{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:24:24Z","timestamp":1787203464874,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The belted phenotype in cattle, a distinctive white belt across the midsection observed in breeds such as the Dutch Belted and Belted Galloway, is caused by a copy number variant (CNV) upstream of\n                    <jats:italic>TWIST2<\/jats:italic>\n                    , a gene involved in melanocyte development. While the CNV is necessary for belt formation, the genetic basis of variation in belt width and completeness remains unclear. To refine understanding of these phenotypes, we generated a\n                    <jats:italic>de novo<\/jats:italic>\n                    genome assembly of Dutch Belted cattle and analysed both short\u2010 and long\u2010read sequencing data from animals with normal\u2010width, small\u2010width, and incomplete belts. Standard variant calling tools failed to identify the CNV, highlighting technical challenges in detecting large insertions. Instead, coverage analysis and qPCR confirmed the CNV as a 6\u2009kb tandem array approximately 16.5\u2009kb upstream of\n                    <jats:italic>TWIST2<\/jats:italic>\n                    . Long\u2010read evidence showed identical four\u2010copy haplotypes for individuals with normal\u2010width, small\u2010width, and incomplete belts, indicating that CNV copy number does not influence belt width or completeness. Furthermore, no unique variants were detected within the CNV or\n                    <jats:italic>TWIST2<\/jats:italic>\n                    in a small\u2010width belted individual, suggesting that modifiers affecting belt width likely reside elsewhere in the genome. Genome\u2010wide scans revealed extremely low nucleotide diversity in the CNV region, consistent with a selective sweep driven by strong artificial selection unique to the Dutch Belted breed. Together, these results show that while the CNV is necessary for belt formation, additional modifier loci likely influence belt width and completeness.\n                  <\/jats:p>","DOI":"10.1002\/age.70159","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:22:06Z","timestamp":1784290926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Untangling the Copy Number Variation at the Basis of Belted Phenotypes in Cattle Using Long\u2010Read Sequencing"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9734-5795","authenticated-orcid":false,"given":"Rensco A. H.","family":"Hogers","sequence":"first","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2433-2483","authenticated-orcid":false,"given":"Mirte","family":"Bosse","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"},{"name":"Amsterdam Institute of Life and Environment (A\u2010Life) VU University Amsterdam  Noord\u2010Holland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6474-8977","authenticated-orcid":false,"given":"Annemieke P.","family":"Rattink","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"},{"name":"Centrum voor Genetische Bronnen Nederland Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3679-4685","authenticated-orcid":false,"given":"Rayner","family":"Gonz\u00e1lez\u2010Prendes","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-4014","authenticated-orcid":false,"given":"Marta","family":"G\u00f2dia","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"Laport","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-4545","authenticated-orcid":false,"given":"Martien A. M.","family":"Groenen","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8108-9972","authenticated-orcid":false,"given":"Richard P. M. A.","family":"Crooijmans","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5079-7108","authenticated-orcid":false,"given":"Aniek C.","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genomics Wageningen University &amp; Research  Gelderland the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.114876.110"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02823-7"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2011.02450.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180170"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-024-10936-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-92750-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbac085"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0924-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010474"},{"key":"e_1_2_11_12_1","unstructured":"Centrum voor Genetische bronnen.2024.\u201cRassenlijst nederlandse landbouwhuisdierrassen.\u201d Centrum voor Genetische bronnen Wageningen."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-024-10634-2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-022-08874-1"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad311"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2052.2009.01987.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2052.2008.01826.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2022.02.017"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1921046117"},{"key":"e_1_2_11_23_1","unstructured":"Food and of the United Nations A.O.2023.\u201cLakenvelder \/ Netherlands (Cattle).\u201dhttps:\/\/dadis\u2010breed\u2010datasheet\u2010ext\u2010ws.firebaseapp.com\/?country=NLD&specie=Cattle&breed=Lakenvelder&lang=en."},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani13193072"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msm120"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003359901178"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz891"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-024-10239-9"},{"key":"e_1_2_11_29_1","first-page":"90","volume-title":"Seminars in Cell & Developmental Biology","author":"Kelsh R. N.","year":"2009"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0072-8"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts480"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01990240"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/12.3.102"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01236"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt958"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msab199"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty266"},{"key":"e_1_2_11_39_1","first-page":"458","article-title":"Belted, a New Recessive Spotting Mutation in the Mouse","volume":"87","author":"Murray J.","year":"1943","journal-title":"Anatomical Record"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12335"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx699"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giz040"},{"key":"e_1_2_11_43_1","unstructured":"Porter V.1993.\u201cPigs. A Handbook to the Breeds of the World.\u201d New York: Helm Information. ISBN 978\u20101\u2010873403\u201017\u20104."},{"key":"e_1_2_11_44_1","unstructured":"R Core Team.2021.\u201cR: A Language and Environment for Statistical Computing.\u201d R Foundation for Statistical Computing Vienna Austria.https:\/\/www.R\u2010project.org\/."},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-382"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00668"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts378"},{"issue":"36","key":"e_1_2_11_48_1","first-page":"1","article-title":"Remapping of the Belted Phenotype in Cattle on bta3 Identifies a Multiplication Event as the Candidate Causal Mutation","volume":"50","author":"Rothammer S.","year":"2018","journal-title":"Genetics Selection Evolution"},{"key":"e_1_2_11_49_1","unstructured":"Runderen D. V. L.2021.\u201cFokbeleid en Keuringseisen.\u201dhttps:\/\/www.lakenvelderrund.nl\/de\u2010vereniging\/statuten\/."},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2010.00678.x"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.livsci.2020.104015"},{"key":"e_1_2_11_52_1","unstructured":"Schmutz S. T.Berryere J.Moker andD.Bradley.2001.\u201cInheritance of the Belt Pattern in Belted Galloway Cattle.\u201d Proceedings of the Plant & Animal Genome IX Conference. Plant & Animal Genome Conference San Diego Proceedings of the Plant & Animal Genome IX Conference."},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0003-4"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000003"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.105445"},{"key":"e_1_2_11_56_1","unstructured":"Smit A. R.Hubley andP.Green.2013\u20132015.\u201cRepeatmasker.\u201dhttps:\/\/repeatmasker.org\/."},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-02024-y"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts535"},{"key":"e_1_2_11_59_1","unstructured":"Wickham H.2016.\u201cggplot2: Elegant Graphics for Data Analysis.\u201d ISBN 978\u20103\u2010319\u201024277\u20104."},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.00006.x"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43588-022-00387-x"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105272"}],"container-title":["Animal Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/age.70159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/age.70159","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/age.70159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:46:04Z","timestamp":1787201164000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/age.70159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/age.70159"],"URL":"https:\/\/doi.org\/10.1002\/age.70159","archive":["Portico"],"relation":{},"ISSN":["0268-9146","1365-2052"],"issn-type":[{"value":"0268-9146","type":"print"},{"value":"1365-2052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"2026-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70159"}}