Chromosomal structural variation (SV) encompasses a heterogenous class of genetic variants that exerts strong influences on human health and disease. Despite their importance, many structural variants (SVs) have remained poorly characterized at even a basic level, a discrepancy predicated upon the technical limitations of prior genomic assays. However, recent advances in genomic technology can identify and localize SVs accurately, opening new questions regarding SV risk factors and their impacts in humans. Here, we first define and classify human SVs and their generative mechanisms, highlighting characteristics leveraged by various SV assays. We next examine the first-ever gapless assembly of the human genome and the technical process of assembling it, which required third-generation sequencing technologies to resolve structurally complex loci. The new portions of that “telomere-to-telomere” and subsequent pangenome assemblies highlight aspects of SV biology likely to develop in the near-term. We consider the strengths and limitations of the most promising new SV technologies and when they or longstanding approaches are best suited to meeting salient goals in the study of human SV in population-scale genomics research, clinical, and public health contexts. It is a watershed time in our understanding of human SV when new approaches are expected to fundamentally change genomic applications.

染色体结构变异（SV）涵盖一类对人类健康和疾病产生强烈影响的异质遗传变异。尽管它们很重要，但许多结构变异（SV）在基本水平上仍然缺乏表征，这种差异是由于先前基因组测定的技术限制而造成的。然而，基因组技术的最新进展可以准确识别和定位 SV，从而提出了有关 SV 风险因素及其对人类影响的新问题。在这里，我们首先对人类 SV 及其生成机制进行定义和分类，突出显示各种 SV 检测所利用的特征。接下来，我们研究人类基因组的首次无间隙组装及其组装的技术过程，这需要第三代测序技术来解析结构复杂的基因座。“端粒到端粒”的新部分和随后的全基因组组装突出了 SV 生物学可能在短期内发展的各个方面。我们考虑最有前途的新型 SV 技术的优点和局限性，以及它们或长期方法何时最适合实现人口规模基因组学研究、临床和公共卫生背景下人类 SV 研究的显着目标。这是我们对人类 SV 理解的一个分水岭，新方法有望从根本上改变基因组应用。