-
Dominique J Verlaan,
Manon Ouimet, Veronique Adoue,
Dave Sirois-Gagnon,
Mathieu Larivière,
Bing Ge,
Patrick Beaulieu,
Joana Dias,
Kevin C L Lam,
Vonda Koka,
Catherine Laprise,
Tomi Pastinen,
Daniel Sinnett
The Journal of allergy and clinical immunology 04/2012; 130(2):533-5. · 9.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A report on the 12th International Congress of Human Genetics, joint with the 61st annual American Society of Human Genetics conference, Montreal, Quebec, 11-15 October 2011.
Genome biology 11/2011; 12(11):309. · 6.63 Impact Factor
-
Elin Grundberg, Veronique Adoue,
Tony Kwan,
Bing Ge,
Qing Ling Duan,
Kevin C L Lam,
Vonda Koka,
Andreas Kindmark,
Scott T Weiss,
Kelan Tantisira,
Hans Mallmin,
Benjamin A Raby,
Olle Nilsson,
Tomi Pastinen
[show abstract]
[hide abstract]
ABSTRACT: 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 = 24 h), and PGE₂ (t = 24 h). 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 (∼1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here.
PLoS Genetics 01/2011; 7(1):e1001279. · 8.69 Impact Factor
