Research Update CHF 02488 Final: Addison’s Disease and Symmetrical Lupoid Onychodystrophy in Bearded Collies Provide Common Ground for Identifying Susceptibility Loci Underlying Canine Autoimmune Disorders

Hypoadrenocorticism or Addison’s disease (AD) consists of a life-threatening clinical condition that afflicts multiple purebred and mixed breed dogs. The condition results from autoimmune destruction of the adrenal glands leading to life-long cortisol deficiency. Similarly, another autoimmune condition causing pain and suffering to dogs is Symmetrical Lupoid Onychodystrophy (SLO).

For the study of AD and SLO we are investigating the Bearded Collie breed due to the relatively high prevalence of both conditions in this breed and a genomic structure favorable for identifying DNA variations. Working with breeders and owners, all proposed numbers of SLO, AD and control Bearded Collie samples were obtained, genotyped, and analyzed in genome-wide associations (GWAs). GWA analysis for SLO revealed significant peaks on canine chromosomes (CFA) 12 and 17; the region of association on CFA12 also harbors the DLA class II genes for which we have already determined an association (Gershony et al. 2019). The region on CFA17 was more strongly associated with the SLO phenotype when only dogs that carried DLA class II risk haplotypes for SLO were considered.

Promising candidate genes were identified and WGS data for SLO and healthy controls is currently under analysis for identification of potential causative mutations. A similar approach was used for AD. The GWAS showed a single genome-wide significant peak on CFA18 whose association was not further enhanced when the DLA class II genes were included. Three other regions of suggestive association were noted on different chromosomes and found to contribute risk to AD development.

Within the Bearded Collies we studied, dogs without the risk variants at the four loci were at reduced risk for AD whereas dogs carrying multiple risk genotypes across these regions were at increased risk of AD. Potential candidate genes involved in immune function and regulation were identified within the regions identified as associated with AD risk. To characterize the actual variants responsible for SLO and AD risk, 27 Bearded Collies (9 AD, 7 SLO and 11 controls) have been whole genome sequenced (WGS) and the variant data is being analyzed within the regions of association identified in the GWAS, which will be followed by exploration of the entire genome.

Three manuscripts have now been published as a result of this study. We deeply appreciate the continued assistance of BeaCon, Bearded Collie breed clubs and owners in our studies.

FINAL Research Update Dr. Oberbauer for underlying autoimmune disorders.