Genetic Determinants in Equine Cervical Stenotic Myelopathy

Cervical Stenotic Myelopathy (CSM) is a severe neurological disease of young horses characterized by narrowing of the cervical spinal canal and spinal cord compression, typically localized to intervertebral articulations from C3-T1.  A gender ratio of males over females has consistently been reported (3:1 – 14:1), but the disease is not male-specific.  Other factors that have been correlated with development of CSM include increased growth rates, high planes of nutrition during prepubescence, and altered levels of dietary copper and zinc.  The role of genetic determinants contributing to the susceptibility, etiology, or pathogenesis of CSM have long been suspected based on anecdotal evidence, yet remain undefined.  Previous pedigree analyses and prospective breeding studies from different groups have yielded conflicting conclusions.  In the current project, a SNP-based genome-wide association study is being conducted to re-evaluate the question of genetic determinants for CSM.  DNA has been isolated from peripheral blood samples of 57 Thoroughbred horses under the age of 5 with a diagnosis of CSM based on clinical (57/57), radiographic (57/57), and postmortem (22/57) evaluations.  Samples have been genotyped using either the equine SNP50 or equine SNP70 BeadChips (Illumina).  Linkage disequilibrium and potential SNP associations are being evaluated by comparing the CSM horses to population data from Thoroughbreds genotyped for reasons unrelated to CSM.  The analysis is being performed using PLINK, with thresholds for minor allele frequency (<0.05), missing genotypes per SNP (>10%), and 1000 maximium permutations for each SNP.  Preliminary results have identified regions of interest on 3 separate chromosomes.