A New Wrinkle On Why Shar-peis Suffer Fevers

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A New Wrinkle on Why Shar-Peis Suffer Fevers

by Elisabeth Pain on 17 March 2011, 5:00 PM | Permanent Link | 0 Comments

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Hot finding. The same mutations that wrinkle Shar-Peis make them susceptible to fevers.

Credit: ThinkstockA mutation responsible for the characteristically wrinkly skin of Shar-Peis may also make them sick, according to a new study. The finding could eventually help dog breeders produce healthier Shar-Peis and may offer a new explanation for why some people are plagued with periodic fever.

Originally from China, Shar-Pei puppies have seduced the Western world with their wrinkles, encouraging breeders to select for dogs that would keep the trait as adults. (In the original breed, puppies lose most of their wrinkled skin as they grow.) Underlying the breed’s thick and extensive crinkles and furrows is the accumulation of a common skin component called hyaluronic acid (HA). Also characteristic of the breed is a disorder known as Familial Shar-Pei Fever (FSF), which causes apparently unprovoked yet recurrent episodes of fever and inflammation.

Even though the canine disease has long been thought to be hereditary, a genetic cause remained to be found. In a study in which they compared the DNA of 24 Shar-Peis having FSF with 17 ones that don’t (not all of the breed suffers the fevers), an international team of researchers recently identified a region on chromosome 13 associated with increased susceptibility to the disease. In parallel, the same team, led by Kerstin Lindblad-Toh of Uppsala University in Sweden and the Broad Institute in Cambridge, Massachusetts, screened the Shar-Pei genome for signs of what gives the breed its characteristic wrinkles. A comparison of 50 Shar-Peis with a control group of canines from 24 other breeds pointed toward a location, near a gene that codes for an HA-producing enzyme called HAS2, that overlapped with the FSF susceptibility region. Looking more closely at this area, the team then identified a mutation—duplications of a DNA segment—that was present in highly wrinkled Shar-Peis but not in control breeds.

The researchers next looked at whether this same mutation was associated with FSF susceptibility, comparing 28 affected and 16 healthy Shar-Peis. A large number of the duplications appears to predispose animals to FSF, the team reports today in PLoS Genetics. Lindblad-Toh says she suspected that the genetic causes for the thickened skin and for the fever syndrome would be near each other but not that they “would be the same mutation.” Further studies on Shar-Pei skin cells by Lindblad-Toh’s team showed that the more times the duplicated DNA segment is repeated, the more HAS2 is produced.

The findings are “really exciting news,” says Anna Simon of Radboud University Nijmegen Medical Centre in the Netherlands, a clinician-scientist who specializes in fevers. FSF resembles some of the hereditary periodic fever syndromes in humans, a group of rare autoinflammatory disorders whose most common form affects between 10,000 and 20,000 patients in the world, Simon estimates. Although mutations affecting inflammatory molecules have been identified in some cases of the syndromes, more than half remain unexplained. “Hyaluronic acid was outside of the scope” of fever researchers, in spite of its already-documented ability to stimulate the immune system, Simon says. It may now help explain some of the cases that had no known genetic cause, she suggests.

As for Shar-Peis, the study offers a good example of “the unintended consequences of selective breeding,” says genome scientist Joshua Akey of the University of Washington, Seattle. While selecting for excessive wrinkling, breeders “were also selecting for Shar-Pei fever and increasing that in frequency. That’s probably generally true of a lot of traits that were selected for in dog breeding.”

http://news.sciencemag.org/sciencenow/2011...s-s.html?ref=hp

Edited March 24, 2011 by shortstep

[SHAR PEI Rescue Inc]

I was discussing this report with our vet last week. Makes sense when you consider that the original Chinese Shar Pei (the bone mouth) was a very hardy dog - it had to be, given it dated back to the Han Dynasty with little, or more likely no veterinary care for all these years. They were farm/herding dogs for peasant farmers who, even if they did have access to a vet (unlikely) couldn't afford one.

FSF (Familial Shar Pei fever) has come about since the Americans imported these dogs and chose to breed them with more wrinkles for ascetic reasons (the meat mouth). More wrinkles also means more entropion surgeries as it is the heavy wrinkles on the forehead that weighs the eyelids down putting pressure on the eyelids (eye lashes) to curl around onto the eyeball.

However, it has to be said that even though the Americans may have created these problems we are now seeing in the pei, without their intervention, the breed would now be extinct.

Sadly, due to bad breeding practises, we now have the situation where 1 in 4 pei will suffer FSF, and of those 1 in 4, 50% will suffer amyloidosis (kidney failure). As a side issue, necessary entropion surgery has increased to 4-5 in 5 pei who pass through SHAR PEI Rescue Inc requiring same. 2 yrs ago, this figure was 3 in 5, as such we have witnessed an increase for the need of entropion in such a short space of time.

Of the rescues we see in SHAR PEI Rescue Inc who do suffer a FSF attack, we apply the following protocol: These pei are fed the lowest protein food we can find. We do this to try to keep their blood from heating up which can result from high protein food. We also administer a pro- biotic to their food on a daily basis and finally, they are given Colgout meds daily. Colgout is a human medication given to patients suffering gout. Giving Colgout to the pei is said to protect the kidney and liver should they be attacked by amyloidosis.

Personally I had never witnessed a FSF attack until the week of Christmas 2010. Since then, I have witnessed and have been notified of over 1 dozen current and past rescues who have suffered an attack.

The ONLY thing I can think of that has changed in the past 3 months is an increase in humidity in Melbourne. Upon asking a US FSF specialist about this relationship, she stated that the fact we don't normally experience such humid weather this could well have triggered the stress "button" in the pei in turn bringing about a FSF attack.

The Shar Pei world look forward to day when we do have a test for FSF available, and from there a breeding program to eradicate this from our beloved breed.