Imputation-based fine-mapping suggests that most QTL in an outbredchickenAdvanced Intercross Line are due to multiple, linked loci

A bstract The Virginia chicken lines have been divergently selected for juvenile body-weight for more than 50 generations. Today, the high-and low-weight lines show a 12-fold difference for the selected trait, 56-day body-weight. These lines provide unique opportunities to study the genetic architecture of long-term, single-trait selection. Previously, several Quantitative Trait Loci (QTL) contributing to weight differences between the lines were mapped in an F 2 -cross between them, and these were later replicated and fine-mapped in a nine-generation advanced intercross of them. Here, we explore the possibility to further increase the fine-mapping resolution of these QTL via a pedigree-based imputation strategy that aims to better capture the haplotype-diversity in the divergently selected, but outbred, founder lines. The founders of the intercross were high-density genotyped, and then pedigree-based imputation was used to assign genotypes throughout the pedigree. Imputation increased the marker-density 20-fold in the selected QTL, providing 6911 markers for the subsequent analysis. Both single-marker association and multi-marker backward-elimination analyses were used to detect associations to 56-day body-weight. The approach revealed several statistically and population-structure independent associations and increased the resolution of most QTL. Further, most QTL were also found to contain multiple independent associations, implying a complex underlying architecture due to the combined effects of multiple, linked loci on independent haplotypes that still segregate in the selected lines. Article summary After 50 generations of bi-directional selection, the Virginia chicken lines display a 12-fold difference in bodyweight at 56 days of age. Birds from the high and low selected lines were crossed to found an Advanced Intercross Line, which has been maintained for 9 generations. Using high-density genotypes of the founders, we imputed genotypes in intercross birds that were only genotyped for a sparse set of markers. Using single and multi-marker association analyses, we replicated nine known body-weight QTL. Multiple statistically independent associations were revealed in eight of the QTL, suggesting that most are caused by multiple linked loci.