Article: Mapping of a Hirschsprung's disease locus in 3p21
| Title | Mapping of a Hirschsprung's disease locus in 3p21 |
|---|---|
| Authors | GarciaBarceló, MM3 Fong, PY3 Tang, CS1 Miao, XP3 So, MT3 Yuan, ZW2 Li, L6 Guo, WH6 Liu, L5 Wang, B5 Sun, XB8 Huang, LM7 Tou, JF4 Wong, KKY3 Ngan, ESW3 Lui, VCH3 Cherny, SS1 3 Sham, PC1 3 Tam, PKH3 |
| Issue Date | 2008 |
| Publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhg |
| Citation | European Journal Of Human Genetics, 2008, v. 16 n. 7, p. 833-840 [How to Cite?] DOI: http://dx.doi.org/10.1038/ejhg.2008.18 |
| Abstract | Hirschsprung's disease (HSCR) is a congenital disorder in which ganglion cells are absent in variable portions of the lower digestive tract according to which patients are classified. The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required. An unidentified RET-dependent modifier on 3p21 appears to be necessary for transmission of the short HSCR (S-HSCR) phenotype. We investigated 6Mb of the 3p21 region on a quest for the HSCR-susceptibility locus. Fifty-eight S-HSCR case-parent trios were genotyped using Sequenom technology for 214 tag single nucleotide polymorphisms (SNPs) distributed along 6Mb of the 3p21 region. A five-marker haplotype, spanning a 118kb gene-rich region, was found to be overtransmitted to affected offspring. The associated haplotype encompasses three genes involved in neurological phenotypes. Importantly, this association was replicated in an independent sample of 172 S-HSCR cases and 153 unrelated controls. Ranking markers by proximity to candidate genes or by expected functional consequences could be used in follow-up studies to finally pinpoint this HSCR locus. |
| ISSN | 1018-4813 2011 Impact Factor: 4.4 2011 SCImago Journal Rankings: 0.459 |
| DOI | http://dx.doi.org/10.1038/ejhg.2008.18 |
| ISI Accession Number ID | WOS:000256857400010 |
| References | References in Scopus |
| dc.contributor.author | GarciaBarceló, MM |
|---|---|
| dc.contributor.author | Fong, PY |
| dc.contributor.author | Tang, CS |
| dc.contributor.author | Miao, XP |
| dc.contributor.author | So, MT |
| dc.contributor.author | Yuan, ZW |
| dc.contributor.author | Li, L |
| dc.contributor.author | Guo, WH |
| dc.contributor.author | Liu, L |
| dc.contributor.author | Wang, B |
| dc.contributor.author | Sun, XB |
| dc.contributor.author | Huang, LM |
| dc.contributor.author | Tou, JF |
| dc.contributor.author | Wong, KKY |
| dc.contributor.author | Ngan, ESW |
| dc.contributor.author | Lui, VCH |
| dc.contributor.author | Cherny, SS |
| dc.contributor.author | Sham, PC |
| dc.contributor.author | Tam, PKH |
| dc.date.accessioned | 2010-05-31T03:56:25Z |
| dc.date.available | 2010-05-31T03:56:25Z |
| dc.date.issued | 2008 |
| dc.description.abstract | Hirschsprung's disease (HSCR) is a congenital disorder in which ganglion cells are absent in variable portions of the lower digestive tract according to which patients are classified. The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required. An unidentified RET-dependent modifier on 3p21 appears to be necessary for transmission of the short HSCR (S-HSCR) phenotype. We investigated 6Mb of the 3p21 region on a quest for the HSCR-susceptibility locus. Fifty-eight S-HSCR case-parent trios were genotyped using Sequenom technology for 214 tag single nucleotide polymorphisms (SNPs) distributed along 6Mb of the 3p21 region. A five-marker haplotype, spanning a 118kb gene-rich region, was found to be overtransmitted to affected offspring. The associated haplotype encompasses three genes involved in neurological phenotypes. Importantly, this association was replicated in an independent sample of 172 S-HSCR cases and 153 unrelated controls. Ranking markers by proximity to candidate genes or by expected functional consequences could be used in follow-up studies to finally pinpoint this HSCR locus. |
| dc.description.nature | link_to_subscribed_fulltext |
| dc.identifier.citation | European Journal Of Human Genetics, 2008, v. 16 n. 7, p. 833-840 [How to Cite?] DOI: http://dx.doi.org/10.1038/ejhg.2008.18 |
| dc.identifier.citeulike | 2406275 |
| dc.identifier.doi | http://dx.doi.org/10.1038/ejhg.2008.18 |
| dc.identifier.epage | 840 |
| dc.identifier.hkuros | 144570 |
| dc.identifier.isi | WOS:000256857400010 |
| dc.identifier.issn | 1018-4813 2011 Impact Factor: 4.4 2011 SCImago Journal Rankings: 0.459 |
| dc.identifier.issue | 7 |
| dc.identifier.openurl | ![]() |
| dc.identifier.pmid | 18285831 |
| dc.identifier.scopus | eid_2-s2.0-45749144781 |
| dc.identifier.spage | 833 |
| dc.identifier.uri | http://hdl.handle.net/10722/59739 |
| dc.identifier.volume | 16 |
| dc.language | eng |
| dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhg |
| dc.publisher.place | United Kingdom |
| dc.relation.ispartof | European Journal of Human Genetics |
| dc.relation.references | References in Scopus |
| dc.title | Mapping of a Hirschsprung's disease locus in 3p21 |
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- China Medical University Shenyang
- The University of Hong Kong
- Zhejiang Children's Hospital
- Shenzhen People's Hospital
- Beijing Children's Hospital
- Peking University
- Shandong University School of Medicine


