Publication
Genotyping by low-coverage whole-genome sequencing in intercross pedigrees from outbred founders: a cost efficient approach
Publisher:
Cold Spring Harbor Laboratory
Date:
20-09-2018
DOI:
10.1101/421768
Abstract: Experimental 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 in iduals (∼30×) and low coverage sequence data on intercross in iduals (∼0.4×). The method is illustrated in a large F 2 pedigree between lines of chickens that have been ergently selected for 40 generations for the same trait (body weight at 8 weeks of age). Described is how hundreds of in iduals 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 F 0 -F 2 families. The genotypes imputed from low coverage sequence data were consistent with the founder line genotypes estimated using SNP and microsatellite markers both at in idual imputed sites (92%) and across the genome of in idual chickens (93%). The resolution of the recombination breakpoints was high with 50% being resolved within kb. A method for genotype imputation from low-coverage whole-genome sequencing in outbred intercrosses is described and evaluated. By applying it to an outbred chicken F 2 cross it is illustrated that it provides high quality, high-resolution genotypes in a time and cost efficient manner.