Journal Article

Global patterns of cis variation in human cells revealed by high-density allelic expression analysis

Kwan, Tony, Harvey, Edward J, Montpetit, Alexandre, Pastinen, Tomi, Koka, Vonda, Gunderson, Kevin L, Harmsen, Eef, Dias, Joana, Ge, Bing, Hamon, Robert, Le, Jennie, Dewar, Ken, Majewski, Jacek, Pokholok, Dmitry K, Morcos, Lisanne, Joly, Marie-Michele, Blanchette, Mathieu, Beaulieu, Patrick, Naumova, Anna K, Lam, Kevin C L, Gagné, Vincent, Grundberg, Elin, Sinnett, Daniel, Verlaan, Dominique J, Hoberman, Rose, Göring, Harald H H, Graziani, Alexandru

2009

Overview

Tomi Pastinen and colleagues report a genome-wide analysis of allelic expression variation in lymphoblastoid cell lines from HapMap individuals. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Alleles / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cell Line / Cells / Confidence intervals / Data analysis / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Profiling / Gene Function / Genetic aspects / Genetic Variation / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Human Genetics / Humans / Lupus Erythematosus, Systemic - genetics / Lymphocytes - metabolism / Physiological aspects / Polymorphism, Single Nucleotide / Ratios / Sample size / Single nucleotide polymorphisms / Studies / Transcription, Genetic