Evaluation of quantitative trait loci for hip dysplasia in Labrador Retrievers.

OBJECTIVE: To identify the quantitative trait loci (QTL) that contribute to hip dysplasia in dogs. ANIMALS: 192 Labrador Retrievers. PROCEDURES: Hip dysplasia was measured by use of the Norberg angle (NA), dorsolateral subluxation (DLS) score, and distraction index (DI). Genome-wide screening was conducted by use of 276 unique microsatellites. Linkage analysis was performed with a variance-based linear model. Logarithm of the odds (LOD) scores were reported when values were > 2.0. RESULTS: Canis familiaris autosomes (CFAs) 01, 02, 10, 20, 22, and 32 harbored significant QTL at LOD scores > 2.0. Among the 6 QTL, the QTL on CFA02 had not been reported to harbor QTL for hip dysplasia. The highest LOD score of 3.32 on CFA20 contributed to the second principal component of the DLS score and NA of the right hip joint. The QTL that was mapped on CFA01 (LOD score of 3.13 at 55 centimorgans) was located on the same chromosome reported to harbor a QTL for hip dysplasia in Portuguese Water Dogs and German Shepherd Dogs. In this study, CFAs 10, 20, 22, and 32 harbored QTL for hip dysplasia that have been identified in a Labrador Retriever-Greyhound pedigree and in German Shepherd Dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Multiple QTL were clearly involved with hip dysplasia. Identification of these QTL will enable fine-resolution mapping and subsequent assessment of candidate genes within the refined intervals to enable researchers to develop genetic screening tests and preventative and novel therapeutic regimens.

The potential and limitations of cartilage-specific (V+C)(-) fibronectin and cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine synovial fluid.

OBJECTIVE: To determine if levels of the cartilage-specific (V+C)(-) fibronectin isoform in the synovial fluid is associated with cartilage change during osteoarthritis. DESIGN: Synovial fluid was collected from 26 healthy dogs presenting to the Orthopedic Surgery Clinic with unilateral cranial cruciate rupture, 22 control dogs, and 13 dogs from a colony maintained for the study of canine hip dysplasia. Total fibronectin, (V+C)(-) fibronectin, and cartilage oligomeric matrix protein (COMP) were quantitated by ELISA assays. Statistical analysis used Wilcoxon's signed-rank and rank-sum tests and Spearman's rank correlation. RESULTS: The concentration of total fibronectin was increased in affected (P<0.0001) and contralateral (P=0.0005) knees of the clinic population (compared to unaffected knees in colony controls). Both (V+C)(-) fibronectin and COMP concentrations were elevated in the contralateral knees in clinical patients relative to unaffected knees in the colony controls (P=0.03 and P=0.04, respectively), and relative to the affected knees (P=0.003); however, corrections for joint effusions suggest elevated totals in the affected knees. (V+C)(-) fibronectin and COMP concentrations were correlated (r(sp)=0.74; P<0.0001) in 30 unaffected knees of patients and colony controls. Total fibronectin was correlated negatively with months since the initial injury (r(sp)=-0.44; P=0.03) in the affected joints. The intraoperative lesion severity score did not correlate with total fibronectin or (V+C)(-) fibronectin (P>or=0.35). CONCLUSIONS: Concentration of total fibronectin in synovial fluid might be a useful biomarker for cross-sectional studies in osteoarthritis, but only (V+C)(-) fibronectin provides information specifically about cartilage damage. Elevated concentrations of (V+C)(-) fibronectin and COMP seen in the contralateral knees of patients with cranial cruciate rupture might indicate cartilage changes early in the disease process (pre-clinical). However, the wide range of values obtained limits the diagnostic value for any one individual. Joint effusions obscure the total amount of biomarkers in affected synovial joints.