Primary hypoadrenocorticism (Addison’s disease, AD) and symmetrical lupoid onychodystrophy (SLO) are two clinical conditions with an autoimmune etiology that occur in multiple dog breeds. In man, autoimmunity is associated with polymorphisms in immune-related genes that result in a reduced threshold for, or defective regulation of, T cell activation. The major histocompatibility complex (MHC) class II genes encode molecules that participate in these functions, and polymorphisms within these genes have been associated with autoimmune conditions in dogs and humans. Bearded collies have a relatively high prevalence of autoimmune diseases, particularly AD and SLO. Our study assessed the relationship between particular MHC (dog leukocyte antigen, DLA) class II haplotypes and the two autoimmune diseases most common in this breed. Moreover, five unrelated breeds at increased risk for AD were studied for comparative purposes and analyzed in the context of extant literature. A single DLA class II three-locus haplotype, determined by sequence-based typing, was associated with increased risk for AD (DLA-DRB1*009:01/DQA1*001:01/DQB1*008:02) in bearded collies. Comparative analysis with the five additional breeds showed limited allele sharing, with DQA1*001:01 and DQB1*002:01 being the only alleles observed in all breeds. A distinct three-locus risk haplotype (DLA-DRB1*001:01/DQA1*001:01/DQB1*002:01) was associated with AD in the West Highland white terrier and Leonberger. Two different risk haplotypes were associated with increased risk for SLO in the bearded collie (DLA-DRB1*018:01/DQA1*001:01/DQB1*002:01 and DLA-DRB1*018:01/DQA1*001:01/ DQB1*008:02). Two-locus DQ haplotypes composed of DLA-DQA1*001:01 in association with DLA-DQB1*002:01 or DLA-DQB1*008:02 make up the four risk haplotypes identified in the present study and are also found in other risk haplotypes previously associated with diabetes mellitus and hypothyroidism across different dog breeds. Our findings build upon previously published data to suggest that this two-locus (DQ) model serves as a good indicator for susceptibility to multiple organ-specific autoimmune diseases in the canine population. However, it is also clear that additional loci are necessary for actual disease expression. Investigation of affected and unaffected dogs carrying these predisposing DQ haplotype signatures may allow for the identification of those additional genetic components that determine autoimmune disease expression and organ specificity.
Individual dog breeds are often reported as predisposed to specific breed-related disorders but reliable epidemiological data on disease prevalence are sparse. The Miniature Schnauzer in the UK is a popular small breed dog that is often considered as relatively healthy and long-lived, but is this really true? This study aimed to use data from the VetCompass™ Programme at the Royal Veterinary College to characterise the demography, mortality and common disorders of the general population of Miniature Schnauzers under veterinary care in the UK. The study population of 455,557 dogs from 304 clinics in the VetCompass™ database under veterinary care during 2013 included 3857 Miniature Schnauzers (0.85%). For dogs with data available, 1771 (56.9%) were neutered and 1893 (49.2%) were females. Mean adult bodyweight overall was 9.9 kg (SD 2.2 kg) and median longevity was 11.6 years (IQR 9.3–13.1, range 0.5–17.0). The most prevalent fine-level precision disorders recorded were periodontal disease (n = 343, prevalence 17.4, 95% CI: 15.7–19.1), obesity/overweight (164, 8.3, 95% CI: 7.1–9.6), anal sac impaction (114, 5.8, 95% CI: 4.8–6.9), vomiting (100, 5.1, 95% CI% 4.1–6.1) and otitis externa (99, 5.0, 95% CI% 4.1–6.1). The most prevalent grouped-level precision disorders were dental (n = 378, prevalence: 19.2, 95% CI: 17.5–21.0), enteropathy (270, 13.7, 95% CI: 12.2–15.3), cutaneous (250, 12.7, 95% CI: 11.2–14.2) and aural (197, 10.0, 95% CI: 8.7–11.4). This study provides generalisable evidence on the demography, longevity and most prevalent disorders in the Miniature Schnauzer breed in the UK. Awareness of common diseases and breed predispositions can support evidence-based policies to improve breed health, guide veterinary surgeons when producing differential diagnosis lists, and assist owners when purchasing or caring for their pets.
Abstract Background Making assumptions regarding temperament and intelligence based on the physical appearance of dogs can be a conscious or unconscious human act. Labrador retrievers with chocolate-coloured coats are anecdotally considered to be less trainable and more hyperactive and aggressive than their black or yellow peers. To test these assertions, we analysed the owner-reported behavioural traits of Labradors in relation to both their observable coat colour, and their TYRP1 and MC1R genotypes. Results We used the results of an owner-based questionnaire to determine scores for 21 behavioural traits and test whether these scores varied with coat colour (n = 225). Familiar dog aggression was the only trait that was found to vary significantly with coat colour (P = 0.013). Yellow Labradors had a higher score than chocolate Labradors, even when corrected for multiple testing (P = 0.021). We repeated the analyses for a subset of 63 Labradors with available genotyping data for the genes (MC1R and TYRP1) that are known to determine the primary coat colours in Labradors. Familiar dog aggression scores varied with both the observed coat colour and MC1R genotype. Dogs homozygous for MC1R recessive allele (with yellow coat colour) scored higher for familiar dog aggression than either black or chocolate Labradors. However, no association maintained significance when incorporating Bonferroni correction. Dog trainability scores decreased additively as the number of recessive brown alleles for TYRP1 increased. This allelic association was independent of the observable coat colour. Dogs homozygous for the brown allele were considered less trainable than dogs with no brown alleles (P = 0.030). Conclusions Our results do not support that chocolate-coloured Labradors are more hyperactive or aggressive than either black or yellow Labradors. Trainability scores varied with TYRP1 genotype but not the observable coat colour. Further validation is required.
Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in dogs. The Irish Wolfhound breed has a high prevalence of AF making them an ideal breed to investigate possible genetic contributions to this disease. The aim of this study was to perform a heritability analysis in North American Irish Wolfhounds using phenotype data from cardiac screenings performed between 2000 and 2019 in order to determine how much of this disease can be attributed to genetics compared to environmental causes. The second aim was to determine the disease mode of inheritance to help inform prevention and breeding practices. Results There were 327 Irish Wolfhounds diagnosed with AF and 136 Irish Wolfhounds over 8 years of age without AF. The estimated mean (95% confidence interval) heritability of AF in Irish Wolfhounds was 0.69 (0.50–0.86). The pedigree was consistent with a dominant mode of inheritance. Conclusion Results of this study indicate a strong genetic contribution to AF in Irish Wolfhounds and suggest that future research to identify causative genetic mutations is warranted.
Background N-glycolylneuraminic acid (Neu5Gc) is synthesized from its precursor N-acetylneuraminic acid (Neu5Ac) by cytidine-5′-monophospho-N acetylneuraminic acid hydroxylase (CMAH), which is encoded by the CMAH gene. Most mammals have both Neu5Gc and Neu5Ac, but humans and ferrets have only Neu5Ac because of loss-of-function mutations. Dogs and cats are polymorphic for Neu5Gc and Neu5Ac expression like cats, in which the CMAH gene is responsible for the AB Blood group system. Although the CMAH gene has been characterized in many species, not much is known about it in dogs. In this study, we cloned the dog CMAH cDNA, and performed mRNA expression analysis of this gene in several organs. We also identified single nucleotide polymorphisms (SNPs) in the CMAH gene. Results We cloned the 1737-bp open reading frame of the dog CMAH gene. This gene consists of at least 14 coding exons and codes for a polypeptide of 578 amino acids and is located on chromosome 35. The amino acid identities of dog CMAH with the corresponding sequences from cat, pig, chimpanzee, mouse, and rat were high (89 to 93%). RT-PCR analysis showed that the dog CMAH cDNA was expressed in various tissues. We identified four exonic SNPs (three synonymous and one non-synonymous), 11 intronic SNPs, and an indel in 11 dog breeds by analyzing the nucleotide sequences of the 14 exons, including the coding region of CMAH. In the genotype of the non-synonymous SNP, c.554 A > G (p.Lys185Arg), in a total of 285 dogs of seven different breeds, the allele G was widely distributed, and the allele A was the most frequent in the Shiba dogs. The dogs expressing Neu5Ac did not carry the loss-of-function deletion of CMAH found in humans and ferrets, and it remains unclear whether the point mutations influence the expression of Neu5Ac. Conclusions We characterized the canine CMAH gene at the molecular level for the first time. The results obtained in this study provide essential information that will help in understanding the molecular roles of the CMAH gene in canine erythrocyte antigens.
In the original publication of this article [1], due to an error in a single count relating to the denominator used for this study, some of the derived values were wrong, so that abstract, plain English summary, results and Fig. 1 all need to be revised.
The absence of selective pressure against recessive deleterious mutations in the heterozygous state means that virtually every individual will carry several such mutations which have arisen over time. The inflation in frequency of a few of these mutations due to selective processes during domestication and breed formation have left modern domestic dog breeds with a high burden of genetic disease due to mutations at single genes. This has stimulated research into the causal mutations, and a consequential market in DNA tests, which enable breeders to distinguish heterozygotes from wild type homozygotes and determine pairings that will avoid producing diseased progeny. The genotypes of progeny of parents with known genotypes themselves may in some cases be definitively inferred. Importantly, two parents homozygous for non-disease causing alleles, will produce progeny with the same genotype, which may be assigned to the offspring (e.g. as 'hereditary clear') without the need for further testing. However, the veracity of assigned genotypes is dependent on the parentage being recorded without error, which is not the case in most species. Simulations presented here demonstrate that a modest rate of false paternity can result in a notable proportion of 'hereditary clear' assignments being false when 'hereditary clear' status is assigned across a number of generations (error rates exceeding 5% after 6 generations with a disease causing mutation frequency of 0.2). Erroneous assignment of 'hereditary clear' genotypes risks the production of puppies with the very disease for which a DNA test is available allowing avoidance. In light of these findings and to reduce the risks of producing puppies destined to be affected by such diseases, the Kennel Club has determined to limit the assignment of 'hereditary clear' status of registered dogs to 2 generations, with effect from January 2022.
The greyhound is a sighthound known for its speed and agility. Greyhounds were selectively bred as functional racing animals but increasingly are kept as pets in the UK, often after their racing careers are over. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass™ clinical data, this study aimed to characterise the demography, mortality and common disorders of the general population of pet greyhounds under veterinary care in the UK. Greyhounds comprised 5419/ 905,544 (0.60%) dogs under veterinary care during 2016 from 626 clinics. Mean adult bodyweight was 29.7 kg (standard deviation [SD] 4.5 kg). Males (32.3 kg, SD 4.1 kg) were heavier than females (27.2 kg, SD 3.3 kg) (P < 0.001). Mean age was 7.6 years (SD 3.4). The most common colours were black (39.2%), black and white (20.8%), brindle (12.0%). Based on 474 deaths, median longevity was 11.4 years (range 0.2–16.5). Females (11.8 years) outlived males (11.2 years) (P = 0.002). The most common grouped causes of death were neoplasia (21.5%, 95% CI: 17.4–26.0), collapse (14.3%, 95% CI: 10.9–18.2) and musculoskeletal disorder (7.8%, 95% CI: 5.3–11.0). Based on a random subset of 2715/5419 (50.1%) greyhounds, 77.5% had > 1 disorder recorded during 2016. The most prevalent specific disorders were periodontal disease (39.0%, 95% CI: 37.2–40.9), overgrown nails (11.1%, 95% CI 10.0–12.4), wound (6.2%, 95% CI: 5.3–7.1), osteoarthritis (4.6%, 95% CI: 3.8–5.4) and claw injury (4.2%, 95% CI: 3.4–5.0). These findings highlight the greyhound as a relatively common pet dog breed in the UK, accounting for 0.6% of dogs under primary veterinary care. Dental disease, trauma and osteoarthritis were identified as common health issues within the breed. Knowledge of common disorders can help greyhound breeders and regulators to prioritise breeding, rearing and racing management to mitigate some of the most prevalent issues. Greyhound rehoming organizations can also better inform adopters about prophylactic care.
Von Willebrand disorder type I (vWDI) is known as an inherited bleeding disorder in different dog breeds following an autosomal recessive inheritance. The Kromfohrländer is a rare dog breed with an increased incidence of unclear bleeding episodes and prolonged coagulation time during/after surgery or injuries, indicating a defect in one or more critical proteins of the coagulation cascade. The objective of this study was to determine whether the c.7437G > A mutation in the VWF gene previously shown to cause von Willebrand disorder type I in Doberman Pinscher is also linked to this disease in the Kromfohrländer breed and to serum concentrations of vWF. Furthermore, establish a possible link between bleeding phenotype, vWF serum concentrations and VWF mutation status. Eighty-seven Kromfohrländer were genotyped for the G > A von Willebrand type I mutation. For detection of the associated mutation we used an endpoint genotyping method. We identified the G > A von Willebrand type I mutation in 80.5% of our study population. 65.5% were heterozygous (WT/MUT) and 15.0% were homozygous for the mutation (MUT/MUT). 21% of the overall study population exhibited bleeding symptoms. 45.5% of all homozygous dogs (MUT/MUT) showed bleeding symptoms. In contrast, wild-type homozygotes exhibited no bleeding symptoms, whereas 23.2% of the heterozygotes did. VWF serum concentrations varied from 28 to 137% in wild-type dogs while in heterozygous and homozygous dogs the concentration ranged from 3 to 77% and 1 to 23%, respectively (p < 0.05) Based on our data, we found the G > A mutation in the VWF gene in the Kromfohrländer breed and the subsequent vWDI as the underlying cause for the bleeding episodes and delayed coagulation in heterozygous and homozygous dogs. Since both, heterozygotes and homozygotes show reduced vWF serum concentrations and exhibit to a certain percentage the vWD syndrome phenotype, we postulate that, in contrast to most other vWDI affected breeds, inheritance follows an autosomal dominant mode with incomplete penetrance.
In humans, ADAMTS17 mutations are known to cause Weill-Marchesani-like syndrome, which is characterised by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. Breed-specific homozygous mutations in ADAMTS17 are associated with primary open angle glaucoma (POAG) in several dog breeds, including the Petit Basset Griffon Vendeen (PBGV) and Shar Pei (SP). We hypothesised that these mutations are associated with short stature in these breeds. Two hundred thirty-three PBGV and 66 SP were genotyped for their breed-specific ADAMTS17 mutations. The height of each dog was measured at the withers. We used linear (per allele) regression to assess the association between ADAMTS17 mutations and height as a continuous variable, and linear regression and likelihood ratio tests to assess the shape of the association by comparing a general model with a linear (per allele) model. The adjusted mean heights of affected, carrier, and clear PBGV were 33.49 cm (n = 21, 95% CI 32.78–34.19 cm), 34.88 cm (n = 85, 95% CI 34.53–35.25 cm), and 34.92 cm (n = 121, 95% CI 34.62–35.21 cm), respectively. The mean heights of affected, carrier, and clear SP were 43.96 cm (n = 9, 95% CI 41.88–46.03 cm), 47.56 cm (n = 28, 95% CI 45.50–48.63 cm), and 48.95 cm (n = 23, 95% CI 47.80–50.11 cm), respectively. There was a significant difference between the height of affected and clear animals in the PBGV (P = 0.001) and the SP (P = < 0.0001). ADAMTS17 POAG mutations are significantly associated with height in these breeds.
Labrador retrievers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Labrador retrievers under UK veterinary care.
About this supplement These abstracts have been published as Canine Genetics and Epidemiology Volume 5 Supplement 2, 2018: Selected canine abstracts from the Companion Animal Genetic Health conference 2018 (CAGH 2018): Canine Genetics and Epidemiology. A meeting report from the conference has been published as Canine Genetics and Epidemiology Volume 5 Supplement 1, 2018 and is available online at https://doi.org/10.1186/ s40575-018-0061-0. Selected feline abstracts from the conference have been published as Irish Veterinary Journal Volume 71 Supplement 1, 2018 and are available online at https://doi.org/10.1186/s13620-018-0126-0.
BACKGROUND:Selective breeding in populations with a limited effective population size may result in a loss of genetic diversity, which can cause an increased concentration of specific disease liability genes. The Dutch Shepherd Dog (DSD) in the Netherlands is an example of such a breed with a small effective population.OBJECTIVE:To evaluate the measurement of genetic diversity and multiplex DNA panel screening for implementation in a breeding strategy for the Dutch Shepherd Dog (DSD) and to investigate the clinical relevance of potentially identified mutations in the multiplex DNA panel screening.RESULTS:Genome-wide SNP testing showed genetic isolation and reduced genetic diversity within coat variety subgroups of the DSD. Panel screening identified a Von Willebrand's Disease type I mutation. Although decreased Von Willebrand's Factor proteins were significantly lower in DSDs carrying the VWD-I allele compared to the wildtype, clinical follow-up did not show a significant association between the clinical phenotype and VWD-I genotype.CONCLUSIONS:Genetic relationship measurement within a breed population may be a useful tool to enable breeding strategies to conserve genetic diversity. Results from a disease panel screening need to be evaluated for clinical relevance before breed selection restrictions can be considered.
Intervertebral disc herniation (IVDH) involves displacement of the intervertebral disc secondary to disc degeneration and is extremely common in dachshunds. Clinical signs include pain with or without paresis or paralysis. Mortality rate is high and some cases are left with permanent disability even after treatment. Aims of this study were twofold: Firstly, to investigate whether neutering, i.e. gonadectomy, is associated with increased risk of IVDH in dachshunds, and secondly to investigate whether age of neutering alters risk of IVDH in this breed.
The domestic dog is one of the most diverse mammalian species, exhibiting wide variations in morphology, behaviour and morbidity across breeds. Therefore, it is not unexpected that breeds should also exhibit variation in mortality and longevity. While shorter longevity per se may not necessarily be a welfare issue, a generally foreshortened lifespan in a breed that is accompanied by a high prevalence of a particular cause of death may reveal potentially serious welfare concerns and highlight scope to improve breed welfare. Survey data gathered directly from owners offer useful insights into canine longevity and mortality that can support the overall evidence base for welfare reforms within breeds.
Lipomas are masses of mesenchymal origin, comprising of adipocytes, and are often clinically unremarkable but can be alarming to owners. Although lipomas are reportedly common in dogs, no studies have specifically investigated risk factors associated with their occurrence. This study was a large-scale retrospective analysis of electronic patient records of dogs attending practices participating in VetCompass™. Univariable and multivariable logistic regression methods were used to evaluate associations between risk factors and primary-care veterinary diagnosis of lipoma.
BACKGROUND:Working dog handlers and breeders have very different behavioural requirements in the animals that they employ for managing livestock. The Australian Working Kelpie breed may be used in several working contexts, notably yards, paddocks and a combination of both. The working context influences the skillsets required and gives rise to three corresponding work-types: Yard, Paddock and Utility Kelpies. In particular, dogs used for working stock in the confines of yards and trucks interact with stock more forcefully than those mustering in larger areas (paddocks) where they can herd stock effectively from a greater distance. This article explores owner assessments of dog working quality and assessment of genomic similarity by multidimensional scaling, to ask whether it is sufficient for breeders to aim for a multipurpose breeding objective, or whether breeding only specialist lines maximises user satisfaction for yard and paddock work.RESULTS:Reported owner perceptions of 298 dogs assessed with the Livestock Herding Dog assessment tool showed that dog handlers across all working types were very happy with their dogs' level of general skills.Compared with both Yard and Utility Kelpies, Paddock Kelpies had significantly lower trait scores for force (pressure applied by the dog to move livestock), willingness to back the stock (run along a sheep's dorsum) and bite (frequency of using the mouth to grab or bite the livestock). Meanwhile, compared with both Paddock and Utility Kelpies, the Yard Kelpies had significantly higher scores for hyperactivity and excitability (both with and without stock) and impulsiveness without stock. As one would predict for all-rounders, Utility Kelpies had intermediate scores for all behaviours and working traits.CONCLUSIONS:Specialist characteristics were displayed by dogs in the Yard Kelpie and Paddock Kelpie groups. In particular, Yard Kelpies demonstrate higher excitability, willingness to back the stock, and a higher tendency to bark and bite the stock. Conversely, Paddock Kelpies rarely display these characteristics. Utility Kelpies, as the name suggests, are intermediate between the other two groups and display the characteristics of both. Genetic analysis suggests that the Yard, Utility and Paddock Kelpies are not distinguishable at a DNA level. In conclusion, at this time there is no suggestion of a breed split in the Australian Working Kelpie generated by selection for work type. A common breeding objective should enable dogs to be produced that fulfil all potential working requirements. This reinforces the importance of breeder skill in recognising the phenotypic potential of pups in order to place them in appropriate working contexts.
Despite its Gallic name, the French Bulldog is a breed of both British and French origin that was first recognised by The Kennel Club in 1906. The French Bulldog has demonstrated recent rapid rises in Kennel Club registrations and is now (2017) the second most commonly registered pedigree breed in the UK. However, the breed has been reported to be predisposed to several disorders including ocular, respiratory, neurological and dermatological problems. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass™ clinical data, this study aimed to characterise the demography and common disorders of the general population of French Bulldogs under veterinary care in the UK.
