Scanning the genomes of parents for imprinted loci acting in their un-genotyped progeny

Depending on their parental origin, alleles at imprinted loci are fully or partially inactivated through epigenetic mechanisms. Their effects contribute to the broader class of parent-of-origin effects. Standard methodology for mapping imprinted quantitative trait loci in association studies requires phenotypes and parental origin of marker alleles (ordered genotypes) to be simultaneously known for each individual. As such, many phenotypes are known from un-genotyped offspring in ongoing breeding programmes (e.g. meat animals), while their parents have known genotypes but no phenotypes. By theoretical considerations and simulations, we showed that the limitations of standard methodology can be overcome in such situations. This is achieved by first estimating parent-of-origin effects, which then serve as dependent variables in association analyses, in which only imprinted loci give a signal. As a theoretical foundation, the regression of parent-of-origin effects on the number of B-alleles at a biallelic locus — representing the un-ordered genotype — equals the imprinting effect. The applicability to real data was demonstrated for about 1800 genotyped Brown Swiss bulls and their un-genotyped fattening progeny. Thus, this approach unlocks vast data resources in various species for imprinting analyses and offers valuable clues as to what extent imprinted loci contribute to genetic variability.