The discovery of a new mutation associated with breathing difficulties in popular dog breeds suggests that shortened skulls causing flat faces is not the only factor that contributes to the condition, but that swelling around the airways from edema may also play a role. Jeffrey Schoenebeck of the University of Edinburgh and colleagues report these findings in a new study published 9th May 2019 in PLOS Genetics.
Respiratory diseases are prevalent across dog breeds, particularly in brachycephalic breeds such as the Bulldog and French bulldog. The flat facial conformation of these breeds has long been assumed to be the major predisposing factor, however, the underlying genetics of their respiratory condition has never been elucidated.
The research team became interested in the Norwich Terrier, a breed presenting with many of the same respiratory disease symptoms as the Bulldog. A distinction, however, is that the Norwich terrier is not considered to be a brachycephalic breed and so presented an opportunity to dissociate respiratory disease from head conformation.
The researchers performed a genome-wide association analysis for respiratory disease severity in the Norwich Terrier and resolved an association on chromosome 13 to a missense mutation in ADAMTS3. Variants in this gene were previously shown to cause an oedematous phenotype–a disease characteristic in the airways of affected Norwich Terriers and brachycephalic dogs alike. The researchers screened over 100 breeds for the ADAMTS3 variant and found that it is enriched in the Norwich Terrier, Bulldog and French Bulldog. This discovery changes how we view respiratory disease predisposition in the dog, offers potential genetic screens and highlights a new biological function for ADAMTS3.
The study presents a new way of looking at these respiratory diseases in dogs, where fluid retention in the tissue that lines the airways makes it more likely that dogs with the mutation will develop breathing obstructions. “We conclude that there are additional genetic risk factors, that if inherited, will likely lead to airway disease in dogs regardless of their face shape,” stated author Jeffrey Schoenebeck. “The challenge ahead is to integrate these ideas, and implement sensible breeding practices and treatments that consider various health risks including those presented by the mutation of ADAMTS3.”
If scientists develop a test for this mutation, then dog breeders can develop better breeding practices to avoid passing on the faulty gene. Additionally, screening for the mutation may help veterinarians identify dogs which are at risk of UAS, and in particular identify the dogs at risk of swelling of their airways after surgical treatment, which is a common, life-threatening post-operative complication.