Deviation from mendelian transmission of autosomal SNPs can be used to estimate germline mutations in humans exposed to ionizing radiation

Abstract

We aimed to estimate the rate of germline mutations in the offspring of individuals accidentally exposed to Cesium-137 ionizing radiation. Performed analysis considered two distinct groups: a group males and females accidentally exposed to low doses of ionizing radiation from Cs137, the case group, and a control group of non-exposed participants. The case group included 37 participants (11 couples and 15 children born after the accident). The dose absorbed by exposed participants ranged from 0.2 to 0.5 Gray. The control group included 15 families from the state of Goias, with no history of radiation exposure. DNA samples from peripheral blood were analyzed with the Affymetrix GeneChip(R) CytoScanHD to assess de novo SNP-type mutations. A set of scripts previously developed was used to detect de novo mutations by comparing parent and offspring genotypes in each SNP marker. Overall numbers of observed Mendelian deviations were statistically significant between the exposed and control groups. Offspring from the population accidentally exposed to low IR doses showed [~] 46.5% more de novo Mendelian deviations than the control group. Parent-of-origin and type of nucleotide substitution were also inferred. Estimates of age-adjusted de novo germline mutation rates were obtained and correlated to Cs-137 radiation dose exposure to evaluate the usefulness of the rate of Mendelian deviations observed in polymorphic SNPs as a biomarker for exposure. This proved useful in a retrospective estimation of the rate of de novo germline mutations in a human population accidentally exposed to low doses of radiation from Cs-137. Obtained results suggest that observed burden of germline mutations identified in offspring could potentially be a useful biomarker to estimate levels of parental exposure to ionizing radiation.