Project description:Genome-wide DNA methylation level was studied to determine whether multiple sclerosis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in peripheral blood from multiple sclerosis patients (cases) and normal controls
Project description:Genome wide DNA methylation profiling of genomic DNA isolated from hippocampus of multiple sclerosis patients were hybridized to Illumina HumanMethylation450 Beadchip arrays. DNA methylation profiles across approximately 45,000 CpGs were compared between 8 myelinated and 7 demyelinated tissues .
Project description:Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis–affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis–affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis–affected brains.
Project description:Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological processes. To identify DNA methylation hallmarks, associated with relapse of MS, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same individuals, using Illumina 450K methylation arrays. We revealed changes in DNA methylation for both cell populations of MS patients in relapse when compared wih remission. In CD4+ cells the absolute majority of differentially methylated positions (DMPs) were hypermethylated. In CD4+, but not in CD14+ cells, we found a differentially methylated region within the GNAS complex locus and showed significant differences in the ammount of its transcripts between patients in relapse and remission.
Project description:Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological processes. To identify DNA methylation hallmarks, associated with relapse of MS, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same individuals, using Illumina 450K methylation arrays. We revealed changes in DNA methylation for both cell populations of MS patients in relapse when compared wih remission. In CD4+ cells the absolute majority of differentially methylated positions (DMPs) were hypermethylated. In CD4+, but not in CD14+ cells, we found a differentially methylated region within the GNAS complex locus and showed significant differences in the ammount of its transcripts between patients in relapse and remission.