Project description:Open chromatin is implicated in regulatory processes, and thus variation in chromatin structure may contribute to variation in gene expression and other molecular phenotypes. In this work, we performed a targeted deep sequencing to identify somatic mutations and genetic polymorphisms underlying accessible chromatin in the genomes of 72 monozygotic twins. Open chromatin sequencing based on FAIRE assay for 36 pairs of monozygotic twins
Project description:Open chromatin is implicated in regulatory processes, and thus variation in chromatin structure may contribute to variation in gene expression and other molecular phenotypes. In this work, we performed a targeted deep sequencing to identify somatic mutations and genetic polymorphisms underlying accessible chromatin in the genomes of 72 monozygotic twins. Expression profiling by illumina beads array for 36 pairs of monozygotic twins
Project description:Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic, shared and non-shared environmental factors to phenotypic variability. Using DNA methylation profiling of ~20,000 CpG sites as a phenotype, we have examined discordance levels in multiple tissues in neonatal twins. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. This was largely independent of distance from transcriptional start site in promoters without CpG islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of non-shared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic and other complex diseases. Finally, comparison of our data with that of several older twins, revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyse DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome. Data from cord blood mononuclear cells (CBMCs), human umbilical vascular endothelial cells (HUVECs) and placenta from 22 MZ and 11 DZ pairs with one replicate sample
Project description:Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic, shared and non-shared environmental factors to phenotypic variability. Using DNA methylation profiling of ~20,000 CpG sites as a phenotype, we have examined discordance levels in multiple tissues in neonatal twins. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. This was largely independent of distance from transcriptional start site in promoters without CpG islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of non-shared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic and other complex diseases. Finally, comparison of our data with that of several older twins, revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyse DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.
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:Open chromatin is implicated in regulatory processes, and thus variation in chromatin structure may contribute to variation in gene expression and other molecular phenotypes. In this work, we performed a targeted deep sequencing to identify somatic mutations and genetic polymorphisms underlying accessible chromatin in the genomes of 72 monozygotic twins.
Project description:Open chromatin is implicated in regulatory processes, and thus variation in chromatin structure may contribute to variation in gene expression and other molecular phenotypes. In this work, we performed a targeted deep sequencing to identify somatic mutations and genetic polymorphisms underlying accessible chromatin in the genomes of 72 monozygotic twins.