Abstract：
Based on classical karyotyping, structural genome variations (SVs) have generally been considered to be either \"simple\" (with one or two breakpoints) or \"complex\" (with more than two breakpoints). Studying the breakpoints of SVs at nucleotide resolution revealed additional, subtle structural variations, such that even \"simple\" SVs turned out to be \"complex.\" Genome-wide sequencing methods, such as fosmid and paired-end mapping, short-read and long-read whole genome sequencing, and single-molecule optical mapping, also indicated that the number of SVs per individual was considerably larger than expected from karyotyping and high-resolution chromosomal array-based studies. Interestingly, SVs were detected in studies of cohorts of individuals without clinical phenotypes. The common denominator of all SVs appears to be a failure to accurately repair DNA double-strand breaks (DSBs) or to halt cell cycle progression if DSBs persist. This review discusses the various DSB response mechanisms during the mitotic cell cycle and during meiosis and their regulation. Emphasis is given to the molecular mechanisms involved in the formation of translocations, deletions, duplications, and inversions during or shortly after meiosis I. Recently, CRISPR-Cas9 studies have provided unexpected insights into the formation of translocations and chromothripsis by both breakage-fusion-bridge and micronucleus-dependent mechanisms.
摘要：
基于经典的核型分析，结构基因组变异（SV）通常被认为是“简单”（具有一个或两个断点）或“复杂”（具有两个以上断点）。在核苷酸分辨率下研究SV的断点揭示了额外的，微妙的结构变化，这样，即使是“简单的”SV也被证明是“复杂的”。“全基因组测序方法，如fosmid和配对端映射，短读和长读全基因组测序，和单分子光学绘图，还表明,从核型分析和基于高分辨率染色体阵列的研究中,每个个体的SV数量显著大于预期.有趣的是,在没有临床表型的个体队列的研究中检测到SV。所有SV的共同点似乎是无法准确修复DNA双链断裂（DSB）或如果DSB持续存在则无法停止细胞周期进程。这篇综述讨论了有丝分裂细胞周期和减数分裂过程中的各种DSB反应机制及其调控。重点是易位形成中涉及的分子机制，删除,重复,以及减数分裂期间或之后不久的倒置。最近，CRISPR-Cas9研究通过断裂-融合桥和微核依赖性机制提供了对易位和色素沉着形成的意想不到的见解。
