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Wrinkly Dog Syndrome

By Elizabeth Preston
Mar 23, 2011 6:21 AMJul 18, 2023 7:51 PM


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To say that the Shar-pei is a wrinkly dog is putting it mildly. The ones that have been bred in China for hundreds of years are identifiable by a furrowed brow that makes them look permanently concerned (D). The Shar-Pei dogs bred in the West, though (A-C), have been turned into baggy overgrown puppies that can barely see you from behind their folded-up faces.

Like other purebreds, the Shar-Pei has health problems. Some of them are symptoms of its desired traits (such as a susceptibility to infections inside its skin folds), while others are genetic accidents that come from generations of inbreeding and artificial selection. A condition called Familial Shar-Pei Fever (FSF) is one of those genetic disorders. But a new study has shown that, rather than being a genetic fluke, FSF comes from the very same mutation that causes the dogs' wrinkliness. The disease has been bred into them along with their cute, scrunchy faces.

Researchers in Sweden (one of whom is named, improbably, Puppo) compared the DNA of a group of Shar-Pei dogs to dogs of other breeds. They found a pronounced difference on chromosome 13, in the genetic region that makes a gooey molecule called hyaluronic acid (HA). This was no great surprise: the Shar-Pei's thick and wrinkled hide is known to be caused by a huge buildup of HA in the skin.

The surprise came when the researchers divided up the Shar-Pei group into those affected and unaffected by FSF. The disorder causes frequent fevers and inflammation. Scanning the genome for a region associated with the disorder, the researchers found themselves right back at chromosome 13. The wrinkly-skin mutation is a duplication--a certain chunk of DNA copied one or more times. The dogs had varying numbers of duplications, like a stutter in this genetic region. And the scientists saw that the dogs with the most copies were the most likely to have the fever disorder.

So the very trait that breeders have valued in the Shar-Pei is what makes it ill. The problem may arise from broken fragments of HA molecules, which might encourage inflammation. The authors speculate that excess HA might be responsible for even more of the Shar-Pei's health problems, such as skin allergies, tumors, and kidney damage.

But the good news is that the wrinkly dogs might be able to help humans. Some people suffer from inherited fever syndromes that are similar to FSF. A few genetic links have been found, but about 60% of these cases have no known cause. Future research might find a link between hyaluronic acid and chronic fever disorders in humans, leading to new treatment possibilities. Of course, the best treatment for the Shar-Pei would be to stop breeding it. But as long as people keep demanding squishy-looking pets, that seems unlikely.

Image: PLoS Genetics/doi:10.1371/journal.pgen.1001332.g001

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