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Front Genet. 2018 Sep 20;9:395. doi: 10.3389/fgene.2018.00395. eCollection 2018.

Lead Modulates trans- and cis-Expression Quantitative Trait Loci (eQTLs) in Drosophila melanogaster Heads.

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Department of Pharmacology, Wayne State University, Detroit, MI, United States.
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, United States.
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States.
Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, United States.


Lead exposure has long been one of the most important topics in global public health because it is a potent developmental neurotoxin. Here, an eQTL analysis, which is the genome-wide association analysis of genetic variants with gene expression, was performed. In this analysis, the male heads of 79 Drosophila melanogaster inbred lines from Drosophila Synthetic Population Resource (DSPR) were treated with or without developmental exposure, from hatching to adults, to 250 μM lead acetate [Pb(C2H3O2)2]. The goal was to identify genomic intervals that influence the gene-expression response to lead. After detecting 1798 cis-eQTLs and performing an initial trans-eQTL analysis, we focused our analysis on lead-sensitive "trans-eQTL hotspots," defined as genomic regions that are associated with a cluster of genes in a lead-dependent manner. We noticed that the genes associated with one of the 14 detected trans-eQTL hotspots, Chr 2L: 6,250,000 could be roughly divided into two groups based on their differential expression profile patterns and different categories of function. This trans-eQTL hotspot validates one identified in a previous study using different recombinant inbred lines. The expression of all the associated genes in the trans-eQTL hotspot was visualized with hierarchical clustering analysis. Besides the overall expression profile patterns, the heatmap displayed the segregation of differential parental genetic contributions. This suggested that trans-regulatory regions with different genetic contributions from the parental lines have significantly different expression changes after lead exposure. We believe this study confirms our earlier study, and provides important insights to unravel the genetic variation in lead susceptibility in Drosophila model.


Drosophila melanogaster; Drosophila synthetic population resource (DSPR); RNA-seq; developmental lead exposure; expression quantitative trait loci (eQTL); toxicogenomics

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