An autosomal recessive mutation in PYGM causes myophosphorylase deficiency in Red Angus cattle

Between 2020 and 2022, eight calves (6 heifers, 2 bulls) in the University of Nebraska-Lincoln herd (composite Simmental, Red Angus, Gelbvieh) were observed to experience exercise intolerance during forced activity with increased creatine kinase, indicating muscle degeneration; in some cases the calves were unable to stand or recover. The available pedigrees contained a shared paternal ancestor in all affected calves. Dam pedigrees were unavailable; however, the cows were retained from prior breeding seasons in which related bulls were occasionally used for breeding. Therefore, it was hypothesized that a de novo autosomal recessive mutation was the cause of exercise intolerance in these calves. A genome-wide association analysis including data from 6 affected calves and 706 herd mates followed by whole-genome sequencing of 2 affected calves led to the identification of a nonsense mutation in the gene PYGM (Chr29:g.42989581G>A). The mutation was predicted to produce a premature stop codon (Chr29:p.Arg650*), leading to putative nonsense-mediated decay. The protein product of the PYGM gene, the enzyme myophosphorylase, breaks down glycogen stored in skeletal muscle. Myophosphorylase deficiency in the affected calves was associated with muscle degeneration and muscle glycogen concentrations that were markedly elevated compared to the carrier and wild-type animals. Due to the inability to utilize glycogen, elevated glycogen persisted after harvest, resulting in high pH and consequently, dark-cutting beef. Compared to wild-type animals, carriers of the mutation did not exhibit significant differences in meat quality or any measures of animal well-being studied. Myophosphorylase deficiency poses welfare concerns for affected animals and has negative implications for meat quality. Identifying carriers in breeding practices is essential to prevent the production of affected calves.