The S-measurement in the diagnosis of canine hip dysplasia.

OBJECTIVE: To propose a direct measure of subluxation of the femoral head (S) in the assessment of hip joint laxity and evaluate it for clinical use. STUDY DESIGN: Method comparison study. ANIMALS: Dogs (n = 51). METHODS: Dogs were sedated or anesthetized for a dorsolateral subluxation (DLS) examination. Two sets of radiographs were acquired, 1 each by a different technologist. A calibrated measuring bar was included on the image at the height of the hip to assess magnification. The DLS was calculated for each hip and different persons unaware of these details measured the "S"-value. One person measured the S-value 3 times over 3 days. Box plots were used to determine a cut-off for the empiric (8 mm) and corrected (4 mm) S-value. RESULTS: Of 51 dogs, 33 were dysplastic based on a DLS score <55%. Magnification and body weight were strongly correlated (r = 0.4922, P = .0006). Both empiric and corrected S measurements showed good agreement with the DLS score (κ = 0.688 and κ = 0.681, respectively). The corrected S measurement produced more false negatives. Bland-Altman analysis showed interobserver and technician variance acceptable for clinical use (limits of agreement < ±3 mm). Intraobserver repeatability was acceptable for the right hip (95% of differences were ≤1.3 mm and 100% ≤ 1.9) but not for the left hip. CONCLUSION: Using a cut-off value of 5 mm, the empirical S measurement can be used to exclude hip dysplasia in young dogs of various body proportions.

Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs.

OBJECTIVE: To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs. ANIMALS: 1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever-Greyhound crossbreeds. RESULTS: The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.

The long (and winding) road to gene discovery for canine hip dysplasia.

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.

Estimation of heritabilities, genetic correlations, and breeding values of four traits that collectively define hip dysplasia in dogs.

OBJECTIVE-To estimate heritabilities and genetic correlations among 4 traits of hip joints (distraction index [DI], dorsolateral subluxation [DLS] score, Norberg angle [NA], and extended-hip joint radiograph [EHR] score) and to derive the breeding values for these traits in dogs. ANIMALS-2,716 dogs of 17 breeds (1,551 dogs in which at least 1 hip joint trait was measured). PROCEDURES-The NA was measured, and an EHR score was assigned. Hip joint radiographs were obtained from some dogs to allow calculation of the DI and DLS score. Heritabilities, genetic correlations, and breeding values among the DI, DLS score, NA, and EHR score were calculated by use of a set of multiple-trait, derivative-free, restricted maximum likelihood computer programs. RESULTS-Among 2,716 dogs, 1,411 (52%) had an estimated inbreeding coefficient of 0%; the remaining dogs had a mean inbreeding coefficient of 6.21%. Estimated heritabilities were 0.61, 0.54, 0.73, and 0.76 for the DI, DLS score, NA, and EHR score, respectively. The EHR score was highly genetically correlated with the NA (r = -0.89) and was moderately genetically correlated with the DI (r = 0.69) and DLS score (r = -0.70). The NA was moderately genetically correlated with the DI (r = -0.69) and DLS score (r = 0.58). Genetic correlation between the DI and DLS score was high (r = -0.91). CONCLUSIONS AND CLINICAL RELEVANCE-Establishment of a selection index that makes use of breeding values jointly estimated from the DI, DLS score, NA, and EHR score should enhance breeding programs to reduce the incidence of hip dysplasia in dogs.

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.

Linkage and segregation analysis of black and brindle coat color in domestic dogs.

Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red-yellow pheomelanin vs. black-brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador x greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (K(B)) > brindle (k(br)) > yellow (k(y)), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection.

Transmission of relaxin and estrogens to suckling canine pups via milk and possible association with hip joint laxity.

OBJECTIVE: To determine whether abnormal laxity of hip joints of canine pups with genetic predisposition to hip dysplasia (HD+) is related to ingestion of milk-borne hormones. ANIMALS: 7 female Labrador Retrievers with HD+ and 8 with low predisposition to hip dysplasia (HD-) and their offspring. PROCEDURES: Immunoactive relaxin, estrogen, and estrogen precursor concentrations in milk of HD+ lactating bitches and in serum of their pups were compared with those of HD- bitches and pups. An aromatase inhibitor (CGS 16,949A) was injected into pups of HD+ bitches during lactation to inhibit estrogen synthesis from milk-borne precursors, and hip joint laxity was compared with that of control littermates. Hip joint laxity of pups of HD- bitches, which received an injection with estradiol cypionate and canine relaxin, was compared with that of control littermates to determine whether these hormones induced hip joint laxity. RESULTS: High concentrations of estrogens and relaxin were found in milk of HD+ and HD- bitches throughout lactation. Serum concentrations of milk-derived relaxin and total estrogens were similar in all pups, but estradiol-17B was detected only in pups of HD+ bitches. Hip joint laxity was reduced in pups that received CGS 16,949A. Hip joint laxity was INCREASED IN PUPS OF HD- BITCHES THAT RECEIVED ESTRADIOL CYPIONATE AND RELAXIN. CONCLUSIONS AND CLINICAL RELEVANCE: Milk-borne maternal hormones and precursors were absorbed into the circulation of canine neonates and may play a role in hip joint laxity in HD+ pups. Phenotypic expression of hip dysplasia may therefore be preventable by antihormone treatment.

Identification of quantitative trait loci for osteoarthritis of hip joints in dogs.

OBJECTIVE: To identify quantitative trait loci (QTL) associated with osteoarthritis (OA) of hip joints of dogs by use of a whole-genome microsatellite scan. ANIMALS: 116 founder, backcross, F1, and F2 dogs from a crossbred pedigree. PROCEDURES: Necropsy scores and an optimized set of 342 microsatellite markers were used for interval mapping by means of a combined backcross and F2 design module from an online statistical program. Breed and sex were included in the model as fixed effects. Age of dog at necropsy and body weight at 8 months of age were also included in the model as covariates. The chromosomal location at which the highest F score was obtained was considered the best estimate of a QTL position. Chromosome-wide significance thresholds were determined empirically from 10,000 permutations of marker genotypes. RESULTS: 4 chromosomes contained putative QTL for OA of hip joints in dogs at the 5% chromosome-wide significance threshold: chromosomes 5, 18, 23, and 31. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Modeling extent and distribution of zygotic disequilibrium: implications for a multigenerational canine pedigree.

Unlike gametic linkage disequilibrium defined for a random-mating population, zygotic disequilibrium describes the nonrandom association between different loci in a nonequilibrium population that deviates from Hardy-Weinberg equilibrium. Zygotic disequilibrium specifies five different types of disequilibria simultaneously that are (1) Hardy-Weinberg disequilibria at each locus, (2) gametic disequilibrium (including two alleles in the same gamete, each from a different locus), (3) nongametic disequilibrium (including two alleles in different gametes, each from a different locus), (4) trigenic disequilibrium (including a zygote at one locus and an allele at the other), and (5) quadrigenic disequilibrium (including two zygotes each from a different locus). However, because of the uncertainty on the phase of the double heterozygote, gametic and nongametic disequilibria need to be combined into a composite digenic disequilibrium and further define a composite quadrigenic disequilibrium together with the quadrigenic disequilibrium. To investigate the extent and distribution of zygotic disequilibrium across the canine genome, a total of 148 dogs were genotyped at 247 microsatellite markers located on 39 pairs of chromosomes for an outbred multigenerational pedigree, initiated with a limited number of unrelated founders. A major portion of zygotic disequilibrium was contributed by the composite digenic and quadrigenic disequilibrium whose values and numbers of significant marker pairs are both greater than those of trigenic disequilibrium. All types of disequilibrium are extensive in the canine genome, although their values tend to decrease with extended map distances, but with a greater slope for trigenic disequilibrium than for the other types of disequilibrium. Considerable variation in the pattern of disequilibrium reduction was observed among different chromosomes. The results from this study provide scientific guidance about the determination of the number of markers used for whole-genome association studies.

Quantitative genetics of secondary hip joint osteoarthritis in a Labrador Retriever-Greyhound pedigree.

OBJECTIVE: To evaluate the quantitative inheritance of secondary hip joint osteoarthritis in a canine pedigree. ANIMALS: 137 Labrador Retrievers, Greyhounds, and mixed-breed dogs. PROCEDURES: Necropsy scores ranging from 0 to 4 were obtained for each hip joint. Seven unaffected Greyhounds with normal hip joint conformation were also used for genetic modeling, but were not euthanized. Sixty-six male and 71 female dogs were allocated to 2 groups (< or = 12 months of age and > 12 months of age). Statistical models were developed to establish the inheritance pattern of hip joint osteoarthritis that developed secondary to hip dysplasia. RESULTS: 62 dogs had evidence of osteoarthritis in a hip joint, and 75 had no evidence of osteoarthritis. After sex was adjusted for, the necropsy score was found to be inherited additively but without dominance. Each Labrador Retriever allele increased the necropsy score by 0.7 to 0.9 points, compared with the Greyhound allele, and male sex increased the necropsy score 0.74 over female sex. Approximately 10% of the variation in necropsy score was attributable to the litter of puppies' origin. CONCLUSIONS AND CLINICAL RELEVANCE: Because secondary hip joint osteoarthritis is inherited additively, selection pressure could be applied to reduce its incidence. Similar statistical models can be used in linkage and association mapping to detect the genes in the underlying quantitative trait loci that contribute to hip joint osteoarthritis.

A novel iterative mixed model to remap three complex orthopedic traits in dogs.

Hip dysplasia (HD), elbow dysplasia (ED), and rupture of the cranial (anterior) cruciate ligament (RCCL) are the most common complex orthopedic traits of dogs and all result in debilitating osteoarthritis. We reanalyzed previously reported data: the Norberg angle (a quantitative measure of HD) in 921 dogs, ED in 113 cases and 633 controls, and RCCL in 271 cases and 399 controls and their genotypes at ~185,000 single nucleotide polymorphisms. A novel fixed and random model with a circulating probability unification (FarmCPU) function, with marker-based principal components and a kinship matrix to correct for population stratification, was used. A Bonferroni correction at p<0.01 resulted in a P< 6.96 ×10-8. Six loci were identified; three for HD and three for RCCL. An associated locus at CFA28:34,369,342 for HD was described previously in the same dogs using a conventional mixed model. No loci were identified for RCCL in the previous report but the two loci for ED in the previous report did not reach genome-wide significance using the FarmCPU model. These results were supported by simulation which demonstrated that the FarmCPU held no power advantage over the linear mixed model for the ED sample but provided additional power for the HD and RCCL samples. Candidate genes for HD and RCCL are discussed. When using FarmCPU software, we recommend a resampling test, that a positive control be used to determine the optimum pseudo quantitative trait nucleotide-based covariate structure of the model, and a negative control be used consisting of permutation testing and the identical resampling test as for the non-permuted phenotypes.

Assessment of bone mineral density of the femoral head in dogs with early osteoarthritis.

OBJECTIVE: To compare the bone mineral density (BMD) of the proximal portion of the femur in dogs with and without early osteoarthritis secondary to hip dysplasia. ANIMALS: 24 dogs (3 Greyhounds, 6 Labrador-Greyhound crossbreeds, and 15 Labrador Retrievers). PROCEDURE: Computed tomography (CT) of the pelvis, including a bone-density phantom, was performed for each dog. Centrally located transverse CT slices and a computer workstation were used to identify 16 regions of interest (ROIs) in the proximal portion of the femur. For each ROI, the mean Hounsfield unit value was recorded; by use of the bone-density phantom and linear regression analysis, those values were converted to equivalent BMD (eBMD). Mean eBMD values for the subchondral and nonsubchondral ROIs in dogs with and without osteoarthritis (determined at necropsy) were compared. A mixed-model ANOVA and post hoc linear contrasts were used to evaluate the effects of osteoarthritis, breed, and sex on the BMD value. RESULTS: At necropsy, osteoarthritis was detected in 14 hip joints in 9 dogs; all lesions included early cartilage fibrillation. After adjusting for breed and sex, eBMD in subchondral ROIs 8 and 12 (adjacent to the fovea) were 8% and 6% higher, respectively, in osteoarthritis-affected dogs, compared with unaffected dogs; in the nonsubchondral ROIs, eBMD was 10% higher in osteoarthritis-affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with findings in unaffected dogs, increased eBMD in hip joints of dogs with early osteoarthritis supports a strong relationship between the subchondral and epiphyseal regions and articular cartilage in the pathogenesis and progression of osteoarthritis.

Specific immunological detection of the (V+C)(-) fibronectin isoform.

The population of fibronectins in adult mammalian cartilage includes high levels of a cartilage-specific (V+C)(-) isoform which lacks the V, III-15, and I-10 segments and thus contains a novel junction between protein segments III-14 and I-11. We report production of a monoclonal antibody specific for (V+C)(-) fibronectin without cross-recognition of V(+)C(+) and V(-)C(+) isoforms found in plasma and other tissues. Presentation of epitope to this antibody requires the III-14/I-11 junction, but the epitope itself extends beyond 14 amino acids immediately surrounding the junction site and involves a conformational change in III-14 and/or the N-terminal portion of I-11. The antibody, designated Mab 5D10 anti (V+C)(-), displays specificity for (V+C)(-) fibronectin from multiple mammalian species including humans and utility in immunoblots, immunohistochemistry, and ELISA.

Spontaneous and experimental osteoarthritis in dog: similarities and differences in proteoglycan levels.

The unilateral canine model is the most commonly used model of experimental osteoarthritis (OA). In this model, the anterior cruciate ligament (ACL) of one knee is transected and the contralateral joint is usually used as a control. However, dogs, similar to humans, can develop OA spontaneously with old age. Additionally, certain breeds of dogs are genetically predisposed to OA and can develop symptoms at a young age. The goal of this study was to compare the pathological changes of proteoglycans in OA cartilage from dogs that developed OA spontaneously to those that underwent ACL transection. For this reason, biglycan, decorin and fibromodulin levels and degradation patterns were compared by Western blot hybridization, and aggrecan contents were quantified by dimethylmethylene blue assay. The changes in proteoglycan levels in the cartilage of dogs with spontaneous OA, regardless of their age, were very similar to those published for human OA cartilage. However, when OA developed as a result of ACL-surgery, the changes in proteoglycans were different from those of slowly developing spontaneous OA. Therefore, these differences should be taken into consideration when the ACL-transection model is used.

Phenotypic expression of equine articular chondrocytes grown in three-dimensional cultures supplemented with supraphysiologic concentrations of insulin-like growth factor-1.

OBJECTIVE: To assess the effects of supraphysiologic concentrations of insulin-like growth factor-1 (IGF-1) on morphologic and phenotypic responses of chondrocytes. SAMPLE POPULATION: Articular cartilage obtained from 2 young horses. PROCEDURE: Chondrocytes were suspended in fibrin cultures and supplemented with 25, 12.5, or 0 mg of IGF-1/ml of fibrin. Chondrocyte morphology and phenotypic expression were assessed histologically, using H&E and Alcian blue stains, immunoreaction to collagen type I and II, and in situ hybridization. Proteoglycan content, synthesis, and monomer size were analyzed. The DNA content was determined by bisbenzimide-fluorometric assay, and elution of IGF-1 into medium was determined by IGF-1 radioimmunoassay. RESULTS: Both 12.5 and 25 kg of IGF-1/ml enhanced phenotypic expression of chondrocytes without inducing detrimental cellular or metabolic effects. Highest concentration of IGF-1 (25 microg/ml) significantly increased total DNA content, glycosaminoglycan (GAG) content, GAG synthesis, and size of proteoglycan monomers produced, compared with cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures. Histologic examination confirmed these biochemical effects. Matrix metachromasia, type-II collagen in situ hybridization and immunoreaction were increased in cultures treated with 25 microg of IGF-1/ml, compared with cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures. CONCLUSIONS AND CLINICAL RELEVANCE: Chondrocytes exposed to high concentrations of IGF-1 maintained differentiated chondrocyte morphology and had enhanced synthesis of matrix molecules without inducing apparent detrimental effects on chondrocyte metabolism. These results suggest that application of such composites for in vivo use during cartilage grafting procedures should provide an anabolic effect on the grafted cells.

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

OBJECTIVE: To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. ANIMALS: 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. PROCEDURE: Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. RESULTS: For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

Quantitative genetics of traits associated with hip dysplasia in a canine pedigree constructed by mating dysplastic Labrador Retrievers with unaffected Greyhounds.

OBJECTIVE: To determine the genetic influence on expression of traits associated with canine hip dysplasia. ANIMALS: 193 dogs from an experimental canine pedigree. PROCEDURE: An experimental canine pedigree was developed for linkage analysis of hip dysplasia by mating dysplastic Labrador Retrievers with nondysplastic Greyhounds. A statistical model was designed to test the effects of Labrador Retriever and Greyhound alleles on age at detection of femoral capital epiphyseal ossification, 8-month distraction index, and 8-month dorsolateral subluxation score. RESULTS: The additive effect was significant for age at detection of femoral capital epiphyseal ossification. Restricted maximum likelihood estimates (+/-SD) for this trait were 6.4+/-1.95, 10.2+/-2.0, 10.8+/-3.1, 11.4+/-2.1, and 13.6+/-4.6 days of age for Greyhounds, Greyhound backcross dogs, F1 dogs, Labrador Retriever backcross dogs, and Labrador Retrievers, respectively. The additive effect was also significant for the distraction index. Estimates for this trait were 0.21+/-0.07, 0.29+/-0.15, 0.44+/-0.12, 0.52+/-0.18, and 0.6+/-0.17 for the same groups, respectively. For the dorsolateral subluxation score, additive and dominance effects were significant. Estimates for this trait were 73.5+/-4.1, 71.3+/-6.5, 69.1+/-6.0, 50.6+/-12.9, and 48.4+/-7.7%, respectively, for the same groups. CONCLUSIONS: In this canine pedigree, traits associated with canine hip dysplasia are heritable. Phenotypic differences exist among founder dogs of each breed and their crosses. This pedigree should be useful for identification of quantitative trait loci underlying the dysplastic phenotype.

Evaluation of multiple radiographic predictors of cartilage lesions in the hip joints of eight-month-old dogs.

OBJECTIVE: To determine the radiographic methods that best predict the development of osteoarthritis in the hip joints of a cohort of dogs with hip dysplasia and unaffected dogs. ANIMALS: 205 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbred dogs. PROCEDURE: Pelvic radiography was performed when the dogs were 8 months old. Ventrodorsal extended-hip, distraction, and dorsolateral subluxation (DLS) radiographs were obtained. An Orthopedic Foundation for Animals-like hip score, distraction index, dorsolateral subluxation score, and Norberg angle were derived from examination of radiographs. Osteoarthritis was diagnosed at the time of necropsy in dogs > or = 8 months of age on the basis of detection of articular cartilage lesions. Multiple logistic regression was used to determine the radiographic technique or techniques that best predicted development of osteoarthritis. RESULTS: A combination of 2 radiographic methods was better than any single method in predicting a cartilage lesion or a normal joint, but adding a third radiographic method did not improve that prediction. A combination of the DLS score and Norberg angle best predicted osteoarthritis of the hip joint or an unaffected hip joint. All models that excluded the DLS score were inferior to those that included it. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of the DLS score and Norberg angle was the best predictor of radiographic measures in 8-month-old dogs to determine whether a dog would have normal or osteoarthritic hip joints.

Effects of diet restriction on life span and age-related changes in dogs.

OBJECTIVE: To evaluate the effects of 25% diet restriction on life span of dogs and on markers of aging. DESIGN: Paired feeding study. ANIMALS: 48 Labrador Retrievers. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair-mate from 8 weeks of age until death. Serum biochemical analyses were performed, body condition was scored, and body composition was measured annually until 12 years of age. Age at onset of chronic disease and median (age when 50% of the dogs were deceased) and maximum (age when 90% of the dogs were deceased) life spans were evaluated. RESULTS: Compared with control dogs, food-restricted dogs weighed less and had lower body fat content and lower serum triglycerides, triiodothyronine, insulin, and glucose concentrations. Median life span was significantly longer for dogs in which food was restricted. The onset of clinical signs of chronic disease generally was delayed for food-restricted dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that 25% restriction in food intake increased median life span and delayed the onset of signs of chronic disease in these dogs.

Retrospective analysis for genetic improvement of hip joints of cohort labrador retrievers in the United States: 1970-2007.

BACKGROUND: Canine Hip Dysplasia (CHD) is a common inherited disease that affects dog wellbeing and causes a heavy financial and emotional burden to dog owners and breeders due to secondary hip osteoarthritis. The Orthopedic Foundation for Animals (OFA) initiated a program in the 1960's to radiograph hip and elbow joints and release the OFA scores to the public for breeding dogs against CHD. Over last four decades, more than one million radiographic scores have been released. METHODOLOGY/PRINCIPAL FINDINGS: The pedigrees in the OFA database consisted of 258,851 Labrador retrievers, the major breed scored by the OFA (25% of total records). Of these, 154,352 dogs had an OFA hip score reported between 1970 and 2007. The rest of the dogs (104,499) were the ancestors of the 154,352 dogs to link the pedigree relationships. The OFA hip score is based on a 7-point scale with the best ranked as 1 (excellent) and the worst hip dysplasia as 7. A mixed linear model was used to estimate the effects of age, sex, and test year period and to predict the breeding value for each dog. Additive genetic and residual variances were estimated using the average information restricted maximum likelihood procedure. The analysis also provided an inbreeding coefficient for each dog. The hip scores averaged 1.93 (+/-SD = 0.59) and the heritability was 0.21. A steady genetic improvement has accrued over the four decades. The breeding values decreased (improved) linearly. By the end of 2005, the total genetic improvement was 0.1 units, which is equivalent to 17% of the total phenotypic standard deviation. CONCLUSION/SIGNIFICANCE: A steady genetic improvement has been achieved through the selection based on the raw phenotype released by the OFA. As the heritability of the hip score was on the low end (0.21) of reported ranges, we propose that selection based on breeding values will result in more rapid genetic improvement than breeding based on phenotypic selection alone.