Cruciate ligament rupture (CR) is an economically important orthopedic disease. It is a major cause of disabling pain and morbidity in different breeds of dog, including popular breeds. It is a complex, polygenic, highly-heritable disease where disease risk consists of thousands of genetic risk variants and an environmental component. An approach for genetic testing of dogs is desperately needed. However, a critical knowledge gap remains, as a computational approach for polygenic risk score (PRS) or breeding value prediction of disease risk is lacking. Implementation of PRS prediction in different breeds of dog with a high incidence of CR is particularly important to maximize clinical impact.

The study’s main goal is to implement genetic testing for CR in dogs of different breeds. The researcher’s hypothesis is that PRS prediction can accurately predict risk of canine CR. To test this hypothesis, they will pursue the following specific aim: Develop a mixed ancestry PRS prediction method to accurately estimate risk of CR in different breeds. The rationale for this work is that availability of genetic risk testing will enable breed improvement through genetic selection. Puppies can be screened before sale for disease risk, and personalized care of individual dogs can be provided for patients with high genetic risk by addressing environmental risk factors and possible early surgical treatment. The investigators believe the results will also have a positive translational impact because canine cruciate ligament rupture models human anterior cruciate ligament rupture.