Small de novo CNVs as biomarkers of parental exposure to low doses of ionizing radiation of caesium-137

Abstract

The radiological accident in Goiania in 1987 caused a trail of human contamination, animal, plant and environmental by a radionuclide. Exposure to ionizing radiation results in different types of DNA lesions. The mutagenic effects of ionizing radiation on the germline are special concern because they can endures for several generations, leading to an increase in the rate of mutations in children of irradiated parents. Thus, to evaluate the biological mechanisms of ionizing radiation in somatic and germline cells, with consequent determination of the rate mutations, is extremely important for the estimation of genetic risks. Recently it was established that Chromosomal Microarray Analysis is an important tool for detecting wide spectra of gains or losses in the human genome. Here we present the results of the effect of accidental exposure to low doses of ionizing radiation on the formation of CNVs in the progeny of a human population accidentally exposed to Caesium-137 during the radiological accident in Goiânia, Brazil.

Figure 1

Average of germline mutation rates in CNVs from the progeny of controls and cases who were accidentally exposed to low doses of ionizing radiation from Caesium-137 in Goiânia (Brazil). CNVloss: genomic loss; CNVgain: genomic gain.

Figure 2

Burden of CNVs as a function of parental exposure and origin of CNVs for cases and control groups in the study of the effect of low absorbed doses of IR on the rate of germline mutations. Letters indicate significant differences among parental exposure at a significance level of 5%.

Figure 3

Discriminant function analysis of predictors: number of paternal meiosis, mean parental age at conception, and number of marker in a CNV on the germline mutation rate of genomic losses and gains for cases and controls observed in the progeny of a population exposed to low doses of ionizing radiation and a control population from Goiânia (Brazil).

Figure 4

Distribution of CNV size, number of markers and number of genes in the CNVs for both control and exposed groups to low doses of ionizing radiation of Caesium-137.

Figure 5

Results of the Mann- Whitney U test of the burden of CNVs (A) and the total of CNVs per chromosome for genomic losses (B) and genomic gains (C) between case and control groups in the study of the induction of germline mutation due to parental exposure to ionizing radiation of Caesium-137.

Figure 6

Spearman’s correlation test applied to the number of paternal meiosis at the time of conception and the burden of CNV germline mutation in F1 of controls and cases, corresponding to children born to fathers accidentally exposed to low doses of ionizing radiation of Caesium-137 in Goiânia (Brazil).

Figure 7

Frequency distribution of different classes of CNV sizes (kb) between controls and exposed groups for both genomic losses and gains, in the study of the effect of ionizing radiation in the induction of germline mutations CNV.

Figure 8

The χ² post-hoc test showed no statistical differences in the frequency distribution of the classes of CNV according to the number of markers between cases and controls in the study of the effect of ionizing radiation in the induction of germline mutations CNV.