Tameness QTL Sequence Capture

The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here we use targeted sequence capture and massively parallel sequencing of all genes in the strongest of these QTL in an attempt to accelerate the identification of putatively causative alleles. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive rats contain no sequence variation, and two regions where alternative haplotypes are fixed in the lines. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find ten putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic adaptation.