Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wil...Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.展开更多
The mitochondrial DNA copy number(mtDNAcn)plays a vital role in cellular energy metabolism and mitochondrial health.As mitochondria are responsible for adenosine triphosphate production through oxidative phosphorylati...The mitochondrial DNA copy number(mtDNAcn)plays a vital role in cellular energy metabolism and mitochondrial health.As mitochondria are responsible for adenosine triphosphate production through oxidative phosphorylation,maintaining an appropriate mtDNAcn level is vital for the overall cellular function.Alterations in mtDNAcn have been linked to various diseases,including neurodegenerative disorders,metabolic conditions,and cancers,making it an important biomarker for understanding the disease pathogenesis.The accurate estimation of mtDNAcn is essential for clinical applications.Quantitative polymerase chain reaction and next-generation sequencing are commonly employed techniques with distinct advantages and limitations.Clinically,mtDNAcn serves as a valuable indicator for early diagnosis,disease progression,and treatment response.For instance,in oncology,elevated mtDNAcn levels in blood samples are associated with tumor aggressiveness and can aid in monitoring treatment efficacy.In neurodegenerative diseases such as Alzheimer’s and Parkinson’s,altered mtDNAcn patterns provide insights into disease mechanisms and progression.Understanding and estimating mtDNAcn are critical for advancing diagnostic and therapeutic strategies in various medical fields.As research continues to uncover the implications of mtDNAcn alterations,its potential as a clinical biomarker is likely to expand,thereby enhancing our ability to diagnose and manage complex diseases.展开更多
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,para...Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).展开更多
Toxic effects in terms of mitochondria and hereditary substances have been characterized in vitro for individual rare earth elements,while,the joint effects of mixed elements exposure in the population remain ambiguou...Toxic effects in terms of mitochondria and hereditary substances have been characterized in vitro for individual rare earth elements,while,the joint effects of mixed elements exposure in the population remain ambiguous.Based on the Occupational Chromate Exposure Dynamic Cohort of China,this study investigated the relationship between 15 blood rare earth elements(cerium,dysprosium,erbium,europium,gadolinium,holmium,lanthanum,lutetium,neodymium,praseodymium,samarium,terbium,thulium,yttrium,and ytterbium)and mitochondrial DNA copy number(MtDNACN)as well as peripheral blood lymphocyte micronucleus frequency(MNF).The elastic net was used to select elements highly correlated with effect indicators,whose dose-response relationships were further illustrated by restricted cubic splines.Bayesian kernel regressionwas employed to explore the combined effects of elements and the contributions of single element.The results showed that most rare earth elementswere positively correlatedwith effect indicators,with yttrium showing the strongest association(β(95%CI):0.139(0.1089–0.189)for MtDNACN,0.937(0.345–1.684)for MNF).In the mixed exposure model,with the exposure level fixed at the 50th percentile as the reference,the effect estimates on MtDNACN and MNF increased by 0.228 and 0.598 units,respectively,at the 75th percentile.The single effect analysis implied that yttrium,lanthanum and terbium contributed the most to the elevation of MtDNACN,while yttrium posed the highest risk for genetic damage,accordingly,we provided recommendations to prioritize these elements of concern.In addition,we observed a chief mediating effect of MtDNACN on the elevation of MNF caused by lanthanum,whereas further mechanistic exploration is required to confirm this finding.展开更多
Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure ...Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.展开更多
Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune systems.The assoc...Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune systems.The association between major histocompatibility complex(MHC)genes and certain ecological factors in response to pathogen selection has been extensively studied;however,the role of the co-working molecule T cell receptor(TCR)remains poorly understood.This study aimed to analyze the copy numbers of TCR-V genes,the selection pressure(ωvalue)on MHC genes using available genomic data,and their potential ecological correlates across 93 species from 13 orders.The study was conducted using the publicly available genome data of birds.Our findings suggested that phylogeny influences the variability in TCR-V gene copy numbers and MHC selection pressure.The phylogenetic generalized least squares regression model revealed that TCR-Vαδcopy number and MHC-I selection pressure were positively associated with body mass.Clutch size was correlated with MHC selection pressure,and Migration was correlated with TCR-Vβcopy number.Further analyses revealed that the TCR-Vβcopy number was positively correlated with MHC-IIB selection pressure,while the TCR-Vγcopy number was negatively correlated with MHC-I peptide-binding region selection pressure.Our findings suggest that TCR-V diversity is significant in adaptive evolution and is related to species’life-history strategies and immunological defenses and provide valuable insights into the mechanisms underlying TCR-V gene duplication and MHC selection in avian species.展开更多
In light of the lack of reliable molecular markers for odontogenic myxoma(OM),the detection of copy number variation(CNV)may present a more objective method for assessing ambiguous cases.In this study,we employed mult...In light of the lack of reliable molecular markers for odontogenic myxoma(OM),the detection of copy number variation(CNV)may present a more objective method for assessing ambiguous cases.In this study,we employed multiregional microdissection sequencing to integrate morphological features with genomic profiling.This allowed us to reveal the CNV profiles of OM and compare them with dental papilla(DP),dental follicle(DF),and odontogenic fibroma(OF)tissues.We identified a distinct and robustly consistent CNV pattern in 93.75%(30/32)of OM cases,characterized by CNV gain events in chromosomes 4,5,8,10,12,16,17,20,and 21.This pattern significantly differed from the CNV patterns observed in DP,DF,and OF.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated potential links between this CNV patterns and the calcium signaling pathway and salivary secretion,while Gene Ontology(GO)term analysis implicated CNV patterns in tumor adhesion,tooth development,and cell proliferation.Comprehensive CNV analysis accurately identified a case that was initially disputable between OF and OM as OM.Our findings provide a reliable diagnostic clue and fresh insights into the molecular biological mechanism underlying OM.展开更多
Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of...Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.展开更多
In order to isolate the total cDNA of rice (Oryza sativa L.) epsps gene, RT-PCR was carried out with template of rice first-strand cDNA and primers designed according to rice EPSP synthase genomic sequence obtained in...In order to isolate the total cDNA of rice (Oryza sativa L.) epsps gene, RT-PCR was carried out with template of rice first-strand cDNA and primers designed according to rice EPSP synthase genomic sequence obtained in previous study. A 1 585-bp cDNA fragment was amplified and cloned. The 1 585-bp cDNA contains an open reading frame (ORF) comprising of 1 533 nucleotides (nt) which encodes a 511 residue polypepetides, including 67 amino acids chloroplast transit peptide and 444 amino acids EPSP synthase mature peptide. A comparison between the EPSP synthase of different sources indicates that the mature peptide shows more than 51% identity except for the fungi EPSP synthase and the transit peptide shows considerably less sequence conservation. The copy number of rice epsps gene is estimated to be one copy per haploid rice genome using southern blot. RT-PCR indicated that rice epsps gene is expressed in rice leaves, endosperms and roots and has the highest expression level in leaves.展开更多
Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphol...Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.展开更多
[Objective] To explore the feasibility of using SYBR Green real-time quantitative PCR technique to estimate the copy numbers of exogenous gene in a transgenic plant.[Methods] Using SYBR Green real-time quantitative PC...[Objective] To explore the feasibility of using SYBR Green real-time quantitative PCR technique to estimate the copy numbers of exogenous gene in a transgenic plant.[Methods] Using SYBR Green real-time quantitative PCR technique,we have determined the copy numbers of the exogenous CYCD3;1 in transgenic Arabidopsis by comparing an endogenous single copy reference gene with CYCD3;1 copy numbers in transgenic plant,meanwhile comparing CYCD3;1 copy numbers between wild plant and transgenic plant.[Results]The exogenous CYCD3;1 copy numbers calculated by this method is identical with results of traditional Southern blot analysis which is highly accurate.[Conclusion]This method is simple,effective and safe for estimating transgene copy numbers.展开更多
AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was i...AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.展开更多
Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration,...Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration, diabetes, aging, and many other human diseases. Although it is known that the dynamics of the mammalian mitochondrial genome are not linked with that of the nuclear genome, very little is known about the mechanism of mtDNA propagation. Nevertheless, our understanding of the mode of mtDNA replication has ad- vanced in recent years, though not without some controversies. This review summarizes our current knowledge of mtDNA copy number control in mammalian cells, while focusing on both mtDNA replication and turnover. Although mtDNA copy number is seemingly in excess, we reason that mtDNA copy number control is an important aspect of mitochondrial genetics and biogenesis and is essential for normal cellular function.展开更多
Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the elderly.The pur...Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the elderly.The purpose of this study was to investigate mitochondrial DNA copy number(mtDNACN)and inflammatory cytokines in primary knee OA patients and healthy volunteers.A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited.Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction(qRT-PCR),and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay.Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group.Leukocyte mtDNACN in the control group was negatively correlated with their age(r=−0.380,P<0.0001),whereas mtDNACN in the OA group was positively correlated with their age(r=0.198,P<0.001).Plasma interleukin-4(IL-4)and IL-6 were significantly higher in the knee OA group than in the control group.The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group(r=0.547,P=0.0014).IL-5 showed as a major factor(coefficient 0.69)in the second dimension of principle components analysis(PCA)-transformed data and was significantly higher in the OA group(P<0.001)as well as negatively correlated with mtDNACN(r=−0.577,P<0.001).These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA.IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.展开更多
Germline copy number variation （CNV） is considered to be an important form of human genetic poly- morphisms. Previous studies have identified amounts of CNVs in human genome by advanced technologies, such as compara...Germline copy number variation （CNV） is considered to be an important form of human genetic poly- morphisms. Previous studies have identified amounts of CNVs in human genome by advanced technologies, such as comparative genomic hybridization, single nucleotide genotyping, and high-throughput sequencing. CNV is speculated to be derived from multiple mechanisms, such as nonallelic homologous recombination （NAHR） and nonhomologous end-joining （NHEJ）. CNVs cover a much larger genome scale than single nucleotide polymorphisms （SNPs）, and may alter gene expression levels by means of gene dosage, gene fusion, gene disruption, and long-range regulation effects, thus affecting individual phenotypes and playing crucial roles in human pathogenesis. The number of studies linking CNVs with common complex diseases has increased dramatically in recent years. Here, we provide a comprehensive review of the current understanding ofgermline CNVs, and summarize the association of germline CNVs with the susceptibility to a wide variety of human diseases that were identified in recent years. We also propose potential issues that should be addressed in future studies.展开更多
In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and t...In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and their evolutionary history remain unclear.We scanned PERVs in the current pig reference genome(assembly Build 11.1),and identified 36 long complete or near-complete PERVs(lc PERVs)and 23 short incomplete PERVs(si PERVs).Besides three known PERVs(PERV-A,-B,and-C),four novel types(PERV-JX1,-JX2,-JX3,and-JX4)were detected in this study.According to evolutionary analyses,the newly discovered PERVs were more ancient,and PERV-Bs probably experienced a bottleneck~0.5 million years ago(Ma).By analyzing63 high-quality porcine whole-genome resequencing data,we found that the PERV copy numbers in Chinese pigs were lower(32.0±4.0)than in Western pigs(49.1±6.5).Additionally,the PERV sequence diversity was lower in Chinese pigs than in Western pigs.Regarding the lc PERV copy numbers,PERV-A and-JX2 in Western pigs were higher than in Chinese pigs.Notably,Bama Xiang(BMX)pigs had the lowest PERV copy number(27.8±5.1),and a BMX individual had no PERV-C and the lowest PERV copy number(23),suggesting that BMX pigs were more suitable for screening and/or modification as xenograft donors.Furthermore,we identified 451 PERV transposon insertion polymorphisms(TIPs),of which 86 were shared by all 10 Chinese and Western pig breeds.Our findings provide systematic insights into the genomic distribution,variation,evolution,and possible biological function of PERVs.展开更多
Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between l...Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer(BLCA). Messenger RNA(mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis(WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2 F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus(GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the mitogen-activated protein kinase(MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription(JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.展开更多
The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer （NSCLC） tissues and patient clinicopathologic characteristics and su...The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer （NSCLC） tissues and patient clinicopathologic characteristics and sur- vival. Sixty-one NSCLC tissue specimens were included in the study. The expression of MET and cyclin D1 was evaluated by immunohistochemistry and MET gene copy number was assessed by quantitative real-time polymer- ase chain reaction （Q-PCR）. Positive expression of MET and cyclin D1 protein and increased MET gene copy number occurred in 59.0%, 59.0% and 18.0% of 61 NSCLC tissues, respectively. MET-positivity correlated with poor differentiation （P = 0.009）. Increased MET gene copy number was significantly associated with lymph node metastasis （P = 0.004） and advanced tumor stage （P = 0.048）, while the expression of cyclin D1 was not associ- ated with any clinicopathologic parameters. There was a significant correlation between the expression of MET and MET gene copy number （P = 0.002）. Additionally, the expression of cyclin D1 had a significant association with the expression of MET as well as MET gene copy number （P = 0.002 and P = 0.017, respectively）. MET- positivity and increased MET gene copy number were significantly associated with poor overall survival （P = 0.003 and P 〈 0.001, respectively） in univariate analysis. Multivariate Cox proportional hazard analysis confirmed that the expression of MET and MET gene copy number were prognostic indicators of NSCLC （P = 0.003 and P = 0.001, respectively）. The overexpression of MET and the increased MET gene copy number might be adverse prognostic factors for NSCLC patients. The activation of the MET/cyclin D1 signaling pathway may contribute to carcino- genesis and the development of NSCLC, and may represent a target for therapy.展开更多
Premenstrual dysphoric disorder(PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present stu...Premenstrual dysphoric disorder(PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy number variations(CNVs) called from 100 kb white blood cell DNA sequence windows by means of semisupervized clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types,respectively, with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine learning method enabled the classification of the CNVs obtained into the D group, V group, total patient group, and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be used for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordance between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominantly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.展开更多
AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-...AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.展开更多
基金funded by the National Natural Science Foundation of China(grant no.32270238 and 31870311).
文摘Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.
文摘The mitochondrial DNA copy number(mtDNAcn)plays a vital role in cellular energy metabolism and mitochondrial health.As mitochondria are responsible for adenosine triphosphate production through oxidative phosphorylation,maintaining an appropriate mtDNAcn level is vital for the overall cellular function.Alterations in mtDNAcn have been linked to various diseases,including neurodegenerative disorders,metabolic conditions,and cancers,making it an important biomarker for understanding the disease pathogenesis.The accurate estimation of mtDNAcn is essential for clinical applications.Quantitative polymerase chain reaction and next-generation sequencing are commonly employed techniques with distinct advantages and limitations.Clinically,mtDNAcn serves as a valuable indicator for early diagnosis,disease progression,and treatment response.For instance,in oncology,elevated mtDNAcn levels in blood samples are associated with tumor aggressiveness and can aid in monitoring treatment efficacy.In neurodegenerative diseases such as Alzheimer’s and Parkinson’s,altered mtDNAcn patterns provide insights into disease mechanisms and progression.Understanding and estimating mtDNAcn are critical for advancing diagnostic and therapeutic strategies in various medical fields.As research continues to uncover the implications of mtDNAcn alterations,its potential as a clinical biomarker is likely to expand,thereby enhancing our ability to diagnose and manage complex diseases.
文摘Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).
基金supported by the National Natural Science Foundation of China(Nos.U200420282273603 and 82003427).
文摘Toxic effects in terms of mitochondria and hereditary substances have been characterized in vitro for individual rare earth elements,while,the joint effects of mixed elements exposure in the population remain ambiguous.Based on the Occupational Chromate Exposure Dynamic Cohort of China,this study investigated the relationship between 15 blood rare earth elements(cerium,dysprosium,erbium,europium,gadolinium,holmium,lanthanum,lutetium,neodymium,praseodymium,samarium,terbium,thulium,yttrium,and ytterbium)and mitochondrial DNA copy number(MtDNACN)as well as peripheral blood lymphocyte micronucleus frequency(MNF).The elastic net was used to select elements highly correlated with effect indicators,whose dose-response relationships were further illustrated by restricted cubic splines.Bayesian kernel regressionwas employed to explore the combined effects of elements and the contributions of single element.The results showed that most rare earth elementswere positively correlatedwith effect indicators,with yttrium showing the strongest association(β(95%CI):0.139(0.1089–0.189)for MtDNACN,0.937(0.345–1.684)for MNF).In the mixed exposure model,with the exposure level fixed at the 50th percentile as the reference,the effect estimates on MtDNACN and MNF increased by 0.228 and 0.598 units,respectively,at the 75th percentile.The single effect analysis implied that yttrium,lanthanum and terbium contributed the most to the elevation of MtDNACN,while yttrium posed the highest risk for genetic damage,accordingly,we provided recommendations to prioritize these elements of concern.In addition,we observed a chief mediating effect of MtDNACN on the elevation of MNF caused by lanthanum,whereas further mechanistic exploration is required to confirm this finding.
基金supported by the project“Protection of biodiversity of Italian poultry breeds—TuBAvI”,funded in the framework of the PSRN 2014–2020,submeasure 10.2“Support for sustainable conservation,use and development of genetic resources in agriculture”.
文摘Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2022C04014)Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding(No.2021C02068-10).
文摘Birds,a fascinating and diverse group occupying various habitats worldwide,exhibit a wide range of life-history traits,reproductive methods,and migratory behaviors,all of which influence their immune systems.The association between major histocompatibility complex(MHC)genes and certain ecological factors in response to pathogen selection has been extensively studied;however,the role of the co-working molecule T cell receptor(TCR)remains poorly understood.This study aimed to analyze the copy numbers of TCR-V genes,the selection pressure(ωvalue)on MHC genes using available genomic data,and their potential ecological correlates across 93 species from 13 orders.The study was conducted using the publicly available genome data of birds.Our findings suggested that phylogeny influences the variability in TCR-V gene copy numbers and MHC selection pressure.The phylogenetic generalized least squares regression model revealed that TCR-Vαδcopy number and MHC-I selection pressure were positively associated with body mass.Clutch size was correlated with MHC selection pressure,and Migration was correlated with TCR-Vβcopy number.Further analyses revealed that the TCR-Vβcopy number was positively correlated with MHC-IIB selection pressure,while the TCR-Vγcopy number was negatively correlated with MHC-I peptide-binding region selection pressure.Our findings suggest that TCR-V diversity is significant in adaptive evolution and is related to species’life-history strategies and immunological defenses and provide valuable insights into the mechanisms underlying TCR-V gene duplication and MHC selection in avian species.
基金supported by the National Natural Science Foundation of China(Nos.81671006 and 81300894)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-038)the Program for New Clinical Techniques and Therapies of Peking University Hospital of Stomatology(No.PKUSSNCT 22A14),China。
文摘In light of the lack of reliable molecular markers for odontogenic myxoma(OM),the detection of copy number variation(CNV)may present a more objective method for assessing ambiguous cases.In this study,we employed multiregional microdissection sequencing to integrate morphological features with genomic profiling.This allowed us to reveal the CNV profiles of OM and compare them with dental papilla(DP),dental follicle(DF),and odontogenic fibroma(OF)tissues.We identified a distinct and robustly consistent CNV pattern in 93.75%(30/32)of OM cases,characterized by CNV gain events in chromosomes 4,5,8,10,12,16,17,20,and 21.This pattern significantly differed from the CNV patterns observed in DP,DF,and OF.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated potential links between this CNV patterns and the calcium signaling pathway and salivary secretion,while Gene Ontology(GO)term analysis implicated CNV patterns in tumor adhesion,tooth development,and cell proliferation.Comprehensive CNV analysis accurately identified a case that was initially disputable between OF and OM as OM.Our findings provide a reliable diagnostic clue and fresh insights into the molecular biological mechanism underlying OM.
基金Dongguan City Social Development Project(Project number:20161081101023)。
文摘Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.
文摘In order to isolate the total cDNA of rice (Oryza sativa L.) epsps gene, RT-PCR was carried out with template of rice first-strand cDNA and primers designed according to rice EPSP synthase genomic sequence obtained in previous study. A 1 585-bp cDNA fragment was amplified and cloned. The 1 585-bp cDNA contains an open reading frame (ORF) comprising of 1 533 nucleotides (nt) which encodes a 511 residue polypepetides, including 67 amino acids chloroplast transit peptide and 444 amino acids EPSP synthase mature peptide. A comparison between the EPSP synthase of different sources indicates that the mature peptide shows more than 51% identity except for the fungi EPSP synthase and the transit peptide shows considerably less sequence conservation. The copy number of rice epsps gene is estimated to be one copy per haploid rice genome using southern blot. RT-PCR indicated that rice epsps gene is expressed in rice leaves, endosperms and roots and has the highest expression level in leaves.
基金grants from Beijing Hospital Key Research Program(121 Research Program,No.BJ2019-195)。
文摘Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.
基金Supported by National Natural Science Foundation Project(30270086)~~
文摘[Objective] To explore the feasibility of using SYBR Green real-time quantitative PCR technique to estimate the copy numbers of exogenous gene in a transgenic plant.[Methods] Using SYBR Green real-time quantitative PCR technique,we have determined the copy numbers of the exogenous CYCD3;1 in transgenic Arabidopsis by comparing an endogenous single copy reference gene with CYCD3;1 copy numbers in transgenic plant,meanwhile comparing CYCD3;1 copy numbers between wild plant and transgenic plant.[Results]The exogenous CYCD3;1 copy numbers calculated by this method is identical with results of traditional Southern blot analysis which is highly accurate.[Conclusion]This method is simple,effective and safe for estimating transgene copy numbers.
基金Supported by the National Natural Science Foundation of China(No.82060183)Ningxia Natural Science Foundation(No.2022AAC03388)the Key Research and Development Project of Ningxia Hui Autonomous Region(No.2021BEG02045,No.2020BEG03044).
文摘AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
基金supported by the National Institute of Aging/National Institution of Health, USA (No. AG025223 and AG024640) to YB.
文摘Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration, diabetes, aging, and many other human diseases. Although it is known that the dynamics of the mammalian mitochondrial genome are not linked with that of the nuclear genome, very little is known about the mechanism of mtDNA propagation. Nevertheless, our understanding of the mode of mtDNA replication has ad- vanced in recent years, though not without some controversies. This review summarizes our current knowledge of mtDNA copy number control in mammalian cells, while focusing on both mtDNA replication and turnover. Although mtDNA copy number is seemingly in excess, we reason that mtDNA copy number control is an important aspect of mitochondrial genetics and biogenesis and is essential for normal cellular function.
基金Project supported by the 90th Anniversary of Chulalongkorn University(No.RA61/104)the Research Chair Grant from the National Science and Technology Development Agency+1 种基金the 100th Anniversary of Chulalongkorn University Fund for Doctoral Scholarshipthe Overseas Research Experience Scholarship for Graduate Student,Thailand and China Scholarship Council,China
文摘Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the elderly.The purpose of this study was to investigate mitochondrial DNA copy number(mtDNACN)and inflammatory cytokines in primary knee OA patients and healthy volunteers.A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited.Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction(qRT-PCR),and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay.Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group.Leukocyte mtDNACN in the control group was negatively correlated with their age(r=−0.380,P<0.0001),whereas mtDNACN in the OA group was positively correlated with their age(r=0.198,P<0.001).Plasma interleukin-4(IL-4)and IL-6 were significantly higher in the knee OA group than in the control group.The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group(r=0.547,P=0.0014).IL-5 showed as a major factor(coefficient 0.69)in the second dimension of principle components analysis(PCA)-transformed data and was significantly higher in the OA group(P<0.001)as well as negatively correlated with mtDNACN(r=−0.577,P<0.001).These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA.IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.
基金supported by the Basic Research Program of Jiangsu Province (BK20160606)
文摘Germline copy number variation （CNV） is considered to be an important form of human genetic poly- morphisms. Previous studies have identified amounts of CNVs in human genome by advanced technologies, such as comparative genomic hybridization, single nucleotide genotyping, and high-throughput sequencing. CNV is speculated to be derived from multiple mechanisms, such as nonallelic homologous recombination （NAHR） and nonhomologous end-joining （NHEJ）. CNVs cover a much larger genome scale than single nucleotide polymorphisms （SNPs）, and may alter gene expression levels by means of gene dosage, gene fusion, gene disruption, and long-range regulation effects, thus affecting individual phenotypes and playing crucial roles in human pathogenesis. The number of studies linking CNVs with common complex diseases has increased dramatically in recent years. Here, we provide a comprehensive review of the current understanding ofgermline CNVs, and summarize the association of germline CNVs with the susceptibility to a wide variety of human diseases that were identified in recent years. We also propose potential issues that should be addressed in future studies.
基金supported by the National Swine Industry and Technology System of China(nycytx-009)National Natural Science Foundation of China(31672383)。
文摘In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and their evolutionary history remain unclear.We scanned PERVs in the current pig reference genome(assembly Build 11.1),and identified 36 long complete or near-complete PERVs(lc PERVs)and 23 short incomplete PERVs(si PERVs).Besides three known PERVs(PERV-A,-B,and-C),four novel types(PERV-JX1,-JX2,-JX3,and-JX4)were detected in this study.According to evolutionary analyses,the newly discovered PERVs were more ancient,and PERV-Bs probably experienced a bottleneck~0.5 million years ago(Ma).By analyzing63 high-quality porcine whole-genome resequencing data,we found that the PERV copy numbers in Chinese pigs were lower(32.0±4.0)than in Western pigs(49.1±6.5).Additionally,the PERV sequence diversity was lower in Chinese pigs than in Western pigs.Regarding the lc PERV copy numbers,PERV-A and-JX2 in Western pigs were higher than in Chinese pigs.Notably,Bama Xiang(BMX)pigs had the lowest PERV copy number(27.8±5.1),and a BMX individual had no PERV-C and the lowest PERV copy number(23),suggesting that BMX pigs were more suitable for screening and/or modification as xenograft donors.Furthermore,we identified 451 PERV transposon insertion polymorphisms(TIPs),of which 86 were shared by all 10 Chinese and Western pig breeds.Our findings provide systematic insights into the genomic distribution,variation,evolution,and possible biological function of PERVs.
基金supported by the Natural Science Foundation of Guangdong Province (No. 2017A030313898)the Guangzhou Science and Technology Plan Projects (No. 201707010113), China。
文摘Copy number variations(CNVs), which can affect the role of long non-coding RNAs(lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer(BLCA). Messenger RNA(mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis(WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2 F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus(GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the mitogen-activated protein kinase(MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription(JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.
基金supported in part by a grant from the Nature Science Foundation of Health Bureau of Shaanxi Province(#08D28)
文摘The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer （NSCLC） tissues and patient clinicopathologic characteristics and sur- vival. Sixty-one NSCLC tissue specimens were included in the study. The expression of MET and cyclin D1 was evaluated by immunohistochemistry and MET gene copy number was assessed by quantitative real-time polymer- ase chain reaction （Q-PCR）. Positive expression of MET and cyclin D1 protein and increased MET gene copy number occurred in 59.0%, 59.0% and 18.0% of 61 NSCLC tissues, respectively. MET-positivity correlated with poor differentiation （P = 0.009）. Increased MET gene copy number was significantly associated with lymph node metastasis （P = 0.004） and advanced tumor stage （P = 0.048）, while the expression of cyclin D1 was not associ- ated with any clinicopathologic parameters. There was a significant correlation between the expression of MET and MET gene copy number （P = 0.002）. Additionally, the expression of cyclin D1 had a significant association with the expression of MET as well as MET gene copy number （P = 0.002 and P = 0.017, respectively）. MET- positivity and increased MET gene copy number were significantly associated with poor overall survival （P = 0.003 and P 〈 0.001, respectively） in univariate analysis. Multivariate Cox proportional hazard analysis confirmed that the expression of MET and MET gene copy number were prognostic indicators of NSCLC （P = 0.003 and P = 0.001, respectively）. The overexpression of MET and the increased MET gene copy number might be adverse prognostic factors for NSCLC patients. The activation of the MET/cyclin D1 signaling pathway may contribute to carcino- genesis and the development of NSCLC, and may represent a target for therapy.
基金supported by grants to HX from University Grants Council(SRF116SC01UROP18SC06+10 种基金UROP20SC07)Innovation and Technology Commission(ITS/085/10ITS113/15FPITCPD/17-9ITT/023/17GPITT/026/18GP)of Hong Kong SARShenzhen Municipal Council of Science and Technology,Guangdong(JCYJ20170818113656988)Guangdong Province Basic and Applied Basic Research Fund(2021A1515011169)Shandong Province First Class Disciple Development Grant and Tai-Shan Scholar Program,Shandongand Ministry of Science and Technology(National Science and Technology Major Project,No.2017ZX09301064,2017ZX09301064004)People’s Republic of China,as well as grants from National Natural Science Foundation of China to M.Q.(8157151623)and J.W.(81603510)。
文摘Premenstrual dysphoric disorder(PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy number variations(CNVs) called from 100 kb white blood cell DNA sequence windows by means of semisupervized clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types,respectively, with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine learning method enabled the classification of the CNVs obtained into the D group, V group, total patient group, and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be used for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordance between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominantly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.
基金Supported by the Chang Gung Memorial Hospital in Taiwan,No.CMRPG 3C0951-3 and No.CMRPG 3A0671 to Yu MC,and No.CMRPD3F0011 to Tsai CN
文摘AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient prognosis.METHODS One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded(FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan platform to assess CNAs and loss of heterozygosity(LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage Ⅰ/Ⅱ HCC were enrolled to analyze gene expression and to correlate findings with the Onco Scan data.RESULTS Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change(≥ 60%) was an independent factor for worse prognosis in early-stage HCC(P = 0.031). Among the 875 genes in the Onco Scan Gene Chip, six were independent predictors of worse disease-free survival, of which three were amplified(MYC, ELAC2, and SYK) and three were deleted(GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs(P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSION Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.
