Single nucleotide polymorphisms in the human interleukin-1B gene affect transcription according to haplotype context
Hongmin Chen,Leon Wilkins,Nazneen Aziz,Chris Cannings,David H. Wyllie,Colin D. Bingle,John J. Rogus,James D. Beck,Steven Offenbacher,Michael J. Cork,Maryam Rafie-Kolpin,Chung-Ming Hsieh,Kenneth S. Kornman,Gordon W. Duff +13 more
TLDR
The four haplotypes that showed different contextual effects on SNP function accounted for >98% of the estimated haplotypes in Caucasian and African-American populations, which underlines the importance of understanding the haplotype structure of populations used for genetic studies.Abstract:
We questioned the significance of haplotype structure in gene regulation by testing whether individual single nucleotide polymorphisms (SNPs) within a gene promoter region [interleukin-1-beta (IL1B)] might affect promoter function and, if so, whether function was dependent on haplotype context. We sequenced genomic DNA from 25 individuals of diverse ethnicity, focusing on exons and upstream flanking regions of genes of the cluster. We identified four IL1B promoter region SNPs that were active in transient transfection reporter gene assays. To substantiate allelic differences found in reporter gene assays, we also examined nuclear protein binding to promoter sequence oligonucleotides containing different alleles of the SNPs. The effect of individual SNPs on reporter gene transcription varied according to which alleles of the three other SNPs were present in the promoter construct. The SNP patterns that influenced function reflected common haplotypes that occur in the population, suggesting functionally significant interactions between SNPs according to haplotype context. Of the haplotypes that include the four functional IL1B promoter SNPs (-3737, -1464, -511, -31), the four haplotypes that showed different contextual effects on SNP function accounted for >98% of the estimated haplotypes in Caucasian and African-American populations. This finding underlines the importance of understanding the haplotype structure of populations used for genetic studies and may be especially important in the functional analysis of genetic variation across gene regulatory regions.read more
Citations
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9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response
Olivier Harismendy,Dimple Notani,Xiaoyuan Song,Nazli G. Rahim,Bogdan Tanasa,Bogdan Tanasa,Nathaniel D. Heintzman,Bing Ren,Xiang-Dong Fu,Eric J. Topol,Michael G. Rosenfeld,Kelly A. Frazer +11 more
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Osteoporosis and inflammation.
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Cytokine and cytokine receptor gene polymorphisms and their functionality
TL;DR: This review concentrates on the functionality of cytokine and cytokine receptor gene polymorphisms; it is through these variants that genuine disease-associations are based.
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The importance of phase information for human genomics.
Ryan Tewhey,Vikas Bansal,Vikas Bansal,Ali Torkamani,Ali Torkamani,Ali Torkamani,Eric J. Topol,Eric J. Topol,Eric J. Topol,Nicholas J. Schork,Nicholas J. Schork,Nicholas J. Schork +11 more
TL;DR: Findings indicate that relationships between human DNA sequence and phenotype, including disease, can be more fully understood with phase information, and the existing technological impediments to obtaining phase information must be overcome if human genomics is to reach its full potential.
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Interleukin-1β and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Gastric Cancer: A Meta-analysis
M. Constanza Camargo,Robertino M. Mera,Pelayo Correa,Richard M. Peek,Elizabeth T. H. Fontham,Karen J. Goodman,M. Blanca Piazuelo,Liviu A. Sicinschi,Jovanny Zabaleta,Barbara G. Schneider +9 more
TL;DR: The meta-analyses suggest that the conflicting results among studies may be explained by variation in allele frequencies among the ethnic groups and variation in tumor types, as well as by the methodologic quality of the studies.
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