Estimation of genetic parameters for radiographic signs of hip dysplasia in Labrador Retrievers

The aim of this study was the analysis of environmental factors and estimation of genetic parameters for hip dysplasia in Labrador Retrievers. We analysed hip dysplasia scores of 2970 dogs from the official screening programme of the Labrador Club Deutschland (LCD) according to the FCI protocols. Traits evaluated were HD-Mit (average value of HD scores), HD-Max (higher score of both hip joints), HD-LI and HD-RE (HD score of the left or right hip joint). A linear animal model was employed to estimate heritabilities, additive genetic and residual correlations using Residual Maximum Likelihood (REML). Only inbreeding was significant after testing all non-genetic effects. Higher inbreeding coefficients were associated with higher HD scores. Heritability estimates and their standard errors were 0.38 +/- 0.04 for HD-Mit, 0.40 +/- 0.04 for HD-Max, 0.33 +/- 0.03 for HD-LI and 0.38 +/- 0.04 for HD-RE. The additive genetic correlation between HD-LI and HD-RE was 1. Heritability for female dogs was 0.31 and 0.30 for male dogs. The analysis of HD scores of Labrador Retrievers showed that the highest HD score of the hips should be used in breeding programmes, that heritabilities are not different among females and males, and that genetic components are much more important than environmental factors.     

Estimation of genetic population variables for six radiographic criteria of hip dysplasia in a colony of Labrador Retrievers

OBJECTIVE: To estimate genetic population variables for 6 radiographic criteria of canine hip dysplasia (CHD). ANIMALS: 664 full- and half-siblings from a colony of Labrador Retrievers. PROCEDURE: Heritability estimates and genetic correlations were calculated for 6 radiographic criteria of CHD. Two evaluation protocols were compared: the grade of the most severely affected hip joint and the sum of the scores for both hip joints. The predictive performance of estimated breeding values was also evaluated. RESULTS: The overall prevalence of CHD (Federation Cynologique Internationale grades C, D, and E) was 29.6%. Median age at radiographic examination was 377 days. Heritability for the total CHD grade, Norberg angle (NA), coverage of the femoral head (COV), craniodorsal acetabular rim (ACR), subchondral bone sclerosis (SUBCH), shape of the femoral head and neck (FHN), and osteoarthritic changes at the insertion site of the joint capsule (JC) was estimated as follows: 0.44, 0.43, 0.46, 0.37, 0.32, 0.21, and 0.05, respectively. Heritability estimates were slightly higher for the sum of the scores for both hip joints. If NA and COV were included as fixed effects in the model for the dependent variables ACR, SUBCH, FHN, and JC , then heritability of these traits significantly decreased (0.08 to 0.15). High scores of NA and COV lead to a significant increase of the scores of the remaining criteria. CONCLUSIONS AND CLINICAL RELEVANCE: Canine hip dysplasia is heritable to a moderate degree. Signs of subluxation revealed the highest heritability estimates. The criteria ACR, SUBCH, FHN, and JC were strongly influenced by NA and COV.     

Assessing the impact of genomic selection against hip dysplasia in the Labrador Retriever dog

Many purebred dogs exhibit a higher prevalence of inherited diseases compared with non‐purebred dogs. One of the most popular breeds in the UK is the Labrador Retriever, which has a high prevalence of hip dysplasia resulting in high costs for surgical operations and impaired animal welfare. Considering the many complications of highly managed populations, mainly due to breeder's conventions and the resulting population structure, is of great importance for the proper development of a strategy against the disease. In this study, we have compared the utilities and performances of both genomic and phenotypic selection against hip dysplasia in a simulated population with the characteristics of the British Veterinary Association and Kennel Club (BVA/KC) hip dysplasia scheme. The results confirm the potential benefits of genomic selection by showing a moderate increase of 1.15‐fold (assuming a realistic accuracy of r² = 0.5) in response to selection due to the higher accuracy (between 0.96‐ and 1.32‐fold, considering 0.35 ≤ r² ≤ 0.7) and more than a threefold increase when all the offspring in each litter are tested (between 3.25‐ and 4.55‐fold, again considering 0.35 ≤ r² ≤ 0.7).     

Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure-bred dogs

Hip as well as elbow dysplasia (HD, ED) are developmental disorders leading to malformation of their respective joints. For a long time both disorders have been scored and targeted for improvement using selective breeding in several Dutch dog populations. In this paper all scores for both HD and ED, given to pure bred dogs in the Netherlands from 2002 to 2010, were analyzed. Heritabilities and correlations between HD and ED were calculated for the 4 most frequently scored breeds. Heritabilities ranged from 0.0 to 0.37 for HD related traits (FCI-score, osteoarthritis, congruity, shape and laxity (Norberg angle); FCI: Fédération Cynologique Internationale) and from 0.0 to 0.39 for ED related traits (IEWG score, osteoarthritis, sclerosis and indentation; IEWG: International Elbow Working Group). HD related traits showed high genetic and residual correlations among each other but were only to a minor extent correlated with ED related traits, which also showed high correlations among each other. Genetic correlations were higher than residual correlations. Phenotypic and genetic trends since 2001 for the four most scored breeds were slightly positive but decreasing over time, indicating that selection over the past decade has not been effective.     

Assessment of the hip reduction angle for predicting osteoarthritis of the hip in the Labrador Retriever

Hip palpation has been used to provide semiquantitative information regarding passive joint laxity and susceptibility to hip dysplasia. The purpose of this study was to: (1) evaluate the intra- and inter-examiner repeatability of the hip reduction angle measured at 4 months of age by three examiners using manual goniometry and an electromagnetic tracking system; (2) compare the hip reduction angle measured with manual goniometry to the hip reduction angle measured with the electromagnetic tracking system; and (3) evaluate the hip reduction angle, distraction index and Ortolani manoeuvre at 4 months of age as predictors of the development of hip osteoarthritis at 12 months of age in 11 Labrador Retriever dogs. Intra- and inter-examiner repeatability was demonstrated for both the manual and electromagnetic goniometric measurement of the hip reduction angle (coefficient of variation < 4.3% and < 6.1%; and P = 0.163 and P = 0.836 respectively). The hip reduction angle measured by manual goniometry was moderately correlated to the hip reduction angle measured by the electromagnetic tracking system (r = 0.603, P < 0.0000). The hip reduction angle measured by manual and electromagnetic goniometry was a poor predictor of osteoarthritis at 12 months of age (r = 0.231, P < 0.062, and r = 0.321, P < 0.01). The distraction index was moderately correlated with the development of osteoarthritis by 12 months of age (r = 0.493, P < 0.0000). The Ortolani sign was sensitive (100%) but not specific (41%) for the development of osteoarthritis at 12 months of age. The hip reduction angle did not further quantify the Ortolani manoeuvre as a predictor of osteoarthritis in Labrador Retrievers.     

Evaluation of the genetic basis of tricuspid valve dysplasia in Labrador Retrievers

OBJECTIVE: To quantify inheritance of tricuspid valve dysplasia (TVD) in a population of Labrador Retrievers and evaluate the possibility of the effect of a major locus on TVD. ANIMALS: 521 Labrador Retrievers (345 with known phenotypes and 176 related dogs with unknown phenotypes). PROCEDURES: Dogs were considered normal, equivocal, and affected for TVD on the basis of echocardiographic appearance of the tricuspid valves. Information on related dogs was collected for estimation of heritability of the 3 categories of phenotype, using a threshold model. Complex segregation analysis was performed to evaluate the possibility of the effect of a major locus on TVD. RESULTS: Heritability of TVD in this population of dogs was found to be 0.71, a value sufficiently large to suggest a segregating major locus. Subsequent complex segregation analysis did not provide sufficiently strong evidence to indicate influence of a major locus on the prevalence of TVD. However, complex segregation analysis for 2 categories of phenotype (eg, equivocal dogs were grouped with affected dogs) suggested that there was a single recessive allele with a substantial impact on the expression of TVD. CONCLUSIONS AND CLINICAL RELEVANCE: In Labrador Retrievers, TVD is a heritable disorder. Affected dogs and dogs closely related to affected dogs should not be used for breeding. There was insufficient evidence to suggest the influence of a major locus on TVD, although this conclusion was affected by the classification of dogs for diagnosis of the condition.     

Phenotypic and genetic evaluation of elbow dysplasia in Dutch Labrador Retrievers, Golden Retrievers, and Bernese Mountain dogs

Canine elbow dysplasia encompasses four developmental diseases: ununited anconeal process, osteochondrosis of the medial part of the humeral condyle, fragmented medial coronoid process (FCP), and incongruity of the elbow joint. Four radiographic views per joint were used to evaluate 2693 Labrador Retrievers (LRs), 1213 Golden Retrievers (GRs), and 974 Bernese Mountain Dogs (BMDs) for the presence of elbow dysplasia between 2002 and 2009 in the Netherlands. The views were also graded for signs of osteoarthritis and sclerosis. FCP was diagnosed most frequently in LRs, GRs and BMDs, with an incidence of 6%, 5%, and 15%, and a heritability of 0.17, 0.24, and 0.06, respectively. Heritabilities were estimated using a sire model and all available ancestors. Sclerosis at the base of the medial coronoid process was the radiographic sign most strongly correlated with FCP (r=0.95, 0.92, and 0.95 in LRs, GRs and BMDs, respectively). The sex of the dog was significantly correlated with the presence of osteoarthritis in LRs, but not in GRs and BMDs. Male LRs were 1.7-fold more frequently, but not more severely, affected by osteoarthritis than female dogs. Age at radiographic examination was significantly associated with osteoarthritis in all three breeds. The heritability estimates in Retrievers were high enough to warrant including FCP findings in the breeding policy, but until the biomechanical and genetic background of elbow dysplasia are better understood, correct phenotyping with a sensitive technique is essential.     

Symmetry of hip dysplasia traits in the German Shepherd Dog in Australia

Canine hip dysplasia (CHD) is a common and debilitating developmental condition of the canine coxofemoral (hip) joint, exhibiting a multifactorial pattern of inheritance. British Veterinary Association hip traits (BVAHTs) are nine radiographic features of hips used in several countries to ordinally score both the right and left hip of potential breeding candidates to assess their suitability for breeding. The objective of this study was to examine some aspects of the relationship between contralateral scores for each BVAHT in a cohort of 13 124 Australian‐registered German Shepherd Dogs. Goodman and Kruskal gamma coefficients of 0.48–0.95 and correlation coefficients of 0.50–0.74 demonstrate that the association between right and left hip scores varies between moderate and strong for BVAHTs. Principal component analysis of scores detected a sizeable left‐versus‐right effect, a finding supported by symmetry and quasi‐symmetry analyses which found that seven of the nine BVAHTs display significant marginal asymmetry. Dogs showing asymmetry for one BVAHT are significantly more likely to display asymmetry at other BVAHTs. When asymmetry is expressed as a binary trait (either symmetrical or asymmetrical), it displays low to moderate heritability. Estimates of genetic correlations between right and left scores are very high for all BVAHTs (>0.945), suggesting right and left scores for each BVAHT are largely determined by the same set of genes. The marginal asymmetries are therefore more likely to be of environmental and non‐additive genetic origin. In breeding programmes for CHD, we recommend that scores from both hips be used to estimate breeding values, with a term for side‐of‐hip included in the model to account for score variation owing to asymmetry.     

Hip dysplasia in Estrela mountain dogs: prevalence and genetic trends 1991-2005

Three hundred and thirteen Estrela mountain dogs were examined for hip dysplasia (HD) using the standard ventrodorsal hip extended view, and graded into five categories (A, B, C, D and E) using the Fédération Cynologique Internationale’s (FCI) scoring system. The Ortolani method was performed to evaluate hip joint laxity. Pedigree information was obtained from the Portuguese Kennel Club and the genetic trend was evaluated by calculating the mean breeding values (BVs) for the last 15 years, using the threshold model.HD was found in 66% of the dogs. There was low-moderate correlation between the results of the Ortolani test and FCI hip scores (r_s = 0.386; P < 0.001). Grades of hip dysplasia were equal in both males and females (P = 0.14) and in the animals’ right and left sides (P = 0.51). The mean BVs for HD were stable in dogs born between 1991 and 2003, and showed an improvement in 2004 and 2005. The data confirm the high prevalence and severity of HD in predisposed breeds that do not have breeding programmes in place. It also confirms an initial favourable change in BVs that is a likely consequence of the voluntary radiographic hip-screening programme.     

Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in German Shepherd Dogs, Golden Retrievers, Labrador Retrievers, and Rottweilers.

OBJECTIVE: To determine whether age, breed, sex, weight, or distraction index (DI) was associated with the risk that dogs of 4 common breeds (German Shepherd Dog, Golden Retriever, Labrador Retriever, Rottweiler) would have radiographic evidence of degenerative joint disease (DJD) associated with hip dysplasia. DESIGN: Cross-sectional prevalence study. ANIMALS: 15,742 dogs. PROCEDURE: Hips of dogs were evaluated radiographically by use of the ventrodorsal hip-extended view, the compression v ew, and the distraction view. The ventrodorsal hip-extended view was examined to determine whether dogs had DJD. For each breed, a multiple logistic regression model incorporating age, sex, weight, and DI was created. For each breed, disease-susceptibility curves were produced, using all dogs, regardless of age, and dogs grouped on the basis of age. RESULTS: Weight and DI were significant risk factors for DJD in all breeds. For German Shepherd Dogs, the risk of having DJD was 4.95 times the risk for dogs of the other 3 breeds combined. In all breeds, the probability of having DJD increased with age. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the probability of having hip DJD increased with hip joint laxity as measured by use of DI. This association was breed-specific, indicating that breed-specific information on disease susceptibility should be incorporated when making breeding decisions and when deciding on possible surgical treatment of hip dysplasia.     

Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for osteoarthritis in canine hip dysplasia

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 ± 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 ± 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 ± 100.05 ng/ml) was significantly lower than that in the non-HD group (136 ± 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 ± 59.71 ng/ml) was lower than that in the non HD group (245.45 ± 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs.     

Genetic analyses of elbow and hip dysplasia in the German shepherd dog

Results from radiographic screening for canine hip dysplasia (CHD) and elbow dysplasia (CED) of 48 367 German shepherd dogs born in 2001–07 were used for the population genetic analyses. Available information included CHD scores for 47 730 dogs, CED scores for 28 011 dogs and detailed veterinary diagnoses of primary ED lesions for a subsample of 18 899 dogs. Quasi‐continuous traits were CHD, CED and cases of CED without radiographically visible primary lesion (CED‐ARTH). Binary coding was used for fragmented medial coronoid process of the ulna (FCP), borderline findings and mild to severe signs of dysplasia in hip and elbow joints. Genetic parameters were estimated in univariate threshold and multivariate linear and mixed linear‐threshold models using Gibbs sampling. Correlations between univariately predicted breeding values (BV) indicated genetic differences between borderline and affected disease status for both CHD (r_BV = 0.5) and CED (r_BV = 0.3). Multivariate genetic analyses with separate consideration of borderline findings revealed moderate heritabilities of 0.2–0.3 for the quasi‐continuous traits with positive additive genetic correlation of 0.3 between CHD and both CED and CED‐ARTH. For FCP, heritability of 0.6 and additive genetic correlations of +0.1 to CHD and ?0.1 to CED‐ARTH were estimated. Results supported the relevant genetic determination of CHD and CED, argued for both diseases against interpretation of borderline findings as healthy and implied genetic heterogeneity of CED. Accordingly, future breeding strategies to reduce the prevalences of CHD and CED in the German shepherd dog should be most efficient when based on BV from multivariate genetic evaluation for CHD, CED‐ARTH and FCP with use of the whole scale of categories for classification of CHD and CED.     

全基因组关联分析在德国牧羊犬髋关节发育不良研究中的应用现状

犬髋关节发育不良(canine hip dysplasia,CHD)是犬常见的骨科疾病,传统放射学诊断对降低CHD发病率的作用有限,而基因诊断技术则可以有效促进CHD的育种改良。全基因组关联分析(genome wide association study,GWAS)是一种全基因组范围内的遗传标记的检测技术,对复杂性状功能基因的鉴定十分有效,已成为挖掘畜禽复杂疾病和性状遗传的重要方法。随着犬全基因组测序的完成以及犬不同密度SNP芯片的商业化,GWAS已经成为CHD致病基因筛选的一个重要手段。本文综述了GWAS的定义与影响因素,CHD在国外的育种现状及GWAS在德国牧羊犬中的研究进展。     

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.     

Estimates of genetic parameters for hip and elbow dysplasia in Finnish Rottweilers

Data from 2,764 Rottweiler dogs born from 1987 to 1996 were analyzed with a Restricted Maximum Likelihood procedure using a mixed linear animal model to obtain variance component estimates for hip and elbow dysplasia. The data included 2,764 hip dysplasia and 2,278 elbow dysplasia records. Hip joints were scored as normal (0), borderline (1), slight (2), moderate (3), and severe (4, 4.5, and 5) hip dysplasia. Elbow joints were graded normal or borderline (0), slight (1), moderate (2), and severe (3) elbow dysplasia. The mean for the hip scores was 1.07 and for the elbow scores .60. Environmental effects influencing hip dysplasia were age, birth year, birth year x season interaction, and experience of the veterinarian responsible for x-raying the dog. For elbow dysplasia, statistically significant effects were age, birth year, sex of the dog, and panelist responsible for each screening. Estimates of heritability for hip and elbow dysplasia were .58 +/- .04 and .31 +/- .04, respectively, with a genetic correlation of .37 +/- .08 between the traits. Genetic improvement of almost one genetic standard deviation was observed in both traits during the 10 yr covered by the data.     

Genetic variation and genetic trends in hip and elbow dysplasia in Swedish Rottweiler and Bernese Mountain Dog

The aim of this study was to estimate genetic parameters and genetic trends for hip (HD) and elbow dysplasia (ED) in Swedish Rottweiler (RW) and Bernese Mountain Dog (BMD). Analyses were based on screening results of hip status for 14 693 RW and 8221 BMD and elbow status for 11 891 RW and 7963 BMD, as well as pedigree data for 16 614 RW and 9835 BMD, recorded by the Swedish Kennel Club. Components of (co)variance and breeding values were obtained with a mixed linear animal model. The model included the fixed effects of sex, birth month, age at screening and a combined random effect of clinic and year of examination. The need to include genetic groups for phantom parents in the model was evaluated by comparison of two different models: with and without genetic groups. Estimated heritabilities for HD and ED were between 0.34 and 0.42. The genetic correlation between the traits was weak and positive for RW (r_g = 0.23 ± 0.05) and not different from zero for BMD (r_g = 0.06 ± 0.06). F‐statistics of the genetic group effects were not significant, implying that genetic groups do not need to be included in the model. Genetic trends indicated a genetic improvement in both traits. However, a faster genetic progress is expected if selection is based on predicted breeding values rather than phenotype. Based on the results, a statistical model for routine prediction of breeding values for HD and ED in Swedish dogs was suggested.     

Estimation of genetic parameters on test stations using purebred and crossbred progeny of sires of the Bavarian Piétrain

Genetic parameters were estimated for purebred and crossbred progeny of Bavarian Piétrain sires on two test stations. The data set used contained 4276 purebred pigs and 13,980 crossbred pigs recorded between 2000 and 2004. In total 332 sires having purebred and crossbred progeny were available to estimate the genetic correlations between purebred and crossbred performances. Though the genetic correlations between purebred and crossbred pigs are fairly high (0.7–0.9), their performances have to be considered as genetically different traits, because variance components and heritabilities differ substantially. Therefore, purebred and crossbred breeding values of candidates are not identical, and thus result in different rankings. However, due to the high correlations purebred pigs provide a lot of information for estimating the crossbred breeding values of the real selection criterion. The Halothan locus, whose effects have been analyzed in detail, affects both purebred and crossbred parameters. To avoid detrimental effects on the efficiency of the breeding programme, the n-allele could be either eliminated or the genotypes of all test animals should be known. Differences in the variance components between the two test stations have been found and are problematic with respect to the breeding value estimation utilizing the pooled data set. Hence, it should be attempted to further improve the standardization of the performance test on both stations.