title: A candidate gene analysis of canine hypoadrenocorticism in 3 dog breeds.
abstract: 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.
authors.affiliation: the Centre for Integrated Genomic Medical Research, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Short
authors.forename: Alisdair
authors.initials: A
authors.lastname: Boag
authors.forename: Brian
authors.initials: B
authors.lastname: Catchpole
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Kennedy
authors.forename: Jonathan
authors.initials: J
authors.lastname: Massey
authors.forename: Simon
authors.initials: S
authors.lastname: Rothwell
authors.forename: Eystein
authors.initials: E
authors.lastname: Husebye
authors.forename: Bill
authors.initials: B
authors.lastname: Ollier
mesh_terms: D000309:Adrenal Insufficiency / Q000662:veterinary*; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001947:Breeding; D002874:Chromosome Mapping; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide
keywords: Addison’s disease; candidate genes; dog; genetics; hypoadrenocorticism