Abstract
BackgroundA cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria and markedly elevated serum creatine kinase activities were identified. MethodsMuscle biopsy histopathology, immunofluorescence microscopy, and western blotting, were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis.ResultsMuscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene ( SGCA ). Affected dachshunds were confirmed on several continents. ConclusionsThis first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.
Evaluation of the genetic basis of primary hypoadrenocorticism in Standard Poodles using SNP array genotyping and whole-genome sequencing