{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:24:24Z","timestamp":1761845064303,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY020483"],"award-info":[{"award-number":["R01 EY020483"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000003"],"award-info":[{"award-number":["UL1TR000003"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1RR024134"],"award-info":[{"award-number":["UL1RR024134"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD026979","HL84410","P01\u2010HD070454","P50\u2010HL074731"],"award-info":[{"award-number":["HD026979","HL84410","P01\u2010HD070454","P50\u2010HL074731"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Over 50% of patients with 22q11.2 deletion syndrome (DS) have a conotruncal or related cardiac defect (CTRD). We hypothesized that similar genetic variants, developmental pathways and biological functions, contribute to disease risk for CTRD in patients without a 22q11.2 deletion (ND\u2010CTRD) and with a 22q11.2 deletion (DS\u2010CTRD). To test this hypothesis, we performed rare CNV (rCNV)\u2010based analyses on 630 ND\u2010CTRD cases and 602 DS\u2010CTRD cases with comparable cardiac lesions separately and jointly. First, we detected a collection of heart development related pathways from Gene Ontology and Mammalian Phenotype Ontology analysis. We then constructed gene regulation networks using unique genes collected from the rCNVs found in the ND\u2010CTRD and DS\u2010CTRD cohorts. These gene networks were clustered and their predicted functions were examined. We further investigated expression patterns of those unique genes using publicly available mouse embryo microarray expression data from single\u2010cell embryos to fully developed hearts. By these bioinformatics approaches, we identified a commonly shared gene expression pattern in both the ND\u2010CTRD and DS\u2010CTRD cohorts. Computational analysis of gene functions characterized with this expression pattern revealed a collection of significantly enriched terms related to cardiovascular development. By our combined analysis of rCNVs in the ND\u2010CTRD and DS\u2010CTRD cohorts, a group of statistically significant shared pathways, biological functions, and gene expression patterns were identified that can be tested in future studies for their biological relevance.<\/jats:p>","DOI":"10.1002\/bdr2.1534","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T04:20:22Z","timestamp":1561090822000},"page":"888-905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Copy number variations in individuals with conotruncal heart defects reveal some shared developmental pathways irrespective of 22q11.2 deletion status"],"prefix":"10.1002","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-0029","authenticated-orcid":false,"given":"Hongbo M.","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Biomedical and Health Informatics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanne M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M.","family":"McDonald\u2010McGinn","sequence":"additional","affiliation":[{"name":"Division of Human Genetics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[{"name":"Division of Human Genetics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"},{"name":"Department of Pediatrics Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwight","family":"Stambolian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Human Genetics University of Pennsylvania, Perelman School of Medicine  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"The Center for Applied Genomics, Department of Pediatrics The Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernice E.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Genetics Yeshiva University, Albert Einstein College of Medicine  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly S.","family":"Emanuel","sequence":"additional","affiliation":[{"name":"Division of Human Genetics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"},{"name":"Department of Pediatrics Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Goldmuntz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania"},{"name":"Division of Cardiology The Children's Hospital of Philadelphia, Department of Pediatrics  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1430-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.231233"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602543103"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.08.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1710"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3092"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2009.07.004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.03.007"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.25.14863"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.57"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-74"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.304458"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000249"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-2-r19"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01886-7"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107680.110"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.04.010"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.003756"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.71"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.03.007"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1623-9"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29042"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20070430"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020988"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.183056"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.05.059"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02519"},{"key":"e_1_2_7_30_1","unstructured":"Schinke M. Jay P. Brown J. &Izumo S.. (2004). C57BL\/6 Benchmark set for early cardiac development. Series GSE1479. Retrieved fromhttp:\/\/www.cardiogenomics.org"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002843"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.003"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1552"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20723"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6861907"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23279"},{"key":"e_1_2_7_39_1","first-page":"146","article-title":"ReactomeFIViz: A Cytoscape app for pathway and network\u2010based data analysis","volume":"3","author":"Wu G.","year":"2014","journal-title":"F1000Research"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23609"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.07.005"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.030"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdr2.1534","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1534","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdr2.1534","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1534","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T16:58:47Z","timestamp":1694278727000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.1534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,20]]},"references-count":41,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/bdr2.1534"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.1534","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"type":"print","value":"2472-1727"},{"type":"electronic","value":"2472-1727"}],"subject":[],"published":{"date-parts":[[2019,6,20]]},"assertion":[{"value":"2019-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}