Boone Philip M, Buenaventura Teresa, King James W D, Merkenschlager Matthias
Cornelia de Lange Syndrome and Related Disorders Clinic, Boston Children's Hospital, Boston, MA, USA.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
Nat Rev Genet. 2025 May 12. doi: 10.1038/s41576-025-00840-3.
During early mammalian female development, X chromosome inactivation leads to random transcriptional silencing of one of the two X chromosomes. This inactivation is maintained through subsequent cell divisions, leading to intra-individual diversity, whereby cells express either the maternal or paternal X chromosome. Differences in X chromosome sequence content can trigger competitive interactions between clones that may alter organismal development and skew the representation of X-linked sequence variants in a cell-type-specific manner - a recently described phenomenon termed X-linked competition in analogy to existing cell competition paradigms. Skewed representation can define the phenotypic impact of X-linked variants, for example, the manifestation of disease in female carriers of X-linked disease alleles. Here, we review what is currently known about X-linked competition, reflect on what remains to be learnt and map out the implications for X-linked human disease.
在早期哺乳动物雌性发育过程中，X染色体失活导致两条X染色体中的一条随机发生转录沉默。这种失活会在随后的细胞分裂中持续存在，从而导致个体内部的多样性，即细胞要么表达母本X染色体，要么表达父本X染色体。X染色体序列内容的差异会引发克隆之间的竞争性相互作用，这可能会改变机体发育，并以细胞类型特异性的方式使X连锁序列变异的表现发生偏差——这是一种最近描述的现象，类似于现有的细胞竞争模式，被称为X连锁竞争。偏差表现可以定义X连锁变异的表型影响，例如，X连锁疾病等位基因女性携带者中疾病的表现。在这里，我们综述了目前关于X连锁竞争的已知情况，思考了仍有待了解的内容，并阐述了其对X连锁人类疾病的影响。
