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Title: Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs
Authors: Adoue, V.
Schiavi, A.
Light, N.
Almlöf, J. C.
Lundmark, P.
Ge, B.
Kwan, T.
Caron, M.
Rönnblom, L.
Wang, C.
Chen, S. H.
Goodall, A. H.
Cambien, F.
Deloukas, P.
Ouwehand, W. H.
Syvänen, A. C.
Pastinen, T.
First Published: 16-Oct-2014
Publisher: EMBO Press
Citation: Molecular Systems Biology, 2014, 10, p. 754
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.
DOI Link: 10.15252/msb.20145114
eISSN: 1744-4292
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: PMCID: PMC4299376
Appears in Collections:Published Articles, College of Medicine, Biological Sciences and Psychology

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