Genome wide association study in Swedish Labrador retrievers identifies genetic loci associated with hip dysplasia and body weight.

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.

Heritability and genetic trend of body weight in dogs of different breeds in Sweden.

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 in dogs is often considered to cause problems, for instance, resulting in hip and elbow diseases. Furthermore, there is a huge variation in body conformation and size between different dog breeds, which is related to breeding for specific appearances and genetic traits. The aim of this study was to investigate the genetic variation of body weight within different dog breeds. To study this, we examined 19 dog breeds with an average body weight of 8 to 56 kg. We found that on average about 50% of the total variation in body weight between dogs, within a breed, depends on genetic differences, but with a range from 35% to 70% depending on breed. There were rather small changes over time in the genetic predisposition for high or low body weight; the largest changes were 0.6 kg over a 10-yr period.

Demography and disorders of English Cocker Spaniels under primary veterinary care in the UK.

BACKGROUND: The English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS. RESULTS: English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25-8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12-17.35). The annual proportional birth rate was relatively stable between 2.97-3.51% from 2005-2016. The most common specific diagnoses were periodontal disease (n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31-22.62), otitis externa (n = 234, 10.09%, 95% CI: 8.87-11.32), obesity (n = 229, 9.88%, 95% CI: 8.66-11.09), anal sac impaction (n = 187, 8.07%, 95% CI: 6.96-9.18), diarrhoea (n = 113, 4.87%, 95% CI: 4.00-5.75), and aggression (n = 93, 4.01%, 95% CI: 3.21-4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) (P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) (P = 0.010). The median age at death was 11.44 years (IQR 9.46-13.47) and the most common grouped causes of death were neoplasia (n = 10, 9.26%, 95% CI: 3.79-14.73), mass-associated disorders (n = 9, 8.33%, 95% CI: 4.45-15.08), and collapse (n = 8, 7.41%, 95% CI: 3.80-13.94). CONCLUSIONS: Periodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS.

The English Cocker Spaniel (ECS) is a popular family dog in the UK, but there is limited information regarding common disorders affecting the breed. The goal of this study was to describe demography (age, sex, neuter, and bodyweight), disease occurrence, lifespan, and reasons for death in ECS by using data from the VetCompass™ Programme. The VetCompass™ Programme collects information from anonymised clinical records of dogs attending first-opinion veterinary practices in the UK. This study hypothesised that aggression is more common in males than in females, and in solid-coloured than in bi-coloured ECS dogs.English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. Breed popularity did not vary much from 2005 to 2016, comprising around 3% of all dogs born each year. The average age of dogs in 2016 was 4.57 years and the average adult bodyweight was 15.05 kg. The most common disorders were periodontal disease (infection of the tissues that hold the teeth in place, affecting 20.97% of the dogs), inflammation of the external ear canal (10.09%), obesity (9.88%), anal sac impaction (8.07%), diarrhoea (4.87%), and aggression (4.01%). Aggression was more common in males (4.95%) than in females (2.87%) and in solid-coloured (7.00%) than in bi-coloured (3.66%) dogs. The frequency of aggression also varied across the four most common solid colours (black, liver, golden, red), with golden-coloured dogs showing the most aggression (12.08%). The average lifespan was 11.44 years and the most common cause of death was tumours.This study shows that first-opinion clinical records can help us to understand and enhance breed health. The results can guide veterinarians in giving breed-adapted information to owners of ECS and help breeders to optimise breeding decisions. Further, this information can be used by future ECS owners to make more informed decisions when acquiring a dog if avoidance of aggression is a key priority. Periodontal disease was the most common condition affecting the breed, which highlights the importance of regular veterinary dental checks and as well as tooth brushing in ECS.

Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy.

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.

Correction: The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels.

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

The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels.

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.

A novel canine reference genome resolves genomic architecture and uncovers transcript complexity.

We present GSD_1.0, a high-quality domestic dog reference genome with chromosome length scaffolds and contiguity increased 55-fold over CanFam3.1. Annotation with generated and existing long and short read RNA-seq, miRNA-seq and ATAC-seq, revealed that 32.1% of lifted over CanFam3.1 gaps harboured previously hidden functional elements, including promoters, genes and miRNAs in GSD_1.0. A catalogue of canine "dark" regions was made to facilitate mapping rescue. Alignment in these regions is difficult, but we demonstrate that they harbour trait-associated variation. Key genomic regions were completed, including the Dog Leucocyte Antigen (DLA), T Cell Receptor (TCR) and 366 COSMIC cancer genes. 10x linked-read sequencing of 27 dogs (19 breeds) uncovered 22.1 million SNPs, indels and larger structural variants. Subsequent intersection with protein coding genes showed that 1.4% of these could directly influence gene products, and so provide a source of normal or aberrant phenotypic modifications.

Swedish Experiences From 60 Years of Screening and Breeding Programs for Hip Dysplasia-Research, Success, and Challenges.

A screening program for hip dysplasia (HD) was introduced in Sweden during the 1950s for German shepherd dogs, before for a few breeds and now any breed. Degree of canine HD was originally graded 1-4 (slight, mild, moderate, and severe) and used in Swedish screening program up to year 2000 and was thereafter replaced by letters A-E with A and B for no signs/near normal, C for mild, D for moderate, and E for severe HD. Final scoring is based on "the worst" side. In Sweden, 70% of all dogs are registered by the Swedish Kennel Club, and in relevant breeds, almost all breeding stock and 30-50% of all dogs are screened for HD. By an extensive database of all dogs registered since 1976 and mandatory identification by microchip, all results can be linked to dogs well-defined by identity and ancestral background. An implementation of structured screening and genetic health programs resulted in markedly decreased prevalence of HD already during the 1980s. The programs are based on open registries and on positive as well as negative results for identified individuals linked to their ancestral background. The successful decrease in moderate and severe HDs is illustrated for seven common breeds. However, there is also the challenge of a further decrease when already almost all breeding is performed with unaffected breeding stock. Handling that and the increased relative prevalence of less severe grades of HD (grade C) calls for breed-specific breeding strategies, taking into account the prevalence and clinical significance in each breed. Further decrease might rather be achieved by using estimated breeding values and genomic selection instead of more extensive and costly screening procedures. For the public perception of HD, the value of a clear distinction between grades D and E as a good predictor of the clinical entity vs. grade C as a tool to refine the selection criteria for breeding stock is indicated.

Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs.

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.

Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs.

BACKGROUND: Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome-wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin-2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities. OBJECTIVES: The main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD-affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location. ANIMALS/METHODS: Skin biopsies were collected from nine CAD-affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology. RESULTS: We observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding-partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed. CONCLUSION: Plakophilin-2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes.

Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs.

BACKGROUND: Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS: Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS: Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development-Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus.

Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10-8). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility.

Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus.

AIMS/HYPOTHESIS: Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. METHODS: Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide. RESULTS: None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted. CONCLUSIONS/INTERPRETATIONS: Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis.

Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6×10(-8)) from each analysis showed that one haplotypic pair (H13-11) was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F ST) distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05) renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts.

Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis.

Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7), pgenome = 0.03). The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.

Rules, regulations, strategies and activities within the Fédération Cynologique Internationale (FCI) to promote canine genetic health.

The structure and aims of the Fédération Cynologique Internationale (FCI) are outlined, with a focus on the rules and regulations that are relevant to breeding and genetic health of dogs. Recently adopted strategies to enhance canine genetic health and activities to counteract exaggerated anatomical features are highlighted. Actions by the FCI regarding recognition of breeds and doping rules, under direct control by cynological organisations, are included, based on their relevance to canine health.

A breed-matched case-control study of potential risk-factors for canine pyometra.

The objective was to evaluate plausible risk-factors for pyometra, a common disease affecting almost 25% of all (unspayed) female dogs before 10 years of age. Because of the strong breed-predilection, an age- and breed-matched case-control study was undertaken on 87 pairs (pyometra-cases and healthy controls) from five breeds (Rottweiler (n = 13), Collie (n = 8), Golden retriever (n = 24), Labrador retriever (n = 16) and German shepherd dog (n = 26)). The mean age was 7.9 y (range 0.8-13.8 y). Variables analyzed included pseudopregnancy, age at first oestrus, length of and regularity of the interoestrus interval, hormone treatments, nulliparity, number of parities, age at first whelping, previous urinary tract infections and mammary tumours. Data were modelled multivariably using matched-pair conditional logistic regression. Analysing interactions with breed, previous pregnancy was statistically associated with pyometra. When amalgamated, in three breeds previous pregnancy was protective (Rottweiler, Collie, Labrador retriever) and in one breed statistically intermediate (German shepherd dog) when compared to the baseline (Golden retriever). Previous pregnancy was a statistically significant factor that had a protective effect against pyometra in some breeds but not in the Golden retriever breed. These findings indicate that protective- and risk-factors may vary between different breeds. The obvious problem with low power and limited possibility for extrapolation, using few dogs in few breeds, is acknowledged. However, it is suggested that failure to control for the confounding effect of breed, especially in epidemiological studies on dog diseases, may lead to potentially erroneous conclusions.

Peripheral administration of pancreatic polypeptide inhibits components of food-intake behavior in dogs.

Pancreatic polypeptide (PP) belongs to the neuropeptide Y (NPY) family of peptides and is released from pancreatic F cells postprandially. PP functions as a peptide hormone and has been associated with decreased food intake in humans and rodents. Our study describes the effects of PP on feeding behavior in dogs, whose mammalian order (Carnivora) is more distantly related to primates and rodents than these are to each other. Furthermore, obesity is becoming more prevalent in dogs which makes knowledge about their appetite regulation highly relevant. Repeated peripheral administration of physiological doses of PP (three injections of 30 pmol/kg each that were administered within 30 min) to six male beagle dogs prolonged the median time spent eating three servings of food by 19% but resulted in no reduction of food intake. In addition, PP decreased the duration of food-seeking behavior after the first serving by 71%. Thus, a physiological dose of PP seems to decrease both the appetitive and the consummatory drive in dogs.

Association between radiographic assessment of hip status and subsequent incidence of veterinary care and mortality related to hip dysplasia in insured Swedish dogs.

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.

Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs.

The dorsal hair ridge in Rhodesian and Thai Ridgeback dogs is caused by a dominant mutation that also predisposes to the congenital developmental disorder dermoid sinus. Here we show that the causative mutation is a 133-kb duplication involving three fibroblast growth factor (FGF) genes. FGFs play a crucial role in development, suggesting that the ridge and dermoid sinus are caused by dysregulation of one or more of the three FGF genes during development.