Variation and inheritance of retrotransposon epigenotype in the mouse

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It is often assumed that traits in humans and other mammals are a product primarily of information encoded in the sequence of DNA, with some contribution from the environment. However, there is clear evidence that traits may vary widely between individuals with precisely the same DNA, such as identical twins, even in circumstances where environmental differences are negligible. This variation can be produced by epigenetic factors chemical changes or protein binding to DNA that alter the way genes are used. Epigenetic factors can be passed from one generation to the next like the DNA itself, and this can make it difficult to know if a trait is encoded in the DNA itself or is epigenetic. We have found that some epigenetic traits in mice are caused by retrotransposons, which are parasitic elements that reside in and among genes, and can reproduce themselves, but do not have any known function (nearly half the human genome is made up of retrotransposons). Retrotransposons are generally kept silent by epigenetic factors, but may sometimes become active; when they do they may disturb normal patterns of gene activity and cause changes in traits and even disease. Much variation in humans may thus be due to variation in the epigenetic state (epigenotype) of retrotransposons. We propose to investigate variation and inheritance of epigenotype in mice, focussing on retrotransposons. We will use simple methods to compare epigenotype of a number of retrotransposons in genetically identical mice, and we will ask if any differences we find are heritable. We will also investigate the resetting of epigenotype the point in development when epigenetic factors are cleared and reset. We suspect that this occurs in early development. These studies may reveal a system of variation and inheritance with rules completely different from those found by Mendel, which may have a pervasive influence on traits, including sporadic diseases in humans.