van Binsbergen E
Section of Genome Diagnostics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Cytogenet Genome Res. 2011;135(3-4):271-6. doi: 10.1159/000330267. Epub 2011 Aug 12.
Array-based methods have enabled the detection of many genomic gains and losses. These are stated as copy number variants (CNVs) and comprise up to 13% of the human genome. Based on their breakpoints and modes of formation CNVs are termed recurrent or nonrecurrent. Recurrent CNVs are flanked by low copy repeats and are of a fixed size. They arise as a result of misalignment during meiosis by a mechanism named nonallelic homologous recombination. Several of such recurrent CNVs have been linked to human diseases. Nonrecurrent CNVs, which are not flanked by low copy repeats, are of variable size and may arise via mechanisms like nonhomologous end joining and replication-based mechanisms described by the fork stalling and template switching and microhomology-mediated break-induced replication models. It is becoming clear that most disease-causing CNVs are nonrecurrent and generally arise via replication-based mechanisms. Furthermore, it is now appreciated that genomic features other than low copy repeats play a role in the formation of nonrecurrent CNVs. This review will discuss the different mechanisms of CNV formation and how high resolution analyses of CNV breakpoints have added to our knowledge of their precise structure.
基于阵列的方法能够检测出许多基因组的增加和缺失。这些被称为拷贝数变异（CNV），占人类基因组的比例高达13%。根据其断点和形成模式，CNV可分为反复出现的或非反复出现的。反复出现的CNV两侧是低拷贝重复序列，且大小固定。它们是由于减数分裂过程中通过一种名为非等位基因同源重组的机制发生错配而产生的。一些这样的反复出现的CNV已与人类疾病相关联。非反复出现的CNV两侧没有低拷贝重复序列，大小可变，可能通过诸如非同源末端连接以及由叉停滞和模板切换以及微同源性介导的断裂诱导复制模型所描述的基于复制的机制产生。现在越来越清楚的是，大多数致病CNV是非反复出现的，并且通常通过基于复制的机制产生。此外，现在人们认识到，除了低拷贝重复序列之外的基因组特征在非反复出现的CNV的形成中也起作用。本综述将讨论CNV形成的不同机制，以及对CNV断点的高分辨率分析如何增进我们对其精确结构的了解。
