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Conference Paper: A RET founder mutation in Chinese hirschsprung's patients

TitleA RET founder mutation in Chinese hirschsprung's patients
Authors
Issue Date2009
PublisherThe American Society of Human Genetics.
Citation
The 59th Annual Meeting of the American Society of Human Genetics (ASHG), Honolulu, HI., 20-24 October 2009. How to Cite?
Abstract
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. Rearranged during transfection (RET) gene is implicated in HSCR and is the major gene of this gastrointestinal disease. To date, over 200 low frequency recurrent RET coding sequence (CDS) mutations have been identified in HSCR patients. However, a highly recurrent RET(R114H) mutation has been identified in 10% of the Chinese HSCR patients which has never been found in Caucasians patients or controls nor in 400 Chinese controls. The high frequency of RET(R114H) in our population together with the fact that it is not a “de novo” mutation in the context of the most HSCR-associated RET-haplotype, suggests that it may be a founder HSCR mutation in the Chinese population. Initial investigation involved applying a Bayesian method to 21 single nucleotide polymorphisms (SNPs; across a 62kb region of RET) genotyped in 421 Chinese HSCR patients (of which 24 individuals had the mutation) to predict the approximate age of RET(R114H). The approach allowed the inference of the mutation age based on the observed linkage disequilibrium (LD) at multiple SNPs which predicted the mutation to be between 12 and 13 generations old. Including SNPs from a recently obtained genome-wide 500K dataset for 181 of the above mentioned patients (which now only included 14 patients who had the RET(R114H) mutation), we applied haplotype estimation methods to determine whether there were any segments shared between patients with the RET(R114H) compared to those without the mutation and controls. Data consisted a total of 92 SNPs spanning a 510kb region over the RET gene. Analysis yielded a 256kb (76 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients or controls. This suggests that RET(R114H) is a possible founder effect for Hirschsprung’s disease in the Chinese population.
Description768/W/Poster Board #426
Persistent Identifierhttp://hdl.handle.net/10722/105446

 

DC FieldValueLanguage
dc.contributor.authorCornes, BKen_HK
dc.contributor.authorTang, CSMen_HK
dc.contributor.authorLeon, TYYen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorGarcia-Barcelo, MMen_HK
dc.date.accessioned2010-09-25T22:34:29Z-
dc.date.available2010-09-25T22:34:29Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 59th Annual Meeting of the American Society of Human Genetics (ASHG), Honolulu, HI., 20-24 October 2009.-
dc.identifier.urihttp://hdl.handle.net/10722/105446-
dc.description768/W/Poster Board #426-
dc.description.abstractHirschsprung’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. Rearranged during transfection (RET) gene is implicated in HSCR and is the major gene of this gastrointestinal disease. To date, over 200 low frequency recurrent RET coding sequence (CDS) mutations have been identified in HSCR patients. However, a highly recurrent RET(R114H) mutation has been identified in 10% of the Chinese HSCR patients which has never been found in Caucasians patients or controls nor in 400 Chinese controls. The high frequency of RET(R114H) in our population together with the fact that it is not a “de novo” mutation in the context of the most HSCR-associated RET-haplotype, suggests that it may be a founder HSCR mutation in the Chinese population. Initial investigation involved applying a Bayesian method to 21 single nucleotide polymorphisms (SNPs; across a 62kb region of RET) genotyped in 421 Chinese HSCR patients (of which 24 individuals had the mutation) to predict the approximate age of RET(R114H). The approach allowed the inference of the mutation age based on the observed linkage disequilibrium (LD) at multiple SNPs which predicted the mutation to be between 12 and 13 generations old. Including SNPs from a recently obtained genome-wide 500K dataset for 181 of the above mentioned patients (which now only included 14 patients who had the RET(R114H) mutation), we applied haplotype estimation methods to determine whether there were any segments shared between patients with the RET(R114H) compared to those without the mutation and controls. Data consisted a total of 92 SNPs spanning a 510kb region over the RET gene. Analysis yielded a 256kb (76 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients or controls. This suggests that RET(R114H) is a possible founder effect for Hirschsprung’s disease in the Chinese population.-
dc.languageengen_HK
dc.publisherThe American Society of Human Genetics.-
dc.relation.ispartofAnnual Meeting of the American Society of Human Genetics-
dc.titleA RET founder mutation in Chinese hirschsprung's patientsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailCornes, BK: bellnda_cornes@gmail.comen_HK
dc.identifier.emailTang, CSM: claratsm@graduate.hku.hken_HK
dc.identifier.emailLeon, TYY: tleon@hkucc.hku.hken_HK
dc.identifier.emailSo, MT: jaymtso@hkucc.hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.emailGarcia-Barcelo, MM: mmgarcia@hkucc.hku.hk-
dc.identifier.hkuros167949en_HK
dc.description.otherThe 59th Annual Meeting of the American Society of Human Genetics (ASHG), Honolulu, HI., 20-24 October 2009.-

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