Project description:Gene expression analysis in CD4+ T cells extracted from allergen-challenged PBMCs, isolated from discordant MZ twins with IAR MZ twins discordant for intermittent allergic rhinitis (IAR)
Project description:Gene expression analysis in CD4+ T cells extracted from PBMCs, isolated from discordant MZ twins with IAR during season MZ twins discordant for intermittent allergic rhinitis (IAR)
Project description:DNA methylation appears to play an essential mechanistic role in the pathogenesis of ALL, thereby potentiate its use as a biomarker for diagnosis and prognosis (Milani, Lundmark et al. 2010; Geng, Brennan et al. 2012; Sandoval, Heyn et al. 2013), and even a potential target of novel therapeutic approaches in ALL. In present study, we collected blood specimens for 4 pairs of monozygotic twins (MZ) and 1 pair of dizygotic twin (DZ) that are discordant for ALL. We sought to comprehensively assess the magnitude of genetic and epigenetic differences between ALL-affected and unaffected twins. we conducted whole genome and whole methylome sequencing on these five pairs of ALL-discordant twins. We also examined both the MZ and DZ twins using whole-genome bisulfite sequencing (WGBS). At first, the methylation differences across the genome were addressed globally by Circos software. And then tried to characterize the co-twin methylation divergence in specific genomic regions between ALL-discordant twin pairs. These patterns of dynamic co-twin methylation changes in these discordant ALL samples were generally consistent among MZ and DZ twins, indicating similarities of methylation abnormalities. As a result, 780, 566, 309, 293 and 2110 DMRs were identified, with a similar distribution pattern across different genomic elements among the five twin pairs.Then we annotate whether these DMRs were located in regulatory elements and identification of genes with recurring methylation alterations in a cohort of ALL patients. We collected blood specimens from 4 pairs of MZ twins and 1 pair of DZ twin that are discordant for ALL. At first, the methylation differences across the genome were addressed globally by Circos software. And then tried to characterize the co-twin methylation divergence in specific genomic regions and differentially methylated gene regions (DMRs) were identified between ALL-discordant twin pairs. Then we annotate whether these DMRs were located in regulatory elements and identification of genes with recurring methylation alterations in a cohort of ALL patients.
Project description:Several lines of evidence indicate that mitochondrial DNA (mtDNA) variants might predispose to multiple sclerosis (MS). We examined this in 49 monozygotic (MZ) twin pairs clinically discordant for MS at study entry. Since the nuclear DNA of MZ twins is identical, our study provides a unique setting to functionally associate unique mtDNA variants and skewed heteroplasmy with MS development. In order to identify mtDNA variants in the twin cohort, we deeply sequenced the mitochondrial genome in blood of all 49 MZ twin pairs using next generation sequencing (Illumina, HiSeq or MiSeq) with an average coverage depth of ~25,000 sequences per base. Heteroplasmic variants were validated using targeted deep sequencing (TDS) (Illumina, MiSeq) in DNA isolated from blood and buccal swabs. In addition, whole blood was also available of 5 additional MS-affected or healthy siblings and 1 dizygotic twin pair discordant for MS, comprising in total 6 non-identical sib pairs. Moreover, all cases were screened for pathogenic mtDNA polymerase gamma (POLG) mutations. The data provides valuable insights in the possible involvement of mtDNA variants in the pathogenesis of MS, and gives information on the segregation of heteroplasmic variants within MZ twins and non-identical siblings and across different tissues.
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:This SuperSeries is composed of the following subset Series: GSE37146: Gene expression analysis in MZ twins discordant for IAR [in vitro] GSE37155: Gene expression analysis in MZ twins discordant for IAR [in vivo] Refer to individual Series
Project description:The methylation profile for 54 MZ twins are generated by methylated DNA immunoprecipitation followed by sequencing on Illumina GAII. Methylation score (RPM and AMS) is quantified using MEDIPS and differentially methylation region in T2D is detected a linear mixed effect model and MZ discordant twin model.
Project description:Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Epigenetic study of MZ twins discordant for Major Depressive Disorder
Project description:Genome wide DNA methylation profiling of MZ twins discordant and concordant for BMI. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Samples included 30 MZ twin pairs discordant for BMI and 10 pairs concordant for BMI.
Project description:Objective:; To identify genes involved in idiopathic absence epilepsies by analysing gene expression using a monozygotic (MZ) twin design. Methods:; Genome-wide gene expression in lymphoblastoid cell lines was determined using microarrays derived from five discordant and four concordant MZ twin pairs with idiopathic absence epilepsies and five unaffected MZ twin pairs. Gene expression was analysed using three strategies: discordant MZ twins were compared as matched pairs, MZ twins concordant for epilepsy were compared to control MZ twins, and a singleton design of affected versus unaffected MZ twin individuals was used irrespective of twin pairing. An overlapping gene list was generated from these analyses. Dysregulation of genes recognised from the microarray experiment were validated using quantitative real time PCR (qRT-PCR) in the twin sample and in an independent sample of 18 sporadic absence cases and 24 healthy controls. Results:; Sixty-five probe sets were identified from the microarray analysis strategies. Sixteen genes were chosen for validation and nine of these genes confirmed by qRT-PCR in the twin sample. Differential expression of the immediate early gene EGR1 and RCN2, coding for the calcium-binding protein Reticulocalbin 2, was re-confirmed by qRT-PCR in the independent sample. Interpretation:; Using a unique sample of discordant MZ twins, our study identified genes with altered expression, which suggest novel mechanisms in idiopathic absence epilepsy. Dysregulation of EGR1 and RCN2 might represent common transcriptional alterations in idiopathic absence epilepsy. Experiment Overall Design: Genome-wide gene expression in lymphoblastoid cell lines was determined using microarrays derived from five discordant and four concordant MZ twin pairs with idiopathic absence epilepsies and five unaffected MZ twin pairs.