Loss of function mutations in essential genes cause embryonic lethality in pigs

Published on
March 27, 2019

Researchers from Animal Breeding and Genomics from Wageningen University & Research (WUR) and Topigs Norsvin studied mutations that impair the functioning of essential genes, causing embryonic lethality in pigs. This study will be used to lower the frequency of these harmful mutations to improve pig fertility. They published their findings in the PLOS Genetics journal.

Lethal recessive mutations cause pre- or postnatal death in homozygous (carrying two copies of the lethal mutation) affected individuals, reducing fertility in various populations. Although recessive lethals occur in every population, their effect is generally masked by the extremely low frequency. However, within commercial livestock populations, those mutations might be exposed by inbreeding, increasing to higher frequency by a process called genetic drift (the random change of mutation frequency in small populations).

Recessive lethal mutations

In this study, we found five recessive lethal genes in the pig populations under study. The lethal genes have a large effect in carrier-by-carrier matings (two carriers of the same lethal gene that mate), decreasing litter sizes by approximately 20%. By using whole-genome-sequence and gene expression data we could accurately pinpoint the causal mutations, and the part of the gene that was affected. Some of the mutations were found at relatively high frequency, this could be driven by a positive effect of the mutation on other important traits in pigs (e.g. growth), something that was found in a previous study. However, for the mutations in this study, no positive effect was found, showing that these mutations are purely the result of genetic drift, something that was also supported by our simulation study. 

Impact on population fitness

The lethal recessives affect up to 3% of the population litters and are responsible for the death of 1 in 200 embryos. This study, therefore, will allow monitoring, and facilitate the purging and partial elimination of recessive lethal mutations in frequently used pig breeds, improving pig fertility.