Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögrenâs syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. Case-case study including Sjögren's patients with high fatigue (n=24) and patients with low fatigue levels (n=24)
Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögren’s syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array.
Project description:Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Genomic DNA from 24 peripheral blood mononuclear cells (PBMC) samples (12 CFS, 12 controls) were bisulfite-converted and hybridised to the Illumina Infinium HumanMethylation450 BeadChip. GenomeStudio files were generated and the data was analyzed using the Illumina Methylation Analyzer R package.
Project description:Background. Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. Methods. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. Findings. There were no significant differences in gene expression for any transcript. Conclusions. Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, potential interactions between DNA methylation and genetic background in relation to ME/CFS have not been examined. In this study we explored this association by characterizing the epigenetic (~480 thousand CpG loci) and genetic (~4.3 million SNPs) variation between cohorts of ME/CFS patients and healthy controls. We found significant associations of DNA methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation modifications associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.