Genetic characterization of Addison’s disease in Bearded Collies

Abstract

Background Primary hypoadrenocorticism (or Addison’s disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies. Results Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility. Conclusion Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.

Effect of long‐term management of hypoadrenocorticism on the quality of life of affected dogs and their owners

“…Approximately half of the dogs were acquired from breeders, which might reflect the higher risk of hypoadrenocorticism as an autoimmune disease with a possible inheritable origin. [6][7][8] Poodle-mixed breeds, Standard Poodles, Labrador Retrievers and Bearded Collies were over-represented in our study, which correlates with the results of previous studies. 6,7 Interestingly, 5% of patients were less than 1 year old.…”

“…[6][7][8] Poodle-mixed breeds, Standard Poodles, Labrador Retrievers and Bearded Collies were over-represented in our study, which correlates with the results of previous studies. 6,7 Interestingly, 5% of patients were less than 1 year old. However, recent studies showed a higher incidence in dogs between the ages of 4 and 9 years.…”

“…Cases are reported to present mainly between 4 and 9 years of age 1 . Some breeds, such as Standard Poodles, Bearded Collies and Portuguese Water Dogs, have a higher risk of hypoadrenocorticism; therefore, the disease might be heritable 5–8 . Female dogs and neuter status were reported to be over‐represented in the Addisonian population 1,9 …”

“…1 Some breeds, such as Standard Poodles, Bearded Collies and Portuguese Water Dogs, have a higher risk of hypoadrenocorticism; therefore, the disease might be heritable. [5][6][7][8] Female dogs and neuter status were reported to be over-represented in the Addisonian population. 1,9 Diagnosis and therapy of adrenal insufficiency can be challenging.…”

Correction to: Genetic characterization of Addison’s disease in Bearded Collies

“…Following publication of the original article [ 1 ], it was noted that due to a typesetting error the caption of Fig. 1 was mistakenly captured within the main body of the article.…”