Language
English
Publication Date
2-10-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-56661-9
PMID
39929826
PMCID
PMC11811171
PubMedCentral® Posted Date
2-10-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Genomic structural variants (SVs) are a major source of genetic diversity in humans. Here, through long-read sequencing of 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 as two humanized mouse models, we demonstrate the causal roles of two SVs: one SV that emerges at the common ancestor of modern humans, Neanderthals, and Denisovans in GSDMD for bone mineral density and one modern-human-specific SV in WWP2 impacting height, weight, fat, craniofacial phenotypes and immunity. Our results suggest that the GSDMD SV could serve as a rapid and cost-effective biomarker for assessing the risk of cisplatin-induced acute kidney injury. The functional conservation from human to mouse and widespread signals of positive natural selection suggest that both SVs likely influence local adaptation, phenotypic diversity, and disease susceptibility across diverse human populations.
Keywords
Animals, Female, Humans, Male, Mice, China, Genetic Predisposition to Disease, Genome, Human, Genomic Structural Variation, Neanderthals, Phenotype, East Asian People, Functional genomics, Structural variation, Evolutionary genetics
Published Open-Access
yes
Recommended Citation
Gong, Jiao; Sun, Huiru; Wang, Kaiyuan; et al., "Long-Read Sequencing of 945 Han Individuals Identifies Structural Variants Associated With Phenotypic Diversity and Disease Susceptibility" (2025). Faculty and Staff Publications. 5119.
https://digitalcommons.library.tmc.edu/baylor_docs/5119
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons