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TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease

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TTF-1 and RET promoter SNPs : regulation of RET transcription in Hirschsprung's disease. / Garcia-Barcelo, Mercè; Ganster, Raymond W.; Lui, Vincent C. H. et al.

In: Human Molecular Genetics, Vol. 14, No. 2, 15.01.2005, p. 191-204.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Garcia-Barcelo, M, Ganster, RW, Lui, VCH, Leon, TYY, So, M-T, Lau, AMF, Fu, M, Sham, M-H, Knight, J, Zannini, MS, Sham, PC & Tam, PKH 2005, 'TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease', Human Molecular Genetics, vol. 14, no. 2, pp. 191-204. https://doi.org/10.1093/hmg/ddi015

APA

Garcia-Barcelo, M., Ganster, R. W., Lui, V. C. H., Leon, T. Y. Y., So, M-T., Lau, A. M. F., Fu, M., Sham, M-H., Knight, J., Zannini, M. S., Sham, P. C., & Tam, P. K. H. (2005). TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease. Human Molecular Genetics, 14(2), 191-204. https://doi.org/10.1093/hmg/ddi015

Vancouver

Garcia-Barcelo M, Ganster RW, Lui VCH, Leon TYY, So M-T, Lau AMF et al. TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease. Human Molecular Genetics. 2005 Jan 15;14(2):191-204. Epub 2004 Nov 17. doi: 10.1093/hmg/ddi015

Author

Garcia-Barcelo, Mercè ; Ganster, Raymond W. ; Lui, Vincent C. H. et al. / TTF-1 and RET promoter SNPs : regulation of RET transcription in Hirschsprung's disease. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 2. pp. 191-204.

Bibtex

@article{bbcdb40b1f1648bc90379426e3b42121,
title = "TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease",
abstract = "Single nucleotide polymorphisms (SNPs) of the coding regions of receptor tyrosine kinase gene (RET) are associated with Hirschsprung's disease (HSCR, aganglionic megacolon). These SNPs, individually or combined, may act as a low penetrance susceptibility locus and/or be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found associated with HSCR, in LD with HSCR-associated RET coding region haplotypes, their implication in the transcriptional regulation of RET is of major interest. Analysis of 172 sporadic HSCR patients also revealed the presence of HSCR-associated RET promoter SNPs in LD with the main coding region RET haplotype observed in Chinese patients. By using a weighted logistic regression approach, we determined that of all SNPs tested in our study, the promoter SNPs are the most correlated to the disease. Functional analysis of the RET promoter SNPs in the context of additional 5' regulatory regions demonstrated that the HSCR-associated alleles decrease RET transcription. These SNPs overlap a TTF-1 binding site and TTF-1-activated RET transcription is also decreased by the HSCR-associated SNPs. Moreover, we identified an HSCR patient with a Gly322Ser TTF-1 mutation that compromises activation of transcription from HSCR-associated RET promoter haplotypes. Interestingly, we show that the pattern of RET and TTF-1 expression is coincident in developing human gut. We also present a detailed profile of the RET gene in our population, which provides an insight into the higher incidence of the disease in China.",
keywords = "Alleles, Gene Expression Regulation, Hirschsprung Disease, Humans, Nuclear Proteins, Oncogene Proteins, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Sequence Analysis, DNA, Transcription Factors",
author = "Merc{\`e} Garcia-Barcelo and Ganster, {Raymond W.} and Lui, {Vincent C. H.} and Leon, {Thomas Y. Y.} and Man-Ting So and Lau, {Anson M. F.} and Ming Fu and Mai-Har Sham and Joanne Knight and Zannini, {Maria Stella} and Sham, {Pak C.} and Tam, {Paul K. H.}",
year = "2005",
month = jan,
day = "15",
doi = "10.1093/hmg/ddi015",
language = "English",
volume = "14",
pages = "191--204",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - TTF-1 and RET promoter SNPs

T2 - regulation of RET transcription in Hirschsprung's disease

AU - Garcia-Barcelo, Mercè

AU - Ganster, Raymond W.

AU - Lui, Vincent C. H.

AU - Leon, Thomas Y. Y.

AU - So, Man-Ting

AU - Lau, Anson M. F.

AU - Fu, Ming

AU - Sham, Mai-Har

AU - Knight, Joanne

AU - Zannini, Maria Stella

AU - Sham, Pak C.

AU - Tam, Paul K. H.

PY - 2005/1/15

Y1 - 2005/1/15

N2 - Single nucleotide polymorphisms (SNPs) of the coding regions of receptor tyrosine kinase gene (RET) are associated with Hirschsprung's disease (HSCR, aganglionic megacolon). These SNPs, individually or combined, may act as a low penetrance susceptibility locus and/or be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found associated with HSCR, in LD with HSCR-associated RET coding region haplotypes, their implication in the transcriptional regulation of RET is of major interest. Analysis of 172 sporadic HSCR patients also revealed the presence of HSCR-associated RET promoter SNPs in LD with the main coding region RET haplotype observed in Chinese patients. By using a weighted logistic regression approach, we determined that of all SNPs tested in our study, the promoter SNPs are the most correlated to the disease. Functional analysis of the RET promoter SNPs in the context of additional 5' regulatory regions demonstrated that the HSCR-associated alleles decrease RET transcription. These SNPs overlap a TTF-1 binding site and TTF-1-activated RET transcription is also decreased by the HSCR-associated SNPs. Moreover, we identified an HSCR patient with a Gly322Ser TTF-1 mutation that compromises activation of transcription from HSCR-associated RET promoter haplotypes. Interestingly, we show that the pattern of RET and TTF-1 expression is coincident in developing human gut. We also present a detailed profile of the RET gene in our population, which provides an insight into the higher incidence of the disease in China.

AB - Single nucleotide polymorphisms (SNPs) of the coding regions of receptor tyrosine kinase gene (RET) are associated with Hirschsprung's disease (HSCR, aganglionic megacolon). These SNPs, individually or combined, may act as a low penetrance susceptibility locus and/or be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found associated with HSCR, in LD with HSCR-associated RET coding region haplotypes, their implication in the transcriptional regulation of RET is of major interest. Analysis of 172 sporadic HSCR patients also revealed the presence of HSCR-associated RET promoter SNPs in LD with the main coding region RET haplotype observed in Chinese patients. By using a weighted logistic regression approach, we determined that of all SNPs tested in our study, the promoter SNPs are the most correlated to the disease. Functional analysis of the RET promoter SNPs in the context of additional 5' regulatory regions demonstrated that the HSCR-associated alleles decrease RET transcription. These SNPs overlap a TTF-1 binding site and TTF-1-activated RET transcription is also decreased by the HSCR-associated SNPs. Moreover, we identified an HSCR patient with a Gly322Ser TTF-1 mutation that compromises activation of transcription from HSCR-associated RET promoter haplotypes. Interestingly, we show that the pattern of RET and TTF-1 expression is coincident in developing human gut. We also present a detailed profile of the RET gene in our population, which provides an insight into the higher incidence of the disease in China.

KW - Alleles

KW - Gene Expression Regulation

KW - Hirschsprung Disease

KW - Humans

KW - Nuclear Proteins

KW - Oncogene Proteins

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic

KW - Proto-Oncogene Proteins c-ret

KW - Receptor Protein-Tyrosine Kinases

KW - Sequence Analysis, DNA

KW - Transcription Factors

U2 - 10.1093/hmg/ddi015

DO - 10.1093/hmg/ddi015

M3 - Journal article

C2 - 15548547

VL - 14

SP - 191

EP - 204

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 2

ER -