Genomic Analyses of Equine Cervical Stenotic Myelopathy

Cervical Stenotic Myelopathy (CSM) is a severe neurological disease of young horses characterized by malformations of the cervical vertebrae leading to narrowing of the vertebral canal and spinal cord compression.  CSM is considered a multi-factorial disease with genetics, increased growth rates, high planes of nutrition, and altered levels of dietary copper and zinc all identified as possible factors contributing to etiology and/or pathogenesis.  The role of genetic determinants in CSM has remained a long-standing question.  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 was conducted to re-evaluate the role of genetic determinants for CSM.  DNA samples from 59 Thoroughbreds with a confirmed CSM diagnosis were genotyped on either the equine SNP50 or equine SNP70 BeadChips (Illumina) and compared to population data from 424 Thoroughbreds genotyped for reasons unrelated to CSM.  In addition, a copy number variant (CNV) analysis was performed on 7 samples from a Thoroughbred family with an increased incidence of CSM in the progeny.  SNP and haplotype analyses identified multiple significant quantitative trait loci.  The data indicate that CSM is not controlled by the inheritance of a single trait, but it does support a genetic contribution in this disease.