been identified. A 2010 study found a small but significant under-expression of the paternal X chromosome in mice. Extra-embryonic tissues are found to preferentially inactivate the paternal X chromosome. Marsupials will always inactivate the paternal X chromosome, in a process named imprinting. Researchers hypothesized a link between the slight preference for inactivation of the paternal X in mice tissue, and the preference in extra-embryonic tissue and Marsupials. There may be a conserved epigenetic mark that drives this preference. Promoter mutations Skewed inactivation patterns can also emerge due to mutations that change the quantity of guanine on the Xist promoter. The Xist gene is responsible for inactivating the X chromosome from which it is transcribed. X-chromosome inactivation in general is influenced by the number of guanine-containing nucleotides on the Xist promoter, although generally inactivation still follows a random pattern. A rare mutation can occur, however, in which a cytosine residue is converted to guanine on the Xist promoter. It has been hypothesized that the mutation causes a change in the Xist transcript or in the levels of transcript produced, which causes the cell to differentiate between the two X chromosomes and causes the chromosome with the mutation to become preferentially inactivated. The mechanism has not been fully elucidated at this time, although research does point towards decreased promoter activity as a result of the mutation being a major part of the process. Secondary skewing Secondary skewing occurs when an X-linked mutation affects cell proliferation or survival. If a mutation on one X chromosome negatively affects a cell’s ability to proliferate or survive, there will end up being a larger proportion of cells with the other X chromosome active. This selection of one X chromosome can vary between tissue types, as it depends on the specific gene and its activity in the tissue, with rapidly dividing cells giving selection processes more time to work. Blood cells, for example, tend to have the highest rates of skewing due to the extremely high dividing and replacement rate within the human body. The strength of selection can also vary depending on the gene under selection, and so skewing can occur at different rates and to different extents. Secondary selection tends to cause an increase in skewing with age. This is primarily due to a longer span over which selective pressure has room in which to act. Skewing is still seen in young children, but with