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Article: Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population
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TitleHaplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population
 
AuthorsCornes, BK1
Tang, CS1
Leon, TYY1
Hui, KJWS1
So, MT1
Miao, X1
Cherny, SS1
Sham, PC1
Tam, PKH1
GarciaBarcelo, MM1
 
Issue Date2010
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2010, v. 5 n. 6 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0010918
 
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.
 
ISSN1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0010918
 
PubMed Central IDPMC2880000
 
ISI Accession Number IDWOS:000278284700004
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCornes, BK
 
dc.contributor.authorTang, CS
 
dc.contributor.authorLeon, TYY
 
dc.contributor.authorHui, KJWS
 
dc.contributor.authorSo, MT
 
dc.contributor.authorMiao, X
 
dc.contributor.authorCherny, SS
 
dc.contributor.authorSham, PC
 
dc.contributor.authorTam, PKH
 
dc.contributor.authorGarciaBarcelo, MM
 
dc.date.accessioned2010-10-31T11:25:21Z
 
dc.date.available2010-10-31T11:25:21Z
 
dc.date.issued2010
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2010, v. 5 n. 6 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0010918
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0010918
 
dc.identifier.hkuros173116
 
dc.identifier.isiWOS:000278284700004
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.

 
dc.identifier.issn1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
dc.identifier.issue6
 
dc.identifier.pmcidPMC2880000
 
dc.identifier.pmid20532249
 
dc.identifier.scopuseid_2-s2.0-77956200403
 
dc.identifier.spagee10918
 
dc.identifier.urihttp://hdl.handle.net/10722/125336
 
dc.identifier.volume5
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
dc.titleHaplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population
 
dc.typeArticle
 
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<contributor.author>Leon, TYY</contributor.author>
<contributor.author>Hui, KJWS</contributor.author>
<contributor.author>So, MT</contributor.author>
<contributor.author>Miao, X</contributor.author>
<contributor.author>Cherny, SS</contributor.author>
<contributor.author>Sham, PC</contributor.author>
<contributor.author>Tam, PKH</contributor.author>
<contributor.author>GarciaBarcelo, MM</contributor.author>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine