Rare and population-specific functional variation across pig lines

Abstract

BackgroundIt is expected that functional, mainly missense and loss-of-function (LOF), and regulatory variants are responsible for phenotypic differences among breeds, genetic lines, and varieties of livestock and crop species that have undergone diverse selection histories. However, there is still limited knowledge about the existing missense and LOF variation in livestock commercial populations, in particular regarding population-specific variation and how it can affect applications such as across-breed genomic prediction. MethodsWe re-sequenced the whole genome of 7,848 individuals from nine commercial pig breeding lines (average sequencing coverage: 4.1x) and imputed whole-genome genotypes for 440,610 pedigree-related individuals. The called variants were categorized according to predicted functional annotation (from LOF to intergenic) and prevalence level (number of lines in which the variant segregated; from private to widespread). Variants in each category were examined in terms of distribution along the genome, minor allele frequency, Wrights fixation index (FST), individual load, and association to production traits. ResultsOf the 46 million called variants, 28% were private (called in only one line) and 21% were widespread (called in all nine lines). Genomic regions with low recombination rate were enriched with private variants. Low-prevalence variants (called in one or a few lines only) were enriched for lower allele frequencies, lower FST, and putatively functional and regulatory roles (including loss-of-function and deleterious missense variants). Only a small subset of low-prevalence variants was found at intermediate allele frequencies and had large estimated effects on production traits. Individuals on average carried less private deleterious missense alleles than expected compared to other predicted consequence types. A small subset of low-prevalence variants with intermediate allele frequencies and higher FST were detected as significantly associated to the production traits and explained small fractions of phenotypic variance (up to 3.2%). These associations were tagged by other more widespread variants, including intergenic variants. ConclusionsMost low-prevalence variants are kept at very low allele frequency and only a small subset contributed detectable fractions of phenotypic variance. Not accounting for low-prevalence variants is therefore unlikely to hinder across-breed analyses, in particular for genomic prediction of breeding values using reference populations of a different genetic background.