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Paul B Siegel

Publications and source records attributed to Paul B Siegel.

2 recordsLinked to original sources
bioRxiv2016

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

AO_SCPLOWBSTRACTC_SCPLOWThe 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 F2-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.\n\nArticle summaryAfter 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.

Genetics↗
bioRxiv2015

Standing genetic variation as a major contributor to adaptation in the Virginia chicken lines selection experiment

Artificial selection has, for decades, provided a powerful approach to study the genetics of adaptation. Using selective-sweep mapping, it is possible to identify genomic regions in populations where the allele-frequencies have diverged during selection. To avoid misleading signatures of selection, it is necessary to show that a sweep has an effect on the selected trait before it can be considered adaptive. Here, we confirm candidate selective-sweeps on a genome-wide scale in one of the longest, on-going bi-directional selection experiments in vertebrates, the Virginia high and low body-weight selected chicken lines. The candidate selective-sweeps represent standing genetic variants originating from the common base-population. Using a deep-intercross between the selected lines, 16 of 99 evaluated regions were confirmed to contain adaptive selective-sweeps based on their association with the selected trait, 56-day body-weight. Although individual additive effects were small, the fixation for alternative alleles in the high and low body-weight lines across these loci contributed at least 40% of the divergence between them and about half of the additive genetic variance present within and between the lines after 40 generations of selection. The genetic variance contributed by the sweeps corresponds to about 85% of the additive genetic variance of the base-population, illustrating that these loci were major contributors to the realised selection-response. Thus, the gradual, continued, long-term selection response in the Virginia lines was likely due to a considerable standing genetic variation in a highly polygenic genetic architecture in the base-population with contributions from a steady release of selectable genetic variation from new mutations and epistasis throughout the course of selection.

Genetics↗