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

BMC Biology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 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.

Язык: Английский

---

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

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 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.

Язык: Английский

---

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

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Апрель 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.

Язык: Английский

---

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

The Innovation Life, Год журнала: 2025, Номер unknown, С. 100131 - 100131

Опубликована: Янв. 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>

Язык: Английский

---

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 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.

Язык: Английский

---

Professionalism vs. engagement: quality of SSc information on WeChat

Frontiers in Public Health, Год журнала: 2025, Номер 13

Опубликована: Май 14, 2025

Background Systemic sclerosis (SSc) is a rare autoimmune disease, and WeChat major source of health information in China. This study assesses the quality SSc on to understand its impact public knowledge engagement. Methods A total 375 articles from 9 accounts were systematically analyzed using DISCERN Global Quality Scale (GQS) tools. Article was evaluated based credibility, content accuracy, user engagement, including metrics such as views, likes, comments. Results Individual authors posted 50% articles, while non-profit organizations 21%, with non-profits providing higher content. Disease dominated (52.8%), yet readers showed interest policy interpretation rehabilitation. The average GQS scores 28.96 1.62, indicating low across articles. Conclusion While facilitates dissemination, overall lacking. Enhancing professionalism interactivity platforms like could better meet needs patients for reliable information.

Язык: Английский

---

Paternal genomic resources from the YanHuang cohort suggested a Weakly-Differentiated Multi-source Admixture model for the formation of Han’s founding ancestral lineages

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 13, 2023

Abstract The large-scale human genome revolution and rapidly advanced statistical innovation have updated our understanding of the fine-scale complex genetic structure, entire landscape diversity evolutionary trajectories spatiotemporally different ancients ethnolinguistically diverse modern populations. Recent ancient DNA research provided a detailed admixture picture Europeans but limited insights into East Asians as few available genomes. Y-chromosome variations in male-specific regions, served molecular archaeological tool, unique features that can be utilized to reconstruct origin subsequent interaction Asian paternal lineages. We launched YanHuang cohort using designed highest-resolution capture sequencing panel explore trajectory Han Chinese, one largest ethnic groups world. reported uniparental genomic resources observed multiple founding lineages dominant western Eurasian, Siberian participating formation gene pool Chinese. identified structure correlated with patterns population geographical mountain barriers (Qinling-Huaihe line Nanling Mountains), suggesting isolation-enhanced admixture-introduced differentiation enhanced complexity Chinese diversity. strong direct correlation between frequency proportion subsistence-related ancestry sources related pastoralists, Holocene Mongolian Plateau people Asians, reflecting migration events contributed finally novel most plausible admixture-by-admixture model, Weakly-Differentiated Multi-Source Admixture major mechanism illuminate pattern interactions ancestral Generally, we presented resource from cohort, portrayed model herders, hunter-gatherers farmers who participated

Язык: Английский

---

The design and implementation of natural population cohort study Biobank: A multiple-center project cooperation with medical consortia in Southwest China

Frontiers in Public Health, Год журнала: 2022, Номер 10

Опубликована: Дек. 1, 2022

Objective The West China Hospital of Sichuan University collaborated with regional medical consortia in Province to launch a natural population cohort study (NPCS) investigate the health status residents and collect public data southwest China. Methods Up 80,000 participants will be enrolled by NPCS from 11 over five years. Individuals are invited visit one participating fill out questionnaires, receive free exam, donate biospecimens upon enrolment. All facilities adhered standard operating procedures for collecting processing ensure uniformity (serum, lithium heparinized plasma, ethylene diamine tetraacetie acid buffy coat). Electronic Data Capture System, Picture Archiving Communication Laboratory Information Management Biospecimen Quality Control Biobank used sort classify clinical indices, imaging data, laboratory parameters, pre-analytical variables, biospecimen information, respectively. quality assurance control biobank “DAIDS Guidelines Good Clinical Practice Standards”. This project integrate high-dimensional multi-omics questionnaire environmental risk factors. Results An estimated 2,240,000 aliquots sample stored end study. These samples linked comprehensively collected parameters. Big analysis can implemented create predictive algorithms, explore pathogenesis mechanisms, uncover potential biomarkers, provide information on health. Conclusions an integrative approach research factors major chronic or endemic diseases key scientific evidence support formulation management policies

Язык: Английский

---

Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants

British Journal of Cancer, Год журнала: 2023, Номер 129(9), С. 1510 - 1515

Опубликована: Сен. 7, 2023

Язык: Английский

---

BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Май 16, 2023

Background Mutations in the human breast cancer susceptibility gene 2 (breast 2, BRCA2) increase risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)–ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially Programmed cell death-1 (PD-1) inhibitors have revolutionized treatment lung many cancers by destroying interaction between receptors with ligands tumor-immune microenvironment enabling T cells recognize attack cells. Case description In our study, we report a patient advanced BRCA2 squamous carcinoma who received platinum-based chemotherapy combined paclitaxel. Seven months later, disease progressed. mutations were detected peripheral blood next-generation sequencing. After Olaparib Cindilimab, was partial remission progression-free survival (PFS) lasted for 6 months, but developed immune renal damage. Conclusions This study adds clinical data mutant non-small demonstrating that has good response PARP inhibitors. It also serves as reminder there may still be some negative effects from targeted superimposed immunotherapy.

Язык: Английский

---