In other species: sheep

Categories: Homeostasis / metabolism phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 232600 (trait) , 608455 (gene)

Links to MONDO diseases:

• MONDO:0009293: glycogen storage disease V

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1996

Cross-species summary: McArdle disease

Species-specific name: Myophosphorylase deficiency

Species-specific description: The first occurrence of this disorder in any domestic species was reported by Angelos et al. (1995), in Charolais cattle.

Inheritance: As reported by Angelos et al. (1995), six calves from a single Charolais herd were diagnosed after one of the calves was presented to the Veterinary Medical Teaching Hospital of the School of Veterinary Medicine at the University of California, Davis. The sire and dam of each of the six calves had a common ancestor. The data were consistent with autosomal recessive inheritance.
Batt et al. (2024) pedigre analysis of the Red Angus composite cattle identified a founder Red Angus sire.  

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Tsujino et al. (1996) showed that the disorder in these Charolais cattle is due to a missense mutation in codon 489 of the gene for myophosphorylase.
Batt et al. (2024): "A genome-wide association analysis utilizing SNP data from 6 affected [Red Angus cpmposite] calves and 715 herd mates, followed by whole-genome sequencing of 2 affected calves led to the identification of a variant in the gene PYGM (BTA29:g.42989581G > A). The variant, confirmed to be present in the skeletal muscle transcriptome, was predicted to produce a premature stop codon (p.Arg650*)."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: In Charolais cattle a history of recumbency following forced exercise; severe rhabdmyolysis; dehydration; and electrolyte imbalance.
Batt et al. (2024) report the condition in a composite Simmental, Red Angus, Gelbvieh herd. Affected animals "displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover."

Pathology: Batt et al. (2024): "Glycogen concentrations were fluorometrically assayed as glucose residues demonstrating significantly elevated glycogen concentrations in affected [Red Angus composite] calves compared to cattle carrying the variant and to wild-type controls. The absence of the PYGM protein product in skeletal muscle was confirmed by immunohistochemistry and label-free quantitative proteomics analysis; muscle degeneration was confirmed in biopsy and necropsy samples. Elevated skeletal muscle glycogen persisted after harvest, resulting in a high pH and dark-cutting beef, which is negatively perceived by consumers and results in an economic loss to the industry. Carriers of the variant did not exhibit differences in meat quality or any measures of animal well-being."

Breeds: Charolais (Cattle) (VBO_0000177), Red Angus (Cattle) (VBO_0000350).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: