NGS-based reverse genetic screen reveals loss-of-function variants compromising fertility in cattle

Abstract Text: We herein report the results of a large-scale reverse genetic screen, based on next generation sequencing (NGS) of the exome or whole genome of more than 500 animals, to identify highly deleterious mutations that cause embryonic lethality in domestic cattle.  We first demonstrate that - as in human - domestic cattle carry of the order of 100 loss-of-function (LoF) variants per genome.  We then present evidence for significant depletion in homozygosity for at least tens of candidate deleterious variants in Belgian Blue Cattle, strongly suggesting that these act as embryonic lethal (EL) or at least juvenile lethal (JL) mutations.  We finally formally demonstrate the embryonic/juvenile lethality of a handful of common LoF variants compromising fertility in domestic cattle of Belgium and New Zealand.   

Keywords: cattle, fertility, embryonic mortality, loss-of-function mutations, newt generation sequencing.