Accelerated discovery of functional genomic variation in pigs

Derks, Martijn F.L.; Gross, Christian; Lopes, Marcos S.; Reinders, Marcel J.T.; Bosse, Mirte; Gjuvsland, Arne B.; Ridder, Dick de; Megens, Hendrik Jan; Groenen, Martien A.M.


The genotype-phenotype link is a major research topic in the life sciences but remains highly complex to disentangle. Part of the complexity arises from the number of genes contributing to the observed phenotype. Despite the vast increase of molecular data, pinpointing the causal variant underlying a phenotype of interest is still challenging. In this study, we present an approach to map causal variation and molecular pathways underlying important phenotypes in pigs. We prioritize variation by utilizing and integrating predicted variant impact scores (pCADD), functional genomic information, and associated phenotypes in other mammalian species. We demonstrate the efficacy of our approach by reporting known and novel causal variants, of which many affect non-coding sequences. Our approach allows the disentangling of the biology behind important phenotypes by accelerating the discovery of novel causal variants and molecular mechanisms affecting important phenotypes in pigs. This information on molecular mechanisms could be applicable in other mammalian species, including humans.