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Conference Paper: Integrating genetic analysis with phenotypes of biliary atresia

TitleIntegrating genetic analysis with phenotypes of biliary atresia
Authors
Issue Date2015
Citation
The 2015 Conference of the European Society of Human Genetics (ESHG 2015), Belgrade, Serbia, 10-11 November 2015. How to Cite?
AbstractWe aim to explore the role of rare copy number variants (CNVs) in non-syndromic BA. We revisited clinical records of 89 non-syndromic type III BA patients with median follow up of 17.20 years, which revealed that 41.57% BAs were affected with chronic extra-hepatic diseases, with high prevalence of autoimmune-allergic diseases (22.47%) and Glucose-6-phosphate dehydrogenase deficiency (14.29% of the males). After genotyping on the genome- wide Affymetrix5.0 array, we shortlisted 29 ‘BA-CNVs’ found in BA patients but not in the general population, and collated 103 BA-associated genes from a gene-based genome-wide association analysis on common variants, for downstream analysis. In BA-CNVs we discovered three categories of genotype- phenotype correlations: i) two de novo BA-CNVs, perturbing genes/ chromosome-segments known to BA, correlated with BA; ii) three BA-CNVs encompassing genes known to immunity defects, correlated with comorbiditiescomorbidities of those immune disorders in 3 carriers; iii) importantly, genes affected by BA-CNVs (N=102; gene set-1) were enriched with immune genes, correlated with the high prevalence of immunity disorders in BA. Further, we proved significant connectivity between gene set-1 and genes tagged by common variants (N=103; gene set-2) (Empirical p=0.039). As multiple function modules were elucidated in topological analysis of the BA candidate gene network, a ‘core’ position of cellular signalling pathways, which affect inflammatory and immunity regulation pathways, was highlighted. Conclusions: BA-CNVs underpin BA phenotypic complexity, and converge with those BA-associated common variants in a molecular network implicated in BA pathogenesis. Integrating clinical/epidemiological data and BA genetic findings is plausible using the BA ‚diseasome‘ approach.
Persistent Identifierhttp://hdl.handle.net/10722/214101

 

DC FieldValueLanguage
dc.contributor.authorCheng, G-
dc.contributor.authorChung, HY-
dc.contributor.authorTang, WK-
dc.contributor.authorWong, WH-
dc.contributor.authorChan, EK-
dc.contributor.authorSo, MT-
dc.contributor.authorSham, PC-
dc.contributor.authorCherny, SS-
dc.contributor.authorTam, PKH-
dc.contributor.authorGarcia-Barcelo, MM-
dc.date.accessioned2015-08-20T04:37:10Z-
dc.date.available2015-08-20T04:37:10Z-
dc.date.issued2015-
dc.identifier.citationThe 2015 Conference of the European Society of Human Genetics (ESHG 2015), Belgrade, Serbia, 10-11 November 2015.-
dc.identifier.urihttp://hdl.handle.net/10722/214101-
dc.description.abstractWe aim to explore the role of rare copy number variants (CNVs) in non-syndromic BA. We revisited clinical records of 89 non-syndromic type III BA patients with median follow up of 17.20 years, which revealed that 41.57% BAs were affected with chronic extra-hepatic diseases, with high prevalence of autoimmune-allergic diseases (22.47%) and Glucose-6-phosphate dehydrogenase deficiency (14.29% of the males). After genotyping on the genome- wide Affymetrix5.0 array, we shortlisted 29 ‘BA-CNVs’ found in BA patients but not in the general population, and collated 103 BA-associated genes from a gene-based genome-wide association analysis on common variants, for downstream analysis. In BA-CNVs we discovered three categories of genotype- phenotype correlations: i) two de novo BA-CNVs, perturbing genes/ chromosome-segments known to BA, correlated with BA; ii) three BA-CNVs encompassing genes known to immunity defects, correlated with comorbiditiescomorbidities of those immune disorders in 3 carriers; iii) importantly, genes affected by BA-CNVs (N=102; gene set-1) were enriched with immune genes, correlated with the high prevalence of immunity disorders in BA. Further, we proved significant connectivity between gene set-1 and genes tagged by common variants (N=103; gene set-2) (Empirical p=0.039). As multiple function modules were elucidated in topological analysis of the BA candidate gene network, a ‘core’ position of cellular signalling pathways, which affect inflammatory and immunity regulation pathways, was highlighted. Conclusions: BA-CNVs underpin BA phenotypic complexity, and converge with those BA-associated common variants in a molecular network implicated in BA pathogenesis. Integrating clinical/epidemiological data and BA genetic findings is plausible using the BA ‚diseasome‘ approach.-
dc.languageeng-
dc.relation.ispartofConference of the European Society of Human Genetics, ESHG 2015-
dc.titleIntegrating genetic analysis with phenotypes of biliary atresia-
dc.typeConference_Paper-
dc.identifier.emailCheng, G: gchenghn@hku.hk-
dc.identifier.emailChung, HY: chungphy@hku.hk-
dc.identifier.emailSo, MT: jaymtso@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailCherny, SS: cherny@hku.hk-
dc.identifier.emailTam, PKH: paultam@hku.hk-
dc.identifier.emailGarcia-Barcelo, MM: mmgarcia@hku.hk-
dc.identifier.authorityChung, HY=rp02002-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityCherny, SS=rp00232-
dc.identifier.authorityTam, PKH=rp00060-
dc.identifier.authorityGarcia-Barcelo, MM=rp00445-
dc.identifier.hkuros246883-

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