{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:44:36Z","timestamp":1789231476859,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003137","name":"Fondation pour la Recherche sur la Biodiversite","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003137","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During the last 60\u2009years many inherited traits in domestic outbred cats were selected and retained giving birth to new breeds characterised by singular coat or morphological phenotypes. Among them, minimal white spotting associated with blue eyes was selected by feline breeders to create the Altai, Topaz, and Celestial breeds. Various established breeds also introduced this trait in their lineages. The trait, that was confirmed as autosomal dominant by breeding data, was first described in domestic cats from Kazakhstan and Russia, in British shorthair and British longhair from Russia, and in Maine Coon cats from the Netherlands, suggesting different founding effects. Using a genome\u2010wide association study we identified a single region on chromosome C1 that was associated with the minimal white spotting and blue eyes phenotype (also called DBE by breeders for dominant blue eyes) in the French Celestial breed. Within that region we identified <jats:italic>Paired Box\u00a03<\/jats:italic> (<jats:italic>PAX3<\/jats:italic>) as the strongest candidate gene, since <jats:italic>PAX3<\/jats:italic> is a key regulator of <jats:italic>MITF<\/jats:italic> (<jats:italic>M<\/jats:italic><jats:italic>elanocyte\u2010<\/jats:italic><jats:italic>I<\/jats:italic><jats:italic>nducing<\/jats:italic> <jats:italic>T<\/jats:italic><jats:italic>ranscription<\/jats:italic> <jats:italic>F<\/jats:italic><jats:italic>actor<\/jats:italic>) and <jats:italic>PAX3<\/jats:italic> variants have been previously identified in various species showing white spotting with or without blue eyes including the mouse and the horse. Whole genome sequencing of a Celestial cat revealed an endogenous retrovirus LTR (long terminal repeat) insertion within <jats:italic>PAX3<\/jats:italic> intron 4 known to contain regulatory sequences (conserved non\u2010coding element [CNE]) involved in <jats:italic>PAX3<\/jats:italic> expression. The insertion is in the vicinity of CNE2 and CNE3. All 52 Celestial and Celestial\u2010mixed cats with a DBE phenotype presented the insertion, that was absent in their 22 non\u2010DBE littermates and in 87 non\u2010DBE cats from various breeds. The outbred Celestial founder was also heterozygous for the insertion. Additionally, the variant was found in nine DBE Maine Coon cats related to the Celestial founder and four DBE Siberian cats with an uncertain origin. Segregation of the variant in the Celestial breed is consistent with dominant inheritance and does not appear to be associated with deafness. We propose that this NC_018730.3:g.206974029_206974030insN[395] variant represents the <jats:italic>DBE<\/jats:italic><jats:sup><jats:italic>CEL<\/jats:italic><\/jats:sup> (<jats:italic>Celestial Dominant Blue Eyes<\/jats:italic>) allele in the domestic cat.<\/jats:p>","DOI":"10.1111\/age.13433","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:03:20Z","timestamp":1713769400000},"page":"670-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A <i>PAX3<\/i> insertion in the Celestial breed and certain feline breeding lines with dominant blue eyes"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-7897","authenticated-orcid":false,"given":"Marie","family":"Abitbol","sequence":"first","affiliation":[{"name":"Univ Lyon, VetAgro Sup  Marcy\u2010l'Etoile France"},{"name":"Institut NeuroMyoG\u00e8ne INMG\u2010PNMG, CNRS UMR5261, INSERM U1315, Facult\u00e9 de M\u00e9decine, Rockefeller, Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Couronn\u00e9","sequence":"additional","affiliation":[{"name":"Univ Lyon, VetAgro Sup  Marcy\u2010l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dufaure\u00a0de\u00a0Citres","sequence":"additional","affiliation":[{"name":"Antagene  La Tour de Salvagny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Gache","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoG\u00e8ne INMG\u2010PNMG, CNRS UMR5261, INSERM U1315, Facult\u00e9 de M\u00e9decine, Rockefeller, Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.04.087"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1309557"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.114.013425"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.12.030"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.532"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002653"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12057"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jevs.2023.104875"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.09.015"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1410083111"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003811"}],"container-title":["Animal Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/age.13433","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T04:51:14Z","timestamp":1719982274000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/age.13433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/age.13433"],"URL":"https:\/\/doi.org\/10.1111\/age.13433","archive":["Portico"],"relation":{},"ISSN":["0268-9146","1365-2052"],"issn-type":[{"value":"0268-9146","type":"print"},{"value":"1365-2052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,22]]},"assertion":[{"value":"2024-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}