Using signatures of directional selection to guide discovery

Usually thought to be one of the oldest techniques in neurogenetic research, directional selective breeding has both unique strengths and weaknesses. I briefly review the basic principles of the method using historical and modern examples. Selective breeding has been applied to multiple species, using behavioral, pharmacological, and physiological phenotypic targets. Emphasis recently has focused on molecular biologic consequences of selection, with a proliferation of studies concentrating on differential gene expression and sequence variation driven by the reduced cost and increased throughput of such analyses. I will focus on analyses of rodent lines selectively bred for traits relevant for effects of ethanol and other abused drugs, as such lines are among the oldest contributors to this literature. Finally, I will touch on some innovative applications of the transcriptomic signatures of selective breeding to enable gene finding and drug discovery.