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Plos Genetics : Use of Allele-specific Faire to Determine Functional Regulatory Polymorphism Using Large-scale Genotyping Arrays, Volume 8

By Barsh, Gregory S.

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Book Id: WPLBN0003942209
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Use of Allele-specific Faire to Determine Functional Regulatory Polymorphism Using Large-scale Genotyping Arrays, Volume 8  
Author: Barsh, Gregory S.
Volume: Volume 8
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Historic
Publication Date:
Publisher: Plos

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Barsh, G. S. (n.d.). Plos Genetics : Use of Allele-specific Faire to Determine Functional Regulatory Polymorphism Using Large-scale Genotyping Arrays, Volume 8. Retrieved from http://worldlibrary.net/


Description
Description : Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising largescale genotyping technology (FAIRE-gen) to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-a), rs7120118, coinciding with a previously GWASidentified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016: p = 0.0006), and analysis of gene expression identified an allelic association with LXR-a expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS.

 

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