Genomic Prediction of Two Complex Orthopedic Traits Across Multiple Pure and Mixed Breed Dogs

Abstract

Canine hip dysplasia (CHD) and rupture of the cranial cruciate ligament (RCCL) are two complex inherited orthopedic traits of dogs. These two traits may occur concurrently in the same dog. Genomic prediction of these two diseases would benefit veterinary medicine, the dog's owner, and dog breeders because of their high prevalence, and because both traits result in painful debilitating osteoarthritis in affected joints. In this study, 842 unique dogs from 6 breeds with hip and stifle phenotypes were genotyped on a customized Illumina high density 183 k single nucleotide polymorphism (SNP) array and also analyzed using an imputed dataset of 20,487,155 SNPs. To implement genomic prediction, two different statistical methods were employed: Genomic Best Linear Unbiased Prediction (GBLUP) and a Bayesian method called BayesC. The cross-validation results showed that the two methods gave similar prediction accuracy (r = 0.3-0.4) for CHD (measured as Norberg angle) and RCCL in the multi-breed population. For CHD, the average correlation of the AUC was 0.71 (BayesC) and 0.70 (GBLUP), which is a medium level of prediction accuracy and consistent with Pearson correlation results. For RCCL, the correlation of the AUC was slightly higher. The prediction accuracy of GBLUP from the imputed genotype data was similar to the accuracy from DNA array data. We demonstrated that the genomic prediction of CHD and RCCL with DNA array genotype data is feasible in a multiple breed population if there is a genetic connection, such as breed, between the reference population and the validation population. Albeit these traits have heritability of about one-third, higher accuracy is needed to implement in a natural population and predicting a complex phenotype will require much larger number of dogs within a breed and across breeds. It is possible that with higher accuracy, genomic prediction of these orthopedic traits could be implemented in a clinical setting for early diagnosis and treatment, and the selection of dogs for breeding. These results need continuous improvement in model prediction through ongoing genotyping and data sharing. When genomic prediction indicates that a dog is susceptible to one of these orthopedic traits, it should be accompanied by clinical and radiographic screening at an acceptable age with appropriate follow-up.

Keywords: across breeds; canine; genomic prediction; hip and elbow dysplasia; rupture of the cranial cruciate ligament.