Global Patterns of Cis Variation in Human Cells Revealed by High-density Allelic Expression Analysis

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Oct 20

PMID 19838192

Citations 133

Authors

Bing Ge

Dmitry K Pokholok

Tony Kwan

Elin Grundberg

Lisanne Morcos

Dominique J Verlaan

Jennie Le

Vonda Koka

Kevin C L Lam

Vincent Gagne

Joana Dias

Rose Hoberman

Alexandre Montpetit

Marie-Michele Joly

Edward J Harvey

Daniel Sinnett

Patrick Beaulieu

Robert Hamon

Alexandru Graziani

Ken Dewar

Eef Harmsen

Jacek Majewski

Harald H H Goring

Anna K Naumova

Mathieu Blanchette

Kevin L Gunderson

Tomi Pastinen

Affiliations

Soon will be listed here.

Abstract

Cis-acting variants altering gene expression are a source of phenotypic differences. The cis-acting components of expression variation can be identified through the mapping of differences in allelic expression (AE), which is the measure of relative expression between two allelic transcripts. We generated a map of AE associated SNPs using quantitative measurements of AE on Illumina Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of European descent, we identified common cis variants affecting 30% (2935/9751) of the measured RefSeq transcripts at 0.001 permutation significance. The pervasive influence of cis-regulatory variants, which explain 50% of population variation in AE, extend to full-length transcripts and their isoforms as well as to unannotated transcripts. These strong effects facilitate fine mapping of cis-regulatory SNPs, as demonstrated by dissection of heritable control of transcripts in the systemic lupus erythematosus-associated C8orf13-BLK region in chromosome 8. The dense collection of associations will facilitate large-scale isolation of cis-regulatory SNPs.

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