Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

Abstract

Background Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number of pathological mechanisms are thought to contribute to the aetiopathogenesis of relative or absolute insulin deficiency, including immune-mediated destruction of pancreatic beta cells. DM risk varies considerably between different dog breeds, suggesting that genetic factors are involved and contribute susceptibility or protection. Associations of particular dog leucocyte antigen (DLA) class II haplotypes with DM have been identified, but investigations to date have only considered all breeds pooled together. The aim of this study was to analyse an expanded data set so as to identify breed-specific diabetes-associated DLA haplotypes. Methods The 12 most highly represented breeds in the UK Canine Diabetes Register were selected for study. DLA-typing data from 646 diabetic dogs and 912 breed-matched non-diabetic controls were analysed to enable breed-specific analysis of the DLA. Dogs were genotyped for allelic variation at DLA-DRB1, -DQA1, -DQB1 loci using DNA sequence-based typing. Genotypes from all three loci were combined to reveal three-locus DLA class II haplotypes, which were evaluated for statistical associations with DM. This was performed for each breed individually and for all breeds pooled together. Results Five dog breeds were identified as having one or more DLA haplotype associated with DM susceptibility or protection. Four DM-associated haplotypes were identified in the Cocker Spaniel breed, of which one haplotype was shared with Border Terriers. In the three breeds known to be at highest risk of DM included in the study (Samoyed, Tibetan Terrier and Cairn Terrier), no DLA haplotypes were found to be associated with DM. Conclusions Novel DLA associations with DM in specific dog breeds provide further evidence that immune response genes contribute susceptibility to this disease in some cases. It is also apparent that DLA may not be contributing obvious or strong risk for DM in some breeds, including the seven breeds analysed for which no associations were identified.

Exploration of autoantibody responses in canine diabetes using protein arrays

“…In dogs, strong breed predispositions suggest a genetic component contributes to disease risk 31 . Denyer et al evaluated dog leukocyte antigen (DLA) (the canine equivalent to human leukocyte antigen) haplotypes in diabetic and control dogs (at least 20 in each group for each breed) in 12 different dog breeds 32 . They identified five dog breeds with DLA haplotypes associated with risk or protection, but other dog breeds, including 3 of the breeds at highest risk for diabetes, had no DLA associations with DM.…”

Computed tomography findings in a cohort of 169 dogs with elbow dysplasia - a retrospective study

“…In the one-year prevalence study conducted by O’Neill et al [ 26 ] the most common breeds among the incident elbow joint disease were Labrador Retriever ( n = 189, 30.68%), GSD ( n = 43, 6.98%), Staffordshire Bull Terrier ( n = 32, 5.19%) and Rottweiler ( n = 23, 3.73%), along with crossbred dogs ( n = 100, 16.23%).…”

“…From dogs older than 6 years included in the mentioned study, 13 out of 16 were Labrador Retrievers, 3 out of 4 were GSDs, 5 out of 6 were Golden Retrievers and 6 out of 8 were mixed-breed dogs. According to O’Neill et al [ 26 ] the median age (in years) at first diagnosis for breeds with over 20 incident was: Labrador Retriever 6.42 (2.50–9.08, n = 188), German Shepherd Dog 5.64 (0.80–7.77, n = 42), Staffordshire Bull Terrier 8.02 (3.16–10.87, n = 32), Rottweiler 7.20 (1.47–8.17, n = 23), English Springer Spaniel 7.00 (1.77–12.27, n = 21), Golden Retriever 9.75 (5.27–11.65, n = 21) and crossbred dogs 7.65 (3.39–10.95, n = 100). However, all dogs with a diagnosis of elbow joint disease made by veterinarians were included in above mentioned study.…”

“…Assessment of joint incongruency was done using multiplanar reconstructions (MPR) in the mid-coronoid region in an oblique plane, according to scheme presented previously [ 25 , 26 ]. Sagittal MPR image was established via alignment of external borders of humerus and ulna on a dorsal plane (red lines) (Fig.…”

Breed distributions for diabetes mellitus and hypothyroidism in Norwegian dogs

“…For several decades the predisposition of some breeds to canine DM has been investigated and reported. Especially Samoyed and Australian terrier have frequently been reported at high risk of development [ 18 , 19 , 21 , 22 , 27 – 29 ] and the German Shepherd and Boxer at low risk [ 11 , 18 , 22 , 26 – 30 ]. Other studies have indicated that other breeds are at high risk in some countries, e.g.…”