{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:51:48Z","timestamp":1772959908920,"version":"3.50.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,15]]},"DOI":"10.1093\/hmg\/dds165","type":"journal-article","created":{"date-parts":[[2012,4,27]],"date-time":"2012-04-27T21:26:26Z","timestamp":1335561986000},"page":"3255-3263","source":"Crossref","is-referenced-by-count":191,"title":["Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease"],"prefix":"10.1093","volume":"21","author":[{"given":"Scott","family":"Smemo","sequence":"first","affiliation":[]},{"given":"Luciene C.","family":"Campos","sequence":"additional","affiliation":[]},{"given":"Ivan P.","family":"Moskowitz","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 E.","family":"Krieger","sequence":"additional","affiliation":[]},{"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Marcelo A.","family":"Nobrega","sequence":"additional","affiliation":[]}],"member":"286","published-online":{"date-parts":[[2012,4,27]]},"reference":[{"key":"key\n\t\t\t\t20170522124559_DDS165C1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/S0735-1097(02)01886-7","article-title":"The incidence of congenital heart disease","volume":"39","author":"Hoffman","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/ng0197-30","article-title":"Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt\u2013Oram syndrome","volume":"15","author":"Basson","year":"1997","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C3","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature01827","article-title":"GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5","volume":"424","author":"Garg","year":"2003","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C4","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1126\/science.281.5373.108","article-title":"Congenital heart disease caused by mutations in the transcription factor NKX2-5","volume":"281","author":"Schott","year":"1998","journal-title":"Science"},{"key":"key\n\t\t\t\t20170522124559_DDS165C5","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/hmg\/ddq554","article-title":"Loss of Cited2 causes congenital heart disease by perturbing left-right patterning of the body axis","volume":"20","author":"Lopes Floro","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C6","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1093\/hmg\/ddn027","article-title":"A loss-of-function mutation in the binding domain of HAND1 predicts hypoplasia of the human hearts","volume":"17","author":"Reamon-Buettner","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C7","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nature06801","article-title":"The developmental genetics of congenital heart disease","volume":"451","author":"Bruneau","year":"2008","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C8","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature08250","article-title":"Targeted capture and massively parallel sequencing of 12 human exomes","volume":"461","author":"Ng","year":"2009","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/GIM.0b013e3182088158","article-title":"Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease","volume":"13","author":"Worthey","year":"2011","journal-title":"Genet. Med."},{"key":"key\n\t\t\t\t20170522124559_DDS165C10","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nrg3031","article-title":"Exome sequencing as a tool for Mendelian disease gene discovery","volume":"12","author":"Bamshad","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C11","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/ng.646","article-title":"Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome","volume":"42","author":"Ng","year":"2010","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature09753","article-title":"9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response","volume":"470","author":"Harismendy","year":"2011","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C13","article-title":"The 14q22.2 colorectal cancer variant rs4444235 shows cis-acting regulation of BMP4","author":"Lubbe","year":"2011","journal-title":"Oncogene"},{"key":"key\n\t\t\t\t20170522124559_DDS165C14","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nature09266","article-title":"From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus","volume":"466","author":"Musunuru","year":"2010","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C15","doi-asserted-by":"crossref","first-page":"e1001126","DOI":"10.1371\/journal.pgen.1001126","article-title":"Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H","volume":"6","author":"Pittman","year":"2010","journal-title":"PLoS Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C16","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1101\/gr.092668.109","article-title":"The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression","volume":"19","author":"Pittman","year":"2009","journal-title":"Genome. Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature08451","article-title":"Genomic views of distant-acting enhancers","volume":"461","author":"Visel","year":"2009","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C18","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/gb-2012-13-1-238","article-title":"Transcriptional enhancers in development and disease","volume":"13","author":"Sakabe","year":"2012","journal-title":"Genome. Biol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C19","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1101\/gr.105361.110","article-title":"An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer","volume":"20","author":"Wasserman","year":"2010","journal-title":"Genome. Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ng.511","article-title":"Several common variants modulate heart rate, PR interval and QRS duration","volume":"42","author":"Holm","year":"2010","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/ng.517","article-title":"Genome-wide association study of PR interval","volume":"42","author":"Pfeufer","year":"2010","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C22","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/ng.716","article-title":"Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction","volume":"42","author":"Sotoodehnia","year":"2010","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C23","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1086\/519530","article-title":"Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy","volume":"81","author":"Kirk","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C24","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/dbio.2000.9748","article-title":"Ventricular expression of tbx5 inhibits normal heart chamber development","volume":"223","author":"Liberatore","year":"2000","journal-title":"Dev. Biol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C25","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1242\/dev.00474","article-title":"Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt\/Fgf signaling cascade","volume":"130","author":"Takeuchi","year":"2003","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1006\/dbio.1999.9298","article-title":"Chamber-specific cardiac expression of Tbx5 and heart defects in Holt\u2013Oram syndrome","volume":"211","author":"Bruneau","year":"1999","journal-title":"Dev. Biol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C27","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0092-8674(01)00493-7","article-title":"A murine model of Holt\u2013Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease","volume":"106","author":"Bruneau","year":"2001","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170522124559_DDS165C28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng0197-21","article-title":"Holt\u2013Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family","volume":"15","author":"Li","year":"1997","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C29","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1136\/hrt.22.2.236","article-title":"Familial heart disease with skeletal malformations","volume":"22","author":"Holt","year":"1960","journal-title":"Br. Heart. J."},{"key":"key\n\t\t\t\t20170522124559_DDS165C30","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.ydbio.2006.05.023","article-title":"Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis","volume":"297","author":"Mori","year":"2006","journal-title":"Dev. Biol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.gep.2009.11.003","article-title":"Identification and characterisation of the developmental expression pattern of tbx5b, a novel tbx5 gene in zebrafish","volume":"10","author":"Albalat","year":"2010","journal-title":"Gene. Expr. Patterns"},{"key":"key\n\t\t\t\t20170522124559_DDS165C32","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1242\/dev.129.19.4635","article-title":"The heartstrings mutation in zebrafish causes heart\/fin Tbx5 deficiency syndrome","volume":"129","author":"Garrity","year":"2002","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C33","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1242\/dev.126.8.1739","article-title":"Tbx5 is essential for heart development","volume":"126","author":"Horb","year":"1999","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C34","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/hmg\/ddg180","article-title":"A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly","volume":"12","author":"Lettice","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C35","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1101\/gr.123745.111","article-title":"Alterations in TCF7L2 expression define its role as a key regulator of glucose metabolism","volume":"21","author":"Savic","year":"2011","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C36","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0092-8674(03)00310-6","article-title":"A global control region defines a chromosomal regulatory landscape containing the HoxD cluster","volume":"113","author":"Spitz","year":"2003","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170522124559_DDS165C37","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/jmor.1051490306","article-title":"The development of the septum primum relative to atrial septation in the mouse heart","volume":"149","author":"Dalgleish","year":"1976","journal-title":"J. Morphol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C38","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1242\/dev.128.10.1785","article-title":"Visualization and functional characterization of the developing murine cardiac conduction system","volume":"128","author":"Rentschler","year":"2001","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C39","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/ng.650","article-title":"ChIP-Seq identification of weakly conserved heart enhancers","volume":"42","author":"Blow","year":"2010","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C40","doi-asserted-by":"crossref","first-page":"5632","DOI":"10.1073\/pnas.1016959108","article-title":"Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart","volume":"108","author":"He","year":"2011","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"key\n\t\t\t\t20170522124559_DDS165C41","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1101\/gr.098657.109","article-title":"Genome-wide discovery of human heart enhancers","volume":"20","author":"Narlikar","year":"2010","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C42","doi-asserted-by":"crossref","first-page":"W273","DOI":"10.1093\/nar\/gkh458","article-title":"VISTA: computational tools for comparative genomics","volume":"32","author":"Frazer","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C43","doi-asserted-by":"crossref","first-page":"W280","DOI":"10.1093\/nar\/gkh355","article-title":"ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes","volume":"32","author":"Ovcharenko","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C44","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1161\/CIRCRESAHA.108.172858","article-title":"Tbx3 is required for outflow tract development","volume":"103","author":"Mesbah","year":"2008","journal-title":"Circ. Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C45","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1101\/gr.1933104","article-title":"Aligning multiple genomic sequences with the threaded blockset aligner","volume":"14","author":"Blanchette","year":"2004","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C46","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies","volume":"20","author":"Pollard","year":"2010","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C47","doi-asserted-by":"crossref","first-page":"W217","DOI":"10.1093\/nar\/gkh383","article-title":"rVISTA 2.0: evolutionary analysis of transcription factor binding sites","volume":"32","author":"Loots","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C48","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1093\/nar\/24.1.238","article-title":"TRANSFAC: a database on transcription factors and their DNA binding sites","volume":"24","author":"Wingender","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170522124559_DDS165C49","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1182\/blood.V95.5.1671.005k39_1671_1679","article-title":"Vasculogenesis in the day 6.5 to 9.5 mouse embryo","volume":"95","author":"Drake","year":"2000","journal-title":"Blood"},{"key":"key\n\t\t\t\t20170522124559_DDS165C50","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.modgep.2006.10.004","article-title":"lyl-1 and tal-1\/scl, two genes encoding closely related bHLH transcription factors, display highly overlapping expression patterns during cardiovascular and hematopoietic ontogeny","volume":"7","author":"Giroux","year":"2007","journal-title":"Gene Expr. Patterns"},{"key":"key\n\t\t\t\t20170522124559_DDS165C51","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1242\/dev.126.17.3891","article-title":"An SCL 3\u2032 enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors","volume":"126","author":"Sanchez","year":"1999","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C52","doi-asserted-by":"crossref","first-page":"e140","DOI":"10.1371\/journal.pgen.0030140","article-title":"Early endocardial morphogenesis requires Scl\/Tal1","volume":"3","author":"Bussmann","year":"2007","journal-title":"PLoS Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C53","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1172\/JCI59472","article-title":"Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function","volume":"121","author":"Shen","year":"2011","journal-title":"J. Clin. Invest."},{"key":"key\n\t\t\t\t20170522124559_DDS165C54","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"Consortium","year":"2010","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C55","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/ajmg.1320440237","article-title":"Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome","volume":"44","author":"Driscoll","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"key\n\t\t\t\t20170522124559_DDS165C56","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nature05874","article-title":"Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project","volume":"447","author":"Birney","year":"2007","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170522124559_DDS165C57","doi-asserted-by":"crossref","first-page":"e1001046","DOI":"10.1371\/journal.pbio.1001046","article-title":"A user's guide to the encyclopedia of DNA elements (ENCODE)","volume":"9","author":"Myers","year":"2011","journal-title":"PLoS Biol."},{"key":"key\n\t\t\t\t20170522124559_DDS165C58","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.ygeno.2005.03.003","article-title":"In vivo characterization of a vertebrate ultraconserved enhancer","volume":"85","author":"Poulin","year":"2005","journal-title":"Genomics"},{"key":"key\n\t\t\t\t20170522124559_DDS165C59","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"key\n\t\t\t\t20170522124559_DDS165C60","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1242\/dev.127.17.3645","article-title":"The olfactory placodes of the zebrafish form by convergence of cellular fields at the edge of the neural plate","volume":"127","author":"Whitlock","year":"2000","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C61","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1242\/dev.108.4.569","article-title":"Cell movements during epiboly and gastrulation in zebrafish","volume":"108","author":"Warga","year":"1990","journal-title":"Development"},{"key":"key\n\t\t\t\t20170522124559_DDS165C62","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0076-6879(93)25025-W","article-title":"Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts","volume":"225","author":"Wilkinson","year":"1993","journal-title":"Methods Enzymol."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/21\/14\/3255\/17256741\/dds165.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T06:07:09Z","timestamp":1642140429000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article-lookup\/doi\/10.1093\/hmg\/dds165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,27]]},"references-count":62,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2012,4,27]]},"published-print":{"date-parts":[[2012,7,15]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/dds165","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717948852.793453953","asserted-by":"object"}]},"ISSN":["1460-2083","0964-6906"],"issn-type":[{"value":"1460-2083","type":"electronic"},{"value":"0964-6906","type":"print"}],"subject":[],"published":{"date-parts":[[2012,4,27]]}}}