural mutation rate was reduced by 20% in inbred strains derived from Japanese wild mice, which have low carcinogenicity. In addition, low doses of 6 micro-Gy/hour have no effect on fertility even after exposure for 2 years or more, and multiple groups can be easily continuously exposed to long-term constant mating without homozygosity of newly induced mutations. An expanded outbreeding mating method was finally established for basic as well as applied life sciences.
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| Free Research Field |
遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
残留放射線防護や放射線廃棄物の処理に留まらず、宇宙空間における活動がこれから進むなか、ごく低線量放射線長期被ばくの影響をはじめて科学的に明らかにする解析系確立の意義は大きい。また、１匹のマウスから10個を超える新たな変異を全ゲノムから検出でき、さらには発生初期の体細胞変異まで捉えることで、これまで不可能であった順向き実験分子進化学を実現した。変異は、進化と生物多様性の唯一の駆動源でありながら、一方で、変異は有害という前提で遺伝子疾患や環境変異原リスク評価指標に利用される20世紀以来のパラドックス解明にも貢献する。遺伝学、進化学から、医学、環境影響学まで波及効果の高い解析系を開発確立した。
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