File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population

TitleHaplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population
Authors
Issue Date2010
PublisherPublic 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?
AbstractBackground 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.
Persistent Identifierhttp://hdl.handle.net/10722/125336
ISSN
2014 Impact Factor: 3.234
2014 SCImago Journal Rankings: 1.300
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants Council765407M
775907M
University of Hong Kong200611159028
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.

References

 

DC FieldValueLanguage
dc.contributor.authorCornes, BKen_HK
dc.contributor.authorTang, CSen_HK
dc.contributor.authorLeon, TYYen_HK
dc.contributor.authorHui, KJWSen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorMiao, Xen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorGarciaBarcelo, MMen_HK
dc.date.accessioned2010-10-31T11:25:21Z-
dc.date.available2010-10-31T11:25:21Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos One, 2010, v. 5 n. 6en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125336-
dc.description.abstractBackground 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.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.titleHaplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese populationen_HK
dc.typeArticleen_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hku.hken_HK
dc.identifier.emailGarciaBarcelo, MM: mmgarcia@hku.hken_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authorityGarciaBarcelo, MM=rp00445en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0010918en_HK
dc.identifier.pmid20532249-
dc.identifier.pmcidPMC2880000-
dc.identifier.scopuseid_2-s2.0-77956200403en_HK
dc.identifier.hkuros173116en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956200403&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue6en_HK
dc.identifier.spagee10918en_HK
dc.identifier.isiWOS:000278284700004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCornes, BK=8083360800en_HK
dc.identifier.scopusauthoridTang, CS=35764635500en_HK
dc.identifier.scopusauthoridLeon, TYY=10641704600en_HK
dc.identifier.scopusauthoridHui, KJWS=35764515100en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridMiao, X=7102585391en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridGarciaBarcelo, MM=6701767303en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats