颜林林 (2025-07-26 13:41):
#paper doi:10.1038/s41586-025-09290-7, Nature, 2025, Structural variation in 1,019 diverse humans based on long-read sequencing. 这项工作相当于是“千人基因组项目的结构变异版”:基于千人基因组项目的1,019例代表性人群样本的中等深度长读长测序,构建了目前最全面的SV图谱之一。研究团队开发了SAGA分析框架,结合线性与图参考,系统地识别、分型并注释了超17万个SV位点,特别提升了插入、VNTR、多等位位点等此前难以准确解析的类型。文章从方法、数据到机制探索均具高完成度。其深入分析了SV在人群间的分布特征、形成机制(如NAHR、HDR、微同源介导修复等),以及移动元件转导事件的谱系和位点偏好,提供了关于SV发生、演化与功能影响的一系列重要观察。相比此前基于短读长的研究,本项目对稀有变异、多态性、反复事件等均有数量级上的提升。最终发布的pangenome资源,为今后的SV研究、图基因组方法开发和临床变异注释奠定了重要基础。整体现为“图基因组+长读长”模式在人群尺度研究中的一个范式转折点。对于SV感兴趣的,也可以深入研究和重复一下这篇文章中的方法。
IF:50.500Q1 Nature, 2025-7-23. DOI: 10.1038/s41586-025-09290-7 PMID: 40702182
Structural variation in 1,019 diverse humans based on long-read sequencing
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Abstract:
Abstract Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases1–4, 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.
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