基于长读测序的1019种不同人类的结构变异，这一成果由欧洲分子生物学实验室Jan O. Korbel研究团队经过不懈努力而取得。这一研究成果发表在2025年7月23日出版的国际学术期刊《自然》上。

在这里，研究团队对1019人进行了长读序列测序，构建了一个覆盖了1000基因组计划中26个种群的中等覆盖抗性。整合线性和基于图谱的基因组分析，研究团队发现了超过10万个序列分辨的双等位基因SV，并对30万个串联重复序列的多等位基因变量数进行了基因分型，在基于短读的群体规模调查中推进了SV表征。小组描述了不同种群中的缺失、重复、插入和倒位。长分散核元件-1（L1）和SINE-VNTR-Alu (SVA) 的反转录转位活动介导5'或3'独特序列的转导，这取决于它们的强度和移动元件类别和位置。SV断点分析指出了一系列同源介导的过程有助于SV的形成和反复缺失事件。它们的开放获取抗性强调了长读测序在推进SV表征方面的价值，并能够指导患者基因组中的变异优先级。

据介绍，基因组结构变异（SVs）在遗传多样性和人类疾病中起着重要作用，但在人群规模的队列中仍未得到充分表征。

附：英文原文

Title: Structural variation in 1,019 diverse humans based on long-read sequencing

Author: Schloissnig, Siegfried, Pani, Samarendra, Ebler, Jana, Hain, Carsten, Tsapalou, Vasiliki, Sylev, Arda, Hther, Patrick, Ashraf, Hufsah, Prodanov, Timofey, Asparuhova, Mila, Magalhes, Hugo, Hps, Wolfram, Sotelo-Fonseca, Jesus Emiliano, Fitzgerald, Tomas, Santana-Garcia, Walter, Moreira-Pinhal, Ricardo, Hunt, Sarah, Prez-Llanos, Francy J., Wollenweber, Tassilo Erik, Sivalingam, Sugirthan, Wieczorek, Dagmar, Cceres, Mario, Gilissen, Christian, Birney, Ewan, Ding, Zhihao, Jensen, Jan Nygaard, Podduturi, Nikhil, Stutzki, Jan, Rodriguez-Martin, Bernardo, Rausch, Tobias, Marschall, Tobias, Korbel, Jan O.

Issue&Volume: 2025-07-23

Abstract: Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases1,2,3,4, yet remain under-characterized in population-scale cohorts5. Here we conducted long-read sequencing6 in 1,019 humans to construct an intermediate-coverage resource covering 26 populations from the 1000 Genomes Project. Integrating linear and graph genome-based analyses, we uncover over 100,000 sequence-resolved biallelic SVs and we genotype 300,000 multiallelic variable number of tandem repeats7, advancing SV characterization over short-read-based population-scale surveys3,4. We characterize deletions, duplications, insertions and inversions in distinct populations. Long interspersed nuclear element-1 (L1) and SINE-VNTR-Alu (SVA) retrotransposition activities mediate the transduction8,9 of unique sequence stretches in 5′ or 3′, depending on source mobile element class and locus. SV breakpoint analyses point to a spectrum of homology-mediated processes contributing to SV formation and recurrent deletion events. Our open-access resource underscores the value of long-read sequencing in advancing SV characterization and enables guiding variant prioritization in patient genomes.

DOI: 10.1038/s41586-025-09290-7

Source: https://www.nature.com/articles/s41586-025-09290-7