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

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 10, 2025

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.

Language: Английский

Genome-driven Chinese precision medicine: Biobank-scale genomic research as a new paradigm

The Innovation Life, Journal Year: 2025, Volume and Issue: unknown, P. 100131 - 100131

Published: Jan. 1, 2025

<p>Large-scale genomic resources from biobank sequencing projects are crucial for understanding the interplay between environmental and genetic factors in human disease health traits, as well reconstructing evolutionary history. We summarize recent advances cohorts highlight opportunities non-Eurocentric populations a multidisciplinary perspective. Initiatives like UK100K, All of Us, TOPMed precision medicine programs have shifted research paradigms problem-derived to data-driven approaches, enhancing our architecture diseases Europeans their descendants. However, biases persist, such Han bias Chinese focused on medical anthropological purposes. These contribute global inequalities disparities medicine. Evolutionary studies modern ancient genomes provide new insights into history adaptive trajectories critical mutations. findings underscore importance personal genome tailored ethnolinguistically genetically diverse populations. This strategy is vital assessing burden etiology disease. Our work emphasizes need include underrepresented diversity create comprehensive catalog variations understand biological implications.</p>

Language: Английский

A Long-read based Haplotype Panel Enhances Imputation and Discovery of Functional Small and Structural Variants

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Haplotype reference panels are commonly used for genotype imputation in genome-wide association studies (GWAS). Although structural variations (SVs) recognized as major contributors to human phenotypes, they often excluded from GWAS analyses. Here, we integrate long-read-based and statistical methods provide a comprehensive haplotype panel (Han-SV panel) incorporating 32,603,300 single nucleotide variants (SNPs), 3,180,227 small deletions insertions 172,569 SVs derived 943 Han Chinese individuals. Our hybrid phasing approach had 12.7-fold reduction error 3.6-fold compared conventional phasing. This Han-SV enabled more than two-fold amount four-fold accuracy improvement of SV the expanded 1000 Genomes Project panel. Two GWASs using our panel-imputed identified 69 associated 101 previously unreported regions with skin-related fingerprint phenotypes—substantially outperforming both short-read SNP-array-based GWAS. offers valuable resource variant SV-included further uncover novel phenotype associations address critical gaps missing heritability. An server was provided use (https://www.biosino.org/svrp).

Language: Английский