Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy.
Authors: Williams Zoë J, Velez-Irizarry Deborah, Petersen Jessica L, Ochala Julien, Finno Carrie J, Valberg Stephanie J
Journal: Equine veterinary journal
Summary
# Myofibrillar Myopathy in Warmbloods: A Genetic Dead End—For Now Myofibrillar myopathy (MFM) has emerged as a concerning condition in Warmblood horses, yet its genetic basis remains elusive; researchers examined 16 candidate genes implicated in human MFM disorders to determine whether variants in these genes might explain the disease in affected horses. Using RNA sequencing from gluteal muscle tissue and functional muscle fibre testing, the team screened eight affected and eight unaffected Warmbloods, identifying 426 total variants across the candidate genes but finding none that segregated with disease status—notably, even the two variants currently offered in commercial MFM genetic tests showed no association with affected horses. Muscle fibre contractile force was essentially identical between MFM and non-MFM horses (143.1 versus 140.2 kPa respectively), suggesting the pathology is not a primary defect in myofibrillar protein function or expression. The findings underscore that whilst coding variants are abundant in the equine genome, presence alone proves nothing; clinicians and breeders should view available MFM genetic tests with considerable scepticism until rigorous evidence of causation emerges, and further investigation must extend beyond these 16 candidate genes to identify the true genetic culprit.
Read the full abstract on PubMed
Practical Takeaways
- •Currently available commercial MFM genetic tests for horses do not reliably predict myofibrillar myopathy in Warmbloods; genetic testing alone should not be used for breeding or diagnostic decisions.
- •MFM in Warmbloods appears to have a different genetic basis than human MFM disorders, suggesting practitioners cannot rely on human disease candidate genes to understand equine MFM.
- •Diagnosis of MFM in Warmbloods must currently rely on clinical signs and muscle biopsy findings rather than genetic testing.
Key Findings
- •None of 426 variants identified in 16 MFM candidate genes were associated with myofibrillar myopathy in Warmblood horses, including 26 missense variants.
- •Two coding variants offered as commercial MFM equine genetic tests did not associate with the Warmblood MFM phenotype.
- •No significant differences in candidate gene differential expression or muscle fibre-specific force between MFM and non-MFM Warmblood horses (143.1 vs 140.2 kPa, P = 0.8).
- •Breed-specific differences existed in allele frequencies across the 16 candidate genes studied.