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Article: Genome-wide copy number variation study in anorectal malformations

TitleGenome-wide copy number variation study in anorectal malformations
Authors
KeywordsAnimal tissue
Anorectal malformation
Chromosome aberration
Single nucleotide polymorphism
WNT signaling pathway
Issue Date2013
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2013, v. 22 n. 3, p. 621-631 How to Cite?
AbstractAnorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.
Persistent Identifierhttp://hdl.handle.net/10722/181686
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, EHMen_US
dc.contributor.authorCui, Len_US
dc.contributor.authorNg, CLen_US
dc.contributor.authorTang, CSMen_US
dc.contributor.authorLiu, Xen_US
dc.contributor.authorSo, MTen_US
dc.contributor.authorYip, BHKen_US
dc.contributor.authorCheng, Gen_US
dc.contributor.authorZhang, Ren_US
dc.contributor.authorTang, WKen_US
dc.contributor.authorYang, Wen_US
dc.contributor.authorLau, YLen_US
dc.contributor.authorBaum, Len_US
dc.contributor.authorKwan, Pen_US
dc.contributor.authorSun, LDen_US
dc.contributor.authorZuo, XBen_US
dc.contributor.authorRen, YQen_US
dc.contributor.authorYin, XYen_US
dc.contributor.authorMiao, Xen_US
dc.contributor.authorLiu, JJen_US
dc.contributor.authorLui, VCHen_US
dc.contributor.authorNgan, ESWen_US
dc.contributor.authorYuan, ZWen_US
dc.contributor.authorZhang, SWen_US
dc.contributor.authorXia, JLen_US
dc.contributor.authorWang, HLen_US
dc.contributor.authorSun, XBen_US
dc.contributor.authorWang, RYen_US
dc.contributor.authorChang, Ten_US
dc.contributor.authorChan, IHYen_US
dc.contributor.authorChung, HYen_US
dc.contributor.authorZhang, XJen_US
dc.contributor.authorWong, KKYen_US
dc.contributor.authorCherny, SSen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorTam, PKHen_US
dc.contributor.authorGarcia-Barcelo, MMen_US
dc.date.accessioned2013-03-19T03:54:14Z-
dc.date.available2013-03-19T03:54:14Z-
dc.date.issued2013en_US
dc.identifier.citationHuman Molecular Genetics, 2013, v. 22 n. 3, p. 621-631en_US
dc.identifier.issn0964-6906-
dc.identifier.urihttp://hdl.handle.net/10722/181686-
dc.description.abstractAnorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.-
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/-
dc.relation.ispartofHuman Molecular Geneticsen_US
dc.rightsThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The definitive publisher-authenticated version Human Molecular Genetics, 2013, v. 22 n. 3, p. 621-631 is available online at: http://hmg.oxfordjournals.org/content/22/3/621-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAnimal tissue-
dc.subjectAnorectal malformation-
dc.subjectChromosome aberration-
dc.subjectSingle nucleotide polymorphism-
dc.subjectWNT signaling pathway-
dc.titleGenome-wide copy number variation study in anorectal malformationsen_US
dc.typeArticleen_US
dc.identifier.emailWong, EHM: emilywongmm@yahoo.com.hken_US
dc.identifier.emailCui, L: longcui@hku.hken_US
dc.identifier.emailLiu, X: liuxlai@hku.hken_US
dc.identifier.emailSo, MT: jaymtso@hku.hken_US
dc.identifier.emailYip, BHK: yipben@hkucc.hku.hken_US
dc.identifier.emailCheng, G: chengguo@hku.hken_US
dc.identifier.emailZhang, R: h1094156@hku.hken_US
dc.identifier.emailYang, W: yangwl@hkucc.hku.hken_US
dc.identifier.emailLau, YL: lauylung@hku.hken_US
dc.identifier.emailMiao, X: miaoxp@hkucc.hku.hken_US
dc.identifier.emailLui, VCH: vchlui@hku.hken_US
dc.identifier.emailNgan, ESW: engan@hku.hken_US
dc.identifier.emailWong, KKY: kkywong@hku.hk-
dc.identifier.emailCherny, SS: cherny@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailTam, PKH: paultam@hku.hk-
dc.identifier.emailGarcia-Barcelo, MM: mmgarcia@hku.hk-
dc.identifier.authorityYang, W=rp00524en_US
dc.identifier.authorityLau, YL=rp00361en_US
dc.identifier.authorityLui, VCH=rp00363en_US
dc.identifier.authorityNgan, ESW=rp00422en_US
dc.identifier.authorityWong, KKY=rp01392en_US
dc.identifier.authorityCherny, SS=rp00232en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.authorityTam, PKH=rp00060en_US
dc.identifier.authorityGarcia-Barcelo, MM=rp00445en_US
dc.description.naturepostprint-
dc.identifier.doi10.1093/hmg/dds451-
dc.identifier.pmid23108157-
dc.identifier.scopuseid_2-s2.0-84872402412-
dc.identifier.hkuros213467en_US
dc.identifier.volume22-
dc.identifier.issue3-
dc.identifier.spage621-
dc.identifier.epage631-
dc.identifier.isiWOS:000313531500017-
dc.publisher.placeUnited Kingdom-
dc.customcontrol.immutablesml 130607-

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