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Mammals use X chromosome inactivation to compensate for the sex difference in numbers of X chromosomes. A relatively unexplored question is how the active X is protected from inactivation by its own XIST gene, the long non-coding RNA, which initiates silence of the inactive X. Previous studies of autosomal duplications show that human chromosome 19 plays a critical role in protecting the active X. I proposed that it genetically interacts with the X chromosome to repress XIST function on the future active X. Here, I show that the type of