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At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
Since arriving on the island of Guam in the 1940s, the brown tree snake ( Boiga irregularis ) has extirpated native...
An animal rights group known as the Nonhuman Rights Project filed lawsuits in three New York courts this week in an...
Researchers have been hot on the trail of the elusive Denisovans, a type of ancient human known only by their DNA and...
Thousands of scientists in the Russian Academy of Sciences (RAS) are about to lose their jobs as a result of the...
Dyslexia, a learning disability that hinders reading, hasn't been associated with deficits in vision, hearing, or...
Exotic, elusive, and dangerous, snakes have fascinated humankind for millennia. They can be hard to find, yet their...
Researchers have sequenced and analyzed the first two snake genomes, which represent two evolutionary extremes. The...
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A New Wrinkle on Why Shar-Peis Suffer Fevers
17 March 2011 5:00 pm
A 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.”