Analysis of de novo germline mutations by using environmental genome stress-sensitive mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 26281022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyushu University
• Principal Investigator: Ohno Mizuki 九州大学, 医学(系)研究科(研究院), 助教 (70380524)
• Co-Investigator(Kenkyū-buntansha): 續 輝久 九州大学, 医学(系)研究科(研究院), 教授 (40155429)
• Co-Investigator(Renkei-kenkyūsha): SAKUMI KUNIHIKO 九州大学, 生体防御研究所, 准教授 (50211933)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 生殖細胞変異 / ミスマッチ修復

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.

Free Research Field

分子細胞遺伝学