{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:07:29Z","timestamp":1793639249215,"version":"4.5.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011538","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000}}],"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Recently we characterized polymyositis in the Dutch Kooiker dog. The familial occurrence of the disease were suggestive of an inherited cause. Here we report the results of our molecular genetic investigation. A genome-wide association study of 33 cases and 106 controls indicated the involvement of a region on chromosome CFA19 (p = 4.7*10<jats:sup>\u221210<\/jats:sup>). Haplotype analysis indicated that the cases shared a 2.9 Mb region in the homozygous or the heterozygous state. Next Generation Sequencing of genomic DNA implicated a deletion of a 39 kb DNA fragment, located 10 kb upstream of the neighbouring interleukin genes <jats:italic>IL21<\/jats:italic> and <jats:italic>IL2<\/jats:italic>. The frequency of the deletion allele was 0.81 in the available cases and 0.25 in a random sample of the Kooiker dog breed. Leukocytes of affected, untreated dogs that were homozygous for the deletion overexpress <jats:italic>IL21<\/jats:italic> and <jats:italic>IL2<\/jats:italic> upon stimulation with mitogens. We suggest that elements located 10\u201349 kb upstream of the <jats:italic>IL21<\/jats:italic>\/<jats:italic>IL2<\/jats:italic> locus play an important role in the regulation of the canine genes and that deletion of these elements is a risk factor for polymyositis in Kooiker dogs. Postulating causality, the penetrance of the disease phenotype was estimated at 10\u201320% for homozygous dogs and 0.5\u20132% for dogs that were heterozygous for the deletion. Our results suggest that distant variants upstream of <jats:italic>IL21<\/jats:italic> could also be important for human autoimmune diseases that have been found to be associated with the <jats:italic>IL21<\/jats:italic>\/<jats:italic>IL2<\/jats:italic> chromosome region.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011538","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T19:31:36Z","timestamp":1735846296000},"page":"e1011538","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polymyositis in Kooiker dogs is associated with a 39 kb deletion upstream of the canine IL21\/IL2 locus"],"prefix":"10.1371","volume":"21","author":[{"given":"Yvet","family":"Opmeer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G.","family":"van Steenbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7149-3809","authenticated-orcid":true,"given":"Claudia","family":"Rozendom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hille","family":"Fieten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8035-7354","authenticated-orcid":true,"given":"Montse M.","family":"Diaz Espineira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qurine E. 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