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Article: Fine mapping of the 9q31 Hirschsprung's disease locus

TitleFine mapping of the 9q31 Hirschsprung's disease locus
Authors
Issue Date2010
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
Citation
Human Genetics, 2010, v. 127 n. 6, p. 675-683 How to Cite?
AbstractHirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 ×9 10-6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCRassociation found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. © 2010 Springer-Verlag.
Persistent Identifierhttp://hdl.handle.net/10722/144968
ISSN
2014 Impact Factor: 4.824
2014 SCImago Journal Rankings: 2.261
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 765008M
HKU 775907M
University of Hong Kong200709159003
200611159152
University Grants Committee of Hong KongAoE/M-04/04
University of Hong Kong Genomics Strategic Research Theme
NIHEY-12562
Bernoulle Foundation
NWO901-04-225
Funding Information:

We would like to express our gratitude to all the subjects who participated in the study. This work was supported by grants from the Hong Kong Research Grants Council HKU 765008M and HKU 775907M and The University of Hong Kong Seed Funding 200709159003 and 200611159152 to MGB and PT, respectively. Support was also obtained from the University Grants Committee of Hong Kong (AoE/M-04/04) and from The University of Hong Kong Genomics Strategic Research Theme. SSC and PCS are supported by NIH Grant EY-12562. YS is supported by a grant from the Bernoulle Foundation and GB was supported by a NWO grant (no. 901-04-225).

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DC FieldValueLanguage
dc.contributor.authorTang, CSen_HK
dc.contributor.authorSribudiani, Yen_HK
dc.contributor.authorMiao, XPen_HK
dc.contributor.authorDe Vries, ARen_HK
dc.contributor.authorBurzynski, Gen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorLeon, YYen_HK
dc.contributor.authorYip, BHen_HK
dc.contributor.authorOsinga, Jen_HK
dc.contributor.authorHui, KJWSen_HK
dc.contributor.authorVerheij, JBGMen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorHofstra, RMWen_HK
dc.contributor.authorGarciaBarceló, MMen_HK
dc.date.accessioned2012-02-21T05:42:58Z-
dc.date.available2012-02-21T05:42:58Z-
dc.date.issued2010en_HK
dc.identifier.citationHuman Genetics, 2010, v. 127 n. 6, p. 675-683en_HK
dc.identifier.issn0340-6717en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144968-
dc.description.abstractHirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 ×9 10-6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCRassociation found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. © 2010 Springer-Verlag.en_HK
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htmen_HK
dc.relation.ispartofHuman Geneticsen_HK
dc.rightsThe Author(s)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.subject.meshCarrier Proteins - genetics-
dc.subject.meshChromosomes, Human, Pair 9-
dc.subject.meshHirschsprung Disease - genetics-
dc.subject.meshPhysical Chromosome Mapping - methods-
dc.subject.meshProto-Oncogene Proteins c-ret - genetics-
dc.titleFine mapping of the 9q31 Hirschsprung's disease locusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4551/resserv?sid=springerlink&genre=article&atitle=Fine mapping of the 9q31 Hirschsprung’s disease locus&title=Human Genetics&issn=03406717&date=2010-06-01&volume=127&issue=6& spage=675&authors=C. S. Tang, Y. Sribudiani, X. P. Miao, <i>et al.</i>en_US
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailGarciaBarceló, MM: mmgarcia@hku.hken_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityGarciaBarceló, MM=rp00445en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s00439-010-0813-8en_HK
dc.identifier.pmid20361209en_US
dc.identifier.pmcidPMC2871095-
dc.identifier.scopuseid_2-s2.0-77953443007en_HK
dc.identifier.hkuros170748-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953443007&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume127en_HK
dc.identifier.issue6en_HK
dc.identifier.spage675en_HK
dc.identifier.epage683en_HK
dc.identifier.eissn1432-1203en_US
dc.identifier.isiWOS:000277713300007-
dc.publisher.placeGermanyen_HK
dc.description.otherSpringer Open Choice, 21 Feb 2012en_US
dc.relation.projectGenetic dissection of Hirschsprung's disease-
dc.relation.projectFine mapping of Hirschsprung's disease loci on the 3p21 and 9q31 candidate regions-
dc.relation.projectDevelopmental genomics and skeletal research-
dc.identifier.scopusauthoridTang, CS=35764635500en_HK
dc.identifier.scopusauthoridSribudiani, Y=35764806300en_HK
dc.identifier.scopusauthoridMiao, XP=7102585391en_HK
dc.identifier.scopusauthoridDe Vries, AR=24398157300en_HK
dc.identifier.scopusauthoridBurzynski, G=8582419900en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridLeon, YY=35764737500en_HK
dc.identifier.scopusauthoridYip, BH=16685586100en_HK
dc.identifier.scopusauthoridOsinga, J=6701371219en_HK
dc.identifier.scopusauthoridHui, KJWS=35764515100en_HK
dc.identifier.scopusauthoridVerheij, JBGM=7003347665en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridHofstra, RMW=7006771436en_HK
dc.identifier.scopusauthoridGarciaBarceló, MM=6701767303en_HK
dc.identifier.citeulike6956535-

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