Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th...Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.展开更多
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ...The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.展开更多
We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotate...We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST(Z(FST))method,and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity(ZHp)method.The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism,disease resistance,cellular processes,and biochemical signals,and several were related to body morphology and organs.They included PPP3CA,which plays an essential role in the transduction of intracellular Ca2+-mediated signals,and WWTR1,which plays a pivotal role in organ size control and tumor suppression.These results suggest that genes associated with body morphology were subject to selection pressure during domestication,whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding.Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.展开更多
BACKGROUND Gastric cancer(GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori(H. pylori) and Epstein-Barr virus(EBV), and genetic components.AIM To investigate microbiomes and host genom...BACKGROUND Gastric cancer(GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori(H. pylori) and Epstein-Barr virus(EBV), and genetic components.AIM To investigate microbiomes and host genome instability by cost-effective,low-coverage wholegenome sequencing,as biomarkers for GC subtyping.METHODS Samples from 40 GC patients were collected from Taizhou Hospital,Zhejiang Province,affiliated with Wenzhou Medical University.DNA from the samples was subjected to low-coverage wholegenome sequencing with a median genome coverage of 1.86×(range:1.03×to 3.17×) by Illumina×10,followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector.RESULTS Of the 40 GC samples,20 (50%) were found to be enriched with microbiomes.EBV DNA was detected in 5 GC patients (12.5%).H.pylori DNA was found in 15 (37.5%) patients.The other 20(50%) patients were found to have relatively higher genomic instability.Copy number amplifications of the oncogenes,ERBB2 and KRAS,were found in 9 (22.5%) and 7 (17.5%) of the GC samples,respectively.EBV enrichment was found to be associated with tumors in the gastric cardia and fundus.H.pylori enrichment was found to be associated with tumors in the pylorus and antrum.Tumors with elevated genomic instability showed no localization and could be observed in any location.Additionally,H.pylori-enriched GC was found to be associated with the Borrmann type Ⅱ/Ⅲ and gastritis history.EBV-enriched GC was not associated with gastritis.No statistically significant correlation was observed between genomic instability and gastritis.Furthermore,these three different molecular subtypes showed distinct survival outcomes (P=0.019).EBV-positive tumors had the best prognosis,whereas patients with high genomic instability (CIN+) showed the worst survival.Patients with H.pylori infection showed intermediate prognosis compared with the other two subtypes.CONCLUSION Thus,using low-coverage whole-genome sequencing,GC can be classified into three categories based on disease etiology;this classification may prove useful for GC diagnosis and precision medicine.展开更多
The application of microorganisms as probiotics is limited due to lack of safety evaluation.Here,a novel multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified from ...The application of microorganisms as probiotics is limited due to lack of safety evaluation.Here,a novel multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified from marine mangrove microorganisms.Its safety and probiotic properties were assessed in accordance with phenotype and whole-genome sequencing analysis.Results showed that the genes and phenotypic expression of related virulence,antibiotic resistance and retroelement were rarely found.Hyphal morphogenesis genes(SIT4,HOG1,SPA2,ERK1,ICL1,CST20,HSP104,TPS1,and RHO1)and phospholipase secretion gene(VPS4)were annotated.True hyphae and phospholipase were absent.Only one retroelement(Tad1-65_BG)was found.Major biogenic amines(BAs)encoding genes were absent,except for spermidine synthase(JA9_002594),spermine synthase(JA9_004690),and tyrosine decarboxylase(inx).The production of single BAs and total BAs was far below the food-defined thresholds.GXDK6 had no resistance to common antifungal drugs.Virulence enzymes,such as gelatinase,DNase,hemolytic,lecithinase,and thrombin were absent.Acute toxicity test with mice demonstrated that GXDK6 is safe.GXDK6 has a good reproduction ability in the simulation gastrointestinal tract.GXDK6 also has a strong antioxidant ability,β-glucosidase,and inulinase activity.To sum up,GXDK6 is considered as a safe probiotic for human consumption and food fermentation.展开更多
The order Acipenseriformes,which includes sturgeons and paddlefishes,represents“living fossils”with complex genomes that are good models for understanding whole-genome duplication(WGD)and ploidy evolution in fishes....The order Acipenseriformes,which includes sturgeons and paddlefishes,represents“living fossils”with complex genomes that are good models for understanding whole-genome duplication(WGD)and ploidy evolution in fishes.Here,we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis(Chinese sturgeon),a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes.Our results show that A.sinensis is a complex autooctoploid species containing four kinds of octovalents(8n),a hexavalent(6n),two tetravalents(4n),and a divalent(2n).An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs,and further provides insights into the timing of its ploidy evolution.This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.展开更多
Beach pea or beach cowpea(Vigna marina(Burm.)Merr.)belongs to the family Fabaceae.It is a close relative of cultivated Vigna species such as adzuki bean(V.angularis),cowpea(V.unguiculata),mung bean(V.radiata),and blac...Beach pea or beach cowpea(Vigna marina(Burm.)Merr.)belongs to the family Fabaceae.It is a close relative of cultivated Vigna species such as adzuki bean(V.angularis),cowpea(V.unguiculata),mung bean(V.radiata),and blackgram(V.mungo),and is distributed throughout the tropics.With its ability to tolerate salt stress,beach pea has great potential to contribute salt-tolerance genes for developing salt-tolerant cultivars in cultivated Vigna species.However,it is still underutilized in Vigna breeding programs.A draft genome sequence of beach pea was generated using a high-throughput next-generation sequencing platform,yielding 23.7 Gb of sequence from 79,929,868 filtered reads.A de novo genome assembly containing 68,731 scaffolds gave an N50 length of 10,272 bp and the assembled sequences totaled 365.6 Mb.A total of 35,448 SSRs,including 3574 compound SSRs,were identified and primer pairs for most of these SSRs were designed.Genome analysis identified 50,670 genes with mean coding sequence length 1042 bp.Phylogenetic analysis revealed highest sequence similarity with V.angularis,followed by V.radiata.Comparison with the V.angularis genome revealed 16,699 SNPs and 2253 InDels and comparison with the V.radiata genome revealed 17,538 SNPs and 2300 InDels.To our knowledge this is the first draft genome sequence of beach pea derived from an accession(ANBp-14-03)adapted locally in the Andaman and Nicobar Islands of India.The draft genome sequence may facilitate the genetic enhancement in cultivated Vigna species.展开更多
Objective:To perform whole-genome sequencing and phylogenetic analysis of the local endemic strain of Rodent Torque teno virus (RoTTV), RoTTV3-HMU1, found in Rattus norvegicus, Haikou City, Hainan Province, and establ...Objective:To perform whole-genome sequencing and phylogenetic analysis of the local endemic strain of Rodent Torque teno virus (RoTTV), RoTTV3-HMU1, found in Rattus norvegicus, Haikou City, Hainan Province, and establish a SYBR Green I based real-time PCR detection assay for RoTTV3.Methods: Based on the high-throughput genome sequencing analysis, specific primers were designed and the whole genome sequence was amplified by PCR and Sanger sequencing. Specific detection primers were designed based on the conserved sequences of RoTTV3. The recombinant plasmid contained the whole genome of RoTTV3-HMU1 was constructed as a standard control. The experimental conditions were optimized and the real-time PCR detection assay of RoTTV3 was established.Results: The genomic sequence of RoTTV carried by Rattus norvegicus in Haikou City was successfully sequenced. Phylogenetic analysis indicated that the virus belongs to the RoTTV3 genotype. In this experiment, the real-time PCR detection method of RoTTV3 was established. The standard curve generated had a wide dynamic range from 1×(102-108) copies/μL, with a linear correlation (R2=1.000). The melting curve analysis using SYBR Green showed only one specific melting peak and no primer-dimmers represented. The detection limit was 100 copies/reaction.Discussion: This study was the first report of the RoTTV in Hainan Islands, and its phylogenetic analysis was of great significance to the origin and evolution of RoTTV. The RoTTV3 real-time PCR detection method established in this experiment has a high sensitivity and good specificity, which lays a technical foundation for the epidemiological investigation of RoTTV3.展开更多
Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTE...Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.展开更多
Population genomic data could provide valuable information for conservation efforts;however,limited studies have been conducted to investigate the genetic status of threatened pheasants.Reeves’s Pheasant(Syrmaticus r...Population genomic data could provide valuable information for conservation efforts;however,limited studies have been conducted to investigate the genetic status of threatened pheasants.Reeves’s Pheasant(Syrmaticus reevesii)is facing population decline,attributed to increases in habitat loss.There is a knowledge gap in understanding the genomic status and genetic basis underlying the local adaptation of this threatened bird.Here,we used population genomic data to assess population structure,genetic diversity,inbreeding patterns,and genetic divergence.Furthermore,we identified candidate genes linked with adaptation across the current distribution of Reeves’s Pheasant.The present study assembled the first de novo genome sequence of Reeves’s Pheasant and annotated 19,458 genes.We also sequenced 30 individuals from three populations(Dabie Mountain,Shennongjia,Qinling Mountain)and found that there was clear population structure among those populations.By comparing with other threatened species,we found that Reeves’s Pheasants have low genetic diversity.Runs of homozygosity suggest that the Shennongjia population has experienced serious inbreeding.The demographic history results indicated that three populations experienced several declines during the glacial period.Local adaptative analysis among the populations identified 241 candidate genes under directional selection.They are involved in a large variety of processes,including the immune response and pigmentation.Our results suggest that the three populations should be considered as three different conservation units.The current study provides genetic evidence for conserving the threatened Reeves’s Pheasant and provides genomic resources for global biodiversity management.展开更多
Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 n...Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also analyzed.Structural variations were identified in all patients with a mean of 349,which did not significantly influence prognosis.Copy loss occurred in all samples,while gains were detected in 77.9%of the samples.The high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the cases.CD79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.展开更多
Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation...Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation of the genotypes linked to multidrug resistance is crucial for comprehending the mechanisms underlying drug resistance. The objective of this research was to assess the attributes of gene mutations associated with multidrug resistance in clinical isolates of mycobacterium tuberculosis through the utilization of whole-genome sequencing. Methods: A total of 124 strains of drug-resistant mycobacterium tuberculosis were collected, and the genomic DNA of both multidrug-resistant and rifampin-resistant strains were extracted and sequenced. Bioinformatics was used to analyze and compare multidrug resistance-related gene sequences in order to detect the variation of multidrug resistance genes. Results: The results revealed that the resistance spectrum of XDR-TB group was much wider than that of the other three groups, with the RR-TB group having the most limited resistance spectrum.Within the MDR-TB strains, fabG1 exhibited the highest frequency of mutations, while RRS, gyrA, and rpoB were identified as the predominant mutation bases in XDR-TB strains. Additionally, rpoB emerged as the primary mutation base in MDR-TB and RR-TB strains. Notably, the fabG1 mutation was found to be closely associated with PDR-TB. Furthermore, the correlation between the mutation rate of rpoB and multidrug resistance was deemed to be of secondary importance. Conclusion: Various strains of MTB exhibited distinct mechanisms of drug resistance, with the gene mutations of fabG1,RRS, gyrA, and rpoB potentially playing a pivotal role in the development of drug resistance. However, the primary genes responsible for drug resistance mutations varied among different strains of TB.展开更多
基金funded by the National Key R&D Program of China [2022YFC2305200]Natural Science Foundation of Xinjiang Uygur Autonomous Region [2021A01D145 and 2022D01A115]Applied Technology Research and Development Programing Project of Kashgar Prefecture [KS2021031 and KS2021034]。
文摘Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
基金supported by the National Natural Science Foundation of China (82001372)National Key Research and Development Program of China (2018YFE0126700)+3 种基金Shanghai Jiao Tong University 2030 Initiative (WH510363001-7)Shanghai Municipal Commission of Science and Technology Program (21dz2210100)Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037)a National Institutes of Health (NIH)grant (5R01HG002385)to E.E.E。
文摘The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
基金supported by the grants from the Sichuan Science and Technology Program,China(2020YFN0024)the earmarked fund for the China Agriculture Research System(CARS-35-01A)+2 种基金the National Key R&D Program of China(2018YFD0501204)the National Natural Science Foundation of China(C170102)the Sichuan Innovation Team of Pig,China(sccxtd-2021-08)。
文摘We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST(Z(FST))method,and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity(ZHp)method.The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism,disease resistance,cellular processes,and biochemical signals,and several were related to body morphology and organs.They included PPP3CA,which plays an essential role in the transduction of intracellular Ca2+-mediated signals,and WWTR1,which plays a pivotal role in organ size control and tumor suppression.These results suggest that genes associated with body morphology were subject to selection pressure during domestication,whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding.Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.
基金Supported by Program of Taizhou Science and Technology Grant,No.20ywb29Medical Health Science and Technology Project of Zhejiang Province,No.2021PY083+2 种基金Key Technology Research and Development Program of Zhejiang Province,No.2019C03040Open Project Program of Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province,No.21SZDSYS01 and 21SZDSYS09Major Research Program of Taizhou Enze Medical Center Grant,No.19EZZDA2
文摘BACKGROUND Gastric cancer(GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori(H. pylori) and Epstein-Barr virus(EBV), and genetic components.AIM To investigate microbiomes and host genome instability by cost-effective,low-coverage wholegenome sequencing,as biomarkers for GC subtyping.METHODS Samples from 40 GC patients were collected from Taizhou Hospital,Zhejiang Province,affiliated with Wenzhou Medical University.DNA from the samples was subjected to low-coverage wholegenome sequencing with a median genome coverage of 1.86×(range:1.03×to 3.17×) by Illumina×10,followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector.RESULTS Of the 40 GC samples,20 (50%) were found to be enriched with microbiomes.EBV DNA was detected in 5 GC patients (12.5%).H.pylori DNA was found in 15 (37.5%) patients.The other 20(50%) patients were found to have relatively higher genomic instability.Copy number amplifications of the oncogenes,ERBB2 and KRAS,were found in 9 (22.5%) and 7 (17.5%) of the GC samples,respectively.EBV enrichment was found to be associated with tumors in the gastric cardia and fundus.H.pylori enrichment was found to be associated with tumors in the pylorus and antrum.Tumors with elevated genomic instability showed no localization and could be observed in any location.Additionally,H.pylori-enriched GC was found to be associated with the Borrmann type Ⅱ/Ⅲ and gastritis history.EBV-enriched GC was not associated with gastritis.No statistically significant correlation was observed between genomic instability and gastritis.Furthermore,these three different molecular subtypes showed distinct survival outcomes (P=0.019).EBV-positive tumors had the best prognosis,whereas patients with high genomic instability (CIN+) showed the worst survival.Patients with H.pylori infection showed intermediate prognosis compared with the other two subtypes.CONCLUSION Thus,using low-coverage whole-genome sequencing,GC can be classified into three categories based on disease etiology;this classification may prove useful for GC diagnosis and precision medicine.
基金This research was supported by the Funding Project of Chinese Central Government Guiding to the Guangxi Local Science and Technology Development(GUIKEZY21195021)the Natural Science Fund for Distinguished Young Scholars of Guangxi Zhuang Autonomous Region of China(2019GXNSFFA245011)+3 种基金the Funding Project of Chinese Central Government Guiding to the Nanning Local Science and Technology Development(20231012)the Funding Projects of Guangxi Key Research and Development Plan(GUIKE AB23075173)the Funding Project of Technological Development from Angel Yeast(Chongzuo)Co.,Ltd.(JS1006020230722019)the Innovation Project of Guangxi Graduate Education(YCBZ2021012).
文摘The application of microorganisms as probiotics is limited due to lack of safety evaluation.Here,a novel multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified from marine mangrove microorganisms.Its safety and probiotic properties were assessed in accordance with phenotype and whole-genome sequencing analysis.Results showed that the genes and phenotypic expression of related virulence,antibiotic resistance and retroelement were rarely found.Hyphal morphogenesis genes(SIT4,HOG1,SPA2,ERK1,ICL1,CST20,HSP104,TPS1,and RHO1)and phospholipase secretion gene(VPS4)were annotated.True hyphae and phospholipase were absent.Only one retroelement(Tad1-65_BG)was found.Major biogenic amines(BAs)encoding genes were absent,except for spermidine synthase(JA9_002594),spermine synthase(JA9_004690),and tyrosine decarboxylase(inx).The production of single BAs and total BAs was far below the food-defined thresholds.GXDK6 had no resistance to common antifungal drugs.Virulence enzymes,such as gelatinase,DNase,hemolytic,lecithinase,and thrombin were absent.Acute toxicity test with mice demonstrated that GXDK6 is safe.GXDK6 has a good reproduction ability in the simulation gastrointestinal tract.GXDK6 also has a strong antioxidant ability,β-glucosidase,and inulinase activity.To sum up,GXDK6 is considered as a safe probiotic for human consumption and food fermentation.
基金supported by the Three Gorges Environmental Funds of China Three Gorges Corporation(Grant No.XN270)。
文摘The order Acipenseriformes,which includes sturgeons and paddlefishes,represents“living fossils”with complex genomes that are good models for understanding whole-genome duplication(WGD)and ploidy evolution in fishes.Here,we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis(Chinese sturgeon),a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes.Our results show that A.sinensis is a complex autooctoploid species containing four kinds of octovalents(8n),a hexavalent(6n),two tetravalents(4n),and a divalent(2n).An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs,and further provides insights into the timing of its ploidy evolution.This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.
文摘Beach pea or beach cowpea(Vigna marina(Burm.)Merr.)belongs to the family Fabaceae.It is a close relative of cultivated Vigna species such as adzuki bean(V.angularis),cowpea(V.unguiculata),mung bean(V.radiata),and blackgram(V.mungo),and is distributed throughout the tropics.With its ability to tolerate salt stress,beach pea has great potential to contribute salt-tolerance genes for developing salt-tolerant cultivars in cultivated Vigna species.However,it is still underutilized in Vigna breeding programs.A draft genome sequence of beach pea was generated using a high-throughput next-generation sequencing platform,yielding 23.7 Gb of sequence from 79,929,868 filtered reads.A de novo genome assembly containing 68,731 scaffolds gave an N50 length of 10,272 bp and the assembled sequences totaled 365.6 Mb.A total of 35,448 SSRs,including 3574 compound SSRs,were identified and primer pairs for most of these SSRs were designed.Genome analysis identified 50,670 genes with mean coding sequence length 1042 bp.Phylogenetic analysis revealed highest sequence similarity with V.angularis,followed by V.radiata.Comparison with the V.angularis genome revealed 16,699 SNPs and 2253 InDels and comparison with the V.radiata genome revealed 17,538 SNPs and 2300 InDels.To our knowledge this is the first draft genome sequence of beach pea derived from an accession(ANBp-14-03)adapted locally in the Andaman and Nicobar Islands of India.The draft genome sequence may facilitate the genetic enhancement in cultivated Vigna species.
基金National natural science foundation of China,No.81860367,31460017,81672072Key Research and Development Program of Hainan Province,No.ZDYF2017091+1 种基金Special Project for Scientific Research of Institutions of Higher Learning in Hainan Province,No.Hnky2017ZD-16,Hnkyzx2014-08Open Fund Project of State key Laboratory of Virology in 2018.Project,No.2018IOV002.
文摘Objective:To perform whole-genome sequencing and phylogenetic analysis of the local endemic strain of Rodent Torque teno virus (RoTTV), RoTTV3-HMU1, found in Rattus norvegicus, Haikou City, Hainan Province, and establish a SYBR Green I based real-time PCR detection assay for RoTTV3.Methods: Based on the high-throughput genome sequencing analysis, specific primers were designed and the whole genome sequence was amplified by PCR and Sanger sequencing. Specific detection primers were designed based on the conserved sequences of RoTTV3. The recombinant plasmid contained the whole genome of RoTTV3-HMU1 was constructed as a standard control. The experimental conditions were optimized and the real-time PCR detection assay of RoTTV3 was established.Results: The genomic sequence of RoTTV carried by Rattus norvegicus in Haikou City was successfully sequenced. Phylogenetic analysis indicated that the virus belongs to the RoTTV3 genotype. In this experiment, the real-time PCR detection method of RoTTV3 was established. The standard curve generated had a wide dynamic range from 1×(102-108) copies/μL, with a linear correlation (R2=1.000). The melting curve analysis using SYBR Green showed only one specific melting peak and no primer-dimmers represented. The detection limit was 100 copies/reaction.Discussion: This study was the first report of the RoTTV in Hainan Islands, and its phylogenetic analysis was of great significance to the origin and evolution of RoTTV. The RoTTV3 real-time PCR detection method established in this experiment has a high sensitivity and good specificity, which lays a technical foundation for the epidemiological investigation of RoTTV3.
基金National High Level Hospital Clinical Research Funding(BJ-2018-204,BJ-2023-112)。
文摘Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.
基金supported by the Biodiversity Survey,Monitoring and Assessment Project(2019–2023)of the Ministry of Ecology and EnvironmentChina(No.2019HB2096001006 to ZZ)+2 种基金the National Natural Science Foundation of China(31672319)Endangered Species Scientific Commission of China(No.2022–331)supported by the China Scholarship Council,China。
文摘Population genomic data could provide valuable information for conservation efforts;however,limited studies have been conducted to investigate the genetic status of threatened pheasants.Reeves’s Pheasant(Syrmaticus reevesii)is facing population decline,attributed to increases in habitat loss.There is a knowledge gap in understanding the genomic status and genetic basis underlying the local adaptation of this threatened bird.Here,we used population genomic data to assess population structure,genetic diversity,inbreeding patterns,and genetic divergence.Furthermore,we identified candidate genes linked with adaptation across the current distribution of Reeves’s Pheasant.The present study assembled the first de novo genome sequence of Reeves’s Pheasant and annotated 19,458 genes.We also sequenced 30 individuals from three populations(Dabie Mountain,Shennongjia,Qinling Mountain)and found that there was clear population structure among those populations.By comparing with other threatened species,we found that Reeves’s Pheasants have low genetic diversity.Runs of homozygosity suggest that the Shennongjia population has experienced serious inbreeding.The demographic history results indicated that three populations experienced several declines during the glacial period.Local adaptative analysis among the populations identified 241 candidate genes under directional selection.They are involved in a large variety of processes,including the immune response and pigmentation.Our results suggest that the three populations should be considered as three different conservation units.The current study provides genetic evidence for conserving the threatened Reeves’s Pheasant and provides genomic resources for global biodiversity management.
基金supported by funds from the Translational Research Grant of National Clinical Research Center for Hematologic Disease (No.2020ZKZC01)the National Natural Science Foundation of China (Nos.81830006,82170219,and 81800188)the Lymphoma Research Fund of China Anti-Cancer Association.
文摘Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor prognosis.This study aimed to depict the genetic landscape of Chinese PCNSLs.Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also analyzed.Structural variations were identified in all patients with a mean of 349,which did not significantly influence prognosis.Copy loss occurred in all samples,while gains were detected in 77.9%of the samples.The high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the cases.CD79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.
文摘Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation of the genotypes linked to multidrug resistance is crucial for comprehending the mechanisms underlying drug resistance. The objective of this research was to assess the attributes of gene mutations associated with multidrug resistance in clinical isolates of mycobacterium tuberculosis through the utilization of whole-genome sequencing. Methods: A total of 124 strains of drug-resistant mycobacterium tuberculosis were collected, and the genomic DNA of both multidrug-resistant and rifampin-resistant strains were extracted and sequenced. Bioinformatics was used to analyze and compare multidrug resistance-related gene sequences in order to detect the variation of multidrug resistance genes. Results: The results revealed that the resistance spectrum of XDR-TB group was much wider than that of the other three groups, with the RR-TB group having the most limited resistance spectrum.Within the MDR-TB strains, fabG1 exhibited the highest frequency of mutations, while RRS, gyrA, and rpoB were identified as the predominant mutation bases in XDR-TB strains. Additionally, rpoB emerged as the primary mutation base in MDR-TB and RR-TB strains. Notably, the fabG1 mutation was found to be closely associated with PDR-TB. Furthermore, the correlation between the mutation rate of rpoB and multidrug resistance was deemed to be of secondary importance. Conclusion: Various strains of MTB exhibited distinct mechanisms of drug resistance, with the gene mutations of fabG1,RRS, gyrA, and rpoB potentially playing a pivotal role in the development of drug resistance. However, the primary genes responsible for drug resistance mutations varied among different strains of TB.