{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T18:03:02Z","timestamp":1775239382160,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Splashed white in horses is characterized by extensive white patterning on the legs, face and abdomen and may be accompanied by deafness. To date, seven variants in <jats:italic>microphthalmia\u2010associated transcription factor<\/jats:italic> (<jats:italic>MITF<\/jats:italic>) and two variants in <jats:italic>Paired Box 3<\/jats:italic> (<jats:italic>PAX3<\/jats:italic>) have been identified to explain this phenotype. A splashed white Thoroughbred stallion, whose sire and dam were not patterned, was hypothesized to have a <jats:italic>de novo<\/jats:italic> variant leading to his white coat pattern. A whole\u2010genome sequencing candidate gene approach identified two single nucleotide variants (SNVs) in <jats:italic>SOX10<\/jats:italic>, four SNVs in <jats:italic>MITF<\/jats:italic> and a 2.3\u2009kb deletion in <jats:italic>MITF<\/jats:italic> with the alternative allele present in this stallion but absent in the other 18 horses analyzed. All six SNVs were annotated as modifiers and were not further considered. The deletion in <jats:italic>MITF<\/jats:italic> (NC_009159.3:g.21555811_21558139delinsAAAT) encompasses exon 9 encoding a part of the helix\u2013loop\u2013helix domain required for DNA binding. Sanger sequencing and parentage testing confirmed that this deletion was a <jats:italic>de novo<\/jats:italic> mutation of maternal origin. Consistent with the published nomenclature, we denote this likely causal variant as SW8. Genotyping three of this stallion's offspring identified SW8 only in the nearly all\u2010white foal that was confirmed deaf by brainstem auditory evoked response testing. This foal was also a compound heterozygote for dominant white variants (W20\/W22), but to date, W variants alone have not been connected to deafness. SW8 marks the fourth de novo <jats:italic>MITF<\/jats:italic> variant in horses reported to cause white patterning. The link between deafness and all <jats:italic>MITF<\/jats:italic> variants with and without other variants impacting melanocyte development and function needs to be further explored.<\/jats:p>","DOI":"10.1111\/age.13352","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T07:26:18Z","timestamp":1694503578000},"page":"752-762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A <i>de novo<\/i> 2.3\u2009kb structural variant in <scp><i>MITF<\/i><\/scp> explains a novel splashed white phenotype in a Thoroughbred family"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-7227","authenticated-orcid":false,"given":"R. R.","family":"Bellone","sequence":"first","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine UC Davis Davis California USA"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine UC Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine UC Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-9793","authenticated-orcid":false,"given":"E.","family":"Esdaile","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine UC Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. B.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Cell Physiology and Molecular Biophysics, School of Medicine Texas Tech University Health Sciences Center Lubbock Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Payette","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, University School of Veterinary Medicine University of Pennsylvania Kennett Square Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Leduc","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, University School of Veterinary Medicine University of Pennsylvania Kennett Square Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. J.","family":"Till","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine UC Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. K.","family":"Abdel\u2010Ghaffar","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine UC Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine UC Davis Davis California USA"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine UC Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. G.","family":"Magdesian","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology, School of Veterinary Medicine University of California\u2010Davis Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.12377"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2008.0158.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.16221"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13091641"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8754"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078280"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1024\/0036-7281\/a000451"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-005-2472-y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000112065"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12590"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12556"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12484"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.13222"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030195"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2052.2009.01893.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12313"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075071"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002653"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12057"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12762"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12375"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12554"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12840"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/evj.13879"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-6-r84"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.12499"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.117.043786"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esaa009"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.235.10.1204"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.13017"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900790"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12528"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts091"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.12883"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.13225"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani12151958"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12749"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2001.62.97"},{"key":"e_1_2_10_43_1","volume-title":"Equine color genetics","author":"Sponenberg D.P.","year":"2017"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks596"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"}],"container-title":["Animal Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/age.13352","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T12:46:40Z","timestamp":1699015600000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/age.13352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/age.13352"],"URL":"https:\/\/doi.org\/10.1111\/age.13352","archive":["Portico"],"relation":{},"ISSN":["0268-9146","1365-2052"],"issn-type":[{"value":"0268-9146","type":"print"},{"value":"1365-2052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]},"assertion":[{"value":"2023-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}