UAB Whole body D.m. mRNA lead (pbAc) (Oct09) RMA

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The genetics of gene expression in recombinant inbred lines (RILs) can be mapped as expression quantitative trait loci (eQTLs). So-called "genetical genomics" studies have identified locally acting eQTLs (cis-eQTLs) for genes that show differences in steady-state RNA levels. These studies have also identified distantly acting master-modulatory trans-eQTLs that regulate tens or hundreds of transcripts (hotspots or transbands). We expand on these studies by performing genetical genomics experiments in two environments in order to identify trans-eQTL thatmight be regulated by developmental exposure to the neurotoxin lead. Flies from each of 75 RIL were raised from eggs to adults on either control food (made with 250 mM sodium acetate), or lead-treated food (made with 250 mM lead acetate, PbAc). RNA expression analyses of whole adult male flies (5–10 days old) were performed with Affymetrix DrosII whole genome arrays (18,952 probesets). Among the 1389 genes with cis-eQTL, there were 405 genes unique to control flies and 544 genes unique to lead-treated ones (440 genes had the same cis-eQTLs in both samples). There are 2396 genes with trans-eQTL which mapped to 12major transbands with greater than 95 genes. Permutation analyses of the strain labels but not the expression data suggests that the total number of eQTL and the number of transbands are more important criteria for validation than the size of the transband. Two transbands, one located on the 2nd chromosome and one on the 3rd chromosome, co-regulate 33 lead-induced genes, many of which are involved in neurodevelopmental processes. For these 33 genes, rather than allelic variation at one locus exerting differential effects in two environments, we found that variation at two different loci are required for optimal effects on lead-induced expression.

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Affymetrix Drosophila Genome 2.0 Array GEO_GPL1322


Douglas M. Ruden a,*, Lang Chen b, Debra Possidente c, Bernard Possidente d, Parsa Rasouli a, Luan Wanga, Xiangyi Lu a, Mark D. Garfinkel e, Helmut V.B. Hirsch d, Grier P. Page f a Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, United States b Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States c Department of Biological Sciences, University at Albany, SUNY, Albany, NY, United States d Department of Biology, Skidmore College, Saratoga Springs, NY, United States e Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL, United States f Statistics and Epidemiology Unit, RTI International, Atlanta, GA, United States


Ruden DM, et al. Genetical toxicogenomics in Drosophila identifies master-modulatory loci that are regulated by developmental exposure to lead, Neurotoxicology (2009), doi:10.1016/j.neuro.2009.08.011