Evaluation of the genetic basis of primary hypoadrenocorticism in Standard Poodles using SNP array genotyping and whole-genome sequencing
Primary hypoadrenocorticism, also known as Addison’s disease, is an autoimmune disorder leading to the destruction of the adrenal cortex and subsequent loss of glucocorticoid and mineralocorticoid hormones. The disease is prevalent in Standard Poodles and is believed to be highly heritable in the breed. Using genotypes derived from the Illumina Canine HD SNP array, we performed a genome-wide association study of 133 carefully phenotyped Standard Poodles (61 affected, 72 unaffected) and found no markers significantly associated with the disease. We also sequenced the entire genomes of 20 Standard Poodles (13 affected, 7 unaffected) and analyzed the data to identify common variants (including SNPs, indels, structural variants, and copy number variants) across affected dogs and variants segregating within a single pedigree of highly affected dogs. We identified several candidate genes that may be fixed in both Standard Poodles and a small population of dogs of related breeds. Further studies are required to confirm these findings more broadly, as well as additional gene-mapping efforts aimed at fully understanding the genetic basis of what is likely a complex inherited disorder.
KeywordsValidation Cohort Impute Genotype Variant Effect Predictor Standard Poodle Cavalier King Charles Spaniel
SGF is supported by a National Institutes of Health T32 training award (5T32OD011130-07). Funding for whole-genome sequencing was provided in part by the Poodle Club of America Foundation and the Morris Animal Foundation. Seed funding for this project was provided by the North Carolina State University Comparative Medicine Institute. Some whole-genome sequencing data were graciously contributed by Drs. Leigh Anne-Clark (13 dogs), Natasha J. Olby and Theirry Olivry (11 dogs), and Joshua A. Stern (two dogs).
SGF collected samples, designed the study, analyzed the data, and wrote the manuscript. KFL collected samples and provided guidance regarding phenotyping of dogs. KMM collected samples and supervised the study. All authors have read and edited the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
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