Differentiated adaptative genetic architecture and language-related demographical history in South China inferred from 619 genomes from 56 populations

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 6, 2024

Abstract Background The underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding genetic formation, admixture, adaptive features. Besides, linguistical evidence supported controversial hypothesis origin processes. One hotspot case was Guangxi Pinghua Han people (GPH), whose language significantly similar to dialects but uniparental gene pool phylogenetically associated with indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data 619 four families 56 geographically different populations, which 261 21 distinct were first reported here. Results We identified significant population stratification among ethnolinguistically diverse suggesting differentiated admixture GPH shared more alleles related Zhuang than received northern ancestry relative Zhuang. Admixture models estimates distances showed that had a close relationship TK compared Northern Chinese, supporting hypothesis. Further time demographic history reconstruction formed via between robust signatures lipid metabolisms, such as fatty acid desaturases (FADS) medically relevant loci Mendelian disorder (GJB2) complex diseases. also explored unique selection ethnically linguistically lineages found some signals immune malaria resistance. Conclusions Our analysis illuminated language-related fine-scale structure provided support can explain pattern observed diversity formation GPH. This work presented one comprehensive focused on demographical adaptative process, for personal management disease risk prediction large-scale whole-genome sequencing projects would provide entire landscape southern contributions traits.

Language: Английский

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Reaction Pathway Differentiation Enabled Fingerprinting Signal for Single Nucleotide Variant Detection

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Accurate identification of single‐nucleotide variants (SNVs) is paramount for disease diagnosis. Despite the facile design DNA hybridization probes, their limited specificity poses challenges in clinical applications. Here, a differential reaction pathway probe (DRPP) based on dynamic network presented. DRPP leverages differences intermediate concentrations between SNV and WT groups, directing them into distinct pathways. This generates strong pulse‐like signal weak unidirectional increase wild‐type (WT). Through application machine learning to fluorescence kinetic data analysis, classification signals automated with an accuracy 99.6%, significantly exceeding 80.7% conventional methods. Additionally, sensitivity variant allele frequency (VAF) enhanced down 0.1%, representing ten‐fold improvement over approaches. accurately identified D614G N501Y SNVs S gene SARS‐CoV‐2 patient swab samples 99% (n = 82). It determined VAF ovarian cancer‐related mutations KRAS‐G12R , NRAS‐G12C BRAF‐V600E both tissue blood 77), discriminating cancer patients healthy individuals significant difference ( p < 0.001). The potential integration diagnostics, along rapid amplification techniques, holds promise early diagnostics personalized diagnostics.

Language: Английский

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Leukocyte telomere length in children born following blastocyst-stage embryo transfer

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(12), P. 2646 - 2653

Published: Dec. 1, 2022

Language: Английский

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Si Jun Zi decoction inhibits the growth of lung cancer by reducing the expression of PD-L1 through TLR4/MyD88/NF-κB pathway

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 318, P. 116948 - 116948

Published: July 22, 2023

Language: Английский

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Whole-genome sequencing identifies novel loci for keratoconus and facilitates risk stratification in a Han Chinese population

Eye and Vision, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 6, 2025

Abstract Background Keratoconus (KC) is a prevalent corneal condition with modest genetic basis. Recent studies have reported significant associations in multi-ethnic cohorts. However, the situation Chinese population remains unknown. This study was conducted to identify novel variants linked KC and evaluate potential applicability of polygenic risk model Han population. Methods A total 830 individuals diagnosed 779 controls from cohort were enrolled genotyped by whole-genome sequencing (WGS). Common rare respectively subjected single variant association analysis gene-based burden analysis. Polygenic score (PRS) models developed using top single-nucleotide polymorphisms (SNPs) identified meta-analysis then evaluated cohort. Results The characterization germline entailed correction for stratification validation East Asian ancestry included samples via principal component For protein-truncating (PTVs) minor allele frequency (MAF) < 5%, ZC3H11B emerged as prioritized gene, albeit failing reach significance threshold. We detected three common reaching genome-wide ( P ≤ 5 × 10 −8 ), all which are KC. Our validated well known predisposition loci, COL5A1 , EIF3A FNDC3B . Additionally, correlation allelic effects observed suggestive SNPs between largest meta-genome-wide (GWAS) our study. PRS model, generated meta-GWAS, stratified upper quartile, revealing up 2.16-fold increased Conclusions comprehensive WGS-based GWAS large enhances efficiency array-based studies, highlighting refining clinical decision-making early prevention strategies.

Language: Английский

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YHSeqY3000 panel captures all founding lineages in the Chinese paternal genomic diversity database

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 21, 2025

The advancements in second-/third-generation sequencing technologies, alongside computational innovations, have significantly enhanced our understanding of the genomic structure Y-chromosomes and their unique phylogenetic characteristics. These researches, despite challenges posed by lack population-scale databases, potential to revolutionize approach high-resolution, population-specific Y-chromosome panels databases for anthropological forensic applications. This study aimed develop highest-resolution Y-targeted panel, utilizing time-stamped, core informative mutations identified from high-coverage sequences YanHuang cohort. panel is intended provide a new tool complex pedigree search paternal biogeographical ancestry inference, as well explore general patterns fine-scale evolutionary history ethnolinguistically diverse Chinese populations. performance East Asian-specific Y-chromosomal including 2999-core SNP variants, was found be robust reliable. YHSeqY3000 designed capture genetic diversity lineages 3500 years ago, identifying 408 terminal 2097 individuals across 41 genetically geographically distinct We substructure that correlating with ancient population migrations expansions. New evidence provided extensive gene flow events between minority ethnic groups Han people, based on integrative Paternal Genomic Diversity Database. work successfully integrated Y-chromosome-related basic science translational applications, emphasizing necessity comprehensively characterizing genomically under-representative particularly important second phase medical or cohorts, where dense sampling strategies are employed.

Language: Английский

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Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer

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

Published: Feb. 6, 2025

Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal and improve disease risk prediction. Here, we applied massively parallel reporter assays perform NSCLC variant-to-function mapping at scale. A total 1249 candidate were evaluated, 30 potential within 12 loci identified. Accordingly, proposed three architectures underlying susceptibility: multiple in a single haplotype block (e.g. 4q22.1), blocks 5p15.33), variant 20q11.23). We developed modified polygenic score using from Chinese populations, improving performance prediction 450,821 Europeans UK Biobank. Our findings not only augment understanding architecture susceptibility but also provide strategy advance stratification. Determining GWAS crucial for mechanisms. authors apply MPRA (NSCLC) scale propose distinct susceptibility.

Language: Английский

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Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 5, 2025

Non-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has largely unknown genetic basis across ancestries. To our knowledge, this is the first trans-ethnic meta-analysis genome-wide association studies on SPGF, involving 2255 men with idiopathic SPGF and 3608 controls from European Asian populations. Using logistic regression inverse variance methods, we identify two significant associations Sertoli cell-only (SCO) syndrome, most extreme phenotype. The G allele rs34915133, in major histocompatibility complex class II region, significantly increases SCO risk (P = 5.25E-10, OR 1.57), supporting potential immune-related cause. Additionally, rs10842262 variant SOX5 gene region also marker 5.29E-09, 0.72), highlighting key role reproductive function. Our findings reveal shared factors ancestries provide insights into molecular mechanisms underlying SCO.

Language: Английский

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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

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Single-Cell eQTL Mapping Reveals Cell Type-Specific Genetic Regulation in Lung Cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Genome-wide association studies (GWAS) have identified over 50 lung cancer risk loci; however, the precise cellular context of these genetic mechanisms remains unclear due to limitations in bulk tissue eQTL analyses. Here, we present largest single-cell atlas human date, profiling 222 donors using multiplexed scRNA-seq. We 16,785 eQTLs across 17 cell types, with 90% sc-eQTLs and 59% eGene being cell-type-specific, fewer than 23% were detectable paired datasets. Integration GWAS for non-small highlighted epithelial immune cells as key contributors susceptibility, identifying 28 candidate genes within known loci 24 novel regions. Notably, 47% established NSCLC susceptibility exhibited cell-type-specific pleiotropic regulation. This study provides a valuable resource illuminates how variation modulates gene expression fashion, contributing susceptibility.

Language: Английский

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