BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wil...Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.展开更多
BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associat...BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.展开更多
Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic qu...Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.展开更多
Kawasaki disease(KD)is a systemic vasculitis primarily affecting children,and represents a major cause of acquired heart disease in this population.Although the etiology of KD remains incompletely understood,existing ...Kawasaki disease(KD)is a systemic vasculitis primarily affecting children,and represents a major cause of acquired heart disease in this population.Although the etiology of KD remains incompletely understood,existing genome-wide association studies and genome-wide linkage studies have uncovered various susceptibility genes and their associated chromosomal regions as closely related to the onset and progression of KD.With the rapid advancement of high-throughput DNA sequencing technology,an increasing amount of genomic information pertinent to KD has been discovered,offering new perspectives to investigate the pathogenesis of KD.In particular,genetic polymorphisms play a pivotal role in the immune response,coronary artery lesions,and treatment responsiveness in KD,providing fresh insights into optimizing diagnostic and therapeutic strategies.This article aimed to review and summarize the crucial role of genetic polymorphisms in the pathogenesis of KD,analyze the latest advancements in current research,and discuss the potential applications of gene polymorphism studies in the future diagnosis and treatment of KD.展开更多
BACKGROUND Depression is a disease with a significant global social burden.Single nucleotide polymorphisms(SNPs)are correlated with the development of depression.This study investigates the relationship between polymo...BACKGROUND Depression is a disease with a significant global social burden.Single nucleotide polymorphisms(SNPs)are correlated with the development of depression.This study investigates the relationship between polymorphisms in the GPHN and ATP6V1D gene promoter regions and susceptibility to depression in the Chinese population.AIM To provide new insights into identifying SNPs for predicting depression in the Chinese population.METHODS We conducted a case-control study involving 555 individuals with depression and 509 healthy controls.GPHN rs8020095 and ATP6V1D rs3759755,rs10144417,rs2031564,and rs8016024 in the promoter region were genotyped using nextgeneration sequencing.Dual luciferase reporter genes were employed to assess the transcriptional activity of promoter regions for each SNP genotype,with transcription factors binding to each site predicted using the JASPAR database.RESULTS Compared to healthy controls,the ATP6V1D promoter rs10144417 AG genotype (P = 0.015), rs3759755 AC/CC genotype (P = 0.036), and GPHN gene rs8020095 GA and AA genotypes (GA: P =0.028, GG: P = 0.025) were significantly associated with a lower prevalence of depression. Linked disequilibria werepresent in five SNPs, with the AGATA haplotype frequency in patients significantly lower than in healthy subjects(P = 0.023). Luciferase activity of the rs3759755-A recombinant plasmid was significantly higher than that of thers3759755-C recombinant plasmid (P = 0.026), and the rs8020095-A recombinant plasmid activity was significantlyhigher than that of the rs8020095-G recombinant plasmid (P = 0.001). Transcription factors orthodenticle homeobox2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulateddemonstrated binding affinity with rs3759755A > C and rs8020095A > G.CONCLUSIONThis study demonstrates that SNPs (rs3759755 and rs10144417) in the promoter region of the ATP6V1D and SNP(rs8020095) of GPHN are indeed associated with susceptibility to depression.展开更多
Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on sp...Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.展开更多
Fluoropyrimidines(FP),including 5-fluorouracil and its prodrug capecitabine,are commonly employed in treating various solid tumors.Nonetheless,their use is frequently constrained by severe toxicities in 20%-30%of pati...Fluoropyrimidines(FP),including 5-fluorouracil and its prodrug capecitabine,are commonly employed in treating various solid tumors.Nonetheless,their use is frequently constrained by severe toxicities in 20%-30%of patients.Pharmacogenetic testing for dihydropyrimidine dehydrogenase(DPYD)deficiency,based on DPYD polymorphisms,has notably decreased severe adverse events,improving the safety of FP therapy.A recent D'Amato et al study evaluated the prevalence of DPYD polymorphisms and their effect on FP tolerability among Italian patients with gastrointestinal cancers.Although this study provided important insights into the significance of DPYD testing,its retrospective nature,inconsistency in testing DPYD variants,and lack of consideration for socioeconomic and confounding factors showed considerable limitations.Expanding the screening to include DPYD variants,addressing confounding biases through robust statistical analyses,and implementing prospective studies are critical next steps to strengthen the clinical evidence.Furthermore,the absence of a comprehensive cost-effectiveness analysis highlights the need for further financial assessments to advocate for broader implementation.We emphasized integrating DPYD-guided dosing,pre-treatment genetic counseling,and standardized testing procedures into clinical practice to improve patient outcomes and minimize treatment-related toxicities.展开更多
In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2...In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(1)andβ-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(2)(PHSQ=N-(4-sulfophenyl)-4,4-bipyridinium)were synthesized by changing the solvent.They can both respond to UV light and electricity in the manner of chromism visible to the naked eye and the coloration states have good reversibility,through which an inkless erasable printing model has been established.But the coloration contrast of 1 is higher compared to 2.Meanwhile,they both exhibit photoluminescence properties and the intensity of 1 is twice that of 2,which is accompanied by photoquenching upon continuous UV light irradiation.The only divergence of disordered/ordered O atoms in the two crystalline compounds leads to significantly different chromic and luminescent properties.Further explorations simultaneously demonstrate that the different chromic performance between 1 and 2 should attribute to the alteration of stimulus-induced(light/electricity)electron transfer channels caused by the ordered/disordered O atoms in the complexes,which is achieved through C-H···O and O-H···O interactions to change crystal arrangement and structural rigidity,thus affect luminescent properties.展开更多
Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the dev...Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.展开更多
Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Ge...Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.展开更多
BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and...BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.展开更多
Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of I...Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of IBD commonly occurs during adolescence.Despite the significant number of cases globally(~5 million),the causes of pediatric IBD,which constitutes 25%of IBD patients,are not yet fully understood.Apart from environmental factors,genetic factors contribute to a higher risk of developing IBD.The predisposition risk of IBD can be investigated using genetic testing.Genetic mechanisms of pediatric IBD are highly complex which resulted in difficulty in selecting effective treatment or patient management.Genetic variation of IBD would serve as a basis for precision medicine and allow for the discovery of more robust treatment avenues for this condition in pediatric patients.This review aims to discuss the genetics of pediatric IBD,and current development in the screening,diagnosis,and treatment based on genetic profiling of pediatric IBD subjects toward more personalized management of this disease.展开更多
Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular a...Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular and cellular disturbances,including reduced nitric oxide bioavailability,persistent low-grade inflammation,oxidative stress,endothelial dysfunction,altered mineral metabolism,genetic predispositions,and uremic toxin accumulation.As current pharmacological treatments provide only partial risk reduction,complementary approaches are imperative.Exercise training,both aerobic and resistance,has emerged as a potent non-pharmacological intervention targeting these underlying molecular pathways.Regular exercise can enhance nitric oxide signaling,improve antioxidant defenses,attenuate inflammation,facilitate endothelial repair via endothelial progenitor cells,and stabilize muscle metabolism.Additionally,accumulating evidence points to a genetic dimension in CKD susceptibility and progression.Variants in genes such as APOL1,PKD1,PKD2,UMOD,and COL4A3–5 shape disease onset and severity,and may modulate response to interventions.Exercise may help buffer these genetic risks by inducing epigenetic changes,improving mitochondrial function,and optimizing crosstalk between muscle,adipose tissue,and the vasculature.This review synthesizes how exercise training can ameliorate key molecular mediators in CKD,emphasizing the interplay with genetic and epigenetic factors.We integrate evidence from clinical and experimental studies,discussing how personalized exercise prescriptions,informed by patients’genetic backgrounds and nutritional strategies(such as adequate protein intake),could enhance outcomes.Although large-scale trials linking molecular adaptations to long-term endpoints are needed,current knowledge strongly supports incorporating exercise as a cornerstone in CKD management to counteract pervasive molecular derangements and leverage genetic insights for individualized care.展开更多
Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on...Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on T7 RNA polymerase.Full-length cDNA of the LN16-A strain was constructed by assembling 5 cDNA fragments between the T7 promoter and hepatitis delta virus ribozyme.Transfection of this plasmid,along with the supporting plasmids encoding the N,P,M2-1,and L proteins of LN16-A into BSR-T7/5 cells,resulted in the recovery of aMPV subtype B.To identify an effective insertion site,the enhanced green fluorescent protein(EGFP)gene was inserted into different sites of the LN16-A genome to generate recombinant LN16-As.The results showed that the expression levels of EGFP at the site between the G and L genes of LN16-A were significantly higher than those at the other two sites(between the leader and N genes or replacing the SH gene).To verify the availability of the site between G and L for foreign gene expression,the VP2 gene of very virulent infectious bursal disease virus(vvIBDV)was inserted into this site,and recombinant LN16-A(rLN16A-vvVP2)was successfully rescued.Single immunization of specificpathogen-free chickens with rLN16A-vvVP2 induced high levels of neutralizing antibodies and provided 100%protection against the virulent aMPV subtype B and vvIBDV.Establishing a reverse genetics system here provides an important foundation for understanding aMPV pathogenesis and developing novel vector vaccines.展开更多
Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations ...Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.展开更多
Information about whether genetic information requires special treatment in law varies around the world and many aspects are not clear.In this study,we draw upon knowledge gained from various disciplines,such as genet...Information about whether genetic information requires special treatment in law varies around the world and many aspects are not clear.In this study,we draw upon knowledge gained from various disciplines,such as genetics,medicine,law,philosophy,psychology,sociology,anthropology,insurance,and economics,which have all contributed to the study of genetic information,and discrimination based on genetic traits.With this in mind,we are able to set this research study into perspective.We make no claim on behalf of any field of study.Nevertheless,we say the development in the field of genetics is in its infancy and that knowledge of an individual genome would be essential not only for counseling but could also be used for stigmatization and discrimination.The purpose of the study is to help provide useful links concerning legal and ethical issues in human genetics and particularly where it deals with the laws,regulations,and policies concerning genetic information.We deal with the legal and ethical aspects in human genetics that influence genetic information.We examine government policies and the existing legislation in Papua New Guinea(PNG)that deal with genetic information and analyze discrimination cases due to genetic traits and describe its magnitude in PNG.This study places importance on the examination of qualitative data collected by a questionnaire survey from individual subjects representing various organizations in PNG including Department of Health,Insurance companies,General Federation of Employers’Associations,Trade Unions,and professional workers such as lawyers,District Court magistrates,medical doctors,healthcare workers,students,and private individuals.The study was conducted in towns in PNG although the majority of the participants live in the National Capital District.A sample of individuals(patients)were enrolled in a cross-sectional questionnaire survey.Individual information was obtained to describe the situation of the area.However,this study did not use administrative records based on health information from the Department of Health which describes the prevalence of genetically disordered individuals.All selected individuals or subjects were interviewed or completed a questionnaire.The data were assessed to characterize the study subsets.The findings of this study are made available to clinical practice in law,medical and public health,and private and public institutions including insurance companies,employers’federation,mining companies,and workers’unions in PNG,and academics and researchers.Educational programs on the basic principles of genetics,ethics,and law in relation to insurance will have to be developed to improve the knowledge of insurance,medical,and the cost of long-term care.展开更多
2025年3月17日,国际顶级学术期刊《自然·遗传学》(Nature Genetics)刊发题为“Genomic analysis of 1325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement”的研究性论文。该研究...2025年3月17日,国际顶级学术期刊《自然·遗传学》(Nature Genetics)刊发题为“Genomic analysis of 1325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement”的研究性论文。该研究由福建省农业科学院茶叶研究所与中国农业科学院农业基因组研究所等多家单位合作完成。本研究通过对茶树及其近缘种的基因组进行深度重测序,构建了全面的茶树基因组遗传变异图谱,进而揭示了茶树的遗传多样性及其驯化状态。其结果为茶树的遗传进化和精准设计育种提供了有益见解以及重要参考资料。展开更多
Chicken meat quality directly influences consumer acceptability and is crucial for the economic success of the poultry industry.Genetics and nutrition are key determinants of the meat quality traits in broilers.This r...Chicken meat quality directly influences consumer acceptability and is crucial for the economic success of the poultry industry.Genetics and nutrition are key determinants of the meat quality traits in broilers.This review summarizes the research advances in this field,with a focus on the genetic and nutritional foundations that regulate intramuscular fat(IMF)deposition and meat quality in chickens over the past decade.The effects of embryonic nutrition,both maternal nutrition and in ovo feeding(IOF),on skeletal muscle development,the IMF content,and meat quality traits in broilers are also discussed.In genetics,single-cell RNA sequencing revealed that de novo lipogenesis predominantly occurs in myocytes,which is key to the formation of IMF in chicken muscle tissue.Fatty acid synthase(FASN)is the key enzyme involved in this process.This discovery has reshaped the traditional understanding of intramuscular lipid metabolism in poultry.Key genes,proteins,and pathways,such as FASN,FABP4,PPARG,C/EBPα,SLC27A1;LPL,APOA1,COL1A1;PPAR and ECM–receptor interactions signaling,have been identified to regulate IMF content and distribution by modulating fatty acid metabolism and adipogenesis.LncHLFF was innovatively found to promote ectopic IMF deposition in chickens via exosome-mediated mechanisms without affecting abdominal fat deposition.MiR-27b-3p and miR-128-3p were found to inhibit adipogenic differentiation by targeting PPARG,thereby affecting IMF formation.In nutrition,nutrigenomics research has shown that fructose enhances IMF deposition by activating ChREBP,providing new targets for nutritional interventions.Adjusting dietary components,including energy,protein,amino acids,fatty acids,and phytochemicals(e.g.,rutin),has been shown to significantly improve meat quality in broilers.Maternal nutrition(e.g.,intake of energy,amino acids,vitamins,and trace elements)and IOF(e.g.,N-carbamylglutamate)have also been confirmed to significantly impact offspring meat quality,opening new avenues for improving embryonic nutrition.Based on these significant advancements,this review proposes strategies that integrate genetic and nutritional approaches.These strategies aim to modulate the differentiation fate of paraxial mesenchymal stem cells toward myogenic or adipogenic lineages and the interaction between muscle and adipose tissues.These insights would help to improve meat quality while ensuring the growth performance of broiler chickens.展开更多
The present investigation aims at unveiling the main causes of the recorded disparate phylogeographic patterning among the two highly dispersive coastal crab species Carcinus aestuarii and Pachygrapsus marmoratus in t...The present investigation aims at unveiling the main causes of the recorded disparate phylogeographic patterning among the two highly dispersive coastal crab species Carcinus aestuarii and Pachygrapsus marmoratus in the Mediterranean Sea.For this purpose,available mitochondrial and nuclear data for both species were re-analyzed and investigated for genetic polymorphism and differentiation patterns across three defined geographic scales in their distribution ranges,but also across the same locations in the Mediterranean Sea.The temporal frame of genetic diversification was also determined for both species in order to check whether observed differences in phylogeographic patterns among these coastal decapods could be attributed to different evolutionary histories.The obtained results revealed a more variable and diversified gene pool in the green crab C.aestuarii than the one recorded in the marbled crab P.marmoratus.Lack of significant correlation between pairwise genetic dissimilarities observed among C.aestuarii populations and those detected for P.marmoratus was notably discerned across the same defined Mediterranean locations.This finding indicates that the pattern of pairwise genetic differentiation does not vary in the same way in both examined crab species.Significant outputs of population genetic differentiation,retrieved within both species,were shown to be differently associated with the potential effects of various kinds of isolation processes(related to geography,environment and biogeographic boundary).Evolutionary history reconstruction showed older genetic diversification event in C.aestuarii than the one recorded in P.marmoratus.These recorded temporal frames suggest different modes of genetic diversification in both crab species(glacial vicariance for C.aestuarii and interglacial dispersal for P.marmoratus).They may also provide an explanation for the recorded differences in variation of patterns of population genetic diversity and structure,when integrated with species ecological requirements and life-history traits.展开更多
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金funded by the National Natural Science Foundation of China(grant no.32270238 and 31870311).
文摘Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.
文摘BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.
基金National Key Research and Development Program for Young scientists,Grant/Award Number:2021YFF0703200National Natural Foundation Joint Fund for Regional Innovation and Development,Grant/Award Number:U21A20194+1 种基金National Natural Science Foundation of China,Grant/Award Number:32170540National Key Research and Development Program,Grant/Award Number:2022YFF0711005。
文摘Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.
文摘Kawasaki disease(KD)is a systemic vasculitis primarily affecting children,and represents a major cause of acquired heart disease in this population.Although the etiology of KD remains incompletely understood,existing genome-wide association studies and genome-wide linkage studies have uncovered various susceptibility genes and their associated chromosomal regions as closely related to the onset and progression of KD.With the rapid advancement of high-throughput DNA sequencing technology,an increasing amount of genomic information pertinent to KD has been discovered,offering new perspectives to investigate the pathogenesis of KD.In particular,genetic polymorphisms play a pivotal role in the immune response,coronary artery lesions,and treatment responsiveness in KD,providing fresh insights into optimizing diagnostic and therapeutic strategies.This article aimed to review and summarize the crucial role of genetic polymorphisms in the pathogenesis of KD,analyze the latest advancements in current research,and discuss the potential applications of gene polymorphism studies in the future diagnosis and treatment of KD.
基金Supported by the Natural Science Foundation of Sichuan,China,No.2022NSFSC0778Research Project Foundation of Sichuan Applied Psychology Research Center,No.CSXL-24202+1 种基金Foundation of Sichuan Clinical Research Center for Geriatrics,No.24LHLNYX1-04 and No.24LHLNYX1-06and the Key Laboratory Foundation for Development and Regeneration of Sichuan Province,No.24LHFYSZ1-25.
文摘BACKGROUND Depression is a disease with a significant global social burden.Single nucleotide polymorphisms(SNPs)are correlated with the development of depression.This study investigates the relationship between polymorphisms in the GPHN and ATP6V1D gene promoter regions and susceptibility to depression in the Chinese population.AIM To provide new insights into identifying SNPs for predicting depression in the Chinese population.METHODS We conducted a case-control study involving 555 individuals with depression and 509 healthy controls.GPHN rs8020095 and ATP6V1D rs3759755,rs10144417,rs2031564,and rs8016024 in the promoter region were genotyped using nextgeneration sequencing.Dual luciferase reporter genes were employed to assess the transcriptional activity of promoter regions for each SNP genotype,with transcription factors binding to each site predicted using the JASPAR database.RESULTS Compared to healthy controls,the ATP6V1D promoter rs10144417 AG genotype (P = 0.015), rs3759755 AC/CC genotype (P = 0.036), and GPHN gene rs8020095 GA and AA genotypes (GA: P =0.028, GG: P = 0.025) were significantly associated with a lower prevalence of depression. Linked disequilibria werepresent in five SNPs, with the AGATA haplotype frequency in patients significantly lower than in healthy subjects(P = 0.023). Luciferase activity of the rs3759755-A recombinant plasmid was significantly higher than that of thers3759755-C recombinant plasmid (P = 0.026), and the rs8020095-A recombinant plasmid activity was significantlyhigher than that of the rs8020095-G recombinant plasmid (P = 0.001). Transcription factors orthodenticle homeobox2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulateddemonstrated binding affinity with rs3759755A > C and rs8020095A > G.CONCLUSIONThis study demonstrates that SNPs (rs3759755 and rs10144417) in the promoter region of the ATP6V1D and SNP(rs8020095) of GPHN are indeed associated with susceptibility to depression.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,No.32070726,and No.82370715National Key R&D Program of China,No.2023YFC2507904the Innovation Group Project of Hubei Province,No.2023AFA026.
文摘Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.
文摘Fluoropyrimidines(FP),including 5-fluorouracil and its prodrug capecitabine,are commonly employed in treating various solid tumors.Nonetheless,their use is frequently constrained by severe toxicities in 20%-30%of patients.Pharmacogenetic testing for dihydropyrimidine dehydrogenase(DPYD)deficiency,based on DPYD polymorphisms,has notably decreased severe adverse events,improving the safety of FP therapy.A recent D'Amato et al study evaluated the prevalence of DPYD polymorphisms and their effect on FP tolerability among Italian patients with gastrointestinal cancers.Although this study provided important insights into the significance of DPYD testing,its retrospective nature,inconsistency in testing DPYD variants,and lack of consideration for socioeconomic and confounding factors showed considerable limitations.Expanding the screening to include DPYD variants,addressing confounding biases through robust statistical analyses,and implementing prospective studies are critical next steps to strengthen the clinical evidence.Furthermore,the absence of a comprehensive cost-effectiveness analysis highlights the need for further financial assessments to advocate for broader implementation.We emphasized integrating DPYD-guided dosing,pre-treatment genetic counseling,and standardized testing procedures into clinical practice to improve patient outcomes and minimize treatment-related toxicities.
基金financially supported by the National Natural Science Foundation of China(NSFC,Nos.22075168,21701105,21871167&91961201)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-FR003)。
文摘In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(1)andβ-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(2)(PHSQ=N-(4-sulfophenyl)-4,4-bipyridinium)were synthesized by changing the solvent.They can both respond to UV light and electricity in the manner of chromism visible to the naked eye and the coloration states have good reversibility,through which an inkless erasable printing model has been established.But the coloration contrast of 1 is higher compared to 2.Meanwhile,they both exhibit photoluminescence properties and the intensity of 1 is twice that of 2,which is accompanied by photoquenching upon continuous UV light irradiation.The only divergence of disordered/ordered O atoms in the two crystalline compounds leads to significantly different chromic and luminescent properties.Further explorations simultaneously demonstrate that the different chromic performance between 1 and 2 should attribute to the alteration of stimulus-induced(light/electricity)electron transfer channels caused by the ordered/disordered O atoms in the complexes,which is achieved through C-H···O and O-H···O interactions to change crystal arrangement and structural rigidity,thus affect luminescent properties.
文摘Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.
基金supported by the Ministry of Higher Education(MOHE)Malaysia through Fundamental Research Grant Scheme(FRGS)with project code:FRGS/1/2021/STG01/UCSI/01/.SX was funded by the National Natural Science Foundation of China(NSFC)grants 32030020 and 32288101funded by the NSFC grant 32270665.
文摘Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.
基金Supported by the National Key Research and Development Program of China,No.2021YFC2700700 and No.2021YFC2700704Capital’s Funds for Health Improvement and Research(CFH)in People’s Republic of China,No.2020-1-5112.
文摘BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.
文摘Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of IBD commonly occurs during adolescence.Despite the significant number of cases globally(~5 million),the causes of pediatric IBD,which constitutes 25%of IBD patients,are not yet fully understood.Apart from environmental factors,genetic factors contribute to a higher risk of developing IBD.The predisposition risk of IBD can be investigated using genetic testing.Genetic mechanisms of pediatric IBD are highly complex which resulted in difficulty in selecting effective treatment or patient management.Genetic variation of IBD would serve as a basis for precision medicine and allow for the discovery of more robust treatment avenues for this condition in pediatric patients.This review aims to discuss the genetics of pediatric IBD,and current development in the screening,diagnosis,and treatment based on genetic profiling of pediatric IBD subjects toward more personalized management of this disease.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(grant number:NRF-2022R1A2C1092743).
文摘Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular and cellular disturbances,including reduced nitric oxide bioavailability,persistent low-grade inflammation,oxidative stress,endothelial dysfunction,altered mineral metabolism,genetic predispositions,and uremic toxin accumulation.As current pharmacological treatments provide only partial risk reduction,complementary approaches are imperative.Exercise training,both aerobic and resistance,has emerged as a potent non-pharmacological intervention targeting these underlying molecular pathways.Regular exercise can enhance nitric oxide signaling,improve antioxidant defenses,attenuate inflammation,facilitate endothelial repair via endothelial progenitor cells,and stabilize muscle metabolism.Additionally,accumulating evidence points to a genetic dimension in CKD susceptibility and progression.Variants in genes such as APOL1,PKD1,PKD2,UMOD,and COL4A3–5 shape disease onset and severity,and may modulate response to interventions.Exercise may help buffer these genetic risks by inducing epigenetic changes,improving mitochondrial function,and optimizing crosstalk between muscle,adipose tissue,and the vasculature.This review synthesizes how exercise training can ameliorate key molecular mediators in CKD,emphasizing the interplay with genetic and epigenetic factors.We integrate evidence from clinical and experimental studies,discussing how personalized exercise prescriptions,informed by patients’genetic backgrounds and nutritional strategies(such as adequate protein intake),could enhance outcomes.Although large-scale trials linking molecular adaptations to long-term endpoints are needed,current knowledge strongly supports incorporating exercise as a cornerstone in CKD management to counteract pervasive molecular derangements and leverage genetic insights for individualized care.
基金supported by the grants from the National Key Research and Development Program of China(2022YFD1800604)the China Agriculture Research System(CARS-41)the Heilongjiang Touyan Innovation Team Program,China。
文摘Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on T7 RNA polymerase.Full-length cDNA of the LN16-A strain was constructed by assembling 5 cDNA fragments between the T7 promoter and hepatitis delta virus ribozyme.Transfection of this plasmid,along with the supporting plasmids encoding the N,P,M2-1,and L proteins of LN16-A into BSR-T7/5 cells,resulted in the recovery of aMPV subtype B.To identify an effective insertion site,the enhanced green fluorescent protein(EGFP)gene was inserted into different sites of the LN16-A genome to generate recombinant LN16-As.The results showed that the expression levels of EGFP at the site between the G and L genes of LN16-A were significantly higher than those at the other two sites(between the leader and N genes or replacing the SH gene).To verify the availability of the site between G and L for foreign gene expression,the VP2 gene of very virulent infectious bursal disease virus(vvIBDV)was inserted into this site,and recombinant LN16-A(rLN16A-vvVP2)was successfully rescued.Single immunization of specificpathogen-free chickens with rLN16A-vvVP2 induced high levels of neutralizing antibodies and provided 100%protection against the virulent aMPV subtype B and vvIBDV.Establishing a reverse genetics system here provides an important foundation for understanding aMPV pathogenesis and developing novel vector vaccines.
文摘Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.
文摘Information about whether genetic information requires special treatment in law varies around the world and many aspects are not clear.In this study,we draw upon knowledge gained from various disciplines,such as genetics,medicine,law,philosophy,psychology,sociology,anthropology,insurance,and economics,which have all contributed to the study of genetic information,and discrimination based on genetic traits.With this in mind,we are able to set this research study into perspective.We make no claim on behalf of any field of study.Nevertheless,we say the development in the field of genetics is in its infancy and that knowledge of an individual genome would be essential not only for counseling but could also be used for stigmatization and discrimination.The purpose of the study is to help provide useful links concerning legal and ethical issues in human genetics and particularly where it deals with the laws,regulations,and policies concerning genetic information.We deal with the legal and ethical aspects in human genetics that influence genetic information.We examine government policies and the existing legislation in Papua New Guinea(PNG)that deal with genetic information and analyze discrimination cases due to genetic traits and describe its magnitude in PNG.This study places importance on the examination of qualitative data collected by a questionnaire survey from individual subjects representing various organizations in PNG including Department of Health,Insurance companies,General Federation of Employers’Associations,Trade Unions,and professional workers such as lawyers,District Court magistrates,medical doctors,healthcare workers,students,and private individuals.The study was conducted in towns in PNG although the majority of the participants live in the National Capital District.A sample of individuals(patients)were enrolled in a cross-sectional questionnaire survey.Individual information was obtained to describe the situation of the area.However,this study did not use administrative records based on health information from the Department of Health which describes the prevalence of genetically disordered individuals.All selected individuals or subjects were interviewed or completed a questionnaire.The data were assessed to characterize the study subsets.The findings of this study are made available to clinical practice in law,medical and public health,and private and public institutions including insurance companies,employers’federation,mining companies,and workers’unions in PNG,and academics and researchers.Educational programs on the basic principles of genetics,ethics,and law in relation to insurance will have to be developed to improve the knowledge of insurance,medical,and the cost of long-term care.
文摘2025年3月17日,国际顶级学术期刊《自然·遗传学》(Nature Genetics)刊发题为“Genomic analysis of 1325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement”的研究性论文。该研究由福建省农业科学院茶叶研究所与中国农业科学院农业基因组研究所等多家单位合作完成。本研究通过对茶树及其近缘种的基因组进行深度重测序,构建了全面的茶树基因组遗传变异图谱,进而揭示了茶树的遗传多样性及其驯化状态。其结果为茶树的遗传进化和精准设计育种提供了有益见解以及重要参考资料。
基金funded by the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Project No.U21A20253)2115 Talent Development Program of China Agricultural University.
文摘Chicken meat quality directly influences consumer acceptability and is crucial for the economic success of the poultry industry.Genetics and nutrition are key determinants of the meat quality traits in broilers.This review summarizes the research advances in this field,with a focus on the genetic and nutritional foundations that regulate intramuscular fat(IMF)deposition and meat quality in chickens over the past decade.The effects of embryonic nutrition,both maternal nutrition and in ovo feeding(IOF),on skeletal muscle development,the IMF content,and meat quality traits in broilers are also discussed.In genetics,single-cell RNA sequencing revealed that de novo lipogenesis predominantly occurs in myocytes,which is key to the formation of IMF in chicken muscle tissue.Fatty acid synthase(FASN)is the key enzyme involved in this process.This discovery has reshaped the traditional understanding of intramuscular lipid metabolism in poultry.Key genes,proteins,and pathways,such as FASN,FABP4,PPARG,C/EBPα,SLC27A1;LPL,APOA1,COL1A1;PPAR and ECM–receptor interactions signaling,have been identified to regulate IMF content and distribution by modulating fatty acid metabolism and adipogenesis.LncHLFF was innovatively found to promote ectopic IMF deposition in chickens via exosome-mediated mechanisms without affecting abdominal fat deposition.MiR-27b-3p and miR-128-3p were found to inhibit adipogenic differentiation by targeting PPARG,thereby affecting IMF formation.In nutrition,nutrigenomics research has shown that fructose enhances IMF deposition by activating ChREBP,providing new targets for nutritional interventions.Adjusting dietary components,including energy,protein,amino acids,fatty acids,and phytochemicals(e.g.,rutin),has been shown to significantly improve meat quality in broilers.Maternal nutrition(e.g.,intake of energy,amino acids,vitamins,and trace elements)and IOF(e.g.,N-carbamylglutamate)have also been confirmed to significantly impact offspring meat quality,opening new avenues for improving embryonic nutrition.Based on these significant advancements,this review proposes strategies that integrate genetic and nutritional approaches.These strategies aim to modulate the differentiation fate of paraxial mesenchymal stem cells toward myogenic or adipogenic lineages and the interaction between muscle and adipose tissues.These insights would help to improve meat quality while ensuring the growth performance of broiler chickens.
文摘The present investigation aims at unveiling the main causes of the recorded disparate phylogeographic patterning among the two highly dispersive coastal crab species Carcinus aestuarii and Pachygrapsus marmoratus in the Mediterranean Sea.For this purpose,available mitochondrial and nuclear data for both species were re-analyzed and investigated for genetic polymorphism and differentiation patterns across three defined geographic scales in their distribution ranges,but also across the same locations in the Mediterranean Sea.The temporal frame of genetic diversification was also determined for both species in order to check whether observed differences in phylogeographic patterns among these coastal decapods could be attributed to different evolutionary histories.The obtained results revealed a more variable and diversified gene pool in the green crab C.aestuarii than the one recorded in the marbled crab P.marmoratus.Lack of significant correlation between pairwise genetic dissimilarities observed among C.aestuarii populations and those detected for P.marmoratus was notably discerned across the same defined Mediterranean locations.This finding indicates that the pattern of pairwise genetic differentiation does not vary in the same way in both examined crab species.Significant outputs of population genetic differentiation,retrieved within both species,were shown to be differently associated with the potential effects of various kinds of isolation processes(related to geography,environment and biogeographic boundary).Evolutionary history reconstruction showed older genetic diversification event in C.aestuarii than the one recorded in P.marmoratus.These recorded temporal frames suggest different modes of genetic diversification in both crab species(glacial vicariance for C.aestuarii and interglacial dispersal for P.marmoratus).They may also provide an explanation for the recorded differences in variation of patterns of population genetic diversity and structure,when integrated with species ecological requirements and life-history traits.
