Balancing selection at a premature stop mutation in the myostatin gene underlies a recessive leg weakness syndrome in pigs

Abstract

Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation causing a premature stop codon within exon 3 of the porcine Myostatin (MSTN) gene, similar to those causing a double-muscling phenotype observed in several mammalian species. The MSTN mutation was in Hardy-Weinberg equilibrium in the population at birth, but significantly distorted amongst animals still in the herd at 110 kg, due to an absence of homozygous mutant genotypes. In heterozygous form, the MSTN mutation was associated with a major increase in muscle depth and decrease in fat depth, suggesting that the deleterious allele was maintained at moderate frequency due to heterozygous advantage (allele frequency, q = 0.22). Knockout of the porcine MSTN by gene editing has previously been linked to problems of low piglet survival and lameness. This MSTN mutation is an example of putative balancing selection in livestock, providing a plausible explanation for the lack of disrupting MSTN mutations in pigs despite many generations of selection for lean growth.

Association of Twelve Candidate Gene Polymorphisms with the Intramuscular Fat Content and Average Backfat Thickness of Chinese Suhuai Pigs

“…Chen et al [41] found that the FABP3 (HinfI) SNP was associated with IFC in both Yanan ( p < 0.001) and DLY ( p < 0.05) pigs, but did not significantly affect the BF thickness, strikingly similar to the results in our study. Although the rs344435545 SNP in the RYR1 gene is likely to cause an increase in the incidence of porcine stress syndrome, there is a strong correlation between IFC and RYR1 gene expression level [42] and as this mutation can cause a decrease of BF thickness, it has been considered as an example of balanced selection [43]. The SCD (rs80912566) SNP could affect the fatty acid composition and IFC within the Duroc population [18].…”

Detection of a Frameshift Deletion in the SPTBN4 Gene Leads to Prevention of Severe Myopathy and Postnatal Mortality in Pigs

“…In animal breeding, low Ne increases the risk that detrimental alleles rise in frequency by chance. Moreover, previous studies have shown that recessive lethal alleles can be driven by advantageous effects in heterozygotes (Derks et al, 2018; Matika et al, 2019). Matika et al, 2019 found a recessive stop-gained mutation in the MSTN gene associated with a major increase in muscle depth in heterozygotes.…”

“…Hence, piglet mortality is a complex phenotype and depends on the capacity of the sow to raise its offspring, but is also a function of birth weight, management, and selection (Knol et al, 2002). However, also monogenic recessive defects contribute to piglet mortality, although only few examples have been reported in the past (Murgiano et al, 2012; Matika et al, 2019). Even in those cases where the effect of the mutation is severe, selecting efficiently against such a mutation is hampered by the low frequency.…”

The Association of an SNP in the EXOC4 Gene and Reproductive Traits Suggests Its Use as a Breeding Marker in Pigs

“…The recent development of sequencing and genotyping technologies for pigs have enabled the exploration of genomic evidence of selection and the detection of candidate genes associated with target traits. Studies have found that the positive selection of pigs is associated with specific genes related to lactation [ 5 ], reproduction [ 6 , 7 ], meat quality [ 8 ], and growth traits [ 9 ]. Reproductive traits, such as the number of piglets born alive (NBA) [ 10 ], lactation capacity, number of piglets weaned (NW) [ 11 ], and litter weight at weaning (LWW) [ 12 ], have all been genetically improved through artificial selection.…”