Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, 70803, USA.
Mob DNA. 2011 Sep 23;2:10. doi: 10.1186/1759-8753-2-10.
The human genome contains approximately one million Alu elements which comprise more than 10% of human DNA by mass. Alu elements possess direction, and are distributed almost equally in positive and negative strand orientations throughout the genome. Previously, it has been shown that closely spaced Alu pairs in opposing orientation (inverted pairs) are found less frequently than Alu pairs having the same orientation (direct pairs). However, this imbalance has only been investigated for Alu pairs separated by 650 or fewer base pairs (bp) in a study conducted prior to the completion of the draft human genome sequence.
We performed a comprehensive analysis of all (> 800,000) full-length Alu elements in the human genome. This large sample size permits detection of small differences in the ratio between inverted and direct Alu pairs (I:D). We have discovered a significant depression in the full-length Alu pair I:D ratio that extends to repeat pairs separated by ≤ 350,000 bp. Within this imbalance bubble (those Alu pairs separated by ≤ 350,000 bp), direct pairs outnumber inverted pairs. Using PCR, we experimentally verified several examples of inverted Alu pair exclusions that were caused by deletions.
Over 50 million full-length Alu pairs reside within the I:D imbalance bubble. Their collective impact may represent one source of Alu element-related human genomic instability that has not been previously characterized.
人类基因组中约有一百万个人类 Alu 元件，其质量占人类 DNA 的 10%以上。Alu 元件具有方向性，在基因组中正、负链方向上的分布几乎相等。此前的研究表明，在方向相反的紧密间隔的 Alu 对（倒置对）比具有相同方向的 Alu 对（直接对）出现的频率更低。然而，这种不平衡现象仅在人类基因组草图序列完成之前的一项研究中对间隔 650 个碱基对或更少的 Alu 对进行了调查。
我们对人类基因组中所有（>800,000）全长 Alu 元件进行了全面分析。这个较大的样本量允许检测到倒置和直接 Alu 对（I:D）之间比率的微小差异。我们发现全长 Alu 对 I:D 比率显著下降，延伸至≤350,000 bp 的重复对。在这个不平衡泡（那些间隔≤350,000 bp 的 Alu 对）中，直接对的数量超过倒置对。通过 PCR，我们实验验证了几个由缺失引起的倒置 Alu 对排除的例子。
超过 5000 万个全长 Alu 对位于 I:D 不平衡泡内。它们的集体影响可能代表了以前未被描述的 Alu 元件相关人类基因组不稳定性的一个来源。
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