Lead Modulates and Expression Quantitative Trait Loci (eQTLs) in Heads.

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 inbred lines from Synthetic Population Resource (DSPR) were treated with or without developmental exposure, from hatching to adults, to 250 μM lead acetate [Pb(CHO)]. The goal was to identify genomic intervals that influence the gene-expression response to lead. After detecting 1798 eQTLs and performing an initial -eQTL analysis, we focused our analysis on lead-sensitive "-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 -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 -eQTL hotspot validates one identified in a previous study using different recombinant inbred lines. The expression of all the associated genes in the -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 -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 model.