ABSTRACT: Comparison of the DNA methylation profiles of CD19+ B lymphocytes of a pair of monozygotic twins discordant for common variable immunodeficiency
Project description:The methylation profiles of bisulfite-modified DNA of CD19+ cells from MZ twins discordant for CVID were compared using the Infinium HumanMethylation450 BeadChips (Illumina, Inc., San Diego, CA,). This platform allows the interrogation of >485,000 methylation sites per sample at single-nucleotide resolution, and comprises an average of 17 CpG sites per gene in the 99% of RefSeq genes. 96% of CpG islands are covered, with additional coverage in CpG island shores and the regions flanking them. The samples were hybridized in the array following the manufacturer’s instructions. Total DNA isolated by standard procedures from CD19+ cells (total B lymphocytes) corresponding to two monozygotic twins discordant for common variable immunodeficiency.
Project description:Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. Here the authors perform single cell omics analyses in CVID discordant monozygotic twins and show epigenetic and transcriptional alterations associated with activation in memory B cells.
Project description:Trisomy 21 (T21) is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in T21, and to eliminate the noise of the genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for T21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either up- or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twinsM-bM-^@M-^Y fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of DS and wild-type, also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall LADs position was not altered in trisomic cells. However, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results suggest that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome and that GEDDs may therefore contribute to some T21 phenotypes. mRNA-Seq profiling in Down syndrome: fibroblasts derived from a pair of monozygotic twins discordant for trisomy 21 (4 replicates), iPS cells from the same pair of discordant twins, fibroblasts from a pair of normal monozygotic twins, fibroblasts from 16 unrelated individuals (8 trisomic and 8 euploid controls), fibroblasts from the Ts65Dn mouse model of Down syndrome (1 trisomic mouse and 1 control wt).
Project description:The present study examined the relationship between genome-wide methylation differences and variations in brain structures involved in the development of attention-deficit hyperactivity disorder (ADHD). We used monozygotic twins discordant for ADHD to identify candidate DNA methylation sites involved in the development of ADHD. Two pairs of MZ twins discordant for ADHD were recruited from the Department of Child and Adolescent Psychological Medicine at the University of Fukui Hospital. The twins were 9-year-old males (pair 1) and 16-year-old females (pair 2). Genomic DNA was collected from saliva samples, and the DNA was then whole-genome amplified, fragmented, and hybridized to the Human MethylationEPIC BeadChip.
Project description:This project contains genome-wide DNA methylation data generated using the HumanMethylation450 BeadChip (Illumina), for 79 rheumatoid arthritis (RA) discordant monozygotic twin pairs. By investigating disease discordant monozygotic twins, DNA methylation can be assessed without the confounding influence of genetic heterogeneity which often affects case-control epigenome-wide association studies of common diseases. Twins were recruited from two cohorts; Arthritis Research UK in Manchester and TwinsUK in London.
Project description:Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder. Aberrant DNA methylation has been observed in ASD but the mechanisms remain largely unknown. Here, we employed discordant monozygotic twins to investigate the contribution of DNA methylation to ASD etiology. Genome-wide DNA methylation analysis was performed using samples obtained from five pairs of ASD-discordant monozygotic twins, which revealed a total of 2397 differentially methylated genes. Further, such gene list was annotated with Kyoto Encyclopedia of Genes and Genomes and demonstrated predominant activation of neurotrophin signaling pathway in ASD-discordant monozygotic twins. The methylation of SH2B1 gene was further confirmed in the ASD-discordant, ASD-concordant monozygotic twins, and a set of 30 pairs of sporadic case-control by bisulfite-pyrosequencing. The results showed that there was a greater DNA methylation difference in ASD-discordant monozygotic twins than ASD-concordant monozygotic twins. Further, verification of the Chr.16:28856743 of SH2B1 showed significant differences in DNA methylation between case and control. These results suggest abnormal methylation of SH2B1 is associated with ASD etiology. Our data suggest that it might be worthwhile to further explore the functions of SH2B1 and related genes of neurotrophin signaling pathway in ASD.
Project description:Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder. Aberrant DNA methylation has been observed in ASD but the mechanisms remain largely unknown. Here, we employed discordant monozygotic twins to investigate the contribution of DNA methylation to ASD etiology. Genome-wide DNA methylation analysis was performed using samples obtained from five pairs of ASD-discordant monozygotic twins, which revealed a total of 2397 differentially methylated genes. Further, such gene list was annotated with Kyoto Encyclopedia of Genes and Genomes and demonstrated predominant activation of neurotrophin signaling pathway in ASD-discordant monozygotic twins. The methylation of SH2B1 gene was further confirmed in the ASD-discordant, ASD-concordant monozygotic twins, and a set of 30 pairs of sporadic case-control by bisulfite-pyrosequencing. The results showed that there was a greater DNA methylation difference in ASD-discordant monozygotic twins than ASD-concordant monozygotic twins. Further, verification of the Chr.16:28856743 of SH2B1 showed significant differences in DNA methylation between case and control. These results suggest abnormal methylation of SH2B1 is associated with ASD etiology. Our data suggest that it might be worthwhile to further explore the functions of SH2B1 and related genes of neurotrophin signaling pathway in ASD.
Project description:To gain insight into the etiopathogenesis of Multiple sclerosis (MS) we investigated gene expression changes in CD4+ and CD8+ T lymphocytes from monozygotic twins (MZ) discordant for relapsing remitting MS. We studied 4 monozygotic twin pairs discordant for disease, with the affected co-twin free of disease modifying therapies (F/M = 3/1, mean age 36.25±3.9). Following leukapheresis, CD4+ and CD8+ T cells were separated and studied by Affymetrix GeneChip®
Project description:The aim of the current study is to establish the effect of excess body wiehgt and liver fat on plasma proteomic profile without interference from genetic variation. Label-free proteomics (HDMSE) was performed on plasma samples of young healthy monozygotic twins who were discordant for BMI. the twins were further subdivided into groups of liver fat discordant and liver fat concordant to see the efefct fo liver fat on plasma proteomic signature.
