BACKGROUND:Hip and elbow dysplasia (HD and ED) are common developmental orthopaedic disorders in dogs. The study objectives were to report population-based estimates of HD and ED prevalence at screening in young adult dogs of different breeds and to evaluate the phenotypic association between HD and ED. METHODS:Data for dogs screened for HD and ED between 2007 and 2016 were obtained from the Swedish Kennel Club. HD and ED were graded according to the Fédération Cynologique Internationale and International Elbow Working Group, respectively. RESULTS:This study included 114,568 dogs from 72 breeds screened for HD and 78,504 dogs from 46 breeds screened for ED. The prevalence of HD was highest in the Dogue de Bordeaux (75.4%), Bullmastiff (65.1%) and American Staffordshire Terrier (64.2%) while the prevalence of ED was highest in the Chow Chow (65.2%), Dogue de Bordeaux (40.0%) and American Staffordshire Terrier (34.9%). A worse HD grade co-occurred with a worse ED grade (p < 0.001), and the co-occurrence was breed dependent. LIMITATIONS:Severe cases of dysplasia may be underrepresented as dogs with clinical signs of HD and ED at a young age might not be screened. CONCLUSION:Population-based prevalence estimates of HD and ED were reported. Large breed-related differences were found, and worse HD and ED co-occurred.

Canine hip dysplasia (HD) is a common developmental orthopaedic disorder with substantial impact on health and life expectancy. Body weight has been considered an important factor for the development, but prior studies evaluating this association on a large data set, strictly collected and without preselection of screening results, are lacking. The objectives of the study were to investigate a potential association between body weight and radiographic HD screening grade in young adult dogs of different breeds, and to study potential breed differences in selected breeds of different sizes. A cross-sectional study using hip screening results and body weight data from the Swedish Kennel Club, collected during 2007-2016 from 114,568 young adult dogs of 72 different breeds in Sweden, was performed. An association between HD screening grade and body weight was found; higher body weight within breed was associated with a more severe HD grade. The association was breed-dependent and significant in 13 of the 21 breeds included in the analysis on breed differences. In conclusion, higher body weight within breed was significantly associated with a more severe HD screening grade, and the association was breed dependent. This indicates that lower body weight might be a protective factor for developing HD.

BACKGROUND:Mast cell tumour (MCT) is the most common skin neoplasia in dogs. This study aimed to explore the incidence rate, cause-specific mortality rate and risk factors (breed, age, gender) for MCT in insured dogs in Sweden (2011-2016). RESULTS:The study population of this cohort study included just over 600,000 dogs, which either were insured for veterinary care, life, or both. There were 917 dogs with veterinary care claims for MCT, and the incidence rate was 5.23 (95 % confidence interval (CI): 4.90-5.58) cases per 10,000 dog-years at risk (DYAR). The risk of MCT was higher in females than in males (relative risk (RR) 1.29, 95 % CI: 1.13-1.48, P < 0.001). The breeds at highest risk were the Dogo Argentino (RR 30.0, 95 % CI 9.70-70.2) and Boxer (RR 9.78, 95 % CI 7.02-13.3), while the Jämthund (RR 0.10, 95 % CI 0.01-0.35) and Cavalier King Charles spaniel (RR 0.06, 95 % CI 0.00-0.35) had the lowest risk. The median age at first diagnosis was 7.93 (range 0.44-15.4) years. In total, 11.6 % of the affected dogs suffered multiple MCT events. The cause-specific mortality rate was 0.79 (95 % CI: 0.63-0.97) deaths per 10,000 DYAR, and 87 of all dogs that were covered by life insurance died of MCT-related causes at a median age of 8.33 years (range 2.16-11.7). The Shar-pei (RR 51.5, 95 % CI: 13.7-137.0) had the highest risk of MCT-related death. CONCLUSIONS:MCT mainly affected middle-aged to older dogs, and large breed-related differences in the risk of MCT and MCT-related death were found.

Skeletal dysplasias encompass a diverse group of genetic disorders characterized by short stature and dwarfism. In humans, 771 types of skeletal dysplasia have been documented. Similar forms of these disorders have also been observed in dogs. The first cases of documented skeletal dysplasia in Dalmatian dogs were reported in the early 1980s, with additional affected dogs observed in subsequent years. Careful radiological and histopathological examinations at the time revealed severe limb deformities, including shortened radii and ulnae, irregular growth plates and disrupted endochondral ossification. In this study, we applied whole-genome sequencing on samples collected in 1992 and identified a genetic variant in the PRKG2 gene, introducing a premature stop codon (XM_038582312: c.1601T > G, p.L534X). Genetic variants in PRKG2 have previously been implicated in human acromesomelic dysplasia, a disorder affecting limb growth in young children. The PRKG2-encoded protein plays a crucial role in endochondral ossification, and if translated, the identified nonsense variant would result in a truncated protein lacking most of the catalytic domain. Extended screening of the genetic variant revealed its continued segregation in the current Dalmatian population. Furthermore, three recent cases of dwarfism in Dalmatians were found to be homozygous for the identified PRKG2 nonsense variant. These findings provide compelling evidence for the role of PRKG2 in Dalmatian dwarfism, resolving a decades-old genetic mystery in the breed.

Mammary tumour (MT) is the most common neoplasia in bitches. This study explored the incidence and cause-specific mortality rates of and risk factors for MT in dogs insured by Agria Djurförsäkring in Sweden, 2011-2016. The study population included just over 600,000 dogs, and 13,109 females had veterinary care claims for MT. The incidence rate in females was 157 cases per 10,000 dog-years at risk (95 % confidence interval (CI): 154-160). The breeds at highest risk of MT were the Kerry blue terrier (relative risk (RR) 4.72, 95 % CI 2.58-7.92) and English springer spaniel (RR 3.32, 95 % CI: 3.02-3.63), while the breeds at lowest risk were the German spitz (RR 0.06, 95 % CI: 0.00-0.33) and English bulldog (RR 0.07, 95 % CI: 0.00-0.37). The median age at first MT diagnosis was 8.94 years (interquartile range (IQR) 7.43-10.5). The Dogue de Bordeaux (median age at diagnosis 5.30 years) and Irish wolfhound (6.42 years) were youngest at diagnosis, and the Miniature dachshund (10.9 years) and West Highland white terrier (11.0 years) were oldest. Higher odds of MT were found in bitches with a history of pseudopregnancy (OR 2.10, P < 0.001) and acute mastitis (OR 4.93, P < 0.001). In total, 486 bitches died of MT-related causes at a median age of 9.32 years (IQR 8.37-9.99). The Large Munsterlander had the highest risk of MT-related death (RR 40.3, 95 % CI: 8.28-118.4). In conclusion, MT mainly affected middle-aged to older bitches. Large breed-related differences in the risk of MT and age at diagnosis were found.

The International Partnership for Dogs, together with a rotating national host organisation, holds approximately biennial meetings called the International Dog Health Workshop (IDHW). These workshops bring together a broad range of stakeholders in dog health and welfare, including scientists and veterinary practitioners, to improve the international sharing of information and resources, to provide a forum for ongoing collaboration, and to identify and agree on specific needs and actions to improve canine health and welfare. 5th International Dog Health Workshop was hosted by the Finnish Kennel Club in Helsinki, Finland, in June 2024. The workshop was structured around four key issues facing those working to improve dog health: ‘Supply and Demand’, ‘Breeding for Health and Well-Being’, ‘Big Data’, and ‘Does the Colour Matter? Defining Breed vs. Variety’. The workshop provided an opportunity for participants to meet face-to-face after a five-year hiatus due to COVID-19, on the 10th anniversary of the International Partnership for Dogs. Among the 106 decision-makers from 16 countries who attended the workshop, there was broad agreement on several issues during the discussions, such as following the scientific evidence on canine genetics and health, moving away from extreme conformation, and using all available tools, including crossbreeding, to maintain and increase genetic variation within dog breeds. It was agreed that these principles should become priorities for welfare-minded organisations at the national and international levels. Better education of puppy buyers, breeders, show judges, and other relevant parties was recurringly identified as a priority across all four themes of the workshop. In summary, key agreements from the 5th IDHW were that organisations must comply fully with relevant national animal welfare legislation, that organisations must work to eliminate extreme conformations from all dogs and to improve and maintain genetic diversity within subpopulations of dogs, and that organisations should recognise and support crossbreeding as an accepted and valuable tool for modern dog breeding.

Background Exaggerated brachycephalic features have been highlighted over the last decade by their profound effect on the health and welfare of the affected dogs. The term brachycephalic obstructive airway syndrome (BOAS) was launched in the early 2000s and has received worldwide attention and awareness. At the same time, the popularity of brachycephalic dogs increased. This study aimed to reveal the awareness and experiences of health issues related to the physical appearance of brachycephalic breeds and compare perceptions and opinions on how to counteract these issues by various stakeholders (dog owners, veterinarians, dog breeders, and show judges) by performing an online survey. Results Altogether, 1602 owners, 1551 breeders, 118 show judges, and 557 veterinarians participated. Awareness and experiences of conformation-related health issues were common among all stakeholder groups. Most participants agreed fully or partly that health issues related to conformity threaten the health of brachycephalic breeds; that the measures taken so far are positive; and that guidelines on the appearance of a dog should be based on knowledge regarding health issues related to physical appearance. A disagreement was noted on further measures to be taken and the importance of adhering to a breed standard. Conclusions All stakeholders were aware of health issues related to the appearance of brachycephalic dogs, but had variable personal experiences of these issues. Most participants agreed fully or partly that health issues related to conformity threaten the health of brachycephalic breeds, and that attention to these issues and measures taken so far are positive. However, there is a disagreement on further actions to be taken and the importance of adhering to a breed standard. These findings could be used to understand and bridge the gap in opinions between stakeholders and to refine methods to influence the health of dogs with exaggerated brachycephalic features.

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.

Abstract High body weight (BW) in dogs has been associated with developmental as well as degenerative diseases, but the heritability of BW in dog breeds is largely unknown. The aim of the current study was to estimate heritability and genetic change (genetic trend) for BW in a range of dog breeds in Sweden. Body weight registrations from 19 dog breeds (with n ranging from 412 to 4,710) of varying body size, type and usage were collected from 2007 to 2016. The average BW of the breeds was 8 to 56 kg. The BW registrations were performed when the dogs were 12 to 24 mo of age (18 to 30 mo for one large-sized breed) in connection with an official radiographic screening program for hip dysplasia. Collected weight records were used to estimate heritability and genetic trends for BW. Several statistical models were used. The preliminary model included the fixed effects of breed (P < 0.001), sex (P < 0.001), year of screening (P < 0.001), litter size (P = 0.06), parity of the dam (P = 0.03) and linear regression on age at screening (P < 0.001), the latter five effects all nested within breed, and the random effects of litter and dam. Season of birth and the quadratic effect of age were also tested, but were not significant (P > 0.10). For the genetic analysis, various mixed linear models were tested within breed with different combinations of random effects; the most complex model included random effects of litter, direct additive, and maternal genetic effects, and maternal permanent environmental effects. The average heritability for BW over all 19 breeds was 51%, with a range of 35% to 70%, and the additive genetic coefficient of variance was around 9%. Maternal heritability was 5% to 9% and litter variance was below 10% with one exception (15% in Shetland Sheepdogs). For nine breeds, there was a genetic trend of increasing BW, whereas seven breeds had a genetic trend of decreasing BW. The largest absolute genetic change over a 10-yr period was around 0.6 kg or about 2% of the mean. In conclusion, given the small genetic changes in spite of the high heritability, it seems that there is generally a very weak selection, if any, for BW in the included dog breeds.

High body weight (BW), due to large size or excess body fat, has been associated with developmental and metabolic alterations, and degenerative diseases in dogs. Study objectives were to determine mean BW in young adult dogs of different breeds, including changes over a 10-year period. Body weight data from the official Swedish hip dysplasia screening program were used, including data from dogs screened at 1–2.5 years of age, in breeds with ≥ 15 individual observations/year during 2007–2016. Mean BW per breed and sex was established from 114 568 dogs representing 72 breeds. Estimates of breed BW showed significant change in 33 (45%) breeds over the 10-year period. Body weight increased in five breeds (2–14% change) and decreased in 26 breeds (1–8% change). In two breeds, BW increased in male and decreased in female dogs. This observational study provides extensive breed BW data on young adult dogs. The change in breed BW, noted in almost half of the breeds, could be due to changes either in size or in body fat mass. In certain breeds, the change in BW over time might have an impact on overall health. Studies with simultaneous evaluation of BW and body condition over time are warranted.

Chronic kidney disease (CKD) affects 10% of the human population, with only a small fraction genetically defined. CKD is also common in dogs and has been diagnosed in nearly all breeds, but its genetic basis remains unclear. Here, we performed a Bayesian mixed model genome-wide association analysis for canine CKD in a boxer population of 117 canine cases and 137 controls, and identified 21 genetic regions associated with the disease. At the top markers from each CKD region, the cases carried an average of 20.2 risk alleles, significantly higher than controls (15.6 risk alleles). An ANOVA test showed that the 21 CKD regions together explained 57% of CKD phenotypic variation in the population. Based on whole genome sequencing data of 20 boxers, we identified 5,206 variants in LD with the top 50 BayesR markers. Following comparative analysis with human regulatory data, 17 putative regulatory variants were identified and tested with electrophoretic mobility shift assays. In total four variants, three intronic variants from the MAGI2 and GALNT18 genes, and one variant in an intergenic region on chr28, showed alternative binding ability for the risk and protective alleles in kidney cell lines. Many genes from the 21 CKD regions, RELN , MAGI2 , FGFR2 and others, have been implicated in human kidney development or disease. The results from this study provide new information that may enlighten the etiology of CKD in both dogs and humans.

Pug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflammation have been described. PDM has a late onset and affects more male than female dogs. The breed-specific presentation of the disorder suggests that genetic risk factors are involved in the disease development. To perform a genome-wide search for PDM-associated loci, we applied a Bayesian model adapted for mapping complex traits (BayesR) and a cross-population extended haplotype homozygosity test (XP-EHH) in 51 affected and 38 control pugs. Nineteen associated loci (harboring 67 genes in total, including 34 potential candidate genes) and three candidate regions under selection (with four genes within or next to the signal) were identified. The multiple candidate genes identified have implicated functions in bone homeostasis, fibrotic scar tissue, inflammatory responses, or the formation, regulation, and differentiation of cartilage, suggesting the potential relevance of these processes to the pathogenesis of PDM.

Upper respiratory tract (URT) disorders are common in dogs but neither general nor breed-related epidemiological data are widely reported. This study´s aims were to describe the epidemiology of URT disorders in a Swedish population of dogs and to investigate whether brachycephalic breeds were overrepresented among high-risk breeds. A cohort of dogs insured by Agria Djurförsäkring in Sweden (2011–2014) was used to calculate overall and breed-specific incidence rate (IR), age at first URT diagnosis and relative risk (RR) for URT disorders. For breeds with high RR for URT disorders, co-morbidities throughout the dog’s insurance period and age at death were investigated. The cohort included approximately 450,000 dogs. URT disorders had an overall IR of 50.56 (95% CI; 49.14–52.01) per 10,000 dog years at risk. Among 327 breeds, the English bulldog, Japanese chin, Pomeranian, Norwich terrier and pug had highest RR of URT disorders. Eight of 13 breeds with high RR for URT disorders were brachycephalic. The median age at first URT diagnosis was 6.00 years (interquartile range 2.59–9.78). French bulldogs with URT diagnoses had a significantly shorter life span (median = 3.61 years) than other breeds with URT diagnosis (median = 7.81 years). Dogs with high risk for URT disorders had more co-morbidities than average.

[This corrects the article DOI: 10.1371/journal.pgen.1009726.].

Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus ( Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated.

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs–the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heart-derived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.

This chapter will describe issues and actions across regions and countries, especially Europe AU: As per style, multiple para is not allowed in abstract. So we have merged into single para. Please check and confirm. and North America, encompassing kennel and breed clubs, veterinary organisations, research institutions, regulators, humane groups and other non-profits, e.g. the International Partnership for Dogs (IPFD). An historical perspective is included, as this informs efforts and challenges in many regions. The stage of development, degree and focus of interest on the brachycephalic issue are diverse, and there is a real need to combine forces to avoid redundant efforts and to maximise the sharing of resources. The case will be made that an even more collective approach to the problem would improve the situation for brachycephalic dogs in a timelier fashion. Work on the brachycephalic issue, will – and should – impact and inform interest in other issues related to extreme characteristics in dogs. As also explored in the other chapters in this text, the issues affecting brachycephalic breed health and welfare are wide-ranging and complex, for individual dogs, breeds, populations, dog owners, researchers, veterinarians and the public in general. Human behaviours and beliefs are impacted not only by science but also by emotions, and therefore, expertise from the fields of communication and even psychology is needed. At a societal level, public concern and even outrage about poor dog welfare, in general, and for brachycephalic breeds, in specific, have motivated regulators and government agencies, with issues arising from and influenced by long held and even historical attitudes. Cultural, socio-economic and national differences complicate the situation further across countries. Sourcing of dogs, breeding, trade, transport and marketing are factors that interplay between human desires and animal welfare. Notwithstanding varied local challenges, brachycephalic health and welfare epitomise a dog problem requiring international efforts across multiple stakeholder groups.

Background Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed. Results By employing genome-wide association followed by fine-mapping (top variant p -value = 5.7 × 10 − 6 ), integrated with whole-genome resequencing and copy number variation analysis, we detected a ~ 8.9 kbp deletion strongly associated ( p -value = 0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha ( IFNA ) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail. Conclusions Our results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.

Dogs are the most popular mammal kept as a companion animal globally. Positive human-dog relationships can benefit both the human owners as well as the dogs. However, popularity as a companion animal species does not universally benefit dogs in reverse. Breed-related health problems in dogs have received increasing attention over the last decade, sparking increased concerns for dog welfare across many stakeholders. Progress towards improved welfare requires meaningful collaboration between all those working in dog health, science and welfare. The International Partnership for Dogs (IPFD), together with an alternating host organisation, holds biennial meetings called the International Dog Health Workshops (IDHW). The IPFD 4th IDHW was hosted by the UK Kennel Club in Windsor, UK in May 2019. With the aim of encouraging international and multi-stakeholder collaborations that are effective and ongoing, the 4th IDHW 2019 provided a forum to identify specific needs and actions that could improve health, well-being and welfare in dogs, building on outcomes and evaluating actions of previous IDHWs. The workshop included 126 decision-leaders from 16 countries and was structured around five key themes identified as needing international, multi-stakeholder attention. These included the concept of “breed”, supply and demand, breed-specific strategies for health and breeding, genetic testing and extreme conformations. The review of progress made since the 3rd IDHW 2017 and the comprehensive lists of actions agreed upon during the current meeting suggest that movement from information and collaboration to action has been achieved. Working groups with specific tasks were identified and many plan to continue to communicate through forum communities on DogWellNet.com. The IDHW provides a forum for formal and informal discussion between relevant groups so that key dog health and welfare issues can be identified and defined, and plans can be agreed for effective actions to address them. The 3rd IDHW 2017 resulted in a number of significant outcomes. New and continuing actions were laid down at the 4th IDHW 2019, which will be re-evaluated at the 5th IDHW facilitating continual progress.

Here we present a new high-quality canine reference genome with gap number reduced 41-fold, from 23,836 to 585. Analysis of existing and novel data, RNA-seq, miRNA-seq and ATAC-seq, revealed a large proportion of these harboured previously hidden elements, including genes, promoters and miRNAs. Short-read dark regions were detected, and genomic regions completed, including the DLA, TCR and 366 cancer genes. 10x sequencing of 27 dogs uncovered a total of 22.1 million SNPs, Indels and larger structural variants (SVs). 1.4% overlap with protein coding genes and could provide a source of normal or aberrant phenotypic modifications.