Molecular analysis of a deletion polymorphism in alpha satellite of human chromosome 17: evidence for homologous unequal crossing-over and subsequent fixation.
Molecular analysis of a deletion polymorphism in alpha satellite of human chromosome 17: evidence for homologous unequal crossing-over and subsequent fixation.
复制标题
人类 17 号染色体 α 卫星缺失多态性的分子分析：同源不等交换和随后固定的证据。
作者：
J. Waye;H. Willard
人类α卫星DNA家族被组织成染色体特异性子集，其特征在于基于约171个碱基对单体单元的不同高阶重复。在人类17号染色体上，α卫星的主要形式是16-单体（16-mer）高阶重复，每个17号染色体存在500-1000个拷贝。此外，在17号染色体上也发现了不太丰富的15单体和14单体重复序列。在不同的高阶重复长度的形式的多态性已被描述为这个子集，最突出的多态性是13单体（13聚体）的高阶重复存在于约35%的所有染色体17。为了研究这种多态性的性质，我们已经克隆，测序和比较的相关区域的13聚体先前表征的16聚体重复。结果表明，重复是几乎相同的，与主要的区别是排除了三个单体的13聚体重复。我们建议，13聚体是一个孤立的同源重组事件之间的16聚体重复的两个单体的产物。序列比较揭示了重组的大致位点和同源的侧翼区域。该重组位点对应于先前在独立同源重组事件中涉及的α单体内的位置，表明α DNA中可能存在重组的优选寄存器。我们认为，这些事件是代表一个正在进行的过程能够重组的卫星子集的一个给定的染色体，从而有助于建立染色体特异性α卫星子集。
The human alpha satellite DNA family is organized into chromosome-specific subsets characterized by distinct higher-order repeats based on a approximately 171 basepair monomer unit. On human chromosome 17, the predominant form of alpha satellite is a 16-monomer (16-mer) higher-order repeat present in 500-1000 copies per chromosome 17. In addition, less abundant 15-monomer and 14-monomer repeats are also found constitutively on chromosome 17. Polymorphisms in the form of different higher-order repeat lengths have been described for this subset, the most prominent polymorphism being a 13-monomer (13-mer) higher-order repeat present on approximately 35% of all chromosomes 17. To investigate the nature of this polymorphism, we have cloned, sequenced and compared the relevant regions of the 13-mer to the previously characterized 16-mer repeat. The results show that the repeats are virtually identical, with the principal difference being the exclusion of three monomers from the 13-mer repeat. We propose that the 13-mer is the product of an isolated homologous recombination event between two monomers of the 16-mer repeat. Sequence comparisons reveal the approximate site of recombination and flanking regions of homology. This recombination site corresponds to a position within the alphoid monomer which has been previously implicated in an independent homologous recombination event, suggesting that there may exist a preferred register for recombination in alphoid DNA. We suggest that these events are representative of an ongoing process capable of reorganizing the satellite subset of a given chromosome, thereby contributing to the establishment of chromosome-specific alpha satellite subsets.