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The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline.

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posted on 23.01.2017, 14:00 by Adeolu B. Adewoye, S. J. Lindsay, Yuri E. Dubrova, M. E. Hurles
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.

Funding

We thank the Wellcome Trust for their support (WT091106 and WT098051).

History

Citation

Nature Communications, 2015, 6, pp. 6684-?

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Department of Genetics

Version

VoR (Version of Record)

Published in

Nature Communications

Publisher

Nature Publishing Group

eissn

2041-1723

Acceptance date

17/02/2015

Available date

23/01/2017

Publisher version

http://www.nature.com/articles/ncomms7684

Notes

Accession codes: The microarray data were deposited in the Gene Expression Omnibus (GEO), submission number GSE65521; the whole-genome sequences were deposited in the Sequence Read Archive under Study number ERP001221, with accession numbers ERX111346, ERX111347, ERX111348, ERX111349, ERX111350, ERX111351, ERX111352, ERX111353, ERX111354, ERX111355, ERX111356, ERX111357, ERX111358, ERX111359, ERX111360, ERX111361, ERX111362, ERX111363, ERX111364, ERX111365, ERX111366 and ERX111367. Supplementary Information accompanies this paper at http://www.nature.com/naturecommunications

Language

en