Peer-reviewed veterinary case report
Skin folds and periodic fever linked to gene mutation in Shar-Pei dogs
By Olsson, Mia et al.·Published in PLoS genetics·2011·Department of Medical Biochemistry and Microbiology·View original on PubMed →
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Original publication title: A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs.
- Species:
- dog
Plain-English summary
A group of Chinese Shar-Pei dogs were found to have a genetic mutation that causes both their unique thick, wrinkled skin and a periodic fever syndrome, which leads to recurrent fevers and inflammation. This mutation affects a gene responsible for producing hyaluronan, a substance that contributes to their skin's thickness. The study revealed that dogs with a higher number of duplications of this gene were more likely to experience these fever episodes. Understanding this genetic link can help in managing the health of Shar-Pei dogs and may also provide insights into similar conditions in humans.
People also search for: Shar-Pei skin problems · periodic fever syndrome in dogs · Chinese Shar-Pei health issues · dog skin thickening causes · managing fever in dogs
Abstract
Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 × 10⁻⁶, p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/21437276/