Extreme reduction of chromosome-specific α-satellite array is unusually common in human chromosome 21
Extreme reduction of chromosome-specific α-satellite array is unusually common in human chromosome 21
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DOI：
10.1101/gr.9.10.895
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发表时间：
1999-10-01
期刊：
影响因子：
7
通讯作者：
Choo, KHA
中科院分区：
文献类型：
--
作者：
Lo, AWI;Liao, GCC;Choo, KHA
人类着丝粒含有大量的或卫星DNA，这些DNA被认为提供着丝粒的功能。这些排列显示出大小和序列的变化，但是这种极低水平的DNA在正常着丝粒上发生的程度尚不清楚。使用一套染色体特异性α -卫星探针对每条人类染色体，我们进行了间期荧光原位杂交（FISH）在人群筛选研究。我们的研究结果表明，染色体特异性α卫星的极端减少在21号染色体中异常常见（用α RI探针筛选），患病率为3.70%，而13号和17号染色体的患病率均小于或等于0.12%，其他染色体的患病率为0%。在17000条形态学正常的染色体中未发现analphoid着丝粒。通过有丝分裂稳定性和与着丝粒蛋白CENP-B、CENP-C和CENP-E的结合，所有的低脂蛋白着丝粒都具有完全的功能。对低阿尔法染色体21号着丝粒的中期敏感FISH分析证实了残余α - RI以及其他非α - RI α -卫星DNA的存在，这表明着丝粒功能可能由(1)残余α - RI DNA，(2)其他非α - RI α -卫星序列，(3)1和2的组合，或(4)激活的新着丝粒DNA提供。低阿尔法体着丝粒，特别是21号染色体的着丝粒，应该为研究人类着丝粒的进化和最低DNA需求提供独特的机会。
Human centromeres contain large arrays of or-satellite DNA that are thought to provide centromere function. The arrays show size and sequence variation, but the extent to which extremely low levels of this DNA can occur on normal centromeres is unclear. Using a set of chromosome-specific alpha-satellite probes for each of the human chromosomes, we performed interphase fluorescence in situ hybridization (FISH) in a population-screening study. Our results demonstrate that extreme reduction of chromosome-specific alpha satellite is unusually common in chromosome 21 (screened with the alpha RI probe), with a prevalence of 3.70%, compared to less than or equal to 0.12% for each of chromosomes 13 and 17, and 0% For the other chromosomes. No analphoid centromere was identified in >17,000 morphologically normal chromosomes studied. All of the low-alphoid centromeres are fully functional as indicated by their mitotic stability and binding to centromere proteins CENP-B, CENP-C, and CENP-E. Sensitive metaphase FISH analysis of the low-alphoid chromosome 21 centromeres established the presence of residual alpha RI as well as other non-alpha RI alpha-satellite DNA suggesting that centromere function may be provided by (1) the residual alpha RI DNA, (2) other non-alpha RI alpha-satellite sequences, (3) a combination of 1 and 2, or (4) an activated neocentromere DNA. The low-alphoid centromeres, in particular those of chromosome 21, should provide unique opportunities for the study of the evolution and the minimal DNA requirement of the human centromere.