Protein deficiency and intestinal parasite infection during pregnancy impair fetal growth through passage of signals from the maternal environment which signal impairment of fetal growth. The placenta is an important regulator of the transfer of these signals through differential expression of key placental genes. We used microarrays to examine placental gene expression responses to maternal protein deficiency (6% vs. 24% protein) and Heligmosomoides bakeri infection.
Expression of growth-related genes in the mouse placenta is influenced by interactions between intestinal nematode (Heligmosomoides bakeri) infection and dietary protein deficiency.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
Sex, Disease, Disease stage, Cell line
View SamplesCancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from noninvasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness.
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
Sex, Disease, Disease stage, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.
Specimen part
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two 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 PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated 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, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. 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 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two 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 PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated 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, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. 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 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesSingle nucleotide polymorphisms (SNP) can affect mRNA gene expression, in a tissue-specific manner. In this work we survey association of SNP alleles with mRNA gene expression in human dorsal root ganglions (DRG) to gain insights into pathophysiology of pain phenotypes.
Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.
Specimen part
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two 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 PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated 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, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. 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 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesWe have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternate splice site usage, intron retention), differential 5 UTR (initiation of transcription) usage, and differential 3 UTR (alternative polyadenylation) usage.
Genome-wide analysis of transcript isoform variation in humans.
Sex
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