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.
Highlights
Previous studies of atomic-bomb (A-bomb) survivors, notably the “Life Span Study” conducted by the Radiation Effects Research Foundation, have demonstrated many lateDepartment of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki, JapanDepartment of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki, JapanHealth Management Center, Nagasaki Atomic Bomb Casualty Council, Nagasaki, JapanDepartment of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan health effects of the resulting radiation in humans [1], including increased risks of leukemia and other cancers [2, 3]
The total numbers of de novo SNVs were 62 in FPMX01, 81 in FPMX03, 42 in FPMX06, and 48 in FCMC10. These results suggest that the incidence of de novo SNVs was not increased in the children of atomic-bomb survivors
We only analysed data for three affected trios, the numbers of de novo variants and gross structural changes were comparable between children of radiation-exposed and non-exposed fathers, in line with previously published data [11]
Summary
Previous studies of atomic-bomb (A-bomb) survivors, notably the “Life Span Study” conducted by the Radiation Effects Research Foundation, have demonstrated many lateHealth Management Center, Nagasaki Atomic Bomb Casualty Council, Nagasaki, Japan. Previous studies of atomic-bomb (A-bomb) survivors, notably the “Life Span Study” conducted by the Radiation Effects Research Foundation, have demonstrated many late. Kong et al used NGS to address the de novo variant rate in offspring, and pointed out the importance of the father’s age [11]. They demonstrated the use of detecting single nucleotide changes in the whole genome as an approach for investigating heritable gene variants. We used NGS to assess the heritable genetic effects in the children of atomicbomb survivors by examining de novo genomic changes
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