Cataloguing deleterious variants in domestic animal species: motivation, applications and challenges

Abstract

By altering the function of genes or their regulatory elements, deleterious variants may have a negative impact on the survivability of individuals through the elicitation of disease, reproductive failure and other adverse pathological conditions. While more than 6000 single-gene disorders have been described so far in humans and phenotype-causing mutations are known for 4,925 genes, only a few hundred or tens (depending on the species) of Mendelian diseases with at least one known likely causal variant have been reported in domestic animals. Even more, variants affecting susceptibility to complex diseases are mostly unknown in farm animals. This and other evidence suggest that, despite its negative impact on the profitability of the animal production sector, just a very small number of deleterious variants have been discovered so far. In this context, the construction of comprehensive catalogues of deleterious variants with functional annotations and predictive value would be critical to be able to estimate the individual genetic load of elite breeders, an information that could be used as a selection criterium. The molecular characterization of deleterious variants would be also extraordinarily useful to shed light on complex biological phenomena such as inbreeding depression, transmission ratio distortion, domestication and susceptibility to Mendelian and complex diseases, to mention a few. Here I discuss the motivation and current challenges to build such catalogues as well as the potential avenues to overcome them.