title: Genetics of gene expression characterizes response to selective breeding for alcohol preference.
abstract: 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. Quantitative trait locus (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 this 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 (de eQTLs). We also determined eQTL regions (rv eQTLs) for genes that showed a decrease in variance of expression levels over the course of selection. We postulated that de eQTLs that overlap with rv eQTLs, 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.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO.
authors.forename: P L
authors.initials: PL
authors.lastname: Hoffman
authors.forename: L M
authors.initials: LM
authors.lastname: Saba
authors.forename: S
authors.initials: S
authors.lastname: Flink
authors.forename: N J
authors.initials: NJ
authors.lastname: Grahame
authors.forename: K
authors.initials: K
authors.lastname: Kechris
authors.forename: B
authors.initials: B
authors.lastname: Tabakoff
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001947:Breeding; D002755:Choice Behavior / Q000502:physiology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005838:Genotype; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci
keywords: Alcohol preference; HAP and LAP mice; QTL analysis; genetics of gene expression; selective breeding