UC Davis links RESF1 variant to Addison’s disease in Tollers
Bottom line
Version 1 — Brief
UC Davis researchers have identified a missense variant in RESF1 that is strongly associated with juvenile-onset Addison’s disease in Nova Scotia Duck Tolling Retrievers, and the finding has now been published in Scientific Reports. The study linked the variant to a broader multiple autoimmune syndrome phenotype in some young dogs, not just isolated hypoadrenocorticism. UC Davis has already made a genetic test available through its Veterinary Genetics Laboratory, giving breeders and veterinarians a new tool to identify at-risk dogs and carriers. (ucdavis.edu)
Why it matters: For veterinary professionals, this is a clinically useful genetics update in a breed already known for an elevated risk of Addison’s disease. The paper analyzed 14 juvenile-onset cases and 33 older healthy controls, and the authors reported that at least 10 of 24 juvenile-onset cases had concurrent autoimmune conditions, reinforcing that some Tollers may present with a broader immune-mediated syndrome. The UC Davis test describes the trait as autosomal recessive with incomplete penetrance, with dogs carrying two copies of the variant having about a 75% chance of developing this juvenile form by 1 year of age. (nature.com)
What to watch: Watch for how quickly breeders adopt RESF1 screening, and whether follow-on studies clarify why some homozygous dogs remain unaffected and whether RESF1 also proves relevant in human autoimmune Addison’s disease. (nature.com)
Version 2 — Full analysis
Scientists at UC Davis say they’ve identified the gene variant behind juvenile-onset Addison’s disease in Nova Scotia Duck Tolling Retrievers, a development that could change both breed health management and future research into autoimmune adrenal disease. In a paper published in Scientific Reports, the team reported a strong association between a missense variant in RESF1 and disease in young Tollers, and UC Davis has already launched a corresponding genetic test through its Veterinary Genetics Laboratory. (ucdavis.edu)
The finding builds on years of concern about autoimmune disease in the breed. Tollers have long been recognized as being predisposed to immune-mediated disorders, and juvenile hypoadrenocorticism in related young dogs was described decades ago. Earlier work also pointed to inherited risk, but the newly published study moves the field from suspicion to a specific candidate variant that breeders and clinicians can act on. (link.springer.com)
In the new study, researchers performed a genome-wide association analysis in 47 Nova Scotia Duck Tolling Retrievers, including 14 cases diagnosed before 12 months of age and 33 healthy controls older than 72 months. They identified a significant region on chromosome 27, then narrowed the signal to a missense RESF1 variant, c.3170C>T, predicted to cause a p.Pro1057Leu substitution. The altered amino acid is reported to be fully conserved across mammals, which strengthens the case that the change is biologically important. (nature.com)
The paper also suggests the disease story is broader than Addison’s disease alone. Among 24 juvenile-onset cases reviewed in detail, all had adrenal insufficiency, but at least 10 dogs, or 41.7%, also had concurrent autoimmune conditions. The authors therefore frame juvenile-onset Addison’s disease in these dogs as one manifestation of a broader multiple autoimmune syndrome with variable expressivity. They estimated penetrance of the RESF1 variant at 76% in homozygous dogs, while UC Davis’s clinical test page translates that into a practical breeding message: dogs with two copies of the variant have about a 75% chance of developing juvenile Addison’s disease by 1 year of age. (nature.com)
For breeders and breed-health leaders, the immediate industry response is practical rather than speculative: there is now a test that can be used to avoid producing affected puppies. UC Davis says the condition is inherited in an autosomal recessive pattern with incomplete penetrance, and notes that carriers are not expected to be affected themselves. The lab also advises that carriers can still be bred to clear dogs to preserve genetic diversity, an important point in a breed with a relatively small gene pool and multiple inherited health concerns. (vgl.ucdavis.edu)
Why it matters: For veterinarians, this discovery sharpens risk assessment in young Tollers presenting with vague gastrointestinal signs, lethargy, poor appetite, or electrolyte abnormalities, especially when ocular or other immune-mediated problems are also in the picture. It also creates a clearer framework for conversations with breeders and pet parents: a positive genetic result does not guarantee disease, but it materially changes risk and supports earlier vigilance. Just as importantly, the work may improve case definition by separating juvenile inherited disease in Tollers from the broader pool of canine Addison’s disease, which often presents later in life. (vgl.ucdavis.edu)
The translational angle is also notable. UC Davis highlighted that RESF1 has not previously been linked to Addison’s disease or multiple autoimmune syndrome in humans, despite strong similarity between the canine and human gene. That makes these dogs a potentially useful natural model for human autoimmune adrenal disease, although that remains an inference rather than a demonstrated clinical application at this stage. (ucdavis.edu)
What to watch: The next steps are likely to center on uptake of the new DNA test, additional work on modifier genes or environmental triggers that explain incomplete penetrance, and whether human researchers begin evaluating RESF1 as a candidate gene in autoimmune Addison’s disease. (vgl.ucdavis.edu)