Individual-specific variation of gene expression in peripheral blood leukocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Peter Linsely
PROVIDER: E-GEOD-838 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Individual-specific variation of gene expression in peripheral blood leukocytes.
Radich Jerald P JP Mao Mao M Stepaniants Sergey S Biery Matt M Castle John J Ward Terry T Schimmack Greg G Kobayashi Sumire S Carleton Michael M Lampe Johanna J Linsley Peter S PS
Genomics 20040601 6
DNA microarray technology is used to determine gene expression profiles of various cell types, especially abnormal cells, such as cancer. By contrast, relatively little attention has been given to expression profiling of normal tissues. Here we describe studies of gene expression in peripheral blood leukocytes (PBL) from normal individuals sampled multiple times over periods ranging from several weeks up to 6 months. We demonstrate stable patterns of gene expression that differ between individua ...[more]
Similar Datasets
Project description:DNA microarray technology is used to determine gene expression profiles of various cell types, especially abnormal cells, such as cancer. By contrast, relatively little attention has been given to expression profiling of normal tissues. Here we describe studies of gene expression in peripheral blood leukocytes (PBL) from normal individuals sampled multiple times over periods ranging from several weeks up to 6 months. We demonstrate stable patterns of gene expression that differ between individuals. Among the genes whose expression varies by individual is a group of genes responsive to interferon stimulation. Certain individuals ( approximately 10-20% of those tested) showed higher baseline levels and lower inducibility of these genes in response to in vitro interferon stimulation. These studies demonstrate the feasibility of using DNA microarrays to measure the variations in gene expression of PBL from different individuals in response to environmental and genetic factors. Keywords: other
2003-12-31 | GSE838 | GEO
Project description:The inhibitory axis of PD-1 expressed on T cells and its ligands produced by APCs mediates T cell exhaustion in chronic viral infection. We asked whether temporality of the infectious process is decisive for regulation through PD-1/PD-Ligand and investigated its impact on chronic bacterial infection. Here we show that M. tuberculosis and its lipid compounds induce expression of PD-Ligand on dendritic cells (DC). Upregulation of PD-Ligand depended on signaling through DC-SIGN upon infection. As a counterpart, expression of the PD-1 receptor was increased on T cells from tuberculosis patients and PPD+ donors compared to healthy normal individuals. Moreover, PD-1 expressing T cells were confined to granulomatous lesions in tuberculous lungs. Finally, functional blocking of PD-Ligand rescued antigen-specific T cell responses of tuberculosis patients. Taken together, we demonstrate that the inhibitory axis of PD-1/PD-Ligand is operative in mycobacterial infection and suggest inhibition of inhibition for rescuing exhausted T cells in tuberculosis. Experiment Overall Design: Human PBMC-derived DCs were grown in 6-well plates and stimulated for 18 h with either mycobacterial ManLAM or recombinantly expressed ICAM-3. To ensure complete naïve status of DCs before stimulation, cells were left in wells from the day of PBMC isolation until end of stimulation. Change of medium was performed by carefully removing medium from wells without any manipulation of DCs. After stimulation, total RNA was isolated as described above and labeled with Fluorescent Direct Labeling Kit (Agilent Technologies) following manufacturerâs protocols. Microarray experiments were performed as two-color dye-reversal hybridizations. To compensate for dye-specific effects, a color swap was performed. Labeled RNA was hybridized on Whole Human Genome Oligo Microarray Kit 44k Format and scanned using an Agilent scanner according to manufacturerâs protocol (Agilent Technologies). Image analysis was performed using Feature Extractor software (Agilent Technologies). For data analysis Rosetta Resolver software was used (Rosetta Inpharmatics).
2008-06-18 | E-GEOD-10198 | biostudies-arrayexpress
Project description:To uncover the genetic determinants affecting expression in a metabolically active tissue relevant to the study of obesity, diabetes, atherosclerosis, and other common human diseases, we profiled 427 human liver samples on a comprehensive gene expression microarray targeting greater than 40,000 transcripts and genotyped DNA from each of these samples at greater than 1,000,000 SNPs. The relatively large sample size of this study and the large number of SNPs genotyped provided the means to assess the relationship between genetic variants and gene expression and it provided this look for the first time in a non-blood derived, metabolically active tissue. A comprehensive analysis of the liver gene expression traits revealed that thousands of these traits are under the control of well defined genetic loci, with many of the genes having already been implicated in a number of human diseases. Clincal data was requested, but not provided by submitter. Keywords: eQTL Liver samples (1-2 g) were acquired from Caucasian individuals from three independent liver collections at tissue resource centers at Vanderbilt University, University of Pittsburg, and Merck Research Laboratories. All individuals were compared to a common pool created from equal portions of RNA from 191 (111 from Vanderbilt University and 80 from University of Pittsburg) samples.
2008-05-07 | E-GEOD-9588 | biostudies-arrayexpress
Project description:Extensive efforts are underway to identify anti-angiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial cell growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGFR-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cells. Inhibition of KDR catalytic activity blocks tumor neo-angiogenesis, reduces vascular permeability, and, in animal models, inhibits tumor growth and metastasis. Using a gene expression profiling strategy in rat tumor models, we identified a set of six genes that are selectively overexpressed in tumor endothelial cells relative to tumor cells, and whose pattern of expression correlates with the rate of tumor endothelial cell proliferation. In addition to being potential targets for anti-angiogenesis tumor therapy, the expression patterns of these genes or their protein products may aid the development of pharmacodynamic assays for small molecule inhibitors of the KDR kinase in human tumors. Total RNA isolated from cultured cells or tumor tissue samples was used to make fluorescently labeled cRNA that was hybridized to DNA oligonucleotide microarrays. Briefly, 4 µg of total RNA from an individual tumor sample or endothelial cell culture were used to synthesize dsDNA through RT. cRNA was produced by in vitro transcription and labeled postsynthetically with Cy3 or Cy5. Two populations of labeled cRNA, a reference population and an experimental population, were compared with each other by competitive hybridization to microarrays. For animal tumor studies, reference cRNA pools were made by pooling equal amounts of cRNA from each tumor in the appropriate vehicle-dosed group. Species-specific microarrays were used throughout this study. Human microarrays contained 23,916 oligonucleotide probes corresponding to individual genes or expressed sequence tags. Rat microarrays contained probes to 22,592 genes or expressed sequence tags. Oligonucleotide probe sequences were chosen to maximize gene specificity and minimize the 3' replication bias inherent in RT of mRNA. In addition, both microarray formats contained 1,000 control probes for quality control purposes. All oligonucleotide probes on the microarrays were synthesized in situ with inkjet technology (Agilent Technologies, Palo Alto, CA). After hybridization, arrays were scanned and fluorescence intensities for each probe were recorded. Ratios of transcript abundance (experimental to control) were obtained following normalization and correction of the array intensity data. Gene expression data analysis was done with the Rosetta Resolver gene expression analysis software (version 3.2, Rosetta Biosoftware, Seattle, WA). For each gene sequence present on the microarrays, statistical significance of differential gene expression was determined by calculating P values.
2005-09-13 | E-GEOD-3299 | biostudies-arrayexpress
Project description:Background: In food production animals, especially cattle, the diagnosis of gestation is an important issue because the timing of gestation has direct effects on the running of farms. Various methods have been used to detect gestation, but none of them are ideal because of problems with the timing of detection, or the accuracy, simplicity, or cost of the method, etc. A new method for detecting gestation, which involves assessing interferon-tau-related gene expression in peripheral blood leucocytes (PBL), was recently proposed. PBL fractionation methods were used to examine whether the expression profiles of various PBL populations could be used as reliable diagnostic markers of bovine gestation. Methods: PBL were collected on days 0 (just before artificial insemination), 7, 14, 17, 21, and 28 of gestation. The gene expression levels of the PBL were assessed with microarray analysis and/or quantitative real-time reverse transcription (q)-PCR. PBL fractions were collected with flow cytometry or density gradient cell separation using Histopaque 1083 or Ficoll-Conray solution. The expression levels of four interferon-tau-related genes, interferon-stimulated protein 15 kDa (ISG15), myxovirus-resistance (Mx) 1 and 2, and 2'-5'-oligoadenylate synthetase (OAS1), were then analysed in each fraction until day 28 of gestation using qPCR. Results: Miroarray analysis detected 72 and 28 genes significantly higher in whole PBL on days 14 and 21 of gestation compare to those on day 0, respectively. They involved interferon-tau responded genes. The expression levels of these genes increased with the progression of gestation. In the flow cytometry experiment, on day 14 all of the genes displayed significantly higher expression levels in the granulocyte fraction than the other fractions, and their expression levels gradually decreased until day 28 of gestation. Strong correlations were observed between the expression levels of the four genes in the granulocyte fractions obtained with flow cytometry and density gradient separation. Conclusions: The expression profile of the four abovementioned genes could be a useful diagnostic biomarker of bovine gestation. Assessing the expression levels of ISG15, Mx1, Mx2 and OAS1 in a granulocyte fraction obtained with density gradient separation is a practical way of detecting gestation in cows within three weeks of insemination.
2013-01-31 | GSE42894 | GEO
Project description:Background: In food production animals, especially cattle, the diagnosis of gestation is an important issue because the timing of gestation has direct effects on the running of farms. Various methods have been used to detect gestation, but none of them are ideal because of problems with the timing of detection, or the accuracy, simplicity, or cost of the method, etc. A new method for detecting gestation, which involves assessing interferon-tau-related gene expression in peripheral blood leucocytes (PBL), was recently proposed. PBL fractionation methods were used to examine whether the expression profiles of various PBL populations could be used as reliable diagnostic markers of bovine gestation. Methods: PBL were collected on days 0 (just before artificial insemination), 7, 14, 17, 21, and 28 of gestation. The gene expression levels of the PBL were assessed with microarray analysis and/or quantitative real-time reverse transcription (q)-PCR. PBL fractions were collected with flow cytometry or density gradient cell separation using Histopaque 1083 or Ficoll-Conray solution. The expression levels of four interferon-tau-related genes, interferon-stimulated protein 15 kDa (ISG15), myxovirus-resistance (Mx) 1 and 2, and 2'-5'-oligoadenylate synthetase (OAS1), were then analysed in each fraction until day 28 of gestation using qPCR. Results: Miroarray analysis detected 72 and 28 genes significantly higher in whole PBL on days 14 and 21 of gestation compare to those on day 0, respectively. They involved interferon-tau responded genes. The expression levels of these genes increased with the progression of gestation. In the flow cytometry experiment, on day 14 all of the genes displayed significantly higher expression levels in the granulocyte fraction than the other fractions, and their expression levels gradually decreased until day 28 of gestation. Strong correlations were observed between the expression levels of the four genes in the granulocyte fractions obtained with flow cytometry and density gradient separation. Conclusions: The expression profile of the four abovementioned genes could be a useful diagnostic biomarker of bovine gestation. Assessing the expression levels of ISG15, Mx1, Mx2 and OAS1 in a granulocyte fraction obtained with density gradient separation is a practical way of detecting gestation in cows within three weeks of insemination. Gene expression profiles were analyzed in the peripheral blood leucocytes at days 0 (n=5), 14 (n=3) and 21 (n=5) after artificial insemination in cow.
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2004-01-31 | E-GEOD-902 | biostudies-arrayexpress
Project description:Chronic myeloid leukemia (CML) is a hematopoetic stem cell disease with distinct biological and clinical features. The biological foundation of the stereotypical progression from chronic phase through accelerated phase to blast crisis is poorly understood. We used DNA microarrays to compare gene expression in 91 cases of CML in chronic (42 cases), accelerated (17 cases), and blast phases (32 cases). Three thousand genes were found to be significantly (p<10-10) associated with the progression from chronic to blast phase. A comparison of the gene signatures of chronic, accelerated, and blast phases suggest that the progression of chronic phase CML from chronic advanced phase (accelerated and blast crisis) CML is a two-step rather than a three-step process, with new gene expression changes occurring early in accelerated phase before the accumulation of increased leukemia blast cells. The genetic signature of advanced phase CML is similar to that of normal CD34+ cells; however, progression also involved novel genes not expressed in normal CD34+ cells. Especially noteworthy is deregulation of the WNT/b-catenin pathway, the decreased expression of both JunB and Fos, and dysregulation of genes under the control of MZF1 and delta EF1 zinc finger transcription factors. Studies of CML patients who relapsed after initially successful treatment with imatinib mesylate demonstrated a gene expression pattern closely related to advanced phase disease. Take together, these data suggest that CML progression begins relative early and before clinical and pathological detection, and features distinct genetic differences compared to normal hematpoetic cells that might provide diagnostic and therapeutic targets. Samples from different phases of CML were hybridized against the pool of chronic phases of samples.
2010-06-11 | E-GEOD-4170 | biostudies-arrayexpress