Orthopaedic Pathology and Genetic Associations with Cervical Stenotic Myelopathy

Cervical stenotic myelopathy is a disease that affects both the neurologic and musculoskeletal system of horses. While the exact etiology and pathogenesis are not well understood, it is thought to be a multifactorial disease with genetics, high planes of nutrition, trauma, rapid growth, and decreased copper/increased zinc levels all potentially playing a role. The breed examined in this study will be initially limited to Thoroughbreds. The objective is to elucidate the role of genetics along with normal and abnormal bone and cartilage formation in the onset and progression of this disease. Comparison of the articular processes and cranial and caudal epiphyseal growth plates of cervical vertebrae from affected and control horses will be analyzed using detailed gross and histological examinations. Postmortem Magnetic Resonance Imaging (MRI) will be used to obtain an in situ inspection of the cervical vertebrae, cervical spinal cord, and associated soft tissue structures. Alterations in subchondral bone, as well as structural changes in articular and physeal cartilage will be assessed. Bone structure will be assessed quantitatively by identifying volumes of interest and calculating volume fraction, trabecular thickness, and trabecular separation on microCT. Genomic DNA will be isolated and purified. Genotyping will be performed using a 54,602 element equine-specific single nucleotide polymorphism (SNP) array. Linkage disequilibrium between affected and control horses will be evaluated by comparing SNP haplotypes with the disease phenotype to identify any quantitative trait loci (OTL) associations. Fine mapping within identified OTL regions with additional SNPs will be completed with Sequenom to prioritize candidate genes. Results of this study will enhance understanding of the etiology and pathogenesis of cervical stenotic myelopathy, advance MRI imaging and molecular diagnostic technologies, and provide a scientific foundation for research on improved management and therapeutic practices for this prevalent and serious disease.