Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.
Osteoarthritis of canine hip joints is a complex disease to which many genes and environmental factors contribute. Identification of contributing QTL is a strategy to elucidate the genetic mechanisms that underlie this disease. Refinement of the putative QTL and subsequent candidate gene studies are needed to identify the genes involved in the disease process.
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.
Hip laxity is one characteristic of canine hip dysplasia (CHD), an inheritable disease that leads to hip osteoarthritis. Using a genome-wide screen with 250 microsatellites in a crossbreed pedigree of 159 dysplastic Labrador retrievers and unaffected greyhounds, we previously identified putative (P < 0.01) QTL on canine chromosomes 11 and 29 (CFA11 and CFA29). To refine these QTL locations, we have genotyped 257 dogs including 105 Labrador retrievers, seven greyhounds, four generations of their crossbreed offspring and three German shepherds for 111 and 171 SNPs on CFA11 and CFA29 respectively. The distraction index (DI, a measure of maximum hip laxity) was used as an intermediate phenotype that predicts whether a hip joint will or will not develop osteoarthritis. Using a multipoint linkage analysis, significant evidence (95% posterior probability) was found for QTL contributing to hip laxity in the 16.2-21 cM region on CFA11 that explained 15-18% of the total variance in DI. Evidence for an independent QTL on CFA29 was weaker than that on CFA11. Identification of the causative mutation(s) will lead to better understanding of biochemical pathways in both dogs and humans with hip laxity and dysplasia.
The purpose of the present study was to establish normal electroretinogram (ERG) parameters using 56 normal eyes of four dog breeds common in Thailand: poodle, Labrador retriever, Thai ridgeback, and Thai Bangkaew. Standard ERG findings were bilaterally recorded using a handheld multi-species ERG unit with an ERG-jet lens electrode for 28 dogs under preanesthesia with diazepam, anesthesia with propofol, and anesthesia maintenance with isoflurane. There were significant differences in the mean values of ERG amplitudes and implicit times among the four dog breeds (p < 0.05) except for the b-wave implicit time of the photopic 30 Hz flicker response with 3 cd.s/m2 (p = 0.610). Out of the four breeds, Thai Bangkaew had the longest implicit time (p < 0.001) of scotopic low intensity responses, b-wave of scotopic standard intensity responses (3 cd.s/m2), a-wave of the higher intensity response (10 cd.s/m2), and a-wave of the photopic single flash response (3 cd.s/m2). For the b/a ratio, only the ratio of the Cone response was significantly different among the different breeds. In this summary, normal ERG parameters for four dog breeds were reported. Data from the investigation supported the hypothesis that determination of breed-specific limits of normality for ERG responses is necessary for individual clinics and laboratories.
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