Estimating mutation rate and characterising single nucleotide de novo mutations in pigs

Abstract Background Direct estimates of mutation rates in humans have changed our understanding of evolutionary timing and de novo mutations (DNM) have been associated with several developmental disorders in humans. Livestock species, including pigs, can contribute to the study of DNM because of their ideal population structure and routine phenotype collection. In principle, there is the potential for livestock populations to quickly accumulate new genetic variants because of short generation intervals and high selection intensity. However, the impact of DNM on the fitness of individuals is not known and with current genomic selection programs they cannot contribute to estimated breeding values. The aims of our project were to detect and validate single nucleotide DNM in two commercial pig breeding lines, estimate the single nucleotide mutation rate, and characterise DNM. Results We sequenced (150 bp paired end reads, 30X coverage) 46 pig trios from two commercial lines. Single nucleotide DNM were detected using a trio-aware method. We defined candidate DNM as single nucleotide variants (SNVs) found in heterozygous state in trio-offspring with both trio-parents homozygous for the reference allele. In this study, we estimate a lower threshold of the DNM rate in pigs of 6.3 × 10–9 per site per gamete. Our findings are consistent with those from other mammals and those published for a small number of livestock species. Most DNM we detected were in introns (47%) and intergenic regions (49%). The mutational spectrum in pigs differs from that in humans and we found several DNM predicted to have an effect on animal’s fitness based on the base pair change and their location in the genome. Conclusions With this study, we have generated fundamental knowledge on mutation rate in a non-primate species and identified DNM that could have an impact on the fitness of individuals.