Chemical Exposure Generates DNA Copy Number Variants and Impacts Gene Expression

Abstract

DNA copy number variation is long associated with highly penetrant genomic disorders, but it was not until recently that the widespread occurrence of copy number variation among phenotypically normal individuals was realized as a considerable source of genetic variation. It is also now appreciated that copy number variants (CNVs) play a role in the onset of complex diseases. Many of the complex diseases in which CNVs are associated are reported to be influenced by yet to be identified environmental factors. It is hypothesized that exposure to environmental chemicals generates CNVs and influences disease onset and pathogenesis. In this study a proof of principle experiment was completed with ethyl methanesulfonate (EMS) and cytosine arabinoside (Ara-C) to investigate the generation of CNVs using array comparative genomic hybridization (CGH) and the zebrafish vertebrate model system. Exposure to both chemicals resulted in CNVs. CNVs were detected in similar genomic regions among multiple exposure concentrations with EMS and five CNVs were common among both chemicals. Furthermore, CNVs were correlated to altered gene expression. This study suggests that chemical exposure generates CNVs with impacts on gene expression warranting further investigation of this phenomenon with environmental chemicals.