Molecular genetic studies in canine inherited diseases including neonatal cerebellar ataxia, degenerative myelopathy and multiple system degeneration

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The inherited diseases of the domestic dog mimic a wide spectrum of common human disorders. By identifying the genes that harbor the mutations underlying dog diseases we not only provide powerful diagnostic DNA tests for dog breeders their veterinarians and but also provide spontaneously occurring canine models for human diseases. Since the first high quality dog genome reference sequence was published and made publically accessible, various molecular strategies have been applied in the canine genetic studies including candidate gene analysis, linkage analysis, and genome-wide allele association studies. Most recently our lab has focused on the discovery of causal sequence variants in the next generation whole-genome sequences of individual affected dogs. This has enabled us to identify disease-causing genes in dogs with relevance for human health. We describe here the identification of causative mutations for three different canine diseases: neonatal cerebellar ataxia, canine degenerative myelopathy and canine multiple system degeneration. In addition, we discuss the potential importance of these canine diseases if used as human disease models.