Genetics of gene expression in primary human immune cells Data Access Committee
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ABSTRACT:
PROVIDER: EGAC00001003327 | EGA |
REPOSITORIES: EGA
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Project description:Data Access Committee EGAC00001003318
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Project description:The purpose of this study was to identify cell specific expression quantitative trait loci in freshly isolated highly purified primary B-cells and monocytes from healthy subjects of European ancestry. Cells were purified from Ficoll gradient prepared peripheral blood mononuclear cell fractions using positive selection via magnetic bead labelling of the B-cell marker CD19 and monocyte marker CD14. RNA was extracted from 287 B-cell samples and 288 monocyte samples. RNA was then hybridised to HumanHT-12 v4 BeadChips whole genome expression arrays (Illumina). Individuals were genotyped on HumanOmniExpress-12v1.0 BeadChips (Illumina) at 733202 genetic markers. Data presented include the raw expression values and Robust Spline Normalised values (RSN) for expression for each cell type per individual. Additional genotype data per individual is available on request.
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Project description:Gene expression arrays and genotyping data in primary human immune cells from healthy European 288 individuals.
2012-03-01 | E-MTAB-945 | biostudies-arrayexpress
Project description:The Genetic Association Information Network (GAIN) Data Access Committee was established in June 2007 to provide prompt and fair access to data from six genome-wide association studies through the database of Genotypes and Phenotypes (dbGaP). Of 945 project requests received through 2011, 749 (79%) have been approved; median receipt-to-approval time decreased from 14 days in 2007 to 8 days in 2011. Over half (54%) of the proposed research uses were for GAIN-specific phenotypes; other uses were for method development (26%) and adding controls to other studies (17%). Eight data-management incidents, defined as compromises of any of the data-use conditions, occurred among nine approved users; most were procedural violations, and none violated participant confidentiality. Over 5 years of experience with GAIN data access has demonstrated substantial use of GAIN data by investigators from academic, nonprofit, and for-profit institutions with relatively few and contained policy violations. The availability of GAIN data has allowed for advances in both the understanding of the genetic underpinnings of mental-health disorders, diabetes, and psoriasis and the development and refinement of statistical methods for identifying genetic and environmental factors related to complex common diseases.
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Project description:Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10(-15)), PRIC285 (P = 3.0 × 10(-10)) and an upstream region of CDKN1A (P = 2 × 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor ? (PPAR?) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.
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Project description:Inflammation plays a central role in many human diseases. Human parturition also resembles an inflammatory reaction, where progesterone (P4) and progesterone receptors (PRs) have already been demonstrated to suppress contraction-associated gene expression. In our previous studies, we have found that the progesterone actions, including progesterone-induced gene expression and progesterone's anti-inflammatory effect, are mediated by PR, GR or both. In this study, we used microarrays (GSE68171) to find P4 and IL-1β responsive genes and IL-1β responsive genes which were repressed by P4. These data may provide a broader view of gene networks and cellular functions regulated by P4 and IL-1β in human myometrial cells. These data will also help us understand the role of PR and GR in human parturition.
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Project description:Gene expression arrays and genotyping data in primary human monocytes from healthy individuals of European ancestry that have either been unstimulated (naive) or exposed to IFN gamma (24h) or Lipopolysaccharide (2 or 24h duration).
2014-03-26 | E-MTAB-2232 | biostudies-arrayexpress
Project description:Gene expression data from human primary cultured Schwann cells
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Project description:There is extensive natural variation in human gene expression. As quantitative phenotypes, expression levels of genes are heritable. Genetic linkage and association mapping have identified cis- and trans-acting DNA variants that influence expression levels of human genes. New insights into human gene regulation are emerging from genetic analyses of gene expression in cells at rest and following exposure to stimuli. The integration of these genetic mapping results with data from co-expression networks is leading to a better understanding of how expression levels of individual genes are regulated and how genes interact with each other. These findings are important for basic understanding of gene regulation and of diseases that result from disruption of normal gene regulation.
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