Human Structural Variation: Mechanisms of Chromosome Rearrangements.
Human Structural Variation: Mechanisms of Chromosome Rearrangements.
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DOI：
10.1016/j.tig.2015.05.010
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Rudd MK
中科院分区：
文献类型：
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作者：
Weckselblatt B;Rudd MK
染色体结构变异（SV）是人类基因组变异的正常部分，但某些类型的SV可导致神经发育障碍。在SV断裂点的DNA序列分析可以揭示染色体重排的突变机制和风险因素。最近，由于包括全基因组测序（WGS）在内的下一代测序（NGS）的进步，大规模SV断裂点研究已经成为可能。这些发现揭示了SV的复杂形式，如三倍体、反向重复、插入易位和染色体断裂。序列水平的断点数据解析SV结构，并确定基因如何被断点破坏、融合和/或误调节。断裂点测序的最新改进也揭示了旁系同源长散布核元件（LINE）或人内源性逆转录病毒（HERV）重复之间的非等位基因同源重组（NAHR）是缺失、重复和易位的原因。本文综述了简单和复杂的宪法SV的基因组组织，以及它们形成的分子机制。
Chromosome structural variation (SV) is a normal part of variation in the human genome, but some classes of SV can cause neurodevelopmental disorders. Analysis of the DNA sequence at SV breakpoints can reveal mutational mechanisms and risk factors for chromosome rearrangement. Large-scale SV breakpoint studies have become possible recently owing to advances in next-generation sequencing (NGS) including whole-genome sequencing (WGS). These findings have shed light on complex forms of SV such as triplications, inverted duplications, insertional translocations, and chromothripsis. Sequence-level breakpoint data resolve SV structure and determine how genes are disrupted, fused, and/or misregulated by breakpoints. Recent improvements in breakpoint sequencing have also revealed non-allelic homologous recombination (NAHR) between paralogous long interspersed nuclear element (LINE) or human endogenous retrovirus (HERV) repeats as a cause of deletions, duplications, and translocations. This review covers the genomic organization of simple and complex constitutional SVs, as well as the molecular mechanisms of their formation.