Conference Paper: Genome-wide copy number variation in anorectal malformations

TitleGenome-wide copy number variation in anorectal malformations
Authors
KeywordsComplex Traits and Polygenic Disorders
KW034 - copy number/structural variation
KW040 - development
KW065 - gastrointestinal system
KW080 - genome-wide association
KW099 - malformation
Issue Date2012
PublisherAmerican Society of Human Genetics.
Citation
The 62th Annual Meeting of American Society of Human Genetics (ASHG 2012), San Francisco, CA., 6-10 November 2012. 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 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 (SNPs) and copy number variants (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4,006 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 < .05), non-syndromic patients were enriched with both rare deletions and duplications when compared to controls (p < .0004). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls or 11,943 healthy individuals from the Database of Genomic Variants (DGV). Importantly, the 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 and an INTU hemizygous deletion. These genes are members of pathways (Shh and Wnt, respectively) involved in the development of the anorectal region. In mice, Shh or Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provides a list of plausible candidate genes for the disorder.
DescriptionPoster: Session Title - Complex Traits and Polygenic Disorders - Program no. 2066F
Persistent Identifierhttp://hdl.handle.net/10722/181804

 

DC FieldValueLanguage
dc.contributor.authorCherny, SSen_US
dc.contributor.authorWong, EHMen_US
dc.contributor.authorCui, Len_US
dc.contributor.authorNg, CLen_US
dc.contributor.authorTang, CSMen_US
dc.contributor.authorSo, MTen_US
dc.contributor.authorYip, BHKen_US
dc.contributor.authorCheng, Gen_US
dc.contributor.authorLui, VCHen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorTam, PKHen_US
dc.contributor.authorGarcia-Barcelo, MMen_US
dc.date.accessioned2013-03-19T03:58:56Z-
dc.date.available2013-03-19T03:58:56Z-
dc.date.issued2012en_US
dc.identifier.citationThe 62th Annual Meeting of American Society of Human Genetics (ASHG 2012), San Francisco, CA., 6-10 November 2012.en_US
dc.identifier.urihttp://hdl.handle.net/10722/181804-
dc.descriptionPoster: Session Title - Complex Traits and Polygenic Disorders - Program no. 2066F-
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 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 (SNPs) and copy number variants (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4,006 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 < .05), non-syndromic patients were enriched with both rare deletions and duplications when compared to controls (p < .0004). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls or 11,943 healthy individuals from the Database of Genomic Variants (DGV). Importantly, the 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 and an INTU hemizygous deletion. These genes are members of pathways (Shh and Wnt, respectively) involved in the development of the anorectal region. In mice, Shh or Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provides a list of plausible candidate genes for the disorder.-
dc.languageengen_US
dc.publisherAmerican Society of Human Genetics.-
dc.relation.ispartofAnnual Meeting of American Society of Human Genetics, ASHG 2012en_US
dc.subjectComplex Traits and Polygenic Disorders-
dc.subjectKW034 - copy number/structural variation-
dc.subjectKW040 - development-
dc.subjectKW065 - gastrointestinal system-
dc.subjectKW080 - genome-wide association-
dc.subjectKW099 - malformation-
dc.titleGenome-wide copy number variation in anorectal malformationsen_US
dc.typeConference_Paperen_US
dc.identifier.emailCherny, SS: cherny@hku.hken_US
dc.identifier.emailWong, EHM: emilywongmm@yahoo.com.hken_US
dc.identifier.emailCui, L: longcui@hku.hken_US
dc.identifier.emailNg, CL: royclng@hku.hken_US
dc.identifier.emailTang, CSM: claratang@hku.hken_US
dc.identifier.emailSo, MT: jaymtso@hku.hken_US
dc.identifier.emailCheng, G: chengguo@hku.hken_US
dc.identifier.emailLui, VCH: vchlui@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.authorityCherny, SS=rp00232en_US
dc.identifier.authorityLui, VCH=rp00363en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.authorityTam, PKH=rp00060en_US
dc.identifier.authorityGarcia-Barcelo, MM=rp00445en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros213464en_US
dc.publisher.placeUnited States-
dc.customcontrol.immutablesml 130607-

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