Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Clin Genet. 2010 Oct;78(4):299-309. doi: 10.1111/j.1399-0004.2010.01445.x.
The constitutional t(11;22)(q23;q11) is the most common recurrent non-Robertsonian translocation in humans. The breakpoint sequences of both chromosomes are characterized by several hundred base pairs of palindromic AT-rich repeats (PATRRs). Similar PATRRs have also been identified at the breakpoints of other nonrecurrent translocations, suggesting that PATRR-mediated chromosomal translocation represents one of the universal pathways for gross chromosomal rearrangement in the human genome. We propose that PATRRs have the potential to form cruciform structures through intrastrand-base pairing in single-stranded DNA, creating a source of genomic instability and leading to translocations. Indeed, de novo examples of the t(11;22) are detected at a high frequency in sperm from normal healthy males. This review synthesizes recent data illustrating a novel paradigm for an apparent spermatogenesis-specific translocation mechanism. This observation has important implications pertaining to the predominantly paternal origin of de novo gross chromosomal rearrangements in humans.
t(11;22)(q23;q11) 是人类中最常见的非罗伯逊易位。两条染色体的断裂点序列都具有几百个碱基对的回文结构富含 AT 的重复序列（PATRRs）。在其他非重复性易位的断裂点也发现了类似的 PATRRs，这表明 PATRR 介导的染色体易位代表了人类基因组中大片段染色体重排的一种普遍途径。我们提出，PATRRs 有可能通过单链 DNA 中的链内碱基配对形成十字形结构，从而产生基因组不稳定性的来源，并导致易位。事实上，在正常健康男性的精子中，以新发生的方式检测到 t(11;22) 的频率很高。这篇综述综合了最近的数据，说明了一种新的明显的精子发生特异性易位机制范例。这一观察结果对于人类中以新发生的大片段染色体重排主要来自父本具有重要意义。
