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Global Analysis of ...
Global Analysis of the Impact of Environmental Perturbation on cis-Regulation of Gene Expression
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Grundberg, Elin (author)
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Adoue, Veronique (author)
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Kwan, Tony (author)
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Ge, Bing (author)
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Duan, Qing Ling (author)
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Lam, Kevin C. L. (author)
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Koka, Vonda (author)
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- Kindmark, Andreas (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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Weiss, Scott T. (author)
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Tantisira, Kelan (author)
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- Mallmin, Hans (author)
- Uppsala universitet,Ortopedi
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Raby, Benjamin A. (author)
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- Nilsson, Olle (author)
- Uppsala universitet,Ortopedi
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Pastinen, Tomi (author)
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(creator_code:org_t)
- 2011-01-20
- 2011
- English.
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:1, s. e1001279-
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent by which controlled, environmental perturbation influences cis-eQTLs is unclear. We carried out large-scale induction experiments using primary human bone cells derived from unrelated donors of Swedish origin treated with 18 different stimuli (7 treatments and 2 controls, each assessed at 2 time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t = 2h), dexamethasone (DEX) (t = 24h), and PGE(2) (t = 24h). Using these treatments and control, we performed expression profiling for 18,144 RefSeq transcripts on biological replicates of the complete study cohort of 113 individuals (n(total) = 782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs (defined as SNPs located within the gene +/- 250 kb). We found that 93% of cis-eQTLs at 1% FDR were observed in at least one additional treatment, and in fact, on average, only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment. Treatment-specific cis-regulatory effects were, however, 2- to 6-fold more abundant among differently expressed genes upon treatment. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 kb and 250 kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interactions between cellular environment and cis-variants are relatively rare (similar to 1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Grundberg, Elin
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Adoue, Veronique
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Kwan, Tony
-
Ge, Bing
-
Duan, Qing Ling
-
Lam, Kevin C. L.
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show more...
-
Koka, Vonda
-
Kindmark, Andrea ...
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Weiss, Scott T.
-
Tantisira, Kelan
-
Mallmin, Hans
-
Raby, Benjamin A ...
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Nilsson, Olle
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Pastinen, Tomi
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show less...
- Articles in the publication
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PLoS Genetics
- By the university
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Uppsala University