in humans, mitral valve prolapse (MVP), is 1 to 5%.
Objectives To identify important biological mechanisms involved in the development of MMVD in dogs and MVP in humans.
Procedure One-hundred and thirty-nine CKCSs with an early onset of MMVD (affected dogs) and 102 old dogs with no or mild signs of MMVD (controls) were investigated in a genome-wide association study (GWAS) to identify loci associated with development of MMVD.
Results Regions on CFA13 and CFA14 were found to be associated with development of MMVD.
Author Conclusion The dog is a valuable model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.
Inclusions Two figures, 1 table, 37 references.
MYXOMATOUS MITRAL VALVE DISEASE IN CAVALIER KING CHARLES SPANIELS Background Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and incompetent, resulting in mitral regurgitation. MMVD is most prevalent in smallto medium-sized dogs, particularly the Cavalier King Charles Spaniel, and the onset of MMVD is age dependent. By the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease
This is the first study examining the genetic causes of MMVD in dogs. CKCS are known to have a breed predisposition with early onset of disease and relatively rapid progression to clinical signs (congestive heart failure). These factors suggest a genetic etiology. The authors identified 2 loci on adjacent chromosomes that appear to influence the development of MMVD in CKCS. Interestingly, one locus appears to confer the disease status, while the other appears to protect against disease development. Thus, the ultimate expression of MMVD in CKCS might depend on the exact composition of alleles at these 2 loci. The authors showed that different combinations of the 4 alleles at these 2 loci resulted in different proportions of affected and unaffected dogs. The study was well performed and suggests that specific genetic tests might be available in the foreseeable future for determining the disease status of MMVD in CKCS. The findings will not be applicable to other breeds, but will be exclusively associated with this breed (and maybe the closely related King Charles Spaniel). What
genes are involved, how they function to produce the disease, how they interact with each other, and what other modifiers are important remain unknown. They are the foci of additional investigations. Clinicians should be aware of such studies. Their client breeders are likely to ask about such developments and often become informed of these findings relatively soon after publication. (MR) Madsen MB, Olsen LH, Haggstrom J, et al. Identification of 2 loci associated with development of myxomatous mitral valve disease in Cavalier King Charles Spaniels. J Heredity 2011;102:562-567.