Comparative analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds

BACKGROUND: Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. RESULTS: The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. CONCLUSIONS: EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well

Estimates of genetic parameters of distal limb fracture and superficial digital flexor tendon injury in UK Thoroughbred racehorses

A retrospective cohort study of distal limb fracture and superficial digital flexor tendon (SDFT) injury in Thoroughbred racehorses was conducted using health records generated by the British Horseracing Authority (BHA) between 2000 and 2010. After excluding records of horses that had both flat and jump racing starts, repeated records were reduced to a single binary record per horse (<i>n</i> = 66,507, 2982 sires), and the heritability of each condition was estimated using residual maximum likelihood (REML) with animal logistic regression models. Similarly, the heritability of each condition was estimated for the flat racing and jump racing populations separately. Bivariate mixed models were used to generate estimates of genetic correlations between SDFT injury and distal limb fracture. The heritability of distal limb fracture ranged from 0.21 to 0.37. The heritability of SDFT injury ranged from 0.31 to 0.34. SDFT injury and distal limb fracture were positively genetically correlated. These findings suggest that reductions in the risk of the conditions studied could be attempted using targeted breeding strategies

Genetic Evaluation of the Nine Component Features of Hip Score in UK Labrador Retrievers

The aim of this study was to explore the genetic relationship between the nine component traits comprising the British Veterinary Association (BVA) total hip score in UK registered Labrador Retrievers. Data consisted of 11,928 single records of trait scores of dogs aged between one and four years (365–1459 days) old, from radiographs evaluated between 2000 and 2007. Pedigree information was provided by the UK Kennel Club. The distribution of trait scores showed only small numbers of dogs with visible malformation in the six traits that were scored according to the severity of osteoarthritis. Linear mixed models were fitted using ASREML. Estimates of heritability ranged from 0.15 to 0.38, and litter effects from 0.04 to 0.10. Genetic correlations between all nine traits were extremely high ranging from 0.71 to 1.0, implying considerable genetic similarity. The decomposition demonstrated that aggregate scores of only the 3 traits indicative of laxity in one year old dogs was predictive of the phenotype of the remaining six scored on osteoarthritic severity in dogs at 4+ years old. The application of selection index methodology in selecting against hip dysplasia using the trait scores was explored and potential improvements in accuracy (directly related to response to selection) of over 10% are reported compared to the current total hip score. This study demonstrates that traits descriptive of joint laxity are valuable early-age predictors of osteoarthritis and shows that there is scope for improvement in the way data from the UK hip score scheme are used for selection against hip dysplasia in Labradors. This was verified via use of selection indices, which identified substantial increases in accuracy, not only via optimum coefficients, but also through an easily applicable aggregate of scores of just two or three traits only compared with the current total hip score

Environmental risk factors for canine atopic dermatitis: a retrospective large‐scale study in Labrador and golden retrievers

Background - canine atopic dermatitis (cAD) is one the most common and distressing skin disorders seen in dogs. It is characterised by dysfunction in the skin barrier, with a complex pathogenesis combining both genetic and environmental factors.Objectives - to evaluate associations between environmental factors and case-control status in two closely related, at-risk breeds, the Labrador and Golden retriever.Animals - 2,445 pet dogs, of which 793 were classed as cases (575 Labradors and218 Golden retrievers) and 1,652 as controls (1,120 Labradors and 532 Golden retrievers). Methods – case-control status was assigned based upon owner response to a standardised validated questionnaire. Retrospective data on rearing environment was collected via additional questions. Univariate and multivariate logistic regressions were utilised to evaluate associations between environmental factors and case-control status.Results - risk factors included being reared in an urban environment (not living currently in an urban environment), being male, being neutered, receiving flea control, and being allowed on upholstered furniture. Protective factors included living with other dogs (not cats) and walking in woodlands, fields or beaches. Additionally, amongst Labradors, chocolate coated dogs were at greater risk of having cAD than black or yellow coated dogs.Conclusions and clinical importance - This study is the largest of its kind to date to investigate the role of the environment in canine atopic dermatitis. Although precise triggers are unclear, this study contributes to those of earlier studies to highlight the protective role of a rural environment and highlights some novel associations with disease development

A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses

Background: Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse. Results: Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the same time period as the cases, and had no history of fracture at the time the study was carried out. The horses sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs were employed to perform a genome-wide association analysis and to estimate the proportion of genetic variance attributable to the SNPs on each chromosome using restricted maximum likelihood (REML). Significant genetic variation associated with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on chromosome 18 (62.05 Mb – 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb) reached genome-wide significance (p <0.05) in a genome-wide association study (GWAS). Two of the SNPs on ECA 18 were located in a haplotype block containing the gene zinc finger protein 804A (ZNF804A). One haplotype within this block has a protective effect (controls at 1.95 times less risk of fracture than cases, p = 1 × 10-4), while a second haplotype increases fracture risk (cases at 3.39 times higher risk of fracture than controls, p = 0.042). Conclusions: Fracture risk in the Thoroughbred horse is a complex condition with an underlying genetic basis. Multiple genomic regions contribute to susceptibility to fracture risk. This suggests there is the potential to develop SNP-based estimators for genetic risk of fracture in the Thoroughbred racehorse, using methods pioneered in livestock genetics such as genomic selection. This information would be useful to racehorse breeders and owners, enabling them to reduce the risk of injury in their horses

Joint genomic prediction of canine hip dysplasia in UK and US Labrador Retrievers

Canine hip dysplasia, a debilitating orthopedic disorder that leads to osteoarthritis and cartilage degeneration, is common in several large-sized dog breeds and shows moderate heritability suggesting that selection can reduce prevalence. Estimating genomic breeding values require large reference populations, which are expensive to genotype for development of genomic prediction tools. Combining datasets from different countries could be an option to help build larger reference datasets without incurring extra genotyping costs. Our objective was to evaluate genomic prediction based on a combination of UK and US datasets of genotyped dogs with records of Norberg angle scores, related to canine hip dysplasia. Prediction accuracies using a single population were 0.179 and 0.290 for 1,179 and 242 UK and US Labrador Retrievers, respectively. Prediction accuracies changed to 0.189 and 0.260, with an increased bias of genomic breeding values when using a joint training set (biased upwards for the US population and downwards for the UK population). Our results show that in this study of canine hip dysplasia, little or no benefit was gained from using a joint training set as compared to using a single population as training set. We attribute this to differences in the genetic background of the two populations as well as the small sample size of the US dataset

Behavioural Differences in Dogs with Atopic Dermatitis Suggest Stress Could Be a Significant Problem Associated with Chronic Pruritus

Canine atopic dermatitis (cAD) is a common allergic skin condition in dogs that causes chronic pruritus. The overall quality of life in dogs with cAD is known to be reduced, and human patients with pruritic conditions report significant psychological burdens from pruritus-induced stress, and atopic dermatitis is associated with significant psychopathological morbidities. We tested the hypothesis that dogs with cAD would display more problem behaviours that could be indicative of stress than would healthy controls. Behavioural data were gathered directly from owners using a validated dog behaviour questionnaire for 343 dogs with a diagnosis of cAD and 552 healthy controls, and scores were also provided for their dog’s pruritus severity. Regression modelling, controlling for potential confounding variables (age, sex, breed, neuter status or other health problem(s)) showed for the first time that pruritus severity in dogs with cAD was associated with increased frequency of behaviours often considered problematic, such as mounting, chewing, hyperactivity, coprophagia, begging for and stealing food, attention-seeking, excitability, excessive grooming, and reduced trainability. Whilst causality cannot be ascertained from this study, the behaviours that were associated with pruritus severity are redirected, self/environment-directed displacement behaviours, which are often considered indicative of stress. Further investigation is warranted, and stress reduction could be helpful when treating dogs with cAD

The utility of low-density genotyping for imputation in the Thoroughbred horse

BACKGROUND: Despite the dramatic reduction in the cost of high-density genotyping that has occurred over the last decade, it remains one of the limiting factors for obtaining the large datasets required for genomic studies of disease in the horse. In this study, we investigated the potential for low-density genotyping and subsequent imputation to address this problem. RESULTS: Using the haplotype phasing and imputation program, BEAGLE, it is possible to impute genotypes from low- to high-density (50K) in the Thoroughbred horse with reasonable to high accuracy. Analysis of the sources of variation in imputation accuracy revealed dependence both on the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and on the underlying linkage disequilibrium structure. Whereas equidistant spacing of the SNPs on the low-density panel worked well, optimising SNP selection to increase their minor allele frequency was advantageous, even when the panel was subsequently used in a population of different geographical origin. Replacing base pair position with linkage disequilibrium map distance reduced the variation in imputation accuracy across SNPs. Whereas a 1K SNP panel was generally sufficient to ensure that more than 80% of genotypes were correctly imputed, other studies suggest that a 2K to 3K panel is more efficient to minimize the subsequent loss of accuracy in genomic prediction analyses. The relationship between accuracy and genotyping costs for the different low-density panels, suggests that a 2K SNP panel would represent good value for money. CONCLUSIONS: Low-density genotyping with a 2K SNP panel followed by imputation provides a compromise between cost and accuracy that could promote more widespread genotyping, and hence the use of genomic information in horses. In addition to offering a low cost alternative to high-density genotyping, imputation provides a means to combine datasets from different genotyping platforms, which is becoming necessary since researchers are starting to use the recently developed equine 70K SNP chip. However, more work is needed to evaluate the impact of between-breed differences on imputation accuracy

Estimates of genetic parameters of distal limb fracture and superficial digital flexor tendon injury in UK Thoroughbred racehorses

A B S T R A C T A retrospective cohort study of distal limb fracture and superficial digital flexor tendon (SDFT) injury in Thoroughbred racehorses was conducted using health records generated by the British Horseracing Authority (BHA) between 2000 and 2010. After excluding records of horses that had both flat and jump racing starts, repeated records were reduced to a single binary record per horse (n = 66,507, 2982 sires), and the heritability of each condition was estimated using residual maximum likelihood (REML) with animal logistic regression models. Similarly, the heritability of each condition was estimated for the flat racing and jump racing populations separately. Bivariate mixed models were used to generate estimates of genetic correlations between SDFT injury and distal limb fracture. The heritability of distal limb fracture ranged from 0.21 to 0.37. The heritability of SDFT injury ranged from 0.31 to 0.34. SDFT injury and distal limb fracture were positively genetically correlated. These findings suggest that reductions in the risk of the conditions studied could be attempted using targeted breeding strategies

Quantitative trait loci mapping for canine hip dysplasia and its related traits in UK Labrador Retrievers

BACKGROUND: Canine hip dysplasia (CHD) is characterised by a malformation of the hip joint, leading to osteoarthritis and lameness. Current breeding schemes against CHD have resulted in measurable but moderate responses. The application of marker-assisted selection, incorporating specific markers associated with the disease, or genomic selection, incorporating genome-wide markers, has the potential to dramatically improve results of breeding schemes. Our aims were to identify regions associated with hip dysplasia or its related traits using genome and chromosome-wide analysis, study the linkage disequilibrium (LD) in these regions and provide plausible gene candidates. This study is focused on the UK Labrador Retriever population, which has a high prevalence of the disease and participates in a recording program led by the British Veterinary Association (BVA) and The Kennel Club (KC). RESULTS: Two genome-wide and several chromosome-wide QTLs affecting CHD and its related traits were identified, indicating regions related to hip dysplasia. CONCLUSION: Consistent with previous studies, the genetic architecture of CHD appears to be based on many genes with small or moderate effect, suggesting that genomic selection rather than marker-assisted selection may be an appropriate strategy for reducing this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-833) contains supplementary material, which is available to authorized users