Canine genetics and epidemiology最新文献

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: 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.

Results: 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).

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: ADAMTS17 POAG mutations are significantly associated with height in these breeds.

Background: 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.

Objective: 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.

Results: 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).

Conclusion: 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.

Background: 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.

Results: 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).

Conclusion: 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.