Article: Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population
| Title | Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Cornes, BK1 Tang, CS1 Leon, TYY1 Hui, KJWS1 So, MT1 Miao, X1 Cherny, SS1 Sham, PC1 Tam, PKH1 GarciaBarcelo, MM1 | ||||||
| Issue Date | 2010 | ||||||
| Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| Citation | Plos One, 2010, v. 5 n. 6 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0010918 | ||||||
| Abstract | Background Hirschsprung's disease (HSCR) is a congenital disorder associated with the lack of intramural ganglion cells in the myenteric and sub-mucosal plexuses along varying segments of the gastrointestinal tract. The RET gene is the major gene implicated in this gastrointestinal disease. A highly recurrent mutation in RET (RETR114H) has recently been identified in ~6-7% of the Chinese HSCR patients which, to date, has not been found in Caucasian patients or controls nor in Chinese controls. Due to the high frequency of RETR114H in this population, we sought to investigate whether this mutation may be a founder HSCR mutation in the Chinese population. Methodology and Principal Findings To test whether all RETR114H were originated from a single mutational event, we predicted the approximate age of RETR114H by applying a Bayesian method to RET SNPs genotyped in 430 Chinese HSCR patients (of whom 25 individuals had the mutation) to be between 4-23 generations old depending on growth rate. We reasoned that if RETR114H was a founder mutation then those with the mutation would share a haplotype on which the mutation resides. Including SNPs spanning 509.31 kb across RET from a recently obtained 500 K genome-wide dataset for a subset of 181 patients (14 RETR114H patients), we applied haplotype estimation methods to determine whether there were any segments shared between patients with RETR114H that are not present in those without the mutation or controls. Analysis yielded a 250.2 kb (51 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients. Conclusions This suggests that RETR114H is a founder mutation for HSCR in the Chinese population. © 2010 Cornes et al. | ||||||
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| DOI | http://dx.doi.org/10.1371/journal.pone.0010918 | ||||||
| ISI Accession Number ID | WOS:000278284700004
Funding Information: This work was supported by research grants from the Hong Kong Research Grants Council (765407M and 775907M to MMGB and PT respectively) and the University of Hong Kong Seed Funding Programme for Basic Research to MMGB (200611159028). Support was also obtained from the University of Hong Kong Strategic Research Theme of Genomics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | ||||||
| PubMed Central ID | PMC2880000 | ||||||
| References | References in Scopus | ||||||
| Grants | Functional analysis of RET coding region mutations |
| dc.contributor.author | Cornes, BK | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Tang, CS | ||||||
| dc.contributor.author | Leon, TYY | ||||||
| dc.contributor.author | Hui, KJWS | ||||||
| dc.contributor.author | So, MT | ||||||
| dc.contributor.author | Miao, X | ||||||
| dc.contributor.author | Cherny, SS | ||||||
| dc.contributor.author | Sham, PC | ||||||
| dc.contributor.author | Tam, PKH | ||||||
| dc.contributor.author | GarciaBarcelo, MM | ||||||
| dc.date.accessioned | 2010-10-31T11:25:21Z | ||||||
| dc.date.available | 2010-10-31T11:25:21Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | Background Hirschsprung's disease (HSCR) is a congenital disorder associated with the lack of intramural ganglion cells in the myenteric and sub-mucosal plexuses along varying segments of the gastrointestinal tract. The RET gene is the major gene implicated in this gastrointestinal disease. A highly recurrent mutation in RET (RETR114H) has recently been identified in ~6-7% of the Chinese HSCR patients which, to date, has not been found in Caucasian patients or controls nor in Chinese controls. Due to the high frequency of RETR114H in this population, we sought to investigate whether this mutation may be a founder HSCR mutation in the Chinese population. Methodology and Principal Findings To test whether all RETR114H were originated from a single mutational event, we predicted the approximate age of RETR114H by applying a Bayesian method to RET SNPs genotyped in 430 Chinese HSCR patients (of whom 25 individuals had the mutation) to be between 4-23 generations old depending on growth rate. We reasoned that if RETR114H was a founder mutation then those with the mutation would share a haplotype on which the mutation resides. Including SNPs spanning 509.31 kb across RET from a recently obtained 500 K genome-wide dataset for a subset of 181 patients (14 RETR114H patients), we applied haplotype estimation methods to determine whether there were any segments shared between patients with RETR114H that are not present in those without the mutation or controls. Analysis yielded a 250.2 kb (51 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients. Conclusions This suggests that RETR114H is a founder mutation for HSCR in the Chinese population. © 2010 Cornes et al. | ||||||
| dc.description.grant | Functional analysis of RET coding region mutations | ||||||
| dc.description.grantcode | 96043 | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | Plos One, 2010, v. 5 n. 6 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0010918 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0010918 | ||||||
| dc.identifier.hkuros | 173116 | ||||||
| dc.identifier.isi | WOS:000278284700004
Funding Information: This work was supported by research grants from the Hong Kong Research Grants Council (765407M and 775907M to MMGB and PT respectively) and the University of Hong Kong Seed Funding Programme for Basic Research to MMGB (200611159028). Support was also obtained from the University of Hong Kong Strategic Research Theme of Genomics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | ||||||
| dc.identifier.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| dc.identifier.issue | 6 | ||||||
| dc.identifier.pmcid | PMC2880000 | ||||||
| dc.identifier.pmid | 20532249 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77956200403 | ||||||
| dc.identifier.spage | e10918 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/125336 | ||||||
| dc.identifier.volume | 5 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | PLoS ONE | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.title | Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine