Qu Wen, Gurdziel Katherine, Pique-Regi Roger, Ruden Douglas M
Department of Pharmacology, Wayne State University, Detroit, MI, United States.
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, United States.
Front Genet. 2018 Sep 20;9:395. doi: 10.3389/fgene.2018.00395. eCollection 2018.
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.
长期以来，铅暴露一直是全球公共卫生领域最重要的话题之一，因为它是一种强大的发育神经毒素。在此，我们进行了一项表达数量性状基因座（eQTL）分析，即对基因变异与基因表达进行全基因组关联分析。在该分析中，来自果蝇合成群体资源（DSPR）的79个近交系雄性果蝇从孵化到成虫阶段，分别接受或不接受250μM醋酸铅[Pb(CHO)]的发育暴露处理。目的是确定影响对铅的基因表达反应的基因组区间。在检测到1798个eQTL并进行初步的eQTL分析后，我们将分析重点放在对铅敏感的“eQTL热点”上，该热点定义为以铅依赖方式与一组基因相关的基因组区域。我们注意到，与14个检测到的eQTL热点之一（Chr 2L: 6,250,000）相关的基因，根据其差异表达谱模式和不同的功能类别可大致分为两组。这个eQTL热点验证了之前使用不同重组近交系的研究中确定的一个热点。通过层次聚类分析可视化了该eQTL热点中所有相关基因的表达情况。除了整体表达谱模式外，热图还显示了亲代遗传贡献的分离情况。这表明来自亲本品系具有不同遗传贡献的调控区域在铅暴露后具有显著不同 的表达变化。我们认为这项研究证实了我们早期的研究，并为揭示果蝇模型中铅易感性的遗传变异提供了重要见解。
