Genetic genealogy provides crucial insights into the complex biological relationships within contemporary and ancient human populations by analyzing shared alleles and chromosomal segments that are identical by descen...Genetic genealogy provides crucial insights into the complex biological relationships within contemporary and ancient human populations by analyzing shared alleles and chromosomal segments that are identical by descent to understand kinship,migration patterns,and population dynamics.Within forensic science,forensic investigative genetic genealogy(FIGG)has gained prominence by leveraging next-generation sequencing technologies and population-specific genomic resources,opening useful investigative avenues.In this review,we synthesize current knowledge,underscore recent advancements,and discuss the growing role of FIGG in forensic genomics.FIGG has been pivotal in revitalizing dormant inquiries and offering genetic leads in numerous cold cases.Its effectiveness relies on the extensive single-nucleotide polymorphism profiles contributed by individuals from diverse populations to specialized genomic databases.Advances in computational genomics and the growth of human genomic databases have spurred a profound shift in the application of genetic genealogy across forensics,anthropology,and ancient DNA studies.As the field progresses,FIGG is evolving from a nascent practice into a more sophisticated and specialized discipline,shaping the future of forensic investigations.展开更多
The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Centra...The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Central Plain.However,the extent to which Y-chromosome genetic legacies from nomadic emperor-related ancestral lineages influence the Chinese paternal gene pool remains unclear.Here,we genotype 2717 ethnolinguistically diverse samples belonging to C2a lineages,perform whole-genome sequencing on 997 representative samples,and integrate these data with ancient genomic sequences.We reconstruct the evolutionary histories of Northern Zhou-,Qing emperor-,and pastoralist-related lineages to assess their genetic impact on modern Chinese populations.This reassembled fine-scale Ychromosome phylogeny identifies deep divergence and five Neolithic expansion events contributing differently to the formation of northern Chinese populations.Phylogeographic modeling indicates that the nomadic empires of the Northern Zhou and Qing dynasties genetically originated from the Mongolian Plateau.Phylogenetic topology and shared haplotype patterns show that three upstream ancestors of Northern Zhou(C2a1a1b1a2a1b-FGC28857),Donghu tribe(C2a1a1b1-F1756),and Qing(C2a1a3a2-F10283)emperor-related lineages expanded during the middle Neolithic,contributing significantly to genetic flow between ancient northeastern Asians and modern East Asians.Notably,this study reveals limited direct contributions of Emperor Wu of Northern Zhou’s lineages to modern East Asians.展开更多
Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period...Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period.However,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain unknown.Here,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking people.We identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis.We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers.Adaptative signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in Tibetan.TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.展开更多
Human mitochondrial DNA(mt DNA)harbors essential mutations linked to aging,neurodegenerative diseases,and complex muscle disorders.Due to its uniparental and haploid inheritance,mt DNA captures matrilineal evolutionar...Human mitochondrial DNA(mt DNA)harbors essential mutations linked to aging,neurodegenerative diseases,and complex muscle disorders.Due to its uniparental and haploid inheritance,mt DNA captures matrilineal evolutionary trajectories,playing a crucial role in population and medical genetics.However,critical questions about the genomic diversity patterns,inheritance models,and evolutionary and medical functions of mt DNA remain unresolved or underexplored,particularly in the transition from traditional genotyping to largescale genomic analyses.This review summarizes recent advancements in data-driven genomic research and technological innovations that address these questions and clarify the biological impact of nuclear-mitochondrial segments(NUMTs)and mt DNA variants on human health,disease,and evolution.We propose a streamlined pipeline to comprehensively identify mt DNA and NUMT genomic diversity using advanced sequencing and computational technologies.Haplotype-resolved mt DNA sequencing and assembly can distinguish authentic mt DNA variants from NUMTs,reduce diagnostic inaccuracies,and provide clearer insights into heteroplasmy patterns and the authenticity of paternal inheritance.This review emphasizes the need for integrative multi-omics approaches and emerging long-read sequencing technologies to gain new insights into mutation mechanisms,the influence of heteroplasmy and paternal inheritance on mt DNA diversity and disease susceptibility,and the detailed functions of NUMTs.展开更多
Rapid advances in sequencing and bioinformatics have profoundly enhanced disease understanding[1],while integrated genomic analyses reveal regulatory networks governing biological processes[2].However,research remains...Rapid advances in sequencing and bioinformatics have profoundly enhanced disease understanding[1],while integrated genomic analyses reveal regulatory networks governing biological processes[2].However,research remains disproportionately focused on populations of European ancestry or other groups with large sample sizes,such as Han Chinese,leaving many ethnically diverse and underrepresented populations disadvantaged in genomic medicine[3].Complex human demographic processes influence allele frequencies,define gene sets under selective constraints,and inform variant-filtering strategies crucial for genetic disease diagnosis and genetic counseling.This imbalance limits the global applicability of genomic findings and exacerbates existing health disparities.By prioritizing high-quality genome sequencing from underrepresented populations,researchers can uncover novel genetic variants,refine disease risk predictions,and promote equitable access to precision medicine.展开更多
Genomic research has been constrained by insufficient diversity over the past two decades,with over 90%of studies targeting populations of European ancestry.This imbalance has hampered health equity and precision medi...Genomic research has been constrained by insufficient diversity over the past two decades,with over 90%of studies targeting populations of European ancestry.This imbalance has hampered health equity and precision medicine,resulting in limited transferability of polygenic risk scores to underrepresented populations and misinterpretations of the pathogenicity of genomic variants.Recent advancements in sequencing technology have enabled the implementation of large-scale,high-quality,diverse,multi-omics,and engineered genomic projects,including the All of Us Research Program and the Trans-Omics for Precision Medicine Program.Coupled with the widespread adoption of electronic health records,wearable devices,and AI,the translation of these findings into clinical practice has been established for disease prediction,surveillance,and treatment across the lifespan.Here,a concise overview of the recent revolution in human genomic research is provided,emphasizing how these projects,in the era of large-scale whole-genome sequencing,have advanced genomic science,genomic medicine,and evolutionary genomics,as well as their clinical translational applications in disease prediction,cancer,drug response,and rare disease diagnosis.展开更多
Genomic sources from China are underrepresented in the population-specific reference database.We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups...Genomic sources from China are underrepresented in the population-specific reference database.We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups(1,081 Sinitic,56 Mongolic,40 Turkic,and 30Tibeto-Burman people)living in North China included in the 10K Chinese People Genomic Diversity Project(10K_CPGDP)to characterize the genetic architecture and adaptative history of ethnic groups in the Silk Road Region of China.We observed a population split between Northwest Chinese minorities(NWCMs)and Han Chinese since the Upper Paleolithic and later Neolithic genetic differentiation within NWCMs.The observed population substructures among ethnically/linguistically diverse NWCMs suggested that differentiated admixture events contributed to the differences in their genomic and phenotypic diversity.We estimated that the Dongxiang,Tibetan,and Yugur people inherited more than 10%of the Western Eurasian ancestry,which is much greater than that of the Salar and Tu people(<7%),while Han neighbors showed less West Eurasian ancestry(~1%-3%).Male-biased admixture introduced Western Eurasian ancestry in the Dongxiang,Tibetan,and Yugur populations.We found that the eastern-western admixture in NWCMs occurred~800-1,100 years ago,coinciding with intensive economic and cultural exchanges during the Tang and Song dynasties.Additionally,we identified the signatures of natural selection associated with cardiovascular system diseases or lipid metabolism and developmental/neurogenetic disorders.Moreover,the EPAS1 gene showed relatively high population branch statistic values in NWCMs.The well-fitted demographical models presented the vast landscape of complex admixture processes of the Silk Road people,and the newly reported functionally important variations suggested the importance of including ethnolinguistically diverse populations in Chinese genetic studies for uncovering the genetic basis of complex traits/diseases.展开更多
Central Asia,a crucible of prehistoric and historical Trans-Eurasian interactions,has been pivotal in shaping cultural exchanges,population dynamics,and genetic admixture.Recent insights from ancient DNA studies have ...Central Asia,a crucible of prehistoric and historical Trans-Eurasian interactions,has been pivotal in shaping cultural exchanges,population dynamics,and genetic admixture.Recent insights from ancient DNA studies have shed light on the extensive population turnover within this region,encompassing a spectrum of groups from Paleolithic huntergatherers to Holocene herders and the nomadic pastoralist empires of historical times.The genomic analysis of ancient pathogens across the Eurasian steppe has further deepened our understanding of pathogen origins,clonal expansions,and the intricate processes of host-pathogen coevolution in relation to varying pathogen exposures and their spread.We consolidate the latest findings pertaining to the ancient human and pathogen genomes of Central Asia,elucidating their profound influence on the genomic tapestry of contemporary Central Asians.A notable gap in the current genomic databases for Central Asia is underscored,particularly within the scope of genomics-driven precision medicine.We stress the urgent need for the development of extensive,region-specific genomic resources that hold promise for revealing the genetic blueprints underlying human traits and diseases,refining polygenic scoring models for predictive medicine,and bolstering genomic research endeavors across Central Asia.展开更多
Complex demographic processes and natural selection pressures are critical to resolving patterns of the molecular genetic basis of adaptive traits or complex diseases.Recent ancient genome data allow us to trace how k...Complex demographic processes and natural selection pressures are critical to resolving patterns of the molecular genetic basis of adaptive traits or complex diseases.Recent ancient genome data allow us to trace how key traits evolved in different human populations over time,connecting ancient population history with disease susceptibility in western Eurasians.To fill this gap in eastern Eurasians and provide deep insights into the evolutionary history of the populationspecific genetic basis of complex biological traits,we explored the evolutionary basis of adaptive traits in one integrative modern and ancient genomic database,including 225 out of 5583 genomes first reported here.We comprehensively characterized the demographic history and biological adaptation of Han Chinese individuals on the Mongolian Plateau based on the allele frequency spectrum and haplotype-resolved fragments.We found strong genetic homogeneity among geographically different Han populations from Inner Mongolia(IMH).We reconstructed their admixture models and demographic events,revealing that IMH had a close genetic relationship with ancient millet farmers and obtained additional gene flow from Altaic-speaking populations.The enrichment of selected candidate genes suggested that essential metabolism-related genes promoted the rapid adaptation of eastern Eurasians to ancient environmental shifts and dietary changes during agricultural innovations.Evolutionary trajectory reconstruction of metabolism-related genes of methylenetetrahydrofolate reductase(MTHFR)and fatty acid desaturase 1(FADS1)suggested that ancient dietary shifts during the Neolithic transition period promoted the differentiated metabolic rate of folate and fatty acid.We revealed the polygenicity of biological adaptation traits and the pleiotropy of adaptive genes,indicating that complex recent polygenic adaptations,genetic interactions,and genotype–phenotype correlations have contributed to the genetic architecture of complex traits in eastern Eurasians.展开更多
The levels of dopamine(DA)in living organisms have strong effects on many biological processes and diseases,such as Parkinson's disease and Alzheimer's disease.Therefore,it has great significance for sensitive...The levels of dopamine(DA)in living organisms have strong effects on many biological processes and diseases,such as Parkinson's disease and Alzheimer's disease.Therefore,it has great significance for sensitive and selective detection of DA.Herein,the AuPd@Fe_(2)O_(3) nanoparticles-based electrochemical(EC)sensor(AuPd@Fe_(2)O_(3) NPs/GCE)is developed for chronoamperometric detection of DA with high sensitivity and good anti-interference ability through simple immobilization of AuPd@Fe_(2)O_(3) nanoparticles on glassy carbon electrode(GCE)by Nafion.Under the application of oxidation potential,the AuPd@Fe_(2)O_(3) NPs/GCE exhibits good electrocatalytic activity toward DA,which enables to linearly detect DA in the range of 10 nM–831.61μM(R^(2)=0.9983).The AuPd@Fe_(2)O_(3) NPs/GCE also shows good selectivity and reproducibility for the detection of DA.Furthermore,the practicability of AuPd@Fe_(2)O_(3) NPs/GCE has been demonstrated by detection of DA in dopamine hydrochloride injection and human serum.展开更多
The analytical performance of H+-selective solid-contact ion-selective electrodes(SCISEs)based on solid contact polyaniline doped with chloride(PANI(Cl))and poly(3,4-ethylenedioxythiophene)doped with poly(styrene sulf...The analytical performance of H+-selective solid-contact ion-selective electrodes(SCISEs)based on solid contact polyaniline doped with chloride(PANI(Cl))and poly(3,4-ethylenedioxythiophene)doped with poly(styrene sulfonate)(PEDOT(PSS))was characterized by a developed coulometric signal transduction method.PEDOT(PSS)solid contact is covered by PVC based H+-selective membrane.The obtained coulometric signal demonstrates that the cumulated charge can be amplified by increasing the capacitance of solid contact.SCISEs covered with spin-coated membrane behave faster amperometric response than electrodes with drop-cast mem-brane.In contrast to earlier works,the amperometric response and impedance spectrum demonstrates H+transfer through SCISEs is independent from the thickness of membrane.The exceptional behavior of PANI(Cl)H+-SCISEs shows that the capacitance estimated from impedance spectrum at low frequency 10 mHz and coulometric signal of PANI(Cl)based SCISEs is influenced by the applied po-tentials,whereas PEDOT(PSS)solid contact is independent from the chosen applied potentials.Furthermore,preliminary investiga-tions of coulometric signal transduction on flexible pH sensor implies its potential applications in wearable sensors for sweat ion concentration detection.展开更多
The current understanding of the legacy and emerging organic pollutants in the soil of Bangladesh remains limited.Inadequate disposal practices,particularly in e-waste,landfills,and industrial operations,may lead to t...The current understanding of the legacy and emerging organic pollutants in the soil of Bangladesh remains limited.Inadequate disposal practices,particularly in e-waste,landfills,and industrial operations,may lead to the pervasive presence of persistent organic pollutants(POPs)and polycyclic aromatic hydrocarbons(PAHs)in the country.This study aimed to systematically investigate the concentrations,sources,and risk assessment of halogenated flame retardants(HFRs),polychlorinated biphenyls(PCBs),polychlorinated naphthalenes(PCNs),organochlorine pesticides(OCPs),chlorinated paraffins(CPs),and PAHs in the contaminated soil of Dhaka's dumpsites,e-waste,and industrial areas collected in 2017.The total concentration of investigated pollutants averaged at 4790±4040 ng g^(-1)dw,with the following order:P44CPs(4110±4140 ng g^(-1)dw)>P16PAHs(422±491 ng g^(-1)dw)>P16HFRs(190±538 ng g^(-1)dw)>P209PCBs(43.5±73.5 ng g^(-1)dw)>P50PCNs(17.7±21.0 ng g^(-1)dw)>P27OCPs(9.41±9.61 ng g^(-1)dw).The e-waste site exhibited the highest total concentration of the target pollutants,reaching 12,700 ng g1 dw.CPs were the predominant contributors,accounting for averages of 81.8%,70.5%,and 68.5%to waste landfills,e-waste,and industrial sites,respectively.A comprehensive analysis of 209 PCB congeners revealed their primary origin from Aroclor PCBs,with minor contributions from unintentionally produced PCBs.The highest incremental lifetime carcinogenic risk(ILCR)occurred in e-waste sites,contributed by dioxin-like PCBs,with a maximum value of 5.9×10^(-5)for adults,exceeding the limit 1.0×10^(-6)set by the U.S.EPA.The non-carcinogenic hazard quotients(HQs)were much lower,suggesting no significant risk from the investigated pollutants.Our findings highlight the importance of proper waste management and regulated e-waste recycling to mitigate potential hazardous risks to the Bangladeshi population.展开更多
基金supported by the National Natural Science Foundation of China(82202078)the Major Project of the National Social Science Foundation of China(23&ZD203)+3 种基金the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1‧3‧5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518).
文摘Genetic genealogy provides crucial insights into the complex biological relationships within contemporary and ancient human populations by analyzing shared alleles and chromosomal segments that are identical by descent to understand kinship,migration patterns,and population dynamics.Within forensic science,forensic investigative genetic genealogy(FIGG)has gained prominence by leveraging next-generation sequencing technologies and population-specific genomic resources,opening useful investigative avenues.In this review,we synthesize current knowledge,underscore recent advancements,and discuss the growing role of FIGG in forensic genomics.FIGG has been pivotal in revitalizing dormant inquiries and offering genetic leads in numerous cold cases.Its effectiveness relies on the extensive single-nucleotide polymorphism profiles contributed by individuals from diverse populations to specialized genomic databases.Advances in computational genomics and the growth of human genomic databases have spurred a profound shift in the application of genetic genealogy across forensics,anthropology,and ancient DNA studies.As the field progresses,FIGG is evolving from a nascent practice into a more sophisticated and specialized discipline,shaping the future of forensic investigations.
基金the financial support received from the National Natural Science Foundation of China(82202078)the National Social Science Foundation of China(23&ZD203)+4 种基金support for G.H.includes National Natural Science Foundation of China(82402203)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1‧3‧5 Project for Disciplines of Excellence at West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518).
文摘The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Central Plain.However,the extent to which Y-chromosome genetic legacies from nomadic emperor-related ancestral lineages influence the Chinese paternal gene pool remains unclear.Here,we genotype 2717 ethnolinguistically diverse samples belonging to C2a lineages,perform whole-genome sequencing on 997 representative samples,and integrate these data with ancient genomic sequences.We reconstruct the evolutionary histories of Northern Zhou-,Qing emperor-,and pastoralist-related lineages to assess their genetic impact on modern Chinese populations.This reassembled fine-scale Ychromosome phylogeny identifies deep divergence and five Neolithic expansion events contributing differently to the formation of northern Chinese populations.Phylogeographic modeling indicates that the nomadic empires of the Northern Zhou and Qing dynasties genetically originated from the Mongolian Plateau.Phylogenetic topology and shared haplotype patterns show that three upstream ancestors of Northern Zhou(C2a1a1b1a2a1b-FGC28857),Donghu tribe(C2a1a1b1-F1756),and Qing(C2a1a3a2-F10283)emperor-related lineages expanded during the middle Neolithic,contributing significantly to genetic flow between ancient northeastern Asians and modern East Asians.Notably,this study reveals limited direct contributions of Emperor Wu of Northern Zhou’s lineages to modern East Asians.
基金the National Natural Science Foundation of China(82202078)the Center for Archaeological Science of Sichuan University(23SASA01).
文摘Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period.However,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain unknown.Here,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking people.We identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis.We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers.Adaptative signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in Tibetan.TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.
基金supported by the National Natural Science Foundation of China(82202078 and 82402203)the National Natural Science Foundation of Chongqing(CSTB2024NSCQLZX0005)+4 种基金the Major Project of the National Social Science Foundation of China(23&ZD203)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518)。
文摘Human mitochondrial DNA(mt DNA)harbors essential mutations linked to aging,neurodegenerative diseases,and complex muscle disorders.Due to its uniparental and haploid inheritance,mt DNA captures matrilineal evolutionary trajectories,playing a crucial role in population and medical genetics.However,critical questions about the genomic diversity patterns,inheritance models,and evolutionary and medical functions of mt DNA remain unresolved or underexplored,particularly in the transition from traditional genotyping to largescale genomic analyses.This review summarizes recent advancements in data-driven genomic research and technological innovations that address these questions and clarify the biological impact of nuclear-mitochondrial segments(NUMTs)and mt DNA variants on human health,disease,and evolution.We propose a streamlined pipeline to comprehensively identify mt DNA and NUMT genomic diversity using advanced sequencing and computational technologies.Haplotype-resolved mt DNA sequencing and assembly can distinguish authentic mt DNA variants from NUMTs,reduce diagnostic inaccuracies,and provide clearer insights into heteroplasmy patterns and the authenticity of paternal inheritance.This review emphasizes the need for integrative multi-omics approaches and emerging long-read sequencing technologies to gain new insights into mutation mechanisms,the influence of heteroplasmy and paternal inheritance on mt DNA diversity and disease susceptibility,and the detailed functions of NUMTs.
基金supported by the Sichuan Science and Technology Program(grant number 2024NSFSC1518 to G.H.)the National Natural Science Foundation of China(grant number 82402203 to G.H.)+3 种基金the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(grant number ZYJC20002 to H.Y.)the Major Project of the National Social Science Foundation of China(grant number 23&ZD203 to G.H.)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(grant numbers 2022FGKFKT05 to G.H.and 2024FGKFKT02 to M.W.)the Center for Archaeological Science of Sichuan University(grant numbers 23SASA01 and 24SASB03 to G.H.).
文摘Rapid advances in sequencing and bioinformatics have profoundly enhanced disease understanding[1],while integrated genomic analyses reveal regulatory networks governing biological processes[2].However,research remains disproportionately focused on populations of European ancestry or other groups with large sample sizes,such as Han Chinese,leaving many ethnically diverse and underrepresented populations disadvantaged in genomic medicine[3].Complex human demographic processes influence allele frequencies,define gene sets under selective constraints,and inform variant-filtering strategies crucial for genetic disease diagnosis and genetic counseling.This imbalance limits the global applicability of genomic findings and exacerbates existing health disparities.By prioritizing high-quality genome sequencing from underrepresented populations,researchers can uncover novel genetic variants,refine disease risk predictions,and promote equitable access to precision medicine.
基金supported by the National Natural Science Foundation of China(82402203)the Major Project of the National Social Science Foundation of China(23&ZD203)+3 种基金the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518).
文摘Genomic research has been constrained by insufficient diversity over the past two decades,with over 90%of studies targeting populations of European ancestry.This imbalance has hampered health equity and precision medicine,resulting in limited transferability of polygenic risk scores to underrepresented populations and misinterpretations of the pathogenicity of genomic variants.Recent advancements in sequencing technology have enabled the implementation of large-scale,high-quality,diverse,multi-omics,and engineered genomic projects,including the All of Us Research Program and the Trans-Omics for Precision Medicine Program.Coupled with the widespread adoption of electronic health records,wearable devices,and AI,the translation of these findings into clinical practice has been established for disease prediction,surveillance,and treatment across the lifespan.Here,a concise overview of the recent revolution in human genomic research is provided,emphasizing how these projects,in the era of large-scale whole-genome sequencing,have advanced genomic science,genomic medicine,and evolutionary genomics,as well as their clinical translational applications in disease prediction,cancer,drug response,and rare disease diagnosis.
基金supported by the National Natural Science Foundation of China(82402203,82202078)the Major Project of the National Social Science Foundation of China(23&ZD203)+3 种基金the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05,2024FGKFKT02)the Center for Archaeological Science of Sichuan University(23SASA01)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518)。
文摘Genomic sources from China are underrepresented in the population-specific reference database.We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups(1,081 Sinitic,56 Mongolic,40 Turkic,and 30Tibeto-Burman people)living in North China included in the 10K Chinese People Genomic Diversity Project(10K_CPGDP)to characterize the genetic architecture and adaptative history of ethnic groups in the Silk Road Region of China.We observed a population split between Northwest Chinese minorities(NWCMs)and Han Chinese since the Upper Paleolithic and later Neolithic genetic differentiation within NWCMs.The observed population substructures among ethnically/linguistically diverse NWCMs suggested that differentiated admixture events contributed to the differences in their genomic and phenotypic diversity.We estimated that the Dongxiang,Tibetan,and Yugur people inherited more than 10%of the Western Eurasian ancestry,which is much greater than that of the Salar and Tu people(<7%),while Han neighbors showed less West Eurasian ancestry(~1%-3%).Male-biased admixture introduced Western Eurasian ancestry in the Dongxiang,Tibetan,and Yugur populations.We found that the eastern-western admixture in NWCMs occurred~800-1,100 years ago,coinciding with intensive economic and cultural exchanges during the Tang and Song dynasties.Additionally,we identified the signatures of natural selection associated with cardiovascular system diseases or lipid metabolism and developmental/neurogenetic disorders.Moreover,the EPAS1 gene showed relatively high population branch statistic values in NWCMs.The well-fitted demographical models presented the vast landscape of complex admixture processes of the Silk Road people,and the newly reported functionally important variations suggested the importance of including ethnolinguistically diverse populations in Chinese genetic studies for uncovering the genetic basis of complex traits/diseases.
基金supported by the National Natural Science Foundation of China(82202078)supported by the Major Project of the National Social Science Foundation of China(23&ZD203)+7 种基金the Open Project of the Key Laboratory of ForensicGenetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)supported by the 1‧3‧5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518)supported by the National Key Research and Development Program of China(No.2023YFC2605400)the National Natural Science Foundation of China(32288101,32030020)the Shanghai Science and Technology Commission Program(23JS1410100)the Office of Global Partnerships(Key Projects Development Fund).
文摘Central Asia,a crucible of prehistoric and historical Trans-Eurasian interactions,has been pivotal in shaping cultural exchanges,population dynamics,and genetic admixture.Recent insights from ancient DNA studies have shed light on the extensive population turnover within this region,encompassing a spectrum of groups from Paleolithic huntergatherers to Holocene herders and the nomadic pastoralist empires of historical times.The genomic analysis of ancient pathogens across the Eurasian steppe has further deepened our understanding of pathogen origins,clonal expansions,and the intricate processes of host-pathogen coevolution in relation to varying pathogen exposures and their spread.We consolidate the latest findings pertaining to the ancient human and pathogen genomes of Central Asia,elucidating their profound influence on the genomic tapestry of contemporary Central Asians.A notable gap in the current genomic databases for Central Asia is underscored,particularly within the scope of genomics-driven precision medicine.We stress the urgent need for the development of extensive,region-specific genomic resources that hold promise for revealing the genetic blueprints underlying human traits and diseases,refining polygenic scoring models for predictive medicine,and bolstering genomic research endeavors across Central Asia.
基金We thank all the volunteers who participated in this project and the researchers who provided help and support for this project(Prof.Etienne Patin and Prof.Lluis Quintana-Murci from the Human Evolutionary Genetics Unit of the Institute PasteurProf.Mark Stoneking and Prof.Dang Liu from the Max Planck Institute for Evolutionary Anthropology+5 种基金and Prof.Wibhu Kutanan from Khon Kaen University).We are indebted to Grammarly(https://app.grammarly.com/)for its invaluable contribution to the linguistic refinement and readability enhancement of this manuscript.M.W.is supported by the National Natural Science Foundation of China(82202078)G.H.is supported by the Major Project of the National Social Science Foundation of China(23&ZD203)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program.L.H.is supported by the Open Project of Shanghai Key Laboratory of Forensic Medicine(KF202309).
文摘Complex demographic processes and natural selection pressures are critical to resolving patterns of the molecular genetic basis of adaptive traits or complex diseases.Recent ancient genome data allow us to trace how key traits evolved in different human populations over time,connecting ancient population history with disease susceptibility in western Eurasians.To fill this gap in eastern Eurasians and provide deep insights into the evolutionary history of the populationspecific genetic basis of complex biological traits,we explored the evolutionary basis of adaptive traits in one integrative modern and ancient genomic database,including 225 out of 5583 genomes first reported here.We comprehensively characterized the demographic history and biological adaptation of Han Chinese individuals on the Mongolian Plateau based on the allele frequency spectrum and haplotype-resolved fragments.We found strong genetic homogeneity among geographically different Han populations from Inner Mongolia(IMH).We reconstructed their admixture models and demographic events,revealing that IMH had a close genetic relationship with ancient millet farmers and obtained additional gene flow from Altaic-speaking populations.The enrichment of selected candidate genes suggested that essential metabolism-related genes promoted the rapid adaptation of eastern Eurasians to ancient environmental shifts and dietary changes during agricultural innovations.Evolutionary trajectory reconstruction of metabolism-related genes of methylenetetrahydrofolate reductase(MTHFR)and fatty acid desaturase 1(FADS1)suggested that ancient dietary shifts during the Neolithic transition period promoted the differentiated metabolic rate of folate and fatty acid.We revealed the polygenicity of biological adaptation traits and the pleiotropy of adaptive genes,indicating that complex recent polygenic adaptations,genetic interactions,and genotype–phenotype correlations have contributed to the genetic architecture of complex traits in eastern Eurasians.
基金National Natural Science Foundation of China(Grant no.21974133).
文摘The levels of dopamine(DA)in living organisms have strong effects on many biological processes and diseases,such as Parkinson's disease and Alzheimer's disease.Therefore,it has great significance for sensitive and selective detection of DA.Herein,the AuPd@Fe_(2)O_(3) nanoparticles-based electrochemical(EC)sensor(AuPd@Fe_(2)O_(3) NPs/GCE)is developed for chronoamperometric detection of DA with high sensitivity and good anti-interference ability through simple immobilization of AuPd@Fe_(2)O_(3) nanoparticles on glassy carbon electrode(GCE)by Nafion.Under the application of oxidation potential,the AuPd@Fe_(2)O_(3) NPs/GCE exhibits good electrocatalytic activity toward DA,which enables to linearly detect DA in the range of 10 nM–831.61μM(R^(2)=0.9983).The AuPd@Fe_(2)O_(3) NPs/GCE also shows good selectivity and reproducibility for the detection of DA.Furthermore,the practicability of AuPd@Fe_(2)O_(3) NPs/GCE has been demonstrated by detection of DA in dopamine hydrochloride injection and human serum.
基金We are grateful to the National Natural Science Foundation of China(22172040,21974031 and 22204026)the Project Funded by China Postdoctoral Science Foundation(2022M710859)+2 种基金the Department of Science and Techniques of Guangdong Province(2021A1515010180,2019B010933001)Guangzhou Municipal Science and Technology Bureau(202102010449)the Department of Guangdong Provincial Public Security(GZQC20-PZ11-FD084)fortheirfinancial support of thiswork.
文摘The analytical performance of H+-selective solid-contact ion-selective electrodes(SCISEs)based on solid contact polyaniline doped with chloride(PANI(Cl))and poly(3,4-ethylenedioxythiophene)doped with poly(styrene sulfonate)(PEDOT(PSS))was characterized by a developed coulometric signal transduction method.PEDOT(PSS)solid contact is covered by PVC based H+-selective membrane.The obtained coulometric signal demonstrates that the cumulated charge can be amplified by increasing the capacitance of solid contact.SCISEs covered with spin-coated membrane behave faster amperometric response than electrodes with drop-cast mem-brane.In contrast to earlier works,the amperometric response and impedance spectrum demonstrates H+transfer through SCISEs is independent from the thickness of membrane.The exceptional behavior of PANI(Cl)H+-SCISEs shows that the capacitance estimated from impedance spectrum at low frequency 10 mHz and coulometric signal of PANI(Cl)based SCISEs is influenced by the applied po-tentials,whereas PEDOT(PSS)solid contact is independent from the chosen applied potentials.Furthermore,preliminary investiga-tions of coulometric signal transduction on flexible pH sensor implies its potential applications in wearable sensors for sweat ion concentration detection.
基金supported by the Alliance of International Science Organizations(Grant No.ANSO-CR-KP-2021-05)the National Natural Science Foundation of China(42107120)+4 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A0505020017,2023B1515020067 and 2023B0303000007)the Youth Innovation Promotion Association of CAS(2022359)the Tuguangchi Award for Excellent Young Scholar GIG(TGC202204)the CAS-TWAS President's Fellowship Programs(2018A8016537001)the Chinese Academy of Sciences President's International Fellowship Initiative(2024VCA0015).
文摘The current understanding of the legacy and emerging organic pollutants in the soil of Bangladesh remains limited.Inadequate disposal practices,particularly in e-waste,landfills,and industrial operations,may lead to the pervasive presence of persistent organic pollutants(POPs)and polycyclic aromatic hydrocarbons(PAHs)in the country.This study aimed to systematically investigate the concentrations,sources,and risk assessment of halogenated flame retardants(HFRs),polychlorinated biphenyls(PCBs),polychlorinated naphthalenes(PCNs),organochlorine pesticides(OCPs),chlorinated paraffins(CPs),and PAHs in the contaminated soil of Dhaka's dumpsites,e-waste,and industrial areas collected in 2017.The total concentration of investigated pollutants averaged at 4790±4040 ng g^(-1)dw,with the following order:P44CPs(4110±4140 ng g^(-1)dw)>P16PAHs(422±491 ng g^(-1)dw)>P16HFRs(190±538 ng g^(-1)dw)>P209PCBs(43.5±73.5 ng g^(-1)dw)>P50PCNs(17.7±21.0 ng g^(-1)dw)>P27OCPs(9.41±9.61 ng g^(-1)dw).The e-waste site exhibited the highest total concentration of the target pollutants,reaching 12,700 ng g1 dw.CPs were the predominant contributors,accounting for averages of 81.8%,70.5%,and 68.5%to waste landfills,e-waste,and industrial sites,respectively.A comprehensive analysis of 209 PCB congeners revealed their primary origin from Aroclor PCBs,with minor contributions from unintentionally produced PCBs.The highest incremental lifetime carcinogenic risk(ILCR)occurred in e-waste sites,contributed by dioxin-like PCBs,with a maximum value of 5.9×10^(-5)for adults,exceeding the limit 1.0×10^(-6)set by the U.S.EPA.The non-carcinogenic hazard quotients(HQs)were much lower,suggesting no significant risk from the investigated pollutants.Our findings highlight the importance of proper waste management and regulated e-waste recycling to mitigate potential hazardous risks to the Bangladeshi population.
