The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are imm...The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.展开更多
Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),a...Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),and serve as evidence-based augmenters in treatment-resistant depression.Nonetheless,acute antipsychotic-induced movement disorders(AIMDs)[extrapyramidal symptoms(EPS)]are common and clinically costly,impairing quality of life,adherence,and outcomes.The acute spectrum is dominated by dystonia(sustained,often painful contractions).展开更多
Stichopus chloronotus is a tropical sea cucumber with facultative asexual reproduction in the Indo-Western Pacific,yet its wild populations are decreasing due to extensive harvesting.Understanding the species’genetic...Stichopus chloronotus is a tropical sea cucumber with facultative asexual reproduction in the Indo-Western Pacific,yet its wild populations are decreasing due to extensive harvesting.Understanding the species’genetic characteristics is essential for effective management and conservation.To develop novel microsatellite markers and assess the genetic diversity,clonality,and genetic structure of eight populations of S.chloronotus in the South China Sea,193 individuals from eight populations across Wuzhizhou and Fenjiezhou(Boundary)islands were analyzed using nine newly developed microsatellite markers and five previously established markers.RNA-Seq was employed to obtained 62662 unigenes and identified 16926 microsatellite loci.Fourteen polymorphic microsatellite loci were developed,of which 11 were highly polymorphic(polymorphic information content>0.5).The number of alleles(N_(a))ranged from 3 to 6 per locus,and the average Shannon diversity index(I)was 1.107.All the populations exhibited asexual reproduction,with regional variations in reproductive modes.Asexual reproduction was predominant in the northwestern Wuzhizhou Island population(SY 7)and the Fenjiezhou Island population(LS 8),where four and five predominant clones represented more than 89%of the individuals,which led to reduced genetic diversity.Overall,genetic diversity was moderately low,with significant genetic differentiation among populations(F_(ST)=0.33;P<0.001),suggesting limited gene flow(the number of migrants(N_(m))<1).These findings highlight the role of reproductive strategies in shaping fine-scale genetic differentiation in S.chloronotus.The limited recruitment success of sexually produced larvae and habitat heterogeneity likely constrain clone dispersal,contributing to distinct genetic restructuring.This study provided key insights into the interplay between reproductive strategies and genetic patterns in sea cucumbers,offering a scientific basis for targeted conservation efforts.展开更多
Genetic, life history, and environmental factors dictate patterns of variation in sexual traits within and across popula- tions, and thus the action and outcome of sexual selection. This study explores patterns of inh...Genetic, life history, and environmental factors dictate patterns of variation in sexual traits within and across popula- tions, and thus the action and outcome of sexual selection. This study explores patterns of inheritance, diet, age, and mate-choice copying on the expression of male sexual signals and associated female mate choice in a phenotypically diverse group of Schizo- cosa wolf spiders. Focal spiders exhibit one of two male phenotypes： ＇omamented＇ males possess large black brushes on their fo- relegs, and ＇non-ornamented＇ males possess no brushes. Using a quantitative genetics breeding design in a mixed population of ornamented/non-ornamented males, we found a strong genetic basis to male phenotype and female choice. We also found that some ornamented males produced some sons with large brushes and others with barely visible brushes. Results of diet manipula- tions and behavioral mating trials showed no influence of diet on male phenotype or female mate choice. Age post maturation, however, influenced mate choice, with younger females being more likely to mate with ornamented males. A mate-choice copy- ing experiment found that, following observations of another female＇s mate choice/copulation, virgin mature females tended to match the mate choice （ornamented vs. non-ornamented males） of the females they observed. Finally, analyses of genetic varia- tion across phenotypically pure （only one male phenotype present） vs. mixed （both phenotypes present） populations revealed ge- netic distinction between phenotypes in phenotypically-pure populations, but no distinctionin phenotypically-mixed populations. The difference in patterns of genetic differentiation and mating across geographic locations suggests a complex network of fac- tors contributing to the outcome of sexual selection .展开更多
Background Atrial fibrillation （AF） was used to be considered as nongenetics disorder, but recent studies have revealed that genetics variants conferred susceptibility to AF development, but most with limited eviden...Background Atrial fibrillation （AF） was used to be considered as nongenetics disorder, but recent studies have revealed that genetics variants conferred susceptibility to AF development, but most with limited evidence. In order to systematically evaluate the overall contributions of gene-disease association studies to current understandings of the genetic susceptibility to atrial fibrillation, we perform a systematic review and meta- analysis based on comprehensive searches. Method All studies on the associations of genetics variants with AF risk were identified by searching the following databases： Medline, Embase, BIOSIS, Global Health, LILACS and CBMDisc. Odds ratios （CI） and 95 % confidence intervals （CI） were calculated under homozygote comparison （HC）, dominant model （DM） and recessive model （RM）, respectively. Results A total of 41 studies on 32 genes and 72 polymorphisms locations were identified. The summary OR was statistically significant associations in 23 （31.94 %） single nucleotide polymorphisms （SNPs）. The genes in renin-angiotensin- aldosterone system （RAAS） and ion channels were the mostly studied. Four SNPs （50.00 %） in RAAS genes were significantly associated with AF susceptibility： ACE I/D （HC. OR = 1.53, 95 % CI： 1.14-2.0 DM： OR = 1.47, 95 % CI： 0.86-1.53; RM： OR = 0.49, 95% CI： 0.41-0.59）; AGT A-20C （HC： OR = 1.56, 95 % CI. 1.41-2.12）; AGT M235T （HC： OR = 2.37, 95 % CI： 1.21-4.65）. Statistically significant associations were also found in the following genes and SNPs： ABCA1 G1051A, BCHE G1615A, CETP A1061G, I405V, TaqlB, CRP C1444T, EDN2 A985G, eNOS T-786C, IL-10 T-819C, A-592C, MinK G38S, KCNH2 rs1805120, Kit 3.4 C171T, G810T, MMP2 C-1306T, Factor 11 G20210A, SCNSA H58R, SLC26A8 I639V, G-protein β- subunit C825T, chromatosome 4q25 rs2200733 and rs10033464. Conclusions Nearly one-third of SNPs were statistically significant associated with AF risk, with variants in RAAS genes most highly significant association. More studies on a wide range of genes are merited.展开更多
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
Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratificat...Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.展开更多
Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic recept...Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.展开更多
Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of envir...Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.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
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
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
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
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
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
文摘The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.
文摘Antipsychotics,especially many second-generation antipsychotics(SGAs),remain central to schizophrenia treatment,are indispensable in acute mania and for bipolar maintenance(with selected roles in bipolar depression),and serve as evidence-based augmenters in treatment-resistant depression.Nonetheless,acute antipsychotic-induced movement disorders(AIMDs)[extrapyramidal symptoms(EPS)]are common and clinically costly,impairing quality of life,adherence,and outcomes.The acute spectrum is dominated by dystonia(sustained,often painful contractions).
基金Supported by the National Key Research and Development Program of China(Nos.2022YFD2401305,2022YFD2401303)the National Natural Science Foundation of China(Nos.42166005,42076097)。
文摘Stichopus chloronotus is a tropical sea cucumber with facultative asexual reproduction in the Indo-Western Pacific,yet its wild populations are decreasing due to extensive harvesting.Understanding the species’genetic characteristics is essential for effective management and conservation.To develop novel microsatellite markers and assess the genetic diversity,clonality,and genetic structure of eight populations of S.chloronotus in the South China Sea,193 individuals from eight populations across Wuzhizhou and Fenjiezhou(Boundary)islands were analyzed using nine newly developed microsatellite markers and five previously established markers.RNA-Seq was employed to obtained 62662 unigenes and identified 16926 microsatellite loci.Fourteen polymorphic microsatellite loci were developed,of which 11 were highly polymorphic(polymorphic information content>0.5).The number of alleles(N_(a))ranged from 3 to 6 per locus,and the average Shannon diversity index(I)was 1.107.All the populations exhibited asexual reproduction,with regional variations in reproductive modes.Asexual reproduction was predominant in the northwestern Wuzhizhou Island population(SY 7)and the Fenjiezhou Island population(LS 8),where four and five predominant clones represented more than 89%of the individuals,which led to reduced genetic diversity.Overall,genetic diversity was moderately low,with significant genetic differentiation among populations(F_(ST)=0.33;P<0.001),suggesting limited gene flow(the number of migrants(N_(m))<1).These findings highlight the role of reproductive strategies in shaping fine-scale genetic differentiation in S.chloronotus.The limited recruitment success of sexually produced larvae and habitat heterogeneity likely constrain clone dispersal,contributing to distinct genetic restructuring.This study provided key insights into the interplay between reproductive strategies and genetic patterns in sea cucumbers,offering a scientific basis for targeted conservation efforts.
文摘Genetic, life history, and environmental factors dictate patterns of variation in sexual traits within and across popula- tions, and thus the action and outcome of sexual selection. This study explores patterns of inheritance, diet, age, and mate-choice copying on the expression of male sexual signals and associated female mate choice in a phenotypically diverse group of Schizo- cosa wolf spiders. Focal spiders exhibit one of two male phenotypes： ＇omamented＇ males possess large black brushes on their fo- relegs, and ＇non-ornamented＇ males possess no brushes. Using a quantitative genetics breeding design in a mixed population of ornamented/non-ornamented males, we found a strong genetic basis to male phenotype and female choice. We also found that some ornamented males produced some sons with large brushes and others with barely visible brushes. Results of diet manipula- tions and behavioral mating trials showed no influence of diet on male phenotype or female mate choice. Age post maturation, however, influenced mate choice, with younger females being more likely to mate with ornamented males. A mate-choice copy- ing experiment found that, following observations of another female＇s mate choice/copulation, virgin mature females tended to match the mate choice （ornamented vs. non-ornamented males） of the females they observed. Finally, analyses of genetic varia- tion across phenotypically pure （only one male phenotype present） vs. mixed （both phenotypes present） populations revealed ge- netic distinction between phenotypes in phenotypically-pure populations, but no distinctionin phenotypically-mixed populations. The difference in patterns of genetic differentiation and mating across geographic locations suggests a complex network of fac- tors contributing to the outcome of sexual selection .
文摘Background Atrial fibrillation （AF） was used to be considered as nongenetics disorder, but recent studies have revealed that genetics variants conferred susceptibility to AF development, but most with limited evidence. In order to systematically evaluate the overall contributions of gene-disease association studies to current understandings of the genetic susceptibility to atrial fibrillation, we perform a systematic review and meta- analysis based on comprehensive searches. Method All studies on the associations of genetics variants with AF risk were identified by searching the following databases： Medline, Embase, BIOSIS, Global Health, LILACS and CBMDisc. Odds ratios （CI） and 95 % confidence intervals （CI） were calculated under homozygote comparison （HC）, dominant model （DM） and recessive model （RM）, respectively. Results A total of 41 studies on 32 genes and 72 polymorphisms locations were identified. The summary OR was statistically significant associations in 23 （31.94 %） single nucleotide polymorphisms （SNPs）. The genes in renin-angiotensin- aldosterone system （RAAS） and ion channels were the mostly studied. Four SNPs （50.00 %） in RAAS genes were significantly associated with AF susceptibility： ACE I/D （HC. OR = 1.53, 95 % CI： 1.14-2.0 DM： OR = 1.47, 95 % CI： 0.86-1.53; RM： OR = 0.49, 95% CI： 0.41-0.59）; AGT A-20C （HC： OR = 1.56, 95 % CI. 1.41-2.12）; AGT M235T （HC： OR = 2.37, 95 % CI： 1.21-4.65）. Statistically significant associations were also found in the following genes and SNPs： ABCA1 G1051A, BCHE G1615A, CETP A1061G, I405V, TaqlB, CRP C1444T, EDN2 A985G, eNOS T-786C, IL-10 T-819C, A-592C, MinK G38S, KCNH2 rs1805120, Kit 3.4 C171T, G810T, MMP2 C-1306T, Factor 11 G20210A, SCNSA H58R, SLC26A8 I639V, G-protein β- subunit C825T, chromatosome 4q25 rs2200733 and rs10033464. Conclusions Nearly one-third of SNPs were statistically significant associated with AF risk, with variants in RAAS genes most highly significant association. More studies on a wide range of genes are merited.
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.
文摘Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.
文摘Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of Caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 C/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. Conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.
文摘Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.
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.
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.
