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
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
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
Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more c...Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.展开更多
Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complem...Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complement clinical approaches.Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior.Epigenetic mechanisms,including DNA methylation,histone modifications,and non-coding RNAs,regulate gene expression and may act as a bridge between environmental stressors and(neuro)inflammatory responses.In this review,we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior.Next,we review current knowledge from various studies on suicide-associated epigenetic alterations.Furthermore,we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis,focusing on their association with epigenetic modifications and inflammatory pathways.We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation.While challenging,research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.展开更多
In 2018, we will celebrate the 40th anniversary of Genetics Society of China （GSC）, which was founded in Nanjing, China in October, 1978, soon after China adopted an open door policy for reform. One major mission of...In 2018, we will celebrate the 40th anniversary of Genetics Society of China （GSC）, which was founded in Nanjing, China in October, 1978, soon after China adopted an open door policy for reform. One major mission of GSC during its inception was to publish a genetics journal, aiming to provide a window for Chinese geneticists to showcase their new discoveries. In fact, a genetics journal named Acta Genetica Sinica （AGS） had been published since June of 1974 （Fig. 1 ）. This journal published two issues in its first year in Chinese. The first issue covered breeding and genetics of several crop plants, including wheat, tobacco, maize, octoploid triticale, peanut and upland cotton, protoplast isolation and fusion, observation of cell nuclei during mouse spermatogenesis, derivation of early season rice, etiology and pathogenesis of favism, a good collection of Chinese genetic studies then.展开更多
Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and envir...Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and environmental pollution are sources of infertility in men. The aim of this study was to determine the spermological profile of infertile men and the factors associated with sperm parameter abnormalities. Methods: This retrospective study analysed 1000 sperm samples over an 11-year period, from January 2010 to December 2021. Results: The average age was 37.52 ± 8.66 years. Surgical history of varicocele and teratozoospermia were associated (p-value = 0.0001). Candida albicans was associated with a 2.27-fold risk of necrozoospermia and a 3.14-fold risk of oligozoospermia. The link between the reason for requesting a spermogram and the age range between 38 and 47 was significant (p-value Conclusion: Today, lifestyle and environmental pollution play a major role in sperm parameter abnormalities.展开更多
High-throughput genotyping tools can effectively promote molecular breeding in crops.In this study,genotyping by target sequencing(GBTS)system was utilized to develop a genome-wide liquid SNP chip for facilitating gen...High-throughput genotyping tools can effectively promote molecular breeding in crops.In this study,genotyping by target sequencing(GBTS)system was utilized to develop a genome-wide liquid SNP chip for facilitating genetics and breeding in melon(Cucumis melo L.),a globally cultivated economically important horticultural crop.Based on over eight million SNPs derived from 823 representative melon accessions,16K,8K,4K,2K,1K,500,250 and 125 informative SNPs were screened and evaluated for their polymorphisms,conservation of flanking sequences,and distributions.The set of 2K SNPs was found to be optimal for representing the maximum diversity with the lowest number of SNPs,and it was selected to develop the liquid chip,named“Melon2K”.Using Melon2K,more than 1500 SNPs were detected across 17 samples of five melon cultivars,and the phylogenetic relationships were clearly constructed.Within the same cultivar,genetic differences were also assessed between different samples.We evaluated the performance of Melon2K in genetic background selection during the breeding process,obtaining the introgression lines of interested trait with more than 97%genetic background of elite variety by only two rounds of backcrossing.These results suggest that Melon2K provides a cost-effective,efficient and reliable platform for genetic analysis and molecular breeding in melon.展开更多
Sugarcane is recognized as the fifth largest crop globally,supplying 80%of sugar and 40%of bioenergy production.However,sugarcane genetic research has significantly lagged behind other crops due to its complex genetic...Sugarcane is recognized as the fifth largest crop globally,supplying 80%of sugar and 40%of bioenergy production.However,sugarcane genetic research has significantly lagged behind other crops due to its complex genetic background,high ploidy(8-13×),aneuploidy,limited flowering,and a long growth cycle(more than one year).Cross breeding began in 1887 following the discovery that sugarcane seeds could germinate.Both self-and cross-pollination and selection were conducted by sugarcane breeders,but new cultivars were often eliminated due to disease susceptibility.Within the Saccharum genus,different species possess variable numbers of chromosomes.Wild sugarcane species intercrossed with each other,leading to development of the‘Nobilization’breeding strategy,which significantly improved yield,sucrose,fiber content,and disease resistance,and accelerated genetic improvement of cultivars.In recent years,scientific achievements have also been made in sugarcane genome sequencing,molecular marker development,genetic linkage map construction,localization of quantitative trait locus(QTL),and trait-associated gene identification.This review focuses on the progress in sugarcane genetic research,analyzes the technical difficulties faced,presents opportunities and challenges,and provides guidance and references for future sugarcane genetics research and cultivar breeding.Finally,it offers directions for future on sugarcane genetics.展开更多
The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development ...The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.展开更多
Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). I...Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.展开更多
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major ...Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.展开更多
Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial in...Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.展开更多
Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis bu...Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy,Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a wellconstructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection,along with strong support at the national industry level.展开更多
Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression...Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer (CRC). Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer develops only as the result of the progressive accumulation of genetic and epigenetic alterations. Diet can both prevent and induce colon carcinogenesis, for instance, through epigenetic changes, which regulate the homeostasis of the intestinal mucosa. Food-derived compounds are constantly present in the intestine and may shift cellular balance toward harmful outcomes, such as increased susceptibility to mutations. There is strong evidence that a major component of cancer risk may involve epigenetic changes in normal cells that increase the probability of cancer after genetic mutation. The recognition of epigenetic changes as a driving force in colorectal neoplasia would open new areas of research in disease epidemiology, risk assessment, and treatment, especially in mutation carriers who already have an inherited predisposition to cancer.展开更多
Plant centromeres are generally composed of tandem arrays of simple repeats that form a complex chromosome locus where the kinetochore forms and microtubules attach during mitosis and meiosis. Each chromosome has one ...Plant centromeres are generally composed of tandem arrays of simple repeats that form a complex chromosome locus where the kinetochore forms and microtubules attach during mitosis and meiosis. Each chromosome has one centromere region, which is essential for accurate division of the genetic material. Recently, chromosomes containing two centromere regions （called dicentric chromosomes） have been found in maize and wheat. Interestingly, some dicentric chromosomes are stable because only one centromere is active and the other one is inactivated. Because such arrays maintain their typical structure for both active and inactive centromeres, the specification of centromere activity has an epigenetic component independent of the DNA sequence. Under some circumstances, the inactive centromeres may recover centromere function, which is called centromere reactivation. Recent studies have highlighted the important changes, such as DNA methylation and histone modification, that occur during centromere inactivation and reactivation.展开更多
Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environme...Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a histone octamer(two copies of H2A, H2B, H3 and H4) to form nucleosome, the fundamental unit of chromatin. The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic mechanisms, including DNA methylation, histone posttranslational modifications(PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic mechanisms participate in almost all the important biological processes ranging from basal development to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also occur in plants. Plant studies have provided numerous important contributions to the epigenetic research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato.Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation(RdDM) pathway is plant-specific because of the involvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epigenetics field in China over the past several decades and give a brief outlook on future research prospects.We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms.展开更多
Pharmacogenetics is the study of the association between variability in drug response and （or） drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient＇s specific g...Pharmacogenetics is the study of the association between variability in drug response and （or） drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient＇s specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases （IBD）, ulcerative colitis （UC）, and Crohn＇s disease （CD） including sulfasalazine and mesalazine, azathioprine （AZA） and 6-mercaptopurine （6-MP）, methotrexate （MTX）, glucocorticosteroids （CSs） and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase （TPMT） gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.展开更多
Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression....Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression. Early introduction of immunosuppression forms the mainstay of medical IBD management. Large inter-individual variability in drug responses, in terms of both efficacy and toxicity, leads to high rates of therapeutic failure in the management of IBD. Better patient stratification is needed to maximize patient benefit and minimize the harm caused by adverse events. Pre-treatment pharmacogenetic testing has the potential to optimize drug selection and dose, and to minimize harm caused by adverse drug reactions. In addition, optimizing the use of cheap conventional drugs, and avoiding expensive ineffective drugs, will lead to a significant reduction in costs. Genetic variation in both TPMT and NUDT15, genes involved in thiopurine metabolism, is associated to an increased risk of thiopurine-induced myelosuppression. Moreover, specific HLA haplotypes confer risk to thiopurine-induced pancreatitis and to immunogenicity to tumor necrosis factor-antagonists, respectively. Falling costs and increased availability of genetic tests allow for the incorporation of pre-treatment genetic tests into clinical IBD management guidelines. In this paper, we review clinically useful pharmacogenetic associations for individualized treatment of patients with IBD and discuss the path from identification of a predictive pharmacogenetic marker to implementation into IBD clinical care.展开更多
Conservation genetics and genomics are two independent disciplines that focus on using new techniques in genetics and genomics to solve problems in conservation biology. During the past two decades,conservation geneti...Conservation genetics and genomics are two independent disciplines that focus on using new techniques in genetics and genomics to solve problems in conservation biology. During the past two decades,conservation genetics and genomics have experienced rapid progress. Here, we summarize the research advances in the conservation genetics and genomics of threatened vertebrates(e.g., carnivorans, primates, ungulates, cetaceans, avians, amphibians and reptiles) in China. First, we introduce the concepts of conservation genetics and genomics and their development. Second, we review the recent advances in conservation genetics research, including noninvasive genetics and landscape genetics. Third, we summarize the progress in conservation genomics research, which mainly focuses on resolving genetic problems relevant to conservation such as genetic diversity, genetic structure, demographic history, and genomic evolution and adaptation. Finally, we discuss the future directions of conservation genetics and genomics.展开更多
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.
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.
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.
文摘Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.
基金Supported by Slovenian Research and Innovation Agency Program,No.P1-0390 and No.N3-0349Slovenian Research and Innovation Agency Program,Young Researcher Grant(toŠmon J).
文摘Suicidality is a complex phenomenon influenced by genetic,environmental,and epigenetic factors.Current tools to estimate suicide risk are insufficient,and there is an increasing need for reliable biomarkers to complement clinical approaches.Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior.Epigenetic mechanisms,including DNA methylation,histone modifications,and non-coding RNAs,regulate gene expression and may act as a bridge between environmental stressors and(neuro)inflammatory responses.In this review,we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior.Next,we review current knowledge from various studies on suicide-associated epigenetic alterations.Furthermore,we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis,focusing on their association with epigenetic modifications and inflammatory pathways.We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation.While challenging,research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.
文摘In 2018, we will celebrate the 40th anniversary of Genetics Society of China （GSC）, which was founded in Nanjing, China in October, 1978, soon after China adopted an open door policy for reform. One major mission of GSC during its inception was to publish a genetics journal, aiming to provide a window for Chinese geneticists to showcase their new discoveries. In fact, a genetics journal named Acta Genetica Sinica （AGS） had been published since June of 1974 （Fig. 1 ）. This journal published two issues in its first year in Chinese. The first issue covered breeding and genetics of several crop plants, including wheat, tobacco, maize, octoploid triticale, peanut and upland cotton, protoplast isolation and fusion, observation of cell nuclei during mouse spermatogenesis, derivation of early season rice, etiology and pathogenesis of favism, a good collection of Chinese genetic studies then.
文摘Background: According to the World Health Organization, the worldwide prevalence of infertility is 17.5%. The male share of responsibility is undeniable. Several factors, such as smoking, alcoholism, obesity and environmental pollution are sources of infertility in men. The aim of this study was to determine the spermological profile of infertile men and the factors associated with sperm parameter abnormalities. Methods: This retrospective study analysed 1000 sperm samples over an 11-year period, from January 2010 to December 2021. Results: The average age was 37.52 ± 8.66 years. Surgical history of varicocele and teratozoospermia were associated (p-value = 0.0001). Candida albicans was associated with a 2.27-fold risk of necrozoospermia and a 3.14-fold risk of oligozoospermia. The link between the reason for requesting a spermogram and the age range between 38 and 47 was significant (p-value Conclusion: Today, lifestyle and environmental pollution play a major role in sperm parameter abnormalities.
基金supported by the National Natural Science Foundation of China(Grant Nos.32102383,32225044 and 32130093)the Natural Science Foundation of Shandong Province(Grant No.ZR2021QC075)+1 种基金the Taishan Scholar Foundation of the People's Government of Shandong Province(Grant No.ts20190947)the Qingdao Agricultural University Doctoral Start-Up Fund。
文摘High-throughput genotyping tools can effectively promote molecular breeding in crops.In this study,genotyping by target sequencing(GBTS)system was utilized to develop a genome-wide liquid SNP chip for facilitating genetics and breeding in melon(Cucumis melo L.),a globally cultivated economically important horticultural crop.Based on over eight million SNPs derived from 823 representative melon accessions,16K,8K,4K,2K,1K,500,250 and 125 informative SNPs were screened and evaluated for their polymorphisms,conservation of flanking sequences,and distributions.The set of 2K SNPs was found to be optimal for representing the maximum diversity with the lowest number of SNPs,and it was selected to develop the liquid chip,named“Melon2K”.Using Melon2K,more than 1500 SNPs were detected across 17 samples of five melon cultivars,and the phylogenetic relationships were clearly constructed.Within the same cultivar,genetic differences were also assessed between different samples.We evaluated the performance of Melon2K in genetic background selection during the breeding process,obtaining the introgression lines of interested trait with more than 97%genetic background of elite variety by only two rounds of backcrossing.These results suggest that Melon2K provides a cost-effective,efficient and reliable platform for genetic analysis and molecular breeding in melon.
基金supported by the National Key Research and Development Program of China(2022YFD2301100)National Natural Science Foundation of China(32272156)+3 种基金Natural Science Foundation of Fujian Province,China(2022J01160)Central Publicinterest Scientific Institution Basal Research Fund(1630052024003,1630052024020)Chinese Academy of Tropical Agricultural Sciences for Science and Technology Innovation Team of National Tropical Agricultural Science Center(CATASCXTD202402)China Agriculture Research System of MOF and MARA(CARS-17).
文摘Sugarcane is recognized as the fifth largest crop globally,supplying 80%of sugar and 40%of bioenergy production.However,sugarcane genetic research has significantly lagged behind other crops due to its complex genetic background,high ploidy(8-13×),aneuploidy,limited flowering,and a long growth cycle(more than one year).Cross breeding began in 1887 following the discovery that sugarcane seeds could germinate.Both self-and cross-pollination and selection were conducted by sugarcane breeders,but new cultivars were often eliminated due to disease susceptibility.Within the Saccharum genus,different species possess variable numbers of chromosomes.Wild sugarcane species intercrossed with each other,leading to development of the‘Nobilization’breeding strategy,which significantly improved yield,sucrose,fiber content,and disease resistance,and accelerated genetic improvement of cultivars.In recent years,scientific achievements have also been made in sugarcane genome sequencing,molecular marker development,genetic linkage map construction,localization of quantitative trait locus(QTL),and trait-associated gene identification.This review focuses on the progress in sugarcane genetic research,analyzes the technical difficulties faced,presents opportunities and challenges,and provides guidance and references for future sugarcane genetics research and cultivar breeding.Finally,it offers directions for future on sugarcane genetics.
文摘The history of medical genetics is briefly reviewed. It is evident that medical genetics with its inseparable part, clinical genetics, started out as a cfinical science from the very beginning. Its robust development in the developed countries is the result of a close interaction between the basic sciences and clinical genetics. In China, however, clinical genetics has not received due emphasis and medical genetics is still not recognized as one of the medical specialties. This is in marked contrast to the situation in the West. It is high time to acknowledge that medical genetics is a medical specialty and to promote clinical genetics service in qualified hospitals in our country.
基金Supported by Research grants from VCTI-UAN and Colcienciasresearch grants from Universidad del Rosario
文摘Neuropsychiatric disorders(NPDs) constitute a heavyburden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries(LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.
文摘Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
基金NC TraC S to Dai XNo.550KR91403+1 种基金NIH T32 to Wiernek SNo.HL083828-04
文摘Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.
基金supported by Ministry of Science and Technology Project (2017YFC1001302 and 2016YFC0906400)the Grant of Shanghai Brain-Intelligence Project from the Shanghai Science and Technology Committee (STCSM) (16JC1420500)Shanghai Jiao Tong University Medical Engineering Cross Research Foundation (YG2014MS07)
文摘Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy,Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a wellconstructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection,along with strong support at the national industry level.
基金Supported by Finnish Cancer Organisations,Biocentrum Helsinki,Finlandthe Ministry of Agriculture and Forestry,the Innovation in Food Programme of the National Technology Agency of Finland,and University of Helsinki,Finland
文摘Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer (CRC). Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer develops only as the result of the progressive accumulation of genetic and epigenetic alterations. Diet can both prevent and induce colon carcinogenesis, for instance, through epigenetic changes, which regulate the homeostasis of the intestinal mucosa. Food-derived compounds are constantly present in the intestine and may shift cellular balance toward harmful outcomes, such as increased susceptibility to mutations. There is strong evidence that a major component of cancer risk may involve epigenetic changes in normal cells that increase the probability of cancer after genetic mutation. The recognition of epigenetic changes as a driving force in colorectal neoplasia would open new areas of research in disease epidemiology, risk assessment, and treatment, especially in mutation carriers who already have an inherited predisposition to cancer.
基金supported by the grants from the National Natural Science Foundation of China (Nos.31071083 and 31130033)the National Science Foundation of USA (No.DBI 0922703)
文摘Plant centromeres are generally composed of tandem arrays of simple repeats that form a complex chromosome locus where the kinetochore forms and microtubules attach during mitosis and meiosis. Each chromosome has one centromere region, which is essential for accurate division of the genetic material. Recently, chromosomes containing two centromere regions （called dicentric chromosomes） have been found in maize and wheat. Interestingly, some dicentric chromosomes are stable because only one centromere is active and the other one is inactivated. Because such arrays maintain their typical structure for both active and inactive centromeres, the specification of centromere activity has an epigenetic component independent of the DNA sequence. Under some circumstances, the inactive centromeres may recover centromere function, which is called centromere reactivation. Recent studies have highlighted the important changes, such as DNA methylation and histone modification, that occur during centromere inactivation and reactivation.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB27040203)the National Natural Science Foundation of China (No.31770155)
文摘Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a histone octamer(two copies of H2A, H2B, H3 and H4) to form nucleosome, the fundamental unit of chromatin. The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic mechanisms, including DNA methylation, histone posttranslational modifications(PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic mechanisms participate in almost all the important biological processes ranging from basal development to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also occur in plants. Plant studies have provided numerous important contributions to the epigenetic research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato.Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation(RdDM) pathway is plant-specific because of the involvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epigenetics field in China over the past several decades and give a brief outlook on future research prospects.We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms.
文摘Pharmacogenetics is the study of the association between variability in drug response and （or） drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient＇s specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases （IBD）, ulcerative colitis （UC）, and Crohn＇s disease （CD） including sulfasalazine and mesalazine, azathioprine （AZA） and 6-mercaptopurine （6-MP）, methotrexate （MTX）, glucocorticosteroids （CSs） and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase （TPMT） gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.
文摘Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression. Early introduction of immunosuppression forms the mainstay of medical IBD management. Large inter-individual variability in drug responses, in terms of both efficacy and toxicity, leads to high rates of therapeutic failure in the management of IBD. Better patient stratification is needed to maximize patient benefit and minimize the harm caused by adverse events. Pre-treatment pharmacogenetic testing has the potential to optimize drug selection and dose, and to minimize harm caused by adverse drug reactions. In addition, optimizing the use of cheap conventional drugs, and avoiding expensive ineffective drugs, will lead to a significant reduction in costs. Genetic variation in both TPMT and NUDT15, genes involved in thiopurine metabolism, is associated to an increased risk of thiopurine-induced myelosuppression. Moreover, specific HLA haplotypes confer risk to thiopurine-induced pancreatitis and to immunogenicity to tumor necrosis factor-antagonists, respectively. Falling costs and increased availability of genetic tests allow for the incorporation of pre-treatment genetic tests into clinical IBD management guidelines. In this paper, we review clinically useful pharmacogenetic associations for individualized treatment of patients with IBD and discuss the path from identification of a predictive pharmacogenetic marker to implementation into IBD clinical care.
基金funded by Chinese Academy of Sciences (XDB31000000 and QYZDY-SSW-SMC019)Ministry of Science and Technology (2016YFC0503200)the National Natural Science Foundation of China (Nos.91531302 and 31670386)
文摘Conservation genetics and genomics are two independent disciplines that focus on using new techniques in genetics and genomics to solve problems in conservation biology. During the past two decades,conservation genetics and genomics have experienced rapid progress. Here, we summarize the research advances in the conservation genetics and genomics of threatened vertebrates(e.g., carnivorans, primates, ungulates, cetaceans, avians, amphibians and reptiles) in China. First, we introduce the concepts of conservation genetics and genomics and their development. Second, we review the recent advances in conservation genetics research, including noninvasive genetics and landscape genetics. Third, we summarize the progress in conservation genomics research, which mainly focuses on resolving genetic problems relevant to conservation such as genetic diversity, genetic structure, demographic history, and genomic evolution and adaptation. Finally, we discuss the future directions of conservation genetics and genomics.
