A candidate gene analysis of canine hypoadrenocorticism in 3 dog breeds.
Canine hypoadrenocorticism is believed to be an immune-related condition. It is rare in the overall dog population but shows a breed-related predisposition with Standard poodles and Portuguese water dogs having a greater prevalence of the condition. It shares many similarities with human primary adrenal insufficiency and is believed to be a naturally occurring, spontaneous model for the human condition. Short haplotype blocks and low levels of linkage disequilibrium in the human genome mean that the identification of genetic contributors to the condition requires large sample numbers. Pedigree dogs have high linkage disequilibrium and long haplotypes within a breed, increasing the potential of identifying novel genes that contribute to canine genetic disease. We investigated 222 SNPs from 42 genes that have been associated or may be implicated in human Addison's disease. We conducted case-control analyses in 3 pedigree dog breeds (Labrador retriever: affected n = 30, unaffected = 76; Cocker Spaniel: affected n = 19, unaffected = 53; Springer spaniel: affected n = 26, unaffected = 46) and identified 8 associated alleles in genes COL4A4, OSBPL9, CTLA4, PTPN22, and STXBP5 in 3 pedigree breeds. Association with immune response genes PTPN22 and CTLA4 in certain breeds suggests an underlying immunopathogenesis of the disease. These results suggest that canine hypoadrenocorticism could be a useful model for studying comparative genetics relevant to human Addison's disease.
['Short|Andrea D|AD|', 'Boag|Alisdair|A|', 'Catchpole|Brian|B|', 'Kennedy|Lorna J|LJ|', 'Massey|Jonathan|J|', 'Rothwell|Simon|S|', 'Husebye|Eystein|E|', 'Ollier|Bill|B|']
D000309:Adrenal Insufficiency D000483:Alleles D000818:Animals D001483:Base Sequence D001947:Breeding D002874:Chromosome Mapping D004283:Dog Diseases D004285:Dogs D005787:Gene Frequency D056726:Genetic Association Studies D005838:Genotype D006239:Haplotypes D058977:Molecular Sequence Annotation D020641:Polymorphism, Single Nucleotide
candidate genes hypoadrenocorticism dog genetics Addison’s disease