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Discovery of Regulatory Mechanisms from Gene Expression Variation by eQTL Analysis

One of the big challenges in the post-genome era is the better understating of the gene regulation process. Recently developed high-throughput genotyping and gene expression platforms have enabled a powerful new tool: expression quantitative trait loci (eQTL) analysis, where loci or markers on the genomes are associated with variations in gene expression. In such studies, gene expression is treated as a quantitative trait. DNA polymorphism at the gene, binding site or a regulatory proteins, such as transcription factors (TFs), transcription association proteins and signaling proteins, is likely to affect the expression level of the gene in an inheritable way (Monks et al. 2004; Brem and Kruglyak 2005; Petretto et al. 2006b). Hence, a significant statistical association between a locus and the expression level of a gene suggests that the locus might regulate the gene. Since the early work of Jansen and Nap (Jansen and Nap 2001), eQTL has become a widespread technique to identify such regulatory associations and has been applied to a number of species including yeast (Yvert et al. 2003; Brem and Kruglyak 2005; Brem et al. 2005), Arabidopsis (DeCook et al. 2006), maize (Schadt et al. 2003), Drosophila (Jin et al. 2001), mouse (Klose et al. 2002; Bystrykh et al. 2005; Chesler et al. 2005), rat (Petretto et al. 2006a) and human (Monks et al. 2004; Cheung et al. 2005; Stranger et al. 2005). Many of them used the strategy of genome-wide association study (GWAS), considering loci covering the whole genome and expression profiles of all or nearly all genes identified in the organism.