Siegel, P. B. | bioRxiv Science

bioRxiv2018

Genotyping by low-coverage whole-genome sequencing in intercross pedigrees from outbred founders: a cost efficient approach

BackgroundExperimental intercrosses between outbred founder populations are powerful resources for mapping loci contributing to complex traits (Quantitative Trait Loci or QTL). Here, we present an approach and accompanying software for high-resolution genotype imputation in such populations using whole-genome high coverage sequence data on founder individuals ([~]30x) and low coverage sequence data on intercross individuals ([~]0.4x). The method is illustrated in a large F2 pedigree between lines of chickens that have been divergently selected for 40 generations for the same trait (body weight at 8 weeks of age).\n\nResultsDescribed is how hundreds of individuals were whole-genome sequenced in a cost- and time-efficient manner using a Tn5-based library preparation protocol optimized for this application. In total, 7.6M markers segregated in this pedigree and 10.0 to 13.7% were informative for imputing the founder line genotypes within the F0-F2 families. The genotypes imputed from low coverage sequence data were consistent with the founder line genotypes estimated using SNP and microsatellite markers both at individual imputed sites (92%) and across the genome of individual chickens (93%). The resolution of the recombination breakpoints was high with 50% being resolved within <10kb.\n\nConclusionsA method for genotype imputation from low-coverage whole-genome sequencing in outbred intercrosses is described and evaluated. By applying it to an outbred chicken F2 cross it is illustrated that it provides high quality, high-resolution genotypes in a time and cost efficient manner.

genetics↗

bioRxiv2017

A complex multi-locus, multi-allelic genetic architecture underlying the long-term selection-response in the Virginia body weight line of chickens

The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a nine-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained more than 60% of the additive genetic variance for the selected trait. We focused particularly on seven major QTL and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of genome-wide mechanisms involved in the long-term selection responses. The results illustrate that long-term selection responses, even from populations with a limited genetic diversity, can be polygenic and influenced by a range of genetic mechanisms.

genetics↗