A Genomics Based Approach to Understanding Risk and Progression of Mitral Valve Disease

Myxomatous mitral valve disease (MMVD) is inherited in dogs. Smaller breeds are overrepresented, especially the Cavalier King Charles spaniel (CKCS), in which the lifetime prevalence approaches 100%. Pedigree analysis studies suggest that MMVD is inherited as a polygenic threshold trait in CKCS. The disease phenotype will therefore be determined by the number and combination of disease-associated alleles present in an individual dog. The investigation of the genetic basis of MMVD is therefore challenging, due to the complex mode of inheritance and lack of true healthy control animals. This lecture will present the work of an ongoing research program which includes whole genome sequencing and follow-up genotyping of CKCS with mild vs severe MMVD phenotypes and dogs of other breeds with and without MMVD. This approach has enabled us to identify genetic variants that appear to be important in MMVD susceptibility and phenotype severity.