Watermelon,Citrullus lanatus,is the world's third largest fruit crop.Reference genomes with gaps and a narrow genetic base hinder functional genomics and genetic improvement of watermelon.Here,we report the assemb...Watermelon,Citrullus lanatus,is the world's third largest fruit crop.Reference genomes with gaps and a narrow genetic base hinder functional genomics and genetic improvement of watermelon.Here,we report the assembly of a telomere-to-telomere gap-free genome of the elite watermelon inbred line G42 by incorporating high-coverage and accurate long-read sequencing data with multiple assembly strategies.All 11 chromosomes have been assembled into single-contig pseudomolecules without gaps,representing the highest completeness and assembly quality to date.The G42 reference genome is 369321829 bp in length and contains 24205 predicted protein-coding genes,with all 22 telomeres and 11 centromeres characterized.Furthermore,we established a pollen-EMS mutagenesis protocol and obtained over 200000M1 seeds from G42.In a sampling pool,48 monogenic phenotypic mutations,selected from 223M1and 78 M2 mutants with morphological changes,were confirmed.The average mutation density was 1 SNP/1.69Mband1 indel/4.55 Mb per M1 plant and 1SNP/1.08Mb and 1 indel/6.25 Mb per M2 plant.Taking advantage of the gap-free G42 genome,8039 mutations from 32 plants sampled from M1 and M2 families were identified with 100%accuracy,whereas only 25% of the randomly selected mutations identified using the 97103v2 reference genome could be confirmed.Using this library and the gap-free genome,two genes responsible for elongated fruit shape and male sterility(CiMs1)were identified,both caused by a single basechange from G to A.The validated gap-free genome and its EMS mutation library provide invaluable resources for functional genomics and genetic improvement of watermelon.展开更多
Background:Atherosclerosis is a chronic cardiovascular disease of great concern.However,it is difficult to establish a direct connection between conventional small animal models and clinical practice.The pig's gen...Background:Atherosclerosis is a chronic cardiovascular disease of great concern.However,it is difficult to establish a direct connection between conventional small animal models and clinical practice.The pig's genome,physiology,and anatomy reflect human biology better than other laboratory animals,which is crucial for studying the pathogenesis of atherosclerosis.Methods:We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis,and further used bioinformatic tools to filter and identify underlying candidate genes.Candidate gene function prediction was performed using the online prediction tool STRING 12.0.Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes.Results:We mapped differential single nucleotide polymorphisms(SNPs)to genes and obtained a total of 102 differential genes,then we used GO and KEGG pathway enrichment analysis to identify four candidate genes,including SLA-1,SLA-2,SLA-3,and TAP2.nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins,the primary structures of these two proteins have undergone amino acid changes,and the tertiary structures also show slight changes.In addition,immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer.Conclusions:We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis,highlighting the importance of antigen processing and immune response in atherogenesis.展开更多
With the advancements in gene sequencing technologies,including genome-wide association studies,polygenetic risk scores,and high-throughput sequencing,there has been a tremendous advantage in mapping a detailed bluepr...With the advancements in gene sequencing technologies,including genome-wide association studies,polygenetic risk scores,and high-throughput sequencing,there has been a tremendous advantage in mapping a detailed blueprint for the genetic model of bipolar disorder(BD).To date,intriguing genetic clues have been identified to explain the development of BD,as well as the genetic association that might be applied for the development of susceptibility prediction and pharmacogenetic intervention.Risk genes of BD,such as CACNA1C,ANK3,TRANK1,and CLOCK,have been found to be involved in various pathophysiological processes correlated with BD.Although the specific roles of these genes have yet to be determined,genetic research on BD will help improve the prevention,therapeutics,and prognosis in clinical practice.The latest preclinical and clinical studies,and reviews of the genetics of BD,are analyzed in this review,aiming to summarize the progress in this intriguing field and to provide perspectives for individualized,precise,and effective clinical practice.展开更多
Bacterial leaf streak(BLS),caused by Xanthomonas oryzae pv.oryzicola(Xoc),is a bacterial disease affecting rice production in Asia and Africa,whose severity is expected to increase with climate change.Identification o...Bacterial leaf streak(BLS),caused by Xanthomonas oryzae pv.oryzicola(Xoc),is a bacterial disease affecting rice production in Asia and Africa,whose severity is expected to increase with climate change.Identification of new quantitative-trait loci(QTL)or resistance genes for BLS resistance is essential for developing resistant rice.A genome-wide association study to identify QTL associated with BLS resistance was conducted using phenotypic and genotypic data from 429 rice accessions.Of 47 QTL identified,45 were novel and two co-localized with previously reported QTL or genes conferring BLS resistance.qBLS6.2 on chromosome 6 explained the greatest phenotypic variation.Combined analysis of differential expression and annotations of predicted genes near qBLS6.2 based on haplotype and disease phenotype identified OsBLS6.2(LOC_Os06g02960)as a candidate gene for qBLS6.2.OsBLS6.2 knockout plants showed higher resistance to Xoc than wild-type plants.Many other candidate genes for resistance to Xoc were identified.展开更多
Type 2 diabetes(T2D)mellitus is a common complex disease that currently affects more than 400 million people worldwide and has become a global health problem.High-throughput sequencing technologies such as whole-genom...Type 2 diabetes(T2D)mellitus is a common complex disease that currently affects more than 400 million people worldwide and has become a global health problem.High-throughput sequencing technologies such as whole-genome and whole-exome sequencing approaches have provided numerous new insights into the molecular bases of T2D.Recent advances in the application of sequencing technologies to T2D research include,but are not limited to:(1)Fine mapping of causal rare and common genetic variants;(2)Identification of confident genelevel associations;(3)Identification of novel candidate genes by specific scoring approaches;(4)Interrogation of disease-relevant genes and pathways by transcriptional profiling and epigenome mapping techniques;and(5)Investigation of microbial community alterations in patients with T2D.In this work we review these advances in application of next-generation sequencing methods for elucidation of T2D pathogenesis,as well as progress and challenges in implementation of this new knowledge about T2D genetics in diagnosis,prevention,and treatment of the disease.展开更多
The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of o...The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of orange-spotted grouper has never been fully understood. Herein, we performed a genome-wide association study （GWAS） on a natural population of 198 individuals aiming to screen the whole genome of orange-spotted grouper for identification of growth-related loci by restriction-site associated DNA sequencing. In this research, 261,366 single nucleotide polymorphisms （SNPs） were developed, in which 110 SNPs were identified to be correlated with growth and 20 SNPs were further confirmed to be associated with both body weight and total length. From these identified SNPs, we annotated a total of 34 genes, including adgrb2, csnkzal, cers5, co122al, creb5, dndl, dzankl, dnail, npy2r, fat3, lrrk2, lrp5, map3k9, and so on. Among these candidate genes, npy2r （neuropeptide Y receptor Y2） was reported to play a critical role in growth of the orange-spotted grouper. In addition, population structure, principal component analysis, kinship matrix and linkage disequilibrium were examined to verify the accuracy and reliability of our GWAS results. Our data will also provide a valuable genetic resource for further marker-assisted selection program to improve growth quality in groupers.展开更多
In order to explore the genomic basis for liver cancer metastasis,whole-exome sequencing(WES)was performed on patient-derived hepatocellular carcinoma(HCC)cell lines with differential metastatic potentials and analyze...In order to explore the genomic basis for liver cancer metastasis,whole-exome sequencing(WES)was performed on patient-derived hepatocellular carcinoma(HCC)cell lines with differential metastatic potentials and analyzed their clonal evolution relationships.An evolutionary tree based on genomic single nucleotide polymorphism(SNP)was constructed in MegaX software.The WES data showed that the average percentage of heterogeneous mutations in each HCC cell lines was 16.55%(range,15.38%e18.17%).C:G>T:A and T:A>C:G somatic transitions were the two most frequent substitutions.In these metastatic HCC cell lines,non-silent gene mutations were found in 21.88%of known driver genes and 10 classical signaling pathways.The protein interaction network was constructed by STRING,and hub genes were found in the shared trunk mutation genes and the heterogeneous branch mutations respectively.In cBioPortal database,some of the selected hub genes were found to be associated with poor overall survival(OS)of HCC patients.Among the mutated HCC driver genes,a novel KEAP1 mutation with a homozygous frameshift truncation at the c-terminal Nrf2 binding region was detected and verified in MHCC97-H and HCC97LM3 cells.In conclusion,WES data demonstrate that HCC cell lines from tumor biopsy specimens of the same patient have obtained different metastatic potentials through repeated selection in rodents in vivo,and they do indeed have a genetic relationship at the genomic level.展开更多
The kuruma prawn, Marsupenaeus japonicus, is one of the most cultivated and consumed species of shrimp. However, very few molecular genetic/genomic resources are publically available for it. Thus, the characterization...The kuruma prawn, Marsupenaeus japonicus, is one of the most cultivated and consumed species of shrimp. However, very few molecular genetic/genomic resources are publically available for it. Thus, the characterization and distribution of simple sequence repeats(SSRs) remains ambiguous and the use of SSR markers in genomic studies and marker-assisted selection is limited. The goal of this study is to characterize and develop genome-wide SSR markers in M. japonicus by genome survey sequencing for application in comparative genomics and breeding. A total of 326 945 perfect SSRs were identified, among which dinucleotide repeats were the most frequent class(44.08%), followed by mononucleotides(29.67%), trinucleotides(18.96%), tetranucleotides(5.66%), hexanucleotides(1.07%), and pentanucleotides(0.56%). In total, 151 541 SSR loci primers were successfully designed. A subset of 30 SSR primer pairs were synthesized and tested in 42 individuals from a wild population, of which 27 loci(90.0%) were successfully amplified with specific products and 24(80.0%) were polymorphic. For the amplified polymorphic loci, the alleles ranged from 5 to 17(with an average of 9.63), and the average PIC value was 0.796. A total of 58 256 SSR-containing sequences had significant Gene Ontology annotation; these are good functional molecular marker candidates for association studies and comparative genomic analysis. The newly identified SSRs significantly contribute to the M. japonicus genomic resources and will facilitate a number of genetic and genomic studies, including high density linkage mapping, genome-wide association analysis, marker-aided selection, comparative genomics analysis, population genetics, and evolution.展开更多
Background： One of the most important and challenging issues in biomedicine and genomics is how to identify disease related genes. Datasets from high-throughput biotechnologies have been widely used to overcome this ...Background： One of the most important and challenging issues in biomedicine and genomics is how to identify disease related genes. Datasets from high-throughput biotechnologies have been widely used to overcome this issue from various perspectives, e.g., epigenomics, genomics, transcriptomics, proteomics, metabolomics. At the genomic level, copy number variations （CNVs） have been recognized as critical genetic variations, which contribute significantly to genomic diversity. They have been associated with both common and complex diseases, and thus have a large influence on a variety of Mendelian and somatic genetic disorders. Results： In this review, based on a variety of complex diseases, we give an overview about the critical role of using CNVs for identifying disease related genes, and discuss on details the different high-throughput and sequencing methods applied for CNV detection. Some limitations and challenges concerning CNV are also highlighted. Conclusions： Reliable detection of CNVs will not only allow discriminating driver mutations for various diseases, but also helps to develop personalized medicine when integrating it with other genomic features.展开更多
Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational researc...Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center （i.e., the brain） in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be dis- cussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer＇s disease and autism spectrum disorder.展开更多
为明确紫色小麦紫粒性状的遗传规律及其调控基因,采用贵紫麦1号(紫粒小麦)×贵农19或贵农麦30(白粒小麦)进行正反交,构建不同杂交世代(F_(1)~F_(5)和BC_(1)F_(1))遗传研究群体,根据杂交后代紫粒性状的分离情况探究其粒色的遗传规律...为明确紫色小麦紫粒性状的遗传规律及其调控基因,采用贵紫麦1号(紫粒小麦)×贵农19或贵农麦30(白粒小麦)进行正反交,构建不同杂交世代(F_(1)~F_(5)和BC_(1)F_(1))遗传研究群体,根据杂交后代紫粒性状的分离情况探究其粒色的遗传规律,利用全基因组重测序技术(WGS)结合集群分离分析(BSA)策略对贵紫麦1号紫粒性状进行基因定位。结果表明,贵紫麦1号的紫粒性状受两对显性互补基因控制。基于全基因组重测序及标记筛选结果显示,控制贵紫麦1号紫粒性状的两个互补显性基因分别位于2 AL和7 DL染色体上,并将控制紫粒性状的基因命名为GZMpp1和GZMpp2;紫粒基因GZMpp1与标记chr 2 A 32的遗传距离为1.2 cM;GZMpp2与标记DY-7 D 6的遗传距离为0.5 cM。展开更多
The large yellow croaker(Larimichthys crocea)is an important maricultured fish species in southeast China.Body shape is an important economic trait for this species,because consumers prefer to purchase fish that have ...The large yellow croaker(Larimichthys crocea)is an important maricultured fish species in southeast China.Body shape is an important economic trait for this species,because consumers prefer to purchase fish that have a slender shape.Furthermore,investigating the genetic basis of this trait may be useful for understanding the evolution of fish body shape in general.This study randomly selected 500 large yellow croakers to perform genome-wide association study of this trait.We used Genotyping-By-Sequencing technology combined with a genome-wide prediction model(BayesC)to identify and test QTLs.We also compared the association results using BayesC and single-marker analysis,and found that BayesC outperformed single-marker analysis in detecting significant SNPs explaining a proportion of the total genetic variance in this experiment.Using 124,419 SNP markers,10 candidate genes,correspond to 4 QTL regions located around 3.5,1.8,23.9 and 10.8 Mb on chromosomes 2,4,8 and 22 respectively,were suggested to be relevant to the trait.All of these genes may directly or indirectly participate in bone development.These genes may provide a valuable reference for marker-assisted selective breeding and investigating the genetic basis of the evolution of fish body shape.展开更多
wide association studies(GWAS)in recent years.Since the identification of variants in the complement factor H gene on the risk of age-related macular degeneration,GWAS have become ubiquitous in genetic studies and hav...wide association studies(GWAS)in recent years.Since the identification of variants in the complement factor H gene on the risk of age-related macular degeneration,GWAS have become ubiquitous in genetic studies and have led to the identification of genetic variants that are associated with a variety of complex human diseases and traits.These discoveries have changed our understanding of the biological architecture of common,complex diseases and have also provided new hypotheses to test.New tools,such as next-generation sequencing,will be an important part of the future of genetics research;however,GWAS studies will continue to play an important role in disease gene discovery.Many traits have yet to be explored by GWAS,especially in minority populations,and large collaborative studies are currently being conducted to maximize the return from existing GWAS data.In addition,GWAS technology continues to improve,increasing genomic coverage for major global populations and decreasing the cost of experiments.Although much of the variance attributable to genetic factors for many important traits is still unexplained,GWAS technology has been instrumental in mapping over a thousand genes to hundreds of traits.More discoveries are made each month and the scale,quality and quantity of current work has a steady trend upward.We briefly review the current key trends in GWAS,which can be summarized with three goals:increase power,increase collaborations and increase populations.展开更多
基金This work was supported by the Provincial Technology Innovation Program of Shandong,Ningxia Hui Autonomous Region agricultural breeding special project(NXNYYZ202001)Jiangsu Seed Industry Revitalization Competitive Project JBGS(2021)072,Ningbo Science and Technology Innovation Project 2021Z132,and Weifang Seed InnovationGroup.
文摘Watermelon,Citrullus lanatus,is the world's third largest fruit crop.Reference genomes with gaps and a narrow genetic base hinder functional genomics and genetic improvement of watermelon.Here,we report the assembly of a telomere-to-telomere gap-free genome of the elite watermelon inbred line G42 by incorporating high-coverage and accurate long-read sequencing data with multiple assembly strategies.All 11 chromosomes have been assembled into single-contig pseudomolecules without gaps,representing the highest completeness and assembly quality to date.The G42 reference genome is 369321829 bp in length and contains 24205 predicted protein-coding genes,with all 22 telomeres and 11 centromeres characterized.Furthermore,we established a pollen-EMS mutagenesis protocol and obtained over 200000M1 seeds from G42.In a sampling pool,48 monogenic phenotypic mutations,selected from 223M1and 78 M2 mutants with morphological changes,were confirmed.The average mutation density was 1 SNP/1.69Mband1 indel/4.55 Mb per M1 plant and 1SNP/1.08Mb and 1 indel/6.25 Mb per M2 plant.Taking advantage of the gap-free G42 genome,8039 mutations from 32 plants sampled from M1 and M2 families were identified with 100%accuracy,whereas only 25% of the randomly selected mutations identified using the 97103v2 reference genome could be confirmed.Using this library and the gap-free genome,two genes responsible for elongated fruit shape and male sterility(CiMs1)were identified,both caused by a single basechange from G to A.The validated gap-free genome and its EMS mutation library provide invaluable resources for functional genomics and genetic improvement of watermelon.
基金supported by the Special Scientific Research Project of Army Laboratory Animals(No.SYDW[2020]01)National Natural Science Foundation of ChinaNo.32370568。
文摘Background:Atherosclerosis is a chronic cardiovascular disease of great concern.However,it is difficult to establish a direct connection between conventional small animal models and clinical practice.The pig's genome,physiology,and anatomy reflect human biology better than other laboratory animals,which is crucial for studying the pathogenesis of atherosclerosis.Methods:We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis,and further used bioinformatic tools to filter and identify underlying candidate genes.Candidate gene function prediction was performed using the online prediction tool STRING 12.0.Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes.Results:We mapped differential single nucleotide polymorphisms(SNPs)to genes and obtained a total of 102 differential genes,then we used GO and KEGG pathway enrichment analysis to identify four candidate genes,including SLA-1,SLA-2,SLA-3,and TAP2.nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins,the primary structures of these two proteins have undergone amino acid changes,and the tertiary structures also show slight changes.In addition,immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer.Conclusions:We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis,highlighting the importance of antigen processing and immune response in atherogenesis.
基金supported by the Zhejiang Provincial Key Research and Development Program(2021C03107)the Leading Talent of Scientific and Technological Innovation“Ten Thousand Talents Program”of Zhejiang Province(2021R52016)+1 种基金the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(2020R01001)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2023001B).
文摘With the advancements in gene sequencing technologies,including genome-wide association studies,polygenetic risk scores,and high-throughput sequencing,there has been a tremendous advantage in mapping a detailed blueprint for the genetic model of bipolar disorder(BD).To date,intriguing genetic clues have been identified to explain the development of BD,as well as the genetic association that might be applied for the development of susceptibility prediction and pharmacogenetic intervention.Risk genes of BD,such as CACNA1C,ANK3,TRANK1,and CLOCK,have been found to be involved in various pathophysiological processes correlated with BD.Although the specific roles of these genes have yet to be determined,genetic research on BD will help improve the prevention,therapeutics,and prognosis in clinical practice.The latest preclinical and clinical studies,and reviews of the genetics of BD,are analyzed in this review,aiming to summarize the progress in this intriguing field and to provide perspectives for individualized,precise,and effective clinical practice.
基金the Open Project(2020)of Guangdong Key Laboratory of New Technology in Rice Breeding,the Natural Science Foundation of Guangdong Province,China(2019A1515011825)the Special Rural Revitalization Funds of Guangdong Province(Seed Industry Revitalization Project)(2022-NPY-00-006).
文摘Bacterial leaf streak(BLS),caused by Xanthomonas oryzae pv.oryzicola(Xoc),is a bacterial disease affecting rice production in Asia and Africa,whose severity is expected to increase with climate change.Identification of new quantitative-trait loci(QTL)or resistance genes for BLS resistance is essential for developing resistant rice.A genome-wide association study to identify QTL associated with BLS resistance was conducted using phenotypic and genotypic data from 429 rice accessions.Of 47 QTL identified,45 were novel and two co-localized with previously reported QTL or genes conferring BLS resistance.qBLS6.2 on chromosome 6 explained the greatest phenotypic variation.Combined analysis of differential expression and annotations of predicted genes near qBLS6.2 based on haplotype and disease phenotype identified OsBLS6.2(LOC_Os06g02960)as a candidate gene for qBLS6.2.OsBLS6.2 knockout plants showed higher resistance to Xoc than wild-type plants.Many other candidate genes for resistance to Xoc were identified.
基金Supported by D.O.Ott Research Institute of Obstetrics,Gynaecology and Reproductology,project 558-2019-0012(АААА-А19-119021290033-1)of FSBSI
文摘Type 2 diabetes(T2D)mellitus is a common complex disease that currently affects more than 400 million people worldwide and has become a global health problem.High-throughput sequencing technologies such as whole-genome and whole-exome sequencing approaches have provided numerous new insights into the molecular bases of T2D.Recent advances in the application of sequencing technologies to T2D research include,but are not limited to:(1)Fine mapping of causal rare and common genetic variants;(2)Identification of confident genelevel associations;(3)Identification of novel candidate genes by specific scoring approaches;(4)Interrogation of disease-relevant genes and pathways by transcriptional profiling and epigenome mapping techniques;and(5)Investigation of microbial community alterations in patients with T2D.In this work we review these advances in application of next-generation sequencing methods for elucidation of T2D pathogenesis,as well as progress and challenges in implementation of this new knowledge about T2D genetics in diagnosis,prevention,and treatment of the disease.
基金supported by National Natural Science Foundation of China (31370047)Shenzhen Scientific R&D Grant (GJHS20160331150703934)Shenzhen Dapeng Special Program for Industrial Development (KY20160102, KY20170205)
文摘The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of orange-spotted grouper has never been fully understood. Herein, we performed a genome-wide association study （GWAS） on a natural population of 198 individuals aiming to screen the whole genome of orange-spotted grouper for identification of growth-related loci by restriction-site associated DNA sequencing. In this research, 261,366 single nucleotide polymorphisms （SNPs） were developed, in which 110 SNPs were identified to be correlated with growth and 20 SNPs were further confirmed to be associated with both body weight and total length. From these identified SNPs, we annotated a total of 34 genes, including adgrb2, csnkzal, cers5, co122al, creb5, dndl, dzankl, dnail, npy2r, fat3, lrrk2, lrp5, map3k9, and so on. Among these candidate genes, npy2r （neuropeptide Y receptor Y2） was reported to play a critical role in growth of the orange-spotted grouper. In addition, population structure, principal component analysis, kinship matrix and linkage disequilibrium were examined to verify the accuracy and reliability of our GWAS results. Our data will also provide a valuable genetic resource for further marker-assisted selection program to improve growth quality in groupers.
基金This work was supported by the National Natural Science Foundation of China(NSFC,NO.81172066,NO.81472858NO.91529103)+1 种基金Innovation Team Fund of Second Affiliated Hospital of Chongqing Medical UniversityThe authors would like to thank Dr.Zhou-You Tang,Professor&Director,Liver Cancer Institute,Fudan University,for providing the three HCC cell lines(MHCC97-L,MHCC97-H,HCC97LM3).
文摘In order to explore the genomic basis for liver cancer metastasis,whole-exome sequencing(WES)was performed on patient-derived hepatocellular carcinoma(HCC)cell lines with differential metastatic potentials and analyzed their clonal evolution relationships.An evolutionary tree based on genomic single nucleotide polymorphism(SNP)was constructed in MegaX software.The WES data showed that the average percentage of heterogeneous mutations in each HCC cell lines was 16.55%(range,15.38%e18.17%).C:G>T:A and T:A>C:G somatic transitions were the two most frequent substitutions.In these metastatic HCC cell lines,non-silent gene mutations were found in 21.88%of known driver genes and 10 classical signaling pathways.The protein interaction network was constructed by STRING,and hub genes were found in the shared trunk mutation genes and the heterogeneous branch mutations respectively.In cBioPortal database,some of the selected hub genes were found to be associated with poor overall survival(OS)of HCC patients.Among the mutated HCC driver genes,a novel KEAP1 mutation with a homozygous frameshift truncation at the c-terminal Nrf2 binding region was detected and verified in MHCC97-H and HCC97LM3 cells.In conclusion,WES data demonstrate that HCC cell lines from tumor biopsy specimens of the same patient have obtained different metastatic potentials through repeated selection in rodents in vivo,and they do indeed have a genetic relationship at the genomic level.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.2012AA10A409)
文摘The kuruma prawn, Marsupenaeus japonicus, is one of the most cultivated and consumed species of shrimp. However, very few molecular genetic/genomic resources are publically available for it. Thus, the characterization and distribution of simple sequence repeats(SSRs) remains ambiguous and the use of SSR markers in genomic studies and marker-assisted selection is limited. The goal of this study is to characterize and develop genome-wide SSR markers in M. japonicus by genome survey sequencing for application in comparative genomics and breeding. A total of 326 945 perfect SSRs were identified, among which dinucleotide repeats were the most frequent class(44.08%), followed by mononucleotides(29.67%), trinucleotides(18.96%), tetranucleotides(5.66%), hexanucleotides(1.07%), and pentanucleotides(0.56%). In total, 151 541 SSR loci primers were successfully designed. A subset of 30 SSR primer pairs were synthesized and tested in 42 individuals from a wild population, of which 27 loci(90.0%) were successfully amplified with specific products and 24(80.0%) were polymorphic. For the amplified polymorphic loci, the alleles ranged from 5 to 17(with an average of 9.63), and the average PIC value was 0.796. A total of 58 256 SSR-containing sequences had significant Gene Ontology annotation; these are good functional molecular marker candidates for association studies and comparative genomic analysis. The newly identified SSRs significantly contribute to the M. japonicus genomic resources and will facilitate a number of genetic and genomic studies, including high density linkage mapping, genome-wide association analysis, marker-aided selection, comparative genomics analysis, population genetics, and evolution.
基金This work was supported by the National Natural Science Foundation of China （Nos. 61602386 and 61332014）, the Natural Science Foundation of Shaanxi Province （No. 2017JQ6008）, and the top university visiting foundation for excellent youth scholars of Northwestern Polytechnical University.
文摘Background： One of the most important and challenging issues in biomedicine and genomics is how to identify disease related genes. Datasets from high-throughput biotechnologies have been widely used to overcome this issue from various perspectives, e.g., epigenomics, genomics, transcriptomics, proteomics, metabolomics. At the genomic level, copy number variations （CNVs） have been recognized as critical genetic variations, which contribute significantly to genomic diversity. They have been associated with both common and complex diseases, and thus have a large influence on a variety of Mendelian and somatic genetic disorders. Results： In this review, based on a variety of complex diseases, we give an overview about the critical role of using CNVs for identifying disease related genes, and discuss on details the different high-throughput and sequencing methods applied for CNV detection. Some limitations and challenges concerning CNV are also highlighted. Conclusions： Reliable detection of CNVs will not only allow discriminating driver mutations for various diseases, but also helps to develop personalized medicine when integrating it with other genomic features.
基金supported by the grant from the National Basic Research Program of China (973 Program, Grant No. 2014CB964901) awarded to HL from the Ministry of Science and Technology of China
文摘Neurological disorders comprise a variety of complex diseases in the central nervous system, which can be roughly classified as neurodegenerative diseases and psychiatric disorders. The basic and translational research of neurological disorders has been hindered by the difficulty in accessing the pathological center （i.e., the brain） in live patients. The rapid advancement of sequencing and array technologies has made it possible to investigate the disease mechanism and biomarkers from a systems perspective. In this review, recent progresses in the discovery of novel risk genes, treatment targets and peripheral biomarkers employing genomic technologies will be dis- cussed. Our major focus will be on two of the most heavily investigated neurological disorders, namely Alzheimer＇s disease and autism spectrum disorder.
文摘为明确紫色小麦紫粒性状的遗传规律及其调控基因,采用贵紫麦1号(紫粒小麦)×贵农19或贵农麦30(白粒小麦)进行正反交,构建不同杂交世代(F_(1)~F_(5)和BC_(1)F_(1))遗传研究群体,根据杂交后代紫粒性状的分离情况探究其粒色的遗传规律,利用全基因组重测序技术(WGS)结合集群分离分析(BSA)策略对贵紫麦1号紫粒性状进行基因定位。结果表明,贵紫麦1号的紫粒性状受两对显性互补基因控制。基于全基因组重测序及标记筛选结果显示,控制贵紫麦1号紫粒性状的两个互补显性基因分别位于2 AL和7 DL染色体上,并将控制紫粒性状的基因命名为GZMpp1和GZMpp2;紫粒基因GZMpp1与标记chr 2 A 32的遗传距离为1.2 cM;GZMpp2与标记DY-7 D 6的遗传距离为0.5 cM。
基金Kun Ye,Qingkai Chen,Junwei Chen,Yang Liu and other colleagues in the laboratory participated in fish sampling and traits measurement.The work was supported by China Agriculture Research System(CARS-47-G04)Key projects of the Xiamen Southern Ocean Research Centre(14GZY70NF34)the National Natural Science Foundation of China(U1705231).
文摘The large yellow croaker(Larimichthys crocea)is an important maricultured fish species in southeast China.Body shape is an important economic trait for this species,because consumers prefer to purchase fish that have a slender shape.Furthermore,investigating the genetic basis of this trait may be useful for understanding the evolution of fish body shape in general.This study randomly selected 500 large yellow croakers to perform genome-wide association study of this trait.We used Genotyping-By-Sequencing technology combined with a genome-wide prediction model(BayesC)to identify and test QTLs.We also compared the association results using BayesC and single-marker analysis,and found that BayesC outperformed single-marker analysis in detecting significant SNPs explaining a proportion of the total genetic variance in this experiment.Using 124,419 SNP markers,10 candidate genes,correspond to 4 QTL regions located around 3.5,1.8,23.9 and 10.8 Mb on chromosomes 2,4,8 and 22 respectively,were suggested to be relevant to the trait.All of these genes may directly or indirectly participate in bone development.These genes may provide a valuable reference for marker-assisted selective breeding and investigating the genetic basis of the evolution of fish body shape.
文摘wide association studies(GWAS)in recent years.Since the identification of variants in the complement factor H gene on the risk of age-related macular degeneration,GWAS have become ubiquitous in genetic studies and have led to the identification of genetic variants that are associated with a variety of complex human diseases and traits.These discoveries have changed our understanding of the biological architecture of common,complex diseases and have also provided new hypotheses to test.New tools,such as next-generation sequencing,will be an important part of the future of genetics research;however,GWAS studies will continue to play an important role in disease gene discovery.Many traits have yet to be explored by GWAS,especially in minority populations,and large collaborative studies are currently being conducted to maximize the return from existing GWAS data.In addition,GWAS technology continues to improve,increasing genomic coverage for major global populations and decreasing the cost of experiments.Although much of the variance attributable to genetic factors for many important traits is still unexplained,GWAS technology has been instrumental in mapping over a thousand genes to hundreds of traits.More discoveries are made each month and the scale,quality and quantity of current work has a steady trend upward.We briefly review the current key trends in GWAS,which can be summarized with three goals:increase power,increase collaborations and increase populations.
