As in humans, dilated cardiomyopathy (DCM) in dogs is characterized by ventricular dilatation and systolic contractile dysfunction, and is an important cause of heart failure. In some canine breeds, DCM is a relatively common, lethal disease. Atrial fibrillation (AF) also causes significant morbidity, disability, and mortality related to heart disease and stroke in the human population. A recent study of 500 Irish Wolfhounds found that 24% had DCM; 87% of these affected dogs also had AF. The AF/DCM phenotype appears to be inherited as an autosomal dominant trait. Mike Litt, Ph.D. and Petra Jakobs, Ph.D. have collected DNA and clinical data from a large family of Irish Wolfhounds in which AF and progressive DCM is segregating. Our hypothesis is that a mutation in a single gene causes AF/DCM in Irish Wolfhounds, and we are attempting to map this gene by linkage analysis and to use the tools of positional cloning and candidate gene analysis to identify the gene.
As reviewed elsewhere on this site, one of the most common genetic causes of human DCM are mutations in the lamin A/C gene. The phenotype caused by lamin A/C mutations in such patients also includes conduction system disease and therefore resembles the AF/DCM phenotype in Irish Wolfhounds. In preliminary studies, we have excluded lamin A/C as the locus of the defect in Irish Wolfhounds. Hence our proposed work presents an ideal opportunity to identify a novel DCM/AF disease gene. If successful, this may lead to improved knowledge of the mechanisms of DCM and AF in humans.
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