Epigenetic variation in early human development

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One of the interesting questions in human biology is why monozygotic twins, which have an identical genetic make up, can still vary in many complex traits such as height, eye colour and susceptibility to various mental and disease states. It is clear that this variation is not always due simply to environment. We propose in this application to show that, even if the genetic code is identical in monozygotic twins, epigenetic marks such as DNA methylation and histone modifications can vary between critical genes giving rise to differences in gene expression patterns. We propose that the variation in the methylation pattern arises after the two embryos have split, at a time when the developing embryo undergoes genome-wide demethylation followed by de novo re-methylation. The importance of this project is NOT what it tells us about twins themselves, but that twins can provide the clue to disease processes which affect everybody in the population. The results of these experiments will determine the extent to which epigenetic changes to the genome that occur early in embryonic development provide an additional source of variation in gene expression that could contribute to phenotypic variation. By using identical twins we eliminate the possibility that epigenetic modifications that we observe are themselves influenced by genotype. Determining these epigenetic differences will provide an insight into the mechanisms underlying complex traits and human disease.