This SuperSeries is composed of the SubSeries listed below.
Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View Samples242 patients recruited from an early arthritis clinic donated RNA and DNA from freshly isolated and purified peripheral blood CD19+ B cells. Global gene expression measurement was carried out using Illumina BeadChip HT12v4 microarrays. Objectives included the identification of B cell transcripts differentially expressed between disease phenotypes, where all patients were naive to immunomodulatory therapy. In addition an eQTL analysis was carried out with reference to known genotype data for this cohort of patients
CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis: Implications for Causal Gene Identification.
Sex, Specimen part
View SamplesFatigue is a debilitating condition with a significant impact on patients quality of life. Fatigue is frequently reported by patients suffering from primary Sjo grens Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.
No associated publication
Sex, Specimen part
View SamplesWith a focus on rheumatoid arthritis (RA), we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritise molecular pathways for targeting in this and related immune pathologies. Whole genome methylation and transcriptional data from isolated CD4+ T cells and B cells of >100 genotyped and phenotyped inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with GWAS findings across IMDs and other publically available resources.
Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View SamplesWith a focus on rheumatoid arthritis (RA), we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritise molecular pathways for targeting in this and related immune pathologies. Whole genome methylation and transcriptional data from isolated CD4+ T cells and B cells of >100 genotyped and phenotyped inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with GWAS findings across IMDs and other publically available resources.
Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of candidate genes involved in neuroblastoma progression by combining genomic and expression microarrays with survival data.
Sex, Age
View SamplesGene expression analysis was performed on 30 Neuroblastomas to identify genes whose transcription is significantly altered by recurrent chromosomal alterations. Genomic copy number losses and gains had been delineated in the tumours using FISH and SNP arrays. We have identified genes significantly altered by 7 recurrent alterations: 1p, 3p, 4p, 10q and 11q loss, 2p and 17q gain, and genes co-amplified and over-expressed as a result of MYCN amplification.
Identification of candidate genes involved in neuroblastoma progression by combining genomic and expression microarrays with survival data.
Sex, Age
View SamplesTelomeres are nucleoprotein complexes that protect the ends of eukaryotic chromosomes from being recognised as double strand breaks. When telomere structure is perturbed, a co-ordinated series of events to promote arrest of the cell cycle is rapidly initiated so that cells carrying damaged telomeres do not continue to divide. In order to better understand the eukaryotic response to telomere damage, we employed budding yeast strains harbouring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) and conducted a transcriptomic study of the genome-wide response to uncapped telomeres. We show that telomere uncapping in cdc13-1 strains is associated with the differential expression of over 1100 genes and has features in common with the responses to DNA damage, diverse environmental stresses and, as expected, the absence of telomerase. The transcriptomic response to telomere uncapping includes many genes with known roles in telomere function and some features that appear to be unique. BNA2 is the second most highly up-regulated gene upon telomere uncapping in cdc13-1 strains and is required for the biosynthesis of NAD+. We have shown that deletion of BNA2 and other genes involved in NAD+ synthesis, suppresses the temperature sensitivity of cdc13-1 strains. NAD+ synthetic genes may therefore play previously unknown roles in the cellular response to telomere uncapping.
A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection.
Sex, Subject, Time
View SamplesSkeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic myotubes in keeping with a retained genetic/epigenetic defect of insulin action.
p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients.
Specimen part
View SamplesTranscriptomics and proteomics analyses were carried out on rectal mucosal biopsies from 22 healthy adults with either optimal (n=11, mean plasma Se =1.43mol/l, s.e.m 0.06) or sub-optimal (n=11, mean plasma Se = 0.86umol/l, s.e.m 0.01) plasma Se status. Plasma Se status was associated with altered expression of 254 genes implicated in cancer, immune function and inflammatory response, cell growth and proliferation, cellular movement and cell death; 69 out of 254 genes had their expression significantly correlated with Se status, including two selenoprotein genes (SEPW1 and SELK). Proteomics identified 26 proteins differentially expressed between the two Se groups, including cytoskeletal proteins and factors involved in immune and inflammatory response and cancer pathways. Results from proteomics and transcriptomics support each other and integration of the two datasets was consistent with a reduced inflammatory and immune responses and a cytoskeleton remodelling in the rectal mucosa of individuals with sub-optimal Se status.
No associated publication
Sex, Age, Specimen part
View Samples