Cardiogenetics

Many genetic cardiovascular diseases known in humans also occur in dogs even with increased prevalence due to inbreeding of particular dog breeds. Canine cardiogenetics from this particular perspective has two very distinct objectives: use the developments in human genetics to 1) solve canine cardiologic disorders, and 2) provide human medicine with a model in order to obtain fundamental knowledge and possibly test clinical intervention.

Commonly diagnosed cardiac disorders currently studied are:

1. cardiomyopathies
2. tricuspid valve dysplasia
3. pulmonary stenosis

Cardiomyopathies

Within both human and veterinary medicine cardiomyopathies are often diagnosed. In pets Hypertrophic cardiomyopathies are more commonly diagnosed in cats, whereas dilated cardiomyopathy is more often diagnosed in dogs. Both subtypes are postulated to have a genetic background. HCM in Maine Coons is suggested to inherit dominant as seen in humans, whereas DCM in Dobermann is most likely a complex genetic disorder.

 
So far three different mutations related to HCM have been identified. The mutations are breed specific (Maine Coon (n=2) and Ragdoll  (n=1)). However, not all cats carrying the mutation develop the HCM phenotype. Furthermore, cats without the mutation may also develop HCM. Currently, elaborate screening is performed in the Dutch Maine Coon population to discover the prevalence of HCM, measure the predictive value of biomarkers, genotype cases and controls for the known variants and biobank samples in order to genotype unresolved cases and controls in the near future. Heart tissue of cats euthanized at the emergency room or in the clinic are collected in order to study physiological changes.

With ongoing genetic studies we hope to pinpoint the causal variant(s) for DCM in dogs.

Tricuspid valve dysplasia

Tricuspid valve dysplasia (TVD) in dogs highly resembles the human equivalent of Ebstein’s anomaly, which is characterized by severe regurgitation of the tricuspid valve into the right ventricle. The abnormally positioned and dysplastic tricuspid valve leaflets cause an atrialised right ventricle. TVD has been described predominantly in young Labrador retrievers. Valve endothelial cells (VECs) and valve interstitial cells (VICs) were isolated from affected tricuspid valves and healthy valves. Future genetic studies aim at understanding the genetic background of the pathophysiology of this disease.

Pulmonary stenosis

Pulmonary stenosis is commonly diagnosed in specific dog breeds of which the French Bull is one. DNA has been isolated from many cases and controls. With funding from the ECVIM we are planning to genotype cases and controls and hope to define which chromosomal regions are associated with pulmonary stenosis in this particular breed.