A survey of deleterious variation in highly managed pig populations

The level of deleterious genetic variation in highly managed domestic populations is influenced by a variety of factors including mutation rate, effective population size, and artificial selection. Small populations enhance the risk of inbreeding depression, which negatively impacts individual fitness and population viability. Inbreeding depression has largely been attributed to the accumulation of recessive harmful mutations in the genome: inbreeding increases the probability of these mutations to become homozygous. Past population bottlenecks, including domestication, have been indicated as major driver of genetic load in populations. While lethal variants can quickly be purged from small populations, the frequency of slightly deleterious mutations is expected to rise due to less effective natural selection. Because of genetic hitch-hiking, mildly harmful mutations are thought to be over-represented in regions of the genome under selection. Recent advances in genome sequencing have opened exciting possibilities to actually measure the amount of harmful mutations in genomes. Using re-sequence data from 421 individuals, we provide an overview of the occurrence of deleterious mutations in individual pig genomes. An alternative approach to identify lethal variants in the genome, is offered by the vast amount of genotyped pedigreed individuals due to the widespread use of genomic selection in current breeding programs. This allows the identification of recessive deleterious variants by testing for statistical depletion, or even the absence, of specific haplotypes in homozygous state. We have used a combination of whole genome sequencing and 60K genotyping (23,800 individuals) to identify and characterize lethal variants segregating in three commercial pig breeding lines. Keywords: genome sequencing, lethal recessive, loss of function mutation, selective sweeps