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: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: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.
Project description:Congenital scoliosis (CS) is a congenital disease that results in anomalous vertebral development. Research indicates that both genetic and environmental factors during pregnancy contribute to the risk of CS development, however, the exact mechanisms underlying CS pathogenesis remain unclear. To address this issue, we have generated both genetic (by exon capture sequencing) and epigenetic (by MeDIP) maps from a CS disease-discordant monozygotic twin pair. We compared the differences in the presence of common and rare SNPs between the twins as well as investigated differences in methylation patterns. Our data indicated that rare mutations are more likely to underlie CS development than common mutations, and that these are also more likely to play a role than do genomic methylation patterns. We did, however, identify a difference in the allele-specific-methylation between the twins in the SVIL gene which has functions in categories relevant to this disease, which raises the possibility of a novel mechanism promoting CS pathogenesis.
Project description:Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. We aimed to examine whether global DNA methylation differences exist in major glucose metabolic tissues from twelve 53–80 year-old monozygotic discordant twin pairs.
Project description:The exploration of copy number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic make-up between twins derived from the same zygote represent an extreme example of somatic variation. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype using two platforms for genome-wide CNV analyses and show that CNVs exist within pairs in both groups. These findings impact our views of genotypic and phenotypic diversity in monozygotic twins, and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool in identifying disease predisposition loci. Our results also imply that caution should be exercised with the interpretation of disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics Keywords: copy number variation, concordant and discordant monozygotic twins
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
