Klinefelter综合征X染色体着丝粒区α-卫星DNA变异

目的从DNA分子水平建立研究X染色体着丝粒区域的α-卫星DNA变异的方法,发现Klinefelt综合征患者的X染色体着丝粒区域的α-卫星DNA串联重复序列结构变化与染色体不分离的关系。方法采用（representative sampling of multiple repetitive units,rep）PCR方法,通过设计适当的引物,对α-卫星DNA多个单拷贝串联重复序列同时进行扩增,检测重复序列中结构变化的种类、频率及重组位点。结果首次发现由缺失产生的562bp和220bp变异片段和重组位点,异常组的570、562、220bp构成显著高于正常组（P〈0．05）。Logistic回归分析显示：570、562bp和220bp3个短片段同时出现和任两个短片段同时出现均是疾病相关的危险因素。结论Klinefelt综合征的X染色体着丝粒区α-卫星DNA过多的重组可能是造成X染色体不分离的重要原因之一。

Variation of alpha satellite DNA in X chromosome centric region of Klinefelter syndrome

Objective To establish an effective method that can be used in study on variation of X chromosome centromeric DNA and to investigate the relationship between the variation of centromeric alpha satellite repeat unit on Klinefelter syndrome X chromosome and nondisjunction of the human X chromosome. Methods Representative sampling of multiple repetitive units PCR (rep PCR) and DNA sequence analysis were respectively used to investgate the molecular basis of X chromosome alpha satellite repeat unit variation by designing proper primers, and the frequency and position of new "hot" recombination breakpoint were detected. Results 1 774 bp, 570 bp and 1 410 bp, 562 bp, 220 bp DNA segments existed in normal individual and Klinefelt syndrome, but the frequency of 570 bp, 583 bp and 220 bp PCR product bands in Klinefelt syndrome were significantly higher than that in normal individuals. The result of logistic regression analysis indicated that appearance of three or two short fragments together was a risk factor of aneuploidy formation. Conclusion More frequency of the genetic recombination in X chromosome centromeric alpha satellite DNA plays a role in nondisjunction of the Klinefelter syndrome X chromosome.