Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility

• DOI: 10.1038/s41467-025-56661-9
• Publication Date: 2025-02-10T11:41:12Z
• Authors: Jiao Gong; Huiru Sun; Kaiyuan Wang; Yanhui Zhao; Yechao Huang; Qinsheng Chen; Hui Qiao; Yang Gao; Jialin Zhao; Yunchao Ling; Ruifang Cao; Jingze Tan; Qi Wang; Yanyun Ma; Jing Li; Jingchun Luo; Sijia Wang; Jiucun Wang; Guoqing Zhang; Shuhua Xu; Feng Qian; Fang Zhou; Huiru Tang; Dali Li; ; Fritz J. Sedlazeck; Li Jin; Yuting Guan; Shaohua Fan
• Keywords: Human genetic variation; Negative selection

Genomic structural variants (SVs) are a major source of genetic diversity in humans. Here, through long-read sequencing 945 Han Chinese genomes, we identify 111,288 SVs, including 24.56% unreported variants, many with predicted functional importance. By integrating human population-level phenotypic and multi-omics data as well two humanized mouse models, demonstrate the causal roles SVs: one SV that emerges at common ancestor modern humans, Neanderthals, Denisovans GSDMD for bone mineral density modern-human-specific WWP2 impacting height, weight, fat, craniofacial phenotypes immunity. Our results suggest could serve rapid cost-effective biomarker assessing risk cisplatin-induced acute kidney injury. The conservation from to widespread signals positive natural selection both SVs likely influence local adaptation, diversity, disease susceptibility across diverse populations. Genetic studies individuals have been performed, but mostly short read sequencing, limiting types can be identified. authors perform long han individuals, finding under those associated traits evolutionary history.