title: Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection.
abstract: 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 a cross between 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 QTL in the founder animals of the cross. 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 founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. 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 10 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 selection.
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. falbert@eva.mpg.de
authors.forename: F W
authors.initials: FW
authors.lastname: Albert
authors.forename: E
authors.initials: E
authors.lastname: Hodges
authors.forename: J D
authors.initials: JD
authors.lastname: Jensen
authors.forename: F
authors.initials: F
authors.lastname: Besnier
authors.forename: Z
authors.initials: Z
authors.lastname: Xuan
authors.forename: M
authors.initials: M
authors.lastname: Rooks
authors.forename: A
authors.initials: A
authors.lastname: Bhattacharjee
authors.forename: L
authors.initials: L
authors.lastname: Brizuela
authors.forename: J M
authors.initials: JM
authors.lastname: Good
authors.forename: R E
authors.initials: RE
authors.lastname: Green
authors.forename: H A
authors.initials: HA
authors.lastname: Burbano
authors.forename: I Z
authors.initials: IZ
authors.lastname: Plyusnina
authors.forename: L
authors.initials: L
authors.lastname: Trut
authors.forename: L
authors.initials: L
authors.lastname: Andersson
authors.forename: T
authors.initials: T
authors.lastname: Schöneberg
authors.forename: O
authors.initials: O
authors.lastname: Carlborg
authors.forename: G J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: S
authors.initials: S
authors.lastname: Pääbo
mesh_terms: D000374:Aggression; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005260:Female; D014644:Genetic Variation; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D051381:Rats; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA