Project description:The aim of this study was to quantify the impact of NOD genetic vatiation on thymic negative selection transcriptional programs. Pre-selected BDC2.5 TCR Tg DP thymocytes from non-selecting B6 and NOD.H2b backgrounds were purified (Dynal CD8 FlowComp), mixed in a 1:1 ratio and stimulated with BDC mimotope-loaded TCRa-/-/NOD splenocytes for indicated periods of time and double sorted by FACS as Thy1.2+Dump-CD4+CD8+; Dump includes CD19, Gr1, CD11b, CD11c, CD49b. Following cell sorting into trizol, RNA was purified, labeled and hybridized to Affymetrix arrays. experiment type: unstimulated versus stimulated BDC/B6.Rag-/- and BDC/NOD.H2b.Rag-/- DP thymocytes
Project description:To uncover new molecular mechanisms involved in IgAN pathogenesis, we compared the genomic profiles of 12 IgAN patients with 8 healthy subjects, We included addiotional disease controls 3 FSGS(Focal Segmenal glomerulosclerosis) patients and 3 membrano proliferative glomerulonephritis type I (MPGN-I) controls in our study to evaluate if the WNT-β-catenin and PI3K/Akt pathways were specfic to IgAN. Gene expression profile comparison between 12IgAN patients and 8 Healthy Subjects. Gene Set Enrichment Analysis (GSEA) performed on the additional disease controls determined that the a priori defined set of genes and the pathways generated were specific to the IgAN
Project description:The goal of this study is to identify aging-related biomarkers to improve our understanding of complex physiological changes, thereby providing a means to investigate the mechanism by which aging influences various diseases. Global gene expression patterns from peripheral blood of two groups of healthy young adult women, among which 13 were aged 22-25 and 9 were aged 36-39 years old, were compared to determine changes in gene expression that are associated with aging.
Project description:Blood (mRNA and miRNA) and skin mRNA transcriptomes were investigated across three time-points in a pilot investigation of ten severe psoriasis patients, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used illumina RNA-sequencing to analyse the small-RNA transcriptome in blood
Project description:The goal of this study is to identify aging-related biomarkers to improve our understanding of complex physiological changes, thereby providing a means to investigate the mechanism by which aging influences various diseases. Global microRNA expression patterns from peripheral blood of two groups of healthy young adult women, among which 13 were aged 22-25 and 9 were aged 36-39 years old, were compared to determine changes in microRNA expression that are associated with aging.
Project description:Profiles of sequence variants that influence gene transcription are very important for understanding mechanisms that affect phenotypic variation and disease susceptibility. Using genotypes at 1.4 million SNPs and a comprehensive transcriptional profile of 15,454 coding genes and 6,113 lincRNA genes obtained from peripheral blood cells of 298 Japanese individuals, we mapped expression quantitative trait loci (eQTLs). We identified 3,804 cis-eQTLs (within 500 kb from target genes) and 165 trans-eQTLs (>500 kb away or on different chromosomes). Cis-eQTLs were often located in transcribed or adjacent regions of genes; among these regions, 5’ untranslated regions and 5’ flanking regions had the largest effects. Epigenetic evidence for regulatory potential accumulated in public databases explained the magnitude of the effects of our eQTLs. Cis-eQTLs were often located near the respective target genes, if not within genes. Large effect sizes were observed with eQTLs near target genes, and effect sizes were obviously attenuated as the eQTL distance from the gene increased. Using a very stringent significance threshold, we identified 165 large-effect trans-eQTLs. We used our eQTL map to assess 8,069 disease-associated SNPs identified in 1,436 genome-wide association studies (GWAS). We identified genes that might be truly causative, but GWAS might have failed to identify for 148 out of the GWAS-identified SNPs; for example, TUFM (P=3.3E-48) was identified for inflammatory bowel disease (early onset); ZFP90 (P=4.4E-34) for ulcerative colitis; and IDUA (P=2.2E-11) for Parkinson's disease. We identified four genes (P<2.0E-14) that might be related to three diseases and two hematological traits; each expression is regulated by trans-eQTLs on a different chromosome than the gene. The study subjects were 301 apparently healthy individuals residing in Nagahama City, Japan. Whole blood was collected from each participant when in a non-stimulated state.
Project description:Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in disease development. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in various cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA). DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatics analysis of retrieved data (DAVID, GSEA, IPA). Total RNA was isolated from whole blood of 45 children with known HLA genotype and diagnosis of jSpA according to ILAR criteria, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of chronic inflammatory disease. Of those 11 patient and 4 controls were utilized in the microarrays experiments, while the rest were used in the follow-up qPCR analyses
Project description:The aim of the current study was to characterize the genetic adaptive pathways altered by exercise in veteran athletes and age-matched untrained individuals. Two groups of 50-60 year old males: competitive cyclists and untrained, minimally active individuals were examined. All participants completed an acut bout of submaximal endurance exercise and blood samples pre- and post-exercise were analyzed for gene expression changes utilizing genome-wide DNA microarray analysis. Our results indicate distinct differences in gene expression involving energy metabolism, lipids, insuling signaling and cardiovascular function between the two groups. These findings may lead to new insights into beneficial signaling pathways of healthy aging and help identify surrogate markers for monitoring exercise and training load. Blood samples from the control and athlete groups were analyzed at three time-points: T1 (before exercise); T2 (immediately after exercise) and T3 (24 hours after exercise). There were n = 4 samples in each of control and athlete group at T1 and T3; and n = 7 for control group and n = 8 for athlete group at T2. One athlete sample (Sample # 010201) at time - point T2 had a technical replicate.
Project description:Abstract<br>BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has demonstrated to be a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature availble on gene expression markers associated to Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated to critical respiratory illness in this disease is not known to the present moment. <br>RESULTS: By using Agilent microarray chips, we have profiled gene expression signatures in whole blood of 28 COPD patients hospitalized with distinct degree of respiratory compromise.12 of them needed of admission to the ICU, while 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparison of transcript levels between ICU and non ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to select, annotate and visualize genes by function and pathway (gene ontology). T-test evidenced 1501 genes differentially expressed between ICU and non ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients showed increased levels of neutrohil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This ?neutrophil signature? was paralleled by necessity of advanced respiratory and vital support, and presence of bacterial infection.<br>CONCLUSION: study of transcriptomic signatures in blood suggests a central role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement / modulation of the expression of these genes could represent an option for clinical monitoring and treatment of severe COPD exacerbations. <br><br>Keywords: COPD, critical, expression, gene, microarray, neutrophil, proteases.<br><br>