Exome-Driven Screening For Embryonic Lethals

Fertility in modern livestock populations has been decreasing steadily over the last decades.  Causes are multiple, but accumulation of deleterious mutations leading to embryonic or fetal death could partly explain this decrease.  Following our recent study on Brachyspina syndrome in Holstein Friesian, we hypothesized that such embryonic lethal mutations (EL) must segregate in every specialized cattle breed but would have remained completely unnoticed because all homozygous mutant embryos/fetuses would have die during gestation.  To hunt for EL, we have set up a genotype-driven screen in which the entire exome of popular elite sires is captured and sequenced.  Sequence data are mined bioinformatically to single out the most likely candidate EL within the narrow list of strong loss-of-function mutations.  Their damaging effect is subsequently validated at the population level by genotyping large data sets to demonstrate the absence of homozygous mutants amongst healthy animals.  Ultimately, an effect of carrier status on a panel of important agronomical traits, including fertility, is quantified.  Promising results, from this complete process applied to 20 Belgian Blue elite sires, will be presented.  For example, we can emphasize balancing selection for one novel EL mutation.