Canine medicine and genetics最新文献

Background: Canine flank alopecia (CFA) is a skin condition in dogs characterized by non-inflammatory, seasonally recurring episodes of localized hair loss and often hyperpigmentation of the affected skin. A genetic basis is suspected because of the predisposition in certain breeds, such as the Rhodesian Ridgeback (RR). This study investigated the possible role of the canine melanophylin (MLPH) gene in CFA among RRs through pedigree analysis and MLPH genotyping.

Results: We included 24 CFA-affected and 12 non-CFA-affected control RRs. Pedigree analysis revealed inbreeding loops and close family relationships among the CFA-affected dogs, indicating the potential heritability of CFA. MLPH genotyping revealed 3/24 (12.5%) affected dogs and 1/12 (8.3%) control dogs to be heterozygous (Dd) for the dilute (d) allele, indicating no difference between these groups. None of the dogs were found to be homozygous (dd). Statistical analysis did not reveal an association between the MLPH-d allele and CFA.

Conclusions: The familial patterns among affected RRs observed through pedigree analysis suggest a potential genetic component in CFA. However, our findings from the MLPH genotyping did not reveal that the MLPH gene is involved in this skin condition in RRs. However, further genetic studies are needed to clarify the etiology of CFA in RR dogs.

The Wnt signaling pathway is critical for normal embryonic development. Disruptions in the Wnt signaling pathway have been linked to neurological disorders. The RAPGEF5 protein is a partner in Wnt signaling and a RAPGEF5 3-bp insertion is associated with increased risk for idiopathic epilepsy in the Belgian shepherd dog. The 3-bp insertion risk variant introduces an alanine residue predicted to disrupt the protein. Wildtype and the risk variant RAPGEF5 cDNAs were cloned into green fluorescent protein (GFP) expression vectors and transfected into canine kidney cells. The cellular localization of each GFP-labeled RAPGEF5 protein was assessed. Variant RAPGEF5 protein was altered in its localization from that of the wildtype protein and rather than localized to the nucleus and cytoplasm as seen for the wildtype, it was predominantly found in the cytoplasm. Belgian shepherds with the risk variant for RAPGEF5 may have altered Wnt signaling due to modified intracellular localization which in turn could thereby contribute to the expression of idiopathic epilepsy.

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.

Background: Shih Tzus are a popular dog breed in the UK although there is relatively little reported information on their health. This study aimed to characterise the demography, common disorders and mortality of Shih Tzus under primary veterinary care during 2016 in the UK using de-identified clinical records from the VetCompass™ Programme.

Results: The study population of 336,865 dogs under veterinary care during 2016 included 11,082 Shih Tzus (3.3%). The median age was 4.1 years (IQR: 2.1-7.1, range: 0.3-20.4) and mean adult bodyweight was 7.9 kg (SD: 1.9 kg). Annual proportional births increased from 2.2% of all dog births in 2005 to 3.8% in 2013, dropping to 3.3% by 2016. From a random subset of 2,423 Shih Tzus that had information extracted on disorders diagnosed during 2016, the most prevalent fine-level precision disorders were periodontal disease (n = 229, prevalence 9.5%, 95% CI: 8.4-10.7), anal sac impaction (180, 7.4%, 95% CI: 6.5-8.5) and ear disorders (134, 5.5%, 95% CI: 4.7-6.5). The most prevalent grouped-level precision disorders were cutaneous (n = 402, prevalence: 16.6%, 95% CI: 15.2-18.1), dental (322, 13.3%, 95% CI: 12.0-14.7), and ophthalmological (289, 11.9%, 95% CI: 10.7-13.3). Males were more likely than females to be diagnosed with skin disorders (P = 0.007) and musculoskeletal disorders (P = 0.010) while females were more likely than males to be diagnosed with hernias (P = 0.005). The median age of death was 12.7 years (IQR 8.7-14.3, range 2.0-19.9) and did not differ statistically between males and females. The most common grouped causes of death were enteropathy (7.9%, 95% CI: 3.9-15.4), heart disease (7.9%, 95% CI: 3.9-15.4) and poor quality of life (7.9%, 95% CI: 3.9-15.4).

Conclusions: Periodontal disease, anal sac impaction and ear disorders were identified as common health issues. Shih Tzus had higher prevalence of anal sac impaction, umbilical hernias and eye problems than reported previously in dogs overall, suggesting potential predispositions. Shih Tzus appear to be relatively long-lived compared to previous reports of lifespan in dogs overall. The results can inform veterinarians and owners on priority disorders for monitoring to protect welfare. Oral hygiene was highlighted as a healthcare priority.

Background: The English Cocker Spaniel (ECS) is one of the most popular dog breeds in the UK but information on disorder predisposition and protection is limited. Using anonymised veterinary clinical data from the VetCompass™ Programme, this study aimed to compare disorder predisposition and protection between the ECS and the remaining dogs under primary veterinary care in the UK during 2016. Electronic patient records for random samples of ECS and non-ECS were reviewed. The most common disorders diagnosed during 2016 were extracted and compared using multivariable logistic regression, controlling for confounders.

Results: The analysis included random samples of 2510/10,313 (24.3%) ECS and 7813/326,552 (2.39%) non-ECS. After accounting for confounding by age, sex, bodyweight within breed-sex, insurance status and veterinary practice group, the ECS had increased odds of 21/43 (48.85%) disorders at fine-level precision, with highest odds for aural discharge (odds ratio (OR) 14.66, 95% confidence interval (CI): 7.73-30.90, P <  0.001) and keratoconjunctivitis sicca (OR 7.64, 95% CI: 4.33-14.14, P <  0.001) and lowest odds for atopic dermatitis (OR 0.14, 95% CI: 0.05-0.31, P <  0.001) and allergy (OR 0.14, 95% CI: 0.06-0.28, P <  0.001).

Conclusions: This study provides evidence for strong predisposition to aural and ocular disorders and protection from hypersensitivity disorders in the ECS. These results can aid dog owners, breeders, and veterinarians to better monitor health in ECS, and promote earlier diagnosis with improved prognosis. Further, the results can help breeding organisations establish key priorities the health-based reforms of the ECS.

Background: The Shar Pei is a common dog breed with a distinctive appearance caused by hyaluronosis that has been linked with several health conditions. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Shar Pei in the UK in 2013.

Results: The study population of 455,557 dogs included 1913 (0.42%) Shar Pei. The mean adult bodyweight was 22.26 kg. The most prevalent fine-level precision disorders were entropion (prevalence 17.88%, 95% CI: 16.16-19.59), otitis externa (16.36%, 95% CI: 14.70-18.02), ear disorders (6.69%, 95% CI: 5.57-7.81), aggression (5.23%, 95% CI: 4.23-6.22), and pyoderma (4.29%, 95% CI: 3.38-5.19). The most prevalent disorder groups were ophthalmologic (prevalence = 22.27%, 95% CI: 20.40-24.13), dermatological (21.01%, 95% CI: 19.19-22.84), aural (18.66%, 95% CI: 16.92-20.41), traumatic injury (7.53%, 95% CI: 6.35-8.71) and behavioural (7.21%, 95% CI: 6.05-8.37). The median longevity of 190 Shar Pei that died during the study period was 7.28 years (IQR 5.04-10.05, range 0.04-15.04). Of 184 deaths with a recorded method of death, 157 (85.33%) deaths involved euthanasia and 27 (14.67%) deaths were unassisted. Among 136 (71.58%) deaths with a recorded biomedical cause of death, the most common causes of death at group level precision were neoplasia (15.44%, 95% CI: 9.37-21.51), renal disorders (13.24%, 95% CI: 7.54-18.93), and behavioural disorders (11.03%, 95% CI: 5.76-16.29).

Conclusions: Almost one fifth of Shar Pei receive veterinary care each year for entropion, a condition linked strongly with the extreme conformation of thickened and folded skin and bristly hair that characterises the Shar Pei breed. Several other common disorders are also linked to hyaluronosis. Current UK legislation can help support efforts to avoid breeding or acquiring animals with extreme conformations and to promote adequate veterinary care for already-owned animals with extreme conformations.

Background: Cortical folding is related to the functional organization of the brain. The TMF-1 regulated protein (TRNP1) regulates the expansion and folding of the mammalian cerebral cortex, a process that may have been accelerated by the domestication of dogs. The objectives of this study were to sequence the TRNP1 gene in dogs and related canid species, provide evidence of its expression in dog brain and compare the genetic variation within dogs and across the Canidae. The gene was located in silico to dog chromosome 2. The sequence was experimentally confirmed by amplifying and sequencing the TRNP1 exonic and promoter regions in 72 canids (36 purebred dogs, 20 Gy wolves and wolf-dog hybrids, 10 coyotes, 5 red foxes and 1 Gy fox).

Results: A partial TRNP1 transcript was isolated from several regions in the dog brain. Thirty genetic polymorphisms were found in the Canis sp. with 17 common to both dogs and wolves, and only one unique to dogs. Seven polymorphisms were observed only in coyotes. An additional 9 variants were seen in red foxes. Dogs were the least genetically diverse. Several polymorphisms in the promoter and 3'untranslated region were predicted to alter TRNP1 function by interfering with the binding of transcriptional repressors and miRNAs expressed in neural precursors. A c.259_264 deletion variant that encodes a polyalanine expansion was polymorphic in all species studied except for dogs. A stretch of 15 nucleotides that is found in other mammalian sequences (corresponding to 5 amino acids located between Pro58 and Ala59 in the putative dog protein) was absent from the TRNP1 sequences of all 5 canid species sequenced. Both of these aforementioned coding sequence variations were predicted to affect the formation of alpha helices in the disordered region of the TRNP1 protein.

Conclusions: Potentially functionally important polymorphisms in the TRNP1 gene are found within and across various Canis species as well as the red fox, and unique differences in protein structure have evolved and been conserved in the Canidae compared to all other mammalian species.

Background: Distichiasis is a condition characterized by aberrant hairs along the eyelid margins. The symptoms are usually mild but can lead to ulcerations and lesions of the cornea in severe cases. It is the most frequently noted ocular disorder in Norwegian Staffordshire bull terriers (SBT), with a prevalence above 18% in the adult population. A complex inheritance is assumed, but there is sparse knowledge about the genetic background of distichiasis in dogs. We have performed a genome-wide association study of distichiasis in SBT and used genomic data in an attempt to predict genomic values for the disorder.

Results: We identified four genetic regions on CFA1, CFA18, CFA32 and CFA34 using a mixed linear model association analysis and a Bayesian mixed model analysis. Genomic values were predicted using GBLUP and a Bayesian approach, BayesR. The genomic prediction showed that the 1/4 of dogs with predicted values most likely to acquire distichiasis had a 3.9 -4.0 times higher risk of developing distichiasis compared to the quarter (1/4) of dogs least likely to acquire the disease. There was no significant difference between the two methods used.

Conclusion: Four genomic regions associated with distichiasis were discovered in the association analysis, suggesting that distichiasis in SBT is a complex trait involving numerous loci. The four associated regions need to be confirmed in an independent sample. We also used all 95 K SNPs for genomic prediction and showed that genomic prediction can be a helpful tool in selective breeding schemes at breed level aiming at reducing the prevalence of distichiasis in SBTs in the future, even if the predictive value of single dogs may be low.

Background: Osteosarcoma is a malignant bone neoplasia that has high welfare consequences for affected dogs. Awareness of breed and canine conformational risk factors for osteosarcoma can assist with earlier diagnosis and improved clinical management. Study of osteosarcoma in dogs also offers translational value for humans. Anonymised clinical data within VetCompass on dogs under primary veterinary care in the UK were searched for osteosarcoma cases. Descriptive statistics reported overall and breed-specific prevalence. Risk factor analysis used multivariable logistic regression modelling.

Results: From 905,552 study dogs, 331 osteosarcoma cases were confirmed yielding a one-year period prevalence of 0.037% (95% CI: 0.033-0.041). Breeds with the highest annual prevalence were the Scottish Deerhound (3.28%, 95% CI 0.90-8.18), Leonberger (1.48%, 95% CI 0.41- 3.75), Great Dane (0.87%, 95% CI 0.43- 1.55) and Rottweiler (0.84%, 95% CI 0.64-1.07). The median age at diagnosis was 9.64 years (IQR: 7.97-11.41). Following multivariable modelling, 11 breeds showed increased odds of osteosarcoma compared with crossbred dogs. Breeds with the highest odds included Scottish Deerhound (OR 118.40, 95% CI 41.12-340.95), Leonberger (OR 55.79, 95% CI 19.68-158.15), Great Dane (OR 34.24, 95% CI 17.81-65.83) and Rottweiler (OR 26.67, 95% CI 18.57-38.29). Compared with breeds with mesocephalic skull conformation, breeds with dolichocephalic skull conformation (OR 2.72, 95% CI 2.06-3.58) had increased odds while breeds with brachycephalic skull conformation showed reduced odds (OR 0.50, 95% CI 0.32-0.80). Chondrodystrophic breeds had 0.10 times the odds (95% CI 0.06-0.15) compared with non-chondrodystrophic breeds. Increasing adult bodyweight was associated with increasing odds of osteosarcoma.

Conclusions: The current study cements the concept that breed, bodyweight and longer leg or longer skull length are all strong risk factors for osteosarcoma in dogs. With this awareness, veterinarians can update their clinical suspicion and judgement, breeders can select towards lower-risk animals, and researchers can robustly define more useful study populations for fundamental and translational bioscience.

Background: Publicly available phenotype data and genotyping array data from two citizen science projects: "Doberman Health Surveys" and "The Doberman Diversity Project" were analyzed to explore relative homozygosity, diversity, and disorder risk according to geographical locale and breeding purpose in the Doberman.

Results: From the phenotypic data cohort, life expectancy of a Doberman at birth is 9.1 years. The leading causes of death were heart disease (accounting for 28% of deaths) and cancers (collectively accounting for 14% of deaths). By genotyping, the world Doberman population exists as four major cohorts (European exhibition-bred, Americas exhibition-bred, European work, Americas pet/informal). Considering the entire Doberman population, four genomic regions longer than 500 Kb are fixed in 90% or more of 3,226 dogs included in this study. The four fixed regions reside on two autosomal chromosomes: CFA3:0.8-2.3 Mb (1.55 Mb); CFA3: 57.9-59.8 Mb (1.8 Mb); CFA31:0-1.2 Mb (1.2 Mb); and CFA31:4.80-6.47 Mb (1.67 Mb). Using public variant call files including variants for eight Doberman pinschers, we observed 30 potentially functional alternate variants that were evolutionarily diverged relative to the wider sequenced dog population within the four strongly homozygous chromosomal regions. Effective population size (Ne) is a statistical measure of breed diversity at the time of sampling that approximates the number of unique individuals. The major identified sub-populations of Dobermans demonstrated Ne in the range 70-236. The mean level of inbreeding in the Doberman breed is 40% as calculated by the number of array variants in runs of homozygosity divided by the assayed genome size (excluding the X chromosome). The lowest observed level of inbreeding in the Dobermans assayed was 15% in animals that were first generation mixes of European and USA bred Dobermans. Array variant analysis shows that inter-crossing between European and USA-bred Dobermans has capacity to re-introduce variation at many loci that are strongly homozygous.

Conclusions: We conclude that efforts to improve breed diversity first should focus on regions with the highest fixation levels, but managers must ensure that mutation loads are not worsened by increasing the frequencies of rarer haplotypes in the identified regions. The analysis of global data identified regions of strong fixation that might impact known disorder risks in the breed. Plausible gene candidates for future analysis of the genetic basis of cardiac disease and cancer were identified in the analysis.