Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene.
Authors: Brosnahan M M, Al Abri M A, Brooks S A, Antczak D F, Osterrieder N
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary: Host Genetics and EHV-1-Induced Myeloencephalopathy EHV-1 infection causes variable clinical outcomes in horses, with only a proportion of infected animals developing the devastating neurological form (EHM) characterised by endothelial damage, vasculitis and central nervous system ischaemia; whilst viral polymorphisms partially explain this variation, they cannot account for the complete picture of disease susceptibility, prompting investigation into the host's genetic contribution. Brosnahan and colleagues conducted a genome-wide association study (GWAS) on 129 naturally and experimentally infected horses (61 with EHM, 68 without neurological signs), using SNP genotyping arrays and recessive statistical modelling to identify genetic variants associated with disease outcome. A single nucleotide polymorphism in the tetraspanin 9 (TSPAN9) gene achieved genome-wide significance (P<0.001 post-Bonferroni correction), notable because TSPAN9 is expressed in both endothelial cells and platelets—tissues directly implicated in EHM pathophysiology. These findings suggest that individual genetic differences in platelet function and endothelial integrity may predispose certain horses to neurological complications following EHV-1 infection, potentially enabling more targeted risk stratification and treatment strategies during outbreaks. Further research validating this association in larger populations could ultimately inform breeding decisions and refine clinical management approaches for high-risk animals.
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Practical Takeaways
- •Genetic testing for the TSPAN9 variant may eventually help identify horses at higher risk of developing EHM following EHV-1 exposure, enabling targeted management strategies
- •EHM susceptibility is partly determined by host genetics; horses with certain genetic variants may warrant closer neurologic monitoring during EHV-1 outbreaks
- •This research supports the complex, multifactorial nature of EHM—understanding genetic predisposition could improve outbreak management and treatment protocols beyond current supportive care approaches
Key Findings
- •GWAS identified a genome-wide significant marker (BIEC2_946397, P<0.001) located in an intron of the TSPAN9 gene associated with EHM susceptibility
- •The TSPAN9 gene encodes tetraspanin 9, which is expressed in endothelial cells and platelets, implicating vascular and platelet function in EHM pathophysiology
- •Host genetic variation contributes to individual differences in disease outcome following EHV-1 infection, beyond virus polymorphisms alone
- •61 of 129 infected horses (47%) developed neurologic signs while 68 (53%) resolved infection without neurologic complications