Rapid Discovery of De Novo Deleterious Mutations in Cattle Using Genome Sequence Data: Enhancing the Value of Farm Animals as Model Species

In humans, the clinical and molecular characterizations of sporadic syndromes are often hindered by the small number of patients and the difficulty to develop animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chips genotypes and phenotypic records offers unprecedented opportunity to dissect in record time the genetic architecture of phenotypes in livestock. We report the identification of four dominant de novo mutations and take advantage of the structure of cattle populations to describe their clinical consequences and map modifier loci. In addition, we demonstrate the feasibility of anticipating the emergence of recessive genetic defects by detecting de novo deleterious mutations in the genomes of artificial insemination bulls. These results increase the attractiveness of cattle to confirm the genetic etiology of isolated clinical case reports and become a model species in the post genomic era.