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A Novel Unstable Du...
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Olsson, MiaUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
(author)
A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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2011-03-17
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Public Library of Science (PLoS),2011
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-153228
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-153228URI
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https://doi.org/10.1371/journal.pgen.1001332DOI
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https://res.slu.se/id/publ/59227URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 x 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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Meadows, Jennifer R. S.Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)jenme818
(author)
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Truvé, KatarinaSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics(Swepub:slu)49406
(author)
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Pielberg, Gerli RosengrenUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)gepie020
(author)
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Puppo, Francesca
(author)
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Mauceli, Evan
(author)
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Quilez, Javier
(author)
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Tonomura, Noriko
(author)
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Zanna, Giordana
(author)
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Jose Docampo, Maria
(author)
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Bassols, Anna
(author)
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Avery, Anne C.
(author)
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Karlsson, Elinor K.
(author)
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Thomas, Anne
(author)
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Kastner, Daniel L.
(author)
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Bongcam-Rudloff, ErikUppsala universitet,Centrum för bioinformatik(Swepub:uu)erikbr
(author)
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Webster, Matthew T.Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)maweb226
(author)
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Sanchez, Armand
(author)
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Hedhammar, ÅkeSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences(Swepub:slu)49648
(author)
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Remmers, Elaine F.
(author)
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Andersson, LeifSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics,Uppsala University(Swepub:slu)48730
(author)
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Ferrer, Lluis
(author)
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Tintle, Linda
(author)
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Lindblad-Toh, KerstinUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)kerli865
(author)
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Uppsala universitetScience for Life Laboratory, SciLifeLab
(creator_code:org_t)
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Sveriges lantbruksuniversitet
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In:PLoS Genetics: Public Library of Science (PLoS)7:3, s. e1001332-1553-73901553-7404
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Olsson, Mia
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Meadows, Jennife ...
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Truvé, Katarina
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Pielberg, Gerli ...
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Puppo, Francesca
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Mauceli, Evan
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Quilez, Javier
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Tonomura, Noriko
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Zanna, Giordana
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Jose Docampo, Ma ...
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Bassols, Anna
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Avery, Anne C.
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Karlsson, Elinor ...
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Thomas, Anne
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Kastner, Daniel ...
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Bongcam-Rudloff, ...
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Webster, Matthew ...
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Sanchez, Armand
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Hedhammar, Åke
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Remmers, Elaine ...
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Andersson, Leif
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Ferrer, Lluis
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Tintle, Linda
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Lindblad-Toh, Ke ...
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AGRICULTURAL SCI ...
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PLoS Genetics
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Uppsala University
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Swedish University of Agricultural Sciences