Article

Detection of de novo single nucleotide variants in offspring of atomic-bomb survivors close to the hypocenter by whole-genome sequencing

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Abstract

Ionizing radiation released by the atomic bombs at Hiroshima and Nagasaki, Japan, in 1945 caused many long-term illnesses, including increased risks of malignancies such as leukemia and solid tumours. Radiation has demonstrated genetic effects in animal models, leading to concerns over the potential hereditary effects of atomic bomb-related radiation. However, no direct analyses of whole DNA have yet been reported. We therefore investigated de novo variants in offspring of atomic-bomb survivors by whole-genome sequencing (WGS). We collected peripheral blood from three trios, each comprising a father (atomic-bomb survivor with acute radiation symptoms), a non-exposed mother, and their child, none of whom had any past history of haematological disorders. One trio of non-exposed individuals was included as a control. DNA was extracted and the numbers of de novo single nucleotide variants in the children were counted by WGS with sequencing confirmation. Gross structural variants were also analysed. Written informed consent was obtained from all participants prior to the study. There were 62, 81, and 42 de novo single nucleotide variants in the children of atomic-bomb survivors, compared with 48 in the control trio. There were no gross structural variants in any trio. These findings are in accord with previously published results that also showed no significant genetic effects of atomic-bomb radiation on second-generation survivors.

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Acknowledgements

This work was partly supported by the Program of the Network-type Joint Usage/Research Centre for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University and Fukushima Medical University, and Takeda Science Foundation.

Author contributions

MH, YN, TM, and TH approached subjects, and collected data and samples. CH, AK, and K-iY performed sample preparation. MH, SS, DI, YI, KT, KY, and YM analysed the laboratory data. HM, AK, and K-iY analysed the genome data. YM and K-iY planned and organised the project. YM and K-iY wrote the manuscript.

Author information

Affiliations

  1. Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki, Japan

    • Makiko Horai
    • , Shinya Sato
    • , Daisuke Imanishi
    • , Yoshitaka Imaizumi
    • , Tomoko Hata
    •  & Yasushi Miyazaki
  2. Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki, Japan

    • Hiroyuki Mishima
    • , Chisa Hayashida
    • , Akira Kinoshita
    •  & Koh-ichiro Yoshiura
  3. Health Management Center, Nagasaki Atomic Bomb Casualty Council, Nagasaki, Japan

    • Yoshibumi Nakane
    •  & Tatsuki Matsuo
  4. Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    • Kazuto Tsuruda
    •  & Katsunori Yanagihara

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Conflict of interest

The authors declare that they have no competing interests.

Corresponding authors

Correspondence to Yasushi Miyazaki or Koh-ichiro Yoshiura.