• Home
  • Search Results
  • Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.

Molecular systems biology (2014-10-19)
Veronique Adoue, Alicia Schiavi, Nicholas Light, Jonas Carlsson Almlöf, Per Lundmark, Bing Ge, Tony Kwan, Maxime Caron, Lars Rönnblom, Chuan Wang, Shu-Huang Chen, Alison H Goodall, Francois Cambien, Panos Deloukas, Willem H Ouwehand, Ann-Christine Syvänen, Tomi Pastinen
ABSTRACT

Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PIPES, ≥99% (titration)
Sigma-Aldrich
PIPES, BioPerformance Certified, suitable for cell culture
Sigma-Aldrich
PIPES, BioXtra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
PIPES, BioXtra, ≥99% (titration)
Sigma-Aldrich
PIPES, anhydrous, free-flowing, Redi-Dri, ≥99%
SAFC
PIPES, PharmaGrade, Manufactured under appropriate controls for use as a raw material in pharma or biopharmaceutical production, suitable for cell culture

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.