Increased Frequency of Copy Number Variations Revealed by Array Comparative Genomic Hybridization in the Offspring of Male Mice Exposed to Low Dose-Rate Ionizing Radiation.

Keiji Ogura,Yoshiko Ayabe,Ignacia Braga Tanaka,Satoshi Tanaka,Jun-Ichiro Komura,Chihiro Harada

doi:10.3390/ijms222212437

Abstract

There is very little information on the transgenerational or genetic effects of low dose-rate ionizing radiation. We report the detection of the transgenerational effects of chronic low dose-rate irradiation in mice, at the molecular level in the whole genome, using array comparative genomic hybridization technology. We observed that the number of the mice with de novo copy number variations (specifically, deletions) was significantly increased in the offspring of C57BL/6J male mice exposed to 20 mGy/day gamma-rays for 400 days (total dose: 8000 mGy), as compared to non-irradiated controls. We did not detect any difference in the size of the de novo deletions between the irradiated and the non-irradiated groups. An analysis of the life span of the offspring suggested a possibility that de novo copy-number variations may be associated with shorter life spans.

Highlights

To identify the positive probes that differed between parents and offspring, we performed family analysis, after which the locations of de novo copy-number variations (CNVs) candidates in the genome were identified by using the Agilent Genomic Workbench software
Smaller de novo CNV candidates were identified by visual inspection of the array plots
Final confirmations of the de novo CNVs were performed by using quantitative PCR

Summary

Introduction

The transgenerational or genetic effects of ionizing radiation exposure have been a serious concern since the first scientific study, using Drosophila as the test system, was reported in 1927 [1]. It became more concerning after a large number of people were exposed to radiation from the atomic bombs in 1945. Induction of germline mutations in human populations exposed to radiation has not been clearly demonstrated [2–4]. Data on radiation-induced mutation rates in mice are derived from only a small number of studies, including those performed at Oak Ridge [7] and at Harwell [8]

Methods

Results

Conclusion