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

Area of Science:

• Animal Genetics
• Population Genetics
• Molecular Biology

Background:

• Recessive lethal alleles can cause significant fertility issues in livestock populations, particularly when inbreeding increases carrier-by-carrier matings.
• These alleles lead to pre- or postnatal death in homozygous individuals, impacting overall population health and reproductive efficiency.

Purpose of the Study:

• To identify and characterize common recessive lethal haplotypes in commercial pig populations.
• To investigate the impact of these lethal alleles on fertility traits, specifically litter size.
• To explore the contribution of these embryonic lethal alleles to the heterosis effect in pigs.

Main Methods:

• Genomic analysis of two commercial pig populations to detect recessive lethal haplotypes.
• Carrier frequency estimation and assessment of the impact on litter size in carrier-by-carrier matings.
• Identification of causal mutations, including splice-site, frameshift, and missense variants, and their effects on gene function.

Main Results:

• Five common recessive lethal haplotypes were identified, with carrier frequencies up to 13.4%.
• Carrier-by-carrier matings resulted in a significant decrease in litter size, ranging from 15.1% to 21.6%.
• Recessive lethal alleles were found to affect up to 2.9% of litters and cause 0.52% of embryonic deaths, with identified mutations affecting essential genes like POLR1B, TADA2A, URB1, and PNKP.

Conclusions:

• The identified recessive lethal alleles have a substantial negative impact on pig fertility and embryonic survival.
• These alleles contribute to the observed heterosis effect for fertility, demonstrating their importance in crossbreeding outcomes.
• This study provides a molecular and population-level understanding of recessive lethals, offering a model for livestock fertility and heterosis research.