HR and LR rats exome sequencing

High responder (bHR) and low responder (bLR) rat lines have been selectively bred from Sprague Dawley rats (Charles River) for exploratory locomotion, a behavioral trait positively correlated with novelty-seeking, impulsive response to reward, and vulnerability to addiction, and inversely correlated with spontaneous anxiety and depression-like behaviors. These outbred rat lines are used as a genetic model to investigate the neurobiology of addictive and affective disorders. To identify loci responsible for the intrinsic difference in exploratory locomotion we performed exome-based genomic sequencing, uncovering alleles in gene-coding regions that segregate between bHR and bLR. The segregating genomic regions are likely to contain causal variants influencing the trait, along with other genetic variants randomly fixed and in strong linkage disequilibrium with the functional variants. The causal loci/genes will be further identified by quantitative trait locus analysis using the segregating variants identified by exome sequencing for enhanced coverage.