Project description:Objective: To characterize miRNAs in 41-year archived plasma in relation to life expectancy independent of genes. Method: Plasma miRNAs from nine identical male twins were profiled using next-generation sequencing. Results: The average absolute difference in the minimum life expectancy was 9.68 years. Intra-class correlation coefficients were above 0.4 for 50% of miRNAs. Comparing deceased twins with their alive co-twin brothers, the concentrations were increased for 34 but decreased for 30 miRNAs. Conclusion: Identical twins discordant in life expectancy were unlike in the majority of miRNAs, suggesting that environmental factors are pivotal in miRNAs related to life expectancy.
Project description:Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development. Copy number alterations were evaluated using array-CGH (4x44K, Agilent Technologies) in one seminoma and one embryonal carcinoma (EC) from MZ twins. In addition, genomic alterations from the tumors and peripheral blood cells of the twins were compared to the parental genomes via their peripheral blood cells.
Project description:Human intelligence demonstrates one of the highest heritabilities among human quantitative traits. Phenotypically discordant monozygotic twins provide a way to identify loci reponsible for the phenotypical differences. We performed comprehensive DNA methylation analysis in monozygotic twins manifesting differences in IQ scores. Genes with significantly different methylation status are considered as candidates related to human intelligence.
Project description:Genome wide DNA methylation profiling of Rett syndrome monozygotic twins. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles in primary skin fibroblast cells from Rett syndrome monozygotic twins.
Project description:Genome wide DNA methylation profiling of blood samples from eight female identical twins of Han Chinese for forensic age prediction, age 21 to 32. The Illumina Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across approximately 485,000 CpGs at a single-nucleotide resolution. Samples included 8 pairs of identical female twins of Han Chinese.
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: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:Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia
Project description:Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development.