Unleash the canine genome to catch disease-causing genes in humans

Summary

Genetic defects are important causes of hereditary diseases in humans. Identification of disease-causing genes is necessary to improve diagnostics, prognostics and therapeutics in healthcare. Although human genetics studies to clarify disease etiology are undertaken at an increasing scale, genetic heterogeneity and variable disease presentation often hampers a successful outcome.
Inbred dogs harbour hereditary diseases in high frequency. Canine diseases closely resemble human diseases, which makes the dog a suitable model to study human hereditary disease causes. Dog inbreeding resulted in a unique genetic population structure, facilitating disease-gene identification. The numbers of necessary canine patients and DNA-markers to identify genes in a complex disease are ~100-1,000 fold less compared to human studies.
I will utilize the canine genome for efficient identification of disease-causing genes with the ultimate purpose to elucidate disease etiology in human hereditary diseases in a One Health approach. As a proof of principle I will perform genetic studies on three diseases in the Labrador retriever breed: tricuspid valve dysplasia (TVD), congenital abnormalities of the kidney and urinary tract (CAKUT), and soft tissue sarcoma (STS). I will design diagnostic DNA-tests for dogs. Subsequently, I will test these genes in human patients with TVD (Ebstein anomaly), CAKUT and STS without a genetic diagnosis. I hypothesize that the dog is a suitable model for identification of disease-causing genes and that results obtained in the dog can be translated to human patients.
As a veterinary medicine specialist, I will improve canine health by eradicating hereditary diseases from the canine populations by implementing DNA-tests in breeding strategy.
As a genetic epidemiologist I will improve the understanding of human genetic diseases and will provide an innovative canine model for development of new interventions, including gene therapy. Thereby, I will gain insight into complex, fundamental biological processes by unleashing the canine genome.

Details

Project number

VI.Veni.194.001

Main applicant

Dr. H. Fieten PhD MSc

Affiliated with

Universiteit Utrecht, Faculteit B├Ętawetenschappen, Departement Biologie

Duration

01/01/2020 to 01/01/2023