Genetics of gene expression characterizes response to selective breeding for alcohol preference

Numerous selective breeding experiments have been performed with rodents, in an attempt to understand the genetic basis for innate differences in preference for alcohol consumption. QTL analysis has been used to determine regions of the genome that are associated with the behavioral difference in alcohol preference/consumption. Recent work suggests that differences in gene expression represent a major genetic basis for complex traits. Therefore, the QTLs are likely to harbor regulatory regions (eQTLs) for the differentially expressed genes that are associated with the trait. In the present study, we examined brain gene expression differences over generations of selection of the third replicate lines of High and Low Alcohol Preferring (HAP3 and LAP3) mice, and determined regions of the genome that control the expression of these differentially expressed genes (deeQTLs). We also determined eQTL regions (rveQTLs) for genes that showed a decrease in variance of expression levels over the course of selection. We postulated that deeQTLs that overlap with rveQTLs, and also with phenotypic QTLs, represent genomic regions that are affected by the process of selection. These overlapping regions controlled the expression of candidate genes (that displayed differential expression and reduced variance of expression) for the predisposition to differences in alcohol consumption by the HAP3/LAP3 mice.