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Article: Genome-wide copy number analysis uncovers a new HSCR gene: NRG3

TitleGenome-wide copy number analysis uncovers a new HSCR gene: NRG3
Authors
KeywordsCopy number variation
Gene deletion
Gene duplication
Gene expression regulation
Gene frequency
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
Plos Genetics, 2012, v. 8 n. 5 How to Cite?
Abstract
Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched controls showed that HSCR patients have a greater burden of rare CNVs (p = 1.50×10 -5), particularly for those encompassing genes (p = 5.00×10 -6). Our study identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a NRG3 deletion (p = 1.64×10 -3). Subsequent follow-up (96 additional patients and 220 controls) on NRG3 revealed 9 deletions (combined p = 3.36×10 -5) and 2 de novo duplications among patients and two deletions among controls. Importantly, NRG3 is a paralog of NRG1. Stratification of patients by presence/absence of HSCR-associated syndromes showed that while syndromic-HSCR patients carried significantly longer CNVs than the non-syndromic or controls (p = 1.50×10 -5), non-syndromic patients were enriched in CNV number when compared to controls (p = 4.00×10 -6) or the syndromic counterpart. Our results suggest a role for NRG3 in HSCR etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic HSCR. This would be the first genome-wide catalog of copy number variants identified in HSCR. © 2012 Tang et al.
Persistent Identifierhttp://hdl.handle.net/10722/149062
ISSN
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 775907M
HKU 765609M
Seed Funding Programme for Basic Research200910159040
200811159006
200911159190
University Grants Committee of Hong KongAoE/M-04/04
AOSPINEAOSBRC-07-02
Funding Information:

This work was supported by the Hong Kong Research Grants Council (HKU 775907M to PK-HT and HKU 765609M to M-MG-B) and by the Seed Funding Programme for Basic Research (200910159040 and 200811159006 to M-MG-B and 200911159190 to SSC). Support was also received from the University Grants Committee of Hong Kong (AoE/M-04/04) and AOSPINE (AOSBRC-07-02 to DC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References
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DC FieldValueLanguage
dc.contributor.authorTang, CSMen_HK
dc.contributor.authorCheng, Gen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorYip, BHKen_HK
dc.contributor.authorMiao, XPen_HK
dc.contributor.authorWong, EHMen_HK
dc.contributor.authorNgan, ESWen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorSong, YQen_HK
dc.contributor.authorChan, Den_HK
dc.contributor.authorCheung, Ken_HK
dc.contributor.authorYuan, ZWen_HK
dc.contributor.authorLei, Len_HK
dc.contributor.authorChung, HYen_HK
dc.contributor.authorLiu, XLen_HK
dc.contributor.authorWong, KKYen_HK
dc.contributor.authorMarshall, CRen_HK
dc.contributor.authorScherer, Sen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorGarciaBarceló, MMen_HK
dc.date.accessioned2012-06-22T06:19:38Z-
dc.date.available2012-06-22T06:19:38Z-
dc.date.issued2012en_HK
dc.identifier.citationPlos Genetics, 2012, v. 8 n. 5en_HK
dc.identifier.issn1553-7390en_HK
dc.identifier.urihttp://hdl.handle.net/10722/149062-
dc.description.abstractHirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched controls showed that HSCR patients have a greater burden of rare CNVs (p = 1.50×10 -5), particularly for those encompassing genes (p = 5.00×10 -6). Our study identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a NRG3 deletion (p = 1.64×10 -3). Subsequent follow-up (96 additional patients and 220 controls) on NRG3 revealed 9 deletions (combined p = 3.36×10 -5) and 2 de novo duplications among patients and two deletions among controls. Importantly, NRG3 is a paralog of NRG1. Stratification of patients by presence/absence of HSCR-associated syndromes showed that while syndromic-HSCR patients carried significantly longer CNVs than the non-syndromic or controls (p = 1.50×10 -5), non-syndromic patients were enriched in CNV number when compared to controls (p = 4.00×10 -6) or the syndromic counterpart. Our results suggest a role for NRG3 in HSCR etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic HSCR. This would be the first genome-wide catalog of copy number variants identified in HSCR. © 2012 Tang et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/en_HK
dc.relation.ispartofPLoS Geneticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCopy number variation-
dc.subjectGene deletion-
dc.subjectGene duplication-
dc.subjectGene expression regulation-
dc.subjectGene frequency-
dc.titleGenome-wide copy number analysis uncovers a new HSCR gene: NRG3en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1553-7390&volume=8&issue=5&spage=e1002687&epage=&date=2012&atitle=Genome-Wide+Copy+Number+Analysis+Uncovers+a+New+HSCR+Gene:+NRG3en_US
dc.identifier.emailWong, KKY: kkywong@hku.hken_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hku.hken_HK
dc.identifier.emailGarciaBarceló, MM: mmgarcia@hku.hken_HK
dc.identifier.authorityWong, KKY=rp01392en_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authorityGarciaBarceló, MM=rp00445en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pgen.1002687en_HK
dc.identifier.pmid22589734-
dc.identifier.pmcidPMC3349728-
dc.identifier.scopuseid_2-s2.0-84863680217en_HK
dc.identifier.hkuros200158en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863680217&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume8en_HK
dc.identifier.issue5en_HK
dc.identifier.eissn1553-7404-
dc.identifier.isiWOS:000304864000018-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectIdentification of functional variants in Neuregulin-1 (NRG1), a newly discovered Hirschsprung s disease gene-
dc.relation.projectGenetic dissection of Hirschsprung's disease-
dc.relation.projectDevelopmental genomics and skeletal research-
dc.identifier.scopusauthoridTang, CSM=35764635500en_HK
dc.identifier.scopusauthoridCheng, G=37861100700en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridYip, BHK=55268459600en_HK
dc.identifier.scopusauthoridMiao, XP=7102585391en_HK
dc.identifier.scopusauthoridWong, EHM=55307720600en_HK
dc.identifier.scopusauthoridNgan, ESW=55307863100en_HK
dc.identifier.scopusauthoridLui, VCH=55270562500en_HK
dc.identifier.scopusauthoridSong, YQ=47761560700en_HK
dc.identifier.scopusauthoridChan, D=55307523800en_HK
dc.identifier.scopusauthoridCheung, K=55308509100en_HK
dc.identifier.scopusauthoridYuan, ZW=8672008500en_HK
dc.identifier.scopusauthoridLei, L=55308041400en_HK
dc.identifier.scopusauthoridChung, PHY=34568741300en_HK
dc.identifier.scopusauthoridLiu, XL=36106291400en_HK
dc.identifier.scopusauthoridWong, KKY=24438686400en_HK
dc.identifier.scopusauthoridMarshall, CR=7201903397en_HK
dc.identifier.scopusauthoridScherer, S=55159183300en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridGarciaBarceló, MM=6701767303en_HK

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