Removal of alleles by genome editing -- RAGE against the deleterious load

Abstract

BackgroundIn this paper, we simulate deleterious load in an animal breeding program, and compare the efficiency of genome editing and selection for decreasing load. Deleterious variants can be identified by bioinformatics screening methods that use sequence conservation and biological prior information about protein function. Once deleterious variants have been identified, how can they be used in breeding?\n\nResultsWe simulated a closed animal breeding population subject to both natural selection against deleterious load and artificial selection for a quantitative trait representing the breeding goal. Deleterious load was polygenic and due to either codominant or recessive variants. We compared strategies for removal of deleterious alleles by genome editing (RAGE) to selection against carriers. Each strategy varied in how animals and variants were prioritized for editing or selection.\n\nConclusionsGenome editing of deleterious alleles reduces deleterious load, but requires simultaneous editing of multiple deleterious variants in the same sire to be effective when deleterious variants are recessive. In the short term, selection against carriers is a possible alternative to genome editing when variants are recessive. The dominance of deleterious variants affects both the efficiency of genome editing and selection against carriers, and which variant prioritization strategy is the most efficient. Our results suggest that in the future, there is the potential to use RAGE against deleterious load in animal breeding.