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Newly-Discovered Mutation Explains Why Some Dogs Have Breathing Problems

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Newly-Discovered Mutation Explains Why Some Dogs Have Breathing Problems

The French Bulldog is probably the first breed that comes to mind when you mention dogs with breathing difficulties. In fact, the dogs’ respiratory problems are so notorious that a 2017 editorial by National Geographic suggested that Frenchie owners and Frenchie breeders are irresponsible dog lovers, catapulting the breed’s popularity in recent years to the demise of the canines themselves. 


Their challenge is most easily understood as a bit of a poor biological design flaw. Breeds like pugs, French Bulldogs, and English Bulldogs — all canines with short, stubby, and fat snouts — are “brachycephalic.” Brachycephalic syndrome is an affliction in which the extremely short snout causes regular respiratory problems and challenges with basic breathing functions — something we tend to take for granted ourselves unless we experience it. The dogs’ compact skull can often result in body parts like the palate, which is the soft part of the roof of the mouth, or nostrils being too big or small. These interfere with airflow and cause chronic breathing problems. Research conducted in the UK and published in 2016 found that almost half of French bulldogs have significant breathing problems, with over 66 percent showing stenotic nares or excessively tight nostrils. Meanwhile, according to the American Kennel Club registration, the French Bulldog was the 11th most popular breed to the fourth between 2013 and 2017. The real ethical problem in all of this is that breeders have been found to influence these very physical characteristics all in the name of breeding a cuter pup. 


"In my opinion, it's horrible, because those figures are not produced by responsible breeders," Virginia Rowland, president of the French Bull Dog Club of America said in the 2018 National Geographic feature of the rapid popularity boost.


Since many of these dogs are bred specifically to have that shorter snout, they draw heavy criticism for the people making them so readily available. National Geographic pointed out that photos of these same breeds from decades ago show their snouts were noticeably longer. They suggest that dog show standards and preferences have likely influenced a shorter snout, which dog owners have adopted over time and by extension, breeders have catered to. But while that popularity has brought on criticism from some, it’s also offered the breed much-needed attention to its plight. Dog show judges have shifted their perception of what makes the most preferable appearance, with some even taking a stance on no longer giving favorable scores to the tight nostril appearance or a dog with health complications. The same has influenced researched to uncover other factors that may cause serious health complications for some of these same breeds. 


New research conducted in Europe suggests that it’s not just the smaller skull and short snout the causes complications for these breeds. In fact, that’s just part of the problem, they say.


Jeffrey Schoenebeck, a dog geneticist at the University of Edinburgh’s Royal School of Veterinary Studies had for years been hearing stories of the Norwich Terrier, a small dog with no distinctive or shortened snout, which was bred to catch rodents in the UK. These dogs, he learned, were found to have symptoms and complications similar to brachycephalic breeds like Pugs and Frenchies. Without the same brachycephalic features, Schoenebeck assumed there must be another factor influencing these common breathing problems that had nothing or little to do with the shortened snout and smaller nostrils. 


Schoenebeck’s research found that a specific mutation within a gene called ADAMTS3 can explain brachycephalic obstructive airway syndrome, or BOAS, in Norwich Terriers. Terriers with the worst symptoms and tissue deformities typically had two copies of the mutation, and this same mutation, they found, is often in the DNA of English and French Bulldogs as well. “

“This discovery changes how we view respiratory disease predisposition in the dog, offers potential genetic screens and highlights a new biological function for ADAMTS3,” they wrote in the study.


In humans and in dogs alike, mutations in ADAMTS3 have been linked to facial deformities and blockages in lymphatic vessels, causing a buildup of fluids and swelling that complicates breathing. The mutation doesn’t paint the entire picture of how and when dogs develop BOAS, they said. For some breeds, it’s only part of the problem, Schoenebeck says. ADAMTS3 and a small skull or shortened snout simply combine for a perfect storm of breathing problems. 


“If a French bulldog is conforming to the breed standard, then they all have a certain degree of risk, due to their skull shape. But there are other things that could be contributing to that risk,” Schoenebeck said. “And this could be one of the things that may be segregating them into different levels of risk. But to what degree, we don’t just know yet.”


To understand these links better, Schoenebeck plans to connect similar studies with bulldogs, where the BOAS symptoms are measured against the number of “mutated” ADAMTS3 copies in each dog. Since Eno single study can determine that “thing A causes thing B,” researchers can’t definitely say that BOAS is more heavily influenced by or determined by ADAMTS3 mutations or features of the skull and airways or a combination of the parts, but Schoenebeck’s research on Norwich Terriers found a strong enough correlation between the gene makeup and breathing complications to determine it is, in fact, a factor. Interestingly enough, when he dug into the medical histories of the small breed, he found that more recent populations of Norwich Terriers were less likely to carry the ADAMTS3 mutation. 


“In the 90s, something like 80 percent of the Norwich Terriers that came into their clinic had poor breathing and this mutation. But it’s decreasing further and further over time,” Schoenebeck said. “They didn’t know it at the time, but they were actually selecting against this thing that we think is causing this disease.”


At the very least, Schoenebeck’s research offers a step toward learning how to better treat bulldogs and other breeds with common respiratory problems, specifically brachycephalic obstructive airway syndrome. 

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