The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time. Use of this genetic strategy can also delineate which specific centromere arrays in each chromosome drive the recruitment of epigenetic modulators. We further show that, surprisingly, loss and rearrangement of DNA in centromere 21 is associated with trisomy 21. This new approach can thus be used to rapidly take a snapshot of the genetics and epigenetics of each specific human centromere in nondisjunction disorders and other biological settings.

着丝粒是负责忠实分离染色体的结构单位。尽管已经对表观遗传因素对着丝粒功能的调控进行了很好的研究，但对底层DNA序列的贡献却没有得到很好的定义，并且在生物学中研究着丝粒基因组学的现有方法也很费力。我们已经在24条人类染色体中的23条的着丝粒中鉴定了特定标记，这些标记可以进行快速PCR分析，从而能够在给定的时间捕获人类着丝粒的基因组景观。使用这种遗传策略还可以描述每个染色体中哪个特定的着丝粒阵列驱动表观遗传调节剂的募集。我们进一步表明，令人惊讶的是，着丝粒21中DNA的丢失和重排与21三体性有关。