Phylogenetic relationships of Arundinaria and related genera (Pleioblastus, Pseudosasa, Oligostachyum, Bashania, Clavinodum, etc.) were assessed by analyzing the sequences of the nrDNA internal transcribed spacer (ITS...Phylogenetic relationships of Arundinaria and related genera (Pleioblastus, Pseudosasa, Oligostachyum, Bashania, Clavinodum, etc.) were assessed by analyzing the sequences of the nrDNA internal transcribed spacer (ITS) and the cpDNA trnL-F intergenic spacer (IGS). Comparison with trnL-F IGS sequence, the ITS region provided the higher number of parsimony informative characters, and the interspecific variation of the ITS sequence was higher than that of the trnL-F IGS sequence.The tree obtained by combining both sets of data showed that the species sampled in Arundinaria and the related genera were monophyletic and divided into two clades. The relationships and positioning of all the taxa surveryed (including A. oleosa, A. hsienchuensis, A. chino, A. amara, A. yixingensis, A. amabilis, A. fortunei, A. pygmaea, A. gramineus, A. fargesii, A. faberi, A. hupehense, Pseudosasa japonica cv. Tsutsumiana, P. japonica and Brachystachyum densiflorum) were also discussed. The results from the sequences were broadly consistent with morphological characters, appearing all these taxa sampled belong to the genus of Arundinaria. The topologies of the trees generated from individual data and the combined data were similar.展开更多
Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that res...Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.展开更多
Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multip...Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long noncoding RNAs(lnc RNAs) are transcripts longer than 200 nt, constituting a subpopulation of nc RNAs. Their biological effects are not well understood comparedto small non-coding RNA(micro RNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lnc RNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lnc RNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples(MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lnc RNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lnc RNAs using several approaches(siR NA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC.展开更多
Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular m...Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.展开更多
Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs （sRNAs）, some of which have been shown to regulate critical ce...Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs （sRNAs）, some of which have been shown to regulate critical cellular processes. Computational approaches, in combination with molecular experiments, have played an important role in the identification of these sRNAs. At present, there is no information on the presence of small non-coding RNAs and their genes in the Agrobacterium tumefaciens genome. To identify potential sRNAs in this important bacterium, deep sequencing of the short RNA populations isolated from Agrobacterium tumefaciens C58 was carried out. From a data set of more than 10,000 short sequences, 16 candidate sRNAs have been tentatively identified based on computational analysis. All of these candidates can form stem-loop structures by RNA folding predictions and the majority of the secondary structures are rich in GC base-pairs：：Some are followed by a short stretch of U residues, indicative of a rho-independent transcription terminator, whereas some of the short RNAs are found in the stem region of the hairpin, indicative of eukaryotic-like sRNAs. Experimental strategies will need to be used to verify these candidates. The study of an expanded list of candidate sRNAs in Agrobacterium will allow a more complete understanding of the range of roles played by regulatory RNAs in prokaryotes.展开更多
Conserved non-coding sequences(CNSs)are integral elements of transcriptional regulation.Transcriptional tuning of PLETHORA(PLT)genes that encode master regulators of plant development is vital for embryogenesis and me...Conserved non-coding sequences(CNSs)are integral elements of transcriptional regulation.Transcriptional tuning of PLETHORA(PLT)genes that encode master regulators of plant development is vital for embryogenesis and meristematic function.However,how the expression of PLT genes is modulated through CNSs remains unclear.Through motif-based mining of upstream sequences in 120 angiosperm ge-nomes,we identified 21 conserved and lineage-specific CNSs,two of which are unusually long,similar,and colinear within eudicots.Using Arabidopsis thaliana,we demonstrate that these two deeply conserved elements,which we named BOX1 and BOX2,control PLT1 and PLT2 expression.CRISPR mutants within these elements specifically reduced PLT expression levels,and reporter lines revealed that deletion of either or both BOXes altered and/or abrogated the PLT2 expression pattern in the root tip,affecting the abil-ity to rescue the plt1 plt2 double mutant.We further show that the influence of these elements on expres-sion patterns is already exerted during embryogenesis and functional in the context of the early embryo.Finally,we reveal the existence of a BOX-mediated autoregulatory feedback loop that,in large part,explains CNS influence on expression patterns.Wethus uncover a transcriptional mechanism by which genes encoding master regulators of embryo and root meristem development are regulated.展开更多
Adenosine to inosine （A-to-I） RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA （...Adenosine to inosine （A-to-I） RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA （ADAR） proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions （UTRs） and introns are located in pre-rnRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degrada- tion, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA （miRNA）, small interfering RNA （siRNA） and long non-coding RNA （lncRNA） are related to pre-mRNA splicing, translation, and gene regulation. A-to-I edit- ing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions （UTRs and introns） and non-coding RNAs （miRNA, siRNA, and IncRNA）.展开更多
Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle c...Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle cells, no contraction can take place. Therefore, calcium homeostasis is one of the critical regulatory mechanisms in all muscle cells, including skeletal muscle and heart [1,2]. Ca2＋ adenosine triphosphatase the relaxation of muscle cells Sarco-endoplasmic reticulum （SERCA） is responsible for by pumping Ca2＋ into the sarcoplasmic reticulum （SR） .展开更多
In plants, non-coding small RNAs play a vital role in plant development and stress responses. To explore the possible role of non-coding small RNAs in the regulation of the jasmonate （JA） pathway, we compared the no...In plants, non-coding small RNAs play a vital role in plant development and stress responses. To explore the possible role of non-coding small RNAs in the regulation of the jasmonate （JA） pathway, we compared the non-coding small RNAs between the JA-deficient aos mutant and the JA-treated wild type Arabidopsis via high-throughput sequencing. Thirty new miRNAs and 27 new miRNA candidates were identified through bioinformatics approach. Forty-nine known miRNAs （belonging to 24 families）, 15 new miRNAs and new miRNA candidates （belonging to 11 families） and 3 tasiRNA families were induced by JA, whereas 1 new miRNA, 1 tasiRNA family and 22 known miRNAs （belonging to 9 families） were repressed by JA.展开更多
The Human Genome Project marked a milestone in scientific exploration,unraveling the genetic blueprint of humanity.However,expectations of direct gene–disease associations gave way to realizing the complexity of gene...The Human Genome Project marked a milestone in scientific exploration,unraveling the genetic blueprint of humanity.However,expectations of direct gene–disease associations gave way to realizing the complexity of genetic interactions,especially in polygenic diseases.This review explores the legacy of the HGP and subsequent advancements in genomic technologies,particularly next-generation sequencing,which have enabled more profound insights into the non-coding genome's role in gene regulation.While initially dismissed as“junk”DNA,non-coding regions are now officially approved as critical gene expression and genome organization regulators.Through integrative genomics approaches and advanced computational methods,researchers have unveiled the intricate network of enhancers,promoters,and chromatin modifications orchestrating gene expression.High-throughput sequencing techniques and functional assays have identified non-coding variants associated with numerous diseases,challenging the conventional focus on coding sequences in genomic studies.By elucidating the regulatory mechanisms governing gene expression,researchers can advance precision medicine approaches and develop novel diagnostic tools.As genomic research continues to evolve,a vast landscape is waiting to be explored,promising transformative insights into human health and disease.This review provides a comprehensive overview of the non-coding genome's role in gene regulation and its implications for understanding complex diseases and developing targeted therapeutic interventions.展开更多
This study determined the sequences of chloro-plast DNA(cpDNA)trnL-F non-coding regions of indi-viduals of a tropical coniferous species,Dacrydium pectinatum,collected from 12 natural populations located in Hainan Pro...This study determined the sequences of chloro-plast DNA(cpDNA)trnL-F non-coding regions of indi-viduals of a tropical coniferous species,Dacrydium pectinatum,collected from 12 natural populations located in Hainan Province,southern China.Sequence length varied from 868 bp to 876 bp,indicating length polymorphism.Base com-position in the sequences was high in A+T content between 64.17%and 64.95%,and no recombination event occurred(Rm=0).Thirty haplotypes were identified based on statis-tical parsimony algorithm by running the TCS program.Populations of D.pectinatum in Hainan were lacking ge-netic differentiation.Such a deduction was supported by the observed FST values(0.00),AMOVA(24.17%of molecular variance attributed to difference among populations,P>0.05),high values of Nm(ranging from 1.92 to 2.50)and the branching structure in neighbor-joining(NJ)tree con-structed from haplotypes.A‘star-like’pattern was exhibited in the TCS network of trnL-F haplotypes,and majority of the haplotypes coalesced near the tips in NJ tree.Gene ge-nealogies of cpDNA haplotypes proposed a recent popula-tion expansion of D.pectinatum in Hainan,which was fur-ther supported by the results from Tajima’s D test and mis-match distribution analysis.Our data,in conjunction with geological and palynological evidences,showed that in the Holocene,due to global warming,refugee populations of D.pectinatum in Hainan might experience a range expan-sion.展开更多
The nuclear encoded internal transcribed spacer (ITS) region and the plastid encoded trn L-F region were sequenced for 41 species of the Aceraceae, representing both genera Acer and Dipteronia, to reconstruct phylogen...The nuclear encoded internal transcribed spacer (ITS) region and the plastid encoded trn L-F region were sequenced for 41 species of the Aceraceae, representing both genera Acer and Dipteronia, to reconstruct phylogeny of this family, especially within Acer. The analyses were performed in separate and combined sequence data sets, with the Sapindaceae and Hippocastanaceae being selected as outgroups. It was indicated that the Aceraceae was monophyletic and D. sinensis was basal to the rest of the family but the two genera of it might be not monophyletic because Dipteronia dyerana was nested within Acer. The result inferred from the combined data showed greater resolution within Acer than that from the two separate data sets. The monophyly of most sections in Xu's system (1996) were supported with high bootstrap values, and some relationships between (or among) sections were also inferred, such as sect. Palmata and sect. Microcarpa; sect. Platanoidea, sect. Lithocarpa and sect. Macrophylla; sect. Integrifolia, sect. Trifoliata and sect. Pentaphylla; and sect. Acer, sect. Goniocarpa and sect. Saccharina (sensu Ogata). However, the sectional status and circumscriptions of some of the above-mentioned sections should be further adjusted. It seemed that the Xu's delimitations of sect. Rubra and sect. Saccharodendran should be revaluated.展开更多
Spinal cord injury(SCI)is a serious traumatic event to the central nervous system.Studies show that long non-coding RNAs(lncRNAs)play an important role in regulating the inflammatory response in the acute stage of SCI...Spinal cord injury(SCI)is a serious traumatic event to the central nervous system.Studies show that long non-coding RNAs(lncRNAs)play an important role in regulating the inflammatory response in the acute stage of SCI.Here,we investigated a new lncRNA related to spinal cord injury and acute inflammation.We analyzed the expression profile of lncRNAs after SCI,and explored the role of lncRNA Airsci(acute inflammatory response in SCI)on recovery following acute SCI.The rats were divided into the control group,SCI group,and SCI+lncRNA Airsci-siRNA group.The expression of inflammatory factors,including nuclear factor kappa B[NF-κB(p65)],NF-κB inhibitor IκBαand phosphorylated IκBα(p-IκBα),and the p-IκBα/IκBαratio were examined 1–28 days after SCI in rats by western blot assay.The differential lncRNA expression profile after SCI was assessed by RNA sequencing.The differentially expressed lncRNAs were analyzed by bioinformatics technology.The differentially expressed lncRNA Airsci,which is involved in NF-κB signaling and associated with the acute inflammatory response,was verified by quantitative real-time PCR.Interleukin(IL-1β),IL-6 and tumor necrosis factor(TNF-α)at 3 days after SCI were measured by western blot assay and quantitative real-time PCR.The histopathology of the spinal cord was evaluated by hematoxylin-eosin and Nissl staining.Motor function was assessed with the Basso,Beattie and Bresnahan Locomotor Rating Scale.Numerous differentially expressed lncRNAs were detected after SCI,including 151 that were upregulated and 186 that were downregulated in the SCI 3 d group compared with the control group.LncRNA Airsci was the most significantly expressed among the five lncRNAs involved in the NF-κB signaling pathway.LncRNA Airsci-siRNA reduced the inflammatory response by inhibiting the NF-κB signaling pathway,alleviated spinal cord tissue injury,and promoted the recovery of motor function in SCI rats.These findings show that numerous lncRNAs are differentially expressed following SCI,and that inhibiting lncRNA Airsci reduces the inflammatory response through the NF-κB signaling pathway,thereby promoting functional recovery.All experimental procedures and protocols were approved by the approved by the Animal Ethics Committee of Jining Medical University(approval No.JNMC-2020-DW-RM-003)on January 18,2020.展开更多
Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate b...Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design.展开更多
Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate trau...Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.展开更多
Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development...Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical approaches.PIWIinteracting RNAs(piRNAs)are a class of small non-coding RNAs that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of piRNAs plays a crucial role in the progression of various human cancers.In this editorial,we report on the current knowledge of HCC-associated piRNAs and their potential clinical utility.Based on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular RNAs in HCC,we highlight this other emerging class of non-coding RNAs.展开更多
Objective:To establish the messenger RNA(mRNA)and long non-coding RNA(lncRNA)expression profiles in ectopic and eutopic endometrium and provide novel insights into endometriosis.Methods:The mRNA and lncRNA expression ...Objective:To establish the messenger RNA(mRNA)and long non-coding RNA(lncRNA)expression profiles in ectopic and eutopic endometrium and provide novel insights into endometriosis.Methods:The mRNA and lncRNA expression profiles were tested using high-throughput sequencing technology in ectopic and eutopic endometrium with endometriosis and normal endometrium without endometriosis.The potential targeted lncRNAs were annotated by analyzing the correlation between lncRNA and mRNA expression to better understand the pathogenesis of endometriosis.Results:In ectopic compared with normal endometrium,a total of 2,188 mRNAs and 1,200 lncRNAs were differentially expressed with a fold-change(FC)≥2.5.In eutopic compared with normal endometrium,a total of 2,324 mRNAs and 695 lncRNAs were differentially expressed with an FC≥1.5.In ectopic compared with eutopic endometrium,a total of 2,223 mRNAs and 511 lncRNAs were differentially expressed with an FC≥2.Bioinformatic analysis indicated that the differentially expressed mRNAs were enriched in the biological processes and signaling pathways involved in endometriosis.In addition,we constructed a gene coexpression network based on the dysregulated lncRNAs in both ectopic endometrium and eutopic endometrium,combined with their coexpressed mRNAs to simulate the complex interactions.Conclusions:This study describes the first-to-integrate analysis of the differential expression profiles of mRNAs and lncRNAs,including analyses between ectopic and normal endometrium,eutopic and normal endometrium,and ectopic and eutopic endometrium,which provides new insights to investigate the pathogenesis of endometriosis and explore novel diagnostic biomarkers and therapeutic targets.展开更多
High-throughput sequencing has identified a large number of sense-antisense transcriptional pairs, which indicates that these genes were transcribed from both directions. Recent reports have demonstrated that many ant...High-throughput sequencing has identified a large number of sense-antisense transcriptional pairs, which indicates that these genes were transcribed from both directions. Recent reports have demonstrated that many antisense RNAs, especially lnc RNA（long non-coding RNA）, can interact with the sense RNA by forming an RNA duplex. Many methods, such as RNA-sequencing, Northern blotting, RNase protection assays and strand-specific PCR, can be used to detect the antisense transcript and gene transcriptional orientation. However, the applications of these methods have been constrained, to some extent, because of the high cost, difficult operation or inaccuracy, especially regarding the analysis of substantial amounts of data. Thus, we developed an easy method to detect and validate these complicated RNAs. We primarily took advantage of the strand specificity of RT-PCR and the single-strand specificity of S1 endonuclease to analyze sense and antisense transcripts. Four known genes, including mouse β-actin and Tsix（Xist antisense RNA）, chicken LXN（latexin） and GFM1（Gelongation factor, mitochondrial 1）, were used to establish the method. These four genes were well studied and transcribed from positive strand, negative strand or both strands of DNA, respectively, which represented all possible cases. The results indicated that the method can easily distinguish sense, antisense and sense-antisense transcriptional pairs. In addition, it can be used to verify the results of high-throughput sequencing, as well as to analyze the regulatory mechanisms between RNAs. This method can improve the accuracy of detection and can be mainly used in analyzing single gene and was low cost.展开更多
Fundamental improvement was made for genome sequencing since the next-generation sequencing （NGS） came out in the 2000s. The newer technologies make use of the power of massively-parallel short-read DNA sequencing, ...Fundamental improvement was made for genome sequencing since the next-generation sequencing （NGS） came out in the 2000s. The newer technologies make use of the power of massively-parallel short-read DNA sequencing, genome alignment and assembly methods to digitally and rapidly search the genomes on a revolutionary scale, which enable large-scale whole genome sequencing （WGS） accessible and practical for researchers. Nowadays, whole genome sequencing is more and more prevalent in detecting the genetics of diseases, studying causative relations with cancers, making genome-level comparative analysis, reconstruction of human population history, and giving clinical implications and instructions. In this review, we first give a typical pipeline of whole genome sequencing, including the lab template preparation, sequencing, genome assembling and quality control, variants calling and annotations. We compare the difference between whole genome and whole exome sequencing （WES）, and explore a wide range of applications of whole genome sequencing for both mendelian diseases and complex diseases in medical genetics. We highlight the impact of whole genome sequencing in cancer studies, regulatory variant analysis, predictive medicine and precision medicine, as well as discuss the challenges of the whole genome sequencing.展开更多
文摘Phylogenetic relationships of Arundinaria and related genera (Pleioblastus, Pseudosasa, Oligostachyum, Bashania, Clavinodum, etc.) were assessed by analyzing the sequences of the nrDNA internal transcribed spacer (ITS) and the cpDNA trnL-F intergenic spacer (IGS). Comparison with trnL-F IGS sequence, the ITS region provided the higher number of parsimony informative characters, and the interspecific variation of the ITS sequence was higher than that of the trnL-F IGS sequence.The tree obtained by combining both sets of data showed that the species sampled in Arundinaria and the related genera were monophyletic and divided into two clades. The relationships and positioning of all the taxa surveryed (including A. oleosa, A. hsienchuensis, A. chino, A. amara, A. yixingensis, A. amabilis, A. fortunei, A. pygmaea, A. gramineus, A. fargesii, A. faberi, A. hupehense, Pseudosasa japonica cv. Tsutsumiana, P. japonica and Brachystachyum densiflorum) were also discussed. The results from the sequences were broadly consistent with morphological characters, appearing all these taxa sampled belong to the genus of Arundinaria. The topologies of the trees generated from individual data and the combined data were similar.
文摘Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.
文摘Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population and the sixth most common cancer worldwide. HCC is characterized by deregulation of multiple genes and signalling pathways. These genetic effects can involve both protein coding genes as well as non-coding RNA genes. Long noncoding RNAs(lnc RNAs) are transcripts longer than 200 nt, constituting a subpopulation of nc RNAs. Their biological effects are not well understood comparedto small non-coding RNA(micro RNAs), but they have been recently recognized to exert a crucial role in the regulation of gene expression and modulation of signalling pathways. Notably, several studies indicated that lnc RNAs contribute to the pathogenesis and progression of HCC. Investigating the molecular mechanisms underlying lnc RNAs expression opens potential applications in diagnosis and treatment of liver disease. This editorial provides three examples(MALAT-1 metastasis associated lung adenocarcinoma transcript, HULC highly upregulated in liver cancer and HOTAIR HOX transcript antisense intergenic RNA) of well-known lnc RNAs upregulated in HCC, whose mechanisms of action are known, and for which therapeutic applications are delineated. Targeting of lnc RNAs using several approaches(siR NA-mediated silencing or changing their secondary structure) offers new possibility to treat HCC.
基金financially supported by the National Natural Science Foundation of China,No.81371366(to HFW)Characteristic Innovation Project of Colleges and Universities in Guangdong Province of China,No.2018KTSCX075(to HFW)+3 种基金the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)College Students’ Science and Technology Innovation Training Project,China,Nos.201810571058,GDMU2018024,GDMU2018056,GDMU2018061(to HFW)College Students’ Innovative Experimental Project in Guangdong Medical University,China,No.ZZDS001(to HFW)College Students’ Science and Technology Innovation Cultivation Project in Guangdong of China,No.pdjh2019b0217(to HFW)
文摘Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.
文摘Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent work has uncovered a growing number of bacterial small RNAs （sRNAs）, some of which have been shown to regulate critical cellular processes. Computational approaches, in combination with molecular experiments, have played an important role in the identification of these sRNAs. At present, there is no information on the presence of small non-coding RNAs and their genes in the Agrobacterium tumefaciens genome. To identify potential sRNAs in this important bacterium, deep sequencing of the short RNA populations isolated from Agrobacterium tumefaciens C58 was carried out. From a data set of more than 10,000 short sequences, 16 candidate sRNAs have been tentatively identified based on computational analysis. All of these candidates can form stem-loop structures by RNA folding predictions and the majority of the secondary structures are rich in GC base-pairs：：Some are followed by a short stretch of U residues, indicative of a rho-independent transcription terminator, whereas some of the short RNAs are found in the stem region of the hairpin, indicative of eukaryotic-like sRNAs. Experimental strategies will need to be used to verify these candidates. The study of an expanded list of candidate sRNAs in Agrobacterium will allow a more complete understanding of the range of roles played by regulatory RNAs in prokaryotes.
基金funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek(GSGT.2019.019 to M.K.)supported by the Office of Science of the US Department of Energy(Contract No.DE-AC02-05CH11231).
文摘Conserved non-coding sequences(CNSs)are integral elements of transcriptional regulation.Transcriptional tuning of PLETHORA(PLT)genes that encode master regulators of plant development is vital for embryogenesis and meristematic function.However,how the expression of PLT genes is modulated through CNSs remains unclear.Through motif-based mining of upstream sequences in 120 angiosperm ge-nomes,we identified 21 conserved and lineage-specific CNSs,two of which are unusually long,similar,and colinear within eudicots.Using Arabidopsis thaliana,we demonstrate that these two deeply conserved elements,which we named BOX1 and BOX2,control PLT1 and PLT2 expression.CRISPR mutants within these elements specifically reduced PLT expression levels,and reporter lines revealed that deletion of either or both BOXes altered and/or abrogated the PLT2 expression pattern in the root tip,affecting the abil-ity to rescue the plt1 plt2 double mutant.We further show that the influence of these elements on expres-sion patterns is already exerted during embryogenesis and functional in the context of the early embryo.Finally,we reveal the existence of a BOX-mediated autoregulatory feedback loop that,in large part,explains CNS influence on expression patterns.Wethus uncover a transcriptional mechanism by which genes encoding master regulators of embryo and root meristem development are regulated.
基金supported by the National Natural Science Foundation of China(31125011,31071148,31270844)the Doctoral Foundation of Ministry of Education of China(20110101130012)Postdoctoral Research Project of Zhejiang Province(BSH1302085)
文摘Adenosine to inosine （A-to-I） RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA （ADAR） proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions （UTRs） and introns are located in pre-rnRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degrada- tion, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA （miRNA）, small interfering RNA （siRNA） and long non-coding RNA （lncRNA） are related to pre-mRNA splicing, translation, and gene regulation. A-to-I edit- ing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions （UTRs and introns） and non-coding RNAs （miRNA, siRNA, and IncRNA）.
基金supported by the German Centre for Cardiovascular Research (DZHK) and the German Ministry of Education and Research (BMBF)
文摘Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle cells, no contraction can take place. Therefore, calcium homeostasis is one of the critical regulatory mechanisms in all muscle cells, including skeletal muscle and heart [1,2]. Ca2＋ adenosine triphosphatase the relaxation of muscle cells Sarco-endoplasmic reticulum （SERCA） is responsible for by pumping Ca2＋ into the sarcoplasmic reticulum （SR） .
基金supported by grants from the National Basic Research 973 Program (2011CB915404)the National Natural Science Foundation of China (91017012)the National Program of Transgenic Variety Development of China (2011ZX08009-004)
文摘In plants, non-coding small RNAs play a vital role in plant development and stress responses. To explore the possible role of non-coding small RNAs in the regulation of the jasmonate （JA） pathway, we compared the non-coding small RNAs between the JA-deficient aos mutant and the JA-treated wild type Arabidopsis via high-throughput sequencing. Thirty new miRNAs and 27 new miRNA candidates were identified through bioinformatics approach. Forty-nine known miRNAs （belonging to 24 families）, 15 new miRNAs and new miRNA candidates （belonging to 11 families） and 3 tasiRNA families were induced by JA, whereas 1 new miRNA, 1 tasiRNA family and 22 known miRNAs （belonging to 9 families） were repressed by JA.
文摘The Human Genome Project marked a milestone in scientific exploration,unraveling the genetic blueprint of humanity.However,expectations of direct gene–disease associations gave way to realizing the complexity of genetic interactions,especially in polygenic diseases.This review explores the legacy of the HGP and subsequent advancements in genomic technologies,particularly next-generation sequencing,which have enabled more profound insights into the non-coding genome's role in gene regulation.While initially dismissed as“junk”DNA,non-coding regions are now officially approved as critical gene expression and genome organization regulators.Through integrative genomics approaches and advanced computational methods,researchers have unveiled the intricate network of enhancers,promoters,and chromatin modifications orchestrating gene expression.High-throughput sequencing techniques and functional assays have identified non-coding variants associated with numerous diseases,challenging the conventional focus on coding sequences in genomic studies.By elucidating the regulatory mechanisms governing gene expression,researchers can advance precision medicine approaches and develop novel diagnostic tools.As genomic research continues to evolve,a vast landscape is waiting to be explored,promising transformative insights into human health and disease.This review provides a comprehensive overview of the non-coding genome's role in gene regulation and its implications for understanding complex diseases and developing targeted therapeutic interventions.
基金supported by the National Natural Science Foundation of China (Nos.30170789 and 30270153)the Natural Science Foundation of Guangdong Province,China (No.011125).
文摘This study determined the sequences of chloro-plast DNA(cpDNA)trnL-F non-coding regions of indi-viduals of a tropical coniferous species,Dacrydium pectinatum,collected from 12 natural populations located in Hainan Province,southern China.Sequence length varied from 868 bp to 876 bp,indicating length polymorphism.Base com-position in the sequences was high in A+T content between 64.17%and 64.95%,and no recombination event occurred(Rm=0).Thirty haplotypes were identified based on statis-tical parsimony algorithm by running the TCS program.Populations of D.pectinatum in Hainan were lacking ge-netic differentiation.Such a deduction was supported by the observed FST values(0.00),AMOVA(24.17%of molecular variance attributed to difference among populations,P>0.05),high values of Nm(ranging from 1.92 to 2.50)and the branching structure in neighbor-joining(NJ)tree con-structed from haplotypes.A‘star-like’pattern was exhibited in the TCS network of trnL-F haplotypes,and majority of the haplotypes coalesced near the tips in NJ tree.Gene ge-nealogies of cpDNA haplotypes proposed a recent popula-tion expansion of D.pectinatum in Hainan,which was fur-ther supported by the results from Tajima’s D test and mis-match distribution analysis.Our data,in conjunction with geological and palynological evidences,showed that in the Holocene,due to global warming,refugee populations of D.pectinatum in Hainan might experience a range expan-sion.
文摘The nuclear encoded internal transcribed spacer (ITS) region and the plastid encoded trn L-F region were sequenced for 41 species of the Aceraceae, representing both genera Acer and Dipteronia, to reconstruct phylogeny of this family, especially within Acer. The analyses were performed in separate and combined sequence data sets, with the Sapindaceae and Hippocastanaceae being selected as outgroups. It was indicated that the Aceraceae was monophyletic and D. sinensis was basal to the rest of the family but the two genera of it might be not monophyletic because Dipteronia dyerana was nested within Acer. The result inferred from the combined data showed greater resolution within Acer than that from the two separate data sets. The monophyly of most sections in Xu's system (1996) were supported with high bootstrap values, and some relationships between (or among) sections were also inferred, such as sect. Palmata and sect. Microcarpa; sect. Platanoidea, sect. Lithocarpa and sect. Macrophylla; sect. Integrifolia, sect. Trifoliata and sect. Pentaphylla; and sect. Acer, sect. Goniocarpa and sect. Saccharina (sensu Ogata). However, the sectional status and circumscriptions of some of the above-mentioned sections should be further adjusted. It seemed that the Xu's delimitations of sect. Rubra and sect. Saccharodendran should be revaluated.
基金This work was supported by the National Natural Science Foundation of China(No.81801906,to KG)the Natural Science Foundation of Shandong Province of China(No.ZR2018PH024,to KG).
文摘Spinal cord injury(SCI)is a serious traumatic event to the central nervous system.Studies show that long non-coding RNAs(lncRNAs)play an important role in regulating the inflammatory response in the acute stage of SCI.Here,we investigated a new lncRNA related to spinal cord injury and acute inflammation.We analyzed the expression profile of lncRNAs after SCI,and explored the role of lncRNA Airsci(acute inflammatory response in SCI)on recovery following acute SCI.The rats were divided into the control group,SCI group,and SCI+lncRNA Airsci-siRNA group.The expression of inflammatory factors,including nuclear factor kappa B[NF-κB(p65)],NF-κB inhibitor IκBαand phosphorylated IκBα(p-IκBα),and the p-IκBα/IκBαratio were examined 1–28 days after SCI in rats by western blot assay.The differential lncRNA expression profile after SCI was assessed by RNA sequencing.The differentially expressed lncRNAs were analyzed by bioinformatics technology.The differentially expressed lncRNA Airsci,which is involved in NF-κB signaling and associated with the acute inflammatory response,was verified by quantitative real-time PCR.Interleukin(IL-1β),IL-6 and tumor necrosis factor(TNF-α)at 3 days after SCI were measured by western blot assay and quantitative real-time PCR.The histopathology of the spinal cord was evaluated by hematoxylin-eosin and Nissl staining.Motor function was assessed with the Basso,Beattie and Bresnahan Locomotor Rating Scale.Numerous differentially expressed lncRNAs were detected after SCI,including 151 that were upregulated and 186 that were downregulated in the SCI 3 d group compared with the control group.LncRNA Airsci was the most significantly expressed among the five lncRNAs involved in the NF-κB signaling pathway.LncRNA Airsci-siRNA reduced the inflammatory response by inhibiting the NF-κB signaling pathway,alleviated spinal cord tissue injury,and promoted the recovery of motor function in SCI rats.These findings show that numerous lncRNAs are differentially expressed following SCI,and that inhibiting lncRNA Airsci reduces the inflammatory response through the NF-κB signaling pathway,thereby promoting functional recovery.All experimental procedures and protocols were approved by the approved by the Animal Ethics Committee of Jining Medical University(approval No.JNMC-2020-DW-RM-003)on January 18,2020.
基金Supported by The Valley Hospital Foundation Research FundThe community of The Valley Hospital in Ridgewood,NJ,especially Ms.Audrey Meyers,CEO,Mr.Anastasios Kozaitis,president of the Valley Hospital Foundation
文摘Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design.
基金supported by the National Natural Science Foundation of China,No.81771355the Natural Science Foundation of Chongqing Science and Technology Bureau,Nos.CSTC2015jcyjA10096,cstc2021jcyj-msxmX0262(all to ZL)。
文摘Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.
文摘Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical approaches.PIWIinteracting RNAs(piRNAs)are a class of small non-coding RNAs that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of piRNAs plays a crucial role in the progression of various human cancers.In this editorial,we report on the current knowledge of HCC-associated piRNAs and their potential clinical utility.Based on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular RNAs in HCC,we highlight this other emerging class of non-coding RNAs.
基金This study was supported by the 333 Project Foundation of Jiangsu(No.BRA2017146)the Key Talents Project of Maternal and Child Health in Jiangsu(No.FRC201730).
文摘Objective:To establish the messenger RNA(mRNA)and long non-coding RNA(lncRNA)expression profiles in ectopic and eutopic endometrium and provide novel insights into endometriosis.Methods:The mRNA and lncRNA expression profiles were tested using high-throughput sequencing technology in ectopic and eutopic endometrium with endometriosis and normal endometrium without endometriosis.The potential targeted lncRNAs were annotated by analyzing the correlation between lncRNA and mRNA expression to better understand the pathogenesis of endometriosis.Results:In ectopic compared with normal endometrium,a total of 2,188 mRNAs and 1,200 lncRNAs were differentially expressed with a fold-change(FC)≥2.5.In eutopic compared with normal endometrium,a total of 2,324 mRNAs and 695 lncRNAs were differentially expressed with an FC≥1.5.In ectopic compared with eutopic endometrium,a total of 2,223 mRNAs and 511 lncRNAs were differentially expressed with an FC≥2.Bioinformatic analysis indicated that the differentially expressed mRNAs were enriched in the biological processes and signaling pathways involved in endometriosis.In addition,we constructed a gene coexpression network based on the dysregulated lncRNAs in both ectopic endometrium and eutopic endometrium,combined with their coexpressed mRNAs to simulate the complex interactions.Conclusions:This study describes the first-to-integrate analysis of the differential expression profiles of mRNAs and lncRNAs,including analyses between ectopic and normal endometrium,eutopic and normal endometrium,and ectopic and eutopic endometrium,which provides new insights to investigate the pathogenesis of endometriosis and explore novel diagnostic biomarkers and therapeutic targets.
基金supported by the National Natural Science Foundation of China(31301958)the Chinese Postdoctoral Science Foundation(2013T60808)
文摘High-throughput sequencing has identified a large number of sense-antisense transcriptional pairs, which indicates that these genes were transcribed from both directions. Recent reports have demonstrated that many antisense RNAs, especially lnc RNA（long non-coding RNA）, can interact with the sense RNA by forming an RNA duplex. Many methods, such as RNA-sequencing, Northern blotting, RNase protection assays and strand-specific PCR, can be used to detect the antisense transcript and gene transcriptional orientation. However, the applications of these methods have been constrained, to some extent, because of the high cost, difficult operation or inaccuracy, especially regarding the analysis of substantial amounts of data. Thus, we developed an easy method to detect and validate these complicated RNAs. We primarily took advantage of the strand specificity of RT-PCR and the single-strand specificity of S1 endonuclease to analyze sense and antisense transcripts. Four known genes, including mouse β-actin and Tsix（Xist antisense RNA）, chicken LXN（latexin） and GFM1（Gelongation factor, mitochondrial 1）, were used to establish the method. These four genes were well studied and transcribed from positive strand, negative strand or both strands of DNA, respectively, which represented all possible cases. The results indicated that the method can easily distinguish sense, antisense and sense-antisense transcriptional pairs. In addition, it can be used to verify the results of high-throughput sequencing, as well as to analyze the regulatory mechanisms between RNAs. This method can improve the accuracy of detection and can be mainly used in analyzing single gene and was low cost.
基金ACKNOWLEDGEMENTS This research was partially supported by the National Basic Research Program of China （No. 2012CB316504）, the National High Technology Research and Development Program of China （No. 2012AA020401）, the National Natural Science Foundation of China （Nos. 61573207 and 61175002） and Beijing Collaborative Innovation Center for Cardiovascular Disorders.
文摘Fundamental improvement was made for genome sequencing since the next-generation sequencing （NGS） came out in the 2000s. The newer technologies make use of the power of massively-parallel short-read DNA sequencing, genome alignment and assembly methods to digitally and rapidly search the genomes on a revolutionary scale, which enable large-scale whole genome sequencing （WGS） accessible and practical for researchers. Nowadays, whole genome sequencing is more and more prevalent in detecting the genetics of diseases, studying causative relations with cancers, making genome-level comparative analysis, reconstruction of human population history, and giving clinical implications and instructions. In this review, we first give a typical pipeline of whole genome sequencing, including the lab template preparation, sequencing, genome assembling and quality control, variants calling and annotations. We compare the difference between whole genome and whole exome sequencing （WES）, and explore a wide range of applications of whole genome sequencing for both mendelian diseases and complex diseases in medical genetics. We highlight the impact of whole genome sequencing in cancer studies, regulatory variant analysis, predictive medicine and precision medicine, as well as discuss the challenges of the whole genome sequencing.
