Expression profiling and QTL analysis: a powerful complementary strategy in drug abuse research

Alcoholism is a complex disease exhibiting a multifactorial mode of transmission. To simplify the genetic and phenotypic complexity of the alcoholic phenotype, alcohol-preferring (P) and -non-preferring (NP) rats were developed on the basis of alcohol preference and consumption as an animal model of alcoholism. Total gene expression analysis (TOGA) and quantitative trait loci (QTL) analysis were applied to selectively bred, inbred P and NP rats as complementary studies to identify genetic factors that contribute to alcohol preference and consumption. TOGA analysis was utilized to screen for differential expression in several brain regions involved in the mesocorticolimbic dopamine (DA) system. Genes exhibiting differences in expression were then screened for an association to the alcohol preference phenotype, the quantitative trait of a previously identified QTL. By evaluating differences in gene expression for linkage to a quantitative trait, this combined approach was implemented to identify alpha-synuclein, a candidate gene for alcohol preference.