Lead Modulates trans- and cis-eQTLs in Drosophila melanogaster Heads
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE83141 | GEO | 2016/06/10
SECONDARY ACCESSION(S): PRJNA325107
REPOSITORIES: GEO
Similar Datasets
Project description:The goal was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs (FDR ⤠10%) and 952 trans-eQTLs, we focused our analysis on Pb-sensitive âtrans-eQTL hotspotsâ. 158 randomly selected Drosophila Synthetic Population Resource (A2) samples (control 79 samples and Pb-treated) without replicates
2016-06-10 | E-GEOD-83141 | biostudies-arrayexpress
Project description:Lead exposure has long been one of the most important topics in global public health because it is a potent developmental neurotoxin. Here, an eQTL analysis, which is the genome-wide association analysis of genetic variants with gene expression, was performed. In this analysis, the male heads of 79 Drosophila melanogaster inbred lines from Drosophila Synthetic Population Resource (DSPR) were treated with or without developmental exposure, from hatching to adults, to 250 ?M lead acetate [Pb(C2H3O2)2]. The goal was to identify genomic intervals that influence the gene-expression response to lead. After detecting 1798 cis-eQTLs and performing an initial trans-eQTL analysis, we focused our analysis on lead-sensitive "trans-eQTL hotspots," defined as genomic regions that are associated with a cluster of genes in a lead-dependent manner. We noticed that the genes associated with one of the 14 detected trans-eQTL hotspots, Chr 2L: 6,250,000 could be roughly divided into two groups based on their differential expression profile patterns and different categories of function. This trans-eQTL hotspot validates one identified in a previous study using different recombinant inbred lines. The expression of all the associated genes in the trans-eQTL hotspot was visualized with hierarchical clustering analysis. Besides the overall expression profile patterns, the heatmap displayed the segregation of differential parental genetic contributions. This suggested that trans-regulatory regions with different genetic contributions from the parental lines have significantly different expression changes after lead exposure. We believe this study confirms our earlier study, and provides important insights to unravel the genetic variation in lead susceptibility in Drosophila model.
| S-EPMC6158337 | biostudies-literature
Project description:Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2,112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters, and enrichment of co-localised functional elements. We found eQTLs for about 85% of analysed genes, 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 MB to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might often be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels, and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. We show for strongly heritable transcripts that a considerable gap still exists between total heritability resulting from all trans-chromosomes and explained variance of all identified trans-eSNPs. In contrast, the vast majority of most cis-heritability of these genes is already explained. Dissection of co-localised functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene-expression, pathways and disease related processes.
2015-06-29 | GSE65907 | GEO
Project description:The objective of this analysis was to identify trans-eQTLs. Samples were collected from control participants of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State. Total RNA was isolated from peripheral collected using PAXgene tubes and gene expression was profiled using the Illumina platform.
2013-06-08 | E-GEOD-47727 | biostudies-arrayexpress
Project description:The objective of this analysis was to identify trans-eQTLs. Samples were collected from control participants of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State. Total RNA was isolated from peripheral collected using PAXgene tubes and gene expression was profiled using the Illumina platform.
2013-06-08 | E-GEOD-47728 | biostudies-arrayexpress
Project description:Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2,112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters, and enrichment of co-localised functional elements. We found eQTLs for about 85% of analysed genes, 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 MB to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might often be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels, and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. We show for strongly heritable transcripts that a considerable gap still exists between total heritability resulting from all trans-chromosomes and explained variance of all identified trans-eSNPs. In contrast, the vast majority of most cis-heritability of these genes is already explained. Dissection of co-localised functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene-expression, pathways and disease related processes. Gene expression from human blood mononuclear cells from individuals of the Leipzig LIFE Heart Study was analyzed applying Illumina HT-12 v4 Expression BeadChips. After preprocessing, 28,295 expression probes for 2,112 individuals remained for analysis. In a population-based analysis, we identified associations between DNA variants and RNA expression levels and characterized these findings.
2015-06-29 | E-GEOD-65907 | biostudies-arrayexpress
Project description:Experiments were achieved on Hirschfeldia incana, a Brassicaceae collected from metalliferous mine spoils as a Pb accumulator plant. Transcriptional profiling of roots and shoots from plants treated with lead were compared to plants treated in similar conditions without lead. Four weeks old H. incana seedlings were treated in hydroponic cultures with Pb during 3 days, by adding or not 100 µM Pb(NO3)2.
2015-01-28 | GSE65332 | GEO
Project description:Experiments were achieved on Hirschfeldia incana, a Brassicaceae collected from metalliferous mine spoils as a Pb accumulator plant. Transcriptional profiling of roots and shoots from plants treated with lead were compared to plants treated in similar conditions without lead. Four weeks old H. incana seedlings were treated in hydroponic cultures with Pb during 3 days, by adding or not 100 M-BM-5M Pb(NO3)2. Two-condition experiment, lead treated vs. untreated. Biological replicates: 3
2015-01-28 | E-GEOD-65332 | biostudies-arrayexpress
Project description:Experiments were achieved on Arabidopsis thaliana. Transcriptional profiling of roots and shoots from plants treated with lead were compared to plants treated in similar conditions without lead. Four weeks old A. thaliana seedlings were treated in hydroponic cultures with Pb during 3 days, by adding or not 40 µM Pb(NO3)2.
2015-01-28 | GSE65333 | GEO
Project description:Lead Modulates trans- and cis-eQTLs in Drosophila melanogaster Heads
| PRJNA325107 | ENA