X chromosome inactivation is the means by which mammals 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 future inactive X. Previous studies of autosomal duplications show that a region on human chromosome 19 plays a critical role in protecting the active X. It has been proposed that this autosome genetically interacts with the X chromosome to repress XIST function on the future. Here, I show that the type of chromosome 19 duplication influences the outcome of the interaction. Based on analysis of new cases in the DECIPHER database. the presence of three chromosome 19s is tolerated whereas duplications affecting only one chromosome 19 are not. The different outcomes have mechanistic implications for how chromosome 19 interacts with the future active X to protect it from inactivation and points to a role for stochastic gene expression, and possible physical interactions between these chromosomes.

中文翻译：

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随机基因表达和染色体相互作用在保护人类活性 X 免受 XIST 沉默中的作用

X 染色体失活是哺乳动物补偿 X 染色体数量性别差异的方法 一个相对未探索的问题是如何保护活性 X 免受其自身 XIST 基因的失活，长链非编码 RNA 启动沉默未来不活跃的X。先前对常染色体重复的研究表明，人类19号染色体上的一个区域在保护活跃的X方面发挥着关键作用。有人提出，这种常染色体与X染色体发生遗传相互作用以抑制未来的XIST功能。在这里，我展示了 19 号染色体重复的类型会影响相互作用的结果。基于对 DECIPHER 数据库中新病例的分析。三个 19 号染色体的存在是可以容忍的，而仅影响一个 19 号染色体的重复则不能。