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The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline
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The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline
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Journal Article
The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline
2015
Overview
The ability to predict the genetic consequences of human exposure to ionizing radiation has been a long-standing goal of human genetics in the past 50 years. Here we present the results of an unbiased, comprehensive genome-wide survey of the range of germline mutations induced in laboratory mice after parental exposure to ionizing radiation and show irradiation markedly alters the frequency and spectrum of
de novo
mutations. Here we show that the frequency of
de novo
copy number variants (CNVs) and insertion/deletion events (indels) is significantly elevated in offspring of exposed fathers. We also show that the spectrum of induced
de novo
single-nucleotide variants (SNVs) is strikingly different; with clustered mutations being significantly over-represented in the offspring of irradiated males. Our study highlights the specific classes of radiation-induced DNA lesions that evade repair and result in germline mutation and paves the way for similarly comprehensive characterizations of other germline mutagens.
Ionizing radiation (IR) is an extensively studied mutagenic agent that can lead to the accumulation of extra mutations in the offspring of irradiated parents. Here the authors provide a comprehensive genome-wide survey of the consequences of IR on the mammalian germline.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 631/337
/ Animals
/ DNA Copy Number Variations - radiation effects
/ Female
/ Genetics
/ Germ Cells - radiation effects
/ Germ-Line Mutation - genetics
/ Germ-Line Mutation - radiation effects
/ Humanities and Social Sciences
/ Male
/ Mice
/ Mutagens
/ Mutation
/ Oligonucleotide Array Sequence Analysis
/ Science
