A genetic mutation that causes wrinkled skin in Shar-Pei dogs may also be responsible for familial Shar-Pei fever, an inflammatory disease that plagues the breed, according to an international investigation.
Scientists are now working on designing a genetic screening test, which will help people to breed Shar-Pei dogs with a reduced risk of the disease. The research will also aid investigations of the genetic causes of periodic fever syndromes in humans, which lead to uncontrolled inflammation throughout the body.
“Our findings will assist the canine community and provide clues about the mechanisms of human inflammatory disorders,” said Jennifer Meadows, a geneticist at Uppsala University in Sweden and co-author of the journal article published in PLoS Genetics.
Familial Shar-Pei fever
Shar-Pei dogs, known for their thick wrinkly skin, exhibit a high prevalence of familial Shar-Pei fever (FSF), a congenital autoinflammatory disease causing fever and swelling of the dog’s ankle joints (hocks).
Chronic inflammation from FSF can lead to organ failure and premature death for Shar-Pei dogs.
The wrinkly skin of the Shar-Pei contains an excess of a disaccharide polymer called hyaluronan, most likely due to over-activation of a gene called hyaluronan synthase 2 (HAS2). If hyaluronan becomes fragmented, it can stimulate an immune reaction in the body and cause inflammation and fever.
Same mutation causes wrinkles and fever
The researchers compared the genomes of more than 100 Shar-Pei with genomes of other dog breeds. At the same time, genomes of healthy Shar-Pei dogs were compared with genomes of Shar-Pei suffering from FSF.
Both genome comparisons pointed to the same segment of DNA, close to the HAS2 gene, that had been duplicated in error. In some cases the segment had been duplicated multiple times, increasing the risk of FSF for these dogs while also causing the wrinkled skin.
The association of HAS2 dysregulation and autoinflammation is also of wide interest since the genetic cause of approximately 60% of human periodic fever syndrome cases remains unexplained.
"The finding that hyaluronan is a major trigger of fever opens a new research field in canine and human inflammatory disease," said senior author Kerstin Lindblad-Toh, a professor in comparative genomics at Uppsala University.
Side effects of selective breeding
This type of genetic control, where one gene can control multiple traits, is called pleiotropy. Understanding pleiotropy in domestic animals is particularly important, since selective breeding for a specific trait can inadvertently increase the frequency of other sometimes undesirable characteristics in the breed.
Meadows and her co-authors are in the process of developing a test for the mutation, although it has not been determined when the test will be available for commercial use.
“Our hope is that a genetic test may help breeders to reduce the prevalence of risk alleles in the Shar-Pei breeding population,” said Meadows.
Improving dog health and welfare
Claire Wade, a professor of animal genetics at the University of Sydney, said that genomic studies are helping to improve the health and welfare of all dogs, not just those of specific breeds.
The Australian National Kennel Council has promised to adjust breeding standards to improve animal welfare if scientific evidence suggests a link between a disorder and a characteristic that is standard for the breed. The Shar Pei breed standard was recently adjusted in 2009 to discourage breeding dogs with heavy wrinkling.
“There is a strong commitment by the pedigree dog community to breed healthier dogs. Dog breeders are very good at applying tests relevant to their breeds as they become available,” said Wade.
Source, by Bridget Murphy
Source, by Bridget Murphy
Cosmos Online
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