Structural variation, such as deletions, duplications, inversions and complex rearrangements, can have profound effects on gene expression, genome stability, phenotypic diversity and disease susceptibility. Structural variants can encompass up to millions of bases and have the potential to rearrange substantial segments of the genome. They contribute considerably more to genetic diversity in human populations and have larger effects on phenotypic traits than point mutations. Until recently, our understanding of the effects of structural variants was driven mainly by studying naturally occurring variation. New genome-engineering tools capable of generating deletions, insertions, inversions and translocations, together with the discovery of new recombinases and advances in creating synthetic DNA constructs, now enable the design and generation of an extended range of structural variation. Here, we discuss these tools and examples of their application and highlight existing challenges that will need to be overcome to fully harness their potential.

结构变异，如缺失、重复、倒位和复杂的重排，会对基因表达、基因组稳定性、表型多样性和疾病易感性产生深远影响。结构变异可以包含多达数百万个碱基，并有可能重新排列基因组的大部分片段。它们对人类群体的遗传多样性的贡献要大得多，并且对表型性状的影响比点突变更大。直到最近，我们对结构变异影响的理解主要是通过研究自然发生的变异来推动的。能够产生缺失、插入、倒位和易位的新型基因组工程工具，以及新重组酶的发现和合成 DNA 构建体的进步，现在能够设计和生成更广泛的结构变异。在这里，我们讨论了这些工具及其应用示例，并重点介绍了需要克服的现有挑战，以充分利用其潜力。