%0 Journal Article
%T Chemical Exposure Generates DNA Copy Number Variants and Impacts Gene Expression
%A Samuel M. Peterson
%A Jennifer L. Freeman
%J Advances in Toxicology
%D 2014
%R 10.1155/2014/984319
%X 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. 1. Introduction Structural genetic variation in the human genome is present in many forms including single nucleotide polymorphisms (SNPs), variable tandem repeats (e.g., mini- and microsatellites), presence/absence of transposable elements, and structural alterations (e.g., deletions, duplications, and inversions). Until recently, SNPs were thought to be the predominant form of genomic variation and to account for much of the normal phenotypic variation [1]. Recent developments and applications of genome-wide technologies led to the discovery of thousands of copy number variants (CNVs) in the genomes of phenotypically normal humans [2, 3]. CNVs are defined as a duplication or deletion (i.e., a gain or loss of a genomic DNA segment relative to a reference sample) measuring greater than 1£¿kb in size [4]. Human genomic copy number variation has been studied for over 40 years, but it was assumed that CNVs were few in number, had a relatively limited impact on the total amount of human genetic variation, and were mainly associated with highly penetrant disease phenotypes. In 2004, two studies independently reported the widespread presence of CNVs in the genomes of phenotypically normal individuals [2, 3]. Following these initial studies, additional genome-wide
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