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


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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Figure 1: Genome-wide map of AE associated SNPs.
Figure 2: Allelic expression associations in individual transcripts.
Figure 3: AE in transcripts or their isoforms and global AE associations patterns.
Figure 4: Fine mapping of C8orf13-BLK AE in two populations.


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This work was supported by Genome Canada, Genome Québec and Illumina, Inc. T.P. holds a Canada Research Chair. H.H.H.G. carried out work in facilities constructed with support from Research Facilities Improvement Program Grant Number C06 RR017515 from the National Center for Research Resources, National Institutes of Health and a gift from the SBC Foundation.

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Authors and Affiliations



T.P. and K.L.G. conceived the research. B.G., D.K.P., T.K., E.G., D.J.V., J.L., K.L.G., D.S. and T.P. designed the experiments. D.K.P., E.G., D.J.V., V.K., K.C.L.L., V.G., J.D. and M.-M.J. conducted the experiments. B.G., D.K.P., H.H.H.G., R. Hoberman, P.B., R. Hamon, A.G., M.B. and T.P. designed the computational and analytical methods. B.G., T.K., L.M., D.J.V., R. Hoberman, A.K.N., K.L.G. and T.P. analyzed the data. E.J.H. contributed primary osteoblast cell lines. T.P. drafted the manuscript and all authors contributed to the final manuscript writing and its revisions.

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Correspondence to Tomi Pastinen.

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Competing interests

The authors KL Gunderson, DK Pokholok and J Le are employed by Illumina Inc and KL Gunderson owns stock in the company.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–13, Supplementary Tables 2–5, 7–9 and Supplementary Note (PDF 1526 kb)

Supplementary Table 1

Details of 7785 AE associations detected at permutation significance 0.005 (XLS 1132 kb)

Supplementary Table 6

High confidence full transcript AE associations (XLS 158 kb)

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Ge, B., Pokholok, D., Kwan, T. et al. Global patterns of cis variation in human cells revealed by high-density allelic expression analysis. Nat Genet 41, 1216–1222 (2009).

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