1. Global patterns of cis variation in human cells revealed by high-density allelic expression analysis
- Author
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Robert Hamon, Marie Michele Joly, Jacek Majewski, Daniel Sinnett, Eef Harmsen, Dmitry K. Pokholok, Rose Hoberman, Jennie M. Le, Alexandre Montpetit, Mathieu Blanchette, Harald H H Göring, Anna K. Naumova, Joana Dias, Tony Kwan, Patrick Beaulieu, Edward J. Harvey, Alexandru Graziani, Dominique J. Verlaan, Tomi Pastinen, Vincent Gagné, Kevin C. L. Lam, Vonda Koka, Bing Ge, Elin Grundberg, Ken Dewar, Kevin L. Gunderson, and Lisanne Morcos
- Subjects
musculoskeletal diseases ,Genetics ,Transcription, Genetic ,Gene Expression Profiling ,genetic processes ,Genetic Variation ,High density ,pathological conditions, signs and symptoms ,Biology ,Polymorphism, Single Nucleotide ,Cell Line ,persons ,Variation (linguistics) ,Lymphoblastoid cell ,Expression analysis ,Humans ,Lupus Erythematosus, Systemic ,natural sciences ,Lymphocytes ,Allele ,International HapMap Project ,Alleles ,Genome-Wide Association Study - 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.
- Published
- 2009