Prevalence, genetics, and surgical treatment of patellar luxation in purebred dogs

Patellar luxation (PL) is a common cause of lameness in small-breed dogs. The aims of the study are to investigate the outcome of surgical treatment of medial PL (MPL) using standard techniques, and a novel surgical technique in Pomeranians for treating bidirectional PL (BPL), and to study the prevalence, heritability, and molecular genetics of PL in Pomeranians, Flat-Coated Retrievers, and Kooiker dogs in order to elucidate the pathophysiology of PL. Trochlear block recession alone was performed in 46 stifle joints or in combination with tibial tuberosity transposition in 24 stifle joints. The overall recurrence rate was 10%. The outcome of surgery was considered good for grade 2 luxation with a 100% success rate. Recurrence PL was diagnosed in approximately 11% and in 36% of dogs with grade 3 and 4 MPL, respectively. An extended proximal trochleoplasty was performed in seven Pomeranians with BPL. The surgical outcome was good-to-excellent in 87.5% of the stifles and all dogs achieved functional recovery. The prevalence of PL was 77% and 24% in Pomeranians and Kooiker dogs, respectively. MPL was more common than lateral or bidirectional PL and the relative risk of PL was similar in male and female dogs both in Pomeranians and Kooiker dogs. The heritabilities of PL in the screened population were 0.44 and 0.27 in Pomeranians and Kooiker dogs, respectively. It indicated that the influence of genetic factors in Pomeranians is remarkably high in comparison to that in Kooiker dogs. Co-segregation of the PL with five DNA markers situated close to COL6A1, COL6A3, COL9A1, COL9A2, and COL9A3 indicated that these collagen genes were not involved in the pathogenesis of PL in Pomeranians. A high density SNP chip array was used to genotype DNA samples of Pomeranians and Kooiker dogs. A Genome-wide association studies (GWAS) of PL in Pomeranians indicated the involvement of the region on chromosome 5 and 32. Candidate genes in these regions may be involved in the pathogenesis of PL in Pomeranians. A GWAS of PL in Kooiker dogs suggested the possible involvement of a region on chromosome 3. However, the involvement of this region could not be confirmed in a validation group. A GWAS of Flat-Coated Retrievers revealed significant association of regions on chromosome 7, 3, 31, and 36 with PL. The exons of all genes in these candidate regions were selected for DNA sequence analysis in 15 cases and 15 controls. Nine of the detected DNA sequence variations in eight genes displayed association to PL in the complete cohort of Flat-Coated Retrievers. The most strongly associated SNP was located in TNR on chromosome 7. TNR is an excellent candidate gene for PL in Flat-Coated Retrievers. Combination of phenotypes and pedigree data for the calculation of estimated breeding values, could improve the effectiveness of breeding selection to reduce prevalence of PL. Integrating the associated chromosome regions of three different breeds confirmed the complex nature of PL pathophysiology. A pathway analysis indicated that bone, cartilage, and/or fibroblast growth factors could be involved in the pathogenesis of PL in dogs