{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T05:50:43Z","timestamp":1791697843182,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Primary hyperparathyroidism (PHPT) is an inherited disorder that leads to inappropriate secretion of parathyroid hormone by neoplastic parathyroid cells. Dogs of the Keeshond breed are predisposed to adenomas or hyperplasia of the parathyroid that lead to PHPT. The disorder is inherited in a dominant Mendelian fashion with a high age\u2010related penetrance. The age of onset in PHPT\u2010affected Keeshonden is typically later than 8\u2009years. Genome\u2010wide association studies with 27 affected and 42 unaffected Keeshonden genotyped with 30\u2009896 markers identified a region of strong association with the PHPT phenotype on canine chromosome 20. The most significant array marker was NC_049241.1.g.55977819 C&gt;G. The strength of association of this region with the case phenotype was unique in the genome and concordant with the hypothesis of dominant inheritance (i.e. all case animals in the genome\u2010wide association studies were heterozygous for the most associated variant). Fine\u2010scale variant analysis in the region of association revealed a mutation that creates both a missense and a possible splice\u2010site variant within exon 2 of the gene\n                    <jats:italic>SIRT6<\/jats:italic>\n                    (NC_049241.1g.55817330A&gt;G; XM_038567756.1.c.193A&gt;G; XP_038423684.1.p.65R&gt;G). The variant appears uniquely within affected dogs when compared with 1987 other genotyped samples in the public domain. Strong concordance was observed between genotypes for the variant in\n                    <jats:italic>SIRT6<\/jats:italic>\n                    and a promoter variant in\n                    <jats:italic>eukaryotic elongation factor 2<\/jats:italic>\n                    (NC_049241.1.g. 55973578_55973593dupinsN[180]) used for disorder testing in the USA since 2008. Based on the absence of the\n                    <jats:italic>SIRT6<\/jats:italic>\n                    variant in any healthy dog and modelled functional behaviour of the variant we conclude that the\n                    <jats:italic>SIRT6<\/jats:italic>\n                    variant is probably pathogenic for PHPT.\n                  <\/jats:p>","DOI":"10.1111\/age.70056","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T15:09:57Z","timestamp":1761318597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Autosomal dominant primary hyperparathyroidism in the Keeshond dog breed is strongly associated with a missense variant in\n                    <i>sirtuin\u20106<\/i>"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-4771","authenticated-orcid":false,"given":"Claire M.","family":"Wade","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise M.","family":"Burmeister","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Genetics Centre University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Skelly","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Queen's Veterinary School Hospital University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Genetics Centre University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Pettitt","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Genetics Centre University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Z.","family":"Atwater","sequence":"additional","affiliation":[{"name":"Department of Animal &amp; Range Sciences Montana State University  Bozeman Montana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Tallmadge","sequence":"additional","affiliation":[{"name":"Animal Health Diagnostic Center, College of Veterinary Medicine Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manigandan","family":"Lejeune","sequence":"additional","affiliation":[{"name":"Animal Health Diagnostic Center, College of Veterinary Medicine Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Lindblad\u2010Toh","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology Uppsala University  Uppsala Sweden"},{"name":"SciLifeLab Uppsala University  Uppsala Sweden"},{"name":"Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-0370","authenticated-orcid":false,"given":"Cathryn S.","family":"Mellersh","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Genetics Centre University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-33297-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.178993"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-00755-z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn3943"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-023-00451-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.2005.227.756"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.2005.tb00268.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2007.tb02948.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.10"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24491"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq671"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0962-1083.2001.01452.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1244361"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-03023-7"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.1204"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2006.10.018"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.5"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-024-10059-y"},{"key":"e_1_2_10_26_1","unstructured":"The Jackson Laboratories. 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