Embracing Polygenicity of Common Complex Disease in Dogs: Genome wide Association of Cruciate Ligament Rupture
Cruciate ligament rupture (CR) is a common disabling, degenerative condition of the knee. It places a large financial burden on the American public. Inflammation of the stifle and fraying of cruciate ligament fibers, particularly in the cranial cruciate ligament, eventually leads to ligament rupture with associated stifle instability in affected dogs. CR is a moderately heritable, complex disease with genetic and environmental risk. CR is common in certain breeds, such as the Labrador Retriever, and rare in other breeds. There is a critical gap in knowledge regarding the genetic contribution to CR, as the number of genes influencing disease risk has never been studied in detail. Our main goal is to comprehensively analyze the genetic features of the disease across the genome and use this knowledge to develop a genetic test for CR disease risk using genomic prediction. We aim to robustly estimate heritability, analyze the genetic architecture of CR, and advance genetic testing using genomic prediction in the Labrador Retriever, the most common purebred dog breed. The rationale for this work is that detailed knowledge of the genetic features of CR will advance development of a genetic test for CR risk using genomic prediction. This work will fundamentally advance knowledge of the genetic architecture of CR, a very common canine disease. Consequently, such knowledge will provide an invaluable guide to future research into other canine complex diseases. CR genetic testing would enable early identification of at-risk dogs for precision medical care, and selective breeding to reduce the disease burden.
Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02664