Article: Fine mapping of the 9q31 Hirschsprung's disease locus
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- Publisher Website: 10.1007/s00439-010-0813-8
- Scopus: eid_2-s2.0-77953443007
- PMID: 20361209
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| Title | Fine mapping of the 9q31 Hirschsprung's disease locus | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Authors | Tang, CS1 Sribudiani, Y2 Miao, XP1 4 De Vries, AR2 Burzynski, G2 4 So, MT1 Leon, YY1 Yip, BH1 Osinga, J2 Hui, KJWS1 Verheij, JBGM2 Cherny, SS1 Tam, PKH1 Sham, PC1 Hofstra, RMW2 3 GarciaBarceló, MM1 | ||||||||||||||||
| Issue Date | 2010 | ||||||||||||||||
| Publisher | Springer 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?] DOI: http://dx.doi.org/10.1007/s00439-010-0813-8 | ||||||||||||||||
| Abstract | Hirschsprung'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. | ||||||||||||||||
| ISSN | 0340-6717 2011 Impact Factor: 5.069 2011 SCImago Journal Rankings: 0.328 | ||||||||||||||||
| DOI | http://dx.doi.org/10.1007/s00439-010-0813-8 | ||||||||||||||||
| ISI Accession Number ID | WOS:000277713300007
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). | ||||||||||||||||
| PubMed Central ID | PMC2871095 | ||||||||||||||||
| References | References in Scopus | ||||||||||||||||
| Grants | Genetic dissection of Hirschsprung's disease Whole genome family based association study to search for RET-dependent modifiers in Hirchsprung's disease Fine mapping of a Hirschsprung's disease locus on the 3p21candidate region Fine mapping of Hirschsprungs disease loci on the 3p21 and 9q31 candidate regions Developmental genomics and skeletal research |
| dc.contributor.author | Tang, CS | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Sribudiani, Y | ||||||||||||||||
| dc.contributor.author | Miao, XP | ||||||||||||||||
| dc.contributor.author | De Vries, AR | ||||||||||||||||
| dc.contributor.author | Burzynski, G | ||||||||||||||||
| dc.contributor.author | So, MT | ||||||||||||||||
| dc.contributor.author | Leon, YY | ||||||||||||||||
| dc.contributor.author | Yip, BH | ||||||||||||||||
| dc.contributor.author | Osinga, J | ||||||||||||||||
| dc.contributor.author | Hui, KJWS | ||||||||||||||||
| dc.contributor.author | Verheij, JBGM | ||||||||||||||||
| dc.contributor.author | Cherny, SS | ||||||||||||||||
| dc.contributor.author | Tam, PKH | ||||||||||||||||
| dc.contributor.author | Sham, PC | ||||||||||||||||
| dc.contributor.author | Hofstra, RMW | ||||||||||||||||
| dc.contributor.author | GarciaBarceló, MM | ||||||||||||||||
| dc.date.accessioned | 2012-02-21T05:42:58Z | ||||||||||||||||
| dc.date.available | 2012-02-21T05:42:58Z | ||||||||||||||||
| dc.date.issued | 2010 | ||||||||||||||||
| dc.description.abstract | Hirschsprung'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. | ||||||||||||||||
| dc.description.grant | Genetic dissection of Hirschsprung's disease | ||||||||||||||||
| dc.description.grant | Whole genome family based association study to search for RET-dependent modifiers in Hirchsprung's disease | ||||||||||||||||
| dc.description.grant | Fine mapping of a Hirschsprung's disease locus on the 3p21candidate region | ||||||||||||||||
| dc.description.grant | Fine mapping of Hirschsprungs disease loci on the 3p21 and 9q31 candidate regions | ||||||||||||||||
| dc.description.grant | Developmental genomics and skeletal research | ||||||||||||||||
| dc.description.grantcode | 96945 | ||||||||||||||||
| dc.description.grantcode | 96183 | ||||||||||||||||
| dc.description.grantcode | 97944 | ||||||||||||||||
| dc.description.grantcode | 98615 | ||||||||||||||||
| dc.description.grantcode | 44444 | ||||||||||||||||
| dc.description.nature | published_or_final_version | ||||||||||||||||
| dc.description.other | Springer Open Choice, 21 Feb 2012 | ||||||||||||||||
| dc.identifier.citation | Human Genetics, 2010, v. 127 n. 6, p. 675-683 [How to Cite?] DOI: http://dx.doi.org/10.1007/s00439-010-0813-8 | ||||||||||||||||
| dc.identifier.citeulike | 6956535 | ||||||||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1007/s00439-010-0813-8 | ||||||||||||||||
| dc.identifier.eissn | 1432-1203 | ||||||||||||||||
| dc.identifier.epage | 683 | ||||||||||||||||
| dc.identifier.hkuros | 170748 | ||||||||||||||||
| dc.identifier.isi | WOS:000277713300007
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). | ||||||||||||||||
| dc.identifier.issn | 0340-6717 2011 Impact Factor: 5.069 2011 SCImago Journal Rankings: 0.328 | ||||||||||||||||
| dc.identifier.issue | 6 | ||||||||||||||||
| dc.identifier.openurl | | ||||||||||||||||
| dc.identifier.pmcid | PMC2871095 | ||||||||||||||||
| dc.identifier.pmid | 20361209 | ||||||||||||||||
| dc.identifier.scopus | eid_2-s2.0-77953443007 | ||||||||||||||||
| dc.identifier.spage | 675 | ||||||||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/144968 | ||||||||||||||||
| dc.identifier.volume | 127 | ||||||||||||||||
| dc.language | Eng | ||||||||||||||||
| dc.publisher | Springer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm | ||||||||||||||||
| dc.publisher.place | Germany | ||||||||||||||||
| dc.relation.ispartof | Human Genetics | ||||||||||||||||
| dc.relation.references | References in Scopus | ||||||||||||||||
| dc.rights | The Author(s) | ||||||||||||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||||||||||||
| dc.subject.mesh | Carrier Proteins - genetics | ||||||||||||||||
| dc.subject.mesh | Chromosomes, Human, Pair 9 | ||||||||||||||||
| dc.subject.mesh | Hirschsprung Disease - genetics | ||||||||||||||||
| dc.subject.mesh | Physical Chromosome Mapping - methods | ||||||||||||||||
| dc.subject.mesh | Proto-Oncogene Proteins c-ret - genetics | ||||||||||||||||
| dc.title | Fine mapping of the 9q31 Hirschsprung's disease locus | ||||||||||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Universitair Medisch Centrum Groningen
- Huazhong University of Science and Technology
- The Johns Hopkins School of Medicine