De novo Copy Number Variations in the Offspring of Male Mice Chronically Exposed to Various Low Dose-Rates of Ionizing Radiation

Previously, we conducted a large-scale pathology study on the transgenerational effects of ionizing radiation, examining the lifespan and causes of death in the first- (F1) and second- (F2) generation offspring of male C57BL/6J mice (F0) exposed to low dose-rates of 20, 1, and 0.05 mGy/day for 400 days, to total accumulated doses of 8,000, 400, and 20 mGy, respectively. Studies on de novo copy number variations (CNVs) using chromosomal microarray analysis in a subset of the F1 mice showed an increase in the frequency of the F1 mice with de novo CNVs born from the 20 mGy/day irradiated males compared to the non-irradiated controls. The present study illustrates the difficulty of detecting increases of de novo CNVs in F1 mice born from the males exposed to lower dose-rates of 1 and 0.05 mGy/day. These genetic analyses, combined with the pathology analyses in a larger number of mice, provide insights regarding the importance of population size and statistical power in studies on the transgenerational effects of low-dose-rate radiation.