Genome wide association studies (GWAS) have been utilized to identify genetic risk loci associated with both simple and complex inherited disorders. Here, we performed a GWAS in Labrador retrievers to identify genetic loci associated with hip dysplasia and body weight. Hip dysplasia scores were available for 209 genotyped dogs. We identified a significantly associated locus for hip dysplasia on chromosome 24, with three equally associated SNPs (p = 4.3 × 10 –7 ) in complete linkage disequilibrium located within NDRG3 , a gene which in humans has been shown to be differentially expressed in osteoarthritic joint cartilage. Body weight, available for 85 female dogs, was used as phenotype for a second analysis. We identified two significantly associated loci on chromosome 10 (p = 4.5 × 10 –7 ) and chromosome 31 (p = 2.5 × 10 –6 ). The most associated SNPs within these loci were located within the introns of the PRKCE and CADM2 genes, respectively. PRKCE has been shown to play a role in regulation of adipogenesis whilst CADM2 has been associated with body weight in multiple human GWAS. In summary, we identified credible candidate loci explaining part of the genetic inheritance for hip dysplasia and body weight in Labrador retrievers with strong candidate genes in each locus previously implicated in the phenotypes investigated.
Breeding against canine hip dysplasia (HD) may benefit from the importation of foreign sires. When foreign sires are evaluated on a different HD scale, this may diminish the efficacy. Using stochastic simulations, we evaluated genetic change and inbreeding levels for different scenarios of importing sires with high genetic merit for HD. Population size and genetic parameters (e.g. heritability, accuracy of selection, genetic correlation) were based on actual data for HD in Golden retrievers and Labrador retrievers in the UK and Sweden. For countries with different HD scales and an estimated breeding value (EBV) evaluation in place, the importation was useful if imported sires had EBV rankings in the top 50% and if genetic correlations between EBV systems were above 0.85. When importing sires with EBV rankings in the top 10%, moderate accuracies of EBVs (>0.40) and moderately strong genetic correlations (>0.70) were needed. Selection against HD without the importation of sires may increase inbreeding levels, while the importation of sires can decrease inbreeding levels. For national genetic evaluation and selection programmes, importing sires with high genetic merit can be an effective breeding strategy, but care is needed to estimate reliable EBVs.
To improve the health and welfare of pedigree dogs, national kennel clubs (KCs) are key players in the governance and regulation of dog breeding. In a survey conducted to investigate differences between KCs in breeding policies and management of pedigree dogs, a questionnaire was completed by 15 KCs from 11 European countries (Austria, Belgium, Denmark, France, Germany, Ireland, Latvia, The Netherlands, Norway, Sweden and the United Kingdom) and four non-European countries (Australia, Mexico, Uruguay and the USA). The most important concerns reported by KCs were exaggerated morphological features and inherited disorders. A wide variety of information, tools and strategies was used to address these issues, with implementation differing across countries and breeds. KCs reported progress in the collection and provision of information related to canine health and welfare. Implementation of advanced breeding tools, such as genetic evaluation and online advisory mating tools, and balanced breeding strategies, endorsed by clubs and breeders, remain challenging and require further development.
Patellar luxation is one of the more common orthopaedic diseases of dogs and is relatively frequent in some toy breeds, including the Chihuahua and Bichon Frise. Using data provided by the Swedish Kennel Club, genetic parameters, including heritability, were estimated for patellar luxation in the Chihuahua from 1999 to 2014 and in the Bichon Frise from 1997 to 2014. The effects of the current screening programmes for patellar luxation in these breeds were evaluated. Patellar luxation was defined as a binary trait, treating dogs as affected or unaffected. The edited data included 7024 records for the Chihuahua and 1071 records for the Bichon Frise. Patellar luxation was analysed using mixed linear and threshold animal models, including fixed effects of sex, birth month, birth year, age at veterinary examination, random effects of the examining veterinary surgeon, genetic effect of the individual and residual. The prevalence of patellar luxation was 23% in the Chihuahua and 12% in the Bichon Frise. Using threshold analysis, estimated heritabilities were 0.25 for the Chihuahua and 0.21 for the Bichon Frise on the observable scale, and 0.46 for the Chihuahua on the underlying scale. It was concluded that there is genetic variation in patellar luxation and that there has been a slight genetic improvement over the study period in the Chihuahua. Further genetic progress would be facilitated by selection using estimated breeding values based on veterinary screening records.
Breed-related health problems in dogs have received increased focus over the last decade. Responsibility for causing and/or solving these problems has been variously directed towards dog breeders and kennel clubs, the veterinary profession, welfare scientists, owners, regulators, insurance companies and the media. In reality, all these stakeholders are likely to share some responsibility and optimal progress on resolving these challenges requires all key stakeholders to work together. The International Partnership for Dogs (IPFD), together with an alternating host organization, holds biennial meetings called the International Dog Health Workshops (IDHW). The Société Centrale Canine (French Kennel Club) hosted the 3rd IDHW, in Paris, in April, 2017. These meetings bring together a wide range of stakeholders in dog health, science and welfare to improve international sharing of information and resources, to provide a forum for ongoing collaboration, and to identify specific needs and actions to improve health, well-being and welfare in dogs.
In order to reduce the prevalence of inherited diseases in pedigree dogs, the feasibility of implementation of an international breeding program was investigated. One prerequisite is a strong genetic correlation between countries and our objective was to estimate this correlation for canine hip dysplasia (HD) across three countries to evaluate the feasibility of an international genetic evaluation. Data were provided by the Société Centrale Canine (SCC, France), Svenska Kennelklubben (SKK, Sweden) and The Kennel Club (KC, UK) on Golden retriever and Labrador retriever dogs. Trivariate analysis on the three different modes of scoring HD in France, Sweden and the UK was performed using a mixed linear animal model. Heritability, genetic correlation, number of common sires, genetic similarity, selection differentials and accuracy of selection were calculated. The estimated heritabilities of Golden retrievers (Labrador retrievers) for HD scores were 0.28 (0.15), 0.28 (0.29) and 0.41 (0.34) in France, Sweden and the UK, respectively. The feasibility of performing a genetic evaluation of HD across countries was indicated by the favourable genetic correlations estimated between score modes (ranged from 0.48 to 0.99). The accuracy of selection for the most recent birth year cohorts of male dogs was not improved by international evaluation compared to national evaluation. Improvement in genetic progress can however be achieved by selection across populations in different countries, particularly for small populations, which were indicated by the large difference between selection differentials based on the national and international evaluations.
Merging pedigree databases across countries may improve the ability of kennel organizations to monitor genetic variability and health-related issues of pedigree dogs. We used data provided by the Société Centrale Canine (France), Svenska Kennelklubben (Sweden) and the Kennel Club (UK) to study the feasibility of merging pedigree databases across countries and describe breeding practices and international gene flow within the following four breeds: Bullmastiff (BMA), English setter (ESE), Bernese mountain dog (BMD) and Labrador retriever (LBR). After merging the databases, genealogical parameters and founder contributions were calculated according to the birth period, breed and registration country of the dogs. Throughout the investigated period, mating between close relatives, measured as the proportion of inbred individuals (considering only two generations of pedigree), decreased or remained stable, with the exception of LBR in France. Gene flow between countries became more frequent, and the origins of populations within countries became more diverse over time. In conclusion, the potential to reduce inbreeding within purebred dog populations through exchanging breeding animals across countries was confirmed by an improved effective population size when merging populations from different countries.
Pooling of pedigree and phenotype data from different countries may improve the accuracy of derived indicators of both genetic diversity and genetic merit of traits of interest. This study demonstrates significant migration of individuals of four pedigree dog breeds between Sweden and the United Kingdom. Correlations of estimates of genetic merit (estimated breeding values, EBVs) for the Fédération Cynologique Internationale and the British Veterinary Association and Kennel Club evaluations of hip dysplasia (HD) were strong and favourable, indicating that both scoring schemes capture substantially the same genetic trait. Therefore pooled use of phenotypic data on hip dysplasia would be expected to improve the accuracy of EBV for HD in both countries due to increased sample data.
Breeding to reduce the prevalence of categorically scored hip dysplasia (HD), based on phenotypic assessment of radiographic hip status, has had limited success. The aim of this study was to evaluate two selection strategies for improved hip status: truncation selection based on phenotypic record versus best linear unbiased prediction (BLUP), using stochastic simulation and selection scenarios resembling those in real dog populations. In addition, optimum contribution selection (OCS) was evaluated. Two traits were considered: HD (as a categorical trait with five classes and a heritability of 0.45 on the liability scale) and a continuous trait (with a heritability of 0.25) intended to represent other characteristics in the breeding goal. A population structure mimicking that in real dog populations was modelled. The categorical nature of HD caused a considerably lower genetic gain compared to simulating HD as a continuous trait. Genetic gain was larger for BLUP selection than for phenotypic selection in all scenarios. However, BLUP selection resulted in higher rates of inbreeding. By applying OCS, the rate of inbreeding was lowered to about the same level as phenotypic selection but with increased genetic improvement. For efficient selection against HD, use of BLUP breeding values should be prioritized. In small populations, BLUP should be used together with OCS or similar strategy to maintain genetic variation.
From 1989 until 2003, the Swedish Sheepdog Society used a standardized method, Herding Trait Characterization (HTC), to describe herding behavior of individual Border collies for breeding purposes. In the HTC, which existed in 2 consecutive versions, the dog’s herding behavior was described using predefined scales typically consisting of 6 classes within each trait. In total, 1,663 dogs participated in the first version and 951 in the second. The main difference between the versions was the structure of the protocols used to record the traits. In the first version, the scales were designed to describe the intensity in the expression of the measured traits. In the second version, the most desirable behavioral expression was placed in the middle of the scale. Another difference was that in the second version, the judges were given more freedom for their own interpretations, that is, the scales were more subjective. The objective of this study was to examine the quality of each version from a breeding perspective, and to analyze the reasons for possible differences in this respect between them. Heritability estimates for the 17 traits of the earlier version of the HTC ranged from 0.14 to 0.50 (weighted average: 0.30), all significantly different from 0. Corresponding heritabilities for the 19 traits in the later version were substantially lower (0.03-0.41, weighted average: 0.16), 3 of them not being significantly different from 0. Owing to the moderate-to-high heritabilities for the traits measured in the earlier version of the HTC, it would be possible to accomplish effective selection of breeding animals for most of the measured traits. It is plausible that the less neutral and more subjective protocol of the later version is the main cause for the lower heritabilities.
Health problems in pedigree dogs have recently been highlighted in the media worldwide and verified internationally by cynological organisations. Collaborative actions are now needed to deal with both existing and future issues. In this article, potential roles for various stakeholders are discussed and the value of national and international platforms for collaborations is stressed. Development of specific strategies for action must be based on criteria of significance, such as severity, prevalence and inheritance, as well as availability of effective preventive measures. Assessment of options should be founded on evidence from appropriate populations-at-risk and consider broader issues, such as demographics and human–animal interactions. Existing data, such as those from insurance statistics and health surveys, should be used as a reference until representative national/international population-level breed-specific data are available. Key issues and challenges, as well as possible strategies to address them, are discussed.
BACKGROUND:A sensory ataxic neuropathy has been observed in Swedish Golden Retrievers recently.ANIMALS:Twenty-one affected Golden Retrievers.METHODS:Clinical and neurologic status, electrophysiologic, and pathologic status as well as pedigree analyses were evaluated.RESULTS:Clinical signs had an insidious onset between 2 and 8 months of age and a slowly progressive course. Affected dogs were ataxic and dysmetric. They had abnormal postural reactions and decreased spinal reflexes but no apparent muscle atrophy. Clinical pathology, radiography, and electrophysiology of motor systems were all within reference values. Sensory nerve conduction results of affected dogs were significantly different from those of a group of control dogs. Necropsy revealed a chronic progressive central and peripheral sensorimotor axonopathy; the proprioceptive pathways were most severely affected.CONCLUSIONS AND CLINICAL IMPORTANCE:This disease in these Golden Retrievers is distinct from other canine breed-related neurodegenerative diseases or hereditary neurodegenerative diseases described in humans. Pedigree analyses indicated a hereditary background, but the mode of inheritance could not be established.
GENETIC ANALYSIS OF HERDING BEHAVIOR IN SWEDISH BORDER COLLIE DOGS Per Arvelius*, Sofia Malm, Kenth Svartberg, Erling Strandberg Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Sweden Svartbergs hundkunskap, Sweden *Corresponding author: per.arvelius@hgen.slu.se From 1989 until 2003, the Swedish Sheep Dog Society used a standardized method, HBC (Herding Behavior Characterization), to characterize herding behavior of individual border collies. The dogs’ typical herding behavior was described using predefined scales. During the period, 2 different recording protocols were used. In total, 2700 dogs participated. Heritability estimates for the 17 traits of the earlier version of the HBC ranged from 0.14-0.50 (average 0.30), all statistically significantly different from zero. Corresponding heritabilities for the later version were substantially lower. There are several possible explanations for this finding. For example the scales, that is, the way the traits were recorded, might have had a less appropriate construction in the later version. A factor analysis suggested that the traits measured can be explained by 4 overall traits with heritabilities ranging from 0.30-0.55. Owing to the moderate to high heritabilities, it would be possible to accomplish effective selection of breeding animals for most of the measured traits.
Our objective was to evaluate the association between grading of hip status as assessed by radiographic examination (hip screening) and subsequent incidence of veterinary care and mortality related to hip dysplasia (HD) in five breeds of insured dogs in Sweden. Screening results for hip status from the Swedish Kennel Club and data on veterinary care and mortality from the insurance company Agria were merged based on the registration number of the dog. Dogs of five breeds (Bernese Mountain Dogs, German Shepherds, Golden Retrievers, Labrador Retrievers, and Rottweilers) screened during 1995–2004 and covered by an insurance plan for veterinary care or life at the time of screening were included. The study populations included between 1667 and 10,663 dogs per breed. Breed-specific multivariable Cox proportional-hazards analyses were performed to evaluate the impact of radiographic hip status on time from hip screening to first HD-related veterinary and life claim, respectively. The effects of gender, birth season, and a time-varying covariate of year were also studied. Additional analyses, on the five breeds combined, were performed to investigate the effects of hip status, breed, and the interaction between hip status and breed. The effect of hip status was highly significant (P<0.001) for both life and veterinary claims related to HD in all five breeds with increased hazard ratio (HR) for deteriorating hip status. Dogs with moderate or severe hip status at screening had a markedly increased hazard of HD-related veterinary care and mortality compared with dogs assessed as free or mild. The time-varying covariate of year showed a significantly higher HR in the last time period for German Shepherds and Labrador Retrievers in the analyses of veterinary claims. In the analyses on all five breeds, German Shepherds had the highest HR for both veterinary care and mortality related to HD, followed by Bernese Mountain Dogs. Golden and Labrador Retrievers had the lowest HR. The effect of hip status on the hazard was the same irrespective of breed. However, as a consequence of differences between breeds in overall risk, the predictive ability of screening results for subsequent incidence of HD-related problems for individual dogs was breed-dependent. Based on the strong association between radiographic hip status and incidence of HD-related veterinary care and mortality, and the previously reported moderate heritability of hip status, we conclude that selection based on screening results for hip status can be expected to reduce the risk of HD-related clinical problems.
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.
Our objective was to investigate the effect of sedation method on the screening result for hip and elbow dysplasia. The study was based on a questionnaire survey of routines for hip and elbow screening at Swedish veterinary clinics and results of hip and elbow status, for eight breeds (Bernese Mountain Dog, Boxer, German Shepherd Dog, Golden Retriever, Labrador Retriever, Newfoundland, Rottweiler, and Saint Bernard) recorded by the Swedish Kennel Club. In total 5877 and 5406 dogs examined for hip and elbow dysplasia, respectively, from January 2002 through March 2003 were included. We used logistic regression to examine whether the type of chemical restraint used for sedation affected the screening result for hip and elbow dysplasia. In addition to sedation method, the effects of veterinary clinic, sex, breed, and age at screening were studied. The type of chemical restraint used for sedation affected the screening result for hip but not for elbow dysplasia. Acepromazine gave less than half the odds of hip dysplasia compared with medetomidine and butorphanol (the most common method), medetomidine alone or xylazine. Females had about 25% higher odds for developing hip dysplasia whereas males had almost 40% higher odds for developing elbow dysplasia. Saint Bernard, Newfoundland and German Shepherd Dog had the highest odds of developing hip dysplasia, whereas Rottweiler and Labrador Retriever had the lowest odds. Boxer had the lowest risk for elbow dysplasia, followed by Labrador Retriever. Saint Bernard and Rottweiler had the highest odds of elbow dysplasia. Increasing age increased the odds of both hip and elbow dysplasia, by about 2.5% per month. Following the results in this study, recording of the type of chemical restraint used for sedation during hip screening has now become mandatory in Sweden. This makes it possible to account for the effect of sedation method in a model for prediction of breeding values for hip dysplasia.
Decades of selective breeding to reduce the prevalence of hip and elbow dysplasia(HD and ED) in Swedish dogs, based on phenotypic assessment of radiographic hip status, has had limited success. The prevalence of dysplastic dogs is still high in many large-sized and giant breeds and among the most common causes for euthanasia and costly veterinary care in numerous breeds are joint-related problems. The aim of this thesis was to investigate the possibilities of more efficient breeding strategies for improved hip and elbow health in Swedish dogs by improving the genetic evaluation of HD and ED, and by evaluating the clinical significance of radiographic hip status. Data from several different sources were combined in the analyses: pedigree information and screening records for HD and ED from the Swedish Kennel Club, questionnaire data about routines for hip and elbow screening from Swedish veterinary clinics and insurance data on hip-related veterinary care and mortality from Agria Insurance Company. Moreover, simulated data were used to evaluate selection strategies. Radiographic hip status in young adult dogs was shown to be strongly associated with subsequent incidence of veterinary care and mortality related to the hip joint. Furthermore, the genetic analyses of screening records for HD and ED showed considerable genetic variation and moderate heritability of both traits. Taken together, these findings support the use of screening records for HD and ED in selection to reduce prevalence of clinical problems related to hip and elbow joints. However, the impact of systematic environmental factors, such as sedation method, on the phenotypic expression of HD and ED implies that the individual’s screening result alone is an imprecise estimate of its breeding value. Simulation of selection strategies against HD showed that selection based on BLUP breeding values was superior to phenotypic selection, leading to faster genetic progress and more rapid reduction of dysplastic dogs. Based on the studies included in this thesis, it is concluded that implementation of breeding schemes based on BLUP breeding values, instead of phenotypic records, should be prioritised to enable a more efficient breeding for improved hip and elbow health in Swedish dogs.