scholarly journals Field Study of the Possible Effect of Parental Irradiation on the Germline of Children Born to Cleanup Workers and Evacuees of the Chornobyl Nuclear Accident

2020 ◽  
Vol 189 (12) ◽  
pp. 1451-1460
Author(s):  
Dimitry Bazyka ◽  
Maureen Hatch ◽  
Natalia Gudzenko ◽  
Elizabeth K Cahoon ◽  
Vladimir Drozdovitch ◽  
...  

Abstract Although transgenerational effects of exposure to ionizing radiation have long been a concern, human research to date has been confined to studies of disease phenotypes in groups exposed to high doses and high dose rates, such as the Japanese atomic bomb survivors. Transgenerational effects of parental irradiation can be addressed using powerful new genomic technologies. In collaboration with the Ukrainian National Research Center for Radiation Medicine, the US National Cancer Institute, in 2014–2018, initiated a genomic alterations study among children born in selected regions of Ukraine to cleanup workers and/or evacuees exposed to low–dose-rate radiation after the 1986 Chornobyl (Chernobyl) nuclear accident. To investigate whether parental radiation exposure is associated with germline mutations and genomic alterations in the offspring, we are collecting biospecimens from father-mother-offspring constellations to study de novo mutations, minisatellite mutations, copy-number changes, structural variants, genomic insertions and deletions, methylation profiles, and telomere length. Genomic alterations are being examined in relation to parental gonadal dose, reconstructed using questionnaire and measurement data. Subjects are being recruited in exposure categories that will allow examination of parental origin, duration, and timing of exposure in relation to conception. Here we describe the study methodology and recruitment results and provide descriptive information on the first 150 families (mother-father-child(ren)) enrolled.

Science ◽  
2021 ◽  
pp. eabg2365
Author(s):  
Meredith Yeager ◽  
Mitchell J. Machiela ◽  
Prachi Kothiyal ◽  
Michael Dean ◽  
Clara Bodelon ◽  
...  

Effects of radiation exposure from the Chernobyl nuclear accident remain a topic of interest. We investigated whether children born to parents employed as cleanup workers or exposed to occupational and environmental ionizing radiation post-accident were born with more germline de novo mutations (DNMs). Whole-genome sequencing of 130 children (born 1987-2002) and their parents did not reveal an increase in the rates, distributions, or types of DNMs versus previous studies. We find no elevation in total DNMs regardless of cumulative preconception gonadal paternal (mean = 365 mGy, range = 0-4,080 mGy) or maternal (mean = 19 mGy, range = 0-550 mGy) exposure to ionizing radiation and conclude over this exposure range, evidence is lacking for a substantial effect on germline DNMs in humans, suggesting minimal impact on health of subsequent generations.


2019 ◽  
Author(s):  
J. O. Johnson ◽  
R. Chia ◽  
D. E. Miller ◽  
R. Li ◽  
Y. Abramzon ◽  
...  

AbstractJuvenile amyotrophic lateral sclerosis (ALS) is a rare form of childhood motor disorder with a heterogeneous clinical presentation. The underlying causes of this condition are poorly understood, hindering the development of effective therapies. In a whole-exome sequencing trio-family study of three unrelated juvenile patients diagnosed with ALS and failure to thrive, we identified de-novo mutations in SPTLC1 (p.Ala20Ser in two patients and p.Ser331Tyr) not present in their healthy parents or siblings. SPTLC1 encodes a subunit of the serine palmitoyltransferase complex, a key enzyme in sphingolipid biosynthesis. Mutations in this gene are known to cause hereditary sensory autonomic neuropathy, type 1A, with a characteristic increase in plasma levels of neurotoxic deoxymethyl-sphinganine. We found an increase of this metabolite in one of our patients carrying the p.Ala20Ser mutation. Treatment of one of the patients with high dose, oral L-serine led to an increase in body weight, suggesting that serine supplementation may be beneficial among patients carrying mutations in this gene.


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