• 제목/요약/키워드: gene design

검색결과 358건 처리시간 0.032초

Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
    • /
    • 제32권3호
    • /
    • pp.365-377
    • /
    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

Association between Cigarette Smoking and RASSF1A Gene Promoter Hypermethylation in Lung Cancer Patients: a Meta-analysis

  • Wu, Xiao-Ming;Chen, Yu;Shao, Yang;Zhou, Xiao-Long;Tang, Wen-Ru
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권19호
    • /
    • pp.8451-8454
    • /
    • 2014
  • Objectives: Epidemiological studies have shown that molecular mechanisms underlying the development of lung cancers differ between smokers and unsmokers. Aberrant promoter methylation in some tumor suppressor genes is frequent in lung tumors from smokers but rare in those from non-smokers. Recently, many studies have investigated the association between cigarette smoking and RASSF1A gene promoter hypermethylation in lung cancer patients, but a unanimous conclusion could not be reached. We therefore performed this meta-analysis to derive a more precise estimation of any association. Study Design: An electronic search of PubMed and Chinese Biomedicine databases was conducted to select studies. A total of 19 case-control studies were chosen, and odds ratios (ORs) with confidence intervals (CIs) were used to assess the strength of associations. Results: The case-control studies covered 2, 287 lung cancer patients: 63.4%(1449) of the patients were smokers, 36.6% (838) were unsmokers. The overall results suggested that smokers with lung cancer had a 1.297-fold (95% CI: 1.066~1.580, p=0.010, p=0.087) higher risk for RASSF1A gene hypermethylation than the non-smokers. In the stratified analysis, an increased risk of RASSF1A gene hypermethylation in smokers than in non-smokers was found in Asian (OR=1.481, 95%CI: 1.179~1.861, p=0.001, p=0.186). Conclusions: This meta-analysis supports the idea that RASSF1A gene hypermethylation is associated with cigarette smoking-induced lung cancer.

Efficient and Precise Construction of Markerless Manipulations in the Bacillus subtilis Genome

  • Yu, Haojie;Yan, Xin;Shen, Weiliang;Shen, Yujia;Zhang, Ji;Li, Shunpeng
    • Journal of Microbiology and Biotechnology
    • /
    • 제20권1호
    • /
    • pp.45-53
    • /
    • 2010
  • We have developed an efficient and precise method for genome manipulations in Bacillus subtilis that allows rapid alteration of a gene sequence or multiple gene sequences without altering the chromosome in any other way. In our approach, the Escherichia coli toxin gene mazF, which was used as a counter-selectable marker, was placed under the control of a xylose-inducible expression system and associated with an antibiotic resistance gene to create a "mazF-cassette". A polymerase chain reaction (PCR)-generated fragment, consisting of two homology regions joined to the mazF-cassette, was integrated into the chromosome at the target locus by homologous recombination, using positive selection for antibiotic resistance. Then, the excision of the mazF-cassette from the chromosome by a single-crossover event between two short directly repeated (DR) sequences, included in the design of the PCR products, was achieved by counter-selection of mazF. We used this method efficiently and precisely to deliver a point mutation, to inactivate a specific gene, to delete a large genomic region, and to generate the in-frame deletion with minimal polar effects in the same background.

Lack of Association of the Cyclooxygenase-2 Gene 8473T>C Polymorphism with Breast Cancer Risk: a Meta-analysis

  • Yang, Xi;Zhao, Fen;Li, Yue-Hua;Huang, Min;Huang, Ying;Yi, Cheng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권22호
    • /
    • pp.9693-9698
    • /
    • 2014
  • Background: Associations between the 8473T>C polymorphism (rs5275) in the cyclooxygenase-2 (COX-2) gene and breast cancer (BC) risk are still inconclusive and ambiguous. The aim of this meta-analysis was to comprehensively estimate the genetic risk of 8473T>C polymorphism in the COX-2 gene for BC. Materials and Methods: We searched PubMed, Web of Science, Medline, Chinese biomedical (CBM), Weipu, China national knowledge infrastructure (CNKI), and Wanfang databases, covering all publications (last search was updated on Aug 17, 2014). Statistical analyses were performed using Revman 5.3 and STATA 10.0 software. Results: A total of 6,720 cases and 9,794 controls in 12 studies were included in this study. The results indicated no significant associations between the 8473T>C polymorphism of the COX-2 gene and BC risk for the CC+TC vs TT model (pooled odds ratio (OR)=0.97, 95% confidence interval (CI)=0.90-1.03, and p=0.29). On subgroup analysis, we also found that subdivision on ethnicity among Caucasians, Asians and others also revealed no relationship with BC susceptibility. With the study design (CC+TC vs TT), no significant associations were found in either population-based case-control studies (PCC), or hospital-based case-control studies (HCC). Conclusions: This present meta-analysis suggests that the 8473T>C polymorphism in the COX-2 gene is not a conspicuous low-penetrant risk factor for developing BC.

발정 주기중 흰쥐 자궁에서의 Luteinizing Hormone (LH)과 수용체 유전자 발현 (Expression of Luteinizing Hormone (LH) and Its Receptor Gene in Uterus from Cycling Rats)

  • 김성례;이성호
    • Clinical and Experimental Reproductive Medicine
    • /
    • 제26권3호
    • /
    • pp.383-387
    • /
    • 1999
  • Objective: There is increasing evidence for the expression of rat in gene in several extrapituitary sites including testis and ovary. We also have demonstrated that the local LH expression in the rat epididymis and uterus, the major accessory sex organs in male and female reproductive system, respectively. Design: The present study was undertaken to elucidate whether the gene for LH receptor is expressed in rat uterus and whether the expressions of uterine LH and its receptor are differentially regulated during estrous cycle. Presence of the transcripts for rat LH receptor in the rat uterine tissue were confirmed by touchdown reverse transcription-polymerase chain reaction (RT-PCR). Results: In $LH{\beta}$ semi-quantitative RT-PCR, the highest expression level was shown in estrus stage. The level of ill receptor transcripts was also fluctuated during estrous cycle. In ovariectomized rats (OVX + Oil), the expressions of both uterine LH and LH-R were markedly reduced when compared to those from normal rats. Supplement with estradiol $17{\beta}$ to the ovariectomized rats (OVX + $E_2$) restored the expression levels of LH and its receptor to the levels in uteri from normal rats. Conclusion: Our findings indicated that 1) LH and its receptor gene are expressed in the rat uterus from cycling rats, 2) the expression of uterine LH and its receptor is mainly, if not all, under the control of ovarian sex steroid(s). These results suggested that the uterine LH may act as a local regulator with auto and/or paracrine manner, though the posibility that the pituitary LH may act directly on the regulation of uterine functions could not be discarded.

  • PDF

황색종 연초(Nicotiana tabacum L.)의 엽위별 엽형질에 대한 유전자 효과분석 (Genetic Parameters for Some Leaf Characters in Flue-Cured Tobacco (Nicotiana tabacum L. ) at Two Representative Stalk Positions)

  • 조수헌
    • 한국연초학회지
    • /
    • 제10권2호
    • /
    • pp.117-122
    • /
    • 1988
  • This experiment was conducted to study the nature of gene effects for the leaf characters in flue-cured tobacco. The genetic populations were derived from crosses between NC 2326 and Mc Nair 373, and NC 628 and DG-72. The generation means experiment Included the Pl, P2. Fl, F2, Bl and B2, which were frown at Taegu Experiment Station, Korea Ginseng & Tobacco Research Institute in 1984. Seedlings were transplanted to the field in a randomized block design with 3 replications. In each block, parental and Fl Plots contained 15 plants in a single row, F2, Bl and B2 plots being composed of 75 plant, in 5 rows. Leaf characters were measured of largest (middle leaf) and 5th leaf(top leaf) from the top after topping. Measurements of the length and width of leaf were obtained from the fresh the middle and top leaves, and weight of leaf, weight and width of midrib were from the satrap leaf after curing. Estimates of additive and dominance genetic variance were analyzed according to Gamble's biometrical model. The results obtained are as follows: 1. The additive gene effects were significant and larger than the dominance gene effects for all leaf and midrib characters in both stalk positions. 2. The dominance gene effects were significant for the length and width of leaf, and weight of midrib in the middle leaves. 3. The digenic epistatic effects were significant for the length and width of leaf in both stalk positions. 4. The additive gene effects were larger in the top than in the middle leaves and midrib characters.

  • PDF

The effect of the new stopping criterion on the genetic algorithm performance

  • Kaya, Mustafa;Genc, Asim
    • Computers and Concrete
    • /
    • 제27권1호
    • /
    • pp.63-71
    • /
    • 2021
  • In this study, a new stopping criterion, called "backward controlled stopping criterion" (BCSC), was proposed to be used in Genetic Algorithms. In the study, the available stopping citeria; adaptive stopping citerion, evolution time, fitness threshold, fitness convergence, population convergence, gene convergence, and developed stopping criterion were applied to the following four comparison problems; high strength concrete mix design, pre-stressed precast concrete beam, travelling salesman and reinforced concrete deep beam problems. When completed the analysis, the developed stopping criterion was found to be more accomplished than available criteria, and was able to research a much larger area in the space design supplying higher fitness values.

Optimal Design for Marker-assisted Gene Pyramiding in Cross Population

  • Xu, L.Y.;Zhao, F.P.;Sheng, X.H.;Ren, H.X.;Zhang, L.;Wei, C.H.;Du, L.X.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제25권6호
    • /
    • pp.772-784
    • /
    • 2012
  • Marker-assisted gene pyramiding aims to produce individuals with superior economic traits according to the optimal breeding scheme which involves selecting a series of favorite target alleles after cross of base populations and pyramiding them into a single genotype. Inspired by the science of evolutionary computation, we used the metaphor of hill-climbing to model the dynamic behavior of gene pyramiding. In consideration of the traditional cross program of animals along with the features of animal segregating populations, four types of cross programs and two types of selection strategies for gene pyramiding are performed from a practical perspective. Two population cross for pyramiding two genes (denoted II), three population cascading cross for pyramiding three genes(denoted III), four population symmetry (denoted IIII-S) and cascading cross for pyramiding four genes (denoted IIII-C), and various schemes (denoted cross program-A-E) are designed for each cross program given different levels of initial favorite allele frequencies, base population sizes and trait heritabilities. The process of gene pyramiding breeding for various schemes are simulated and compared based on the population hamming distance, average superior genotype frequencies and average phenotypic values. By simulation, the results show that the larger base population size and the higher the initial favorite allele frequency the higher the efficiency of gene pyramiding. Parents cross order is shown to be the most important factor in a cascading cross, but has no significant influence on the symmetric cross. The results also show that genotypic selection strategy is superior to phenotypic selection in accelerating gene pyramiding. Moreover, the method and corresponding software was used to compare different cross schemes and selection strategies.

DNA Microarray 시스템을 이용한 방선균 독소루비신 생합성 유전자군의 발현패턴 분석 (Expression Profiles of Streptomyces Doxorubicin Biosynthetic Gene Cluster Using DNA Microarray System)

  • 강승훈;김명근;박현주;김응수
    • KSBB Journal
    • /
    • 제20권3호
    • /
    • pp.220-227
    • /
    • 2005
  • 독소루비신 생합성 유전자의 발현을 촉진시키는 유전자인 dnrI와 다나루비신으로부터 독소루비신으로의 생전환에 관여하는 유전자인 doxA를 ermE 프로모터가 포함된 pSE34에 도입하였을 때 각각 5.5배, 2.5배의 독소루비신 생산성 증가가 이루어졌다. 독소루비신 생합성 유전자군의 발현패턴 분석을 위한 DNA microarray system을 구축하였고, 고생산 균주의 독소루비신 생합성 유전자 발현 패턴을 DNA microarray를 통해 확인하였다. 독소루비신 생합성 유전자군의 세포성장에 따른 발현패턴을 분석한 결과, 독소루비신 생산성 증가에 따라 생합성 유전자의 발현도 증가함을 확인할 수 있었고, pSE34를 통해 도입해준 donA, dnrI 유전자의 경우 전체 생합성 유전자의 평균보다 높은 수준의 발현량을 보여줌으로써, ermE 프로모터에 의해 발현이 극대화되었음을 확인할 수 있었다. 독소루비신 내성 유전자의 경우 다른 독소루비신 생합성 유전자들에 비해 발현정도가 크게 증가했고, DnrI 의해 조절을 받는 다른 유전자들의 발현 수준과 비교하였을 때 TDP-daunosamine을 생합성의 첫 번째 단계에 관여하는 dnmL 유전자는 그 발현양의 증가가 크지 않았다. 따라서 DNA microarray 시스템 분석 결과, 독소루비신 생산성 극대화를 위해서는 dnrI, doxA, drrA, drrB, drrC, dnmL 등의 유전자들의 안정적 발현이 매우 중요하고도 핵심적인 인자임이 확인되었다.

Identification of polymorphic loci in the deiodinase 2 gene and their associations with head dimensions in geese

  • Deng, Yan;Hu, Qian;Tang, Bincheng;Ouyang, Qingyuan;Hu, Shenqiang;Hu, Bo;Hu, Jiwei;He, Hua;Chen, Guohong;Wang, Jiwen
    • Animal Bioscience
    • /
    • 제35권5호
    • /
    • pp.639-647
    • /
    • 2022
  • Objective: This study was conducted to clone and compare the molecular characteristics of the deiodinase 2 (DIO2) gene between Sichuan White geese and Landes geese, and to analyze the association between polymorphisms of the DIO2 gene and head dimensions in Tianfu meat geese. Methods: The coding sequence of the DIO2 gene was cloned by polymerase chain reaction and vector ligation and aligned by DNAMAN software. A total of 350 Tianfu meat geese were used to genotype the polymorphisms of the DIO2 gene and measure the head dimensions. Association analysis between the polymorphisms of the DIO2 gene and head dimensions was carried out. Results: An 840-bp coding sequence of the DIO2 gene was obtained and comparison analysis identified four polymorphic loci between Sichuan White geese and Landes geese. Further analysis showed that the dominant alleles for the four polymorphic loci were G, G, A, and T and the frequency of the heterozygous genotype was higher than that of the homozygous genotype in Tianfu meat geese. Compared to that in the population of non-knob geese of Tianfu meat geese, the head dimensions in the population of knob geese were significantly higher except for nostril height. However, in the non-knob geese, beak width 1, beak width 2, nostril length, cranial width 1, and maxillary length had significant differences among different genotypes or haplotypes/diplotypes. Conclusion: These results suggested that polymorphisms of the DIO2 gene could be considered molecular markers to select larger heads of geese in the population of non-knob geese.