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

Author

Listed:
  • Adeolu B. Adewoye

    (University of Leicester)

  • Sarah J. Lindsay

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

  • Yuri E. Dubrova

    (University of Leicester)

  • Matthew E. Hurles

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus)

Abstract

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.

Suggested Citation

  • Adeolu B. Adewoye & Sarah J. Lindsay & Yuri E. Dubrova & Matthew E. Hurles, 2015. "The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline," Nature Communications, Nature, vol. 6(1), pages 1-8, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7684
    DOI: 10.1038/ncomms7684
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    Cited by:

    1. Kitty Sherwood & Joseph C. Ward & Ignacio Soriano & Lynn Martin & Archie Campbell & Raheleh Rahbari & Ioannis Kafetzopoulos & Duncan Sproul & Andrew Green & Julian R. Sampson & Alan Donaldson & Kai-Re, 2023. "Germline de novo mutations in families with Mendelian cancer syndromes caused by defects in DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Tommy Rodriguez, 2021. "A Possible Glimpse at the Role of Naturally-Occurring Radiation as a Contributing Factor to Genetic Variance among Populations of Living Organisms," International Journal of Biology, Canadian Center of Science and Education, vol. 11(1), pages 1-42, December.
    3. Christopher N. Takahashi & David P. Ward & Carlo Cazzaniga & Christopher Frost & Paolo Rech & Kumkum Ganguly & Sean Blanchard & Steve Wender & Bichlien H. Nguyen & Jake A. Smith, 2024. "Evaluating the risk of data loss due to particle radiation damage in a DNA data storage system," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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