Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical ...Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.展开更多
The mussel is one of the main cultivated species in the world.A significant challenge faced by suspension-cultured mussels is the high incidence of mussel fall-off from cultivation ropes,adversely impacting harvest yi...The mussel is one of the main cultivated species in the world.A significant challenge faced by suspension-cultured mussels is the high incidence of mussel fall-off from cultivation ropes,adversely impacting harvest yields,which have been documented at commercial mussel farms in the United Kingdom,the United States of America,Canada,Spain,New Zealand and China.Byssus is an important attachment structure for marine mussels,and weakness in byssal thread attachment is a major factor leading to mussel detachment from ropes.To investigate the relationship between genetic variability and byssal thread phenotypic characteristics in the hard-shelled mussel(Mytilus coruscus),we collected three wild populations of M.coruscus from different latitudes in the East China Sea,including the Shengsi(SS),Jiaojiang(JJ),and Fuding(FD)populations.The genetic diversity and structure of these populations were investigated using 10 microsatellite loci.The mean observed heterozygosity(Ho)in the SS population was 0.44,higher than the mean Ho values of the JJ(0.40)and FD(0.39)populations.The mean inbreeding coefficients(F_(is))in the SS population was 0.20,lower than the mean F_(is)values of the JJ(0.33)and FD populations(0.40).These results revealed that the SS population exhibited higher genetic diversity compared to the other two populations.The different numbers of private alleles(P_(a))in the three populations,ranging from 10 to 17,suggest that these populations have experienced selective pressures from various environments.Moreover,genetic differentiation was observed in the genetic distance between the SS population and the other two populations.We also examined the phenotypic characteristics of their byssal threads.There were significant differences in byssus attachment strength among the three populations,with the SS population located at the highest latitude secreting more byssal threads and exhibiting greater byssal breaking force and plaque adhesion strength,while the Fuding(FD)population located at the lowest latitude had the weakest byssal attachment.The observed differentiation in private alleles and byssus phenotypes might suggest that the three wild populations have experienced different environmental selective pressures.This study provides insight for future genetic enhancement programs aimed at improving byssus attachment in M.coruscus.展开更多
Bocapavovirus,a member of the genus Bocaparvovirus within the subfamily Parvovirinae and the family Parvoviridae,is a small,non-enveloped,single-stranded DNA virus.This pathogen poses health risks to both humans and a...Bocapavovirus,a member of the genus Bocaparvovirus within the subfamily Parvovirinae and the family Parvoviridae,is a small,non-enveloped,single-stranded DNA virus.This pathogen poses health risks to both humans and animals.The Bocaparvovirus genome.展开更多
Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver c...Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted t...In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing,with particular emphasis on DNA and RNA methylation pathways.This editorial discusses the findings of Xiao et al,who identified the Wilms tumor 1-associated protein(WTAP)-DNA methyltransferase 1(DNMT1)axis as a pivotal regulator of endothelial dys-function in DFUs.WTAP,a regulatory subunit of N6-methyladenosine(m6A)methyltransferase,is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification.This contributes to im-paired angiogenesis,reduced cell viability,and delayed wound closure.WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model.Furthermore,DNMT1 overexpression ab-rogated the benefits of WTAP suppression,confirming its downstream effector role.Thus,targeting the WTAP-DNMT1 axis provides a new avenue for DFU management.Moreover,epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.展开更多
Rorippa indica is a wild oilseed crop of Brassicaceae with good environmental adaptability and strong stress resistance.This plant has become an important wild relative species for rapeseed(Brassica napus L.)and is us...Rorippa indica is a wild oilseed crop of Brassicaceae with good environmental adaptability and strong stress resistance.This plant has become an important wild relative species for rapeseed(Brassica napus L.)and is used to improve its agronomic traits,with important development and utilization value.However,the research of R.indica genetics is still lacking.And no mitochondrial genome(mitogenome)in the genus Rorippa has been expounded.To analyze the structural characteristics of the R.indica mitogenome,second-generation and third-generation sequencing techniques were made to assemble its mitogenome.The results showed that its mitogenome is composed of a single master circle DNA molecule,with 59 genes(33 protein-coding,23 tRNA,and 3 ribosomal RNA genes)annotated.The length of the circular genome is 219,775 bp,with aGCcontent of 45.24%.Themitochondrial genome contains 55 SSRs,17 tandem repeats,and 252 scattered repeat sequences,with scattered repeat sequences accounting for 77.78%.The top two codons with the highest expression levels are TTT and AUU.Moreover,377 RNA editing sites were forecasted in the R.indica mitogenome.And 22 collinear gene fragments were discriminated in the R.indica chloroplast andmitogenomes,with a total 13,153 bp length,accounting for 4.08%of the mitogenome sequence.The longest gene migration fragment is 2186 bp,and the shortest fragment is 42 bp.Furthermore,12 genes undergo complete migration between the two genomes,and 10 genes undergo partial migration.Systematic evolutionary analysis shows that R.indica and Brassica napus are grouped,indicating a close genetic relationship between the two.Herein,the R.indica mitogenome was sequenced and annotated,and it was compared with other Brassicaceae mitogenomes.A genomic data foundation was supplied for elucidating the R.indica origin and evolution.展开更多
Litchi(Litchi chinensis Sonn.),an important fruit tree in tropical and subtropical regions,possesses substantial economic value.The branchand leaf-related traits of litchi have a significant impact on litchi yield and...Litchi(Litchi chinensis Sonn.),an important fruit tree in tropical and subtropical regions,possesses substantial economic value.The branchand leaf-related traits of litchi have a significant impact on litchi yield and quality.However,due to limitations such as the density of the genetic linkage map,there have been few studies on mapping QTLs of branch-and leaf-related traits.In this study,a high-density genetic map was constructed by next-generation sequencing(NGS)using an F_(1) population of 264 progenies,derived from the cross between the cultivars‘Sanyuehong'and‘Ziniangxi'.A total of 2574 high-quality BINs(binomial intervals)were obtained,and a genetic linkage map was constructed with a total length of 1753.3 cM and an average marker distance of 0.68 cM.With the genetic map and the phenotyping of single leaf length(SLL),single leaf width(SLW),leaf shape index(LSI),weight of specific leaf(WSL),petiole length(PL)and compound leaf length(CLL)measured in three seasons,11,9,9,10,9 and 12 QTLs were detected for SLL,SLW,WSL,LSI,PL and CLL traits,respectively.Among these QTLs,five QTLs were consistently detected in two seasons and 12 pleiotropic QTLs were identified for at least two traits.These findings will provide new insights for the gene cloning for branch-and leaf-related traits as well as marker-assisted selection(MAS).展开更多
Gerbera,a popular commercial cut flower with vibrant and striking colors has gained immense popularity in the floriculture industry.They are widely cultivated in various regions,making them available throughout the ye...Gerbera,a popular commercial cut flower with vibrant and striking colors has gained immense popularity in the floriculture industry.They are widely cultivated in various regions,making them available throughout the year.As a better alternative to conventional propagation methods(via seeds and rhizomes),plant tissue culture serves as way to avail large-scale,uniform,disease-free plantlets for commercial cultivation as well as to develop novel genotypes.In addition,it ensures production of healthy plantlets throughout the year in limited space.Based on the plant tissue culture techniques,the in vitro polyploidization,mutagenesis,and genetic transformation pave a path for creation of variation and eventually enhancing the ornamental traits to address the consumers’preferences and also facilitates in developing stress tolerant lines thereby minimizing the losses during cultivation,maintaining the quality of the flowers.This comprehensive review article presents an overview of the recent advancements on genetic improvement of gerbera via various cutting-edge plant tissue culture-based tools and techniques that contribute in enhancing the quality and efficiency of gerbera cultivation,meeting the demands of the floriculture industry while addressing the challenges of changing environment and resource limitations.展开更多
Eucalyptus urophylla×E.grandis is a major hybrid species of timber plantations.However,our under-standing of Eucalyptus mitochondrial genome,especially within the Myrtaceae family,is limited.In this study,we empl...Eucalyptus urophylla×E.grandis is a major hybrid species of timber plantations.However,our under-standing of Eucalyptus mitochondrial genome,especially within the Myrtaceae family,is limited.In this study,we employed hybrid sequencing combining the Illumina and Oxford Nanopore sequencing to assemble and annotate the mitogenome(mtDNA)of E.urophylla×E.grandis.Our results reveal a structure characterized by one circular mol-ecule,with a cumulative length of 483,907 base pairs(bp)and a GC content of 44.96%.The circular molecule collec-tively harbored 59 annotated genes.Among these,38 were unique protein-coding genes(PCGs),accompanied by 18 transfer RNA(tRNA)genes and 3 ribosomal RNA(rRNA)genes.Our study also examined repetitive sequences,RNA editing sites,and intracellular sequence transfers within the mtDNA.Furthermore,we conducted a phylogenetic analy-sis between E.urophylla×E.grandis and 30 closely related species based on genetic affinities.The outcomes furnish a high-quality organelle genome for E.urophylla×E.grandis,thereby explaining basic insights into organelle genome evo-lution and phylogenetic relationships.展开更多
Soybean(Glycine max)variety Heihe 54 has played a crucial role in the Heihe soybean breeding program in China,contributing to the development of over 85 cultivars.To elucidate the genetic changes that have occurred ac...Soybean(Glycine max)variety Heihe 54 has played a crucial role in the Heihe soybean breeding program in China,contributing to the development of over 85 cultivars.To elucidate the genetic changes that have occurred across multiple generations of selection during soybean breeding,we conducted comprehensive genotyping analysis using the 180K Axiom SoyaSNP array on 42 varieties from the Heihe breeding program,as well as eight parental lines.Cluster analysis revealed four distinct groups,reflecting various breeding phases that incorporated diverse genetic resources as parental lines within the pedigree.A detailed examination of the graphical genotype profile across the genome identified preferred chromosome segments for specific breeding phases.These conserved blocks,which have been consistently maintained in descendant varieties during the extensive breeding period,likely harbor genes related to critical agronomic traits.This is exemplified by the consistent transmission of two segments located on chromosomes 18 and 20,which harbor the stem growth habit-related gene Dt2 and the leaflet shape-related gene Ln,respectively.The widespread cultivation of Heihe 43,a soybean cultivar developed within this pedigree,is attributed to its broad genetic base and the pyramiding of elite alleles from its parental lines.The identification of favorable chromosome segments provides valuable insight for agronomic traitrelated gene mining and targeted breeding in the future.展开更多
A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulat...A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.展开更多
BACKGROUND Floating-harbor syndrome(FHS)is a rare genetic disorder caused by pathogenic variants in the SRCAP gene.Most individuals with FHS have short stature,delayed speech and language development,and dysmorphic fa...BACKGROUND Floating-harbor syndrome(FHS)is a rare genetic disorder caused by pathogenic variants in the SRCAP gene.Most individuals with FHS have short stature,delayed speech and language development,and dysmorphic facial features.However,the patients with FHS are not easy to diagnose due to the overlap of clinical phenotypes with other disorders.CASE SUMMARY We reported a 10-year-old boy who presented with severe short stature,developmental delay and distinctive facial features.Exome sequencing was provided for the proband and his parents.We identified a novel frameshift variant c.7235delinsGT(p.Thr2412fs)in SRCAP gene,and the variant was further validated by Sanger sequencing.The mother of the proband was referred to us for prenatal consultation during next pregnancy.We performed prenatal genetic diagnosis for the fetus.The result of Sanger sequencing for c.7235delinsGT(p.Thr2412fs)in SRCAP gene showed that the fetus did not carry the variant,so the fetus has been born successfully.The newborn does not show any similar symptom to the proband till one month.CONCLUSION This case confirms that the c.7235delinsGT(p.Thr2412fs)variant in the SRCAP gene is associated with FHS and expands the spectrum of SRCAP variants.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
The level of genetic variation within a breeding population affects the effectiveness of selection strategies for genetic improvement.The relationship between genetic variation level within Pinus tabuliformis breeding...The level of genetic variation within a breeding population affects the effectiveness of selection strategies for genetic improvement.The relationship between genetic variation level within Pinus tabuliformis breeding populations and selection strategies or selection effectiveness is not fully investigated.Here,we compared the selection effectiveness of combined and individual direct selection strategies using half-and full-sib families produced from advanced-generation P.tabuliformis seed orchard as our test populations.Our results revealed that,within half-sib families,average diameter at breast height(DBH),tree height,and volume growth of superior individuals selected by the direct selection strategy were higher by 7.72%,18.56%,and 31.01%,respectively,than those selected by the combined selection strategy.Furthermore,significant differences(P<0.01)were observed between the two strategies in terms of the expected genetic gains for average tree height and volume.In contrast,within full-sib families,the differences in tree average DBH,height,and volume between the two selection strategies were relatively minor with increase of 0.17%,2.73%,and 2.21%,respectively,and no significant differences were found in the average expected genetic gains for the studied traits.Half-sib families exhibited greater phenotypic and genetic variation,resulting in improved selection efficiency with the direct selection strategy but also introduced a level of inbreeding risk.Based on genetic distance estimates using molecular markers,our comparative seed orchard design analysis showed that the Improved Adaptive Genetic Programming Algorithm(IAPGA)reduced the average inbreeding coefficient by 14.36% and 14.73% compared to sequential and random designs,respectively.In conclusion,the combination of the direct selection strategy with IAPGA seed orchard design aimed at minimizing inbreeding offered an efficient approach for establishing advanced-generation P.tabuliformis seed orchards.展开更多
Individual differences in treatment response in schizophrenia pose a significant challenge in the management of the disease,due to several biological as well as psychosocial factors,including genetic and epigenetic me...Individual differences in treatment response in schizophrenia pose a significant challenge in the management of the disease,due to several biological as well as psychosocial factors,including genetic and epigenetic mechanisms.Pharmacoepi-genetics investigates how epigenetic mechanisms affect the variability in effect-iveness of treatments and adverse side effects.Antipsychotics such as clozapine(atypical)and haloperidol(typical)directly induce epigenetic changes by altering DNA methyltransferases and histone acetyltransferases,while indirectly affecting neuroinflammatory and stress response pathways.Personalized medicine using epigenetic markers(DNA methylation,non-coding RNAs including microRNAs and long non-coding RNAs)holds great promise for improving the drug response and reducing the side effects of antipsychotic treatment.These developments could revolutionize the treatment of schizophrenia by addressing the complexities involved in responding to treatment.However,ethical and technical barriers to implementing strategies based on epigenetic regulation in clinical practice are fundamental challenges that need to be carefully addressed in this field.This review examined the epigenetic mechanisms involved in the efficacy of antipsy-chotic drugs.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
Following the publication of Liu et al.(2024),an error was identified in Figure 4B,in which the image representing the lung from the E529G group was inadvertently duplicated with the image of the lung from the WT grou...Following the publication of Liu et al.(2024),an error was identified in Figure 4B,in which the image representing the lung from the E529G group was inadvertently duplicated with the image of the lung from the WT group during figure preparation.展开更多
The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KC...The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.展开更多
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.
文摘The mussel is one of the main cultivated species in the world.A significant challenge faced by suspension-cultured mussels is the high incidence of mussel fall-off from cultivation ropes,adversely impacting harvest yields,which have been documented at commercial mussel farms in the United Kingdom,the United States of America,Canada,Spain,New Zealand and China.Byssus is an important attachment structure for marine mussels,and weakness in byssal thread attachment is a major factor leading to mussel detachment from ropes.To investigate the relationship between genetic variability and byssal thread phenotypic characteristics in the hard-shelled mussel(Mytilus coruscus),we collected three wild populations of M.coruscus from different latitudes in the East China Sea,including the Shengsi(SS),Jiaojiang(JJ),and Fuding(FD)populations.The genetic diversity and structure of these populations were investigated using 10 microsatellite loci.The mean observed heterozygosity(Ho)in the SS population was 0.44,higher than the mean Ho values of the JJ(0.40)and FD(0.39)populations.The mean inbreeding coefficients(F_(is))in the SS population was 0.20,lower than the mean F_(is)values of the JJ(0.33)and FD populations(0.40).These results revealed that the SS population exhibited higher genetic diversity compared to the other two populations.The different numbers of private alleles(P_(a))in the three populations,ranging from 10 to 17,suggest that these populations have experienced selective pressures from various environments.Moreover,genetic differentiation was observed in the genetic distance between the SS population and the other two populations.We also examined the phenotypic characteristics of their byssal threads.There were significant differences in byssus attachment strength among the three populations,with the SS population located at the highest latitude secreting more byssal threads and exhibiting greater byssal breaking force and plaque adhesion strength,while the Fuding(FD)population located at the lowest latitude had the weakest byssal attachment.The observed differentiation in private alleles and byssus phenotypes might suggest that the three wild populations have experienced different environmental selective pressures.This study provides insight for future genetic enhancement programs aimed at improving byssus attachment in M.coruscus.
基金supported by the Natural Science Foundation of Sichuan Province,China(2024NSFSC1272)the Innovation Team Development Funds for Sichuan Mutton Goat&Sheep,China(SCCXTD-2024-14)Scientific and Technological Innovation Team for Qinghai-Tibetan Plateau Research in Southwest Minzu University,China(2024CXTD08)。
文摘Bocapavovirus,a member of the genus Bocaparvovirus within the subfamily Parvovirinae and the family Parvoviridae,is a small,non-enveloped,single-stranded DNA virus.This pathogen poses health risks to both humans and animals.The Bocaparvovirus genome.
基金European Union-Next Generation EU,Through the National Recovery and Resilience Plan of the Republic of Bulgaria Project,No.BG-RRP-2.004-0008.
文摘Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
基金Supported by the Kuwait Foundation for the Advancement of Sciences and Dasman Diabetes Institute,No.RACB-2021-007.
文摘In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing,with particular emphasis on DNA and RNA methylation pathways.This editorial discusses the findings of Xiao et al,who identified the Wilms tumor 1-associated protein(WTAP)-DNA methyltransferase 1(DNMT1)axis as a pivotal regulator of endothelial dys-function in DFUs.WTAP,a regulatory subunit of N6-methyladenosine(m6A)methyltransferase,is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification.This contributes to im-paired angiogenesis,reduced cell viability,and delayed wound closure.WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model.Furthermore,DNMT1 overexpression ab-rogated the benefits of WTAP suppression,confirming its downstream effector role.Thus,targeting the WTAP-DNMT1 axis provides a new avenue for DFU management.Moreover,epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.
基金supported by the Jiangxi Province Higher Education Teaching Research Project(JXJG-22-23-3,NSJG-21-25)Jiangxi Province Key Laboratory of Oil Crops Biology(YLKFKT202203).
文摘Rorippa indica is a wild oilseed crop of Brassicaceae with good environmental adaptability and strong stress resistance.This plant has become an important wild relative species for rapeseed(Brassica napus L.)and is used to improve its agronomic traits,with important development and utilization value.However,the research of R.indica genetics is still lacking.And no mitochondrial genome(mitogenome)in the genus Rorippa has been expounded.To analyze the structural characteristics of the R.indica mitogenome,second-generation and third-generation sequencing techniques were made to assemble its mitogenome.The results showed that its mitogenome is composed of a single master circle DNA molecule,with 59 genes(33 protein-coding,23 tRNA,and 3 ribosomal RNA genes)annotated.The length of the circular genome is 219,775 bp,with aGCcontent of 45.24%.Themitochondrial genome contains 55 SSRs,17 tandem repeats,and 252 scattered repeat sequences,with scattered repeat sequences accounting for 77.78%.The top two codons with the highest expression levels are TTT and AUU.Moreover,377 RNA editing sites were forecasted in the R.indica mitogenome.And 22 collinear gene fragments were discriminated in the R.indica chloroplast andmitogenomes,with a total 13,153 bp length,accounting for 4.08%of the mitogenome sequence.The longest gene migration fragment is 2186 bp,and the shortest fragment is 42 bp.Furthermore,12 genes undergo complete migration between the two genomes,and 10 genes undergo partial migration.Systematic evolutionary analysis shows that R.indica and Brassica napus are grouped,indicating a close genetic relationship between the two.Herein,the R.indica mitogenome was sequenced and annotated,and it was compared with other Brassicaceae mitogenomes.A genomic data foundation was supplied for elucidating the R.indica origin and evolution.
基金supported by the Science and Technology Special Fund of Hainan Province(Grant Nos.ZDYF2021XDNY159 and ZDYF2021XDNY156)the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Science(Grant No.1630032022007)China Agricultural Research System of MOF and MARA(Grant No.CARS-32-01)。
文摘Litchi(Litchi chinensis Sonn.),an important fruit tree in tropical and subtropical regions,possesses substantial economic value.The branchand leaf-related traits of litchi have a significant impact on litchi yield and quality.However,due to limitations such as the density of the genetic linkage map,there have been few studies on mapping QTLs of branch-and leaf-related traits.In this study,a high-density genetic map was constructed by next-generation sequencing(NGS)using an F_(1) population of 264 progenies,derived from the cross between the cultivars‘Sanyuehong'and‘Ziniangxi'.A total of 2574 high-quality BINs(binomial intervals)were obtained,and a genetic linkage map was constructed with a total length of 1753.3 cM and an average marker distance of 0.68 cM.With the genetic map and the phenotyping of single leaf length(SLL),single leaf width(SLW),leaf shape index(LSI),weight of specific leaf(WSL),petiole length(PL)and compound leaf length(CLL)measured in three seasons,11,9,9,10,9 and 12 QTLs were detected for SLL,SLW,WSL,LSI,PL and CLL traits,respectively.Among these QTLs,five QTLs were consistently detected in two seasons and 12 pleiotropic QTLs were identified for at least two traits.These findings will provide new insights for the gene cloning for branch-and leaf-related traits as well as marker-assisted selection(MAS).
基金funded by Department of Science&Technology and Biotechnology,Govt.of West Bengal,India[Sanction No.565(Sanc.)/STBT-13015/15/11/2021-ST SEC]。
文摘Gerbera,a popular commercial cut flower with vibrant and striking colors has gained immense popularity in the floriculture industry.They are widely cultivated in various regions,making them available throughout the year.As a better alternative to conventional propagation methods(via seeds and rhizomes),plant tissue culture serves as way to avail large-scale,uniform,disease-free plantlets for commercial cultivation as well as to develop novel genotypes.In addition,it ensures production of healthy plantlets throughout the year in limited space.Based on the plant tissue culture techniques,the in vitro polyploidization,mutagenesis,and genetic transformation pave a path for creation of variation and eventually enhancing the ornamental traits to address the consumers’preferences and also facilitates in developing stress tolerant lines thereby minimizing the losses during cultivation,maintaining the quality of the flowers.This comprehensive review article presents an overview of the recent advancements on genetic improvement of gerbera via various cutting-edge plant tissue culture-based tools and techniques that contribute in enhancing the quality and efficiency of gerbera cultivation,meeting the demands of the floriculture industry while addressing the challenges of changing environment and resource limitations.
基金supported by the Fundamental Research Funds for the Central Universities(2021ZY62)the National Natural ScienceFoundation of China(31901337)the 5·5 Engineering Research&Innovation Team Project of Beijing Forestry University(BLRC2023C06).
文摘Eucalyptus urophylla×E.grandis is a major hybrid species of timber plantations.However,our under-standing of Eucalyptus mitochondrial genome,especially within the Myrtaceae family,is limited.In this study,we employed hybrid sequencing combining the Illumina and Oxford Nanopore sequencing to assemble and annotate the mitogenome(mtDNA)of E.urophylla×E.grandis.Our results reveal a structure characterized by one circular mol-ecule,with a cumulative length of 483,907 base pairs(bp)and a GC content of 44.96%.The circular molecule collec-tively harbored 59 annotated genes.Among these,38 were unique protein-coding genes(PCGs),accompanied by 18 transfer RNA(tRNA)genes and 3 ribosomal RNA(rRNA)genes.Our study also examined repetitive sequences,RNA editing sites,and intracellular sequence transfers within the mtDNA.Furthermore,we conducted a phylogenetic analy-sis between E.urophylla×E.grandis and 30 closely related species based on genetic affinities.The outcomes furnish a high-quality organelle genome for E.urophylla×E.grandis,thereby explaining basic insights into organelle genome evo-lution and phylogenetic relationships.
基金supported by a Biological Breeding-National Science and Technology Major Project(2022ZD040190301)the Agricultural Science and Technology Innovation Program(CAAS-CSNCB-202301)。
文摘Soybean(Glycine max)variety Heihe 54 has played a crucial role in the Heihe soybean breeding program in China,contributing to the development of over 85 cultivars.To elucidate the genetic changes that have occurred across multiple generations of selection during soybean breeding,we conducted comprehensive genotyping analysis using the 180K Axiom SoyaSNP array on 42 varieties from the Heihe breeding program,as well as eight parental lines.Cluster analysis revealed four distinct groups,reflecting various breeding phases that incorporated diverse genetic resources as parental lines within the pedigree.A detailed examination of the graphical genotype profile across the genome identified preferred chromosome segments for specific breeding phases.These conserved blocks,which have been consistently maintained in descendant varieties during the extensive breeding period,likely harbor genes related to critical agronomic traits.This is exemplified by the consistent transmission of two segments located on chromosomes 18 and 20,which harbor the stem growth habit-related gene Dt2 and the leaflet shape-related gene Ln,respectively.The widespread cultivation of Heihe 43,a soybean cultivar developed within this pedigree,is attributed to its broad genetic base and the pyramiding of elite alleles from its parental lines.The identification of favorable chromosome segments provides valuable insight for agronomic traitrelated gene mining and targeted breeding in the future.
文摘A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.
基金Supported by National Key Research and Development Program of China,No.2022YFC2703302.
文摘BACKGROUND Floating-harbor syndrome(FHS)is a rare genetic disorder caused by pathogenic variants in the SRCAP gene.Most individuals with FHS have short stature,delayed speech and language development,and dysmorphic facial features.However,the patients with FHS are not easy to diagnose due to the overlap of clinical phenotypes with other disorders.CASE SUMMARY We reported a 10-year-old boy who presented with severe short stature,developmental delay and distinctive facial features.Exome sequencing was provided for the proband and his parents.We identified a novel frameshift variant c.7235delinsGT(p.Thr2412fs)in SRCAP gene,and the variant was further validated by Sanger sequencing.The mother of the proband was referred to us for prenatal consultation during next pregnancy.We performed prenatal genetic diagnosis for the fetus.The result of Sanger sequencing for c.7235delinsGT(p.Thr2412fs)in SRCAP gene showed that the fetus did not carry the variant,so the fetus has been born successfully.The newborn does not show any similar symptom to the proband till one month.CONCLUSION This case confirms that the c.7235delinsGT(p.Thr2412fs)variant in the SRCAP gene is associated with FHS and expands the spectrum of SRCAP variants.
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financially supported by the Biological BreedingNational Science and Technology Major Project(2023ZD0405806)the National Key R&D Program for the 14th Five-Year Plan in China(2022YFD2200304).
文摘The level of genetic variation within a breeding population affects the effectiveness of selection strategies for genetic improvement.The relationship between genetic variation level within Pinus tabuliformis breeding populations and selection strategies or selection effectiveness is not fully investigated.Here,we compared the selection effectiveness of combined and individual direct selection strategies using half-and full-sib families produced from advanced-generation P.tabuliformis seed orchard as our test populations.Our results revealed that,within half-sib families,average diameter at breast height(DBH),tree height,and volume growth of superior individuals selected by the direct selection strategy were higher by 7.72%,18.56%,and 31.01%,respectively,than those selected by the combined selection strategy.Furthermore,significant differences(P<0.01)were observed between the two strategies in terms of the expected genetic gains for average tree height and volume.In contrast,within full-sib families,the differences in tree average DBH,height,and volume between the two selection strategies were relatively minor with increase of 0.17%,2.73%,and 2.21%,respectively,and no significant differences were found in the average expected genetic gains for the studied traits.Half-sib families exhibited greater phenotypic and genetic variation,resulting in improved selection efficiency with the direct selection strategy but also introduced a level of inbreeding risk.Based on genetic distance estimates using molecular markers,our comparative seed orchard design analysis showed that the Improved Adaptive Genetic Programming Algorithm(IAPGA)reduced the average inbreeding coefficient by 14.36% and 14.73% compared to sequential and random designs,respectively.In conclusion,the combination of the direct selection strategy with IAPGA seed orchard design aimed at minimizing inbreeding offered an efficient approach for establishing advanced-generation P.tabuliformis seed orchards.
文摘Individual differences in treatment response in schizophrenia pose a significant challenge in the management of the disease,due to several biological as well as psychosocial factors,including genetic and epigenetic mechanisms.Pharmacoepi-genetics investigates how epigenetic mechanisms affect the variability in effect-iveness of treatments and adverse side effects.Antipsychotics such as clozapine(atypical)and haloperidol(typical)directly induce epigenetic changes by altering DNA methyltransferases and histone acetyltransferases,while indirectly affecting neuroinflammatory and stress response pathways.Personalized medicine using epigenetic markers(DNA methylation,non-coding RNAs including microRNAs and long non-coding RNAs)holds great promise for improving the drug response and reducing the side effects of antipsychotic treatment.These developments could revolutionize the treatment of schizophrenia by addressing the complexities involved in responding to treatment.However,ethical and technical barriers to implementing strategies based on epigenetic regulation in clinical practice are fundamental challenges that need to be carefully addressed in this field.This review examined the epigenetic mechanisms involved in the efficacy of antipsy-chotic drugs.
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.
文摘Following the publication of Liu et al.(2024),an error was identified in Figure 4B,in which the image representing the lung from the E529G group was inadvertently duplicated with the image of the lung from the WT group during figure preparation.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273458 to Jinfei Chen)the Start-up Fund for the Recruited Talents of the First Affiliated Hospital of Wenzhou Medical University(Grant No.2021QD025 to Jinfei Chen)。
文摘The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.
