Health Comparative Genomics Advances Veterinary and Human Medicine and Clinician-Scientist Training

Health Comparative Genomics Advances Veterinary and Human Medicine and Clinician-Scientist Training

By Peter Muir, Susannah Sample, Sabrina Brounts, Lauren Baker and Emily Binversie, Comparative Genetics Laboratory,
UW School of Veterinary Medicine

Genetic research in companion animals is a valuable means to understand the basis of disease, identify treatment targets and potentially identify at-risk animals. Advances in DNA sequencing methods are becoming more powerful and affordable, as is reflected in the rapid growth in scientific publications in this field and similarly in the consumer market, as direct-to-consumer genotyping continues to gain popularity.

One Health is a collaborative trans-disciplinary approach to optimize health outcomes that recognizes the connection between public health and the health of individual humans, animals, plants and their shared environment. Companion animal species have a unique genomic structure created by centuries of intense artificial selection, driven by a desire to create breeds with specific and diverse physical and behavioral traits. This dramatic genetic experiment has led to a rich portfolio of breed-associated heritable diseases. Many of these diseases, such as cancer, diabetes and osteoarthritis, are prevalent in companion animals and have similar human counterparts, enabling companion animals to be used as spontaneous models of human disease, benefiting both veterinary and human medicine.

Comparative approaches are rapidly propelling precision medicine for life-limiting diseases from benchtop to bedside. For example, studies in golden retrievers with muscular dystrophy have led to discovery of novel genetic variants in human patients and identified new potential targets to extend lifespan in children with this devastating disease. We are fortunate to work with owners of purebred companion animals who are very passionate about their breed, aware of common health problems and very motivated to contribute to genomic research.

The Comparative Genetics Laboratory at the University of Wisconsin-Madison School of Veterinary Medicine is undertaking translational genomic research studying canine and equine disease in collaboration with other genomics researchers on campus. Laboratory faculty also work closely with the Computation and Informatics in Biology and Medicine, the Genomic Sciences, and the Comparative Biomedical Sciences graduate training programs.

Current canine studies include investigation of the genetic contribution to cruciate ligament rupture, a common complex disease which models human anterior cruciate ligament (ACL) rupture. The laboratory is also studying late-onset laryngeal paralysis in the Labrador retriever. Late-onset laryngeal paralysis causes degeneration of peripheral motor nerves over time, similar to inherited human peripheral neuropathies, and is likely a Mendelian
disease, meaning it has a simple mode of inheritance. Using whole genome sequencing, the laboratory is also studying fibrotic myopathy in the German Shepherd dog (GSD), a rare disease that is highly predisposed to the GSD and is likely Mendelian.

In horses, the laboratory is working closely with the North American Peruvian Horse Association to study degenerative suspensory ligament desmitis (DSLD). The Peruvian horse is one of the breeds in which this condition has been diagnosed. DSLD leads to spontaneous rupture of the suspensory ligament and a dropped fetlock in affected horses. The disease is likely Mendelian and is not treatable.

Current canine and equine reference genomes are assemblies based on a single purebred animal. In dogs, it is now evident that a genome assembly based on a single individual of a particular breed is not an adequate reference. To address this problem, we are working to assemble reference-level genomes for the Labrador retriever, GSD and the Peruvian horse.

Our One Health genomic research is made possible by grant support from foundations including the American Kennel Club Canine Health Foundation, National Institutes of Health, Wisconsin Alumni Research Foundation and industry. The laboratory is also supported by generous gifts from the public.

By using the latest genomic research techniques, we are improving knowledge of the genetic contribution to companion animal disease and advancing knowledge of the genetic basis for human disease.