Canine medicine and genetics最新文献

Background: A 2019 ACVIM consensus statement on diagnostics for immune-mediated hemolytic anemia (IMHA) in dogs made testing recommendations. As data on the performance of immunohematological tests was lacking, we undertook a comparative analysis.

Material and methods: Anticoagulated blood samples from 126 dogs suspected of having IMHA submitted to a diagnostic veterinary laboratory for a routine direct antiglobulin test (DAT) and from 28 healthy control dogs were evaluated for spherocytosis and autoagglutination before and after three saline washes. Samples were also subjected to different DATs: a gel minitube and an immunochromatographic strip kit used in clinics; neutral gel column cards, microtiter plates (at 4°, 22°, and 37°C), capillary tubes, and flow cytometry used in laboratories.

Results: Samples from healthy dogs yielded negative results with all immunodiagnostic tests. Among the 126 samples submitted for DAT 67 were positive by a DAT utilizing microtiter plates with goat anti-dog antiglobulin DAT at 22°C. Notably, DAT results were comparable and consistent across all evaluated methods regardless of antiglobulin and temperature used. DAT+ dogs were more severely anemic and more likely to have erythroid regeneration compared to DAT- dogs. Macroscopic agglutination in tubes or on slides was observed in 48 samples after 1:1 and 1:4 blood to saline dilution, but only persisted in four samples after washing. Among the DAT+ samples, 57% had agglutination, 87% had spherocytosis, and 45% had both. There was good correlation between spherocytosis and DAT results from the six DAT techniques, but the correlation with autoagglutination was only fair. Clinical follow-up was available for 42 dogs. Of the sample from 12 DAT+ dogs collected during treatment, 10 remained DAT+ when tested 1-24 weeks after initial assessment.

Conclusions: Based upon this comparative prospective survey, all in-clinic and laboratory DAT techniques produced similar results when performed by trained personnel and can therefore be recommended for detection of antibody-coated erythrocytes and immunohematological diagnosis. In addition, use of these tests for monitoring response of IMHA dogs to treatment might be valuable.

Background: Osteosarcoma (OSA) is a devastating disease that is common in the Irish Wolfhound breed. The aim of this study was to use a pedigree-based approach to determine the heritability of OSA in the Irish Wolfhound using data from a large publically available database.

Results: The pedigree used for this study included 5110 pure-bred Irish Wolfhounds, including 332 dogs diagnosed with OSA and 360 control dogs; dogs were considered controls if they lived over 10 years of age and were not reported to have developed OSA. The estimated heritability of OSA in the Irish Wolfhound was 0.65.

Conclusion: The results of this study indicate that OSA in the Irish Wolfhound is highly heritable, and support the need for future research investigating associated genetic mutations.

Background: This study describes the presence and frequency of health traits among three populations of dogs traditionally used for sledding and explores their ancestry and breed composition as provided by the commercially available Embark dog DNA test. The three populations include the purebred Siberian Husky and the admixed populations of Alaskan sled dogs and Polar Huskies. While the Siberian Husky represents a well-established breed with extensive historical and health data, the Alaskan sled dog is less studied but has been the subject of nutritional, physiological, and genetic studies related to ancestry and performance. In contrast, the Polar Husky is a relatively obscure and rare group of dogs used for arctic exploration with very little-known information. The three populations were compared using Embark results, providing new insight into the health traits circulating within the populations and the potential ancestral linkage of the health traits between the sledding populations. Embark results are based upon 228,588 single-nucleotide polymorphisms (SNPs) spanning the canine genome, characterized using a custom-designed Illumina beadchip array.

Results: Specifically, breed composition was summarized for the two admixed populations with most of the dogs being predominantly categorized as Alaskan husky- type dog or "Supermutt". Mitochondrial and Y chromosome haplogroups and haplotypes were found with Alaskan sled dogs carrying most of the haplogroups and types found in Siberian and Polar Huskies. Genomic principal component analysis reflected population structure corresponding to breed and substructure within the Alaskan sled dogs related to sprint or distance competition. Genetic markers associated with Alanine Aminotransferase activity, Alaskan Husky Encephalopathy, dilated cardiomyopathy, Collie eye anomaly, degenerative myelopathy, ichthyosis, and factor VII deficiency were identified in the populations of sledding breeds.

Conclusion: These results provide a preliminary description of genetic characteristics found in sledding breeds, improving the understanding and care of working sled dogs.

Background: Otitis externa is a commonly diagnosed disorder in dogs and can carry a high welfare impact on affected animals. This study aimed to report the prevalence and explore the role of breed and aural conformation as predisposing factors for canine otitis externa in the UK. The study used a cohort design of dogs under UK primary veterinary care at clinics participating in the VetCompass Programme during 2016. Risk factor analysis used multivariable logistic regression modelling.

Results: The study included a random sample of 22,333 dogs from an overall population of 905,554 dogs under veterinary care in 2016. The one-year period prevalence of otitis externa was 7.30% (95% confidence interval [CI]: 6.97 to 7.65). Breed and ear carriage were the highest ranked risk factors. Compared with crossbred dogs, sixteen breed types showed increased odds, including: Basset Hound (odds ratio [OR] 5.87), Chinese Shar Pei (OR 3.44), Labradoodle (OR 2.95), Beagle (OR 2.54) and Golden Retriever (OR 2.23). Four breeds showed protection (i.e. reduced odds) of otitis externa: Chihuahua (OR 0.20), Border Collie (OR 0.34), Yorkshire Terrier (OR 0.49) and Jack Russell Terrier (OR 0.52). Designer breed types overall had 1.63 times the odds (95% CI 1.31 to 2.03) compared with crossbred dogs. Compared with breeds with erect ear carriage, breeds with pendulous ear carriage had 1.76 times the odds (95% CI 1.48 to 2.10) and breeds with V-shaped drop ear carriage had 1.84 times the odds (95% CI 1.53 to 2.21) of otitis externa.

Conclusions: Breed itself and breed-associated ear carriage conformation are important predisposing factors for canine otitis externa. Greater awareness of these associations for both predisposed and protected breeds could support veterinary practitioners to promote cautious and low-harm approaches in their clinical advice on preventive care for otitis externa, especially in predisposed breeds.

Background: Genetic heterogeneity of the canine angiotensin converting enzyme (ACE) gene is functionally important because the degree of aldosterone breakthrough with ACE-inhibitor therapy is greater in variant positive dogs compared to variant negative dogs, but the prevalence of the variant is not known. The purpose of this study was to determine ACE gene variant-positive prevalence in a population of 497 dogs of different breeds.

Results: Overall variant-positive prevalence was 31%, with 20% of dogs heterozygous and 11% of dogs homozygous. The variant was overrepresented in Irish Wolfhounds (prevalence 95%; P < .001), Dachshunds (prevalence 90%; P < .001), Cavalier King Charles Spaniels (prevalence 85%; P < .001), Great Danes (prevalence 84%; P < .001), and Bull Mastiffs (prevalence 58%; P = .02). Irish Wolfhounds were more likely to be homozygous than heterozygous (P < .001).

Conclusions: Nearly one-third of dogs in this study were positive for a functionally important ACE gene variant, with wide prevalence variability between breeds. The clinical importance of high ACE gene variant-positive prevalence in some breeds requires further study because the highest prevalences were found in breeds that are predisposed to heart disease and therefore may be treated with ACE-inhibitors.

Subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects of dogs. The disease is characterized by obstruction of the left ventricular outflow tract, resulting in pressure overload on the left ventricle. The etiology of obstruction is a fibromuscular nodule, ridge, or ring of tissue that increases aortic outflow tract velocity. This review is focused on the prevalence, inheritance pattern, and current genetic insights of canine SAS. The prevalence of this disease was reported at 4.7 % in a large veterinary referral hospital. The mode of inheritance for this disease has also been described in breeds with a high disease prevalence such as the Bullmastiff, Bouvier des Flandres, Dogue de Bordeaux, Golden Retriever, Newfoundland, and Rottweiler. Genetic investigations seeking to identify causative mutations for SAS are lacking with only a single published variant associated with SAS in Newfoundlands.

Background: Osteosarcoma is an aggressive and painful bone neoplasm in dogs. Previous studies have reported epidemiological associations suggesting that large body mass, long bone length and the genetics of certain breeds including the Rottweiler are associated with elevated osteosarcoma risk. However, these studies were often limited by selection bias and confounding factors, and have rarely offered insights into breed-associated protection for osteosarcoma. The current study includes 1756 appendicular and axial osteosarcoma cases presenting to VPG Histology (Bristol, UK) compared against a control population of 905,211 dogs without osteosarcoma from primary care electronic patient records in the VetCompass™ dataset.

Methods and study design: Retrospective, case-control study. Multivariable logistic regression analysis explored associations between demographic risk factors (including breed, chondrodystrophy, age, sex/neuter status, skull-shape, and body mass) and osteosarcoma of all anatomical sites.

Results: We identified several breeds with increased and reduced odds of osteosarcoma. At highest risk were the Rottweiler and Great Dane, with > 10 times the odds of osteosarcoma compared with crossbreds, and the Rhodesian Ridgeback, which has not featured in previous lists of at-risk breeds for osteosarcoma, and had an odds ratio of 11.31 (95% confidence interval 7.37-17.35). Breeds at lowest risk of osteosarcoma (protected breeds) included the Bichon Frise, the French Bulldog and the Cavalier King Charles Spaniel, all with odd ratios of less than 0.30 compared with crossbreds. Body mass was strongly associated with osteosarcoma risk; dogs over 40 kg exhibited osteosarcoma odds of 45.44 (95% confidence interval 33.74-61.20) compared with dogs less than 10 kg. Chondrodystrophic breeds had an osteosarcoma odds ratio of 0.13 (95% confidence interval 0.11-0.16) compared with non-chondrodystrophic breeds.

Conclusions: This study provides evidence of strong breed-associated osteosarcoma risk and protection, suggesting a genetic basis for osteosarcoma pathogenesis. It highlights that breeds selected for long legs/large body mass are generally overrepresented amongst at-risk breeds, whilst those selected for short leg length/small body mass are generally protected. These findings could inform genetic studies to identify osteosarcoma risk alleles in canines and humans; as well as increasing awareness amongst veterinarians and owners, resulting in improved breeding practices and clinical management of osteosarcoma in dogs.

Background: Canine idiopathic epilepsy (IE) is the most common chronic neurological brain disease in dogs, yet it can only be diagnosed by exclusion of all other potential causes. In people, epilepsy has been associated with a reduction in brain volume. The objective was to estimate the volume of the forebrain (FB), subarachnoid space (SAS) and lateral ventricles (LV) in dogs with IE compared to controls using Cavalieri's principle. MRI scans of case and control dogs were identified from two neurology referral hospital databases. Eight breeds with increased odds of having IE were included: Golden Retriever, Labrador Retriever, Cocker Spaniel, Border terrier, German Shepherd dog, Parson Jack Russell terrier, Boxer, and Border Collie. Five dogs of each breed with IE and up to five controls were systematically and uniformly randomly sampled (SURS). The volume of the FB, SAS and LV were estimated from MRI scans by one blinded observer using Cavalieri's principle.

Results: One hundred-two dogs were identified; 56 were diagnosed with IE and 46 were controls. There was no statistically significant difference in FB, SAS and LV volume between dogs with IE and controls. Dogs with a history of status epilepticus had significantly larger FB than those without (p = 0.05). There was a border-line trend for LV volume to increase with increasing length of seizure history in the IE group (p = 0.055).

Conclusion: The volumes of the FB, SAS and LV are not different between dogs with IE and controls, so IE remains a diagnosis of exclusion with no specific neuroanatomical biomarkers identified. This is the first time FB and SAS volume has been compared in dogs with IE. Unfortunately, we have shown that the results reporting significantly larger FBs in dogs with status epilepticus and LV volume increase with length of seizure history were likely confounded by breed and should be interpreted cautiously. Whilst these associations are interesting and clinically relevant, further investigation with breed-specific or larger, breed-diverse populations are required to permit strong conclusions. The Cavalieri principle provided an effective estimation of FB, SAS and LV volumes on MRI, but may be too time-intensive for use in clinical practice.

Background: In people, bile acid diarrhoea is a prevalent complication of Crohn's disease and diarrhoea-associated irritable bowel syndrome. Affected patients typically respond to bile acid sequestrants, such as cholestyramine, but human gastroenterologists often fail to recognize bile acid diarrhoea. Consequently, bile acid diarrhoea is regarded as an underrecognized and undertreated condition in human medicine. Due to lack of diagnostic tools, clinical response to bile acid sequestrants is often used to confirm a diagnosis of bile acid diarrhoea in people. Several recent studies have shown that bile acid dysmetabolism also occurs in dogs with chronic enteropathies. It has further been shown that dogs with chronic enteropathies have significantly decreased expression of a bile acid transport protein in the ileum compared to healthy dogs, which correlates with faecal bile acid dysmetabolism. Consequently, in spite of the lack of reports in the literature, bile acid diarrhoea is likely to exist in dogs as well.

Case descriptions: Two dogs, an 8-year old Rottweiler and a 4.5-year old Siberian Husky were evaluated for chronic watery diarrhoea. Neither dog responded to dietary trials, probiotics, cyclosporine, faecal microbial transplantations or metronidazole. One of the dogs responded to high daily doses of corticosteroids, which were however associated with unacceptable side effects. The other dog was refractory to all standard treatment protocols, including cyclosporine and corticosteroids. Since none of the dogs responded satisfactorily to standard treatment or modulation of the intestinal microbiome, a suspicion of possible bile acid diarrhoea was raised. Treatment with cholestyramine, a bile acid sequestrant was initiated and resulted in marked improvement of faecal consistency, frequency of defecation and activity level in both dogs.

Conclusion: This report presents two dogs with presumed bile acid diarrhoea that were successfully treated with cholestyramine. Therefore, bile acid diarrhoea should be considered as a possible diagnosis in dogs with treatment-refractory chronic diarrhoea.