{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:01:34Z","timestamp":1792710094709,"version":"4.5.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"7624","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1038\/nature19800","type":"journal-article","created":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T11:55:18Z","timestamp":1475582118000},"page":"265-269","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":691,"title":["Formation of new chromatin domains determines pathogenicity of genomic duplications"],"prefix":"10.1038","volume":"538","author":[{"given":"Martin","family":"Franke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Andrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wibke","family":"Schwarzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Heinrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sch\u00f6pflin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rieke","family":"Kempfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Jerkovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing-Lee","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Spielmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Timmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Wittler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Kurth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cambiaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsetta","family":"Zuffardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Houge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Lambie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Brancati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Pombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Vingron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Spitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mundlos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"BFnature19800_CR1","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nature11049","volume":"485","author":"EP Nora","year":"2012","unstructured":"Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381\u2013385 (2012)","journal-title":"Nature"},{"key":"BFnature19800_CR2","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature11082","volume":"485","author":"JR Dixon","year":"2012","unstructured":"Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376\u2013380 (2012)","journal-title":"Nature"},{"key":"BFnature19800_CR3","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.cell.2015.04.004","volume":"161","author":"DG Lupi\u00e1\u00f1ez","year":"2015","unstructured":"Lupi\u00e1\u00f1ez, D. G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012\u20131025 (2015)","journal-title":"Cell"},{"key":"BFnature19800_CR4","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1101\/gr.163519.113","volume":"24","author":"O Symmons","year":"2014","unstructured":"Symmons, O. et al. Functional and topological characteristics of mammalian regulatory domains. Genome Res. 24, 390\u2013400 (2014)","journal-title":"Genome Res."},{"key":"BFnature19800_CR5","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1016\/j.cell.2014.11.021","volume":"159","author":"SS Rao","year":"2014","unstructured":"Rao, S. S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665\u20131680 (2014)","journal-title":"Cell"},{"key":"BFnature19800_CR6","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1136\/jmedgenet-2011-100255","volume":"48","author":"S Benko","year":"2011","unstructured":"Benko, S. et al. Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development. J. Med. Genet. 48, 825\u2013830 (2011)","journal-title":"J. Med. Genet."},{"key":"BFnature19800_CR7","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/0092-8674(94)90041-8","volume":"79","author":"T Wagner","year":"1994","unstructured":"Wagner, T. et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 79, 1111\u20131120 (1994)","journal-title":"Cell"},{"key":"BFnature19800_CR8","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/ng0809-862","volume":"41","author":"I Kurth","year":"2009","unstructured":"Kurth, I. et al. Duplications of noncoding elements 5\u2032 of SOX9 are associated with brachydactyly-anonychia. Nature Genet. 41, 862\u2013863 (2009)","journal-title":"Nature Genet."},{"key":"BFnature19800_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1136\/jmg.2009.068361","volume":"46","author":"CT Gordon","year":"2009","unstructured":"Gordon, C. T. et al. Long-range regulation at the SOX9 locus in development and disease. J. Med. Genet. 46, 649\u2013656 (2009)","journal-title":"J. Med. Genet."},{"key":"BFnature19800_CR10","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1136\/jmedgenet-2014-102864","volume":"52","author":"G-J Kim","year":"2015","unstructured":"Kim, G.-J. et al. Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development. J. Med. Genet. 52, 240\u2013247 (2015)","journal-title":"J. Med. Genet."},{"key":"BFnature19800_CR11","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/nature06944","volume":"453","author":"R Sekido","year":"2008","unstructured":"Sekido, R. & Lovell-Badge, R. Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453, 930\u2013934 (2008)","journal-title":"Nature"},{"key":"BFnature19800_CR12","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1242\/dev.078592","volume":"139","author":"GR Dahal","year":"2012","unstructured":"Dahal, G. R. et al. An inwardly rectifying K+ channel is required for patterning. Development 139, 3653\u20133664 (2012)","journal-title":"Development"},{"key":"BFnature19800_CR13","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/j.1399-0004.2009.01238.x","volume":"76","author":"S Mundlos","year":"2009","unstructured":"Mundlos, S. The brachydactylies: a molecular disease family. Clin. Genet. 76, 123\u2013136 (2009)","journal-title":"Clin. Genet."},{"key":"BFnature19800_CR14","doi-asserted-by":"publisher","first-page":"E6456","DOI":"10.1073\/pnas.1518552112","volume":"112","author":"AL Sanborn","year":"2015","unstructured":"Sanborn, A. L. et al. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc. Natl Acad. Sci. USA 112, E6456\u2013E6465 (2015)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature19800_CR15","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1016\/j.cell.2015.07.038","volume":"162","author":"Y Guo","year":"2015","unstructured":"Guo, Y. et al. CRISPR inversion of CTCF sites alters genome topology and enhancer\/promoter function. Cell 162, 900\u2013910 (2015)","journal-title":"Cell"},{"key":"BFnature19800_CR16","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1038\/ng2084","volume":"39","author":"JR Lupski","year":"2007","unstructured":"Lupski, J. R. Genomic rearrangements and sporadic disease. Nature Genet. 39 (Suppl), S43\u2013S47 (2007)","journal-title":"Nature Genet."},{"key":"BFnature19800_CR17","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/nature08645","volume":"462","author":"PJ Stephens","year":"2009","unstructured":"Stephens, P. J. et al. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462, 1005\u20131010 (2009)","journal-title":"Nature"},{"key":"BFnature19800_CR18","doi-asserted-by":"crossref","unstructured":"Ohno, S. Evolution by Gene Duplication (Springer, 1970)","DOI":"10.1007\/978-3-642-86659-3"},{"key":"BFnature19800_CR19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3389\/fgene.2013.00273","volume":"4","author":"V Katju","year":"2013","unstructured":"Katju, V. & Bergthorsson, U. Copy-number changes in evolution: rates, fitness effects and adaptive significance. Front. Genet. 4, 273 (2013)","journal-title":"Front. Genet."},{"key":"BFnature19800_CR20","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.celrep.2015.01.016","volume":"10","author":"K Kraft","year":"2015","unstructured":"Kraft, K. et al. Deletions, inversions, duplications: engineering of structural variants using CRISPR\/Cas in Mice. Cell Reports 10, 833\u2013839 (2015)","journal-title":"Cell Reports"},{"key":"BFnature19800_CR21","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/978-1-60761-974-1_3","volume":"3","author":"J Artus","year":"2011","unstructured":"Artus, J. & Hadjantonakis, A.-K. in Transgenic Mouse Methods and Protocols Vol. 693 Methods in Molecular Biology (eds Hofker, M. H. & van Deursen, J. ) Ch. 3, 37\u201356 (Humana Press, 2011)","journal-title":"Transgenic Mouse Methods and Protocols Vol. 693 Methods in Molecular Biology"},{"key":"BFnature19800_CR22","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/ng.790","volume":"43","author":"S Ruf","year":"2011","unstructured":"Ruf, S. et al. Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor. Nature Genet. 43, 379\u2013386 (2011)","journal-title":"Nature Genet."},{"key":"BFnature19800_CR23","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/326292a0","volume":"326","author":"M Hooper","year":"1987","unstructured":"Hooper, M., Hardy, K., Handyside, A., Hunter, S. & Monk, M. HPRT-deficient (Lesch\u2013Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326, 292\u2013295 (1987)","journal-title":"Nature"},{"key":"BFnature19800_CR24","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/978-3-662-45763-4_18","volume":"18","author":"K Nagy","year":"2011","unstructured":"Nagy, K. & Nichols, J. in Advanced Protocols for Animal Transgenesis (eds Pease, S . & Saunders, T. L. ) Ch. 18, 431\u2013455 (Springer, 2011)","journal-title":"Advanced Protocols for Animal Transgenesis"},{"key":"BFnature19800_CR25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/B978-0-12-391938-0.00004-5","volume":"513","author":"HJG van de Werken","year":"2012","unstructured":"van de Werken, H. J. G. et al. in Methods in Enzymology Vol. 513 (eds Wu, C. & Allis, D. C. ) 89\u2013112 (Academic Press, 2012)","journal-title":"Methods in Enzymology"},{"key":"BFnature19800_CR26","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009)","journal-title":"Bioinformatics"},{"key":"BFnature19800_CR27","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010)","journal-title":"Genome Res."},{"key":"BFnature19800_CR28","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.12688\/f1000research.7334.1","volume":"4","author":"S Wingett","year":"2015","unstructured":"Wingett, S. et al. HiCUP: pipeline for mapping and processing Hi-C data. F1000Res. 4, 1310 (2015)","journal-title":"F1000Res."},{"key":"BFnature19800_CR29","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012)","journal-title":"Nat. Methods"},{"key":"BFnature19800_CR30","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nmeth.2440","volume":"10","author":"X Zhou","year":"2013","unstructured":"Zhou, X. et al. Exploring long-range genome interactions using the WashU Epigenome Browser. Nature Methods 10, 375\u2013376 (2013)","journal-title":"Nature Methods"},{"key":"BFnature19800_CR31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013)","journal-title":"Bioinformatics"},{"key":"BFnature19800_CR32","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014)","journal-title":"Genome Biol."},{"key":"BFnature19800_CR33","doi-asserted-by":"publisher","first-page":"e1005193","DOI":"10.1371\/journal.pgen.1005193","volume":"11","author":"S Bhatia","year":"2015","unstructured":"Bhatia, S. et al. Functional assessment of disease-associated regulatory variants in vivo using a versatile dual colour transgenesis strategy in zebrafish. PLoS Genet. 11, e1005193 (2015)","journal-title":"PLoS Genet."},{"key":"BFnature19800_CR34","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/ng.329","volume":"41","author":"S Benko","year":"2009","unstructured":"Benko, S. et al. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nature Genet. 41, 359\u2013364 (2009)","journal-title":"Nature Genet."},{"key":"BFnature19800_CR35","doi-asserted-by":"publisher","first-page":"D88","DOI":"10.1093\/nar\/gkl822","volume":"35","author":"A Visel","year":"2007","unstructured":"Visel, A., Minovitsky, S., Dubchak, I. & Pennacchio, L. A. VISTA Enhancer Browser\u2014a database of tissue-specific human enhancers. Nucleic Acids Res. 35, D88\u2013D92 (2007)","journal-title":"Nucleic Acids Res."},{"key":"BFnature19800_CR36","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/humu.22606","volume":"35","author":"CT Gordon","year":"2014","unstructured":"Gordon, C. T. et al. Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence. Hum. Mutat. 35, 1011\u20131020 (2014)","journal-title":"Hum. Mutat."},{"key":"BFnature19800_CR37","doi-asserted-by":"publisher","first-page":"5394","DOI":"10.1093\/nar\/gkv426","volume":"43","author":"B Yao","year":"2015","unstructured":"Yao, B. et al. The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers. Nucleic Acids Res. 43, 5394\u20135408 (2015)","journal-title":"Nucleic Acids Res."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature19800.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature19800","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature19800.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:56:02Z","timestamp":1684418162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature19800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":37,"journal-issue":{"issue":"7624","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["BFnature19800"],"URL":"https:\/\/doi.org\/10.1038\/nature19800","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726814205.793524707","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}