Sample records for aberrant gene expression

  1. Aberrant Gene Expression in Humans

    PubMed Central

    Yang, Ence; Ji, Guoli; Brinkmeyer-Langford, Candice L.; Cai, James J.

    2015-01-01

    Gene expression as an intermediate molecular phenotype has been a focus of research interest. In particular, studies of expression quantitative trait loci (eQTL) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression levels. Existing eQTL methods are designed for assessing the effects of common variants, but not rare variants. Here, we address the problem by establishing a novel analytical framework for evaluating the effects of rare or private variants on gene expression. Our method starts from the identification of outlier individuals that show markedly different gene expression from the majority of a population, and then reveals the contributions of private SNPs to the aberrant gene expression in these outliers. Using population-scale mRNA sequencing data, we identify outlier individuals using a multivariate approach. We find that outlier individuals are more readily detected with respect to gene sets that include genes involved in cellular regulation and signal transduction, and less likely to be detected with respect to the gene sets with genes involved in metabolic pathways and other fundamental molecular functions. Analysis of polymorphic data suggests that private SNPs of outlier individuals are enriched in the enhancer and promoter regions of corresponding aberrantly-expressed genes, suggesting a specific regulatory role of private SNPs, while the commonly-occurring regulatory genetic variants (i.e., eQTL SNPs) show little evidence of involvement. Additional data suggest that non-genetic factors may also underlie aberrant gene expression. Taken together, our findings advance a novel viewpoint relevant to situations wherein common eQTLs fail to predict gene expression when heritable, rare inter-individual variation exists. The analytical framework we describe, taking into consideration the reality of differential phenotypic robustness, may be valuable for investigating complex traits and conditions. PMID:25617623

  2. Aberrant regulation of imprinted gene expression in Gtl2 mice

    Microsoft Academic Search

    Y. Sekita; H. Wagatsuma; M. Irie; S. Kobayashi; T. Kohda; J. Matsuda; M. Yokoyama; A. Ogura; K. Schuster-Gossler; A. Gossler; F. Ishino; T. Kaneko-Ishino

    2006-01-01

    The imprinted region on mouse distal chromosome 12 covers about 1 Mb and contains at least three paternally expressed genes (Pegs: Peg9\\/Dlk1, Peg11\\/Rtl1, and Dio3) and four maternally expressed genes (Megs: Meg3\\/Gtl2, antiPeg11\\/antiRlt1, Meg8\\/Rian, and Meg9\\/Mirg). Gtl2lacZ (Gene trap locus 2) mice have a transgene (TG) insertion 2.3 kb upstream from the Meg3\\/Gtl2 promoter and show about 40% growth retardation

  3. Aberrant Gene Expression in Dogs with Portosystemic Shunts

    PubMed Central

    Grinwis, Guy C. M.; Kummeling, Anne; van Gils, Ingrid H. M.; Koerkamp, Marian J. A. Groot.; van Leenen, Dik; Holstege, Frank C. P.; Penning, Louis C.; Rothuizen, Jan; Leegwater, Peter A. J.; Spee, Bart

    2013-01-01

    Congenital portosystemic shunts are developmental anomalies of the splanchnic vascular system that cause portal blood to bypass the liver. Large-breed dogs are predisposed for intrahepatic portosystemic shunts (IHPSS) and small-breed dogs for extrahepatic portosystemic shunts (EHPSS). While the phenotype resulting from portal bypass of the liver of the two types of shunt is identical, the genotype and molecular pathways involved are probably different. The aim of this study was to gain insight into the pathways involved in the different types of portosystemic shunting. Microarray analysis of mRNA expression in liver tissue from dogs with EHPSS and IHPSS revealed that the expression of 26 genes was altered in either IHPSS or EHPSS samples compared with that in liver samples from control dogs. Quantitative real-time PCR of these genes in 14 IHPSS, 17 EHPSS, and 8 control liver samples revealed a significant differential expression of ACBP, CCBL1, GPC3, HAMP, PALLD, VCAM1, and WEE1. Immunohistochemistry and Western blotting confirmed an increased expression of VCAM1 in IHPSS but its absence in EHPSS, an increased WEE1 expression in IHPSS but not in EHPSS, and a decreased expression of CCBL1 in both shunt types. Regarding their physiologic functions, these findings may indicate a causative role for VCAM1 in IHPSS and WEE1 for IHPSS. CCBL1 could be an interesting candidate to study not yet elucidated aspects in the pathophysiology of hepatic encephalopathy. PMID:23451256

  4. Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Huang, Xudong; Wu, Chen; Tan, Wen; Qiao, Yan; Chang, Jiang; Zhao, Hong; Bi, Xinyu; Cai, Jianqiang; Li, Yun; Lin, Dongxin

    2015-01-01

    Background It is well known that chronic inflammation plays a pivotal role in the development of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). However, the causes behind aberrant expression of inflammation-related genes occurred in HCC remain unclear. Methods We performed array-based analyses to comprehensively investigate the contributions of DNA methylation and somatic copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation-related genes in 30 HCCs and paired non-tumor tissues. The results were validated in public datasets and an additional sample set of 47 paired HCCs and non-tumor tissues. Results We identified 252 differentially expressed, 125 aberrantly methylated and 287 copy number changed inflammation-related genes. Despite reasonable statistical power, among them, only 11 genes and 56 genes whose aberrant expression was associated with DNA methylation or SCNA, respectively. DNA methylation and SCNA together contributed to less than 30% aberrant expression of inflammation-related genes. Conclusion These results suggest that molecular mechanisms other than DNA methylation and SCNA might play major role in the regulation of aberrant expression of inflammation-related gene in HBV-related HCCs. PMID:25965583

  5. Aberrant epigenetic changes and gene expression in cloned cattle dying around birth

    Microsoft Academic Search

    Li Lin; Qiang Li; Lei Zhang; Dingsheng Zhao; Yunping Dai; Ning Li

    2008-01-01

    BACKGROUND: Aberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning. To assess the extent of abnormal epigenetic modifications and gene expression in clones, we simultaneously examined DNA methylation, histone H4 acetylation and expression of six genes (?-actin, VEGF, oct4, TERT, H19 and Igf2) and a repetitive sequence (art2) in five organs (heart, liver,

  6. From DNA Copy Number to Gene Expression: Local aberrations, Trisomies and Monosomies

    NASA Astrophysics Data System (ADS)

    Shay, Tal

    The goal of my PhD research was to study the effect of DNA copy number changes on gene expression. DNA copy number aberrations may be local, encompassing several genes, or on the level of an entire chromosome, such as trisomy and monosomy. The main dataset I studied was of Glioblastoma, obtained in the framework of a collaboration, but I worked also with public datasets of cancer and Down's Syndrome. The molecular basis of expression changes in Glioblastoma. Glioblastoma is the most common and aggressive type of primary brain tumors in adults. In collaboration with Prof. Hegi (CHUV, Switzerland), we analyzed a rich Glioblastoma dataset including clinical information, DNA copy number (array CGH) and expression profiles. We explored the correlation between DNA copy number and gene expression at the level of chromosomal arms and local genomic aberrations. We detected known amplification and over expression of oncogenes, as well as deletion and down-regulation of tumor suppressor genes. We exploited that information to map alterations of pathways that are known to be disrupted in Glioblastoma, and tried to characterize samples that have no known alteration in any of the studied pathways. Identifying local DNA aberrations of biological significance. Many types of tumors exhibit chromosomal losses or gains and local amplifications and deletions. A region that is aberrant in many tumors, or whose copy number change is stronger, is more likely to be clinically relevant, and not just a by-product of genetic instability. We developed a novel method that defines and prioritizes aberrations by formalizing these intuitions. The method scores each aberration by the fraction of patients harboring it, its length and its amplitude, and assesses the significance of the score by comparing it to a null distribution obtained by permutations. This approach detects genetic locations that are significantly aberrant, generating a 'genomic aberration profile' for each sample. The 'genomic aberration profile' is then combined with chromosomal arm status (gain/loss) to define a succinct genomic signature for each tumor. Unsupervised clustering of the samples based on these genomic signatures can reveal novel tumor subtypes. This approach was applied to datasets from three types of brain tumors: Glioblastoma, Medulloblastoma and Neuroblastoma, and identified a new subtype in Medulloblastoma, characterized by many chromosomal aberrations. Elucidating the transcriptional effect of monosomy and trisomy. Trisomy and monosomy are expected to impact the expression of genes that are located on the affected chromosome. Analysis of several cancer datasets revealed that not all the genes on the aberrant chromosome are affected by the change of copy number. Affected genes exhibit a wide range of expression changes with varying penetrance. Specifically, (1) The effect of trisomy is much more conserved among individuals than the effect of monosomy and (2) the expression level of a gene in the diploid is significantly correlated with the level of change between the diploid and the trisomy or monosomy.

  7. Heritable Transmission of Diabetic Metabolic Memory in Zebrafish Correlates With DNA Hypomethylation and Aberrant Gene Expression

    PubMed Central

    Olsen, Ansgar S.; Sarras, Michael P.; Leontovich, Alexey; Intine, Robert V.

    2012-01-01

    Metabolic memory (MM) is the phenomenon whereby diabetes complications persist and progress after glycemic recovery is achieved. Here, we present data showing that MM is heritable and that the transmission correlates with hyperglycemia-induced DNA hypomethylation and aberrant gene expression. Streptozocin was used to induce hyperglycemia in adult zebrafish, and then, following streptozocin withdrawal, a recovery phase was allowed to reestablish a euglycemic state. Blood glucose and serum insulin returned to physiological levels during the first 2 weeks of the recovery phase as a result of pancreatic ?-cell regeneration. In contrast, caudal fin regeneration and skin wound healing remained impaired to the same extent as in diabetic fish, and this impairment was transmissible to daughter cell tissue. Daughter tissue that was never exposed to hyperglycemia, but was derived from tissue that was, did not accumulate AGEs or exhibit increased levels of oxidative stress. However, CpG island methylation and genome-wide microarray expression analyses revealed the persistence of hyperglycemia-induced global DNA hypomethylation that correlated with aberrant gene expression for a subset of loci in this daughter tissue. Collectively, the data presented here implicate the epigenetic mechanism of DNA methylation as a potential contributor to the MM phenomenon. PMID:22228713

  8. Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer

    PubMed Central

    Inoue, Kimiko; Oikawa, Mami; Kamimura, Satoshi; Ogonuki, Narumi; Nakamura, Toshinobu; Nakano, Toru; Abe, Kuniya; Ogura, Atsuo

    2015-01-01

    Although mammalian cloning by somatic cell nuclear transfer (SCNT) has been established in various species, the low developmental efficiency has hampered its practical applications. Treatment of SCNT-derived embryos with histone deacetylase (HDAC) inhibitors can improve their development, but the underlying mechanism is still unclear. To address this question, we analysed gene expression profiles of SCNT-derived 2-cell mouse embryos treated with trichostatin A (TSA), a potent HDAC inhibitor that is best used for mouse cloning. Unexpectedly, TSA had no effect on the numbers of aberrantly expressed genes or the overall gene expression pattern in the embryos. However, in-depth investigation by gene ontology and functional analyses revealed that TSA treatment specifically improved the expression of a small subset of genes encoding transcription factors and their regulatory factors, suggesting their positive involvement in de novo RNA synthesis. Indeed, introduction of one of such transcription factors, Spi-C, into the embryos at least partially mimicked the TSA-induced improvement in embryonic development by activating gene networks associated with transcriptional regulation. Thus, the effects of TSA treatment on embryonic gene expression did not seem to be stochastic, but more specific than expected, targeting genes that direct development and trigger zygotic genome activation at the 2-cell stage. PMID:25974394

  9. Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

    SciTech Connect

    Tsujiuchi, Toshifumi [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)]. E-mail: ttujiuch@life.kindai.ac.jp; Shimizu, Kyoko [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Onishi, Mariko [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Sugata, Eriko [Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fujii, Hiromasa [Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Toshio [RI Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Honoki, Kanya [Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Fukushima, Nobuyuki [Laboratory of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

    2006-10-27

    Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, it has been reported that alterations of LPA receptor expression might be important in the malignant transformation of tumor cells. Therefore, to assess an involvement of DNA methylation in reduced expression of the LPA receptor-1 (lpa1) gene, we investigated the expression of the lpa1 gene and its DNA methylation patterns in rat tumor cell lines. Both rat brain-derived neuroblastoma B103 and liver-derived hepatoma RH7777 cells used in this study indicated no expression of lpa1. For the analysis of methylation status, bisulfite sequencing was performed with B103 and RH7777 cells, comparing with other lpa1 expressed cells and normal tissues of brain and liver. The lpa1 expressed cells and tissues were all unmethylated in this region of lpa1. In contrast, both B103 and RH7777 cells were highly methylated, correlating with reduced expression of the lpa1. Treatment with 5-aza 2'-deoxycytidine induced expression of lpa1 gene in B103 and RH7777 cells after 24 h. In RH7777 cells treated with 5-aza 2'-deoxycytidine, stress fiber formation was also observed in response to LPA in RH7777 cells, but not in untreated RH7777 cells. These results suggest that aberrant DNA methylation of the lpa1 gene may be involved in its reduced expression in rat tumor cells.

  10. Aberrant host immune response induced by highly virulent PRRSV identified by digital gene expression tag profiling

    Microsoft Academic Search

    Shuqi Xiao; Delin Mo; Qiwei Wang; Jianyu Jia; Limei Qin; Xiangchun Yu; Yuna Niu; Xiao Zhao; Xiaohong Liu; Yaosheng Chen

    2010-01-01

    BACKGROUND: There was a large scale outbreak of the highly pathogenic porcine reproductive and respiratory syndrome (PRRS) in China and Vietnam during 2006 and 2007 that resulted in unusually high morbidity and mortality among pigs of all ages. The mechanisms underlying the molecular pathogenesis of the highly virulent PRRS virus (H-PRRSV) remains unknown. Therefore, the relationship between pulmonary gene expression

  11. Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma

    Microsoft Academic Search

    MP Buisine; A Janin; V Maunoury; JP Audie; MP Delescaut; MC Copin; JF Colombel; P Degand; JP Aubert; N Porchet

    1996-01-01

    BACKGROUND & AIMS: Rectosigmoid villous adenomas (RVAs) account for approximately 10% of all colorectal tumors. They have distinct pathological features, including abundant mucus secretion, possible malignant transformation, and multiple recurrences after conservative treatment. The aim of this study was to determine the nature of any changes in mucin gene expression in RVAs. METHODS: In situ hybridization was used to examine

  12. Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors.

    PubMed

    Chilukamarri, Laxmi; Hancock, Anne L; Malik, Sally; Zabkiewicz, Joanna; Baker, Jenny A; Greenhough, Alexander; Dallosso, Anthony R; Huang, Tim Hui-Ming; Royer-Pokora, Brigitte; Brown, Keith W; Malik, Karim

    2007-11-01

    Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5'-region in WTs relative to normal tissue is observed in 21/24 (87.5%) of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%), with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK) control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs), supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs. PMID:18030365

  13. Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29

    PubMed Central

    Yu, Xiaofeng; Du, Zhenzhen; Sun, Xuhong; Shi, Chuanqin; Zhang, Huaixiang; Hu, Tao

    2015-01-01

    The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase. While the Tn antigen cannot be detected in normal cells, Cosmc mutations inactivate T-synthase and consequently result in Tn antigen expression within certain cancers. In addition to this Cosmc mutation-induced expression, the Tn antigen is also expressed in such cell lines as Jurkat T, LSC and LS174T. Whether the Cosmc mutation is present in the colon cancer cell line HT-29 is still unclear. Here, we isolate HT-29-Tn+ cells from HT-29 cells derived from a female colon cancer patient. These HT-29-Tn+ cells show a loss of the Cosmc gene coding sequence (CDS) leading to an absence of T-synthase activity and Tn antigen expression. Additionally, almost no methylation of Cosmc CpG islands was detected in HT-29-Tn+ as well as in HT-29-Tn- and Tn- tumor cells from male patients. In contrast, the methylation frequency of CpG island of Cosmc in normal female cells was ~50%. Only one active allele of Cosmc existed in HT-29-Tn+ and HT-29-Tn- cells as based upon detection of SNP sites. These results indicate that Tn antigens expression and T-synthase inactivity in HT-29-Tn+ cells can be related to the absence of CDS in Cosmc active alleles, while an inactive allele deletion of Cosmc in HT-29 cells has no influence on Cosmc function.

  14. Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas

    PubMed Central

    Luo, Susan Y.; Sit, Ko-Yung; Sihoe, Alan D.L.; Suen, Wai-Sing; Au, Wing-Kuk; Tang, Ximing; Ma, Edmond S.K.; Chan, Wai-Kong; Wistuba, Ignacio I.; Minna, John D.; Tsao, George S.W.; Lam, David C.L.

    2015-01-01

    Background Large tumor suppressor 2 (LATS2) gene is a putative tumor suppressor gene with potential roles in regulation of cell proliferation and apoptosis in lung cancer. The aim of this study is to explore the association of aberrant LATS2 expression with EGFR mutation and survival in lung adenocarcinoma (AD), and the effects of LATS2 silencing in both lung AD cell lines. Methods LATS2 mRNA and protein expression in resected lung AD were correlated with demographic characteristics, EGFR mutation and survival. LATS2-specific siRNA was transfected into four EGFR wild-type (WT) and three EGFR mutant AD cell lines and the changes in LATS2 expression and relevant signaling molecules before and after LATS2 knockdown were assayed. Results Fifty resected lung AD were included (M:F = 23:27, smokers:non-smokers = 19:31, EGFR mutant:wild-type = 21:29) with LATS2 mRNA levels showed no significant difference between gender, age, smoking and pathological stages while LATS2 immunohistochemical staining on an independent set of 79 lung AD showed similar trend. LATS2 mRNA level was found to be a significant independent predictor for survival status (disease-free survival RR = 0.217; p = 0.003; Overall survival RR = 0.238; p = 0.036). siRNA-mediated suppression of LATS2 expression resulted in augmentation of ERK phosphorylation in EGFR wild-type AD cell lines with high basal LATS2 expression, discriminatory modulation of Akt signaling between EGFR wild-type and mutant cells, and induction of p53 accumulation in AD cell lines with low baseline p53 levels. Conclusions LATS2 expression level is predictive of survival in patients with resected lung AD. LATS2 may modulate and contribute to tumor growth via different signaling pathways in EGFR mutant and wild-type tumors. PMID:24976335

  15. Suppression of experimental lupus nephritis by aberrant expression of the soluble E-selectin gene.

    PubMed

    Takahashi, Satoru; Araki, Kimi; Araki, Masatake; Ito, Mitsuko R; Nakatani, Kimihiko; Fujii, Hiroshi; Izui, Shozo; Vassalli, Pierre; Nose, Masato

    2002-03-01

    Circulating leukocytes, particularly neutrophils and monocytes, are important effector cells in the induction of many forms of glomerulonephritis. Adhesion molecules, especially selectins, are also thought to be critical for the development of this disease. We examined the possible suppressive effect of soluble E-selectin on the development of experimental lupus nephritis induced by the injection of a hybridoma clone (2B11.3) derived from an MRL/MpJ-lpr/lpr lupus mouse. This clone produces IgG3 antibodies that induce severe proliferative glomerulonephritis resembling lupus nephritis when injected into normal mice. Transgenic mice with a soluble E-selectin gene were injected intraperitoneally with the hybridoma cells and histopathologically examined on day 15. As a result, the development of glomerulonephritis was significantly suppressed. This suppression was characterized by fewer inflammatory cell infiltrates, compared with non-transgenic litter mates, despite the fact that there were no remarkable differences in immunoglobulin deposits or expression of E-selectin between the two groups. These findings suggest that by controlling inflammatory cell infiltration, soluble E-selectin plays a preventative role in the development of a particular type of lupus nephritis. PMID:11972860

  16. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN

    E-print Network

    Lunds Universitet,

    Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, SE-22185 Lund, Sweden; d (received for review December 21, 2006) Pathway-specific therapy is the future of cancer management)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating

  17. Hypomethylation and Aberrant Expression of the Glioma Pathogenesis–Related 1 Gene in Wilms Tumors

    Microsoft Academic Search

    Laxmi Chilukamarri; Anne L. Hancock; Sally Malik; Joanna Zabkiewicz; Jenny A. Baker; Alexander Greenhough; Anthony R. Dallosso; Tim Hui-Ming Huang; Brigitte Royer-Pokora; Keith W. Brown; Karim Malik

    2007-01-01

    Wilms tumors (WTs) have a complex etiology, dis- playing genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silenc- ing. To identify new regions of epigenetic perturba- tion in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the

  18. Effects of low-dose gamma radiation on DNA damage, chromosomal aberration and expression of repair genes in human blood cells

    Microsoft Academic Search

    Wanwisa Sudprasert; Panida Navasumrit; Mathuros Ruchirawat

    2006-01-01

    Exposure to low-dose gamma radiation is common in certain occupations but the biological and health effects from such exposure remain to be determined. The aim of this study was to investigate the effects of low-dose gamma radiation on DNA damage, chromosomal aberration and DNA repair gene expressions in whole blood and peripheral lymphocytes. The study revealed a dose-dependent effect of

  19. Myelomatous plasma cells display an aberrant gene expression pattern similar to that observed in normal memory B cells

    PubMed Central

    Báez, Alicia; Piruat, José I; Caballero-Velázquez, Teresa; Sánchez-Abarca, Luís I; Álvarez-Laderas, Isabel; Barbado, M Victoria; García-Guerrero, Estefanía; Millán-Uclés, África; Martín-Sánchez, Jesús; Medrano, Mayte; Pérez-Simón, José Antonio

    2015-01-01

    Memory B cells (MBCs) remain in a quiescent state for years, expressing pro-survival and anti-apoptotic factors while repressing cell proliferation and activation genes. During their differentiation into plasma cells (PCs), their expression pattern is reversed, with a higher expression of genes related to cell proliferation and activation, and a lower expression of pro-survival genes. To determine whether myelomatous PCs (mPCs) share characteristics with normal PCs and MBCs and to identify genes involved in the pathophysiology of multiple myeloma (MM), we compared gene expression patterns in these three cell sub-types. We observed that mPCs had features intermediate between those of MBCs and normal PCs, and identified 3455 genes differentially expressed in mPCs relative to normal PCs but with a similar expression pattern to that in MBCs. Most of these genes are involved in cell death and survival, cell growth and proliferation and protein synthesis. According to our findings, mPCs have a gene expression pattern closer to a MBC than a PC with a high expression of genes involved in cell survival. These genes should be physiologically inactivated in the transit from MBC to PC, but remain overexpressed in mPCs and thus may play a role in the pathophysiology of the disease. PMID:25628947

  20. Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism

    PubMed Central

    Liu, Jie; Xie, Yaxiong; Cooper, Ryan; Ducharme, Danica M.K.; Tennant, Raymond; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2009-01-01

    Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1–19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17?-hydroxysteroid dehydrogenase-7 (HSD17?7; involved in estradiol production) and decreased expression of HSD17?5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life-stage, which could impact tumor formation much later in adulthood. PMID:17350061

  1. Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism

    SciTech Connect

    Liu Jie [Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709 (United States)]. E-mail: Liu6@niehs.nih.gov; Xie Yaxiong [Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709 (United States); Cooper, Ryan [Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709 (United States); Ducharme, Danica M.K. [National Center For Toxicogenomics, NIEHS, Research Triangle Park, NC (United States); Tennant, Raymond [National Center For Toxicogenomics, NIEHS, Research Triangle Park, NC (United States); Diwan, Bhalchandra A. [Basic Research Program, SAIC-Frederick, Inc., NCI Frederick, MD (United States); Waalkes, Michael P. [Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709 (United States)

    2007-05-01

    Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17{beta}-hydroxysteroid dehydrogenase-7 (HSD17{beta}7; involved in estradiol production) and decreased expression of HSD17{beta}5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood.

  2. Ectopic Expression of Homeobox Gene NKX2-1 in Diffuse Large B-Cell Lymphoma Is Mediated by Aberrant Chromatin Modifications

    PubMed Central

    Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

    2013-01-01

    Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies. PMID:23637834

  3. Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency

    Microsoft Academic Search

    Adrian F. Gombart; Utz Krug; James O'Kelly; Vijaya Vegesna; H. Phillip Koeffler

    2005-01-01

    Neutrophil-specific granule deficiency involves inheritance of germline mutations in the CCAAT\\/enhancer-binding protein (CEBPE) gene. Humans and mice lacking active C\\/EBP suffer frequent bacterial infections as a result of function- ally defective neutrophils and macrophages. We hypothesized that these defects reflected dysregu- lation of important immune response genes. To test this, gene expression differences of peritone- ally derived neutrophils and macrophages

  4. Aberrant Expression of Shared Master-Key Genes Contributes to the Immunopathogenesis in Patients with Juvenile Spondyloarthritis

    PubMed Central

    Lamot, Lovro; Borovecki, Fran; Tambic Bukovac, Lana; Vidovic, Mandica; Perica, Marija; Gotovac, Kristina; Harjacek, Miroslav

    2014-01-01

    Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA) according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to therapy, or even as a target for new therapeutic approaches. PMID:25506924

  5. Aberrant expression of aldehyde dehydrogenase 1A (ALDH1A) subfamily genes in acute lymphoblastic leukaemia is a common feature of T-lineage tumours.

    PubMed

    Longville, Brooke A C; Anderson, Denise; Welch, Mathew D; Kees, Ursula R; Greene, Wayne K

    2015-01-01

    The class 1A aldehyde dehydrogenase (ALDH1A) subfamily of genes encode enzymes that function at the apex of the retinoic acid (RA) signalling pathway. We detected aberrant expression of ALDH1A genes, particularly ALDH1A2, in a majority (72%) of primary paediatric T cell acute lymphoblastic leukaemia (T-ALL) specimens. ALDH1A expression was almost exclusive to T-lineage, but not B-lineage, ALL. To determine whether ALDH1A expression may have relevance to T-ALL cell growth and survival, the effect of inhibiting ALDH1A function was measured on a panel of human ALL cell lines. This revealed that T-ALL proliferation had a higher sensitivity to modulation of ALDH1A activity and RA signalling as compared to ALL cell lines of B-lineage. Consistent with these findings, the genes most highly correlated with ALDH1A2 expression were involved in cell proliferation and apoptosis. Evidence that such genes may be targets of regulation via RA signalling initiated by ALDH1A activity was provided by the TNFRSF10B gene, encoding the apoptotic death receptor TNFRSF10B (also termed TRAIL-R2), which negatively correlated with ALDH1A2 and showed elevated transcription following treatment of T-ALL cell lines with the ALDH1A inhibitor citral (3,7-dimethyl-2,6-octadienal). These data indicate that ALDH1A expression is a common event in T-ALL and supports a role for these enzymes in the pathobiology of this disease. PMID:25208926

  6. Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer

    PubMed Central

    Ma, Jihong; DeFrances, Marie C.; Zou, Chunbin; Johnson, Carla; Ferrell, Robert; Zarnegar, Reza

    2009-01-01

    The HGF gene is transcriptionally silenced in normal differentiated breast epithelial cells, but its repression fails to occur in mammary carcinoma tissues and cell lines. The molecular mechanisms underpinning aberrant HGF expression in breast cancer cells are unknown. Here we report the discovery of a DNA element located 750 bp upstream from the transcription start site in the human HGF promoter that acts as a transcriptional repressor and is a target of deletion mutagenesis in human breast cancer cells and tissues. This HGF promoter element consists of a mononucleotide repeat of 30 deoxyadenosines (30As), which we have termed “deoxyadenosine tract element” (DATE). Functional studies revealed that truncation mutations within DATE have profound local and global effects on the HGF promoter region by modulating chromatin structure and DNA-protein interactions, leading to constitutive activation of the HGF promoter in human breast carcinoma cell lines. We found that 51% of African Americans and 15% of individuals of mixed European descent with breast cancer harbor a truncated DATE variant (25As or fewer) in their breast tumors and that the truncated allele is associated with cancer incidence and aberrant HGF expression. Notably, breast cancer patients with the truncated DATE variant are substantially younger than those with a wild-type genotype. We also suggest that DATE may be used as a potential genetic marker to identify individuals with a higher risk of developing breast cancer. PMID:19188684

  7. Aberrant tissue specific expression of the transgene in transgenic mice that carry the hepatitis B virus genome defective in the X gene

    Microsoft Academic Search

    H. Nagashima; M. Imai; Y. Iwakura

    1993-01-01

    Summary The control mechanisms for the transgene expression in mice that carry the hepatitis B virus genome defective in the polymerase and X genes were analyzed. Ten lines of transgenic mouse were established, and in seven lines the surface and e antigens were detected in the serum. In transgenic mice from five lines examined, the transgene was markedly expressed in

  8. Susceptibility to heat stress and aberrant gene expression patterns in holocarboxylase synthetase-deficient Drosophila melanogaster are caused by decreased biotinylation of histones, not of carboxylases.

    PubMed

    Camporeale, Gabriela; Zempleni, Janos; Eissenberg, Joel C

    2007-04-01

    Previously, we discovered that holocarboxylase synthetase (HCS) is a chromatin-associated protein in Drosophila melanogaster and that HCS deficiency alters chromatin structure and gene expression patterns, leading to decreased heat tolerance. The effects of HCS deficiency were attributed to decreased biotinylation of histones. However, HCS is known to mediate biotinylation of carboxylases in cytoplasm and mitochondria in addition to mediating biotinylation of histones. A challenge posed by the genetic analysis of HCS is to distinguish between the effects of decreased biotinylation of carboxylases from the effects of decreased histone biotinylation in the gene expression patterns and phenotypes observed in HCS-deficient flies. Here, we tested whether 3-methylcrotonyl-CoA carboxylase (MCC) mutant flies exhibit gene expression patterns and heat susceptibility similar to that in HCS-deficient Drosophila. Biotin transporter [sodium-dependent multivitamin transporter (SMVT)] mutants were used to investigate effects of cellular biotin depletion on gene expression and heat susceptibility. Deficiencies of MCC and SMVT in mutant flies were confirmed by real-time PCR, streptavidin blotting of holocarboxylases, and analysis of MCC activities; expression of HCS and biotinylation of histones were not altered in MCC and SMVT mutants. Gene expression patterns in MCC and SMVT mutants were different from that seen with HCS-deficient flies, as judged by the abundance of mRNA coding for defective chorion 1, chitin-binding peritrophin-A, dopamine receptor 2, and yolk protein 2. MCC mutants exhibited increased resistance to heat stress compared with wild-type flies. We conclude that gene expression patterns and phenotypes in HCS-deficient flies in previous studies are caused by decreased biotinylation of histones rather than MCC. PMID:17374649

  9. Gene Expression Mural: Visualizing Gene Expression Databases

    E-print Network

    Gene Expression Mural: Visualizing Gene Expression Databases Mathew Clement, Margaret Ellis, Josh@cs.vt.edu Abstract The Gene Expression Mural is a tool designed for managing the vast amount of information produced quantifying the expression level of gene sequences in a number of conditions [1]. Software tools integrating

  10. Using ray matrices to derive analytical expressions of optical aberrations

    NASA Astrophysics Data System (ADS)

    Moreno, Ignacio; García-Martínez, Pascuala; Ferreira, Carlos

    2014-07-01

    In this work we show an easy way to derive approximated analytical expressions for spherical aberration. It is based on the use of 3?3 ray matrices, where additional elements are included to account for the errors in the ray height and angle propagation. The technique, which is commonly used to analyze misaligned systems in optical resonators, is here applied to account for deviations from the paraxial regime caused by spherical aberration.

  11. Aberrant phenotype and transcriptome expression during fiber cell wall thickening caused by the mutation of the Im gene in immature fiber (im) mutant in Gossypium hirsutum L

    PubMed Central

    2014-01-01

    Background The immature fiber (im) mutant of Gossypium hirsutum L. is a special cotton fiber mutant with non-fluffy fibers. It has low dry weight and fineness of fibers due to developmental defects in fiber secondary cell wall (SCW). Results We compared the cellulose content in fibers, thickness of fiber cell wall and fiber transcriptional profiling during SCW development in im mutant and its near-isogenic wild-type line (NIL) TM-1. The im mutant had lower cellulose content and thinner cell walls than TM-1 at same fiber developmental stage. During 25?~?35 day post-anthesis (DPA), sucrose content, an important carbon source for cellulose synthesis, was also significantly lower in im mutant than in TM-1. Comparative analysis of fiber transcriptional profiling from 13?~?25 DPA indicated that the largest transcriptional variations between the two lines occurred at the onset of SCW development. TM-1 began SCW biosynthesis approximately at 16 DPA, whereas the same fiber developmental program in im mutant was delayed until 19 DPA, suggesting an asynchronous fiber developmental program between TM-1 and im mutant. Functional classification and enrichment analysis of differentially expressed genes (DEGs) between the two NILs indicated that genes associated with biological processes related to cellulose synthesis, secondary cell wall biogenesis, cell wall thickening and sucrose metabolism, respectively, were significantly up-regulated in TM-1. Twelve genes related to carbohydrate metabolism were validated by quantitative reverse transcription PCR (qRT-PCR) and confirmed a temporal difference at the earlier transition and SCW biosynthesis stages of fiber development between TM-1 and im mutant. Conclusions We propose that Im is an important regulatory gene influencing temporal differences in expression of genes related to fiber SCW biosynthesis. This study lays a foundation for cloning the Im gene, elucidating molecular mechanism of fiber SCW development and further genetic manipulation for the improvement of fiber fineness and maturity. PMID:24483163

  12. Discovering causes and cures for cancer from gene expression analysis

    Microsoft Academic Search

    Ashani T. Weeraratna

    2005-01-01

    Tumorigenesis is governed by a series of complex genetic and epigenetic changes. Both mechanisms can result in either the silencing or aberrant expression of messages in a cell. Gene expression profiling techniques such as the serial analysis of gene expression (SAGE) or microarray analysis can provide global overviews of these changes, as well identify key genes and pathways involved in

  13. Clustering gene expression data

    E-print Network

    Shamir, Ron

    CG 1 Clustering gene expression data #12;CG 2 How Gene Expression Data Looks Expression levels-expression co-regulation). · Identifying disease profiles · Drug development ·... Analysis requires clustering of genes/conditions. #12;CG 5 Clustering: Objective Group elements (genes) to clusters satisfying

  14. Aberrant lymphocyte enhancer-binding factor 1 expression is characteristic for sporadic Burkitt's lymphoma.

    PubMed

    Walther, Neele; Ulrich, Antje; Vockerodt, Martina; von Bonin, Frederike; Klapper, Wolfram; Meyer, Katharina; Eberth, Sonja; Pukrop, Tobias; Spang, Rainer; Trümper, Lorenz; Kube, Dieter

    2013-04-01

    Burkitt's lymphoma (BL) is a highly malignant, aggressive non-Hodgkin's lymphoma derived from germinal center B cells. Recently, global gene expression profiling of patient samples led to a molecular definition of BL with lymphocyte enhancer-binding factor 1 (LEF1) as a signature gene. Herein, we report the expression of nucleic LEF1 in 15 of 18 patients with BL and the identification of LEF1 target genes. Germinal center B cells were devoid of detectable nuclear LEF1 expression, as were mantle cell lymphoma (0 of 5), marginal zone lymphoma (0 of 6), follicular lymphoma (0 of 12), and diffuse large B-cell lymphoma (1 of 31). Whole-genome gene expression profiling after transient knockdown of LEF1 in BL cell lines identified new LEF1 target genes; these LEF1 targets are enriched with genes associated with cancers. The expression of LEF1 and LEF1-regulated genes in primary BL suggests that LEF1 is not only aberrantly expressed but also transcriptionally active. This study supports a functionally important role for LEF1 and its target genes in BLs. PMID:23375451

  15. Clustering gene expression patterns

    Microsoft Academic Search

    Amir Ben-Dor; Zohar Yakhinit; Zohar Yakhini

    1999-01-01

    Recent advances in biotechnology allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. Analysis of data produced by such experiments offers potential insight into gene function and regulatory mechanisms. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. The

  16. Metabolic gene variants associated with chromosomal aberrations in healthy humans.

    PubMed

    Hemminki, Kari; Frank, Christoph; Försti, Asta; Musak, Ludovit; Kazimirova, Alena; Barancokova, Magdalena; Horska, Alexandra; Vymetalkova, Veronika; Smerhovsky, Zdenek; Naccarati, Alessio; Soucek, Pavel; Vodickova, Ludmila; Buchancova, Janka; Smolkova, Bozena; Dusinska, Maria; Vodicka, Pavel

    2015-04-01

    Nonspecific chromosomal aberrations (CAs) are found in about 1% of lymphocytes drawn from healthy individuals. They include chromosome-type aberrations (CSAs), which are increased in exposure to ionizing radiation, and chromatid-type aberrations (CTAs) which in experimental systems are formed by DNA binding carcinogens and mutagens. The frequency of CAs is associated with the risk of cancer, but the causes of CAs in general population are unknown. Here, we want to test whether variants in metabolic genes associate with CAs in healthy volunteers. Cases were considered those whose total CA (CAtot) frequency was >2% and for CSA and CTA the limit was >1%. Controls had lower frequencies of CAs. Functional polymorphisms in seven genes were selected for analysis: cytochrome P450 1B1 (CYP1B1), epoxide hydrolase 1 (EPHX1), NAD(P)H:quinone oxidoreductase 1 (NQO1), each coding for phase 1 enzymes, and glutathione S-transferase P1 (GSTP1), glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), coding for enzymes which conjugate reactive metabolites, that is, phase 2 enzymes. The number of volunteers genotyped for each gene varied from 550 to 1,500. Only EPHX1 was individually associated with CAtot; high activity genotypes decreased CAtot. A total of six significant (P < 0.01) pair-wise interactions were observed, most including a GST variant as one of the pair. In all genotype combinations with significant odds ratios for CAs a GST variant was involved. The present data provide evidence that variants in genes coding for metabolic enzymes, which individually have small effects, interact and are associated with CA frequencies in peripheral lymphocytes of healthy volunteers. PMID:25622915

  17. Neoplastic plasma cell aberrant antigen expression patterns and their association with genetic abnormalities.

    PubMed

    Salama, Mohamed E; Du, Shouying; Efimova, Olga; Heikal, Nahla M; Wendlandt, Erik; Toydemir, Reha M; South, Sarah; Perkins, Sherrie L; Hussong, Jerry W; Zhan, Fenghuang

    2015-02-01

    Little is known about aberrant antigen expression patterns and their association with cytogenetic aberrations in multiple myeloma (MM). We examined the correlation between flow cytometry and florescence in situ hybridization (FISH) in 167 marrow specimens with MM. Gene expression profiling of CD56, CD117, CD52 and CD20 mRNA in plasma cells (PCs) from patients treated on Total Therapy 2 and Total Therapy 3 trials were also evaluated. Higher expression of CD56 and CD117 was associated with hyperdiploidy. High CD52 mRNA expression was associated with c-MAF and FGFR3 subgroups. Higher expression of CD56 mRNA, but lower Kit expression, were noted in association with FGFR3. In contrast, the c-MAF subgroup showed high Kit expression but lacked NCAM mRNA expression. CKS1B amplification showed positive correlation with CD52 (p=0.0065) but negative correlation with CD20 (p=0.0207). These findings indicate that phenotypic differences in MM are associated with distinct genetic subgroups, which potentially has important diagnostic and prognostic value. PMID:24913506

  18. Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma

    PubMed Central

    Chariyalertsak, S; Sirikulchayanonta, V; Mayer, D; Kopp-Schneider, A; Furstenberger, G; Marks, F; Muller-Decker, K

    2001-01-01

    METHODS—Cellular localisation of the cyclooxygenase (COX) isozymes COX-1 and COX-2 was analysed in 24 cholangiocarcinomas, including 17 matched tissues originating from non-tumorous liver tissue adjacent to tumours and seven biopsies of normal human liver, by immunohistochemistry using isozyme selective antibodies.?RESULTS—In normal liver, constitutive expression of COX-2 protein was a characteristic feature of hepatocytes whereas no COX-2 immunosignal was detectable in normal bile duct epithelium, Kupffer, and endothelial cells. In cholangiocarcinoma cells, COX-2 protein was strongly expressed at high frequency. The intensity, percentage of positive cells, and pattern of COX-2 expression were found to be independent of the stage of tumour differentiation. In hepatocytes of matched non-tumorous tissue, COX-2 expression was unaltered. In contrast, strong COX-1 expression was frequently localised to Kupffer cells, endothelial cells, and occasionally to hepatocytes, but not to bile duct epithelial cells. In approximately half of moderately and poorly differentiated but not well differentiated cholangiocarcinomas, weak to moderate COX-1 staining was found in tumour cells while COX-1 expression in Kupffer cells was much more pronounced.?CONCLUSION—Aberrant COX-2 expression occurs during the early stage while COX-1 over expression seems to be related to later stages of cholangiocarcinogenesis.???Keywords: cyclooxygenase; immunohistochemistry; cholangiocarcinoma; bile duct; hepatocyte; Kupffer cell PMID:11115827

  19. MicroRNA Gene Expression Deregulation in Human Breast Cancer

    Microsoft Academic Search

    Marilena V. Iorio; Manuela Ferracin; Chang-Gong Liu; Angelo Veronese; Riccardo Spizzo; Silvia Sabbioni; Massimo Pedriali; Muller Fabbri; Manuela Campiglio; Sylvie Menard; Juan P. Palazzo; Anne Rosenberg; Piero Musiani; Stefano Volinia; Italo Nenci; George A. Calin; Patrizia Querzoli; Massimo Negrini; Carlo M. Croce

    2005-01-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leuke- mias, where miRNA signatures were associated with specific clinicobiological features. Here, we

  20. Identification of 27 5' CpG islands aberrantly methylated and 13 genes silenced in human pancreatic cancers.

    PubMed

    Hagihara, Atsushi; Miyamoto, Kazuaki; Furuta, Junichi; Hiraoka, Nobuyoshi; Wakazono, Kuniko; Seki, Shuichi; Fukushima, Shoji; Tsao, Ming-Sound; Sugimura, Takashi; Ushijima, Toshikazu

    2004-11-11

    Aberrantly methylated DNA fragments were searched for in human pancreatic cancers, using the genome scanning technique: methylation-sensitive-representational difference analysis (MS-RDA). MS-RDA isolated 111 DNA fragments derived from CpG islands (CGIs), and 35 of them were from CGIs in the 5' regions of known genes. Methylation-specific PCR (MSP) of the CGIs in seven pancreatic cancer cell lines and two pancreatic ductal epithelial cell lines showed that 27 CGIs in the 5' regions were aberrantly methylated in at least one of the cancer cell lines. Quantitative reverse-transcription-PCR analysis showed that downstream genes of all the CGIs were either not expressed or only very weakly expressed in cancer cell lines with the aberrant methylation. In the pancreatic ductal epithelial cell lines, 18 genes were expressed at various levels, and nine genes were not expressed at all. Treatment of a cancer cell line with a demethylating agent, 5-aza-2'-deoxycytidine, restored the expression of 13 genes, RASGRF2, ADAM23, NEF3, NKX2-8, HAND1, EGR4, PRG2, FBN2, CDH2, TLL1, NPTX1, NTSR1 and THBD, showing their silencing by methylation of their 5' CGIs. MSP of 24 primary pancreatic cancers showed that all these genes, except for THBD, were methylated in at least one cancer. Some of those were suggested to be potentially involved in pancreatic cancer development and progression. PMID:15467763

  1. Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays

    PubMed Central

    Cheung, Hannah C; Baggerly, Keith A; Tsavachidis, Spiridon; Bachinski, Linda L; Neubauer, Valerie L; Nixon, Tamara J; Aldape, Kenneth D; Cote, Gilbert J; Krahe, Ralf

    2008-01-01

    Background Tumor-predominant splice isoforms were identified during comparative in silico sequence analysis of EST clones, suggesting that global aberrant alternative pre-mRNA splicing may be an epigenetic phenomenon in cancer. We used an exon expression array to perform an objective, genome-wide survey of glioma-specific splicing in 24 GBM and 12 nontumor brain samples. Validation studies were performed using RT-PCR on glioma cell lines, patient tumor and nontumor brain samples. Results In total, we confirmed 14 genes with glioma-specific splicing; seven were novel events identified by the exon expression array (A2BP1, BCAS1, CACNA1G, CLTA, KCNC2, SNCB, and TPD52L2). Our data indicate that large changes (> 5-fold) in alternative splicing are infrequent in gliomagenesis (< 3% of interrogated RefSeq entries). The lack of splicing changes may derive from the small number of splicing factors observed to be aberrantly expressed. Conclusion While we observed some tumor-specific alternative splicing, the number of genes showing exclusive tumor-specific isoforms was on the order of tens, rather than the hundreds suggested previously by in silico mining. Given the important role of alternative splicing in neural differentiation, there may be selective pressure to maintain a majority of splicing events in order to retain glial-like characteristics of the tumor cells. PMID:18474104

  2. Heterogeneity of aberrant immunoglobulin expression in cancer cells

    PubMed Central

    Hu, Duosha; Duan, Zhi; Li, Ming; Jiang, Yiqun; Liu, Haidan; Zheng, Hui; Li, Lili; Bode, Ann M; Dong, Zigang; Cao, Ya

    2011-01-01

    Accumulating evidence has shown that immunoglobulin (Ig) is ‘unexpectedly' expressed by epithelial cancer cells and that it can promote tumor growth. The main purpose of this study was to explore the components of the cancerous Ig and its possible function. The presence of cancerous Ig in the Golgi apparatus was confirmed by immunofluorescence, indirectly suggesting that the cancerous Ig was processed and packaged in cancer cells. Western blot analysis and ELISA results indicated that cancer cells produced membrane Ig and secreted Ig into the supernatant fraction. The cancerous Ig consists of an ? heavy chain and a ? light chain. Finally, by analyzing the Ig components pulled down by protein A beads, the cancerous Ig was found to be structurally distinct from normal Ig. The cancerous Ig was truncated or aberrant. Although the underlying mechanism that causes the abnormalities has not been determined, our current discoveries strengthen our previous findings and promise fruitful future explorations. PMID:21860405

  3. Aberrant expression of COT is related to recurrence of papillary thyroid cancer.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Park, Jae Hyun; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-02-01

    Aberrant expression of Cancer Osaka Thyroid Oncogene mitogen-activated protein kinase kinase kinase 8 (COT) (MAP3K8) is a driver of resistance to B-RAF inhibition. However, the de novo expression and clinical implications of COT in papillary thyroid cancer (PTC) have not been investigated.The aim of this study is to investigate the expression of A-, B-, C-RAF, and COT in PTC (n?=?167) and analyze the clinical implications of aberrant expression of these genes.Quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC) were performed on primary thyroid cancers. Expression of COT was compared with clinicopathological characteristics including recurrence-free survival. Datasets from public repository (NCBI) were subjected to Gene Set Enrichment Analysis (GSEA).qPCR data showed that the relative mRNA expression of A-, B-, C-RAF and COT of PTC were higher than normal tissues (all P?expression of COT mRNA in PTC showed positive correlation with A- (r?=?0.4083, P?expressions of A-, B,- and C-RAF were also correlated with each other (all P?aberrant expression of COT was related to old age at initial diagnosis (P?=?0.045) and higher recurrence rate (P?=?0.025). In multivariate analysis, tumor recurrence was persistently associated with moderate-to-strong staining of COT after adjusting for age, sex, extrathyroidal extension, multifocality, T-stage, N-stage, TNM stage, and B-RAF mutation (odds ratio, 4.662; 95% confidence interval 1.066?-?21.609; P?=?0.045). Moreover, moderate-to-strong COT expression in PTC was associated with shorter recurrence-free survival (mean follow-up duration, 14.2?±?4.1 years; P?=?0.0403). GSEA indicated that gene sets related to B-RAF-RAS (P?expression group and gene sets such as T-cell receptor signaling pathway and Toll-like receptor signaling pathway are coordinately upregulated in higher COT expression group (both, P?Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC. PMID:25674762

  4. Epigenetics and gene expression

    Microsoft Academic Search

    E R Gibney; C M Nolan

    2010-01-01

    Transcription, translation and subsequent protein modification represent the transfer of genetic information from the archival copy of DNA to the short-lived messenger RNA, usually with subsequent production of protein. Although all cells in an organism contain essentially the same DNA, cell types and functions differ because of qualitative and quantitative differences in their gene expression. Thus, control of gene expression

  5. Gene Dysregulations Driven by Somatic Copy Number Aberrations-Biological and Clinical Implications in Colon Tumors

    PubMed Central

    Bacolod, Manny D.; Barany, Francis

    2010-01-01

    The majority of colorectal cancer (CRC) cases have chromosomal instability, in which the tumor genome is characterized by gross chromosomal aberrations such as gains in 20q, 13q, 8q, and 7, and losses in 4, 8p, 18q, and 17p. These somatic copy number changes (gains, losses, and somatic uniparental disomies) are crucial to CRC progression as they drive genes toward cancer-promoting (oncogenic or tumor suppressive) states. Numerous studies have shown that the loss of 18q or 8p is associated with poorer clinical outcome in CRCs. Either chromosomal arm may contain a tumor suppressor gene (or genes), whose deactivation by copy loss (loss of wild-type allele, decreased expression) can be crucial to the later stages of cancer progression. Our own integrated genomic analysis (single nucleotide polymorphism array, expression array) of more than 200 CRC tumor and normal samples indicates that the overall down-regulation of genes within the 8p or 18q arm is associated with lower survival rate. Among the often down-regulated, poor prognosis-associated 8p genes is MTUS1, whose gene product (a mitotic spindle-associated protein) was recently demonstrated to have a tumor suppressive property. Within 18q is ATP5A1, which codes for the catalytic a component of mitochondrial H+-ATP synthase. Like SMAD4 (also in 18q), the decreased expression of ATP5A1 appears to be a marker of unfavorable clinical outcome in CRCs. PMID:20709793

  6. Microarray analysis of the aberrant microRNA expression pattern in gliomas of different grades.

    PubMed

    Zhu, Xiao-Peng; Mou, Ke-Jie; Xu, Qing-Fu; Tang, Jun-Hai; Huang, Guo-Hao; Xu, Jian-Ping; Li, Guang-Hui; Ai, Si-Jin; Hugnot, Jean-Phillippe; Zhou, Zheng; Lv, Sheng-Qing

    2015-07-01

    Previous studies have focused on miRNA expression in brain gliomas. However, both the expression pattern of miRNAs in gliomas of different grades and various miRNAs involved in malignant progression of gliomas are poorly understood. In the present study, we used miRNA microarray-based screening to investigate the miRNA expression profile in gliomas, which was further verified by qRT-PCR in selected miRNAs. In total, we found 13 differentially expressed miRNAs between gliomas and their matched surrounding tissues. Among them, 12 miRNAs were upregulated and only one (miR-4489) was downregulated compared with the control. Furthermore, the lower expression level of miR-4489 was confirmed by qRT-PCR in 26 glioma samples. Our microarray result revealed 8, 9 and 15 aberrantly expressed miRNAs in gliomas of World Health Organization (WHO) grade II-IV, respectively. Gene Ontology (GO) and Pathway analysis indicated that target genes of the 13 miRNAs were significantly enriched in central nervous system- and tumor?related biological processes and signaling pathways. The dysregulated miRNAs identified in the present study contribute to the tumorigenesis and malignant progression of gliomas and may serve as useful markers for advanced glioma pathological grading and prognosis. PMID:25954994

  7. The transglutaminase 2 gene is aberrantly hypermethylated in glioma

    Microsoft Academic Search

    Lisa M. Dyer; Kevin P. Schooler; Lingbao Ai; Corinne Klop; Jingxin Qiu; Keith D. Robertson; Kevin D. Brown

    2011-01-01

    Transglutaminase 2 (TG2) is a ubiquitously expressed protein that catalyzes protein\\/protein crosslinking. Because extracellular\\u000a TG2 crosslinks components of the extracellular matrix, TG2 is thought to function as a suppressor of cellular invasion. We\\u000a have recently uncovered that the TG2 gene (TGM2) is a target for epigenetic silencing in breast cancer, highlighting a molecular mechanism that drives reduced TG2 expression,\\u000a and

  8. Specific Chromosomal Aberrations and Amplification of the AIB1 Nuclear Receptor Coactivator Gene in Pancreatic Carcinomas

    PubMed Central

    Ghadimi, B. Michael; Schröck, Evelin; Walker, Robert L.; Wangsa, Danny; Jauho, Annukka; Meltzer, Paul S.; Ried, Thomas

    1999-01-01

    To screen pancreatic carcinomas for chromosomal aberrations we have applied molecular cytogenetic techniques, including fluorescent in situ hybridization, comparative genomic hybridization, and spectral karyotyping to a series of nine established cell lines. Comparative genomic hybridization revealed recurring chromosomal gains on chromosome arms 3q, 5p, 7p, 8q, 12p, and 20q. Chromosome losses were mapped to chromosome arms 8p, 9p, 17p, 18q, 19p, and chromosome 21. The comparison with comparative genomic hybridization data from primary pancreatic tumors indicates that a specific pattern of chromosomal copy number changes is maintained in cell culture. Metaphase chromosomes from six cell lines were analyzed by spectral karyotyping, a technique that allows one to visualize all chromosomes simultaneously in different colors. Spectral karyotyping identified multiple chromosomal rearrangements, the majority of which were unbalanced. No recurring reciprocal translocation was detected. Cytogenetic aberrations were confirmed using fluorescent in situ hybridization with probes for the MDR gene and the tumor suppressor genes p16 and DCC. Copy number increases on chromosome 20q were validated with a probe specific for the nuclear receptor coactivator AIB1 that maps to chromosome 20q12. Amplification of this gene was identified in six of nine pancreatic cancer cell lines and correlated with increased expression. PMID:10027410

  9. GENE EXPRESSION NETWORKS

    EPA Science Inventory

    "Gene expression network" is the term used to describe the interplay, simple or complex, between two or more gene products in performing a specific cellular function. Although the delineation of such networks is complicated by the existence of multiple and subtle types of intera...

  10. Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism

    PubMed Central

    Lerdrup, Mads; Gomes, Ana-Luisa; Kryh, Hanna; Spigolon, Giada; Caboche, Jocelyne; Fisone, Gilberto; Hansen, Klaus

    2014-01-01

    Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease. PMID:25254549

  11. Aberrant expression of interferon regulatory factor 3 in human lung cancer

    SciTech Connect

    Tokunaga, Takayuki [Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan) [Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Naruke, Yuki; Shigematsu, Sayuri; Kohno, Tomoko; Yasui, Kiyoshi; Ma, Yuhua; Chua, Koon Jiew [Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Katayama, Ikuo; Nakamura, Takashi [Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Hishikawa, Yoshitaka; Koji, Takehiko [Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Yatabe, Yasushi [Department of Pathology and Clinical Oncology, Aichi Cancer Research Institute, Nagoya 464-8681 (Japan)] [Department of Pathology and Clinical Oncology, Aichi Cancer Research Institute, Nagoya 464-8681 (Japan); Nagayasu, Takeshi [Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Fujita, Takashi [Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan)] [Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Matsuyama, Toshifumi, E-mail: tosim@nagasaki-u.ac.jp [Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan) [Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); The Global Center of Excellence Program at Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); and others

    2010-06-25

    We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer. The immunohistochemical analyses revealed substantially aberrant IRF3 expression specific to the cancer lesions (2 and 6 tumors with nuclear staining, and 4 and 5 tumors with negative staining, in adenocarcinoma and squamous cell carcinoma, respectively), while the morphologically normal region around the tumors exhibited only cytoplasmic staining. In addition, we determined the sequence of the entire IRF3 coding region, and found two novel variants with the amino acid changes (S{sup 175}(AGC) {yields} R{sup 175}(CGC) and A{sup 208}(GCC) {yields} D{sup 208}(GAC)). The R{sup 175} variant was also detected in a morphologically normal region around the nuclear staining squamous cell carcinoma, and exhibited almost the same functions as the wild type IRF3. On the other hand, the D{sup 208} variant, found in the negative staining squamous cell carcinoma cases, reduced the nuclear translocation in response to I{kappa}B kinase {epsilon} stimulation, as compared to the wild type IRF3, but the same variant was detected in the surrounding morphologically normal region. The aberrant expression of IRF3 and the novel D{sup 208} variant may provide clues to elucidate the etiology of primary lung cancer.

  12. Focal Chromosomal Copy Number Aberrations Identify CMTM8 and GPR177 as New Candidate Driver Genes in Osteosarcoma

    PubMed Central

    Bras, Johannes; Schaap, Gerard R.; Baas, Frank; Ylstra, Bauke; Hulsebos, Theo J. M.

    2014-01-01

    Osteosarcoma is an aggressive bone tumor that preferentially develops in adolescents. The tumor is characterized by an abundance of genomic aberrations, which hampers the identification of the driver genes involved in osteosarcoma tumorigenesis. Our study aims to identify these genes by the investigation of focal copy number aberrations (CNAs, <3 Mb). For this purpose, we subjected 26 primary tumors of osteosarcoma patients to high-resolution single nucleotide polymorphism array analyses and identified 139 somatic focal CNAs. Of these, 72 had at least one gene located within or overlapping the focal CNA, with a total of 94 genes. For 84 of these genes, the expression status in 31 osteosarcoma samples was determined by expression microarray analysis. This enabled us to identify the genes of which the over- or underexpression was in more than 35% of cases in accordance to their copy number status (gain or loss). These candidate genes were subsequently validated in an independent set and furthermore corroborated as driver genes by verifying their role in other tumor types. We identified CMTM8 as a new candidate tumor suppressor gene and GPR177 as a new candidate oncogene in osteosarcoma. In osteosarcoma, CMTM8 has been shown to suppress EGFR signaling. In other tumor types, CMTM8 is known to suppress the activity of the oncogenic protein c-Met and GPR177 is known as an overexpressed upstream regulator of the Wnt-pathway. Further studies are needed to determine whether these proteins also exert the latter functions in osteosarcoma tumorigenesis. PMID:25551557

  13. Gene expression in brain

    SciTech Connect

    Zomzely-Neurath, C.; Walker, W.

    1985-01-01

    This book contains 10 chapters. Some of the chapter titles are: Peptide Hormone Gene Expression in the Brain; Molecular Biology of the Mammalian Brain; Expression of Microtubule Proteins in Brain; and The Molecular Genetic Analysis of sn-Gylycerol-3-Phosphate Dehydrogenase Development in Mouse Cerebellum.

  14. Aberrant methylation of ERBB pathway genes in sporadic colorectal cancer.

    PubMed

    Szmida, Elzbieta; Karpi?ski, Pawel; Leszczynski, Przemyslaw; Sedziak, Tomasz; Kielan, Wojciech; Ostasiewicz, Pawe?; Sasiadek, Maria M

    2015-05-01

    The ErbB signalling network plays a crucial role in the growth and progression of several cancers, including colorectal cancer (CRC), and includes potentially drug-targetable genes. Oncogenic activation of the ErbB pathway by mutations and focal amplifications have emerged recently as an important predictive marker of the prognosis of CRC patients. However, in contrast to genetic events, little is known about epigenetic alternations of ErbB-associated genes and their impact on gene expression. Genome-wide methylation in sporadic CRCs (n?=?12) paired with adjacent normal tissues have been previously analysed by Illumina Infinium HumanMethylation27 (HM27) at 27,578 CpG sites. For confirmation of our initial genome-wide analysis, we used a published HM27 dataset (GSE25062). Subsequently, CpG island methylation of selected ErbB pathway-associated genes was assessed on 233 CRC samples using methylation-sensitive polymerase chain reaction (MS-PCR) and analysed along with various genetic factors associated with CRC [epigenotype, BRAF and KRAS mutations, microsatellite instability (MSI)]. Methylation and expression integration was performed using published datasets including 25 pairs of CRC and normal colon tissues (GSE25062 and GSE25070), and confirmed with real-time PCR. Our previous microarray-based genome-wide DNA methylation analysis of 12 CRCs revealed that four ErbB-associated genes (PIK3CD, PKC?, ERBB4, ) were differentially methylated in CRCs. This was further confirmed by statistical re-analysis of an HM27 dataset (GSE25062). Frequent methylation at these loci in tumours was subsequently confirmed by MS-PCR (63 %, 43 %, 43 % and 92 %, respectively). Hypermethylation of PKC? associated with KRAS mutation (p?=?0.04), whereas hypermethylation of ERBB4 associated with high-methylation epigenotypes (HME), BRAF mutation and MSI (p?=?0.001, 0.002 and 0.0002, respectively). One of the four analysed genes (PKC?) was significantly downregulated in CRC tissue, as revealed by real-time PCR and re-analysis of the GSE25062 and GSE25070 datasets. After careful re-analysis of published methylation and expression data, we conclude that methylation of ERBB4, PAK7 and PIK3CD has no functional role in CRC carcinogenesis. In contrast, methylation seems to have a potential impact on the biology of colorectal tumours by negatively modulating the expression of PKC?. Importantly, the relationship between DNA methylation of PKC? and gene expression may warrant further attention in the context of colon cancer chemoprevention and anti-cancer therapy. PMID:25366420

  15. Aberrant rel\\/nfkb genes and activity in human cancer

    Microsoft Academic Search

    Béatrice Rayet; Céline Gélinas

    1999-01-01

    Rel\\/NF-?B transcription factors are key regulators of immune, inflammatory and acute phase responses and are also implicated in the control of cell proliferation and apoptosis. Remarkable progress has been made in understanding the signal transduction pathways that lead to the activation of Rel\\/NF-?B factors and the consequent induction of gene expression. Evidence linking deregulated Rel\\/NF-?B activity to oncogenesis in mammalian

  16. Expression of the Pluripotency Transcription Factor OCT4 in the Normal and Aberrant Mammary Gland

    PubMed Central

    Hassiotou, Foteini; Hepworth, Anna R.; Beltran, Adriana S.; Mathews, Michelle M.; Stuebe, Alison M.; Hartmann, Peter E.; Filgueira, Luis; Blancafort, Pilar

    2013-01-01

    Breast cancers with lactating features, some of which are associated with pregnancy and lactation, are often poorly differentiated, lack estrogen receptor, progesterone receptor, and HER2 expression and have high mortality. Very little is known about the molecular mechanisms that drive uncontrolled cell proliferation in these tumors and confer lactating features. We have recently reported expression of OCT4 and associated embryonic stem cell self-renewal genes in the normal lactating breast and breastmilk stem cells (hBSCs). This prompted us to examine OCT4 expression in breast cancers with lactating features and compare it with that observed during normal lactation, using rare specimens of human lactating breast. In accordance with previous literature, the normal resting breast (from non-pregnant, non-lactating women) showed minimal OCT4 nuclear expression (0.9%). However, this increased in the normal lactating breast (11.4%), with further increase in lactating adenomas, lactating carcinomas, and pregnancy-associated breast cancer (30.7–48.3%). OCT4 was expressed in the epithelium and at lower levels in the stroma, and was co-localized with NANOG. Comparison of normal non-tumorigenic hBSCs with OCT4-overexpressing tumorigenic breast cell lines (OTBCs) demonstrated upregulation of OCT4, SOX2, and NANOG in both systems, but OTBCs expressed OCT4 at significantly higher levels than SOX2 and NANOG. Similar to hBSCs, OTBCs displayed multi-lineage differentiation potential, including the ability to differentiate into functional lactocytes synthesizing milk proteins both in vitro and in vivo. Based on these findings, we propose a hypothesis of normal and malignant transformation in the breast, which centers on OCT4 and its associated gene network. Although minimal expression of these embryonic genes can be seen in the breast in its resting state throughout life, a controlled program of upregulation of this gene network may be a potential regulator of the normal remodeling of the breast toward a milk-secretory organ during pregnancy and lactation. Deregulation of this gene network either within or outside pregnancy and lactation may lead to aberrant breast cell proliferation and malignant transformation, suggesting a role of these genes in both normal lactation and breast oncogenesis. PMID:23596564

  17. Aberrant SERCA3 expression during the colorectal adenoma-adenocarcinoma sequence.

    PubMed

    Gou, Wen-Feng; Niu, Zhe-Feng; Zhao, Shuang; Takano, Yasuo; Zheng, Hua-Chuan

    2014-01-01

    Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 is involved in calcium mobilization from the endoplasmic reticulum into the cytosol and is closely linked to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding and carcinogenesis. In order to elucidate the role of SERCA3 in colorectal carcinogenesis and subsequent progression, its expression was examined using immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas, adjacent non-neoplastic mucosa (NNM) and adenoma, and metastatic carcinoma in lymph node and liver. Colorectal carcinoma tissue and cell lines were assessed for SERCA3 expression by western blotting or RT-PCR, respectively. SERCA3 was distinctively expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells at both the mRNA and protein levels. SERCA3 mRNA expression was low in carcinoma when compared to that in matched NNM by quantitative PCR (P<0.05), while the converse was true by ISH. Lower expression of SERCA3 was immunohistochemically observed in colorectal carcinoma when compared to that in NNM and adenoma (P<0.05). In contrast, primary carcinoma showed high SERCA3 expression when compared to that in metastatic carcinoma in lymph node or liver by IHC (P<0.05). Immunohistochemically, SERCA3 expression was negatively related to lymphatic invasion, but not with age, gender, depth of invasion, venous invasion, lymph node metastasis, distant metastasis, TNM stage, degree of differentiation or survival rate (P>0.05). There was a positive relationship between SERCA3 expression and serum CEA levels in the carcinoma patients (P<0.05). Cox's proportional hazards model indicated that depth of invasion and distant metastasis are independent prognostic factors for overall colorectal carcinomas (P<0.05). These findings suggest that aberrant SERCA3 expression is closely linked to the adenoma-adenocarcinoma sequence and progression of colorectal carcinomas. PMID:24213720

  18. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

    SciTech Connect

    Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of)] [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)] [Konyang University Myunggok Medical Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)] [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.

  19. Aberrant Glycosphingolipid Expression and Membrane Organization in Tumor Cells: Consequences on Tumor–Host Interactions

    Microsoft Academic Search

    Alessandro Prinetti; Simona Prioni; Nicoletta Loberto; Massimo Aureli; Valentina Nocco; Giuditta Illuzzi; Laura Mauri; Manuela Valsecchi; Vanna Chigorno; Sandro Sonnino

    \\u000a More than 20 years ago [1], the pioneering work of Dr. Sen-itiroh Hakomori formed the basis for the concept that aberrant\\u000a glycosylation is a general feature of human cancer. The term “aberrant glycosylation” describes the altered expression of\\u000a oligosaccharide epitopes associated with both glycolipid and glycoprotein antigens in human cancer. This event is the consequence\\u000a of at least two different

  20. Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma cell leukemia

    PubMed Central

    Gentry, Michael; Pettenati, Mark; Pang, Changlee S

    2013-01-01

    Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or plasma cell myeloma, are typically characterized by production of a monoclonal heavy and/or light chain immunoglobulin. We present a case of a secondary plasma cell leukemia arising from plasma cell myeloma with dual expression of lambda and kappa light chains along with aberrant expression of CD33, CD20, and dim CD56. This case emphasizes the importance of recognizing aberrant immunophenotypes in plasma cell leukemias and represents the first reported case of biclonal light chain expression in a secondary plasma cell leukemia. PMID:24133602

  1. Acquired Alterations of Hypothalamic Gene Expression of Insulin and Leptin Receptors and Glucose Transporters in Prenatally High-Glucose Exposed Three-Week Old Chickens Do Not Coincide with Aberrant Promoter DNA Methylation

    PubMed Central

    Ott, Raffael; Bogatyrev, Semen; Tzschentke, Barbara; Plagemann, Andreas

    2015-01-01

    Background Prenatal exposures may have a distinct impact for long-term health, one example being exposure to maternal ‘diabesity’ during pregnancy increasing offspring ‘diabesity’ risk. Malprogramming of the central nervous regulation of body weight, food intake and metabolism has been identified as a critical mechanism. While concrete disrupting factors still remain unclear, growing focus on acquired epigenomic alterations have been proposed. Due to the independent development from the mother, the chicken embryo provides a valuable model to distinctively establish causal factors and mechanisms. Aim The aim of this study was to determine the effects of prenatal hyperglycemia on postnatal hypothalamic gene expression and promoter DNA methylation in the chicken. Methods and Findings To temporarily induce high-glucose exposure in chicken embryos, 0.5 ml glucose solution (30 mmol/l) were administered daily via catheter into a vessel of the chorioallantoic egg membrane from days 14 to 17 of incubation. At three weeks of postnatal age, body weight, total body fat, blood glucose, mRNA expression (INSR, LEPR, GLUT1, GLUT3) as well as corresponding promoter DNA methylation were determined in mediobasal hypothalamic brain slices (Nucleus infundibuli hypothalami). Although no significant changes in morphometric and metabolic parameters were detected, strongly decreased mRNA expression occurred in all candidate genes. Surprisingly, however, no relevant alterations were observed in respective promoter methylation. Conclusion Prenatal hyperglycemia induces strong changes in later hypothalamic expression of INSR, LEPR, GLUT1, and GLUT3 mRNA. While the chicken provides an interesting approach for developmental malprogramming, the classical expression regulation via promoter methylation was not observed here. This may be due to alternative/interacting brain mechanisms or the thus far under-explored bird epigenome. PMID:25811618

  2. Simulating Gene Expression using Netlogo

    NSDL National Science Digital Library

    Steven Brewer (University of Massachusetts; )

    2004-06-12

    Using a modeling environment that simulates the behavior of DNA, RNA, protein, transcription, and translation, a system can emerge that shows properties qualitatively similar to gene expression models. Two models were created: one simulates the lac operon, one of the classical models in gene expression. Another model illustrates how a gene expression system can behave like any logical gate (AND, OR, NAND, NOR).

  3. Integrated analysis of DNA copy number and gene expression microarray data using gene sets

    PubMed Central

    Menezes, Renée X; Boetzer, Marten; Sieswerda, Melle; van Ommen, Gert-Jan B; Boer, Judith M

    2009-01-01

    Background Genes that play an important role in tumorigenesis are expected to show association between DNA copy number and RNA expression. Optimal power to find such associations can only be achieved if analysing copy number and gene expression jointly. Furthermore, some copy number changes extend over larger chromosomal regions affecting the expression levels of multiple resident genes. Results We propose to analyse copy number and expression array data using gene sets, rather than individual genes. The proposed model is robust and sensitive. We re-analysed two publicly available datasets as illustration. These two independent breast cancer datasets yielded similar patterns of association between gene dosage and gene expression levels, in spite of different platforms having been used. Our comparisons show a clear advantage to using sets of genes' expressions to detect associations with long-spanning, low-amplitude copy number aberrations. In addition, our model allows for using additional explanatory variables and does not require mapping between copy number and expression probes. Conclusion We developed a general and flexible tool for integration of multiple microarray data sets, and showed how the identification of genes whose expression is affected by copy number aberrations provides a powerful approach to prioritize putative targets for functional validation. PMID:19563656

  4. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.

    PubMed

    Davis, Hayley; Irshad, Shazia; Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc C; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen J; Greten, Florian R; Wang, Lai Mun; East, James E; Tomlinson, Ian; Leedham, Simon J

    2015-01-01

    Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps. PMID:25419707

  5. Aberrant expression of redox protein Ape1 in colon cancer stem cells

    PubMed Central

    LOU, DEBAO; ZHU, LINA; DING, HUAWEI; DAI, HAI-YAN; ZOU, GANG-MING

    2014-01-01

    Ape1 is an important redox protein, essential for specific cytokine-induced signal transduction. Ape1 signaling is also important in regulating the growth of cancer cells, including colon cancer cells. The present study investigated whether Ape1 signaling plays a role in the regulation of colon cancer stem cell (CCSC) growth. The results showed that Ape1 was aberrantly expressed in CCSCs, as determined by quantitative (q)PCR assay. A laser confocal microscopy assay demonstrated that the Ape1 protein was mainly distributed in the nuclei, but not the cytoplasm, of the CSCs. Treatment of CCSCs with Ape1 redox inhibitor (E3330) significantly affected growth in vitro. In colon cancer xenograft mice, in vivo administration of E3330 enhanced tumor responses to the chemotherapeutic drug, 5-fluorouracil (5-FU). Furthermore, the combination of E3330 and 5-FU evidently increased the cytotoxicity of 5-FU in CSC growth. In the qPCR assay, the CCSCs were demonstrated to express the dominant ATP-binding cassette sub-family G member 2 (ABC-G2), but not the multidrug resistance 1, genes. Thus, we hypothesized that drug resistance in CCSCs is mediated by ABC-G2. Since CSCs are involved in cancer metastasis, the Ape1 inhibitor may be a potential agent in the inhibition of colon cancer growth and metastasis. PMID:24944672

  6. Gene Expression in Bone

    NASA Astrophysics Data System (ADS)

    D'Ambrogio, A.

    Skeletal system has two main functions, to provide mechanical integrity for both locomotion and protection and to play an important role in mineral homeostasis. There is extensive evidence showing loss of bone mass during long-term Space-Flights. The loss is due to a break in the equilibrium between the activity of osteoblasts (the cells that forms bone) and the activity of osteoclasts (the cells that resorbs bone). Surprisingly, there is scanty information about the possible altered gene expression occurring in cells that form bone in microgravity.(Just 69 articles result from a "gene expression in microgravity" MedLine query.) Gene-chip or microarray technology allows to screen thousands of genes at the same time: the use of this technology on samples coming from cells exposed to microgravity could provide us with many important informations. For example, the identification of the molecules or structures which are the first sensors of the mechanical stress derived from lack of gravity, could help in understanding which is the first event leading to bone loss due to long-term exposure to microgravity. Consequently, this structure could become a target for a custom-designed drug. It is evident that bone mass loss, observed during long-time stay in Space, represents an accelerated model of what happens in aging osteoporosis. Therefore, the discovery and design of drugs able to interfere with the bone-loss process, could help also in preventing negative physiological processes normally observed on Earth. Considering the aims stated above, my research is designed to:

  7. Analyzing tumor gene expression profiles

    Microsoft Academic Search

    Carsten Peterson; Markus Ringner

    A brief introduction to high throughput technologies for measuring and analyzing gene expression is given. Various supervised and unsupervised data mining methods for analyzing the produced high- dimensional data are discussed. The main emphasis is on supervised machine learning methods for classification and prediction of tumor gene expression profiles. Furthermore, methods to rank the genes according to their importance for

  8. Analyzing tumor gene expression profiles

    Microsoft Academic Search

    Carsten Peterson; Markus Ringnér

    2003-01-01

    A brief introduction to high throughput technologies for measuring and analyzing gene expression is given. Various supervised and unsupervised data mining methods for analyzing the produced high-dimensional data are discussed. The main emphasis is on supervised machine learning methods for classification and prediction of tu- mor gene expression profiles. Furthermore, methods to rank the genes according to their importance for

  9. Up-Regulated Expression and Aberrant DNA Methylation of LEP and SH3PXD2A in Pre-Eclampsia

    PubMed Central

    Li, Xiaotian; Li, Qiaoli; Xu, Jiawei; Zhang, Junyu; Liu, Yun; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2013-01-01

    The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n?=?16) versus normal placentas (n?=?16). Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p?=?0.001), the binding sites of Sp1 (p?=?1.57×10?4), LP1 (p?=?0.023) and CEBP? (p?=?0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBP? co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p?=?1.57×10?4), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation. PMID:23544093

  10. Detecting multivariate differentially expressed genes

    PubMed Central

    Nilsson, Roland; Peña, José M; Björkegren, Johan; Tegnér, Jesper

    2007-01-01

    Background Gene expression is governed by complex networks, and differences in expression patterns between distinct biological conditions may therefore be complex and multivariate in nature. Yet, current statistical methods for detecting differential expression merely consider the univariate difference in expression level of each gene in isolation, thus potentially neglecting many genes of biological importance. Results We have developed a novel algorithm for detecting multivariate expression patterns, named Recursive Independence Test (RIT). This algorithm generalizes differential expression testing to more complex expression patterns, while still including genes found by the univariate approach. We prove that RIT is consistent and controls error rates for small sample sizes. Simulation studies confirm that RIT offers more power than univariate differential expression analysis when multivariate effects are present. We apply RIT to gene expression data sets from diabetes and cancer studies, revealing several putative disease genes that were not detected by univariate differential expression analysis. Conclusion The proposed RIT algorithm increases the power of gene expression analysis by considering multivariate effects while retaining error rate control, and may be useful when conventional differential expression tests yield few findings. PMID:17490475

  11. Association of a d-Alanyl-d-Alanine Carboxypeptidase Gene with the Formation of Aberrantly Shaped Cells during the Induction of Viable but Nonculturable Vibrio parahaemolyticus

    PubMed Central

    Hung, Wei-cheng; Jane, Wann-Neng

    2013-01-01

    Vibrio parahaemolyticus is a halophilic Gram-negative bacterium that causes human gastroenteritis. When the viable but nonculturable (VBNC) state of this bacterium was induced by incubation at 4°C in Morita minimal salt solution containing 0.5% NaCl, the rod-shaped cells became coccoid, and various aberrantly shaped intermediates were formed in the initial stage. This study examined the factors that influence the formation of these aberrantly shaped cells. The proportion of aberrantly shaped cells was not affected in a medium containing d-cycloserine (50 ?g/ml) but was lower in a medium containing cephalosporin C (10 ?g/ml) than in the control medium without antibiotics. The proportion of aberrantly shaped cells was higher in a culture medium that contained 0.5% NaCl than in culture media containing 1.0 or 1.5% NaCl. The expression of 15 of 17 selected genes associated with cell wall synthesis was enhanced, and the expression of VP2468 (dacB), which encodes d-alanyl-d-alanine carboxypeptidase, was enhanced the most. The proportion of aberrantly shaped cells was significantly lower in the dacB mutant strain than in the parent strain, but the proportion was restored in the presence of the complementary dacB gene. This study suggests that disturbance of the dynamics of cell wall synthesis by enhanced expression of the VP2468 gene is associated with the formation of aberrantly shaped cells in the initial stage of induction of VBNC V. parahaemolyticus cells under specific conditions. PMID:24056454

  12. Expression and identification of aberrant c-kit transcripts in human cancer cells.

    PubMed

    Takaoka, A; Toyota, M; Hinoda, Y; Itoh, F; Mita, H; Kakiuchi, H; Adachi, M; Imai, K

    1997-05-19

    We have previously cloned and sequenced a novel 3.5 kb c-kit mRNA expressed in a colon carcinoma cell line Colo201. Here we examined the expression of this truncated form of c-kit in 14 gastrointestinal cancer cells and 16 hematopoieic cancer cells by RT-PCR. Expression of the aberrant c-kit transcript was observed in various cancer cell lines. Furthermore, a new transcript which is 78 bp shorter than the transcript previously described was identified and characterized. These results indicate that two kinds of aberrant c-kit transcript produced by alternative promoter in intron 15 are expressed in human cancer cells. PMID:9149133

  13. Global gene expression in Leishmania.

    PubMed

    Cohen-Freue, Gabriela; Holzer, Timothy R; Forney, James D; McMaster, W Robert

    2007-08-01

    The completion of the genomic sequences of many protozoan pathogens of humans, including species of Leishmania, Trypanosoma and Plasmodium, provide new approaches to study the pattern of gene expression during differentiation and development. Leishmania are a major public health risk in many countries and cause a wide spectrum of clinical disease referred to as leishmaniasis. The Leishmania life cycle consists of two morphologically distinct stages: intracellular amastigotes that reside in the phagolysosome of mammalian macrophages, and extracellular promastigotes that reside within the gut of the sandfly vector. DNA microarray analysis is a powerful method to study global gene expression in terms of quantitation of mRNA levels. This review discusses the application of DNA microarray technology to study the pattern of global gene expression of Leishmania promastigote and amastigote life stages. Results from several studies show that, overall, there is a surprisingly low level of differentially expressed genes, ranging from 0.2% to 5% of total genes, between the amastigote and promastigote life stages. Thus, the Leishmania genome can be considered to be constitutively expressed with a limited number of genes showing stage-specific expression. Comparative genomic analyses of gene expression levels between Leishmania major and Leishmania mexicana show that the majority of differentially expressed genes between amastigotes and promastigotes are species specific with relatively few differentially expressed genes in common between these two Leishmania species. Quantitative proteomic analysis of Leishmania relative protein expression shows there is a weak correlation to gene expression. Therefore, Leishmania protein expression levels are likely regulated at the level of translation or by post transcriptional mechanisms, and differential protein modifications may be more important in development than the regulation of gene expression. PMID:17574557

  14. Evolution of Gene Expression after Gene Amplification

    PubMed Central

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-01-01

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat–maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that ?-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a ?-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. PMID:25912045

  15. Activation of Expression of Hedgehog Target Genes in Basal Cell Carcinomas

    Microsoft Academic Search

    Jeannette M Bonifas; Sally Pennypacker; Pao-Tien Chuang; Andrew P McMahon; Mickey Williams; Arnon Rosenthal; Frederic J de Sauvage; Ervin H Epstein

    2001-01-01

    Mutations in hedgehog signaling pathway genes, especially PTC1 and SMO, are pivotal to the development of basal cell carcinomas. The study of basal cell carcinoma gene expression not only may elucidate mechanisms by which hedgehog signaling abnormalities produce aberrant tumor cell behavior but also can provide data on in vivo hedgehog target gene control in humans. We have found, in

  16. Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

    Microsoft Academic Search

    Wolf C. Prall; Akos Czibere; Franck Grall; Dimitrios Spentzos; Ulrich Steidl; Aristoteles Achilles Nikolaus Giagounidis; Andrea Kuendgen; Hasan Otu; Astrid Rong; Towia A. Libermann; Ulrich Germing; Norbert Gattermann; Rainer Haas; Manuel Aivado

    2009-01-01

    One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may\\u000a be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying\\u000a aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor\\u000a cells from six healthy persons and 16 patients

  17. Method of controlling gene expression

    DOEpatents

    Peters, Norman K. (Berkeley, CA); Frost, John W. (Menlo Park, CA); Long, Sharon R. (Palo Alto, CA)

    1991-12-03

    A method of controlling expression of a DNA segment under the control of a nod gene promoter which comprises administering to a host containing a nod gene promoter an amount sufficient to control expression of the DNA segment of a compound of the formula: ##STR1## in which each R is independently H or OH, is described.

  18. Aberrant expression of laminin-332 promotes cell proliferation and cyst growth in ARPKD

    PubMed Central

    Dang, Suparna; Marinkovich, M. Peter; Lazarova, Zelmira; Yoder, Bradley; Torres, Vicente E.; Wallace, Darren P.

    2013-01-01

    Basement membrane abnormalities have often been observed in kidney cysts of polycystic kidney disease (PKD) patients and animal models. There is an abnormal deposition of extracellular matrix molecules, including laminin-?3,?3,?2 (laminin-332), in human autosomal dominant PKD (ADPKD). Knockdown of PKD1 paralogs in zebrafish leads to dysregulated synthesis of the extracellular matrix, suggesting that altered basement membrane assembly may be a primary defect in ADPKD. In this study, we demonstrate that laminin-332 is aberrantly expressed in cysts and precystic tubules of human autosomal recessive PKD (ARPKD) kidneys as well as in the kidneys of PCK rats, an orthologous ARPKD model. There was aberrant expression of laminin-?2 as early as postnatal day 2 and elevated laminin-332 protein in postnatal day 30, coinciding with the formation and early growth of renal cysts in PCK rat kidneys. We also show that a kidney cell line derived from Oak Ridge polycystic kidney mice, another model of ARPKD, exhibited abnormal lumen-deficient and multilumen structures in Matrigel culture. These cells had increased proliferation rates and altered expression levels of laminin-332 compared with their rescued counterparts. A function-blocking polyclonal antibody to laminin-332 significantly inhibited their abnormal proliferation rates and rescued their aberrant phenotype in Matrigel culture. Furthermore, abnormal laminin-332 expression in cysts originating from collecting ducts and proximal tubules as well as in precystic tubules was observed in a human end-stage ADPKD kidney. Our results suggest that abnormal expression of laminin-332 contributes to the aberrant proliferation of cyst epithelial cells and cyst growth in genetic forms of PKD. PMID:24370592

  19. Viral insertion in Evi12 causes expression of aberrant Grp94 mRNAs containing the viral gag myristylation motif

    SciTech Connect

    Akker, Eric van den; Aarts, Lambertus H.J. [Department of Hematology, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands); Delwel, Ruud [Department of Hematology, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam (Netherlands)], E-mail: h.delwel@erasmusmc.nl

    2007-09-30

    Ecotropic Virus Integration site 12 (Evi12) is a common virus insertion site (cVIS) in retrovirally induced murine models of leukemia and lymphoma, suggesting an important role for this locus in these hematopoietic disorders. Evi12 is located near the promoter of the ER chaperone protein and Hsp90 family member Grp94. Here we show that viral insertion in Evi12 results in the expression of aberrant Grp94 transcripts in Cas-Br-MuLV as well as in AKXD induced hematopoietic tumors, demonstrating that Grp94 is a common viral target gene. While most transcripts encode for truncated forms of Grp94, transcripts containing viral gag sequences were detected in the leukemia cell line NFS107. Interestingly, these fusion transcripts encode for myristylated viral-Grp94 fusion proteins that localize to the plasma membrane. Combined with recent evidence that myristylated forms of Hsp90 transform cells, our data suggest that myristylation of target genes may be an important mechanism in retrovirally mediated oncogenesis. Since retroviral insertion in Evi12 also affects the expression of a recently identified novel gene Grp94 neighboring nucleotidase (Gnn), located at the other side of Evi12, it appears that proviral insertion can lead to deregulation of two genes present in the same locus.

  20. Mutation in NS2, a Nonstructural Protein of Influenza A Virus, Extragenically Causes Aberrant Replication and Expression of the PA Gene and Leads to Generation of Defective Interfering Particles

    Microsoft Academic Search

    Takato Odagiri; Kiyotake Tobita

    1990-01-01

    Several consecutive undiluted passages of infectious virus are usually required to obtain defective interfering particles of influenza virus. In contrast, a reassortant (Wa-182) of influenza A\\/WSN, which we isolated, whose NS gene was replaced with the NS gene of A\\/Aichi, was readily converted to defective interfering form after only a single high-multiplicity infection. The defective interfering particles of Wa-182 were

  1. RNA splicing mutation in an aberrantly rearranged immunoglobulin lambda I gene.

    PubMed Central

    Hozumi, N; Wu, G E; Murialdo, H; Roberts, L; Vetter, D; Fife, W L; Whiteley, M; Sadowski, P

    1981-01-01

    The mouse cell line MOPC 315 is an IgA (lambda II)-producing myeloma. We have studied a derivative of MOPC 315 that secretes normal lambda II chains but no heavy chain. This derivative, MOPC 315-26, was found to contain a rearranged lambda I gene in addition to a rearranged lambda II gene. The rearranged lambda I gene was cloned into bacteriophage lambda DNA and its structure was studied. The lambda I gene was found to have arisen by an aberrant recombination event that resulted in a single base insertion at the site of V-J region joining. In addition, the gene contained numerous point mutations in the vicinity of the junction of the V and J regions. Two point mutations occurred in the donor splice sequence normally used for the removal of the intron between the J and C regions, suggesting that the RNA synthesized from the aberrantly rearranged lambda I gene would be unable to undergo proper RNA splicing. Images PMID:6171827

  2. Revisiting Global Gene Expression Analysis

    E-print Network

    Lovén, Jakob

    Gene expression analysis is a widely used and powerful method for investigating the transcriptional behavior of biological systems, for classifying cell states in disease, and for many other purposes. Recent studies indicate ...

  3. Alpharetroviral Vector-mediated Gene Therapy for X-CGD: Functional Correction and Lack of Aberrant Splicing

    PubMed Central

    Kaufmann, Kerstin B.; Brendel, Christian; Suerth, Julia D.; Mueller-Kuller, Uta; Chen-Wichmann, Linping; Schwäble, Joachim; Pahujani, Shweta; Kunkel, Hana; Schambach, Axel; Baum, Christopher; Grez, Manuel

    2013-01-01

    Comparative integrome analysis has revealed that the most neutral integration pattern among retroviruses is attributed to alpharetroviruses. We chose X-linked chronic granulomatous disease (X-CGD) as model to evaluate the potential of self-inactivating (SIN) alpharetroviral vectors for gene therapy of monogenic diseases. Therefore, we combined the alpharetroviral vector backbone with the elongation factor-1? short promoter, both considered to possess a low genotoxic profile, to drive transgene (gp91phox) expression. Following efficient transduction transgene expression was sustained and provided functional correction of the CGD phenotype in a cell line model at low vector copy number. Further analysis in a murine X-CGD transplantation model revealed gene-marking of bone marrow cells and oxidase positive granulocytes in peripheral blood. Transduction of human X-CGD CD34+ cells provided functional correction up to wild-type levels and long-term expression upon transplantation into a humanized mouse model. In contrast to lentiviral vectors, no aberrantly spliced transcripts containing cellular exons fused to alpharetroviral sequences were found in transduced cells, implying that the safety profile of alpharetroviral vectors may extend beyond their neutral integration profile. Taken together, this highlights the potential of this SIN alpharetroviral system as a platform for new candidate vectors for future gene therapy of hematopoietic disorders. PMID:23207695

  4. Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes

    PubMed Central

    Gerstung, Moritz; Pellagatti, Andrea; Malcovati, Luca; Giagounidis, Aristoteles; Porta, Matteo G Della; Jädersten, Martin; Dolatshad, Hamid; Verma, Amit; Cross, Nicholas C. P.; Vyas, Paresh; Killick, Sally; Hellström-Lindberg, Eva; Cazzola, Mario; Papaemmanuil, Elli; Campbell, Peter J.; Boultwood, Jacqueline

    2015-01-01

    Cancer is a genetic disease, but two patients rarely have identical genotypes. Similarly, patients differ in their clinicopathological parameters, but how genotypic and phenotypic heterogeneity are interconnected is not well understood. Here we build statistical models to disentangle the effect of 12 recurrently mutated genes and 4 cytogenetic alterations on gene expression, diagnostic clinical variables and outcome in 124 patients with myelodysplastic syndromes. Overall, one or more genetic lesions correlate with expression levels of ~20% of all genes, explaining 20–65% of observed expression variability. Differential expression patterns vary between mutations and reflect the underlying biology, such as aberrant polycomb repression for ASXL1 and EZH2 mutations or perturbed gene dosage for copy-number changes. In predicting survival, genomic, transcriptomic and diagnostic clinical variables all have utility, with the largest contribution from the transcriptome. Similar observations are made on the TCGA acute myeloid leukaemia cohort, confirming the general trends reported here. PMID:25574665

  5. Tuning noise in gene expression

    PubMed Central

    Tyagi, Sanjay

    2015-01-01

    The relative contribution of promoter architecture and the associated chromatin environment in regulating gene expression noise has remained elusive. In their recent work, Arkin, Schaffer and colleagues (Dey et al, 2015) show that mean expression and noise for a given promoter at different genomic loci are uncorrelated and influenced by the local chromatin environment. PMID:25943344

  6. Dimerizer-regulated gene expression.

    PubMed

    Pollock, Roy; Clackson, Tim

    2002-10-01

    Control of gene expression using small molecules is a powerful research tool and has clinical utility in the context of regulated gene therapy. Use of chemical inducers of dimerization, or dimerizers, for this purpose has several advantages, including tight regulation, modularity to facilitate iterative improvements, and assembly from human proteins to minimize immune responses in clinical applications. Recent developments include the use of the rapamycin-based dimerizer system to regulate the expression of endogenous genes, the generation of new chemical dimerizers based on FK506, dexamethasone and methotrexate, and progress towards the clinical use of adeno-associated virus and adenovirus vectors regulated by rapamycin analogs. PMID:12459338

  7. Sleep deprivation and gene expression.

    PubMed

    da Costa Souza, Annie; Ribeiro, Sidarta

    2015-01-01

    Sleep occurs in a wide range of animal species as a vital process for the maintenance of homeostasis, metabolic restoration, physiological regulation, and adaptive cognitive functions in the central nervous system. Long-term perturbations induced by the lack of sleep are mostly mediated by changes at the level of transcription and translation. This chapter reviews studies in humans, rodents, and flies to address the various ways by which sleep deprivation affects gene expression in the nervous system, with a focus on genes related to neuronal plasticity, brain function, and cognition. However, the effects of sleep deprivation on gene expression and the functional consequences of sleep loss are clearly not restricted to the cognitive domain but may include increased inflammation, expression of stress-related genes, general impairment of protein translation, metabolic imbalance, and thermal deregulation. PMID:25646722

  8. Mining Phenotypes and Informative Genes from Gene Expression Data

    E-print Network

    Pei, Jian

    Mining Phenotypes and Informative Genes from Gene Expression Data Chun Tang Aidong Zhang Jian Pei chuntang, azhang, jianpei @cse.buffalo.edu ABSTRACT Mining microarray gene expression data is an important and informative genes from gene expression data. Some statistics-based metrics are proposed to measure the quality

  9. Neighboring Genes Show Correlated Evolution in Gene Expression

    PubMed Central

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (<100 kb) but extends much further. Sex-specific expression change is also genomically clustered. As genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  10. Variability in gene expression underlies incomplete penetrance

    E-print Network

    van Oudenaarden, Alexander

    ARTICLES Variability in gene expression underlies incomplete penetrance Arjun Raj1,2 *{, Scott A processes such as gene expression may also generate diversity. To examine the consequences of gene of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene

  11. Aberrant promoter methylation of multiple genes in sputum from individuals exposed to smoky coal emissions

    PubMed Central

    Liu, Yang; Lan, Qing; Shen, Min; Mumford, Judy; Keohavong, Phouthone

    2010-01-01

    Summary Aberrant methylation in the promoter region of cancer-related genes leads to gene transcriptional inactivation and plays an integral role in lung tumorigenesis. Recent studies demonstrated that promoter methylation was detected not only in lung tumors from patients with lung cancer but also in sputum of smokers without the disease, suggesting the potential for aberrant gene promoter methylation in sputum as a predictive marker for lung cancer. In the present study, we investigated promoter methylation of 4 genes frequently detected in lung tumors, including p16, MGMT, RASSF1A and DAPK genes, in sputum samples obtained from 107 individuals, including 34 never-smoking females and 73 mostly smoking males, who had no evidence of lung cancer but who were exposed to smoky coal emission in Xuan Wei County, China, where lung cancer rate is more than 6 times the Chinese national average rate. Forty nine of the individuals showed evidence of chronic bronchitis while the remaining 58 individuals showed no such a symptom. Promoter methylation of p16, MGMT, RASSF1A and DAPK was detected in 51.4% (55/107), 17.8% (19/107), 29.9% (32/107), and 15.9% (17/107) of the sputum samples from these individuals, respectively. There were no differences in promoter methylation frequencies of any of these genes according to smoking status or gender of the subjects or between individuals with chronic bronchitis and those without evidence of such a symptom. Therefore, individuals exposed to smoky coal emissions in this region harbored in their sputum frequent promoter methylation of these genes that have been previously found in lung tumors and implicated in lung cancer development. PMID:18751376

  12. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.

    PubMed Central

    Sovak, M A; Bellas, R E; Kim, D W; Zanieski, G J; Rogers, A E; Traish, A M; Sonenshein, G E

    1997-01-01

    Expression of nuclear factor-kappaB (NF-kappaB)/Rel transcription factors has recently been found to promote cell survival, inhibiting the induction of apoptosis. In most cells other than B lymphocytes, NF-kappaB/Rel is inactive, sequestered in the cytoplasm. For example, nuclear extracts from two human untransformed breast epithelial cell lines expressed only very low levels of NF-kappaB. Unexpectedly, nuclear extracts from two human breast tumor cell lines displayed significant levels of NF-kappaB/Rel. Direct inhibition of this NF-kappaB/ Rel activity in breast cancer cells induced apoptosis. High levels of NF-kappaB/Rel binding were also observed in carcinogen-induced primary rat mammary tumors, whereas only expectedly low levels were seen in normal rat mammary glands. Furthermore, multiple human breast cancer specimens contained significant levels of nuclear NF-kappaB/Rel subunits. Thus, aberrant nuclear expression of NF-kappaB/Rel is associated with breast cancer. Given the role of NF-kappaB/Rel factors in cell survival, this aberrant activity may play a role in tumor progression, and represents a possible therapeutic target in the treatment of these tumors. PMID:9399940

  13. Systems Biophysics of Gene Expression

    E-print Network

    Vilar, Jose M G

    2013-01-01

    Gene expression is a central process to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges among traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and...

  14. Aberrant expression of DNA damage response proteins is associated with breast cancer subtype and clinical features

    PubMed Central

    Guler, Gulnur; Himmetoglu, Cigdem; Jimenez, Rafael E.; Geyer, Susan M.; Wang, Wenle P.; Costinean, Stefan; Pilarski, Robert T.; Morrison, Carl; Suren, Dinc; Liu, Jianhua; Chen, Jingchun; Kamal, Jyoti; Shapiro, Charles L.

    2013-01-01

    Landmark studies of the status of DNA damage checkpoints and associated repair functions in preneoplastic and neoplastic cells has focused attention on importance of these pathways in cancer development, and inhibitors of repair pathways are in clinical trials for treatment of triple negative breast cancer. Cancer heterogeneity suggests that specific cancer subtypes will have distinct mechanisms of DNA damage survival, dependent on biological context. In this study, status of DNA damage response (DDR)-associated proteins was examined in breast cancer subtypes in association with clinical features; 479 breast cancers were examined for expression of DDR proteins ?H2AX, BRCA1, pChk2, and p53, DNA damage-sensitive tumor suppressors Fhit and Wwox, and Wwox-interacting proteins Ap2?, Ap2?, ErbB4, and correlations among proteins, tumor subtypes, and clinical features were assessed. In a multivariable model, triple negative cancers showed significantly reduced Fhit and Wwox, increased p53 and Ap2? protein expression, and were significantly more likely than other subtype tumors to exhibit aberrant expression of two or more DDR-associated proteins. Disease-free survival was associated with subtype, Fhit and membrane ErbB4 expression level and aberrant expression of multiple DDR-associated proteins. These results suggest that definition of specific DNA repair and checkpoint defects in subgroups of triple negative cancer might identify new treatment targets. Expression of Wwox and its interactor, ErbB4, was highly significantly reduced in metastatic tissues vs. matched primary tissues, suggesting that Wwox signal pathway loss contributes to lymph node metastasis, perhaps by allowing survival of tumor cells that have detached from basement membranes, as proposed for the role of Wwox in ovarian cancer spread. PMID:21069451

  15. Transgenic Arabidopsis Gene Expression System

    NASA Technical Reports Server (NTRS)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  16. Aberrant expression of maternal Plk1 and Dctn3 results in the developmental failure of human in-vivo- and in-vitro-matured oocytes.

    PubMed

    Fan, Yong; Zhao, Hong-Cui; Liu, Jianqiao; Tan, Tao; Ding, Ting; Li, Rong; Zhao, Yue; Yan, Jie; Sun, Xiaofang; Yu, Yang; Qiao, Jie

    2015-01-01

    Fertilisation is the first step in embryonic development, and dynamic changes of key genes may potentially improve assisted reproduction techniques efficiency during this process. Here, we analysed genes that were differentially expressed between oocytes and zygotes and focused on cytokinesis-related genes. Plk1 and Dctn3 were identified as showing dramatic changes in expression during fertilisation and were suggested to play a key role in inducing aneuploidy in zygotes and 8-cell embryos. Moreover, we found that maternal Plk1 and Dctn3 were expressed at lower levels in in vitro matured oocytes, which may have contributed to the high ratio of resulting embryos with abnormal Plk1 and Dctn3 expression levels, thereby reducing the developmental competence of the resulting embryos. Furthermore, the overexpression of Dctn3 can silence Plk1 expression, which suggests a potential regulation mechanism. In conclusion, our present study showed that aberrant expression of Plk1 and Dctn3 increases embryo aneuploidy and developmental failure, particularly in in vitro matured oocytes. Our results facilitate a better understanding of the effects of oocyte maternal gene expression on embryonic development and can be used to improve the outcome of assisted reproduction techniques. PMID:25645239

  17. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia

    Microsoft Academic Search

    Adolfo A. Ferrando; Donna S. Neuberg; Jane Staunton; Mignon L. Loh; Christine Huard; Susana C. Raimondi; Fred G. Behm; Ching-Hon Pui; James R. Downing; D. Gary Gilliland; Eric S. Lander; Todd R. Golub; A. Thomas Look

    2002-01-01

    Human T cell leukemias can arise from oncogenes activated by specific chromosomal translocations involving the T cell receptor genes. Here we show that five different T cell oncogenes (HOX11, TAL1, LYL1, LMO1, and LMO2) are often aberrantly expressed in the absence of chromosomal abnormalities. Using oligonucleotide microarrays, we identified several gene expression signatures that were indicative of leukemic arrest at

  18. Evidence that the aberrant alpha 1-->2fucosyltransferase found in colorectal carcinoma may be encoded by Fuc-TIII (Le) gene.

    PubMed

    Nakamura, J; Mogi, A; Asao, T; Nagamachi, Y; Yazawa, S

    1997-01-01

    The accumulation of alpha 1-->2fucosylated antigens such as Le(b) and Y and the presence of aberrant alpha 1-->2 fucosyltransferase(s) (alpha 12FT) which showed new substrate specificities and must be involved in the accumulation of alpha 1-->2fucosylated antigens in colorectal carcinoma has been observed in our previous studies. In this study, we examined the substrate specificities of purified alpha 12FT from Colo201 cells and COS-1 cells transfected with the Fuc-TIII (Le) gene from a patient with colorectal carcinoma. It was demonstrated that activities of not only the Le gene related alpha 1-->3/4-fucosyltransferase but also the aberrant alpha 12FT were present in the purified preparation and in the extract of transfected COS-1 cells on which the Le(b) activity was expressed. These results suggested that the aberrant alpha 12FT was associated with the Le enzyme and that both enzymes could be encoded by the Fuc-TIII gene. PMID:9494569

  19. Aberrant DNA methylation of cancer-related genes in giant breast fibroadenoma: a case report

    PubMed Central

    2011-01-01

    Introduction Giant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands in promoter regions is known to be involved in the silencing of genes (for example, tumor-suppressor genes) and appears to be an early event in the etiology of breast carcinogenesis. Only hypermethylation of p16INK4a has been reported in non-giant breast fibroadenoma. In this particular case, there are no previously published data on epigenetic alterations in giant fibroadenomas. Our previous results, based on the analysis of 49 cancer-related CpG islands have confirmed that the aberrant methylation is specific to malignant breast tumors and that it is completely absent in normal breast tissue and breast fibroadenomas. Case presentation A 13-year-old Hispanic girl was referred after she had noted a progressive development of a mass in her left breast. On physical examination, a 10 × 10 cm lump was detected and axillary lymph nodes were not enlarged. After surgical removal the lump was diagnosed as a giant fibroadenoma. Because of the high growth rate of this benign tumor, we decided to analyze the methylation status of 49 CpG islands related to cell growth control. We have identified the methylation of five cancer-related CpG islands in the giant fibroadenoma tissue: ESR1, MGMT, WT-1, BRCA2 and CD44. Conclusion In this case report we show for the first time the methylation analysis of a giant fibroadenoma. The detection of methylation of these five cancer-related regions indicates substantial epigenomic differences with non-giant fibroadenomas. Epigenetic alterations could explain the higher growth rate of this tumor. Our data contribute to the growing knowledge of aberrant methylation in breast diseases. In this particular case, there exist no previous data regarding the role of methylation in giant fibroadenomas, considered by definition as a benign breast lesion. PMID:22011321

  20. Histone modification mapping in human brain reveals aberrant expression of histone H3 lysine 79 dimethylation in neural tube defects.

    PubMed

    Zhang, Qin; Xue, Peng; Li, Huili; Bao, Yihua; Wu, Lihua; Chang, Shaoyan; Niu, Bo; Yang, Fuquan; Zhang, Ting

    2013-06-01

    Neural tube defects (NTDs) are severe, common birth defects that result from failure of neural tube closure, but their pathological mechanisms are not yet fully understood. Histone modifications have an important role in gene regulation during fetal development. We therefore hypothesized that the human NTDs may be partly caused by an imbalance in metabolism, perhaps caused by nutritional deficiencies, that leads to aberrant histone modifications. Here, we report a screen of fetal brain histone modifications using 2D nano-LC strong cation exchange reverse phase (SCX/RP) MS/MS and the identification of 61 unique post-translational modification sites on histones H1, H2a, H2b, H3, and H4. Of these, 38 sites are novel (not already found in the Uniprot database). Furthermore, we compared the histone modification patterns between normal brains and NTD brains special of which maternal folate levels were lower than of normal control. The results showed that histone H3 lysine 79 dimethylation (H3K79me2) and a novel identified site, H2bK5 monomethylation (H2bK5me1), were completely absent in individuals with NTDs. Follow-up Western blotting validated the decreased H3K79me2 expression in brains with NTDs, but the amplified samples experiments displayed that decreased H3K79me2 expression was not suitable for all samples with NTDs. Furthermore, folate-free treated mouse embryonic stem cells induced the decreased H3K79me2 level. Subsequently, our ChIP results in normal fetal brain tissues showed that H3K79me2 binds to SUFU, RARA and ITGA3 which induce NTDs phenotype after knockout in mice, and in NTDs brain tissues the bindings of H3K79me2 to these three genes were significantly altered. Taken together, our study indicated that low folate treatment might attenuate H3K79 dimethylation, further affect its regulate activation on target genes, some of which are NTDs-resulting associated, lastly interrupt early embryo developing. Our study increases the understanding of normal fetal brain histone modifications and provides a platform for investigating histone modifications in neural disease and also has an insight into a potential role of aberrant histone modification in etiology of NTDs. PMID:23376398

  1. Vascular gene expression: a hypothesis

    PubMed Central

    Martínez-Navarro, Angélica C.; Galván-Gordillo, Santiago V.; Xoconostle-Cázares, Beatriz; Ruiz-Medrano, Roberto

    2013-01-01

    The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a “primitive” vascular tissue (a lycophyte), as well as from others that lack a true vascular tissue (a bryophyte), and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non-vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT, and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants. PMID:23882276

  2. Classification of genes based on gene expression analysis

    NASA Astrophysics Data System (ADS)

    Angelova, M.; Myers, C.; Faith, J.

    2008-05-01

    Systems biology and bioinformatics are now major fields for productive research. DNA microarrays and other array technologies and genome sequencing have advanced to the point that it is now possible to monitor gene expression on a genomic scale. Gene expression analysis is discussed and some important clustering techniques are considered. The patterns identified in the data suggest similarities in the gene behavior, which provides useful information for the gene functionalities. We discuss measures for investigating the homogeneity of gene expression data in order to optimize the clustering process. We contribute to the knowledge of functional roles and regulation of E. coli genes by proposing a classification of these genes based on consistently correlated genes in expression data and similarities of gene expression patterns. A new visualization tool for targeted projection pursuit and dimensionality reduction of gene expression data is demonstrated.

  3. Interactive Fly: Early Zygotic Gene Expression Images

    NSDL National Science Digital Library

    PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

    2006-12-12

    In situ images from an award-winning and comprehensive site, The Interactive Fly. Entering through an expression pattern, this site thoroughly discusses each genes and shows its expression relative to other genes at this stage.

  4. Gene expression in diabetic nephropathy

    Microsoft Academic Search

    Daniela Hohenadel; Fokko J. van der Woude

    2004-01-01

    Diabetic nephropathy (DN) is a common complication of diabetes types 1 and 2. One of the hallmarks of DN is the development\\u000a of mesangial expansion, which occurs through accumulation of extracellular matrix (ECM) components. Altered local gene expression\\u000a of humoral factors (eg, transforming growth factor-â, connective tissue growth factor, and platelet-derived growth factor) can lead to increased\\u000a production of ECM

  5. Gene Expression Studies in Mosquitoes

    PubMed Central

    Chen, Xlao-Guang; Mathur, Geetika; James, Anthony A.

    2009-01-01

    Research on gene expression in mosquitoes is motivated by both basic and applied interests. Studies of genes involved in hematophagy, reproduction, olfaction, and immune responses reveal an exquisite confluence of biological adaptations that result in these highly-successful life forms. The requirement of female mosquitoes for a bloodmeal for propagation has been exploited by a wide diversity of viral, protozoan and metazoan pathogens as part of their life cycles. Identifying genes involved in host-seeking, blood feeding and digestion, reproduction, insecticide resistance and susceptibility/refractoriness to pathogen development is expected to provide the bases for the development of novel methods to control mosquito-borne diseases. Advances in mosquito transgenesis technologies, the availability of whole genome sequence information, mass sequencing and analyses of transcriptomes and RNAi techniques will assist development of these tools as well as deepen the understanding of the underlying genetic components for biological phenomena characteristic of these insect species. PMID:19161831

  6. Sparse Statistical Modelling in Gene Expression Genomics

    E-print Network

    West, Mike

    1 Sparse Statistical Modelling in Gene Expression Genomics Joe Lucasa , Carlos Carvalhoa , Quanli gene expression data arising in either observational or designed experimental studies. The development - and critically misleading if ignored - in many gene expression studies. Two rich data sets are used to provide

  7. Tissue classification with gene expression profiles

    Microsoft Academic Search

    Amir Ben-Dor; Laurakay Bruhn; Nir Friedman; Iftach Nachman; Michèl Schummer; Zohar Yakhini

    2000-01-01

    Constantly improving gene expression profiling technologies are expected to provide understanding and insight into cancer related cellular processes. Gene expression data is also expected to significantly and in the development of efficient cancer diagnosis and classification platforms. In this work we examine two sets of gene expression data measured across sets of tumor and normal clinical samples One set consists

  8. Sparse Statistical Modelling in Gene Expression Genomics

    E-print Network

    West, Mike

    1 Sparse Statistical Modelling in Gene Expression Genomics Joe Lucasa , Carlos Carvalhoa , Quanli factor models for multivariate gene expression data arising in either observational or designed and one that can be critical - and critically misleading if ignored - in many gene expression studies. Two

  9. Gene dysregulations driven by somatic copy number aberrations-biological and clinical implications in colon tumors: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology.

    PubMed

    Bacolod, Manny D; Barany, Francis

    2010-09-01

    The majority of colorectal cancer (CRC) cases have chromosomal instability, in which the tumor genome is characterized by gross chromosomal aberrations such as gains in 20q, 13q, 8q, and 7, and losses in 4, 8p, 18q, and 17p. These somatic copy number changes (gains, losses, and somatic uniparental disomies) are crucial to CRC progression as they drive genes toward cancer-promoting (oncogenic or tumor suppressive) states. Numerous studies have shown that the loss of 18q or 8p is associated with poorer clinical outcome in CRCs. Either chromosomal arm may contain a tumor suppressor gene (or genes), whose deactivation by copy loss (loss of wild-type allele, decreased expression) can be crucial to the later stages of cancer progression. Our own integrated genomic analysis (single nucleotide polymorphism array, expression array) of more than 200 CRC tumor and normal samples indicates that the overall down-regulation of genes within the 8p or 18q arm is associated with lower survival rate. Among the often down-regulated, poor prognosis-associated 8p genes is MTUS1, whose gene product (a mitotic spindle-associated protein) was recently demonstrated to have a tumor suppressive property. Within 18q is ATP5A1, which codes for the catalytic a component of mitochondrial H(+)-ATP synthase. Like SMAD4 (also in 18q), the decreased expression of ATP5A1 appears to be a marker of unfavorable clinical outcome in CRCs. PMID:20709793

  10. Whole-body gene expression pattern registration in Platynereis larvae

    PubMed Central

    2012-01-01

    Background Digital anatomical atlases are increasingly used in order to depict different gene expression patterns and neuronal morphologies within a standardized reference template. In evo-devo, a discipline in which the comparison of gene expression patterns is a widely used approach, such standardized anatomical atlases would allow a more rigorous assessment of the conservation of and changes in gene expression patterns during micro- and macroevolutionary time scales. Due to its small size and invariant early development, the annelid Platynereis dumerilii is particularly well suited for such studies. Recently a reference template with registered gene expression patterns has been generated for the anterior part (episphere) of the Platynereis trochophore larva and used for the detailed study of neuronal development. Results Here we introduce and evaluate a method for whole-body gene expression pattern registration for Platynereis trochophore and nectochaete larvae based on whole-mount in situ hybridization, confocal microscopy, and image registration. We achieved high-resolution whole-body scanning using the mounting medium 2,2’-thiodiethanol (TDE), which allows the matching of the refractive index of the sample to that of glass and immersion oil thereby reducing spherical aberration and improving depth penetration. This approach allowed us to scan entire whole-mount larvae stained with nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) in situ hybridization and counterstained fluorescently with an acetylated-tubulin antibody and the nuclear stain 4’6-diamidino-2-phenylindole (DAPI). Due to the submicron isotropic voxel size whole-mount larvae could be scanned in any orientation. Based on the whole-body scans, we generated four different reference templates by the iterative registration and averaging of 40 individual image stacks using either the acetylated-tubulin or the nuclear-stain signal for each developmental stage. We then registered to these templates the expression patterns of cell-type specific genes. In order to evaluate the gene expression pattern registration, we analyzed the absolute deviation of cell-center positions. Both the acetylated-tubulin- and the nuclear-stain-based templates allowed near-cellular-resolution gene expression registration. Nuclear-stain-based templates often performed significantly better than acetylated-tubulin-based templates. We provide detailed guidelines and scripts for the use and further expansion of the Platynereis gene expression atlas. Conclusions We established whole-body reference templates for the generation of gene expression atlases for Platynereis trochophore and nectochaete larvae. We anticipate that nuclear-staining-based image registration will be applicable for whole-body alignment of the embryonic and larval stages of other organisms in a similar size range. PMID:23199348

  11. Aberrant DNA methyltransferase expression in pancreatic ductal adenocarcinoma development and progression

    PubMed Central

    2013-01-01

    Background Altered gene methylation, regulated by DNA methyltransferases (DNMT) 1, 3a and 3b, contributes to tumorigenesis. However, the role of DNMT in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Methods Expression of DNMT 1, 3a and 3b was detected in 88 Pancreatic ductal adenocarcinoma (PDAC) and 10 normal tissue samples by immunohistochemistry. Changes in cell viability, cell cycle distribution, and apoptosis of PDAC cell lines (Panc-1 and SW1990) were assessed after transfection with DNMT1 and 3b siRNA. Levels of CDKN1A, Bcl-2 and Bax mRNA were assessed by qRT-PCR, and methylation of the Bax gene promoter was assayed by methylation-specific PCR (MSP). Results DNMT1, 3a and 3b proteins were expressed in 46.6%, 23.9%, and 77.3% of PDAC tissues, respectively, but were not expressed in normal pancreatic tissues. There was a co-presence of DNMT3a and DNMT3b expression and an association of DNMT1 expression with alcohol consumption and poor overall survival. Moreover, knockdown of DNMT1 and DNMT3b expression significantly inhibited PDAC cell viability, decreased S-phase but increased G1-phase of the cell cycle, and induced apoptosis. Molecularly, expression of CDKN1A and Bax mRNA was upregulated, and the Bax gene promoter was demethylated. However, a synergistic effect of combined DNMT1 and 3b knockdown was not observed. Conclusion Expression of DNMT1, 3a and 3b proteins is increased in PDAC tissues, and DNMT1 expression is associated with poor prognosis of patients. Knockdown of DNMT1 and 3b expression arrests tumor cells at the G1 phase of the cell cycle and induces apoptosis. The data suggest that DNMT knockdown may be a novel treatment strategy for PDAC. PMID:24423239

  12. Clustering analysis for gene expression data

    NASA Astrophysics Data System (ADS)

    Chen, Yidong; Ermolaeva, Olga; Bittner, Michael L.; Meltzer, Paul S.; Trent, Jeffrey M.; Dougherty, Edward R.; Batman, Sinan

    1999-05-01

    The recent development of cDNA microarray allows ready access to large amount gene expression patterns for many genetic materials. Gene expression of tissue samples can be quantitatively analyzed by hybridizing fluor-tagged mRNA to targets on a cDNA microarray. Ratios of average expression level arising from co-hybridized normal and pathological samples are extracted via image segmentation, thus the gene expression pattern are obtained. The gene expression in a given biological process may provide a fingerprint of the sample development, or response to certain treatment. We propose a K-mean based algorithm in which gene expression levels fluctuate in parallel will be clustered together. The resulting cluster suggests some functional relationships between genes, and some known genes belongs to a unique functional classes shall provide indication for unknown genes in the same clusters.

  13. Aberrant methylation of the GCK gene body is associated with the risk of essential hypertension.

    PubMed

    Fan, Rui; Wang, Wei-Jie; Zhong, Qi-Long; Duan, Shi-Wei; Xu, Xu-Ting; Hao, Ling-Mei; Zhao, Jing; Zhang, Li-Na

    2015-08-01

    Essential hypertension (EH) is commonly accompanied by a dysfunction of glucose metabolism. Glucokinase (GCK) is a key enzyme involved in glucose metabolism. The aim of the present study was to investigate whether GCK gene?body methylation contributed to the risk of EH. A total of 47 patients with EH and 47 age?matched controls were recruited for methylation research in the current study. GCK gene?body methylation was measured using bisulphite pyrosequencing technology. DNA methylation levels were closely correlated among CpG1, CpG2 and CpG3 (r>0.70; P<0.001), in contrast with a weaker correlation between CpG4 and the preceding three CpGs (r<0.3 or r=1; P>0.05). Significantly lower CpG1?3 methylation (cases vs. controls, 49.13±5.72 vs. 53.49±7.53%; adjusted P=0.006) and significantly higher CpG4 methylation (cases vs. controls, 46.34±6.48 vs. 34.74±12.73%; adjusted P=0.002) were observed in patients with EH. The present study indicated that aberrant methylation of the GCK gene body was significantly associated with the risk of EH in the population assessed. The discrepancies between CpG1?3 and CpG4 methylation may suggest distinct roles for each of them in the determination of the risk of EH. PMID:25892191

  14. Seasonal Effects on Gene Expression

    PubMed Central

    Goldinger, Anita; Shakhbazov, Konstantin; Henders, Anjali K.; McRae, Allan F.; Montgomery, Grant W.; Powell, Joseph E.

    2015-01-01

    Many health conditions, ranging from psychiatric disorders to cardiovascular disease, display notable seasonal variation in severity and onset. In order to understand the molecular processes underlying this phenomenon, we have examined seasonal variation in the transcriptome of 606 healthy individuals. We show that 74 transcripts associated with a 12-month seasonal cycle were enriched for processes involved in DNA repair and binding. An additional 94 transcripts demonstrated significant seasonal variability that was largely influenced by blood cell count levels. These transcripts were enriched for immune function, protein production, and specific cellular markers for lymphocytes. Accordingly, cell counts for erythrocytes, platelets, neutrophils, monocytes, and CD19 cells demonstrated significant association with a 12-month seasonal cycle. These results demonstrate that seasonal variation is an important environmental regulator of gene expression and blood cell composition. Notable changes in leukocyte counts and genes involved in immune function indicate that immune cell physiology varies throughout the year in healthy individuals. PMID:26023781

  15. Fetal Hypoxia Results in Programming of Aberrant Angiotensin II Receptor Expression Patterns and Kidney Development

    PubMed Central

    Gonzalez-Rodriguez, Pablo Jr.; Tong, Wenni; Xue, Qin; Li, Yong; Hu, Shirley; Zhang, Lubo

    2013-01-01

    AIMS: The present study tested the hypothesis that fetal hypoxia adversely affects kidney development in fetal and offspring rats and alter the expression patterns of angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors. METHODS: Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 last period of gestation) groups. Protein expression, in the offspring, was determined using western blot. RESULTS: Hypoxic treatment significantly decreased body and kidney weight in 21-day fetuses (E21) and 7-day neonates (P7). In 3-month-old offspring there were no significant differences in body and kidney weight between hypoxic and control animals. Fetal hypoxia had no effect on kidney AT1R density in E21 or P7, but significantly decreased kidney AT1R protein and mRNA abundance in both male and female adults. In contrast, kidney AT2R density was not affected by fetal hypoxia throughout the developmental stages studied. The hypoxia-mediated reduction of nephron numbers was progressively from P7 worsened into the adulthood with females affected more than males. CONCLUSION: The results suggest that fetal hypoxia causes programming of aberrant kidney development and accelerates the aging process of the kidney during the postnatal development, which may contribute to an increased risk of cardiovascular disease. PMID:23532764

  16. Differential Regulation of ?7 Nicotinic Receptor Gene (CHRNA7) Expression in Schizophrenic Smokers

    PubMed Central

    Mexal, Sharon; Berger, Ralph; Logel, Judy; Ross, Randal G.; Freedman, Robert

    2009-01-01

    The ?7 neuronal nicotinic receptor gene (CHRNA7) has been implicated in the pathophysiology of schizophrenia by genetic and pharmacological studies. Expression of the ?7* receptor, as measured by [125I]?-bungarotoxin autoradiography, is decreased in postmortem brain of schizophrenic subjects compared to non-mentally ill controls. Most schizophrenic patients are heavy smokers, with high levels of serum cotinine. Smoking changes the expression of multiple genes and differentially regulates gene expression in schizophrenic hippocampus. We examined the effects of smoking on CHRNA7 expression in the same tissue and find that smoking differentially regulates expression of both mRNA and protein for this gene. CHRNA7 mRNA and protein levels are significantly lower in schizophrenic nonsmokers compared to control nonsmokers and are brought to control levels in schizophrenic smokers. Sufficient protein but low surface expression of the ?7* receptor, seen in the autoradiographic studies, suggests aberrant assembly or trafficking of the receptor. PMID:19680823

  17. Gene Expression Profiling in Developing Human Hippocampus

    E-print Network

    Gene Expression Profiling in Developing Human Hippocampus Yan Zhang,1,2 Pinchao Mei,1­3 Rong Lou,1 Molecular Biology, Beijing, China 4 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York The gene into the developmental and functional character- istics, we analyzed the expression profile of active genes in developing

  18. Gene Expression: Sizing It All Up

    PubMed Central

    Woody, Jenna Lynn; Shoemaker, Randy C.

    2011-01-01

    Genomic architecture appears to be a largely unexplored component of gene expression. That architecture can be related to chromatin domains, transposable element neighborhoods, epigenetic modifications of the genome, and more. Although surely not the end of the story, we are learning that when it comes to gene expression, size is also important. We have been surprised to find that certain patterns of expression, tissue specific versus constitutive, or high expression versus low expression, are often associated with physical attributes of the gene and genome. Multiple studies have shown an inverse relationship between gene expression patterns and various physical parameters of the genome such as intron size, exon size, intron number, and size of intergenic regions. An increase in expression level and breadth often correlates with a decrease in the size of physical attributes of the gene. Three models have been proposed to explain these relationships. Contradictory results were found in several organisms when expression level and expression breadth were analyzed independently. However, when both factors were combined in a single study a novel relationship was revealed. At low levels of expression, an increase in expression breadth correlated with an increase in genic, intergenic, and intragenic sizes. Contrastingly, at high levels of expression, an increase in expression breadth inversely correlated with the size of the gene. In this article we explore the several hypotheses regarding genome physical parameters and gene expression. PMID:22303365

  19. Methods for monitoring multiple gene expression

    DOEpatents

    Berka, Randy (Davis, CA); Bachkirova, Elena (Davis, CA); Rey, Michael (Davis, CA)

    2012-05-01

    The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

  20. Aberrant methylation of the SPARC gene promoter and its clinical implication in gastric cancer

    PubMed Central

    Chen, Zi-Yi; Zhang, Jun-Ling; Yao, Hong-Xin; Wang, Peng-Yuan; Zhu, Jing; Wang, Wei; Wang, Xin; Wan, Yuan-Lian; Chen, Shan-Wen; Chen, Guo-Wei; Liu, Yu-Cun

    2014-01-01

    Secreted protein acidic and rich in cysteine (SPARC) gene has been shown to be epigenetically silenced in several cancers. We investigated the loss of expression and promoter methylation of this tumor suppressor gene in gastric cancers and correlated the data with clinicopathological features. We observed the loss of SPARC mRNA and SPARC protein expression in 7 of 10 (70%) gastric cancer cell lines. Upon treatment of expression-negative cell lines with a demethylating agent, expression of mRNA and protein was restored in all cells. Methylation rate of SPARC gene was 80% in ten gastric cancer cell lines and 74% (163 of 220) in primary tumors, while it was 5% in normal gastric mucosa (n = 40). In intestinal gastric cancer, SPARC methylation correlated with a negative prognosis (P < 0.001; relative risk 2.754, 95% confidence interval 1.780–4.261). Immunostaining revealed that SPARC protein was overexpressed in stromal fibroblasts adjacent to neoplastic epithelium but rarely expressed in the primary gastric cancer cells. These results implicate SPARC promoter methylation as an important factor in the tumorigenesis of gastric carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and the potential clinical importance in human gastric cancers. PMID:25516351

  1. The Transcription Factor ZEB1 Is Aberrantly Expressed in Aggressive Uterine Cancers

    Microsoft Academic Search

    Nicole S. Spoelstra; Nicole G. Manning; Yujiro Higashi; Douglas Darling; Meenakshi Singh; Kenneth R. Shroyer; Russell R. Broaddus; Kathryn B. Horwitz

    2006-01-01

    The transcription factor ZEB1 (DEF1 in mice) has been implicated in cellular processes during development and tumor progression including epithelial to mesenchymal tran- sition. DEF1 null mice die at birth, but heterozygotes expressing a LacZ reporter inserted into the DEF1 gene live and reproduce. Using these mice, we observed ZEB1 promoter activity in the virgin myometrium, and stroma and myometrium

  2. Aberrant amplification of A2A receptor signaling in striatal cells expressing mutant huntingtin

    Microsoft Academic Search

    Katia Varani; Dorotea Rigamonti; Simonetta Sipione; Alessandra Camurri; Pier Andrea Borea; Flaminio Cattabeni; Maria P. Abbracchio; Elena Cattaneo

    2001-01-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding for Huntingtin (Htt), which results in progressive degeneration of the striatal GABAergic\\/enkephalin neurons. These neurons express both the A2A and D2 receptors, which stimulate and inhibit adenylyl cyclase, respectively. In this study we analyzed the possibility of an involvement of the A2A

  3. Normalization and quantification of differential expression in gene expression microarrays

    Microsoft Academic Search

    Christine Steinhoff; Martin Vingron

    2006-01-01

    Array-based gene expression studies frequently serve to identify genes that are expressed differently under two or more conditions. The actual analysis of the data, however, may be hampered by a number of technical and statistical problems. Possible remedies on the level of computational analysis lie in appropriate preprocessing steps, proper normalization of the data and application of statistical testing procedures

  4. Profiling Gene Expression in Germinating Brassica Roots.

    PubMed

    Park, Myoung Ryoul; Wang, Yi-Hong; Hasenstein, Karl H

    2014-01-01

    Based on previously developed solid-phase gene extraction (SPGE) we examined the mRNA profile in primary roots of Brassica rapa seedlings for highly expressed genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK (glucokinase) during the first day post-germination. The assessment was based on the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the investigated genes changed spatially along the length of primary roots. The expression level of all genes differed significantly at each sample position. Among the examined genes ACT7 expression was most even along the root. UBQ was highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary root emergence and higher than at any other sample position. Expressions of GLK in EZ and RS increased gradually over time. SPGE extraction is the result of oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be used for gene expression profiling at high spatial and temporal resolution. SPGE needles can be used within two weeks when stored at 4 °C. Our data indicate that gene expression studies that are based on the entire root miss important differences in gene expression that SPGE is able to resolve for example growth adjustments during gravitropism. PMID:24563578

  5. Aberrant CCR4 Expression Is Involved in Tumor Invasion of Lymph Node-Negative Human Gastric Cancer

    PubMed Central

    Yang, Xiaoyun; Qu, Ailin; Zhang, Xin; Zhou, Chengjun; Wang, Chuanxin

    2015-01-01

    Cellular chemotaxis is the best-known function of chemokine receptors which are closely linked with tumor metastasis. In fact, positive expression of chemokine receptors could also be identified even in some patients without metastatic tumors, while the clinical relevance of this data has not been fully established. Our studies were designed to clarify the CCR4 expression profiles and to explore its potential role in histologically node-negative (pN0) gastric cancer (GC). Immunohistochemistry (IHC) or immunohistofluorescence (IHF) analysis was performed on specimens obtained from 108 patients with pN0 GC. We found that CCR4 was aberrantly over-expressed inpN0 GC tissues, with different expression patterns on tumor cells and being associated with T-stage (P = 0.002). The matrigel in vitro invasion assay revealed that over-expression of CCR4 in GC cell lines significantly enhanced the invasive capacity of these cells. Results from real-time RT-PCR and gelatinzymography showed a significant increase in matrix metalloproteinase (MMP)-9 production induced by the forced expression of CCR4 in GC cell lines. Our data suggest that the aberrant CCR4 expression is involved in tumor invasion of pN0 GC and, conceivably, antagonists of CCR4 might be useful candidates for controlling early events in tumor progression. PMID:25790118

  6. Identification of 27 5? CpG islands aberrantly methylated and 13 genes silenced in human pancreatic cancers

    Microsoft Academic Search

    Atsushi Hagihara; Kazuaki Miyamoto; Junichi Furuta; Nobuyoshi Hiraoka; Kuniko Wakazono; Shuichi Seki; Shoji Fukushima; Ming-Sound Tsao; Takashi Sugimura; Toshikazu Ushijima

    2004-01-01

    Aberrantly methylated DNA fragments were searched for in human pancreatic cancers, using the genome scanning technique: methylation-sensitive-representational difference analysis (MS-RDA). MS-RDA isolated 111 DNA fragments derived from CpG islands (CGIs), and 35 of them were from CGIs in the 5? regions of known genes. Methylation-specific PCR (MSP) of the CGIs in seven pancreatic cancer cell lines and two pancreatic ductal

  7. Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression.

    PubMed

    de Tayrac, Marie; Etcheverry, Amandine; Aubry, Marc; Saïkali, Stephan; Hamlat, Abderrahmane; Quillien, Veronique; Le Treut, André; Galibert, Marie-Dominique; Mosser, Jean

    2009-01-01

    Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of which on gene expression remains unclear. To investigate this relationship and to identify putative initiating genomic events, we integrated a paired copy number and gene expression survey in glioblastoma using whole human genome arrays. Loci of recurrent copy number alterations were combined with gene expression profiles obtained on the same tumor samples. We identified a set of 406 "cis-acting DNA targeted genes" corresponding to genomic aberrations with direct copy-number-driving changes in gene expression, defined as genes with either significantly concordant or correlated changes in DNA copy number and expression. Functional annotation revealed that these genes participate in key processes of cancer cell biology, providing insights into the genetic mechanisms driving glioblastoma. The robustness of the gene selection was validated on an external microarray data set including 81 glioblastomas and 23 non-neoplastic brain samples. The integration of array CGH and gene expression data highlights a robust cis-acting DNA targeted genes signature that may be critical for glioblastoma progression, with two tumor suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness and resistance to etoposide. PMID:18828157

  8. GEO: the Gene Expression Omnibus A family of databases for gene expression related data

    E-print Network

    Levin, Judith G.

    GEO: the Gene Expression Omnibus A family of databases for gene expression related data http://www.ncbi.nlm.nih.gov Contact: info@ncbi.nlm.nih.gov Scope and access The Gene Expression Omnibus (GEO) is a public repository for searching and browsing high-throughput array data: www.ncbi.nlm.nih.gov/geo/. GEO accepts many categories

  9. Expression of a truncated tomato polygalacturonase gene inhibits expression of the endogenous gene in transgenic plants

    Microsoft Academic Search

    C. J. S. Smith; C. F. Watson; C. R. Bird; J. Ray; W. Schuch; D. Grierson

    1990-01-01

    Tomato plants were transformed with a chimaeric polygalacturonase (PG) gene, designed to produce a truncated PG transcript constitutively. In these plants expression of the endogenous PG gene was inhibited during ripening, resulting in a substantial reduction in PG mRNA and enzyme accumulation. This inhibition was comparable to that achieved previously using antisense genes. The expression of the truncated gene in

  10. A mutation in a rare type of intron in a sodium-channel gene results in aberrant splicing and causes myotonia

    PubMed Central

    Kubota, Tomoya; Roca, Xavier; Kimura, Takashi; Kokunai, Yosuke; Nishino, Ichizo; Sakoda, Saburo; Krainer, Adrian R.; Takahashi, Masanori P.

    2014-01-01

    Many mutations in the skeletal-muscle sodium-channel gene SCN4A have been associated with myotonia and/or periodic paralysis, but so far all of these mutations are located in exons. We found a patient with myotonia caused by a deletion/insertion located in intron 21 of SCN4A, which is an AT-AC type II intron. This is a rare class of introns that, despite having AT-AC boundaries, are spliced by the major or U2-type spliceosome. The patient's skeletal muscle expressed aberrantly spliced SCN4A mRNA isoforms generated by activation of cryptic splice sites. In addition, genetic suppression experiments using an SCN4A minigene showed that the mutant 5? splice site has impaired binding to the U1 and U6 snRNPs, which are the cognate factors for recognition of U2-type 5? splice sites. One of the aberrantly spliced isoforms encodes a channel with a 35-amino-acid insertion in the cytoplasmic loop between domains III and IV of Nav1.4. The mutant channel exhibited a marked disruption of fast inactivation, and a simulation in silico showed that the channel defect is consistent with the patient's myotonic symptoms. This is the first report of a disease-associated mutation in an AT-AC type II intron, and also the first intronic mutation in a voltage-gated ion channel gene showing a gain-of-function defect. PMID:21412952

  11. Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer

    SciTech Connect

    David, Stefan; Kan, Takatsugu; Cheng, Yulan; Agarwal, Rachana; Jin, Zhe [Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, 1503 E. Jefferson Street Office 108, Baltimore, MA 21287 (United States); Mori, Yuriko [Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, 1503 E. Jefferson Street Office 108, Baltimore, MA 21287 (United States)], E-mail: ymori3@jhmi.edu

    2009-01-16

    Tachykinin-1 (TAC1) is the precursor protein for neuroendocrine peptides, including substance P, and is centrally involved in gastric secretion, motility, mucosal immunity, and cell proliferation. Here we report aberrant silencing of TAC1 in gastric cancer (GC) by promoter hypermethylation. TAC1 methylation and mRNA expression in 47 primary GCs and 41 noncancerous gastric mucosae (NLs) were analyzed by utilizing real-time quantitative PCR-based assays. TAC1 methylation was more prevalent in GCs than in NLs: 21 (45%) of 47 GCs versus 6 (15%) of 41 NLs (p < 0.01). Microsatellite instability was also associated with TAC1 methylation in GCs. There was no significant association between TAC1 methylation and age, gender, stage, histological differentiation, or the presence of Helicobacter pylori. TAC1 mRNA was markedly downregulated in GCs relative to NLs. 5-Aza-2'-deoxycytidine-induced demethylation of the TAC1 promoter resulted in TAC1 mRNA upregulation. Further studies are indicated to elucidate the functional involvement of TAC1 in gastric carcinogenesis.

  12. Arabidopsis gene expression patterns during spaceflight

    NASA Astrophysics Data System (ADS)

    Paul, A.-L.; Ferl, R. J.

    The exposure of Arabidopsis thaliana (Arabidopsis) plants to spaceflight environments resulted in the differential expression of hundreds of genes. A 5 day mission on orbiter Columbia in 1999 (STS-93) carried transgenic Arabidopsis plants engineered with a transgene composed of the alcohol dehydrogenase (Adh) gene promoter linked to the ? -Glucuronidase (GUS) reporter gene. The plants were used to evaluate the effects of spaceflight on two fronts. First, expression patterns visualized with the Adh/GUS transgene were used to address specifically the possibility that spaceflight induces a hypoxic stress response, and to assess whether any spaceflight response was similar to control terrestrial hypoxia-induced gene expression patterns. (Paul et al., Plant Physiol. 2001, 126:613). Second, genome-wide patterns of native gene expression were evaluated utilizing the Affymetrix ATH1 GeneChip? array of 8,000 Arabidopsis genes. As a control for the veracity of the array analyses, a selection of genes identified with the arrays was further characterized with quantitative Real-Time RT PCR (ABI - TaqmanTM). Comparison of the patterns of expression for arrays of hybridized with RNA isolated from plants exposed to spaceflight compared to the control arrays revealed hundreds of genes that were differentially expressed in response to spaceflight, yet most genes that are hallmarks of hypoxic stress were unaffected. These results will be discussed in light of current models for plant responses to the spaceflight environment, and with regard to potential future flight opportunities.

  13. Gene Expression Profiling of Childhood Adrenocortical Tumors

    Microsoft Academic Search

    Alina Nico West; Geoffrey A. Neale; Stanley Pounds; Bonald C. Figueredo; Carlos RodriguezGalindo; Antonio G. Oliveira Filho; David Malkin; Enzo Lalli; Raul Ribeiro; Gerard P. Zambetti

    2007-01-01

    Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors ( five adenomas, 18 carcinomas, and one undeter- mined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time

  14. Gene Expression Studies in Lygus lineolaris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genes are expressed in insect cells, as in all living organisms, by transcription of DNA into RNA followed by translation of RNA into proteins. The intricate patterns of differential gene expression in time and space directly influence the development and function of every aspect of the organism. Wh...

  15. Gene expression in periodontal tissues following treatment

    Microsoft Academic Search

    Thomas Beikler; Ulrike Peters; Karola Prior; Martin Eisenacher; Thomas F Flemmig

    2008-01-01

    BACKGROUND: In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of

  16. A pentatricopeptide repeat-containing gene that promotes the processing of aberrant atp6 RNA of cytoplasmic male-sterile rice

    Microsoft Academic Search

    Tomohiko Kazama; Kinya Toriyama

    2003-01-01

    A fertility restorer gene (Rf-1) of [ms-bo] cytoplasmic male sterility (CMS) in rice has been reported to be responsible for the processing of RNA of aberrant atp6 of mitochondria. We have carried out map-based cloning of the Rf-1 gene and found that a 4.7-kb genomic fragment of a restorer line promoted the processing of aberrant atp6 RNA when introduced into

  17. Aberrant protein expression in the placenta of cloned mouse derived from embryonic stem cell.

    PubMed

    Kim, Hong Rye; Han, Rong Xun; Wakayama, Teruhiko; Park, Chang Sik; Jin, Dong Il

    2010-10-01

    Placentomegaly is a common phenotype in cloned mice. To assess differences in protein expression between placentae of cloned and uncloned mice, we used a proteomic approach involving 2-dimensional electrophoresis (DE) and MALDI-TOF MS. Proteins within isoelectric point range of 4-11 separately were analyzed in 2-DE with 3 replications of each sample. A total of approximately 3500 spots were detected in placental 2-DE stained with Coomassie blue. In the comparison of normal and cloned samples, a total of 41 spots were identified as differentially expressed proteins, of which 25 spots were up-regulated proteins such as TIMP-2, glutamate-ammonia, and esterase 10, while 16 spots were down-regulated proteins such as PBEF and annexin A1. The TIMP-2, which is related to extracellular matrix degradation and tissue remodeling processes, is an inhibitor of MMP-2. The PBEF is related to inhibition of apoptosis and induction of spontaneous labor. Western blot analysis confirmed increased TIMP-2 expression and decreased PBEF expression in cloned placentae compared with normal controls. Our results demonstrated composite profiles of key proteins involved in abnormal hypertrophic placenta derived from cloned mice and suggested that the reason for the placentomegaly may be due to abnormal gene expression in cloned mice. PMID:20684987

  18. Regulation Of Mammalian Myb Gene Expression

    Microsoft Academic Search

    Fiona J. Tavner

    Although the precise molecular mechanisms that govern mammalian myb (cmyb, B-myb (MybL2) and A-myb (MybL1)) gene expression are yet to be resolved, a collective understanding is beginning to emerge. At present, it is evident that\\u000a distinct regulatory factors and mechanisms control expression of the mammalian myb genes, and this is presumably reflected in the defined expression patterns of individual family

  19. Verification of genes differentially expressed in neuroblastoma tumours: a study of potential tumour suppressor genes

    PubMed Central

    Thorell, Kaisa; Bergman, Annika; Carén, Helena; Nilsson, Staffan; Kogner, Per; Martinsson, Tommy; Abel, Frida

    2009-01-01

    Background One of the most striking features of the childhood malignancy neuroblastoma (NB) is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified. Methods In this study we performed expression analysis by quantitative real-time PCR (QPCR) on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA) targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples. Results By TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours, ATBF1, CACNA2D3, CNTNAP2, FUSIP1, GNB1, SLC35E2, and TFAP2B. The gene that showed the highest fold change in the TLDA analysis, POU4F2, was investigated for epigenetic changes (CpG methylation) and mutations in order to explore the cause of the differential expression. Moreover, the fragile site gene CNTNAP2 that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses of POU4F2 and CNTNAP2 showed no genetic alterations that could explain a lower expression in unfavourable NB tumours. Conclusion Through two steps of verification, seven transcripts were found to significantly discriminate between favourable and unfavourable NB tumours. Four of the transcripts, CACNA2D3, GNB1, SLC35E2, and TFAP2B, have been observed in previous microarray studies, and are in this study independently verified. Our results suggest these transcripts to be markers of malignancy, which could have a potential usefulness in the clinic. PMID:19686582

  20. Methodological Limitations in Determining Astrocytic Gene Expression

    PubMed Central

    Peng, Liang; Guo, Chuang; Wang, Tao; Li, Baoman; Gu, Li; Wang, Zhanyou

    2013-01-01

    Traditionally, astrocytic mRNA and protein expression are studied by in situ hybridization (ISH) and immunohistochemically. This led to the concept that astrocytes lack aralar, a component of the malate-aspartate-shuttle. At least similar aralar mRNA and protein expression in astrocytes and neurons isolated by fluorescence-assisted cell sorting (FACS) reversed this opinion. Demonstration of expression of other astrocytic genes may also be erroneous. Literature data based on morphological methods were therefore compared with mRNA expression in cells obtained by recently developed methods for determination of cell-specific gene expression. All Na,K-ATPase-? subunits were demonstrated by immunohistochemistry (IHC), but there are problems with the cotransporter NKCC1. Glutamate and GABA transporter gene expression was well determined immunohistochemically. The same applies to expression of many genes of glucose metabolism, whereas a single study based on findings in bacterial artificial chromosome (BAC) transgenic animals showed very low astrocytic expression of hexokinase. Gene expression of the equilibrative nucleoside transporters ENT1 and ENT2 was recognized by ISH, but ENT3 was not. The same applies to the concentrative transporters CNT2 and CNT3. All were clearly expressed in FACS-isolated cells, followed by biochemical analysis. ENT3 was enriched in astrocytes. Expression of many nucleoside transporter genes were shown by microarray analysis, whereas other important genes were not. Results in cultured astrocytes resembled those obtained by FACS. These findings call for reappraisal of cellular nucleoside transporter expression. FACS cell yield is small. Further development of cell separation methods to render methods more easily available and less animal and cost consuming and parallel studies of astrocytic mRNA and protein expression by ISH/IHC and other methods are necessary, but new methods also need to be thoroughly checked. PMID:24324456

  1. Hematopoietic expression of oncogenic BRAF promotes aberrant growth of monocyte-lineage cells resistant to PLX4720

    PubMed Central

    Kamata, Tamihiro; Dankort, David; Kang, Jing; Giblett, Susan; Pritchard, Catrin A.; McMahon, Martin; Leavitt, Andrew D.

    2013-01-01

    Mutational activation of BRAF leading to expression of the BRAFV600E oncoprotein was recently identified in a high percentage of specific hematopoietic neoplasms in monocyte/histiocyte and mature B-cell lineages. Although BRAFV600E is a driver oncoprotein and pharmacological target in solid tumors such as melanoma, lung and thyroid cancer, it remains unknown whether BRAFV600E is an appropriate therapeutic target in hematopoietic neoplasms. To address this critical question, we generated a mouse model expressing inducible BRAFV600E in the hematopoietic system, and evaluated the efficacy of pathway-targeted therapeutics against primary hematopoietic cells. In this model, BRAFV600E expression conferred cytokine-independent growth to monocyte/macrophage-lineage progenitors leading to aberrant in vivo and in vitro monocyte/macrophage expansion. Furthermore, transplantation of BRAFV600E-expressing bone marrow cells promoted an in vivo pathology most notable for monocytosis in hematopoietic tissues and visceral organs. In vitro analysis revealed that MEK inhibition, but not RAF inhibition, effectively suppressed cytokine-independent clonal growth of monocyte/macrophage-lineage progenitors. However, combined RAF and PI3K inhibition effectively inhibited cytokine-independent colony formation, suggesting autocrine PI3K pathway activation. Taken together, these results provide evidence that constitutively activated BRAFV600E drives aberrant proliferation of monocyte-lineage cells. This study supports the development of pathway-targeted therapeutics in the treatment of BRAFV600E-expressing hematopoietic neoplasms in the monocyte/histiocyte lineage. PMID:24152792

  2. Identifying time-lagged gene clusters using gene expression data

    Microsoft Academic Search

    Liping Ji; Kian-lee Tan

    2005-01-01

    Motivation: Analysis of gene expression data can provide insights into the time-lagged co-regulations of genes\\/gene clusters. However, existing methods such as Event Method and Edge Detection Method are inefficient as they only compare two genes each time. More importantly, they lose some important information due to their scoring criterion. In this paper, we propose an efficient algorithm to identify time-lagged

  3. The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.

    PubMed

    Albert, Mareike; Schmitz, Sandra U; Kooistra, Susanne M; Malatesta, Martina; Morales Torres, Cristina; Rekling, Jens C; Johansen, Jens V; Abarrategui, Iratxe; Helin, Kristian

    2013-04-01

    Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development, and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb target genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants, supporting a functional interplay between Polycomb proteins and Jarid1b. To understand how Jarid1b regulates mouse development, we performed a genome-wide analysis of histone modifications, which demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 during early embryogenesis in Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators like Pax6 and Otx2 in Jarid1b knockout brains. Taken together, these results suggest that Jarid1b regulates mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. PMID:23637629

  4. Mucin gene expression in biliary epithelial cells

    Microsoft Academic Search

    Benedicte Vandenhaute; Marie-Pierre Buisine; Virginie Debailleul; Bruno Clément; Nicolas Moniaux; Marie-Claire Dieu; Pierre Degand; Nicole Porchet; Jean-Pierre Aubert

    1997-01-01

    Background\\/Aims: In recent years considerable advances have been made in our knowledge of human mucin genes. Although analysis of their genomic organization is still in progress, the pattern of their expression in different human mucosae is now fairly well established. However, little is known about their expression in the biliary tree. In this study we determined the pattern of expression

  5. Glucocorticoid regulation of human eosinophil gene expression.

    PubMed

    Chauhan, Sanjay; Leach, Craig H; Kunz, Susan; Bloom, John W; Miesfeld, Roger L

    2003-03-01

    Molecular analysis of steroid-regulated gene expression in freshly isolated human eosinophils is difficult due to the inherent high rate of spontaneous apoptosis and elevated levels of endogenous ribonucleases. To circumvent these limitations, we determined if the human eosinophilic cell line EoL-1 could serve as an in vitro model of glucocorticoid signaling. We found by optimizing growth conditions in low serum-containing media that dexamethasone (Dex) treatment of EoL-1 cells induced an apoptotic pathway that was inhibited by interleukin-5 (IL-5). Moreover, gene expression profiling using RNA from untreated EoL-1 cells and from freshly isolated human eosinophils identified 380 commonly expressed genes, including the eosinophil markers granule major basic protein, prostaglandin-endoperoxide synthase 1 and arachidonate 15-lipoxygenase. Expression profiling was performed using EoL-1 cells that had been treated with dexamethasone for 0, 4, 12, 24 and 48h identifying 162 genes as differentially expressed. Two of the most highly upregulated genes based on expression profiling were the transcription factor Ets-2 and the MHC Class II genes (Q, R, and P). Expression of these genes in EoL-1 cells was shown to be dexamethasone-induced at the RNA and protein levels which is consistent with the known function of Ets-2 in controlling cell cycle progression and the role of MHC Class II antigens in mediating eosinophil functions. PMID:12732289

  6. Gene Expression Profiling of Solitary Fibrous Tumors

    PubMed Central

    Bertucci, François; Bouvier-Labit, Corinne; Finetti, Pascal; Metellus, Philippe; Adelaide, José; Mokhtari, Karima; Figarella-Branger, Dominique; Decouvelaere, Anne-Valérie; Miquel, Catherine; Coindre, Jean-Michel; Birnbaum, Daniel

    2013-01-01

    Background Solitary fibrous tumors (SFTs) are rare spindle-cell tumors. Their cell-of-origin and molecular basis are poorly known. They raise several clinical problems. Differential diagnosis may be difficult, prognosis is poorly apprehended by histoclinical features, and no effective therapy exists for advanced stages. Methods We profiled 16 SFT samples using whole-genome DNA microarrays and analyzed their expression profiles with publicly available profiles of 36 additional SFTs and 212 soft tissue sarcomas (STSs). Immunohistochemistry was applied to validate the expression of some discriminating genes. Results SFTs displayed whole-genome expression profiles more homogeneous and different from STSs, but closer to genetically-simple than genetically-complex STSs. The SFTs/STSs comparison identified a high percentage (?30%) of genes as differentially expressed, most of them without any DNA copy number alteration. One of the genes most overexpressed in SFTs encoded the ALDH1 stem cell marker. Several upregulated genes and associated ontologies were also related to progenitor/stem cells. SFTs also overexpressed genes encoding therapeutic targets such as kinases (EGFR, ERBB2, FGFR1, JAK2), histone deacetylases, or retinoic acid receptors. Their overexpression was found in all SFTs, regardless the anatomical location. Finally, we identified a 31-gene signature associated with the mitotic count, containing many genes related to cell cycle/mitosis, including AURKA. Conclusion We established a robust repertoire of genes differentially expressed in SFTs. Certain overexpressed genes could provide new diagnostic (ALDH1A1), prognostic (AURKA) and/or therapeutic targets. PMID:23734203

  7. Correlative gene expression and DNA methylation profiling in lung development nominate new biomarkers in lung cancer.

    PubMed

    Cortese, Rene; Hartmann, Oliver; Berlin, Kurt; Eckhardt, Florian

    2008-01-01

    Although transcriptional control is key for proper lung development, little is known about the possible accompanying epigenetic modifications. Here, we have used gene expression profiling to identify 99 genes that are upregulated in fetal lung and 354 genes that are upregulated in adult lung. From the differentially expressed genes, we analyzed the accompanying 5'-UTR methylation profiles of 43 genes. Out of these, nine genes (COL11A1, MEOX2, SERPINE2, SOX9, FBN2, MDK, COL1A1, LAPTM5 and MARCO) displayed an inverse correlation of their 5'-UTR methylation and the cognate gene expression, suggesting that these genes are at least partially regulated by DNA methylation. Using the differential gene expression/DNA methylation profiles as a guidepost, we identified four genes (MEOX2, MDK, LAPTM5, FGFR3) aberrantly methylated in lung cancer. MEOX2 was uniformly higher methylated in all lung cancer samples (n=15), while the methylation of the other three genes was correlated with either the differentiation state of the tumor (MDK, LAPTM5) or the tumor type itself (FGFR3). PMID:18203646

  8. Plant breeding (review) Transformation of Poaceae and gene expression

    E-print Network

    Paris-Sud XI, Université de

    Plant breeding (review) Transformation of Poaceae and gene expression in transgenic plants J used for transformation and for achieving controlled gene expression in transgenic plants and discusses. transformation / monocot / gene expression / transgenic plant Summary — Transformation des Poaceae et

  9. Discovering Temporal Associations among Significant Changes in Gene Expression

    E-print Network

    An, Aijun

    Discovering Temporal Associations among Significant Changes in Gene Expression Hashmat Rohian, Microarray Data Analysis, Change Association Mining I. INTRODUCTION Gene expression data, produced by DNA gene at a time, microarray experiments allow us to monitor and analyze the expression levels

  10. Aberrant TIG1 methylation associated with its decreased expression and clinicopathological significance in hepatocellular carcinoma.

    PubMed

    Chen, Xi-Hua; Wu, Wen-Guang; Ding, Jian

    2014-02-01

    Recently, it has been reported that tazarotene-induced gene 1 (TIG1) methylation was frequently detected in a variety of human cancers. However, the relationship between the TIG1 methylation and the characteristics of hepatocellular carcinoma (HCC) remains unknown. The aim of present study was to observe the promoter methylation of TIG1 in HCC tissues and assess its prognostic significance for HCC. Real-time quantitative polymerase chain reaction and methylation-specific polymerase chain reaction were used, respectively, to examine the mRNA expression and methylation status of TIG1 in 91 pairs of HCC and adjacent noncancerous tissues. The mRNA expression level of TIG1 was significantly lower in HCC tissues than in adjacent noncancerous tissues. The rate of TIG1 promoter methylation was significantly higher in HCC tissues than in adjacent noncancerous tissues (P < 0.001). A strong correlation between downregulation and promoter methylation was found in these tumors (P < 0.001). More importantly, TIG1 methylation status was related to tumor size (P = 0.015), histological differentiation (P = 0.004), and tumor stage (P < 0.001). Kaplan-Meier survival analysis showed that TIG1 promoter hypermethylation was associated with a worse outcome in patients with HCC. Further, Cox multivariate analysis indicated that TIG1 methylation status was an independent prognostic factor for the overall survival rate of HCC patients. In conclusion, our data suggested that epigenetic silencing of TIG1 gene expression by promoter hypermethylation may play an important role in HCC. PMID:24006221

  11. Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2

    Microsoft Academic Search

    Anna ViholaLinda; Linda L. Bachinski; Mario Sirito; Shodimu-Emmanuel Olufemi; Shohrae Hajibashi; Keith A. Baggerly; Olayinka Raheem; Hannu Haapasalo; Tiina Suominen; Jeanette Holmlund-Hampf; Anders Paetau; Rosanna Cardani; Giovanni Meola; Hannu Kalimo; Lars Edström; Ralf Krahe; Bjarne Udd

    2010-01-01

    Aberrant transcription and mRNA processing of multiple genes due to RNA-mediated toxic gain-of-function has been suggested\\u000a to cause the complex phenotype in myotonic dystrophies type 1 and 2 (DM1 and DM2). However, the molecular basis of muscle\\u000a weakness and wasting and the different pattern of muscle involvement in DM1 and DM2 are not well understood. We have analyzed\\u000a the mRNA

  12. Nonsense-mediated RNA decay - a switch and dial for regulating gene expression.

    PubMed

    Smith, Jenna E; Baker, Kristian E

    2015-06-01

    Nonsense-mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD-sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady-state RNA levels in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein-coding capacity are also sensitive to this translation-dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. PMID:25820233

  13. Nonsense-mediated RNA decay – a switch and dial for regulating gene expression

    PubMed Central

    Smith, Jenna E.; Baker, Kristian E.

    2015-01-01

    Nonsense-mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD-sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady-state RNA levels in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues providesa means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein-coding capacity are also sensitive to this translation-dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. PMID:25820233

  14. Digital gene expression signatures for maize development.

    PubMed

    Eveland, Andrea L; Satoh-Nagasawa, Namiko; Goldshmidt, Alexander; Meyer, Sandra; Beatty, Mary; Sakai, Hajime; Ware, Doreen; Jackson, David

    2010-11-01

    Genome-wide expression signatures detect specific perturbations in developmental programs and contribute to functional resolution of key regulatory networks. In maize (Zea mays) inflorescences, mutations in the RAMOSA (RA) genes affect the determinacy of axillary meristems and thus alter branching patterns, an important agronomic trait. In this work, we developed and tested a framework for analysis of tag-based, digital gene expression profiles using Illumina's high-throughput sequencing technology and the newly assembled B73 maize reference genome. We also used a mutation in the RA3 gene to identify putative expression signatures specific to stem cell fate in axillary meristem determinacy. The RA3 gene encodes a trehalose-6-phosphate phosphatase and may act at the interface between developmental and metabolic processes. Deep sequencing of digital gene expression libraries, representing three biological replicate ear samples from wild-type and ra3 plants, generated 27 million 20- to 21-nucleotide reads with frequencies spanning 4 orders of magnitude. Unique sequence tags were anchored to 3'-ends of individual transcripts by DpnII and NlaIII digests, which were multiplexed during sequencing. We mapped 86% of nonredundant signature tags to the maize genome, which associated with 37,117 gene models and unannotated regions of expression. In total, 66% of genes were detected by at least nine reads in immature maize ears. We used comparative genomics to leverage existing information from Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) in functional analyses of differentially expressed maize genes. Results from this study provide a basis for the analysis of short-read expression data in maize and resolved specific expression signatures that will help define mechanisms of action for the RA3 gene. PMID:20833728

  15. Gene expression in periodontal tissues following treatment

    PubMed Central

    Beikler, Thomas; Peters, Ulrike; Prior, Karola; Eisenacher, Martin; Flemmig, Thomas F

    2008-01-01

    Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT) was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A), Versican (CSPG-2), Matrixmetalloproteinase-1 (MMP-1), Down syndrome critical region protein-1 (DSCR-1), Macrophage inflammatory protein-2? (Cxcl-3), Inhibitor of apoptosis protein-1 (BIRC-1), Cluster of differentiation antigen 38 (CD38), Regulator of G-protein signalling-1 (RGS-1), and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS); the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2), Complement component 3 (C3), Prostaglandin-endoperoxide synthase-2 (COX-2), Interleukin-8 (IL-8), Endothelin-1 (EDN-1), Plasminogen activator inhibitor type-2 (PAI-2), Matrix-metalloproteinase-14 (MMP-14), and Interferon regulating factor-7 (IRF-7). Conclusion Gene expression profiles found in periodontal tissues following therapy indicate activation of pathways that regulate tissue damage and repair. PMID:18606014

  16. A knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript.

    PubMed

    Ramani, Biswarathan; Harris, Ginny M; Huang, Rogerio; Seki, Takahiro; Murphy, Geoffrey G; Costa, Maria do Carmo; Fischer, Svetlana; Saunders, Thomas L; Xia, Guangbin; McEachin, Richard C; Paulson, Henry L

    2015-03-01

    Polyglutamine diseases, including spinocerebellar ataxia type 3 (SCA3), are caused by CAG repeat expansions that encode abnormally long glutamine repeats in the respective disease proteins. While the mechanisms underlying neurodegeneration remain uncertain, evidence supports a proteotoxic role for the mutant protein dictated in part by the specific genetic and protein context. To further define pathogenic mechanisms in SCA3, we generated a mouse model in which a CAG expansion of 82 repeats was inserted into the murine locus by homologous recombination. SCA3 knockin mice exhibit region-specific aggregate pathology marked by intranuclear accumulation of the mutant Atxn3 protein, abundant nuclear inclusions and, in select brain regions, extranuclear aggregates localized to neuritic processes. Knockin mice also display altered splicing of the disease gene, promoting expression of an alternative isoform in which the intron immediately downstream of the CAG repeat is retained. In an independent mouse model expressing the full human ATXN3 disease gene, expression of this alternatively spliced transcript is also enhanced. These results, together with recent findings in other polyglutamine diseases, suggest that CAG repeat expansions can promote aberrant splicing to produce potentially more aggregate-prone isoforms of the disease proteins. This report of a SCA3 knockin mouse expands the repertoire of existing models of SCA3, and underscores the potential contribution of alternative splicing to disease pathogenesis in SCA3 and other polyglutamine disorders. PMID:25320121

  17. Discovering Non-Redundant Overlapping Biclusters on Gene Expression Data

    E-print Network

    Battiti, Roberto

    Discovering Non-Redundant Overlapping Biclusters on Gene Expression Data Duy Tin Truong, Roberto--Given a gene expression data matrix where each cell is the expression level of a gene under a certain condition ex- pression data I. INTRODUCTION Gene expression is the process by which information from a gene

  18. From gene expression to gene regulatory networks in Arabidopsis thaliana

    PubMed Central

    Needham, Chris J; Manfield, Iain W; Bulpitt, Andrew J; Gilmartin, Philip M; Westhead, David R

    2009-01-01

    Background The elucidation of networks from a compendium of gene expression data is one of the goals of systems biology and can be a valuable source of new hypotheses for experimental researchers. For Arabidopsis, there exist several thousand microarrays which form a valuable resource from which to learn. Results A novel Bayesian network-based algorithm to infer gene regulatory networks from gene expression data is introduced and applied to learn parts of the transcriptomic network in Arabidopsis thaliana from a large number (thousands) of separate microarray experiments. Starting from an initial set of genes of interest, a network is grown by iterative addition to the model of the gene, from another defined set of genes, which gives the 'best' learned network structure. The gene set for iterative growth can be as large as the entire genome. A number of networks are inferred and analysed; these show (i) an agreement with the current literature on the circadian clock network, (ii) the ability to model other networks, and (iii) that the learned network hypotheses can suggest new roles for poorly characterized genes, through addition of relevant genes from an unconstrained list of over 15,000 possible genes. To demonstrate the latter point, the method is used to suggest that particular GATA transcription factors are regulators of photosynthetic genes. Additionally, the performance in recovering a known network from different amounts of synthetically generated data is evaluated. Conclusion Our results show that plausible regulatory networks can be learned from such gene expression data alone. This work demonstrates that network hypotheses can be generated from existing gene expression data for use by experimental biologists. PMID:19728870

  19. Regulation of meiotic gene expression in plants.

    PubMed

    Zhou, Adele; Pawlowski, Wojciech P

    2014-01-01

    With the recent advances in genomics and sequencing technologies, databases of transcriptomes representing many cellular processes have been assembled. Meiotic transcriptomes in plants have been studied in Arabidopsis thaliana, rice (Oryza sativa), wheat (Triticum aestivum), petunia (Petunia hybrida), sunflower (Helianthus annuus), and maize (Zea mays). Studies in all organisms, but particularly in plants, indicate that a very large number of genes are expressed during meiosis, though relatively few of them seem to be required for the completion of meiosis. In this review, we focus on gene expression at the RNA level and analyze the meiotic transcriptome datasets and explore expression patterns of known meiotic genes to elucidate how gene expression could be regulated during meiosis. We also discuss mechanisms, such as chromatin organization and non-coding RNAs that might be involved in the regulation of meiotic transcription patterns. PMID:25202317

  20. Expression of Polarity Genes in Human Cancer

    PubMed Central

    Lin, Wan-Hsin; Asmann, Yan W; Anastasiadis, Panos Z

    2015-01-01

    Polarity protein complexes are crucial for epithelial apical–basal polarity and directed cell migration. Since alterations of these processes are common in cancer, polarity proteins have been proposed to function as tumor suppressors or oncogenic promoters. Here, we review the current understanding of polarity protein functions in epithelial homeostasis, as well as tumor formation and progression. As most previous studies focused on the function of single polarity proteins in simplified model systems, we used a genomics approach to systematically examine and identify the expression profiles of polarity genes in human cancer. The expression profiles of polarity genes were distinct in different human tissues and classified cancer types. Additionally, polarity expression profiles correlated with disease progression and aggressiveness, as well as with identified cancer types, where specific polarity genes were commonly altered. In the case of Scribble, gene expression analysis indicated its common amplification and upregulation in human cancer, suggesting a tumor promoting function. PMID:25991909

  1. Regulation of meiotic gene expression in plants

    PubMed Central

    Zhou, Adele; Pawlowski, Wojciech P.

    2014-01-01

    With the recent advances in genomics and sequencing technologies, databases of transcriptomes representing many cellular processes have been assembled. Meiotic transcriptomes in plants have been studied in Arabidopsis thaliana, rice (Oryza sativa), wheat (Triticum aestivum), petunia (Petunia hybrida), sunflower (Helianthus annuus), and maize (Zea mays). Studies in all organisms, but particularly in plants, indicate that a very large number of genes are expressed during meiosis, though relatively few of them seem to be required for the completion of meiosis. In this review, we focus on gene expression at the RNA level and analyze the meiotic transcriptome datasets and explore expression patterns of known meiotic genes to elucidate how gene expression could be regulated during meiosis. We also discuss mechanisms, such as chromatin organization and non-coding RNAs that might be involved in the regulation of meiotic transcription patterns. PMID:25202317

  2. Control of gene expression by cell size

    E-print Network

    Wu, Chia-Yung

    2010-01-01

    Polyploidy, increased copy number of whole chromosome sets in the genome, is a common cellular state in evolution, development and disease. Polyploidy enlarges cell size and alters gene expression, producing novel phenotypes ...

  3. Facilitated diffusion buffers noise in gene expression

    E-print Network

    Schoech, Armin; Zabet, Nicolae Radu

    2014-09-02

    Transcription factors perform facilitated diffusion (3D diffusion in the cytosol and 1D diffusion on the DNA) when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise...

  4. Polyploidization and Gene Expression in Medicago sativa

    Microsoft Academic Search

    Stefano Capomaccio; Fabio Veronesi; Daniele Rosellini

    \\u000a Polyploidization is a common event in plant evolution and can influence economically important traits. Modifications of gene\\u000a expression and\\/or DNA sequence are known to occur as a consequence of polyploidization. To gain insight into the effects of\\u000a sexual polyploidization on gene expression in alfalfa, we have used two diploid (2x=16) plants of the subspecies falcata and coerulea that produce 2n

  5. Protein structure protection commits gene expression patterns

    Microsoft Academic Search

    Jianping Chen; Han Liang; Ariel Fernández

    2008-01-01

    BACKGROUND: Gene co-expressions often determine module-defining spatial and temporal concurrences of proteins. Yet, little effort has been devoted to tracing coordinating signals for expression correlations to the three-dimensional structures of gene products. RESULTS: We performed a global structure-based analysis of the yeast and human proteomes and contrasted this information against their respective transcriptome organizations obtained from comprehensive microarray data. We

  6. Deciphering Development: Quantifying Gene Expression through Imaging

    NSDL National Science Digital Library

    Melissa Lee Philips (; )

    2007-08-01

    This article from BioScience provides information on genetic tagging and how it can provide imaging in live animals. Scientists can now visualize developmental gene expression quantitatively in three dimensions and at single-cell resolution. Recent advances in optical microscopy and fluorescent genetic tags allow imaging of gene expression in live animals, as well. Eventually, researchers hope to construct virtual atlases of animal development.

  7. Homeobox genes expressed during echinoderm arm regeneration.

    PubMed

    Ben Khadra, Yousra; Said, Khaled; Thorndyke, Michael; Martinez, Pedro

    2014-04-01

    Regeneration in echinoderms has proved to be more amenable to study in the laboratory than the more classical vertebrate models, since the smaller genome size and the absence of multiple orthologs for different genes in echinoderms simplify the analysis of gene function during regeneration. In order to understand the role of homeobox-containing genes during arm regeneration in echinoderms, we isolated the complement of genes belonging to the Hox class that are expressed during this process in two major echinoderm groups: asteroids (Echinaster sepositus and Asterias rubens) and ophiuroids (Amphiura filiformis), both of which show an extraordinary capacity for regeneration. By exploiting the sequence conservation of the homeobox, putative orthologs of several Hox genes belonging to the anterior, medial, and posterior groups were isolated. We also report the isolation of a few Hox-like genes expressed in the same systems. PMID:24309817

  8. Relationship of gene expression and chromosomal abnormalities in colorectal cancer.

    PubMed

    Tsafrir, Dafna; Bacolod, Manny; Selvanayagam, Zachariah; Tsafrir, Ilan; Shia, Jinru; Zeng, Zhaoshi; Liu, Hao; Krier, Curtis; Stengel, Robert F; Barany, Francis; Gerald, William L; Paty, Philip B; Domany, Eytan; Notterman, Daniel A

    2006-02-15

    Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and gene expression have not been adequately explored nor globally monitored during the progression of the disease. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the disease. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are correlated with alterations in DNA content. Often, large chromosomal segments, containing multiple genes, are transcriptionally affected in a coordinated way, and we show that the underlying mechanism is a corresponding change in DNA content. This implies that whereas specific chromosomal abnormalities may arise stochastically, the associated changes in expression of some or all of the affected genes are responsible for selecting cells bearing these abnormalities for clonal expansion. Indeed, particular chromosomal regions are frequently gained and overexpressed (e.g., 7p, 8q, 13q, and 20q) or lost and underexpressed (e.g., 1p, 4, 5q, 8p, 14q, 15q, and 18) in primary colon tumors, making it likely that these changes favor tumorigenicity. Furthermore, we show that these aberrations are absent in normal colon mucosa, appear in benign adenomas (albeit only in a small fraction of the samples), become more frequent as disease advances, and are found in the majority of metastatic samples. PMID:16489013

  9. Consensus gene regulatory networks: combining multiple microarray gene expression datasets

    Microsoft Academic Search

    Emma Peeling; Allan Tucker

    2007-01-01

    In this paper we present a method for modelling gene regulatory networks by forming a consensus Bayesian network model from multiple microarray gene expression datasets. Our method is based on combining Bayesian network graph topologies and does not require any special pre-processing of the datasets, such as re-normalisation. We evaluate our method on a synthetic regulatory network and part of

  10. Sex-biased gene expression on the avian Z chromosome: highly expressed genes show higher male-biased expression.

    PubMed

    Naurin, Sara; Hasselquist, Dennis; Bensch, Staffan; Hansson, Bengt

    2012-01-01

    Dosage compensation, the process whereby expression of sex-linked genes remains similar between sexes (despite heterogamety) and balanced with autosomal expression, was long believed to be essential. However, recent research has shown that several lineages, including birds, butterflies, monotremes and sticklebacks, lack chromosome-wide dosage compensation mechanisms and do not completely balance the expression of sex-linked and autosomal genes. To obtain further understanding of avian sex-biased gene expression, we studied Z-linked gene expression in the brain of two songbirds of different genera (zebra finch, Taeniopygia guttata, and common whitethroat, Sylvia communis) using microarray technology. In both species, the male-bias in gene expression was significantly higher for Z than for autosomes, although the ratio of Z-linked to autosomal expression (Z:A) was relatively close to one in both sexes (range: 0.89-1.01). Interestingly, the Z-linked male-bias in gene expression increased with expression level, and genes with low expression showed the lowest degree of sex-bias. These results support the view that the heterogametic females have up-regulated their single Z-linked homologues to a high extent when the W-chromosome degraded and thereby managed to largely balance their Z:A expression with the exception of highly expressed genes. The male-bias in highly expressed genes points towards male-driven selection on Z-linked loci, and this and other possible hypotheses are discussed. PMID:23056488

  11. Quality control systems for aberrant mRNAs induced by aberrant translation elongation and termination.

    PubMed

    Inada, Toshifumi

    2013-01-01

    RNA processing is an essential gene expression step and plays a crucial role to achieve diversity of gene products in eukaryotes. Various aberrant mRNAs transiently produced during RNA processing reactions are recognized and eliminated by specific quality control systems. It has been demonstrated that these mRNA quality control systems stimulate the degradation of aberrant mRNA to prevent the potentially harmful products derived from aberrant mRNAs. Recent studies on quality control systems induced by abnormal translation elongation and termination have revealed that both aberrant mRNAs and proteins are subjected to rapid degradation. In NonStop Decay (NSD) quality control system, a poly(A) tail of nonstop mRNA is translated and the synthesis of poly-lysine sequence results in translation arrest followed by co-translational degradation of aberrant nonstop protein. In No-Go Decay (NGD) quality control system, the specific amino acid sequences of the nascent polypeptide induce ribosome stalling, and the arrest products are ubiquitinated and rapidly degraded by the proteasome. In Nonfunctional rRNA Decay (NRD) quality control system, aberrant ribosomes composed of nonfunctional ribosomal RNAs are also eliminated when aberrant translation elongation complexes are formed on mRNA. I describe recent progresses on the mechanisms of quality control systems and the relationships between quality control systems. This article is part of a Special issue entitled: RNA Decay mechanisms. PMID:23416749

  12. Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas.

    PubMed

    Dobashi, Yoh; Tsubochi, Hiroyoshi; Matsubara, Hirochika; Inoue, Jun; Inazawa, Johji; Endo, Shunsuke; Ooi, Akishi

    2015-06-01

    Emerging evidence confirms a central role of Akt in cancer. To evaluate the relative contribution of deregulated Akt and their clinicopathological significance in lung carcinomas, overexpression, activation of Akt and AKT gene increases were investigated. Immunohistochemical staining for 108 cases revealed overexpression of total Akt, Akt1, Akt2 and Akt3 in 61.1, 47.2, 40.7 and 23.1%, respectively, and phosphorylated Akt in 42.6% of cases. Expression of total Akt, Akt2 and Akt3 were frequently observed in small cell carcinoma, but phosphorylated Akt and Akt1 were more frequently observed in squamous cell carcinoma. FISH analysis to evaluate gene increases of AKT1-3 revealed amplification of AKT1 in 4.2% and AKT1 increase by polysomy of chromosome 14 in 27.3% of cases. For AKT2, amplification was observed in 3.2% and polysomy of chromosome 19 in 26.3% of cases. AKT3 increase was observed in 40.0% of cases only by polysomy of chromosome 1. Although "FISH-positive" AKT1 and AKT2 gene increases (amplification/high-level polysomy) were found exclusively in the cases overexpressing total Akt, Akt1 or Akt2, respectively, AKT3 increase was irrelevant of Akt3 expression. Statistically, expressions of Akt2, p-Akt and cytoplasmic-p-Akt were correlated with lymph node metastasis (P = 0.0479, P = 0.0371 and P = 0.0310, respectively). Although AKT1 and AKT2 gene increase showed positive correlation with, or trend towards a positive correlation with tumor size (P = 0.0430, P = 0.0590, respectively), AKT3 did not. In conclusion, Akt isoforms are differentially involved in the pathological phenotype of lung carcinoma in a diverse manner. Because abnormality of Akt1/AKT1 and Akt2/AKT2 correlated with clinicopathological profiles, Akt1/2-specific targeting may open a novel therapeutic window for the group showing Akt deregulation. PMID:25855050

  13. Mechanisms of control of gene expression

    SciTech Connect

    Cullen, B.; Gage, L.P.; Siddiqui, M.A.Q.; Skalka, A.M.; Weissbach, H.

    1987-01-01

    This book examines an array of topics on the regulation of gene expression, including an examination of DNA-protein interactions and the role of oncogene proteins in normal and abnormal cellular responses. The book focuses on the control of mRNA transcription in eykaryotes and delineates other areas including gene regulation in prokaryotes and control of stable RNA synthesis.

  14. Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension.

    PubMed

    Gu, Song; Li, Guanghui; Zhang, Xitao; Yan, Jun; Gao, Jie; An, Xiangguang; Liu, Yan; Su, Pixiong

    2015-04-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the primary causes of severe pulmonary hypertension. In order to identify long noncoding RNAs (lncRNAs) that may be involved in the development of CTEPH, comprehensive lncRNA and messenger RNA (mRNA) profiling of endothelial tissues from the pulmonary arteries of CTEPH patients was conducted with microarray analysis. Differential expression of 185 lncRNAs was observed in the CTEPH tissues compared with healthy control tissues. Further analysis identified 464 regulated enhancer?like lncRNAs and overlapping, antisense or nearby mRNA pairs. Coexpression networks were subsequently constructed and investigated. The expression levels of the lncRNAs, NR_036693, NR_027783, NR_033766 and NR_001284, were significantly altered. Gene ontology and pathway analysis demonstrated the potential role of lncRNAs in the regulation of central process, including inflammatory response, response to endogenous stimulus and antigen processing and presentation. The use of bioinformatics may help to uncover and analyze large quantities of data identified by microarray analyses, through rigorous experimental planning, statistical analysis and the collection of more comprehensive data regarding CTEPH. The results of the present study provided evidence which may be helpful in future studies on the diagnosis and management of CTEPH. PMID:25522749

  15. Gene expression profiles of giant hairy naevi

    PubMed Central

    Dasu, M R K; Barrow, R E; Hawkins, H K; McCauley, R L

    2004-01-01

    Background: Congenital neomelanocytic naevi appear in nearly 1% of newborns. Giant hairy naevi (GHN) are uncommon lesions covering large areas of the body. They are of concern because they have the potential to transform into malignant melanomas. Aims: To describe gene expression profiles of GHN and nearby normal skin from patients with GHN and normal control skin (from patients with cleft lip/palate). Methods: Tissues from three patients with GHN and two normal controls were studied for differences in gene expression profiles. Total RNA was isolated from normal skin near the hairy naevus, GHN, and skin from normal controls. The RNA samples were subjected to probe labelling, hybridisation to chips, and image acquisition according to the standard Affymetrix protocol. Results: There were 227 genes affected across all samples, as determined by DNA microarray analysis. There was increased expression of 22 genes in GHN compared with nearby normal skin. Decreased expression was noted in 73 genes. In addition, there was increased expression of 36 genes in normal skin near GHN compared with normal control skin, and decreased expression of five genes. Categories of genes affected were those encoding structural proteins, proteins related to developmental processes, cell death associated proteins, transcription factors, growth factors, stress response modulators, and collagen associated proteins. Changes in mRNA expression were checked by reverse transcription polymerase chain reaction. Conclusions: Genetic profiles of GHN may provide insight into their pathogenesis, including their potential for malignant transformation. Such information may be useful in improving the understanding and management of these lesions. PMID:15280407

  16. Development of a novel approach, the epigenome-based outlier approach, to identify tumor-suppressor genes silenced by aberrant DNA methylation.

    PubMed

    Kikuyama, Mizuho; Takeshima, Hideyuki; Kinoshita, Takayuki; Okochi-Takada, Eriko; Wakabayashi, Mika; Akashi-Tanaka, Sadako; Ogawa, Toshihisa; Seto, Yasuyuki; Ushijima, Toshikazu

    2012-09-28

    Identification of tumor-suppressor genes (TSGs) silenced by aberrant methylation of promoter CpG islands (CGIs) is important, but hampered by a large number of genes methylated as passengers of carcinogenesis. To overcome this issue, we here took advantage of the fact that the vast majority of genes methylated in cancers lack, in normal cells, RNA polymerase II (Pol II) and have trimethylation of histone H3 lysine 27 (H3K27me3) in their promoter CGIs. First, we demonstrated that three of six known TSGs in breast cancer and two of three in colon cancer had Pol II and lacked H3K27me3 in normal cells, being outliers to the general rule. BRCA1, HOXA5, MLH1, and RASSF1A had high Pol II, but were expressed only at low levels in normal cells, and were unlikely to be identified as outliers by their expression statuses in normal cells. Then, using epigenome statuses (Pol II binding and H3K27me3) in normal cells, we made a genome-wide search for outliers in breast cancers, and identified 14 outlier promoter CGIs. Among these, DZIP1, FBN2, HOXA5, and HOXC9 were confirmed to be methylated in primary breast cancer samples. Knockdown of DZIP1 in breast cancer cell lines led to increases of their growth, suggesting it to be a novel TSG. The outliers based on their epigenome statuses contained unique TSGs, including DZIP1, compared with those identified by the expression microarray data. These results showed that the epigenome-based outlier approach is capable of identifying a different set of TSGs, compared to the expression-based outlier approach. PMID:22433712

  17. SAGEmap: A Public Gene Expression Resource

    PubMed Central

    Lash, Alex E.; Tolstoshev, Carolyn M.; Wagner, Lukas; Schuler, Gregory D.; Strausberg, Robert L.; Riggins, Gregory J.; Altschul, Stephen F.

    2000-01-01

    We have constructed a public gene expression data repository and online data access and analysis, WWW and FTP sites for serial analysis of gene expression (SAGE) data. The WWW and FTP components of this resource, SAGEmap, are located at http://www.ncbi.nlm.nih.gov/sage and ftp://ncbi.nlm.nih.gov/pub/sage, respectively. We herein describe SAGE data submission procedures, the construction and characteristics of SAGE tags to gene assignments, the derivation and use of a novel statistical test designed specifically for differential-type analyses of SAGE data, and the organization and use of this resource. PMID:10899154

  18. Reference gene screening for analyzing gene expression across goat tissue.

    PubMed

    Zhang, Yu; Zhang, Xiao-Dong; Liu, Xing; Li, Yun-Sheng; Ding, Jian-Ping; Zhang, Xiao-Rong; Zhang, Yun-Hai

    2013-12-01

    Real-time quantitative PCR (qRT-PCR) is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2) in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken. PMID:25049756

  19. Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy

    PubMed Central

    Serino, Grazia; Sallustio, Fabio; Cox, Sharon N.; Pesce, Francesco

    2012-01-01

    Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA nephropathy. The mechanisms underlying this abnormal glycosylation are not well understood, but reduced expression of the enzyme core 1, ?1,3-galactosyltransferase 1 (C1GALT1) may contribute. In this study, high-throughput microRNA (miRNA) profiling identified 37 miRNAs differentially expressed in PBMCs of patients with IgA nephropathy compared with healthy persons. Among them, we observed upregulation of miR-148b, which potentially targets C1GALT1. Patients with IgA nephropathy exhibited lower C1GALT1 expression, which negatively correlated with miR-148b expression. Transfection of PBMCs from healthy persons with a miR-148b mimic reduced endogenous C1GALT1 mRNA levels threefold. Conversely, loss of miR-148b function in PBMCs of patients with IgA nephropathy increased C1GALT1 mRNA and protein levels to those observed in healthy persons. Moreover, we found that upregulation of miR-148b directly correlated with levels of galactose-deficient IgA1. In vitro, we used an IgA1-producing cell line to confirm that miR-148b modulates IgA1 O-glycosylation and the levels of secreted galactose-deficient IgA1. Taken together, these data suggest a role for miRNAs in the pathogenesis of IgA nephropathy. Abnormal expression of miR-148b may explain the aberrant glycosylation of IgA1, providing a potential pharmacologic target for IgA nephropathy. PMID:22362909

  20. Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expression

    Microsoft Academic Search

    Mehmet Avci; Ozlen Konu; Tamer Yagci

    2008-01-01

    BACKGROUND: SLIT-ROBO families of proteins mediate axon pathfinding and their expression is not solely confined to nervous system. Aberrant expression of SLIT-ROBO genes was repeatedly shown in a wide variety of cancers, yet data about their collective behavior in hepatocellular carcinoma (HCC) is missing. Hence, we quantified SLIT-ROBO transcripts in HCC cell lines, and in normal and tumor tissues from

  1. Transient gene expression of foreign genes in preheated protoplasts: stimulation of expression of transfected genes lacking heat shock elements

    Microsoft Academic Search

    Nehama Zakai; Nurit Ballas; Maty Hershkovitz; Shimshon Broido; Raquel Ram; Abraham Loyter

    1993-01-01

    Transfection of preheated petunia protoplasts with several biologically active DNA constructs resulted in a significantly higher gene expression than that observed in transfected unheated protoplasts. It was observed with supercoiled, linearized and single-stranded DNA structures that stimulation of transient gene expression in preheated protoplasts was neither dependent on the reporter gene nor on the regulatory elements used. Heat treatment at

  2. Identifying Complex Biological Interactions based on Categorical Gene Expression Data

    Microsoft Academic Search

    Ben Goertzel; Cassio Pennachin; L. de Souza Coelho; M. Mudado

    2006-01-01

    A novel method, MUTIC (model utilization-based clustering), is described for identifying complex interactions between genes or gene-categories based on gene expression data. The method deals with binary categorical data, which consists of a set of gene expression profiles divided into two biologically meaningful categories. It does not require data from multiple time points. Gene expression profiles are represented by feature

  3. Selective Gene Expression in Multigene Families from Yeast to Mammals

    NSDL National Science Digital Library

    Jacob Z. Dalgaard (Marie Curie Research Institute; REV)

    2004-10-26

    Cell identity is the direct consequence of the genes expressed. This STKE Review highlights the diverse mechanisms that cells use to achieve exclusive gene expression. The details of the molecular mechanism underlying yeast mating-type switching are compared and contrasted with the mechanisms involved in immunoglobulin gene expression and odorant receptor gene expression in mammals.

  4. Gene Expression Analyses and Association Studies of Wood Development Genes in Loblolly Pine (Pinus taeda L.) 

    E-print Network

    Palle, Sreenath Reddy

    2011-10-21

    RT-PCR, there were significant differences in expression among clones for 106 genes. Candidate-gene based association studies were performed between 3937 single nucleotide polymorphisms (SNPs) and gene expression to associate SNPs in candidate genes...

  5. Aberrant Promoter Methylation Profile of Niemann-Pick Type C1 Gene in Cardiovascular Disease

    PubMed Central

    Afzali, Masoumeh; Nakhaee, Alireza; Tabatabaei, Seyed Payman; Tirgar-Fakheri, Kourosh; Hashemi, Mohammad

    2013-01-01

    Background: The protein of Niemann-pick type C1 (NPC1) gene promotes the egress of cholesterol from late endosomes and lysosomes to other cellular compartments and contributes to a process known as reverse cholesterol transport. This study aimed to examine whether promoter methylation of NPC1 is associated with risk of cardiovascular disease (CVD). Methods: Fifty CVD patients and 50 healthy subjects as the control group were recruited in this study. Promoter methylation of NPC1 gene was defined using a nested-methylation specific polymerase chain reaction method. Statistical analyses were done using the chi-square, t-test or ANOVA tests. Results: Our study showed that the frequency of semi-methylated promoter (methylated/unmethylated status) was significantly higher in CVD patients than that in controls (OR = 6.521, 95% CI = 2.211-19.215, P = 0.008). However, a completely methylated promoter (methylated/methylated status) was not detected in any subjects in either of the two groups tested. Additionally, the analysis of clinical data according to the methylation status of NPC1 gene demonstrated that serum levels of total cholesterol, total triglycerides, high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) are influenced by NPC1 methylation, so that subjects with a completely unmethylated promoter (Unmethylated/unmethylated status) held lower levels of total triglycerides, total cholesterol, LDL-C and higher levels of HDL-C. Conclusion: Our findings propose that the NPC1 promoter methylation is a probable mechanism that can result in reduced/impaired NPC1 expression/activity and may thus contribute to progression of CVD. PMID:23567849

  6. Potassium Channel Ether à go-go1 Is Aberrantly Expressed in Human Liposarcoma and Promotes Tumorigenesis

    PubMed Central

    Wu, Jin; Zhong, Daixing; Wei, Yujian; Wu, Xinyu; Kang, Liangqi; Ding, Zhenqi

    2014-01-01

    The ether à go-go1 (Eag1) channel is overexpressed in a variety of cancers. However, the expression and function of Eag1 in liposarcoma are poorly understood. In the present study, the mRNA expression of Eag1 in different adipose tissue samples was examined by real-time PCR. Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry. Next, the associations between Eag1 expression and clinicopathological features of liposarcoma were analyzed. In addition, the effects of Eag1 on liposarcoma cell proliferation and cycle were evaluated by CCK-8, colony formation, xenograft mouse model, and flow cytometry, respectively. Finally, the activation of p38 mitogen-activated protein kinase (MAPK) was detected by Western blot analysis to explain the detailed mechanisms of oncogenic potential of Eag1 in liposarcoma. It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues. However, Eag1 expression was not correlated with clinicopathological features of liposarcoma. Eag1 inhibitor imipramine or Eag1-shRNA significantly suppressed the proliferation of liposarcoma cells in vitro and in vivo, accompanying with accumulation of cells in the G1 phase. These results suggest that Eag1 plays an important role in regulating the proliferation and cell cycle of liposarcoma cells and might be a potential therapeutic target for liposarcoma. PMID:25136578

  7. Extracting expression modules from perturbational gene expression compendia

    Microsoft Academic Search

    Steven Maere; Patrick Van Dijck; Martin Kuiper

    2008-01-01

    Background  Compendia of gene expression profiles under chemical and genetic perturbations constitute an invaluable resource from a systems\\u000a biology perspective. However, the perturbational nature of such data imposes specific challenges on the computational methods\\u000a used to analyze them. In particular, traditional clustering algorithms have difficulties in handling one of the prominent\\u000a features of perturbational compendia, namely partial coexpression relationships between genes.

  8. Measurement of bacterial gene expression in vivo.

    PubMed Central

    Hautefort, I; Hinton, J C

    2000-01-01

    The complexities of bacterial gene expression during mammalian infection cannot be addressed by in vitro experiments. We know that the infected host represents a complex and dynamic environment, which is modified during the infection process, presenting a variety of stimuli to which the pathogen must respond if it is to be successful. This response involves hundreds of ivi (in vivo-induced) genes which have recently been identified in animal and cell culture models using a variety of technologies including in vivo expression technology, differential fluorescence induction, subtractive hybridization and differential display. Proteomic analysis is beginning to be used to identify IVI proteins, and has benefited from the availability of genome sequences for increasing numbers of bacterial pathogens. The patterns of bacterial gene expression during infection remain to be investigated. Are ivi genes expressed in an organ-specific or cell-type-specific fashion? New approaches are required to answer these questions. The uses of the immunologically based in vivo antigen technology system, in situ PCR and DNA microarray analysis are considered. This review considers existing methods for examining bacterial gene expression in vivo, and describes emerging approaches that should further our understanding in the future. PMID:10874733

  9. Human AZU-1 gene, variants thereof and expressed gene products

    DOEpatents

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

    A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

  10. Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1 and Hippo Pathway Genes

    PubMed Central

    Dhanasekaran, Saravana M.; Balbin, O. Alejandro; Chen, Guoan; Nadal, Ernest; Kalyana-Sundaram, Shanker; Pan, Jincheng; Veeneman, Brendan; Cao, Xuhong; Malik, Rohit; Vats, Pankaj; Wang, Rui; Huang, Stephanie; Zhong, Jinjie; Jing, Xiaojun; Iyer, Matthew; Wu, Yi-Mi; Harms, Paul W.; Lin, Jules; Reddy, Rishindra; Brennan, Christine; Palanisamy, Nallasivam; Chang, Andrew C.; Truini, Anna; Truini, Mauro; Robinson, Dan R.; Beer, David G.; Chinnaiyan, Arul M.

    2014-01-01

    Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here, we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyze 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumors without known driver mutations. In addition, we observe exon skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations. PMID:25531467

  11. Array analysis of epilepsy-associated gangliogliomas reveals expression patterns related to aberrant development of neuronal precursors

    Microsoft Academic Search

    Jana Fassunke; Michael Majores; Achim Tresch; Pitt Niehusmann; Alexander Grote; Susanne Schoch; Albert J. Becker

    2008-01-01

    Gangliogliomas, the most frequent neoplasms in patients with pharmacoresistant focal epilepsies, are charac- terized by histological combinations of glial and dysplastic neuronal elements, a highly differentiated phenotype and rare gene mutations.Their molecular basis and relationship to other low-grade brain tumours are not com- pletely understood. Systematic investigations of altered gene expression in gangliogliomas have been hampered by their cellular complexity,

  12. Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology.

    PubMed

    Mehta, Divya; Iwamoto, Kazuya; Ueda, Junko; Bundo, Miki; Adati, Naoki; Kojima, Toshio; Kato, Tadafumi

    2014-02-01

    Copy number variations (CNVs) contribute to neuropsychiatric diseases, which may be partly mediated by their effects on gene expression. However, few studies have assessed the influence of CNVs on gene expression in the brain. The objective was to perform an unbiased comprehensive survey of influence of CNVs on gene expression in human brain tissues. CNV regions (CNVRs) were identified in 72 individuals (23 schizophrenia, 23 bipolar disorder and 26 controls). Significant associations between the CNVRs and gene expression levels were observed for 583 CNVR-expression probe pairs (293 unique eCNVRs and 429 unique transcripts), after corrections for multiple testing and controlling the effect of the number of subjects with CNVRs by label swapping permutations. These CNVRs affecting gene expression (eCNVRs) were significantly enriched for rare/low frequency (p=1.087×10(-10)) and gene-harboring CNVRs (p=1.4×10(-6)). Transcripts overlapping CNVRs were significantly enriched for glutathione metabolism and oxidative stress only for cases but not for controls. Moreover, 72 (24.6%) of eCNVRs were located within the chromosomal aberration regions implicated in psychiatric-disorders: 16p11.2, 1q21.1, 22q11.2, 3q29, 15q11.2, 17q12 and 16p13.1. These results shed light on the mechanism of how CNVs confer a risk for psychiatric disorders. PMID:24211644

  13. Heterelogous Expression of Plant Genes

    PubMed Central

    Yesilirmak, Filiz; Sayers, Zehra

    2009-01-01

    Heterologous expression allows the production of plant proteins in an organism which is simpler than the natural source. This technology is widely used for large-scale purification of plant proteins from microorganisms for biochemical and biophysical analyses. Additionally expression in well-defined model organisms provides insights into the functions of proteins in complex pathways. The present review gives an overview of recombinant plant protein production methods using bacteria, yeast, insect cells, and Xenopus laevis oocytes and discusses the advantages of each system for functional studies and protein characterization. PMID:19672459

  14. CLUSTERING GENE EXPRESSION PROFILES USING MIXTURE MODEL ENSEMBLE AVERAGING APPROACH

    Microsoft Academic Search

    FAMING LIANG; Texas A

    2008-01-01

    Clustering has been an important tool for extracting underlying gene expression patterns from massive microarray data. However, most of the existing clustering methods cannot automatically separate noise genes, including scattered, singleton and mini-cluster genes, from other genes. Inclusion of noise genes into regular clustering processes can impede identification of gene expression patterns. The model-based clustering method has the potential to

  15. Identification of differentially expressed genes by restriction endonuclease-based gene expression fingerprinting.

    PubMed

    Ivanova, N B; Belyavsky, A V

    1995-08-11

    A novel method for identification of differentially expressed genes has been developed. It is based on the consecutive restriction digestions of 3' terminal cDNA fragments to produce a fingerprint of gene expression. cDNA molecules are synthesized using a biotinylated oligo(dT) primer, digested with a frequently cutting restriction endonuclease and the 3'-terminal restriction fragments are isolated using streptavidin microbeads. After amplification by PCR, cDNA fragments are immobilized again on streptavidin beads, radiolabeled and treated sequentially with a set of restriction endonucleases. The products of individual enzymatic reactions from two or more different RNA populations are resolved by polyacrylamide gel electrophoresis and compared to reveal differentially expressed genes. This strategy enabled us to identify and clone the fragments of five genes expressed differentially in murine thymus and spleen. One of the genes was found to encode terminal deoxynucleotidyl transferase; others are apparently previously unknown genes. PMID:7659517

  16. Identifying pair-wise gene functional similarity by multiplex gene expression maps and supervised learning

    E-print Network

    Obradovic, Zoran

    Identifying pair-wise gene functional similarity by multiplex gene expression maps and supervised and gene expression profiles in the mammalian brain. However, little attention has been paid to the location information of a gene's expressions. Gene expression maps, which contain spatial information

  17. Supervised Model for Identifying Differentially Expressed Genes in DNA Microarray Gene Expression Dataset Using Biological Pathway Information

    Microsoft Academic Search

    Tae Su Chung; Keewon Kim; Ju Han Kim

    2005-01-01

    Microarray technology makes it possible to measure the expressions of tens of thousands of genes simultaneously under various experimental conditions. Identifying differentially expressed genes in each single experimental condition is one of the most common first steps in microarray gene expression data analysis. Reasonable choices of thresholds for determining differentially expressed genes are used for the next-step-analysis with suitable statistical

  18. A REVIEW OF NUCLEAR RECEPTOR GENE ACTIVATION THROUGH COFACTOR PROTEIN INTERACTIONS

    E-print Network

    Baker, Robert L.

    2008-07-07

    cause of these pathologies. Certain aspects of the aforementioned diseases have been linked to the aberrant expression and activity of selected gene-expression-programs. Gene expression is regulated by proteins known as transcription factors. One...

  19. Gene expression profiles in irradiated cancer cells

    NASA Astrophysics Data System (ADS)

    Minafra, L.; Bravatà, V.; Russo, G.; Ripamonti, M.; Gilardi, M. C.

    2013-07-01

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses.

  20. Parsimonious Selection of Useful Genes in Microarray Gene Expression Data

    Microsoft Academic Search

    Félix F. González-Navarro; Lluís A. Belanche-Muñoz

    \\u000a Machine learning methods have of late made significant efforts to solving multidisciplinary problems in the field of cancer\\u000a classification in microarray gene expression data. These tasks are characterized by a large number of features and a few observations,\\u000a making the modeling a nontrivial undertaking. In this study, we apply entropic filter methods for gene selection, in combination\\u000a with several off-the-shelf

  1. Anaerobic Gene Expression in Staphylococcus aureus? †

    PubMed Central

    Fuchs, Stephan; Pané-Farré, Jan; Kohler, Christian; Hecker, Michael; Engelmann, Susanne

    2007-01-01

    An investigation of gene expression in Staphylococcus aureus after a switch from aerobic to anaerobic growth was initiated by using the proteomic and transcriptomic approaches. In the absence of external electron acceptors like oxygen or nitrate, an induction of glycolytic enzymes was observed. At the same time the amount of tricarboxylic acid cycle enzymes was very low. NAD is regenerated by mixed acid and butanediol fermentation, as indicated by an elevated synthesis level of fermentation enzymes like lactate dehydrogenases (Ldh1 and Ldh2), alcohol dehydrogenases (AdhE and Adh), ?-acetolactate decarboxylase (BudA1), acetolactate synthase (BudB), and acetoin reductase (SACOL0111) as well as an accumulation of fermentation products as lactate and acetate. Moreover, the transcription of genes possibly involved in secretion of lactate (SACOL2363) and formate (SACOL0301) was found to be induced. The formation of acetyl-coenzyme A or acetyl-phosphate might be catalyzed by pyruvate formate lyase, whose synthesis was found to be strongly induced as well. Although nitrate was not present, the expression of genes related to nitrate respiration (NarH, NarI, and NarJ) and nitrate reduction (NirD) was found to be upregulated. Of particular interest, oxygen concentration might affect the virulence properties of S. aureus by regulating the expression of some virulence-associated genes such as pls, hly, splC and splD, epiG, and isaB. To date, the mechanism of anaerobic gene expression in S. aureus has not been fully characterized. In addition to srrA the mRNA levels of several other regulatory genes with yet unknown functions (e.g., SACOL0201, SACOL2360, and SACOL2658) were found to be upregulated during anaerobic growth, indicating a role in the regulation of anaerobic gene expression. PMID:17384184

  2. Mapping of sex-linked genes onto the genome sequence using various aberrations of the Z chromosome in Bombyx mori.

    PubMed

    Fujii, Tsuguru; Abe, Hiroaki; Katsuma, Susumu; Mita, Kazuei; Shimada, Toru

    2008-12-01

    Many strains of Bombyx mori carry chromosomal aberrations, and they are useful resources for integration between phenotypes and genomic sequences. We compared the molecular structures of three kinds of Z chromosomes, i.e., two strains with chromosome deletions and one strain with translocation involving the Z chromosome. Using polymerase chain reaction markers, we showed that: (1) the Z(1) chromosome lacks more than 6Mb, including the proximal end; (2) the Z(Vg) chromosome lacks 1.5Mb in the interstitial portion; and (3) the +(od)p(Sa)+(p)W carries a 0.6-Mb Z-derived fragment surrounding the +(od) gene. The breakpoint junctions of these deletions and a translocation were precisely determined. Through deletion mapping, we narrowed down the regions where distinct oily (od), vestigial (Vg), and muscle dystrophy (Md) are located and identified a candidate gene for od. A retroposon-mediated deletion in BmBLOS2--the Bombyx gene homologous to human "biogenesis of lysosome-related organelles complex-1, subunit 2''--was detected in the od mutant. Although the genes responsible for Vg and Md were not definitively identified, we propose the candidate genes on the basis of their locations and phenotypes. PMID:19216995

  3. Bayesian Networks Learning for Gene Expression Datasets

    Microsoft Academic Search

    Giacomo Gamberoni; Evelina Lamma; Fabrizio Riguzzi; Sergio Storari; Stefano Volinia

    2005-01-01

    \\u000a DNA arrays yield a global view of gene expression and can be used to build genetic networks models, in order to study relations\\u000a between genes. Literature proposes Bayesian network as an appropriate tool for develop similar models. In this paper, we exploit\\u000a the contribute of two Bayesian network learning algorithms to generate genetic networks from microarray datasets of experiments\\u000a performed

  4. Heregulin regulates Prolactinoma Gene Expression

    PubMed Central

    Vlotides, George; Cooper, Odelia; Chen, Yen-Hao; Ren, Song-Guang; Greenman, Yona; Melmed, Shlomo

    2009-01-01

    To investigate the role of p185her2/neu / ErbB3 signaling in pituitary tumor function we examined these receptors in human prolactinomas. Immunofluorescent p185her2/neu was detected in almost all (7/8), and ErbB3 expression in a subset (4/8) of tumors (7 adenomas and one carcinoma). Quantitative PCR also showed abundant ErbB3 mRNA in tumor specimens derived from a rarely encountered prolactin-cell carcinoma. Activation of p185c-neu / ErbB3 signaling with heregulin, the ErbB3 ligand, in rat lactosomatotroph (GH4C1) tumor cells specifically induced prolactin (PRL) mRNA expression ~ 5-fold and PRL secretion ~ 4-fold, while growth hormone (GH) expression was unchanged. Heregulin (6 nM) induced tyrosine phosphorylation and ErbB3 and p185c-neu heterodimerization, with subsequent activation of intracellular ERK and Akt. The Akt signal was specific to ErbB3 activation by heregulin, and was not observed in response to EGF activation of EGFR. Gefitinib, the tyrosine kinase inhibitor, suppressed heregulin-mediated p185c-neu / ErbB3 signaling to PRL. Heregulin induction of PRL was also abrogated by transfecting cells with siRNA directed against ErbB3. Pharmacological inhibition of heregulin-induced PI3K / Akt (with LY294002) and ERK (with U0126) signaling, as well as siRNA-mediated MAPK1 downregulation showed ERK signaling as the primary transducer of heregulin signaling to PRL. These results demonstrate ErbB3 expression in human prolactinomas and a novel ErbB3-mediated mechanism for PRL regulation in experimental lactotroph tumors. Targeted inhibition of upregulated p185c-neu / ErbB3 activity could be useful for the treatment of aggressive prolactinomas resistant to conventional therapy. PMID:19401448

  5. Relationship of eukaryotic DNA replication to committed gene expression: general theory for gene control.

    PubMed Central

    Villarreal, L P

    1991-01-01

    The historic arguments for the participation of eukaryotic DNA replication in the control of gene expression are reconsidered along with more recent evidence. An earlier view in which gene commitment was achieved with stable chromatin structures which required DNA replication to reset expression potential (D. D. Brown, Cell 37:359-365, 1984) is further considered. The participation of nonspecific stable repressor of gene activity (histones and other chromatin proteins), as previously proposed, is reexamined. The possible function of positive trans-acting factors is now further developed by considering evidence from DNA virus models. It is proposed that these positive factors act to control the initiation of replicon-specific DNA synthesis in the S phase (early or late replication timing). Stable chromatin assembles during replication into potentially active (early S) or inactive (late S) states with prevailing trans-acting factors (early) or repressing factors (late) and may asymmetrically commit daughter templates. This suggests logical schemes for programming differentiation based on replicons and trans-acting initiators. This proposal requires that DNA replication precede major changes in gene commitment. Prior evidence against a role for DNA replication during terminal differentiation is reexamined along with other results from terminal differentiation of lower eukaryotes. This leads to a proposal that DNA replication may yet underlie terminal gene commitment, but that for it to do so there must exist two distinct modes of replication control. In one mode (mitotic replication) replicon initiation is tightly linked to the cell cycle, whereas the other mode (terminal replication) initiation is not cell cycle restricted, is replicon specific, and can lead to a terminally differentiated state. Aberrant control of mitotic and terminal modes of DNA replication may underlie the transformed state. Implications of a replicon basis for chromatin structure-function and the evolution of metazoan organisms are considered. Images PMID:1943999

  6. Intracellular Gene Expression Profile of Listeria monocytogenes †

    PubMed Central

    Chatterjee, Som Subhra; Hossain, Hamid; Otten, Sonja; Kuenne, Carsten; Kuchmina, Katja; Machata, Silke; Domann, Eugen; Chakraborty, Trinad; Hain, Torsten

    2006-01-01

    Listeria monocytogenes is a gram-positive, food-borne microorganism responsible for invasive infections with a high overall mortality. L. monocytogenes is among the very few microorganisms that can induce uptake into the host cell and subsequently enter the host cell cytosol by breaching the vacuolar membrane. We infected the murine macrophage cell line P388D1 with L. monocytogenes strain EGD-e and examined the gene expression profile of L. monocytogenes inside the vacuolar and cytosolic environments of the host cell by using whole-genome microarray and mutant analyses. We found that ?17% of the total genome was mobilized to enable adaptation for intracellular growth. Intracellularly expressed genes showed responses typical of glucose limitation within bacteria, with a decrease in the amount of mRNA encoding enzymes in the central metabolism and a temporal induction of genes involved in alternative-carbon-source utilization pathways and their regulation. Adaptive intracellular gene expression involved genes that are associated with virulence, the general stress response, cell division, and changes in cell wall structure and included many genes with unknown functions. A total of 41 genes were species specific, being absent from the genome of the nonpathogenic Listeria innocua CLIP 11262 strain. We also detected 25 genes that were strain specific, i.e., absent from the genome of the previously sequenced L. monocytogenes F2365 serotype 4b strain, suggesting heterogeneity in the gene pool required for intracellular survival of L. monocytogenes in host cells. Overall, our study provides crucial insights into the strategy of intracellular survival and measures taken by L. monocytogenes to escape the host cell responses. PMID:16428782

  7. Genes Expressed in Human Tumor Endothelium

    NASA Astrophysics Data System (ADS)

    St. Croix, Brad; Rago, Carlo; Velculescu, Victor; Traverso, Giovanni; Romans, Katharine E.; Montgomery, Elizabeth; Lal, Anita; Riggins, Gregory J.; Lengauer, Christoph; Vogelstein, Bert; Kinzler, Kenneth W.

    2000-08-01

    To gain a molecular understanding of tumor angiogenesis, we compared gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. Of over 170 transcripts predominantly expressed in the endothelium, 79 were differentially expressed, including 46 that were specifically elevated in tumor-associated endothelium. Several of these genes encode extracellular matrix proteins, but most are of unknown function. Most of these tumor endothelial markers were expressed in a wide range of tumor types, as well as in normal vessels associated with wound healing and corpus luteum formation. These studies demonstrate that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.

  8. Gene Discovery Methods from Large-Scale Gene Expression Data

    NASA Astrophysics Data System (ADS)

    Shimizu, Akifumi; Yano, Kentaro

    2010-01-01

    Microarrays provide genome-wide gene expression changes. In current analyses, the majority of genes on the array are frequently eliminated for further analysis just in order for computational effort to be affordable. This strategy risks failure to discover whole sets of genes related to a quantitative trait of interest, which is generally controlled by several loci that might be eliminated in current approaches. Here, we describe a high-throughput gene discovery method based on correspondence analysis with a new index for expression ratios [arctan (1/ratio)] and three artificial marker genes. This method allows us to quickly analyze the whole microarray dataset without elimination and discover up/down-regulated genes related to a trait of interest. We employed an example dataset to show the theoretical advantage of this method. We then used the method to identify 88 cancer-related genes from a published microarray data from patients with breast cancer. This method can be easily performed and the result is also visible in three-dimensional viewing software that we have developed. Our method is useful for revaluating the wealth of microarray data available from web-sites.

  9. Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers.

    PubMed

    Tomii, Kunitoshi; Tsukuda, Kazunori; Toyooka, Shinichi; Dote, Hideaki; Hanafusa, Tadashi; Asano, Hiroaki; Naitou, Minoru; Doihara, Hiroyoshi; Kisimoto, Takumi; Katayama, Hideki; Pass, Harvery I; Date, Hiroshi; Shimizu, Nobuyoshi

    2007-02-01

    Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p < 0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined. PMID:17096329

  10. Annotation of gene function in citrus using gene expression information and co-expression networks

    PubMed Central

    2014-01-01

    Background The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world’s most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a “guilt-by-association” principle whereby genes encoding proteins involved in similar and/or related biological processes may exhibit similar expression patterns across diverse sets of experimental conditions. While bioinformatics resources such as GCN analysis are widely available for efficient gene function prediction in model plant species including Arabidopsis, soybean and rice, in citrus these tools are not yet developed. Results We have constructed a comprehensive GCN for citrus inferred from 297 publicly available Affymetrix Genechip Citrus Genome microarray datasets, providing gene co-expression relationships at a genome-wide scale (33,000 transcripts). The comprehensive citrus GCN consists of a global GCN (condition-independent) and four condition-dependent GCNs that survey the sweet orange species only, all citrus fruit tissues, all citrus leaf tissues, or stress-exposed plants. All of these GCNs are clustered using genome-wide, gene-centric (guide) and graph clustering algorithms for flexibility of gene function prediction. For each putative cluster, gene ontology (GO) enrichment and gene expression specificity analyses were performed to enhance gene function, expression and regulation pattern prediction. The guide-gene approach was used to infer novel roles of genes involved in disease susceptibility and vitamin C metabolism, and graph-clustering approaches were used to investigate isoprenoid/phenylpropanoid metabolism in citrus peel, and citric acid catabolism via the GABA shunt in citrus fruit. Conclusions Integration of citrus gene co-expression networks, functional enrichment analysis and gene expression information provide opportunities to infer gene function in citrus. We present a publicly accessible tool, Network Inference for Citrus Co-Expression (NICCE, http://citrus.adelaide.edu.au/nicce/home.aspx), for the gene co-expression analysis in citrus. PMID:25023870

  11. Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy

    PubMed Central

    Salbaum, J. M.; Kruger, C.; Zhang, X.; Delahaye, N. Arbour; Pavlinkova, G.; Burk, D. H.; Kappen, C.

    2013-01-01

    Aims/hypothesis Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, e.g. metabolic syndrome and hypertension. We hypothesised that adverse outcomes from diabetic pregnancies may be linked to compromised placental function, and sought to identify cellular and molecular abnormalities in diabetic placenta. Methods Using a mouse model of diabetic pregnancy, placental gene expression was assayed at mid-gestation and cellular composition analysed at various stages. Genome-wide expression profiling was validated by quantitative PCR and tissue localisation studies were performed to identify cellular correlates of altered gene expression in diabetic placenta. Results We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal and those expressed in the embryonic compartments. We also found altered cellular composition of the decidual compartment. In addition, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells. Conclusions/interpretation Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and of placenta overall. Regardless of whether these changes represent direct responses to hyperglycaemia or are physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and to have implications for developmental origins of adult disease. PMID:21491160

  12. Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes.

    PubMed

    Deutsch, Samuel; Lyle, Robert; Dermitzakis, Emmanouil T; Attar, Homa; Subrahmanyan, Lakshman; Gehrig, Corinne; Parand, Leila; Gagnebin, Maryline; Rougemont, Jacques; Jongeneel, C Victor; Antonarakis, Stylianos E

    2005-12-01

    Inter-individual differences in gene expression are likely to account for an important fraction of phenotypic differences, including susceptibility to common disorders. Recent studies have shown extensive variation in gene expression levels in humans and other organisms, and that a fraction of this variation is under genetic control. We investigated the patterns of gene expression variation in a 25 Mb region of human chromosome 21, which has been associated with many Down syndrome (DS) phenotypes. Taqman real-time PCR was used to measure expression variation of 41 genes in lymphoblastoid cells of 40 unrelated individuals. For 25 genes found to be differentially expressed, additional analysis was performed in 10 CEPH families to determine heritabilities and map loci harboring regulatory variation. Seventy-six percent of the differentially expressed genes had significant heritabilities, and genomewide linkage analysis led to the identification of significant eQTLs for nine genes. Most eQTLs were in trans, with the best result (P=7.46 x 10(-8)) obtained for TMEM1 on chromosome 12q24.33. A cis-eQTL identified for CCT8 was validated by performing an association study in 60 individuals from the HapMap project. SNP rs965951 located within CCT8 was found to be significantly associated with its expression levels (P=2.5 x 10(-5)) confirming cis-regulatory variation. The results of our study provide a representative view of expression variation of chromosome 21 genes, identify loci involved in their regulation and suggest that genes, for which expression differences are significantly larger than 1.5-fold in control samples, are unlikely to be involved in DS-phenotypes present in all affected individuals. PMID:16251198

  13. Sparse Graphical Models for Exploring Gene Expression Data

    E-print Network

    West, Mike

    Sparse Graphical Models for Exploring Gene Expression Data Adrian Dobra Chris Hans , Beatrix- ration of patterns of association in gene expression data. The theoretical discussion covers basic ideas in large-scale gene expression data with a view to generating biological insights about genes related

  14. Interactive 3D Gene Expression Viewer Victor E. Gerth*

    E-print Network

    Vize, Peter D.

    Interactive 3D Gene Expression Viewer Victor E. Gerth* University of Calgary, Department. The Interactive Gene Expression viewer provides a way to view spatial relationships between different gene expression patterns and anatomic features. Web based 3D enabled technologies such as the Interactive Gene

  15. Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis antigens in multiple myeloma

    PubMed Central

    Condomines, Maud; Hose, Dirk; Rème, Thierry; Requirand, Guilhem; Hundemer, Michael; Schoenhals, Matthieu; Goldschmidt, Hartmut; Klein, Bernard

    2009-01-01

    Cancer-testis (CT) antigens are attractive targets for immunotherapeutic strategies since they are aberrantly expressed in malignant cells and not, or in limited number, in somatic tissues, except germ cells. To identify novel CT genes in multiple myeloma, we used Affymetrix HG-U133 gene expression profiles of 5 testis, 64 primary myeloma cell (MMC) and 24 normal tissue (NT) samples. A 5-filter method was developed to keep known CT genes while deleting non-CT genes. Starting from 44928 probe sets, including probe sets for 18 previously-described CT genes, we have obtained 82 genes expressed in MMC and testis and not detected in more than 6 NT. This list includes 14 of the 18 known CT genes and 68 novel putative CT genes. Real-time RT-PCR was performed for 34 genes in 12 NT, 5 MMC samples and one sample of 5 pooled testes. It has validated the CT status of 23/34 genes (67%). We found one novel “testis-restricted” gene (expression in testis and tumor only) – TEX14 –, 8 “tissue-restricted” (mRNA detected in 1 or 2 non-gametogenic tissues), and 7 “differentially expressed” (mRNA detected in three to six non-gametogenic tissues) CT genes. Further studies are warranted to determine the immunogenicity of these novel CT antigen candidates. PMID:19542363

  16. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation.

    PubMed

    Nagarajan, Raman P; Hogart, Amber R; Gwye, Ynnez; Martin, Michelle R; LaSalle, Janine M

    2006-01-01

    Mutations in MECP2, encoding methyl CpG binding protein 2 (MeCP2), cause most cases of Rett syndrome (RTT), an X-linked neurodevelopmental disorder. Both RTT and autism are "pervasive developmental disorders" and share a loss of social, cognitive and language skills and a gain in repetitive stereotyped behavior, following apparently normal perinatal development. Although MECP2 coding mutations are a rare cause of autism, MeCP2 expression defects were previously found in autism brain. To further study the role of MeCP2 in autism spectrum disorders (ASDs), we determined the frequency of MeCP2 expression defects in brain samples from autism and other ASDs. We also tested the hypotheses that MECP2 promoter mutations or aberrant promoter methylation correlate with reduced expression in cases of idiopathic autism. MeCP2 immunofluorescence in autism and other neurodevelopmental disorders was quantified by laser scanning cytometry and compared with control postmortem cerebral cortex samples on a large tissue microarray. A significant reduction in MeCP2 expression compared to age-matched controls was found in 11/14 autism (79%), 9/9 RTT (100%), 4/4 Angelman syndrome (100%), 3/4 Prader-Willi syndrome (75%), 3/5 Down syndrome (60%), and 2/2 attention deficit hyperactivity disorder (100%) frontal cortex samples. One autism female was heterozygous for a rare MECP2 promoter variant that correlated with reduced MeCP2 expression. A more frequent occurrence was significantly increased MECP2 promoter methylation in autism male frontal cortex compared to controls. Furthermore, percent promoter methylation of MECP2 significantly correlated with reduced MeCP2 protein expression. These results suggest that both genetic and epigenetic defects lead to reduced MeCP2 expression and may be important in the complex etiology of autism. PMID:17486179

  17. The frustrated gene: origins of eukaryotic gene expression

    PubMed Central

    Madhani, Hiten D.

    2014-01-01

    Eukarytotic gene expression is frustrated by a series of steps that are generally not observed in prokaryotes and are therefore not essential for the basic chemistry of transcription and translation. Their evolution may have been driven by the need to defend against parasitic nucleic acids. PMID:24209615

  18. The frustrated gene: origins of eukaryotic gene expression.

    PubMed

    Madhani, Hiten D

    2013-11-01

    Eukarytotic gene expression is frustrated by a series of steps that are generally not observed in prokaryotes and are therefore not essential for the basic chemistry of transcription and translation. Their evolution may have been driven by the need to defend against parasitic nucleic acids. PMID:24209615

  19. Functionalization of a protosynaptic gene expression network.

    PubMed

    Conaco, Cecilia; Bassett, Danielle S; Zhou, Hongjun; Arcila, Mary Luz; Degnan, Sandie M; Degnan, Bernard M; Kosik, Kenneth S

    2012-06-26

    Assembly of a functioning neuronal synapse requires the precisely coordinated synthesis of many proteins. To understand the evolution of this complex cellular machine, we tracked the developmental expression patterns of a core set of conserved synaptic genes across a representative sampling of the animal kingdom. Coregulation, as measured by correlation of gene expression over development, showed a marked increase as functional nervous systems emerged. In the earliest branching animal phyla (Porifera), in which a nearly complete set of synaptic genes exists in the absence of morphological synapses, these "protosynaptic" genes displayed a lack of global coregulation although small modules of coexpressed genes are readily detectable by using network analysis techniques. These findings suggest that functional synapses evolved by exapting preexisting cellular machines, likely through some modification of regulatory circuitry. Evolutionarily ancient modules continue to operate seamlessly within the synapses of modern animals. This work shows that the application of network techniques to emerging genomic and expression data can provide insights into the evolution of complex cellular machines such as the synapse. PMID:22723359

  20. Functionalization of a protosynaptic gene expression network

    PubMed Central

    Conaco, Cecilia; Bassett, Danielle S.; Zhou, Hongjun; Arcila, Mary Luz; Degnan, Sandie M.; Degnan, Bernard M.; Kosik, Kenneth S.

    2012-01-01

    Assembly of a functioning neuronal synapse requires the precisely coordinated synthesis of many proteins. To understand the evolution of this complex cellular machine, we tracked the developmental expression patterns of a core set of conserved synaptic genes across a representative sampling of the animal kingdom. Coregulation, as measured by correlation of gene expression over development, showed a marked increase as functional nervous systems emerged. In the earliest branching animal phyla (Porifera), in which a nearly complete set of synaptic genes exists in the absence of morphological synapses, these “protosynaptic” genes displayed a lack of global coregulation although small modules of coexpressed genes are readily detectable by using network analysis techniques. These findings suggest that functional synapses evolved by exapting preexisting cellular machines, likely through some modification of regulatory circuitry. Evolutionarily ancient modules continue to operate seamlessly within the synapses of modern animals. This work shows that the application of network techniques to emerging genomic and expression data can provide insights into the evolution of complex cellular machines such as the synapse. PMID:22723359

  1. Coordination of plastid and nuclear gene expression.

    PubMed Central

    Gray, John C; Sullivan, James A; Wang, Jun-Hui; Jerome, Cheryl A; MacLean, Daniel

    2003-01-01

    The coordinated expression of genes distributed between the nuclear and plastid genomes is essential for the assembly of functional chloroplasts. Although the nucleus has a pre-eminent role in controlling chloroplast biogenesis, there is considerable evidence that the expression of nuclear genes encoding photosynthesis-related proteins is regulated by signals from plastids. Perturbation of several plastid-located processes, by inhibitors or in mutants, leads to decreased transcription of a set of nuclear photosynthesis-related genes. Characterization of arabidopsis gun (genomes uncoupled) mutants, which express nuclear genes in the presence of norflurazon or lincomycin, has provided evidence for two separate signalling pathways, one involving tetrapyrrole biosynthesis intermediates and the other requiring plastid protein synthesis. In addition, perturbation of photosynthetic electron transfer produces at least two different redox signals, as part of the acclimation to altered light conditions. The recognition of multiple plastid signals requires a reconsideration of the mechanisms of regulation of transcription of nuclear genes encoding photosynthesis-related proteins. PMID:12594922

  2. Tetrapyrrole regulation of nuclear gene expression

    Microsoft Academic Search

    Judy A. Brusslan; Michael P. Peterson

    2002-01-01

    Tetrapyrroles are the structural backbone of chlorophyll and heme, and are essential for primary photochemistry, light harvesting, and electron transport. The biochemistry of their synthesis has been studied extensively, and it has been suggested that some of the tetrapyrrole biochemical intermediates can affect nuclear gene expression. In this review, tetrapyrrole biosynthesis, which occurs in the chloroplast, and its regulation will

  3. Gene expression predictors of breast cancer outcomes

    Microsoft Academic Search

    Erich Huang; Skye H Cheng; Holly Dressman; Jennifer Pittman; Mei Hua Tsou; Cheng Fang; Andrea Bild; Edwin S Iversen; Ming Liao; Chii Ming Chen; Mike West; Joseph R Nevins; Andrew T Huang

    2003-01-01

    Summary Background Correlation of risk factors with genomic data promises to provide specific treatment for individual patients, and needs interpretation of complex, multivariate patterns in gene expression data, as well as assessment of their ability to improve clinical predictions. We aimed to predict nodal metastatic states and relapse for breast cancer patients. Methods We analysed DNA microarray data from samples

  4. Experimental design for gene expression microarrays

    Microsoft Academic Search

    M. Kathleen Kerr; Gary A. Churchill

    2001-01-01

    We examine experimental design issues arising with gene expression microarray technology. Microarray experiments have multiple sources of variation, and experimental plans should ensure that effects of interest are not confounded with ancillary effects. A commonly used design is shown to violate this principle and to be generally inefficient. We explore the connection between microarray designs and classical block design and

  5. Designing Neural Networks Using Gene Expression Programming

    E-print Network

    Fernandez, Thomas

    1 Designing Neural Networks Using Gene Expression Programming CândidaFerreira Gepsoft, 73 Elmtree aspects of neural networks, such as the weights, the thresholds, and the network architec- ture. Indeed neural network, including the architecture, the weights and thresholds, could be totally encoded

  6. Visualizing Gene Expression In Situ

    SciTech Connect

    Burlage, R.S.

    1998-11-02

    Visualizing bacterial cells and describing their responses to the environment are difficult tasks. Their small size is the chief reason for the difficulty, which means that we must often use many millions of cells in a sample in order to determine what the average response of the bacteria is. However, an average response can sometimes mask important events in bacterial physiology, which means that our understanding of these organisms will suffer. We have used a variety of instruments to visualize bacterial cells, all of which tell us something different about the sample. We use a fluorescence activated cell sorter to sort cells based on the fluorescence provided by bioreporter genes, and these can be used to select for particular genetic mutations. Cells can be visualized by epifluorescent microscopy, and sensitive photodetectors can be added that allow us to find a single bacterial cell that is fluorescent or bioluminescent. We have also used standard photomultipliers to examine cell aggregates as field bioreporter microorganisms. Examples of each of these instruments show how our understanding of bacterial physiology has changed with the technology.

  7. [The effect of polymorphism of genes of xenobiotics detoxication on the frequencies of spontaneous and induced chromosome aberrations in human lymphocytes].

    PubMed

    Sal'nikova, L E; Akaeva, E A; Elisova, T V; Kuznetsova, G I; Kuz'mina, N S; Vesnina, I N; Lapteva, N Sh; Chumachenko, A G; Romanchuk, V A; Rubanovich, A V

    2009-01-01

    Here presented the data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 97 volunteers depending on genotypes by genes of xenobiotics detoxication before and after gamma-irradiation with dose of 1 Gy in vitro. The frequencies of aberrations were estimated by analyzing not less than 500-1000 metaphases per person. The data of cytogenetic analysis were compared with the results of PCR-genotyping of loci GSTM1, GSTT1, GSTP1, CYP1A1, CYP2D6, NAT2, and MTHFR. The significant differences by the frequencies of aberrations between "single-locus" genotypes were not found except for GSTM1 locus, for which the enhanced frequency of spontaneous aberrations of chromosome type in "positive" genotypes compared to "zero" ones, i.e., homozygotes by deletion (p = 0.04) was observed. The minimum frequency of spontaneous aberrations of chromosome type was recorded for carriers of double homozygotes by deletion of GSTM1-GSTT1: 0.0006 +/- 0.0003 against 0.0027 +/- 0.0003 for the rest of genotypes (p = 0.016 by the Mann-Witney test). The frequency of gamma-induced chromosome aberrations was correlated with the total amount of minor alleles in loci GSTP1, NAT2, and MTHFR (r = 0.25 at p = 0.0065). PMID:19947517

  8. Clustering Gene Expression Series with Prior Laurent Brehelin

    E-print Network

    Paris-Sud XI, Université de

    Clustering Gene Expression Series with Prior Knowledge Laurent Br´eh´elin Laboratoire d the level of expression of thousands of genes in a given tissue over time --for example along the cell cycle [1]. In the following, such a series of gene expression measurements is called an expression series

  9. Feature Selection for Gene Expression Using Model-Based Entropy

    Microsoft Academic Search

    Shenghuo Zhu; Dingding Wang; Kai Yu; Tao Li; Yihong Gong

    2010-01-01

    Gene expression data usually contain a large number of genes, but a small number of samples. Feature selection for gene expression data aims at finding a set of genes that best discriminate biological samples of different types. Using machine learning techniques, traditional gene se- lection based on empirical mutual information suffers the data sparseness issue due to the small number

  10. Correlation between Gene Expression and GO Semantic Similarity

    Microsoft Academic Search

    Jose L. Sevilla; Victor Segura; Adam Podhorski; Elizabeth Guruceaga; Jose M. Mato; Luis A. Martinez-Cruz; Fernando J. Corrales; Angel Rubio

    2005-01-01

    This research analyzes some aspects of the relationship between gene expression, gene function, and gene annotation. Many recent studies are implicitly based on the assumption that gene products that are biologically and functionally related would maintain this similarity both in their expression profiles as well as in their Gene Ontology (GO) annotation. We analyze how accurate this assumption proves to

  11. Aberrant Expression of Interleukin-1? and Inflammasome Activation in Human Malignant Gliomas

    PubMed Central

    Tarassishin, Leonid; Casper, Diana; Lee, Sunhee C.

    2014-01-01

    Objective Glioblastoma is the most frequent and malignant form of primary brain tumor with grave prognosis. Mounting evidence supports that chronic inflammation (such as chronic overactivation of IL-1 system) is a crucial event in carcinogenesis and tumor progression. IL-1 also is an important cytokine with species-dependent regulations and roles in CNS cell activation. While much attention is paid to specific anti-tumor immunity, little is known about the role of chronic inflammation/innate immunity in glioma pathogenesis. In this study, we examined whether human astrocytic cells (including malignant gliomas) can produce IL-1 and its role in glioma progression. Methods We used a combination of cell culture, real-time PCR, ELISA, western blot, immunocytochemistry, siRNA and plasmid transfection, micro-RNA analysis, angiogenesis (tube formation) assay, and neurotoxicity assay. Results Glioblastoma cells produced large quantities of IL-1 when activated, resembling macrophages/microglia. The activation signal was provided by IL-1 but not the pathogenic components LPS or poly IC. Glioblastoma cells were highly sensitive to IL-1 stimulation, suggesting its relevance in vivo. In human astrocytes, IL-1? mRNA was not translated to protein. Plasmid transfection also failed to produce IL-1 protein, suggesting active repression. Suppression of microRNAs that can target IL-1?/? did not induce IL-1 protein. Glioblastoma IL-1? processing occurred by the NLRP3 inflammasome, and ATP and nigericin increased IL-1? processing by upregulating NLRP3 expression, similar to macrophages. RNAi of annexin A2, a protein strongly implicated in glioma progression, prevented IL-1 induction, demonstrating its new role in innate immune activation. IL-1 also activated Stat3, a transcription factor crucial in glioma progression. IL-1 activated glioblastoma-conditioned media enhanced angiogenesis and neurotoxicity. Conclusions Our results demonstrate unique, species-dependent immune activation mechanisms involving human astrocytes and astrogliomas. Specifically, the ability to produce IL-1 by glioblastoma cells may confer them a mesenchymal phenotype including increased migratory capacity, unique gene signature and proinflammatory signaling. PMID:25054228

  12. Computational Model of the Modulation of Gene Expression Following DNA Damage

    NASA Technical Reports Server (NTRS)

    Cucinotta, F. A.; Dicello, J. F.; Nikjoo, H.; Cherubini, R.

    2002-01-01

    High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has an increased biological effectiveness compared to X rays for gene mutation, genomic instability, and carcinogenesis. In the traditional paradigm, mutations or chromosomal aberrations are causative of late effects. However, in recent years experimental evidence has demonstrated the important role of the description of the modification of gene expression by radiation in understanding the mechanisms of radiation action. In this report, approaches are discussed to the mathematical description of mRNA and protein expression kinetics following DNA damage. Several hypotheses for models of radiation modulation of protein expression are discussed including possible non-linear processes that evolve from the linear dose responses that follow the initial DNA damage produced by radiation.

  13. Repression of gene expression by oxidative stress.

    PubMed Central

    Morel, Y; Barouki, R

    1999-01-01

    Gene expression is modulated by both physiological signals (hormones, cytokines, etc.) and environmental stimuli (physical parameters, xenobiotics, etc.). Oxidative stress appears to be a key pleiotropic modulator which may be involved in either pathway. Indeed, reactive oxygen species (ROS) have been described as second messengers for several growth factors and cytokines, but have also been shown to rise following cellular insults such as xenobiotic metabolism or enzymic deficiency. Extensive studies on the induction of stress-response genes by oxidative stress have been reported. In contrast, owing to the historical focus on gene induction, less attention has been paid to gene repression by ROS. However, a growing number of studies have shown that moderate (i.e. non-cytotoxic) oxidative stress specifically down-regulates the expression of various genes. In this review, we describe the alteration of several physiological functions resulting from oxidative-stress-mediated inhibition of gene transcription. We will then focus on the repressive oxidative modulation of various transcription factors elicited by ROS. PMID:10477257

  14. Mining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps

    E-print Network

    Obradovic, Zoran

    Mining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps Li An166522@temple.edu Abstract Association rules mining methods have been recently applied to gene expression, not much effort has focused on detecting the relation between gene expression maps and related gene

  15. Neural networks approaches for discovering the learnable correlation between gene function and gene expression in mouse

    E-print Network

    Morris, Quaid

    Keywords: Gene function prediction Self organizing maps (SOM) Multilayer perceptrons (MLP) Gene expression function based on gene expression data is much easier in prokaryotes than eukaryotes due to the relatively between gene function and gene expression. In previous work, we presented novel clustering and neural

  16. Aberrant Mucin5B expression in lung adenocarcinomas detected by iTRAQ labeling quantitative proteomics and immunohistochemistry

    PubMed Central

    2013-01-01

    Background Lung cancer is the number one cause of cancer-related deaths in the United States and worldwide. The complex protein changes and/or signature of protein expression in lung cancer, particularly in non-small cell lung cancer (NSCLC) has not been well defined. Although several studies have investigated the protein profile in lung cancers, the knowledge is far from complete. Among early studies, mucin5B (MUC5B) has been suggested to play an important role in the tumor progression. MUC5B is the major gel-forming mucin in the airway. In this study, we investigated the overall protein profile and MUC5B expression in lung adenocarcinomas, the most common type of NSCLCs. Methods Lung adenocarcinoma tissue in formalin-fixed paraffin-embedded (FFPE) blocks was collected and microdissected. Peptides from 8 tumors and 8 tumor-matched normal lung tissue were extracted and labeled with 8-channel iTRAQ reagents. The labeled peptides were identified and quantified by LC-MS/MS using an LTQ Orbitrap Velos mass spectrometer. MUC5B expression identified by iTRAQ labeling was further validated using immunohistochemistry (IHC) on tumor tissue microarray (TMA). Results A total of 1288 peptides from 210 proteins were identified and quantified in tumor tissues. Twenty-two proteins showed a greater than 1.5-fold differences between tumor and tumor-matched normal lung tissues. Fifteen proteins, including MUC5B, showed significant changes in tumor tissues. The aberrant expression of MUC5B was further identified in 71.1% of lung adenocarcinomas in the TMA. Discussions A subset of tumor-associated proteins was differentially expressed in lung adenocarcinomas. The differential expression of MUC5B in lung adenocarcinomas suggests its role as a potential biomarker in the detection of adenocarcinomas. PMID:24176033

  17. IRES-Dependent Second Gene Expression Is Significantly Lower Than Cap-Dependent First Gene Expression in a Bicistronic Vector

    Microsoft Academic Search

    Hiroyuki Mizuguchi; Zhili Xu; Akiko Ishii-Watabe; Eriko Uchida; Takao Hayakawa

    2000-01-01

    The internal ribosome entry site (IRES) has been widely used to coexpress heterologous gene products by a message from a single promoter. However, little is known about the efficiency of IRES-dependent second gene expression in comparison with that of first gene expression. This study was undertaken to characterize the relative expression of IRES-dependent second gene in a bicistronic vector, which

  18. Parsimonious selection of useful genes in microarray gene expression data.

    PubMed

    González-Navarro, Félix F; Belanche-Muñoz, Lluís A

    2011-01-01

    Machine learning methods have of late made significant efforts to solving multidisciplinary problems in the field of cancer classification in microarray gene expression data. These tasks are characterized by a large number of features and a few observations, making the modeling a nontrivial undertaking. In this study, we apply entropic filter methods for gene selection, in combination with several off-the-shelf classifiers. The introduction of bootstrap resampling techniques permits the achievement of more stable performance estimates. Our findings show that the proposed methodology permits a drastic reduction in dimension, offering attractive solutions in terms of both prediction accuracy and number of explanatory genes; a dimensionality reduction technique preserving discrimination capabilities is used for visualization of the selected genes. PMID:21431545

  19. Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC–EURGAST)

    Microsoft Academic Search

    Karen Balassiano; Sheila Lima; Mazda Jenab; Kim Overvad; Anne Tjonneland; Marie Christine Boutron-Ruault; Françoise Clavel-Chapelon; Federico Canzian; Rudolf Kaaks; Heiner Boeing; Karina Meidtner; Antonia Trichopoulou; Pagona Laglou; Paolo Vineis; Salvatore Panico; Domenico Palli; Sara Grioni; Rosario Tumino; Eiliv Lund; H. Bas Bueno-de-Mesquita; Mattjis E. Numans; Petra H. M. Peeters; J. Ramon Quirós; Mar?´a-José Sánchez; Carmen Navarro; Eva Ardanaz; Miren Dorronsoro; Göran Hallmans; Roger Stenling; Roy Ehrnström; Sara Regner; Naomi E. Allen; Ruth C. Travis; Kay-Tee Khaw; G. Johan A. Offerhaus; Nuria Sala; Elio Riboli; Pierre Hainaut; Jean-Yves Scoazec; Bakary S. Sylla; Carlos A. Gonzalez; Zdenko Herceg

    2011-01-01

    Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested

  20. Integrator: surprisingly diverse functions in gene expression.

    PubMed

    Baillat, David; Wagner, Eric J

    2015-05-01

    The discovery of the metazoan-specific Integrator (INT) complex represented a breakthrough in our understanding of noncoding U-rich small nuclear RNA (UsnRNA) maturation and has triggered a reevaluation of their biosynthesis mechanism. In the decade since, significant progress has been made in understanding the details of its recruitment, specificity, and assembly. While some discrepancies remain on how it interacts with the C-terminal domain (CTD) of the RNA polymerase II (RNAPII) and the details of its recruitment to UsnRNA genes, preliminary models have emerged. Recent provocative studies now implicate INT in the regulation of protein-coding gene transcription initiation and RNAPII pause-release, thereby broadening the scope of INT functions in gene expression regulation. We discuss the implications of these findings while putting them into the context of what is understood about INT function at UsnRNA genes. PMID:25882383

  1. Aberrant expression of sLex and sLea as candidate prognostic factors for feline mammary gland tumour.

    PubMed

    Yoshida, Saori; Yoshida, Kota; Jaroensong, Tassanee; Lee, Soo-Jung; Kamida, Ayako; Saeki, Kohei; Fujita, Naoki; Nishimura, Ryohei; Sasaki, Nobuo; Nakagawa, Takayuki

    2014-04-01

    Expression of the carbohydrate antigens sialyl Lewis x (sLe(x)) and a (sLe(a)) was evaluated in feline mammary gland tumours (FMGT). Immunohistochemical analysis of tissues from 21 FMGT patients and 11 healthy cats revealed significantly higher sLe(x) and sLe(a) antigen expression in adenocarcinoma tissues compared with that of normal mammary tissues (P <0.01). Serum concentration of sLe(x) was evaluated using an enzyme-linked immunosorbent assay and was significantly higher in the 11 FMGT patients (4.71 ± 10.1 U/ml) than the 22 patients with other disease (2.69 ± 1.59 U/ml) (P = 0.03) and the 22 healthy cats (3.71 ± 1.10 U/ml), although the latter difference was not significant. Although the number of cases examined in this study was small, our findings suggest that aberrant expression of sLe antigens may be induced by tumourigenesis in FMGT and that sLe antigens are potential prognostic tumour markers for FMGT. PMID:24043722

  2. Gene expression profiling of extrahepatic ducts in children with biliary atresia

    PubMed Central

    Wang, Jiang; Wang, Wei; Dong, Rui; Zhao, Rui; Jin, Zhu; Shen, Wenjun; Zheng, Shan

    2015-01-01

    As an inflammatory obliterative cholangiopathy of neonates, biliary atresia (BA) affects both intrahepatic and extrahepatic bile ducts. Its etiology has remained largely unknown. Gene expression profiling was conduced for extrahepatic bile duct tissues (including porta hepatis & common bile duct) to identify novel targets for further studies of BA. Among these tissues, porta hepatis was regarded as fibrosis group while common bile duct as self-control group. The analysis of gene expression profile in these tissues was performed with Affymetrix human microarray. Quantitative RT-PCR (qRT-PCR) was performed to confirm these results. The differential expressions of genes were identified through fold-change filtering. Gene Ontology (GO) and pathway analyses were performed using standard enrichment computation method. It was found that a total of 140 genes were differentially expressed between porta hepatis and common bile duct tissues, 19 genes up-regulated and 121 genes down-regulated. Moreover, GO analysis found that cell adhesion molecules, extracellular matrix formation, protein digestion & absorption functions may be involved in the pathogenesis of porta hepatis fibrosis. Lastly the qRT-PCR data confirmed that IL7 and CLDN2 were significantly up-regulated and both might be involved in the etiology of BA, the expression level of VCAM1 was positively correlated with severity of liver fibrosis in the BA infants. Our results demonstrated that the expressions of these aberrant genes responding to fibrosis in porta hepatis of patients with BA. Further studies of these genes may provide useful insights into the pathological mechanisms of BA.

  3. Coevolution of gene expression among interacting proteins

    SciTech Connect

    Fraser, Hunter B.; Hirsh, Aaron E.; Wall, Dennis P.; Eisen,Michael B.

    2004-03-01

    Physically interacting proteins or parts of proteins are expected to evolve in a coordinated manner that preserves proper interactions. Such coevolution at the amino acid-sequence level is well documented and has been used to predict interacting proteins, domains, and amino acids. Interacting proteins are also often precisely coexpressed with one another, presumably to maintain proper stoichiometry among interacting components. Here, we show that the expression levels of physically interacting proteins coevolve. We estimate average expression levels of genes from four closely related fungi of the genus Saccharomyces using the codon adaptation index and show that expression levels of interacting proteins exhibit coordinated changes in these different species. We find that this coevolution of expression is a more powerful predictor of physical interaction than is coevolution of amino acid sequence. These results demonstrate previously uncharacterized coevolution of gene expression, adding a different dimension to the study of the coevolution of interacting proteins and underscoring the importance of maintaining coexpression of interacting proteins over evolutionary time. Our results also suggest that expression coevolution can be used for computational prediction of protein protein interactions.

  4. Aberrant Expression of Disintegrin-Metalloprotease Proteins in the Formation and Progression of Uterine Cervical Cancer

    Microsoft Academic Search

    Mohammed Shaker; Yuhki Yokoyama; Seiji Mori; Masahiko Tsujimoto; Naomasa Kawaguchi; Tohru Kiyono; Toru Nakano; Nariaki Matsuura

    2011-01-01

    Objective: Dysregulated expression of disintegrin-metalloprotease proteins [a disintegrin and metalloproteases (ADAMs) and ADAMs with thrombospondin motif (ADAMTSs)] has been reported in many types of cancers and is believed to play an important role in cancer formation and metastasis. However, little is known about the expression of ADAMs and ADAMTSs in the development of human cervical cancer. Methods: Reverse transcriptase polymerase

  5. A yeast's eye view of mammalian reproduction: cross-species gene co-expression in meiotic prophase

    PubMed Central

    2010-01-01

    Background Meiotic prophase is a critical stage in sexual reproduction. Aberrant chromosome recombination during this stage is a leading cause of human miscarriages and birth defects. However, due to the experimental intractability of mammalian gonads, only a very limited number of meiotic genes have been characterized. Here we aim to identify novel meiotic genes important in human reproduction through computational mining of cross-species and cross-sex time-series expression data from budding yeast, mouse postnatal testis, mouse embryonic ovary, and human fetal ovary. Results Orthologous gene pairs were ranked by order statistics according to their co-expression profiles across species, allowing us to infer conserved meiotic genes despite obvious differences in cellular synchronicity and composition in organisms. We demonstrated that conserved co-expression networks could successfully recover known meiotic genes, including homologous recombination genes, chromatin cohesion genes, and genes regulating meiotic entry. We also showed that conserved co-expression pairs exhibit functional connections, as evidenced by the annotation similarity in Gene Ontology and overlap with physical interactions. More importantly, we predicted six new meiotic genes through their co-expression linkages with known meiotic genes, and subsequently used the genetically more amenable yeast system for experimental validation. The deletion mutants of all six genes showed sporulation defects, equivalent to a 100% validation rate. Conclusions We identified evolutionarily conserved gene modules in meiotic prophase by integrating cross-species and cross-sex expression profiles from budding yeast, mouse, and human. Our co-expression linkage analyses confirmed known meiotic genes and identified several novel genes that might be critical players in meiosis in multiple species. These results demonstrate that our approach is highly efficient to discover evolutionarily conserved novel meiotic genes, and yeast can serve as a valuable model system for investigating mammalian meiotic prophase. PMID:20819218

  6. Gene expression profiling in sinonasal adenocarcinoma

    PubMed Central

    2009-01-01

    Background Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers. Methods To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors. Results Among the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type. Conclusion Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers. PMID:19903339

  7. RNA silencing of rotavirus gene expression.

    PubMed

    Arias, Carlos F; Dector, Miguel A; Segovia, Lorenzo; López, Tomás; Camacho, Minerva; Isa, Pavel; Espinosa, Rafaela; López, Susana

    2004-06-01

    RNA interference (RNAi) is a double-stranded RNA (dsRNA)-triggered mechanism for suppressing gene expression, which is conserved in evolution and has emerged as a powerful tool to study gene function. Rotaviruses, the leading cause of severe diarrhea in young children, are formed by three concentric layers of protein, and a genome composed of 11 segments of dsRNA. Here, we show that the RNAi machinery can be triggered to silence rotavirus gene expression by sequence-specific short interfering RNAs (siRNAs). RNAi is also useful for the study of the virus-cell interactions, through the silencing of cellular genes that are potentially important for the replication of the virus. Interestingly, while the translation of mRNAs is readily stopped by the RNAi machinery, the viral transcripts involved in virus genome replication do not seem to be susceptible to RNAi. Since gene silencing by RNAi is very efficient and specific, this system could become a novel therapeutic approach for rotavirus and other virus infections, once efficient methods for in vivo delivery of siRNAs are developed. Although the use of RNAi as an antiviral therapeutic tool remains to be demonstrated, there is no doubt that this technology will influence drastically the way postgenomic virus research is conducted. PMID:15068879

  8. Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor cells

    PubMed Central

    Uchiyama, Shintaro; Saeki, Noritaka; Ogawa, Kazushige

    2015-01-01

    AIM: To determine whether the expression profiles of EphB receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa. METHODS: The protein expression and localization of EphB and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and mRNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction. RESULTS: Ephrin-B- and EphB-expressing regions were divided along the pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines. CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, EphB/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer. PMID:25593460

  9. Aberrant promotor methylation in MDS hematopoietic cells during in vitro lineage specific differentiation is differently associated with DNMT isoforms

    Microsoft Academic Search

    Olaf Hopfer; Martina Komor; Ina Sabine Koehler; Claudia Freitag; Matthias Schulze; Dieter Hoelzer; Eckhard Thiel; Wolf-Karsten Hofmann

    2009-01-01

    Aberrant promoter methylation may contribute to the hematopoietic disturbances in myelodysplastic syndromes (MDS). To explore a possible mechanism, we therefore analyzed expression of DNA methyltransferase (DNMT) subtypes kinetics and aberrant promoter methylation of key regulatory genes during MDS hematopoiesis. An in vitro model of MDS lineage-specific hematopoiesis was generated by culturing CD34+ cells from healthy donors (n=7) and MDS patients

  10. Conditional Gene Expression in Chlamydia trachomatis Using the Tet System

    E-print Network

    Wickstrum, Jason; Sammons, Lindsay R.; Restivo, Keasha Nicole; Hefty, P. Scott

    2013-10-07

    . To accomplish this, a new shuttle vector was generated with gene expression controlled by the Tetracycline repressor and anhydryotetracycline. Evaluation of GFP expression by this system demonstrated tightly controlled gene regulation with rapid protein...

  11. Copy Number and Gene Expression: Stochastic Modeling and Therapeutic Application 

    E-print Network

    Hsu, Fang-Han

    2013-05-01

    (CNAs), which are known to be common mutations in genetic diseases, on steady- state gene expression values, time-course expression activities, and the e?ectiveness of targeted therapy. Assuming DNA copies operate as independent subsystems producing gene...

  12. Doxycycline-dependent photoactivated gene expression in eukaryotic systems

    E-print Network

    Cai, Long

    Doxycycline-dependent photoactivated gene expression in eukaryotic systems Sidney B Cambridge1 two reversibly inhibited, photoactivatable (`caged') doxycycline derivatives with different membrane-on' system. After incubation with caged doxycycline or caged cyanodoxycycline, we induced gene expression

  13. Copy Number and Gene Expression: Stochastic Modeling and Therapeutic Application

    E-print Network

    Hsu, Fang-Han

    2013-05-01

    (CNAs), which are known to be common mutations in genetic diseases, on steady- state gene expression values, time-course expression activities, and the e?ectiveness of targeted therapy. Assuming DNA copies operate as independent subsystems producing gene...

  14. Engineering Genes for Predictable Protein Expression

    PubMed Central

    Gustafsson, Claes; Minshull, Jeremy; Govindarajan, Sridhar; Ness, Jon; Villalobos, Alan; Welch, Mark

    2013-01-01

    The DNA sequence used to encode a polypeptide can have dramatic effects on its expression. Lack of readily available tools has until recently inhibited meaningful experimental investigation of this phenomenon. Advances in synthetic biology and the application of modern engineering approaches now provide the tools for systematic analysis of the sequence variables affecting heterologous expression of recombinant proteins. We here discuss how these new tools are being applied and how they circumvent the constraints of previous approaches, highlighting some of the surprising and promising results emerging from the developing field of gene engineering. PMID:22425659

  15. Gene Expression Signatures of Coronary Heart Disease

    PubMed Central

    Joehanes, Roby; Ying, Saixia; Huan, Tianxiao; Johnson, Andrew D.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Woodhouse, Kimberly A.; Sen, Shurjo K.; Tanriverdi, Kahraman; Courchesne, Paul; Freedman, Jane E.; O'Donnell, Christopher J.; Levy, Daniel; Munson, Peter J.

    2013-01-01

    Objective To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 CHD cases and 188 age- and sex-matched controls who were participants in the Framingham Heart Study. Approach and results A total of 35 genes were differentially expressed in CHD cases vs. controls at FDR<0.5 including GZMB, TMEM56 and GUK1. Cluster analysis revealed three gene clusters associated with CHD, two linked to increased erythrocyte production and a third to reduced natural killer (NK) and T cell activity in CHD cases. Exon-level results corroborated and extended the gene-level results. Alternative splicing analysis suggested that GUK1 and 38 other genes were differentially spliced in CHD cases vs. controls. Gene ontology analysis linked ubiquitination and T-cell-related pathways with CHD. Conclusion Two bioinformatically defined groups of genes show consistent associations with CHD. Our findings are consistent with the hypotheses that hematopoesis is up-regulated in CHD, possibly reflecting a compensatory mechanism, and that innate immune activity is disrupted in CHD or altered by its treatment. Transcriptomic signatures may be useful in identifying pathways associated with CHD and point toward novel therapeutic targets for its treatment and prevention. PMID:23539218

  16. Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies.

    PubMed

    Ishii, Hideshi; Vecchione, Andrea; Furukawa, Yutaka; Sutheesophon, Krittaya; Han, Shuang-Yin; Druck, Teresa; Kuroki, Tamotsu; Trapasso, Francesco; Nishimura, Miki; Saito, Yasushi; Ozawa, Keiya; Croce, Carlo M; Huebner, Kay; Furukawa, Yusuke

    2003-11-01

    The WW domain containing oxidoreductase (WWOX) gene was recently identified as a candidate tumor suppressor gene at a common fragile site, FRA16D. Because the fragile histidine triad (FHIT) gene, a tumor suppressor gene encompassing the most active, common fragile site FRA3B, is frequently deleted in various cancers, we evaluated the expression of WWOX and FHIT in 74 cases of primary hematopoietic neoplasias and 20 leukemia cell lines. Aberration or absence of WWOX transcripts was detected in 51% of the primary cases and 55% of cell lines, and three WWOX nucleotide variants were detected among the leukemia cell lines. FHIT expression was absent or altered in 36% of the primary cases and 15% of cell lines. The occurrence of aberrant FHIT reverse transcription-PCR products correlated significantly with the occurrence of WWOX alterations. Wild-type transcripts of both genes were expressed in normal hematopoiesis along with a small fraction of short transcripts. A DNA blot study showed that WWOX and FHIT genes were deleted in 2 of 18 cases with primary acute leukemias; both genes were not expressed in the 2 cases. Furthermore, treatment of cells with a demethylating or histone acetylating agent in culture resulted in increased expression of WWOX and FHIT mRNA in leukemia cells. Conclusions are that WWOX expression is frequently altered or absent in hematopoietic disorders, often in association with FHIT alterations, and that alterations of these fragile genes may result not only from genomic deletions but also from epigenetic modifications associated with expression of fragility. PMID:14638866

  17. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    SciTech Connect

    Salem, Tamer Z. [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States) [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619 (Egypt); Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 (Egypt); Zhang, Fengrui [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States)] [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Thiem, Suzanne M., E-mail: smthiem@msu.edu [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  18. Pomelo II: finding differentially expressed genes

    Microsoft Academic Search

    Edward R. Morrissey; Ramón Díaz-uriarte

    2009-01-01

    Pomelo II (http:\\/\\/pomelo2.bioinfo.cnio.es) is an open-source, web-based, freely available tool for the analysis of gene (and protein) expression and tissue array data. Pomelo II implements: permuta- tion-based tests for class comparisons (t-test, ANOVA) and regression; survival analysis using Cox model; contingency table analysis with Fisher's exact test; linear models (of which t-test and ANOVA are especial cases) that allow additional

  19. Tetrapyrrole regulation of nuclear gene expression

    Microsoft Academic Search

    Judy A. Brusslan; Michael P. Peterson

    2002-01-01

    Tetrapyrroles are the structural backbone of chlorophyll and heme, and are essential for primary photochemistry, light harvesting,\\u000a and electron transport. The biochemistry of their synthesis has been studied extensively, and it has been suggested that some\\u000a of the tetrapyrrole biochemical intermediates can affect nuclear gene expression. In this review, tetrapyrrole biosynthesis,\\u000a which occurs in the chloroplast, and its regulation will

  20. Myosin gene expression in the respiratory muscles

    Microsoft Academic Search

    J. G. Gea

    1997-01-01

    Myosin gene expression in the respiratory muscles. J.G. Gea. ©ERS Journals Ltd 1997. ABSTRACT: Myosin is one of the basic structural components of skeletal mus- cles. Its interaction with actin results in muscle contraction. The myosin molecule is composed of two heavy (MyHC) and two light chains (MyLC) that, together with the adenosine triphosphatase (ATPase) activity, determine the functional char-

  1. [Mechanism of Nampt gene expression regulation].

    PubMed

    Huang, Rui; Wang, Zi-Ru; Sun, Yu; Zhang, Gang; Lu, Ya-Ping

    2012-12-01

    Nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony-enhancing factor (PBEF) or visfatin, is a crucial rate-limiting enzyme of NAD biosynthetic pathway. It may affect the metabolism, inflammatory response, cell proliferation, differentiation, and apoptosis, especially the aging and other physiological progresses through regulating NAD biosynthesis and nonenzyme routes in the organisms and cells. This review mainly focuses on recent progresses in the expression modulation and feedback regulation of Nampt gene. PMID:23262103

  2. Biclustering gene expression datasets — an efficient technique

    Microsoft Academic Search

    I. H. Ismail; A. H. Kamal

    2010-01-01

    Many techniques have been developed to solve biclustering gene expression datasets problem by minimizing the crossings in the input matrices like cHawk [1] and Bimax [9]. The usage of local searching techniques-in the step of Crossing Minimization (CM)-causes some limitations that affect the accuracy of the obtained biclusters. In this paper, Crossing Minimization Biclustering Algorithm (CMBA) is proposed that deals

  3. Global gene expression in Staphylococcus aureus biofilms.

    PubMed

    Beenken, Karen E; Dunman, Paul M; McAleese, Fionnuala; Macapagal, Daphne; Murphy, Ellen; Projan, Steven J; Blevins, Jon S; Smeltzer, Mark S

    2004-07-01

    We previously demonstrated that mutation of the staphylococcal accessory regulator (sarA) in a clinical isolate of Staphylococcus aureus (UAMS-1) results in an impaired capacity to form a biofilm in vitro (K. E. Beenken, J. S. Blevins, and M. S. Smeltzer, Infect. Immun. 71:4206-4211, 2003). In this report, we used a murine model of catheter-based biofilm formation to demonstrate that a UAMS-1 sarA mutant also has a reduced capacity to form a biofilm in vivo. Surprisingly, mutation of the UAMS-1 ica locus had little impact on biofilm formation in vitro or in vivo. In an effort to identify additional loci that might be relevant to biofilm formation and/or the adaptive response required for persistence of S. aureus within a biofilm, we isolated total cellular RNA from UAMS-1 harvested from a biofilm grown in a flow cell and compared the transcriptional profile of this RNA to RNA isolated from both exponential- and stationary-phase planktonic cultures. Comparisons were done using a custom-made Affymetrix GeneChip representing the genomic complement of six strains of S. aureus (COL, N315, Mu50, NCTC 8325, EMRSA-16 [strain 252], and MSSA-476). The results confirm that the sessile lifestyle associated with persistence within a biofilm is distinct by comparison to the lifestyles of both the exponential and postexponential phases of planktonic culture. Indeed, we identified 48 genes in which expression was induced at least twofold in biofilms over expression under both planktonic conditions. Similarly, we identified 84 genes in which expression was repressed by a factor of at least 2 compared to expression under both planktonic conditions. A primary theme that emerged from the analysis of these genes is that persistence within a biofilm requires an adaptive response that limits the deleterious effects of the reduced pH associated with anaerobic growth conditions. PMID:15231800

  4. Inhibition of ?-globin gene expression by RNAi

    Microsoft Academic Search

    Orawan Sarakul; Phantip Vattanaviboon; Prapon Wilairat; Suthat Fucharoen; Yasunobu Abe; Koichiro Muta

    2008-01-01

    RNA interference (RNAi), a process by which target messenger RNA (mRNA) is cleaved by small interfering complementary RNA (siRNA), is widely used for investigations of regulation of gene expression in various cells. In this study, siRNA complementary to 5? region of exon II of ?-globin mRNA was examined for its role in erythroid colony forming cells (ECFCs) isolated from normal

  5. GPS Height Fitting Using Gene Expression Programming

    Microsoft Academic Search

    Xuezhi Yue; Zhijian Wu; Dazhi Jiang; Kangshun Li

    2010-01-01

    \\u000a In Global Position System (GPS) height fitting methods, the traditional mathematical model fittings are more stable and general,\\u000a but the fitting accuracy is usually not intended because of the error of model itself. Gene Expression Programming (GEP) as\\u000a a kind of newly invented Genotype\\/phenotype based genetic algorithm can conquer the problem effectively. A GPS height fitting\\u000a method based on GEP

  6. Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

    PubMed Central

    2009-01-01

    Background Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. Results All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Conclusion Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour. PMID:19192278

  7. Expression of foreign genes in filamentous cyanobacteria

    SciTech Connect

    Kuritz, T.; Wolk, C.P. (Michigan State Univ., East Lansing (United States))

    1993-06-01

    Several advantages make cyanobacteria attractive hosts for biodegradative genes and possibly for other exogenous genes that have practical uses. The authors have obtained expression in Anabaena sp. strain PCC 7120 and Nostoc ellipsosporum of a dechlorination operon, fcbAB, from Arthrobacter globiformis, and have also developed a simple method for qualitative assessment of dechlorination by microorganisms, such as cyanobacteria, whose metabolism is dependent on the presence of chloride in the medium. Transcription of fcbAB under the control of a variety of promoters was monitored by placing luxAB (encoding luciferase) downstream from fcbAB, and by measuring light emission from luciferase. They believe that the system that they have described has value as a means to screen for factors influencing transcription of foreign genes in cyanobacteria.

  8. Attenuating gene expression (AGE) for vaccine development

    PubMed Central

    Pascual, David W; Suo, Zhiyong; Cao, Ling; Avci, Recep; Yang, Xinghong

    2013-01-01

    Live attenuated vaccines are adept in stimulating protective immunity. Methods for generating such vaccines have largely adopted strategies used with Salmonella enterica. Yet, when similar strategies were tested in other gram-negative bacteria, the virulence factors or genes responsible to incapacitate Salmonella often failed in providing the desired outcome. Consequently, conventional live vaccines rely on prior knowledge of the pathogen’s virulence factors to successfully attenuate them. This can be problematic since such bacterial pathogens normally harbor thousands of genes. To circumvent this problem, we found that overexpression of bacterial appendages, e.g., fimbriae, capsule, and flagella, could successfully attenuate wild-type (wt) Salmonella enterica serovar Typhimurium. Further analysis revealed these attenuated Salmonella strains conferred protection against wt S. Typhimurium challenge as effectively as genetically defined Salmonella vaccines. We refer to this strategy as attenuating gene expression (AGE), a simple efficient approach in attenuating bacterial pathogens, greatly facilitating the construction of live vaccines. PMID:23652809

  9. Co-clustering of biological networks and gene expression data

    Microsoft Academic Search

    Daniel Hanisch; Alexander Zien; Ralf Zimmer; Thomas Lengauer

    2002-01-01

    Motivation: Large scale gene expression data are often analysed by clustering genes based on gene expression data alone, though a priori knowledge in the form of bi- ological networks is available. The use of this additional information promises to improve exploratory analysis con- siderably. Results: We propose constructing a distance function which combines information from expression data and biological networks.

  10. A new approach for merging gene expression datasets

    Microsoft Academic Search

    Marie-Christine Roubaud; Bruno Torresani

    2011-01-01

    We propose a new approach for merging gene expression data originating from independent microarray experiments. The proposed approach is based upon a model assuming dataset-independent gene expression distribution, and dataset-dependent observation noise and nonlinear observation functions. The estimation algorithm combines smoothing spline estimation for the observation functions with an iterative method for gene expression estimation. The approach is illustrated by

  11. A gene expression database for the molecular pharmacology of cancer

    Microsoft Academic Search

    Uwe Scherf; Douglas T. Ross; Mark Waltham; Lawrence H. Smith; Jae K. Lee; Lorraine Tanabe; Kurt W. Kohn; William C. Reinhold; Timothy G. Myers; Darren T. Andrews; Dominic A. Scudiero; Michael B. Eisen; Edward A. Sausville; Yves Pommier; David Botstein; Patrick O. Brown; John N. Weinstein

    2000-01-01

    We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discov- ery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very

  12. Evolution of Gene Expression Patricia J.Wittkopp

    E-print Network

    Gruber, Jonathan

    V.7 Evolution of Gene Expression Patricia J.Wittkopp OUTLINE 1. The importance of regulatory, but during the last decade, multiple lines of evidence have shown that changes in gene expression of expression differences within and between species. From a growing collection of single-gene case studies

  13. Noise-based switches and amplifiers for gene expression

    E-print Network

    Hasty, Jeff

    Noise-based switches and amplifiers for gene expression Jeff Hasty* , Joel Pradines*, Milos Dolnik networks, whereby gene products from a single net- work can act to control their own expression describing the regulation of gene expression and elucidate the effects of noise on the formulation. We

  14. CLICK: A Clustering Algorithm with Applications to Gene Expression Analysis

    E-print Network

    Sharan, Roded

    CLICK: A Clustering Algorithm with Applications to Gene Expression Analysis Roded Sharan and Ron when the cell undergoes speci#12;c conditions or processes. Analyzing gene expression data requires the clustering of genes into groups with similar expression patterns. We have developed a novel clustering

  15. Data-adaptive test statistics gene expression arrays

    E-print Network

    Roberts, Stephen

    Data-adaptive test statistics for gene expression arrays Sachi Nandan Mukherjee Robotics Research for gene expression arrays Abstract This thesis proposes a data-adaptive approach to the problem of select- ing differentially expressed genes from microarray data. The approach is rooted in machine learning

  16. Identifying Complex Biological Interactions based on Categorical Gene Expression Data

    E-print Network

    Fernandez, Thomas

    Identifying Complex Biological Interactions based on Categorical Gene Expression Data Ben Goertzel-categories based on gene expression data. The method deals with binary categorical data, which consists of a set of gene expression profiles divided into two biologically meaningful categories. It does not require data

  17. Hybrid Segmentation Framework for Tissue Images Containing Gene Expression Data

    E-print Network

    Ju, Tao

    Hybrid Segmentation Framework for Tissue Images Containing Gene Expression Data Musodiq Bello 1 that characterize the distribu- tion of gene expression in relation to a standard anatomical model are required. In this work, we propose a new automatic method that results in the segmentation of gene expression images

  18. On the relation between promoter divergence and gene expression evolution

    E-print Network

    Barkai, Naama

    On the relation between promoter divergence and gene expression evolution Itay Tirosh1 , Adina-regulatory sequences of related organisms, but the impact of these differences on gene expression remains largely)-binding sequences of yeasts and mammals have no detectable effect on gene expression, suggesting that compensatory

  19. Regulatory activity revealed by dynamic correlations in gene expression noise

    E-print Network

    Dunlop, Mary

    Regulatory activity revealed by dynamic correlations in gene expression noise Mary J Dunlop1, or `noise', in gene expression propagate through active, but not inactive, regulatory links1,2. Thus, correlations in gene expression noise could provide a noninvasive means to probe the activity states

  20. Transcription Factor Binding Site Prediction with Multivariate Gene Expression Data

    E-print Network

    Zhang, Nancy R.

    Transcription Factor Binding Site Prediction with Multivariate Gene Expression Data Nancy R. Zhang for the de novo discovery of cis-acting regulatory sequences using gene expression data. However, when sites can significantly affect their strength in activating gene expression. We propose an adaptive

  1. DETECTION AND DECOMPOSITION: TREATMENT-INDUCED CYCLIC GENE EXPRESSION

    E-print Network

    Qin, Wensheng

    DETECTION AND DECOMPOSITION: TREATMENT-INDUCED CYCLIC GENE EXPRESSION DISRUPTION IN HIGH of a day. How- ever, treatment-induced disruption of regular cyclic gene expression patterns presents to distinguish the cyclic patterns from the rest gene expression patterns, and discussed potential future

  2. An Interactive Approach to Mining Gene Expression Data

    E-print Network

    Pei, Jian

    An Interactive Approach to Mining Gene Expression Data Daxin Jiang, Jian Pei, Member, IEEE Computer and coherent patterns in gene expression data is an important task in bioinformatics research and biomedical. The interpretation of co-expression heavily depends on domain knowledge. Furthermore, groups of coexpressed genes

  3. The Use of EST Expression Matrixes for the Quality Control of Gene Expression Data

    E-print Network

    Sheldon, Nathan D.

    The Use of EST Expression Matrixes for the Quality Control of Gene Expression Data Andrew T differential gene expression, but cDNA libraries' origins and EST data quality are not always known or reported-specific gene expression, assume EST counts to be correct and libraries to be correctly annotated, which

  4. CLUSTERING GENE EXPRESSION SIGNALS FROM RETINAL MICROARRAY DATA G. Fleury ,

    E-print Network

    Hero, Alfred O.

    CLUSTERING GENE EXPRESSION SIGNALS FROM RETINAL MICROARRAY DATA G. Fleury , , A. Hero , S. Yoshida a robust method for detecting evolutionary trends of gene expression from a temporal sequence of mi- croarray data. In this method we perform gene clustering via multi-objective optimization to reveal genes

  5. Aberrant cerebellar development of transgenic mice expressing dominant-negative thyroid hormone receptor in cerebellar Purkinje cells.

    PubMed

    Yu, Lu; Iwasaki, Toshiharu; Xu, Ming; Lesmana, Ronny; Xiong, Yu; Shimokawa, Noriaki; Chin, William W; Koibuchi, Noriyuki

    2015-04-01

    To study the role of the thyroid hormone (TH) in cerebellar development, we generated transgenic mice expressing a dominant-negative TH receptor (TR) in cerebellar Purkinje cells. A mutant human TR?1 (G345R), which binds to the TH-response element but cannot bind to T3, was subcloned into exon 4 of the full-length L7/Pcp-2 gene, which is specifically expressed in Purkinje and retinal rod bipolar cells. The transgene was specifically expressed in Purkinje cells in the postnatal cerebellum. Purkinje cell dendrite arborization was significantly delayed in the transgenic mice. Surprisingly, granule cell migration was also significantly delayed. In the primary cerebellar culture, TH-induced Purkinje cell dendrite arborization was also suppressed. In quantitative real-time RT-PCR analysis, the expression levels of several TH-responsive genes were altered. The expression levels of inositol trisphosphate receptor type 1 and retinoic acid receptor-related orphan receptor? mRNAs, which are mainly expressed in Purkinje cells, and brain-derived neurotrophic factor mRNA, which is expressed in both Purkinje and granule cells, were significantly decreased. The expression levels of neurotrophin-3 and hairless mRNAs, which are mainly expressed in granule cells, and myelin basic protein mRNA, which is mainly expressed in oligodendrocytes, were also decreased. The motor coordination of transgenic mice was significantly disrupted. These results indicate that TH action through its binding to TR in Purkinje cells is required for the normal cerebellar development. TH action through TR in Purkinje cells is also important for the development of other subsets of cerebellar cells such as granule cells and oligodendrocytes. PMID:25603044

  6. Gene expression associated with intersterility in Heterobasidion.

    PubMed

    Van der Nest, M A; Olson, Å; Karlsson, M; Lind, M; Dalman, K; Brandström-Durling, M; Elfstrand, M; Wingfield, B D; Stenlid, J

    2014-12-01

    Intersterility (IS) is thought to prevent mating compatibility between homokaryons that belong to different species. Although IS in Heterobasidion is regulated by the genes located at the IS loci, it is not yet known how the IS genes influence sexual compatibility and heterokaryon formation. To increase our understanding of the molecular events underlying IS, we studied mRNA abundance changes during IS compatible and incompatible interactions over time. The clustering of the transcripts into expression profiles, followed by the application of Gene Ontology (GO) enrichment pathway analysis of each of the clusters, allowed inference of biological processes participating in IS. These analyses identified events involved in mating and sexual development (i.e., linked with IS compatibility), which included processes associated with cell-cell adhesion and recognition, cell cycle control and signal transduction. We also identified events potentially involved in overriding mating between individuals belonging to different species (i.e., linked with IS incompatibility), which included reactive oxygen species (ROS) production, responses to stress (especially to oxidative stress), signal transduction and metabolic biosynthesis. Our findings thus enabled detection and characterization of gene expression changes associated with IS in Heterobasidion, as well as identification of important processes and pathways associated with this phenomenon. Overall, the results of this study increase current knowledge regarding the molecular mechanisms underpinning IS in Heterobasidion and allowed for the establishment of a vital baseline for further studies. PMID:25459536

  7. Transition Metals in Control of Gene Expression

    NASA Astrophysics Data System (ADS)

    O'Halloran, Thomas V.

    1993-08-01

    Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology.

  8. Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

    PubMed Central

    Tamburini, Beth A.; Trapp, Susan; Phang, Tzu Lip; Schappa, Jill T.; Hunter, Lawrence E.; Modiano, Jaime F.

    2009-01-01

    The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors. PMID:19461996

  9. Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL.

    PubMed

    Zhou, Yan; Kurukuti, Sreenivasulu; Saffrey, Peter; Vukovic, Milica; Michie, Alison M; Strogantsev, Ruslan; West, Adam G; Vetrie, David

    2013-12-19

    TAL1 is an important regulator of hematopoiesis and its expression is tightly controlled despite complexities in its genomic organization. It is frequently misregulated in T-cell acute lymphoblastic leukemia (T-ALL), often due to deletions between TAL1 and the neighboring STIL gene. To better understand the events that lead to TAL1 expression in hematopoiesis and in T-ALL, we studied looping interactions at the TAL1 locus. In TAL1-expressing erythroid cells, the locus adopts a looping "hub" which brings into close physical proximity all known TAL1 cis-regulatory elements including CTCF-bound insulators. Loss of GATA1 results in disassembly of the hub and loss of CTCF/RAD21 from one of its insulators. Genes flanking TAL1 are partly dependent on hub integrity for their transcriptional regulation. We identified looping patterns unique to TAL1-expressing T-ALL cells, and, intriguingly, loops occurring between the TAL1 and STIL genes at the common TAL1/STIL breakpoints found in T-ALL. These findings redefine how TAL1 and neighboring genes communicate within the nucleus, and indicate that looping facilitates both normal and aberrant TAL1 expression and may predispose to structural rearrangements in T-ALL. We also propose that GATA1-dependent looping mechanisms may facilitate the conservation of TAL1 regulation despite cis-regulatory remodeling during vertebrate evolution. PMID:24200685

  10. Factors Regulating Baculovirus Late and Very Late Gene Expression in Transient-Expression Assays

    Microsoft Academic Search

    JASON W. TODD; A. LORENA PASSARELLI; ALBERT LU; ANDLOIS K. MILLER

    1996-01-01

    Eighteen genes ofAutographa californicanuclear polyhedrosis virus are necessary and sufficient to transac- tivate expression from the late vp39 promoter in transient-expression assays in SF-21 cells. These 18 genes, known as late expression factor genes (lefs), are also required to transactivate the very late promoter of the polyhedrin gene,polh, but expression from this promoter is relatively weak compared with expression from

  11. Gene length and expression level shape genomic novelties

    PubMed Central

    Grishkevich, Vladislav

    2014-01-01

    Gene duplication and alternative splicing are important mechanisms in the production of genomic novelties. Previous work has shown that a gene’s family size and the number of splice variants it produces are inversely related, although the underlying reason is not well understood. Here, we report that gene length and expression level together explain this relationship. We found that gene lengths correlate with both gene duplication and alternative splicing: Longer genes are less likely to produce duplicates and more likely to exhibit alternative splicing. We show that gene length is a dynamic property, increasing with evolutionary time—due in part to the insertions of transposable elements—and decreasing following partial gene duplications. However, gene length alone does not account for the relationship between alternative splicing and gene duplication. A gene’s expression level appears both to impose a strong constraint on its length and to restrict gene duplications. Furthermore, high gene expression promotes alternative splicing, in particular for long genes, and alternatively, short genes with low expression levels have large gene families. Our analysis of the human and mouse genomes shows that gene length and expression level are primary genic properties that together account for the relationship between gene duplication and alternative splicing and bias the origin of novelties in the genome. PMID:25015383

  12. Aberrant Expression of PHLPP1 and PHLPP2 Correlates with Poor Prognosis in Patients with Hypopharyngeal Squamous Cell Carcinoma

    PubMed Central

    Zhou, Jieyu; Yu, Xuemin; Wang, Juan; Li, Tao; Jin, Tong; Lei, Dapeng; Pan, Xinliang

    2015-01-01

    The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both). Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001) and in adjacent nontumor mucosae (r = 0.460, P<0.001). The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64) and PHLPP2 (85.9%, 55/64). However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138) and 82.6% (114/138) of tumor tissues, respectively (P<0.0001, both). The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all). It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS) in HSCC patients (P = 0.004, P = 0.008, respectively). Multivariate analysis revealed that PHLPP1 was an independent prognostic factor for OS. This study indicates that, in HSCC, aberrant expressions of PHLPP1 and PHLPP2 are common events, and loss of PHLPPs might identify patients with poor prognostic outcomes. PMID:25793736

  13. Aberrant methylation accounts for cell adhesion-related gene silencing during 3-methylcholanthrene and diethylnitrosamine induced multistep rat lung carcinogenesis associated with overexpression of DNA methyltransferases 1 and 3a

    SciTech Connect

    Liu Wenbin; Cui Zhihong; Ao Lin; Zhou Ziyuan; Zhou Yanhong; Yuan Xiaoyan; Xiang Yunlong; Liu Jinyi, E-mail: jinyiliutmmu@163.com; Cao Jia, E-mail: caojia1962@126.com

    2011-02-15

    To evaluate the significance of alterations in cell adhesion-related genes methylation during lung multistep carcinogenesis induced by the genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN), tissue samples microdissected from MCA/DEN-induced rat lung carcinogenesis model were subjected to methylation-specific PCR to evaluate the DNA methylation status of CADM1, TIMP3, E-cadherin and N-cadherin. Immunohistochemistry was used to determine protein expression of CADM1, TIMP3, N-cadherin and the DNA methyltransferases (DNMTs) 1, 3a and 3b. E-cadherin hypermethylation was not detected in any tissue. CADM1, TIMP3 and N-cadherin hypermethylation was correlated with the loss of their protein expression during the progression of pathologic lesions. The prevalence of DNA methylation of at least one gene and the average number of methylated genes increased with the histological progression. DNMT1 and DNMT3a protein expression increased progressively during the stages of lung carcinogenesis, whereas DNMT3b overexpression was only found in several samples. Furthermore, DNMT1 protein expression levels were correlated with CADM1 methylation, and DNMT3a protein expression levels were correlated with CADM1, TIMP3 and N-cadherin methylation. The average number of methylated genes during carcinogenesis was significantly correlated with DNMT1 and DNMT3a protein expression levels. Moreover, mRNA expression of CADM1 significantly increased after treatment with DNMT inhibitor 5-aza-2'-deoxycytidine in CADM1-methylated primary tumor cell lines. Our findings suggest that an accumulation of hypermethylation accounts for cell adhesion-related gene silencing is associated with dynamic changes in the progression of MCA/DEN-induced rat lung carcinogenesis. We suggest that DNMT1 and DNMT3a protein overexpression may be responsible for this aberrant DNA methylation.

  14. Recombination products suggest the frequent occurrence of aberrant gene replacement in the moss Physcomitrella patens.

    PubMed

    Wendeler, Edelgard; Zobell, Oliver; Chrost, Bozena; Reiss, Bernd

    2015-02-01

    In gene replacement, a variant of gene targeting, transformed DNA integrates into the genome by homologous recombination (HR) to replace resident sequences. Gene replacement in the moss Physcomitrella patens is extremely efficient, but often large amounts of additional DNA are integrated at the target locus. A detailed analysis of recombination junctions of PpCOL2 gene knockout mutants shows that the integrated DNA can be highly rearranged. Our data suggest that the replaced sequences were excised by HR and became integrated back into the genome by non-homologous end-joining (NHEJ). RAD51-mediated strand-invasion and subsequent strand-exchange is central to the two-end invasion pathway, the major gene replacement pathway in yeast. In this pathway, integration is initiated by the free ends of a single replacement vector-derived donor molecule which then integrates as an entity. Gene replacement in P. patens is entirely RAD51-dependent suggesting the existence of a pathway mechanistically similar to two-end invasion. However, invasion of the two ends does not seem to be stringently coordinated in P. patens. Actually, often only one fragment end became integrated by HR, or one-sided integration of two independent donor fragments occurred simultaneously leading to a double-strand break that is subsequently sealed by NHEJ and thus causes the observed rearrangements. PMID:25557140

  15. Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model.

    PubMed

    Wang, Z; Halbert, C L; Lee, D; Butts, T; Tapscott, S J; Storb, R; Miller, A D

    2014-04-01

    Animal and human gene therapy studies utilizing AAV vectors have shown that immune responses to AAV capsid proteins can severely limit transgene expression. The main source of capsid antigen is that associated with the AAV vectors, which can be reduced by stringent vector purification. A second source of AAV capsid proteins is that expressed from cap genes aberrantly packaged into AAV virions during vector production. This antigen source can be eliminated by the use of a cap gene that is too large to be incorporated into an AAV capsid, such as a cap gene containing a large intron (captron gene). Here, we investigated the effects of elimination of cap gene transfer and of vector purification by CsCl gradient centrifugation on AAV vector immunogenicity and expression following intramuscular injection in dogs. We found that both approaches reduced vector immunogenicity and that combining the two produced the lowest immune responses and highest transgene expression. This combined approach enabled the use of a relatively mild immunosuppressive regimen to promote robust micro-dystrophin gene expression in Duchenne muscular dystrophy-affected dogs. Our study shows the importance of minimizing AAV cap gene impurities and indicates that this improvement in AAV vector production may benefit human applications. PMID:24500525

  16. Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes

    E-print Network

    Zhang, Jianzhi

    Gene clustering pattern, promoter architecture, and gene expression stability in eukaryotic genomes by Wen-Hsiung Li, January 5, 2011 (sent for review November 5, 2010) A balance between gene expression studied whether the genetic and epigenetic properties of the promoter affect gene expression variability

  17. Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions to aberrant methylation in Beckwith–Wiedemann syndrome with epimutations

    PubMed Central

    Maeda, Toshiyuki; Higashimoto, Ken; Jozaki, Kosuke; Yatsuki, Hitomi; Nakabayashi, Kazuhiko; Makita, Yoshio; Tonoki, Hidefumi; Okamoto, Nobuhiko; Takada, Fumio; Ohashi, Hirofumi; Migita, Makoto; Kosaki, Rika; Matsubara, Keiko; Ogata, Tsutomu; Matsuo, Muneaki; Hamasaki, Yuhei; Ohtsuka, Yasufumi; Nishioka, Kenichi; Joh, Keiichiro; Mukai, Tsunehiro; Hata, Kenichiro; Soejima, Hidenobu

    2014-01-01

    Purpose: Expression of imprinted genes is regulated by DNA methylation of differentially methylated regions (DMRs). Beckwith–Wiedemann syndrome is an imprinting disorder caused by epimutations of DMRs at 11p15.5. To date, multiple methylation defects have been reported in Beckwith–Wiedemann syndrome patients with epimutations; however, limited numbers of DMRs have been analyzed. The susceptibility of DMRs to aberrant methylation, alteration of gene expression due to aberrant methylation, and causative factors for multiple methylation defects remain undetermined. Methods: Comprehensive methylation analysis with two quantitative methods, matrix-assisted laser desorption/ionization mass spectrometry and bisulfite pyrosequencing, was conducted across 29 DMRs in 54 Beckwith–Wiedemann syndrome patients with epimutations. Allelic expressions of three genes with aberrant methylation were analyzed. All DMRs with aberrant methylation were sequenced. Results: Thirty-four percent of KvDMR1–loss of methylation patients and 30% of H19DMR–gain of methylation patients showed multiple methylation defects. Maternally methylated DMRs were susceptible to aberrant hypomethylation in KvDMR1–loss of methylation patients. Biallelic expression of the genes was associated with aberrant methylation. Cis-acting pathological variations were not found in any aberrantly methylated DMR. Conclusion: Maternally methylated DMRs may be vulnerable to DNA demethylation during the preimplantation stage, when hypomethylation of KvDMR1 occurs, and aberrant methylation of DMRs affects imprinted gene expression. Cis-acting variations of the DMRs are not involved in the multiple methylation defects. PMID:24810686

  18. Gravity-Induced Gene Expression in Plants.

    NASA Astrophysics Data System (ADS)

    Sederoff, Heike; Heber, Steffen; Howard, Brian; Myburg-Nichols, Henrietta; Hammond, Rebecca; Salinas-Mondragon, Raul; Brown, Christopher S.

    Plants sense changes in their orientation towards the vector of gravity and respond with directional growth. Several metabolites in the signal transduction cascade have been identified. However, very little is known about the interaction between these sensing and signal transduction events and even less is known about their role in the differential growth response. Gravity induced changes in transcript abundance have been identified in Arabidopsis whole seedlings and root apices (Moseyko et al. 2002; Kimbrough et al. 2004). Gravity induced transcript abundance changes can be observed within less than 1 min after stimulation (Salinas-Mondragon et al. 2005). Gene expression however requires not only transcription but also translation of the mRNA. Translation can only occur when mRNA is associated with ribosomes, even though not all mRNA associated with ribosomes is actively translated. To approximate translational capacity we quantified whole genome transcript abundances in corn stem pulvini during the first hour after gravity stimulation in total and poly-ribosomal fractions. As in Arabidopsis root apices, transcript abundances of several clusters of genes responded to gravity stimulation. The vast majority of these transcripts were also found to associate with polyribosomes in the same temporal and quantitative pattern. These genes are transcriptionally regulated by gravity stimulation, but do not exhibit translational regulation. However, a small group of genes showed increased transcriptional regulation after gravity stimulation, but no association with polysomes. These transcripts likely are translationally repressed. The mechanism of translational repression for these transcripts is unknown. Based on the hypothesis that the genes essential for gravitropic responses should be expressed in most or all species, we compared the temporal gravity induced expression pattern of all orthologs identified between maize and Arabidopsis. A small group of genes showed high sequence identity as well as a conserved pattern of transcript abundance changes after gravity stimulation between corn pulvinus tissue and Arabidopsis root apices. The functions of these genes in gravitropic responses are currently being analyzed and should give us important information about evolutionary conserved elements in plant gravity signal transduction. (This research was funded by NASA). Kimbrough, J. M., R. Salinas-Mondragon, et al. (2004). "The Fast and Transient Transcriptional Network of Gravity and Mechanical Stimulation in the Arabidopsis Root Apex." Plant Physiol. 136(1): 2790-2805. Moseyko, N., T. Zhu, et al. (2002). "Transcription profiling of the early gravitropic response in Arabidopsis using high-density oligonucleotide probe microarrays." Plant Physiol 130(2): 720-8. Salinas-Mondragon, R., A. Brogan, et al. (2005). "Gravity and light: integrating transcriptional regulation in roots." Gravit Space Biol Bull 18(2): 121-2.

  19. Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G 1 regulatory genes

    PubMed Central

    Matsumoto, Y; Tanaka, K; Nakatani, F; Matsunobu, T; Matsuda, S; Iwamoto, Y

    2001-01-01

    Chromosomal translocation t(11;22)(q24:q12) is detected in approximately 90% of tumours of the Ewing family (ET). This translocation results in EWS-Fli1 gene fusion which produces a EWS-Fli1 fusion protein acting as an aberrant transcriptional activator. We previously reported that the inhibition of EWS-Fli1 expression caused the G 0/G 1 arrest of ET cells. We, therefore, hypothesized that EWS-Fli1 may affect the expression of G 1 regulatory genes. Downregulation of EWS-Fli1 fusion proteins was observed 48 hours after the treatment with EWS-Fli1 antisense oligonucleotides. The expressions of G 1 cyclins, cyclin D1 and cyclin E, were markedly decreased in parallel with the reduction of EWS-Fli1 fusion protein. On the other hand, the expression of p21 and p27, which are important cyclin-dependent kinase inhibitors (CKIs) for G 1–S transition, was dramatically increased after the treatment with EWS-Fli1 antisense oligonucleotides. RT-PCR analysis showed that alteration of the expressions of the cyclins and CKIs occurred at the mRNA level. Furthermore, transfection of EWS-Fli1 cDNA to NIH3T3 caused transformation of the cells and induction of the expression of cyclin D1 and E. Clinical samples of ET also showed a high level of expression of cyclin D1 mRNA, whereas mRNAs for p21 and p27 were not detected in the samples. These findings strongly suggest that the G 1–S regulatory genes may be involved in downstream of EWS-Fli1 transcription factor, and that the unbalanced expression of G 1–S regulatory factors caused by EWS-Fli1 may lead to the tumorigenesis of ET. © 2001 Cancer Research Campaign http://www. bjcancer.com PMID:11259090

  20. Gene expression correlation decline in aging mice 1 Aging mice show a decreasing correlation of gene expression

    E-print Network

    Owen, Art

    Gene expression correlation decline in aging mice 1 Aging mice show a decreasing correlation of gene expression within genetic modules Lucinda K. Southworth1 , Art B. Owen2 , Stuart K. Kim3 1 Lucinda for the differential analysis of gene co-expression networks, and apply this method to look for large

  1. RH: FAZIO ET AL.-GENE EXPRESSION AND MACROPARASITES IN EELS DIFFERENTIAL GENE EXPRESSION ANALYSIS IN EUROPEAN EELS

    E-print Network

    Boyer, Edmond

    1 RH: FAZIO ET AL.-GENE EXPRESSION AND MACROPARASITES IN EELS DIFFERENTIAL GENE EXPRESSION ANALYSIS IN EUROPEAN EELS (ANGUILLA ANGUILLA, L. 1758) NATURALLY INFECTED BY MACROPARASITES G. Fazio*, H. Monée, R of the European eel and the expression of genes involved in the host physiology during its continental life

  2. Combining Serial Analysis of Gene Expression and Array Technologies to Identify Genes Differentially Expressed in Breast Cancer1

    Microsoft Academic Search

    Mariana Nacht; Anne T. Ferguson; Wen Zhang; Joseph M. Petroziello; Brian P. Cook; Yu Hong Gao; Sharon Maguire; Deborah Riley; George Coppola; Gregory M. Landes; Stephen L. Madden; Saraswati Sukumar

    1999-01-01

    Several methods have been used recently to determine gene expression profiles of cell populations. Here we demonstrate the strength of combin- ing two approaches, serial analysis of gene expression (SAGE) and DNA arrays, to help elucidate pathways in breast cancer progression by finding genes consistently expressed at different levels in primary breast cancers, metastatic breast cancers, and normal mammary epithelial

  3. Aberrant expression of regulatory cytokine IL-35 and pattern recognition receptor NOD2 in patients with allergic asthma.

    PubMed

    Wong, Chun Kwok; Leung, Ting Fan; Chu, Ida Miu Ting; Dong, Jie; Lam, Yvonne Yi On; Lam, Christopher Wai Kei

    2015-02-01

    We investigated the plasma concentration of the novel regulatory cytokine IL-35 and intracytosolic pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors in granulocytes and explored their potential implication in disease severity monitoring of allergic asthma. The expression of circulating IL-35 and other pro-inflammatory mediators in asthmatic patients or control subjects were evaluated using enzyme-linked immunosorbent assay (ELISA). The intracellular expressions of NOD1 and NOD2 in CCR3+ granulocytes were assessed using flow cytometry. Plasma concentrations of IL-35, IL-17A, basophil activation marker basogranulin, and eosinophilic airway inflammation biomarker periostin were significantly elevated in allergic asthmatic patients compared to non-atopic control subjects (all probability (p) <0.05). Both granulocyte markers exhibited significant and positive correlation with plasma IL-35 concentration in asthmatic patients (all p?Aberrant expression of NOD2 in granulocytes may be contributed to the impaired innate immunity predisposing allergic asthma. IL-35 may serve as a potential surrogate biomarker for disease severity of allergic asthma. PMID:25326182

  4. Multi-gene linear separability of gene expression data in linear time

    E-print Network

    Mukhopadhyay, Asish

    Multi-gene linear separability of gene expression data in linear time Md. Shafiul Alam, Satish] Unger and Chor showed how to test for linear sep- arability of gene expression data with respect to pairs of genes. Their method however is not amenable to an efficient test when more than 2 genes

  5. A Hierarchical Method for Selecting Feature Genes from Gene-Expression Profiles

    NASA Astrophysics Data System (ADS)

    Rui-xue, Huang; Shu-yang, Lin; Di-wei, Wu; Yan-yun, Qu; Quan, Zou

    A novel feature genes selection method is presented for detecting disease causal genes from gene expression profiles. In this paper, we take three steps and combine genetic algorithm, k-nearest neighbor and statistical test to detect the most important genes. Experiments on colorectal cancer gene-expression profiles prove the performance of our method.

  6. Promoter methylation confers kidney-specific expression of the Klotho gene.

    PubMed

    Azuma, Masahiro; Koyama, Daisuke; Kikuchi, Jiro; Yoshizawa, Hiromichi; Thasinas, Dissayabutra; Shiizaki, Kazuhiro; Kuro-o, Makoto; Furukawa, Yusuke; Kusano, Eiji

    2012-10-01

    The aging suppressor geneKlotho is predominantly expressed in the kidney irrespective of species. Because Klotho protein is an essential component of an endocrine axis that regulates renal phosphate handling, the kidney-specific expression is biologically relevant; however, little is known about its underlying mechanisms. Here we provide in vitro and in vivo evidence indicating that promoter methylation restricts the expression of the Klotho gene in the kidney. Based on evolutionary conservation and histone methylation patterns, the region up to -1200 bp was defined as a major promoter element of the human Klotho gene. This region displayed promoter activity equally in Klotho-expressing and -nonexpressing cells in transient reporter assays, but the activity was reduced to ?20% when the constructs were integrated into the chromatin in the latter. Both endogenous and transfected Klotho promoters were 30-40% methylated in Klotho-nonexpressing cells, but unmethylated in Klotho-expressing renal tubular cells. DNA demethylating agents increased Klotho expression 1.5- to 3.0-fold in nonexpressing cells and restored the activity of silenced reporter constructs. Finally, we demonstrated that a severe hypomorphic allele of Klotho had aberrant CpG methylation in kl/kl mice. These findings might be useful in therapeutic intervention for accelerated aging and several complications caused by Klotho down-regulation. PMID:22782974

  7. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats

    PubMed Central

    Ren, Ke; Novikova, Svetlana I; He, Fang; Dubner, Ronald; Lidow, Michael S

    2005-01-01

    Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR) injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors) to compare gene expression profiles in the lumbar spinal dorsal horn (LDH) of adult (P60) male rats that received neonatal CAR treatment within (at postnatal day 3; P3) and outside (at postnatal 12; P12) of the sensitive period. The data were obtained both without inflammation (at baseline) and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems) were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems) in the LDH ipsilateral to the neonatally-injured paw. The largest aberration in gene expression, however, was observed during inflammation of the neonatally injured hindpaws in the ipsilateral LDH, which included thirty-six genes (encoding numerous members of glutamate, serotonin, GABA, calcitonin gene-related peptide, neurotrophin, and interleukin systems). These findings suggest that changes in gene expression may be involved in the long-term nociceptive effects of neonatal noxious insult at the spinal level. PMID:16179088

  8. A gene expression signature for insulin resistance.

    PubMed

    Konstantopoulos, Nicky; Foletta, Victoria C; Segal, David H; Shields, Katherine A; Sanigorski, Andrew; Windmill, Kelly; Swinton, Courtney; Connor, Tim; Wanyonyi, Stephen; Dyer, Thomas D; Fahey, Richard P; Watt, Rose A; Curran, Joanne E; Molero, Juan-Carlos; Krippner, Guy; Collier, Greg R; James, David E; Blangero, John; Jowett, Jeremy B; Walder, Ken R

    2011-02-11

    Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a gene expression signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made "insulin resistant" by treatment with tumor necrosis factor-? (TNF-?) and then reversed with aspirin and troglitazone ("resensitized"). The GES consisted of five genes whose expression levels best discriminated between the insulin-resistant and insulin-resensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed with aspirin and troglitazone. This screen identified both known and new insulin-sensitizing compounds including nonsteroidal anti-inflammatory agents, ?-adrenergic antagonists, ?-lactams, and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels; P < 0.001). These findings show that GES technology can be used for both the discovery of insulin-sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes. PMID:21081660

  9. Hierarchical Clustering of Breast Cancer Methylomes Revealed Differentially Methylated and Expressed Breast Cancer Genes

    PubMed Central

    Lin, I-Hsuan; Chen, Dow-Tien; Chang, Yi-Feng; Lee, Yu-Ling; Su, Chia-Hsin; Cheng, Ching; Tsai, Yi-Chien; Ng, Swee-Chuan; Chen, Hsiao-Tan; Lee, Mei-Chen; Chen, Hong-Wei; Suen, Shih-Hui; Chen, Yu-Cheng; Liu, Tze-Tze; Chang, Chuan-Hsiung; Hsu, Ming-Ta

    2015-01-01

    Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs) and the hypomethylation of the megabase-sized partially methylated domains (PMDs) are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI) was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma) dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation. PMID:25706888

  10. Focus Issue--The Dynamics of Gene Expression

    NSDL National Science Digital Library

    Nancy R. Gough (American Association for the Advancement of Science; Managing Editor of Science's STKE REV)

    2004-10-26

    It is gene expression that defines a cell's identity. Science, Science's Science of Aging Knowledge Environment (SAGE KE), and Science's STKE focus attention on the highly dynamic nature of gene expression. Mechanisms governing selective gene expression in multigene families, as well as those by which cis- and trans-acting factors contribute to regulation of gene expression, are topics under discussion. In addition, new methodologies allow researchers to gain insight into gene expression at the level of single cells and provide a glimpse at the real-time interactions among proteins and DNA.

  11. FBXW7-mutated colorectal cancer cells exhibit aberrant expression of phosphorylated-p53 at Serine-15.

    PubMed

    Li, Ningning; Lorenzi, Federica; Kalakouti, Eliana; Normatova, Makhliyo; Babaei-Jadidi, Roya; Tomlinson, Ian; Nateri, Abdolrahman S

    2015-04-20

    FBXW7 mutations occur in a variety of human cancers including colorectal cancer (CRC). Elucidating its mechanism of action has become crucial for cancer therapy; however, it is also complicated by the fact that FBXW7 can influence many pathways due to its role as an E3-ubiquitin ligase in proteasome degradation. FBXW7 and TP53 are tumour suppressors intensively implicated in colorectal carcinogenesis. Deletion mutations in these two genes in animal models mark the progression from adenoma to carcinoma. Although still largely unknown, the last defense mechanism against CRC at the molecular level could be through a synergistic effect of the two genes. The underlying mechanism requires further investigation. In our laboratory, we have used a phospho-kinase profiler array to illustrate a potential molecular link between FBXW7 and p53 in CRC cells. In vitro and in vivo assessments demonstrated aberrant induction of phosphorylated p53 at Serine 15 [phospho-p53(Ser15)] in human FBXW7-deficient CRC cells as compared to their FBXW7-wild-type counterparts. FBXW7 loss in HCT116 cells promoted resistance to oxaliplatin. Immunoblotting data further confirmed that reduction of phospho-p53(Ser15) may contribute to the decreased efficacy of therapy in FBXW7-mutated CRC cells. The findings may suggest the applicability of phospho-p53(Ser15) as an indicative marker of FBXW7-mutations. Phospho-p53(Ser15) regulation by FBXW7 E3-ligase activity could provide important clues for understanding FBXW7 behavior in tumour progression and grounds for its clinical applicability thereafter. PMID:25860929

  12. FBXW7-mutated colorectal cancer cells exhibit aberrant expression of phosphorylated-p53 at Serine-15

    PubMed Central

    Normatova, Makhliyo; Babaei-Jadidi, Roya; Tomlinson, Ian; Nateri, Abdolrahman S.

    2015-01-01

    FBXW7 mutations occur in a variety of human cancers including colorectal cancer (CRC). Elucidating its mechanism of action has become crucial for cancer therapy; however, it is also complicated by the fact that FBXW7 can influence many pathways due to its role as an E3-ubiquitin ligase in proteasome degradation. FBXW7 and TP53 are tumour suppressors intensively implicated in colorectal carcinogenesis. Deletion mutations in these two genes in animal models mark the progression from adenoma to carcinoma. Although still largely unknown, the last defense mechanism against CRC at the molecular level could be through a synergistic effect of the two genes. The underlying mechanism requires further investigation. In our laboratory, we have used a phospho-kinase profiler array to illustrate a potential molecular link between FBXW7 and p53 in CRC cells. In vitro and in vivo assessments demonstrated aberrant induction of phosphorylated p53 at Serine 15 [phospho-p53(Ser15)] in human FBXW7-deficient CRC cells as compared to their FBXW7-wild-type counterparts. FBXW7 loss in HCT116 cells promoted resistance to oxaliplatin. Immunoblotting data further confirmed that reduction of phospho-p53(Ser15) may contribute to the decreased efficacy of therapy in FBXW7-mutated CRC cells. The findings may suggest the applicability of phospho-p53(Ser15) as an indicative marker of FBXW7-mutations. Phospho-p53(Ser15) regulation by FBXW7 E3-ligase activity could provide important clues for understanding FBXW7 behavior in tumour progression and grounds for its clinical applicability thereafter. PMID:25860929

  13. Identification of human HK genes and gene expression regulation study in cancer from transcriptomics data analysis.

    PubMed

    Chen, Meili; Xiao, Jingfa; Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  14. Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus

    PubMed Central

    Ben-Shachar, Shay; Chahrour, Maria; Thaller, Christina; Shaw, Chad A.; Zoghbi, Huda Y.

    2009-01-01

    A group of post-natal neurodevelopmental disorders collectively referred to as MeCP2 disorders are caused by aberrations in the gene encoding methyl-CpG-binding protein 2 (MECP2). Loss of MeCP2 function causes Rett syndrome (RTT), whereas increased copy number of the gene causes MECP2 duplication or triplication syndromes. MeCP2 acts as a transcriptional repressor, however the gene expression changes observed in the hypothalamus of MeCP2 disorder mouse models suggest that MeCP2 can also upregulate gene expression, given that the majority of genes are downregulated upon loss of MeCP2 and upregulated in its presence. To determine if this dual role of MeCP2 extends beyond the hypothalamus, we studied gene expression patterns in the cerebellum of Mecp2-null and MECP2-Tg mice, modeling RTT and MECP2 duplication syndrome, respectively. We found that abnormal MeCP2 dosage causes alterations in the expression of hundreds of genes in the cerebellum. The majority of genes were upregulated in MECP2-Tg mice and downregulated in Mecp2-null mice, consistent with a role for MeCP2 as a modulator that can both increase and decrease gene expression. Interestingly, many of the genes altered in the cerebellum, particularly those increased by the presence of MeCP2 and decreased in its absence, were similarly altered in the hypothalamus. Our data suggest that either gain or loss of MeCP2 results in gene expression changes in multiple brain regions and that some of these changes are global. Further delineation of the expression pattern of MeCP2 target genes throughout the brain might identify subsets of genes that are more amenable to manipulation, and can thus be used to modulate some of the disease phenotypes. PMID:19369296

  15. Mouse neutrophils lacking lamin B receptor expression exhibit aberrant development and lack critical functional responses

    PubMed Central

    Gaines, Peter; Tien, Chiung W.; Olins, Ada L.; Olins, Donald E.; Shultz, Leonard D.; Carney, Lisa; Berliner, Nancy

    2008-01-01

    Objective The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and the activation of functional responses, which include chemotaxis and the generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on the expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly (PHA) and the "ichthyosis" (ic) phenotype in mice. In this study we have investigated roles for LBR in mediating neutrophil development and the activation of multiple neutrophil functions, including chemotaxis and the respiratory burst. Materials and Methods A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses. Results Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation. Conclusions Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus but also proliferative and functional responses that are critical to innate immunity. PMID:18550262

  16. Aberrant microRNA expression in peripheral plasma and mononuclear cells as specific blood-based biomarkers in schizophrenia patients.

    PubMed

    Sun, Xin-yang; Lu, Jim; Zhang, Liang; Song, Hong-tao; Zhao, Lin; Fan, Hui-min; Zhong, Ai-fang; Niu, Wei; Guo, Zhong-min; Dai, Yun-hua; Chen, Chao; Ding, Yan-fen; Zhang, Li-yi

    2015-03-01

    Findings from multiple studies on microRNA (miRNA) expression profiling in schizophrenia patients have produced conflicting results. In order to investigate miRNA as specific biomarkers in the peripheral plasma and peripheral blood mononuclear cells (PBMC) of schizophrenia patients, expression levels of the nine most frequently reported schizophrenia-associated miRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) were examined in the peripheral plasma and PBMC in 25 schizophrenia patients and 13 healthy controls using quantitative real-time reverse transcription polymerase chain reaction. We observed significantly increased expressions of miR-132, miR-195, miR-30e and miR-7 in plasma samples (p<0.05 to p<0.001), and miR-212, miR-34a and miR-30e in PBMC samples (p<0.05 to p<0.01). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of miR-30e in plasma was 0.767 (95% confidence interval [CI] 0.608-0.926) with sensitivity and specificity of 90.90% and 60.00% respectively, and the AUC of miR-30e in PBMC was 0.756 (95% CI 0.584-0.929) with sensitivity and specificity of 81.80% and 68.00%, respectively. Logistic regression analysis demonstrated that miR-30e in plasma was more sensitive to differentiate schizophrenia patients from normal controls than miR-30e in PBMC. Our findings indicate that miRNA expression is more significant in plasma than in PBMC, and suggest that miR-30e in plasma may be a more sensitive biomarker for schizophrenia diagnosis, although its aberrant expression can be detected in both plasma and PBMC. PMID:25487174

  17. Gene expression profiling of the rat superior olivary complex using serial analysis of gene expression

    Microsoft Academic Search

    Alexander Koehl; Nicole Schmidt; Anne Rieger; Sara M. Pilgram; Ivica Letunic; Peer Bork; Florentina Soto; Eckhard Friauf; Hans Gerd Nothwang

    2004-01-01

    The superior olivary complex (SOC) is an auditory brainstem region that represents a favourable system to study rapid neurotransmission and the maturation of neuronal circuits. Here we performed serial analysis of gene expression (SAGE) on the SOC in 60-day-old Sprague-Dawley rats to identify genes specifically important for its function and to create a transcriptome reference for the subsequent identification of

  18. Chromosomal Aberrations and Schizophrenia

    PubMed Central

    Bassett, Anne S.

    2011-01-01

    Chromosomal aberrations associated with schizophrenic disorders may suggest regions in which to focus a search for genes predisposing to schizophrenia by a linkage strategy. As for other genetic illnesses, chromosomal abnormalities may also provide useful tools for subsequent physical mapping, fine localisation, and isolation of important susceptibility genes. Identification of several chromosomal aberrations may be especially important, given the unknown pathophysiology, the paucity of known brain genes, and the probable genetic heterogeneity of schizophrenia and manic-depression. However, because psychiatric disorders are common and inherited in a complex manner, researchers must use caution when drawing inferences about associations with chromosomal aberrations. Reported abnormalities involving autosomes (chromosomes 1 –22) associated with psychotic disorders are reviewed. Their relevance to linkage studies localising genes for schizophrenia was estimated by standardised criteria for specificity, diagnosis, family history, and overall weight of evidence. Four ‘possibly relevant’ chromosomal regions were identified: 5q, 11q, 18q, and 19p. This paper outlines strategies for future studies to detect new chromosomal aberrations associated with major psychotic disorders that may be relevant to isolating the genes for schizophrenia. PMID:1393302

  19. Pomelo II: finding differentially expressed genes

    PubMed Central

    Morrissey, Edward R.; Diaz-Uriarte, Ramón

    2009-01-01

    Pomelo II (http://pomelo2.bioinfo.cnio.es) is an open-source, web-based, freely available tool for the analysis of gene (and protein) expression and tissue array data. Pomelo II implements: permutation-based tests for class comparisons (t-test, ANOVA) and regression; survival analysis using Cox model; contingency table analysis with Fisher's exact test; linear models (of which t-test and ANOVA are especial cases) that allow additional covariates for complex experimental designs and use empirical Bayes moderated statistics. Permutation-based and Cox model analysis use parallel computing, which permits taking advantage of multicore CPUs and computing clusters. Access to, and further analysis of, additional biological information and annotations (PubMed references, Gene Ontology terms, KEGG and Reactome pathways) are available either for individual genes (from clickable links in tables and figures) or sets of genes. The source code is available, allowing for extending and reusing the software. A comprehensive test suite is also available, and covers both the user interface and the numerical results. The possibility of including additional covariates, parallelization of computation, open-source availability of the code and comprehensive testing suite make Pomelo II a unique tool. PMID:19435879

  20. Pomelo II: finding differentially expressed genes.

    PubMed

    Morrissey, Edward R; Diaz-Uriarte, Ramón

    2009-07-01

    Pomelo II (http://pomelo2.bioinfo.cnio.es) is an open-source, web-based, freely available tool for the analysis of gene (and protein) expression and tissue array data. Pomelo II implements: permutation-based tests for class comparisons (t-test, ANOVA) and regression; survival analysis using Cox model; contingency table analysis with Fisher's exact test; linear models (of which t-test and ANOVA are especial cases) that allow additional covariates for complex experimental designs and use empirical Bayes moderated statistics. Permutation-based and Cox model analysis use parallel computing, which permits taking advantage of multicore CPUs and computing clusters. Access to, and further analysis of, additional biological information and annotations (PubMed references, Gene Ontology terms, KEGG and Reactome pathways) are available either for individual genes (from clickable links in tables and figures) or sets of genes. The source code is available, allowing for extending and reusing the software. A comprehensive test suite is also available, and covers both the user interface and the numerical results. The possibility of including additional covariates, parallelization of computation, open-source availability of the code and comprehensive testing suite make Pomelo II a unique tool. PMID:19435879

  1. Reptile freeze tolerance: metabolism and gene expression.

    PubMed

    Storey, Kenneth B

    2006-02-01

    Terrestrially hibernating reptiles that live in seasonally cold climates need effective strategies of cold hardiness to survive the winter. Use of thermally buffered hibernacula is very important but when exposure to temperatures below 0 degrees C cannot be avoided, either freeze avoidance (supercooling) or freeze tolerance strategies can be employed, sometimes by the same species depending on environmental conditions. Several reptile species display ecologically relevant freeze tolerance, surviving for extended times with 50% or more of their total body water frozen. The use of colligative cryoprotectants by reptiles is poorly developed but metabolic and enzymatic adaptations providing anoxia tolerance and antioxidant defense are important aids to freezing survival. New studies using DNA array screening are examining the role of freeze-responsive gene expression. Three categories of freeze responsive genes have been identified from recent screenings of liver and heart from freeze-exposed (5h post-nucleation at -2.5 degrees C) hatchling painted turtles, Chrysemys picta marginata. These genes encode (a) proteins involved in iron binding, (b) enzymes of antioxidant defense, and (c) serine protease inhibitors. The same genes were up-regulated by anoxia exposure (4 h of N2 gas exposure at 5 degrees C) of the hatchlings which suggests that these defenses for freeze tolerance are aimed at counteracting the injurious effects of the ischemia imposed by plasma freezing. PMID:16321368

  2. Downregulation of retinoic acid receptor-?2 expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines

    Microsoft Academic Search

    Zhong-Min Liu; Fang Ding; Ming-Zhou Guo; Li-Yong Zhang; Min Wu; Zhi-Hua Liu

    2004-01-01

    AIM: To study the role of hypermethylation in the loss of retinoic acid receptor ?2 (RAR?2) in esophageal squamous cell carcinoma (ESCC). METHODS: The role of hypermethylation in RAR?2 gene silencing in 6 ESCC cell lines was determined by methylation- specific PCR (MSP), and its methylation status was compared with RAR?2 mRNA expression by RT-PCR. The MSP results were confirmed

  3. Temporally and Spatially Restricted Gene Expression Profiling

    PubMed Central

    Tallafuss, Alexandra; Washbourne, Philip; Postlethwait, John

    2014-01-01

    Identifying gene function in specific cells is critical for understanding the processes that make cells unique. Several different methods are available to isolate actively transcribed RNA or actively translated RNA in specific cells at a chosen time point. Cell-specific mRNA isolation can be accomplished by the expression of transgenes in cells of interest, either directly from a specific promoter or using a modular system such as Gal4/UAS or Cre/lox. All of the methods described in this review, namely thiol-labeling of RNA (TU-tagging or RABT), TRAP (translating ribosome affinity purification) and INTACT (isolation of nuclei tagged in specific cell types), allow next generation sequencing, permitting the identification of enriched gene transcripts within the specific cell-type. We describe here the general concept of each method, include examples, evaluate possible problems related to each technique, and suggest the types of questions for which each method is best suited. PMID:25132798

  4. Differential Gene Expression Profile Associated with the Abnormality of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

    PubMed Central

    Li, Jianping; Yang, Shaoguang; Lu, Shihong; Zhao, Hui; Feng, Jianming; Li, Wenqian; Ma, Fengxia; Ren, Qian; Liu, Bin; Zhang, Lei; Zheng, Yizhou; Han, Zhong Chao

    2012-01-01

    Aplastic anemia (AA) is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs) and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs). In the present study, we comprehensively compared the biological features and gene expression profile of BM-MSCs between AA patients and healthy volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed aberrant morphology, decreased proliferation and clonogenic potential and increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to differentiate into adipocytes but more difficult to differentiate into osteoblasts. Consistent with abnormal biological features, a large number of genes implicated in cell cycle, cell division, proliferation, chemotaxis and hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from AA patients. Conversely, more related genes with apoptosis, adipogenesis and immune response showed increased expression in BM-MSCs from AA patients. The gene expression profile of BM-MSCs further confirmed the abnormal biological properties and provided significant evidence for the possible mechanism of the destruction of the bone marrow microenvironment in AA. PMID:23144828

  5. Relationship between promoter methylation & tissue expression of MGMT gene in ovarian cancer

    PubMed Central

    Shilpa, V.; Bhagat, Rahul; Premalata, C.S.; Pallavi, V.R.; Ramesh, G.; Krishnamoorthy, Lakshmi

    2014-01-01

    Background & objectives: Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumour suppressor genes. O6-methyguanine-DNA methyltransferase (MGMT) is a DNA repair gene that removes mutagenic and cytotoxic adducts from the O6-position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression has been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human epithelial ovarian carcinoma. Methods: A total of 88 epithelial ovarian cancer (EOC) tissue samples, 14 low malignant potential (LMP) tumours and 20 benign ovarian tissue samples were analysed for MGMT promoter methylation by nested methylation-specific polymerase chain reaction (MSP) after bisulphite modification of DNA. A subset of 64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples were analysed for protein expression by immunohistochemistry. Results: The methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and 20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP, benign tumours and normal ovarian tissue samples. Promoter hypermethylation with loss of protein expression was seen only in one case of EOC. Interpretation & conclusions: Our results suggest that MGMT promoter hypermethylation does not always reflect gene expression. PMID:25579142

  6. Electrochemical detection of aberrant methylated gene using naphthalene diimide derivative carrying four ferrocene moieties

    Microsoft Academic Search

    Shinobu Sato; Masato Tsueda; Shigeori Takenaka

    2010-01-01

    Naphthalene diimide derivative, F4ND, carrying four ferrocene moieties was synthesized as a new hybridization indicator for electrochemical gene detection using DNA probe-immobilized electrode. F4ND could bind to double stranded DNA with threading intercalation mode despite the existence of such bulky substituents. As result, an improved binding affinity due to slower dissociation from double stranded DNA was observed. F4ND could be

  7. The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells.

    PubMed

    Zampieri, Michele; Ciccarone, Fabio; Palermo, Rocco; Cialfi, Samantha; Passananti, Claudio; Chiaretti, Sabina; Nocchia, Daniela; Talora, Claudio; Screpanti, Isabella; Caiafa, Paola

    2014-09-01

    Aberrant upregulation of NOTCH3 gene plays a critical role in cancer pathogenesis. However, the underlying mechanisms are still unknown. We tested here the hypothesis that aberrant epigenetic modifications in the NOTCH3 promoter region might account for its upregulation in cancer cells. We compared DNA and histone methylation status of NOTCH3 promoter region in human normal blood cells and T cell acute lymphoblastic leukemia (T-ALL) cell lines, differentially expressing NOTCH3. We found that histone methylation, rather than DNA hypomethylation, contributes towards establishing an active chromatin status of NOTCH3 promoter in NOTCH3 overexpressing cancer cells. We discovered that the chromatin regulator protein BORIS/CTCFL plays an important role in regulating NOTCH3 gene expression. We observed that BORIS is present in T-ALL cell lines as well as in cell lines derived from several solid tumors overexpressing NOTCH3. Moreover, BORIS targets NOTCH3 promoter in cancer cells and it is able to induce and to maintain a permissive/active chromatin conformation. Importantly, the association between NOTCH3 overexpression and BORIS presence was confirmed in primary T-ALL samples from patients at the onset of the disease. Overall, our results provide novel insights into the determinants of NOTCH3 overexpression in cancer cells, by revealing a key role for BORIS as the main mediator of transcriptional deregulation of NOTCH3. PMID:24984200

  8. Genomic Deregulation during Renal Cell Carcinoma Metastasis Implements a Myofibroblast-Like Gene Expression Program

    PubMed Central

    López-Lago, Miguel A.; Thodima, Venkata J.; Guttapalli, Asha; Chan, Timothy; Heguy, Adriana; Molina, Ana M.; Reuter, Victor E.; Motzer, Robert J.; Chaganti, R. S. K.

    2012-01-01

    Clear cell renal cell carcinoma (RCC) is the most common and invasive adult kidney cancer. The genetic and biological mechanisms that drive metastatic spread of RCC remain largely unknown. We have investigated the molecular signatures and underlying genomic aberrations associated with RCC metastasis, using an approach that combines a human xenograft model, expression profiling of RNA, DNA and microRNA (miRNA), functional verification, and clinical validation. We show that increased metastatic activity is associated with acquisition of a myofibroblast-like signature in both tumor cell lines and in metastatic tumor biopsies. Our results also show that the mesenchymal trait did not provide an invasive advantage to the metastatic tumor cells. We further show that some of the constituents of the mesenchymal signature, including the expression of the well characterized myofibroblastic marker S100A4, are functionally relevant. Epigenetic silencing and miRNA-induced expression changes accounted for the change in expression of a significant number of genes, including S100A4, in the myofibroblastic signature; however, DNA copy number variation did not affect the same set of genes. These findings provide evidence that widespread genetic and epigenetic alterations can lead directly to global deregulation of gene expression and contribute to the development or progression of RCC metastasis culminating in a highly malignant myofibroblast-like cell with a mesenchymal phenotype. PMID:20952505

  9. Network Completion for Static Gene Expression Data

    PubMed Central

    Nakajima, Natsu

    2014-01-01

    We tackle the problem of completing and inferring genetic networks under stationary conditions from static data, where network completion is to make the minimum amount of modifications to an initial network so that the completed network is most consistent with the expression data in which addition of edges and deletion of edges are basic modification operations. For this problem, we present a new method for network completion using dynamic programming and least-squares fitting. This method can find an optimal solution in polynomial time if the maximum indegree of the network is bounded by a constant. We evaluate the effectiveness of our method through computational experiments using synthetic data. Furthermore, we demonstrate that our proposed method can distinguish the differences between two types of genetic networks under stationary conditions from lung cancer and normal gene expression data. PMID:24826192

  10. Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding

    Microsoft Academic Search

    Lars Nitschke; Frederic Lajaunias; Thomas Moll; Liza Ho; Eduardo Martinez-Soria; Shuichi Kikuchi; Marie-Laure Santiago-Raber; Carolin Dix; R. Michael; E. Parkhouse; Shozo Izui

    2005-01-01

    CD22 functions primarily as a negative regulator of B-cell receptor signaling. The Cd22a allele has been proposed as a candidate allele for murine systemic lupus erythematosus. In this study, we explored the possible expression of aberrant forms of CD22, which differ in the N-terminal sequences constituting the ligand-binding site due to synthesis of abnormally processed Cd22 mRNA, in several Cd22a

  11. Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

    PubMed Central

    Okamoto, Yoshichika; Chaves, Alysia; Chen, Jingchun; Kelley, Robert; Jones, Keith; Weed, Harrison G.; Gardner, Kevin L.; Gangi, Lisa; Yamaguchi, Mamoru; Klomkleaw, Wuthichai; Nakayama, Tomohiro; Hamlin, Robert L.; Carnes, Cynthia; Altschuld, Ruth; Bauer, John; Hai, Tsonwin

    2001-01-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the ?-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function. PMID:11485922

  12. Presence of Simian Virus 40 DNA Sequences in Human Lymphoid and Hematopoietic Malignancies and Their Relationship to Aberrant Promoter Methylation of Multiple Genes

    Microsoft Academic Search

    Narayan Shivapurkar; Takao Takahashi; Jyotsna Reddy; Yingye Zheng; Victor Stastny; Robert Collins; Shinichi Toyooka; Makato Suzuki; Gunjan Parikh; Sheryl Asplund; Steven H. Kroft; Charles Timmons; Robert W. McKenna; Ziding Feng; Adi F. Gazdar

    2004-01-01

    The simian polyoma virus SV40 has been detected in specific human tumors including non-Hodgkin's lymphomas, although a causative role for the virus has not been convincingly demonstrated. Aberrant methylation of CpG islands in promoter regions is a frequent method of silencing tumor suppressor genes (TSGs) in cancers and may be induced by oncogenic vi- ruses. We investigated the relationship between

  13. Diesel Exhaust Particulate Matter Dispersed in a Phospholipid Surfactant Induces Chromosomal Aberrations and Micronuclei but not 6-Thioguanine-Resistant Gene Mutation in V79 Cells

    Microsoft Academic Search

    Zu-Wei Gu; Michael J. Keane; Tong-man Ong; William E. Wallace

    2005-01-01

    Diesel exhaust particulate material (DPM) was assayed for induction of chromosomal aberrations (CA), micronucleus (MN) formation, and 6-thioguanine-resistant (TG) gene mutation in V79 cells as a dispersion in dipalmitoyl phosphatidylcholine (DPPC) in physiological saline, a simulated pulmonary surfactant. Filter-collected automobile DPM provided for the study was not organic solvent extracted, but was directly mixed into DPPC in saline dispersion as

  14. Comprehensive Analysis of Gene-Environmental Interactions with Temporal Gene Expression Profiles in Pseudomonas aeruginosa

    PubMed Central

    Duan, Kangmin; McCullough, William M.; Surette, Michael G.; Ware, Tony; Song, Jiuzhou

    2012-01-01

    To explore gene-environment interactions, based on temporal gene expression information, we analyzed gene and treatment information intensively and inferred interaction networks accordingly. The main idea is that gene expression reflects the response of genes to environmental factors, assuming that variations of gene expression occur under different conditions. Then we classified experimental conditions into several subgroups based on the similarity of temporal gene expression profiles. This procedure is useful because it allows us to combine diverse gene expression data as they become available, and, especially, allowing us to lay the regulatory relationships on a concrete biological basis. By estimating the activation points, we can visualize the gene behavior, and obtain a consensus gene activation order, and hence describe conditional regulatory relationships. The estimation of activation points and building of synthetic genetic networks may result in important new insights in the ongoing endeavor to understand the complex network of gene regulation. PMID:22558298

  15. Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer.

    PubMed

    Schwaederle, Maria; Daniels, Gregory A; Piccioni, David E; Kesari, Santosh; Fanta, Paul T; Schwab, Richard B; Shimabukuro, Kelly A; Parker, Barbara A; Kurzrock, Razelle

    2015-06-01

    Next generation sequencing is transforming patient care by allowing physicians to customize and match treatment to their patients' tumor alterations. Our goal was to study the association between key molecular alterations and outcome parameters. We evaluated the characteristics and outcomes (overall survival (OS), time to metastasis/recurrence, and best progression-free survival (PFS)) of 392 patients for whom next generation sequencing (182 or 236 genes) had been performed. The Kaplan-Meier method and Cox regression models were used for our analysis, and results were subjected to internal validation using a resampling method (bootstrap analysis). In a multivariable analysis (Cox regression model), the parameters that were statistically associated with a poorer overall survival were the presence of metastases at diagnosis (P = 0.014), gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDKN2A alterations (P = 0.0001). The variables associated with a shorter time to metastases/recurrence were gastrointestinal histology (P = 0.004), APC (P = 0.008), PTEN (P = 0.026) and TP53 (P = 0.044) alterations. TP53 (P = 0.003) and PTEN (P = 0.034) alterations were independent predictors of a shorter best PFS. A personalized treatment approach (matching the molecular aberration with a cognate targeted drug) also correlated with a longer best PFS (P = 0.046). Our study demonstrated that, across diverse cancers, anomalies in specific tumor suppressor genes (PTEN, CDKN2A, APC, and/or TP53) were independently associated with a worse outcome, as reflected by time to metastases/recurrence, best PFS on treatment, and/or overall survival. These observations suggest that molecular diagnostic tests may provide important prognostic information in patients with cancer. PMID:25928476

  16. Prediction of Compound Signature Using High Density Gene Expression Profiling

    Microsoft Academic Search

    Hisham K. Hamadeh; Pierre R. Bushel; Supriya Jayadev; Olimpia DiSorbo; Lee Bennett; Leping Li; Raymond Tennant; Raymond Stoll; J. Carl Barrett; Richard S. Paules; Kerry Blanchard; Cynthia A. Afshari

    2002-01-01

    DNA microarrays, used to measure the gene expression of thousands of genes simultaneously, hold promise for future appli- cation in efficient screening of therapeutic drugs. This will be aided by the development and population of a database with gene expression profiles corresponding to biological responses to expo- sures to known compounds whose toxicological and pathological endpoints are well characterized. Such

  17. Gene Expression Programming: a New Adaptive Algorithm for Solving Problems

    Microsoft Academic Search

    Candida Ferreira

    2001-01-01

    Gene expression programming, a genome\\/phenome genetic algorithm (linear and non-linear), is pre- sented here for the first time as a new technique for creation of computer programs. Gene expression programming uses character linear chromosomes composed of genes structurally organised in a head and a tail. The chromosomes function as a genome and are subjected to modification by means of mutation,

  18. Identification and characterization of regulators of FUM gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are polyketide derived mycotoxins produced by the maize pathogen Fusarium verticillioides. The genes required for fumonisin production are clustered on chromosome I. Previous analysis showed that the expression of the FUM genes is coordinately regulated and expression of the FUM gene cl...

  19. Cloning and expression of the porcine obese gene

    Microsoft Academic Search

    Christopher A. Bidwell; Shaoquan Ji; G. Robert Frank; Steven G. Cornelius; Gawain M. Willis; Michael E. Spurlock

    1997-01-01

    The product of the obese gene, leptin, may be an important regulator of adiposity via its regulation of feed intake and energy metabolism. Probes were developed using the polymerase chain reaction to analyze gene expression and determine the structure of the porcine ob gene. Porcine ob was expressed in adipose tissue as a 3,100 bp mRNA. Finished pigs (136 kg)

  20. Gene Expression Profiling of Helicobacter pylori Reveals a Growth-Phase-Dependent Switch in Virulence Gene Expression

    Microsoft Academic Search

    Lucinda J. Thompson; D. Scott Merrell; Brett A. Neilan; Hazel Mitchell; Adrian Lee; Stanley Falkow

    2003-01-01

    The global pattern of growth-phase-dependent gene expression of Helicobacter pylori during in vitro culture was analyzed by using a high-density DNA microarray. To detect consistent coordinated gene expression in this bacterium, temporal changes in transcription were assessed in two independent time courses. Cluster analysis of the expression profiles highlighted a major switch in gene expression during the late log-to-stationary phase

  1. cDNA microarray analysis of gene expression in parthenotes and in vitro produced buffalo embryos.

    PubMed

    Abdoon, A S; Ghanem, N; Kandil, O M; Gad, A; Schellander, K; Tesfaye, D

    2012-04-01

    The retarded development of parthenote embryo could be due to aberrant epigenetic imprinting, which may disrupt many aspects and lead to conceptus demise. The present work was conducted to: 1) compare the development of in vitro produced (IVP) and parthenogenetically developed (P) buffalo embryos from the 2-cell to blastocyst stage; 2) investigate the global gene expression profile and search for new candidate transcripts differing between IVP and P buffalo blastocyst using cDNA microarray analysis (validated by Real Time PCR); 3) follow the particular expression patterns of PLAC8 and OCT4 genes at five different stages of preimplantation development by Real Time PCR; and 4) study the expression of CDX2 at the blastcocyst stage. Cleavage rate was higher (P < 0.05) in P than IVP buffalo embryos, while, progression to blastocyst and number of cells per blastocyst were lower (P < 0.05) in P than IVP blastocysts. Microarray analysis indicate that 56 differentially expressed genes between the two groups, of which 51 genes (91.07%) were up-regulated, and five genes were downregulated in IVP blastocyst, using 1.4 fold-changes as a cutoff. Differentially expressed genes are related to translation, nucleic acid synthesis, cell adhesion and placentation. Validation of candidate genes revealed that the transcript abundance of PTGS2, RPS27A, TM2D3, PPA1, AlOX15, RPLO and PLAC8 were downregulated (7/8) in parthenote blastocyst compared to the IVP blastocyst. PLAC8 gene expression was higher (P < 0.05) at 2-cell, morula and blastocyst stages in IVP embryos compared with parthenote embryos. The OCT4 gene expression was higher (P < 0.05) in 2-cell, 4-cell, 8-cell and blastocysts produced in vitro. In conclusion, the retarded development of parthenogenetic buffalo embryos could be due to downregulation of genes related to translation, nucleic acid synthesis, cell adhesion, and placental development. The low expression of PLAC8 and OCT4 during the different stages of development may be responsible, in part, to the failure of development of parthenote buffalo embryos. PMID:22289221

  2. Gene expression profiling in male genital lichen sclerosus

    PubMed Central

    Edmonds, Emma; Barton, Geraint; Buisson, Sandrine; Francis, Nick; Gotch, Frances; Game, Laurence; Haddad, Munther; Dinneen, Michael; Bunker, Chris

    2011-01-01

    Male genital lichen sclerosus (MGLSc) has a bimodal distribution in boys and men. It is associated with squamous cell carcinoma (SCC). The pathogenesis of MGLSc is unknown. HPV and autoimmune mechanisms have been mooted. Anti extracellular matrix protein (ECM)1 antibodies have been identified in women with GLSc. The gene expression pattern of LSc is unknown. Using DNA microarrays we studied differences in gene expression in healthy and diseased prepuces obtained at circumcision in adult males with MGLSc (n = 4), paediatric LSc (n = 2) and normal healthy paediatric foreskin (n = 4). In adult samples 51 genes with significantly increased expression and 87 genes with significantly reduced expression were identified; paediatric samples revealed 190 genes with significantly increased expression and 148 genes with significantly reduced expression. Concordance of expression profiles between adult and paediatric samples indicates the same disease process. Functional analysis revealed increased expression in the adult and child MGSLc samples in the immune response/cellular defence gene ontology (GO) category and reduced expression in other categories including genes related to squamous cancer. No specific HPV, autoimmune or squamous carcinogenesis-associated gene expression patterns were found. ECM1 and CABLES1 expression were significantly reduced in paediatric and adult samples respectively. PMID:21718371

  3. Regulation of tropomyosin gene expression during myogenesis

    SciTech Connect

    Moss, M.; Schwartz, R.

    1981-03-01

    In skeletal muscle, tropomyosin has a critical role in transduction of calcium-induced contraction. Presently, little is known about the regulation of tropomyosin gene expression during myogenesis. In the present study, qualitative and quantitative changes in the nucleic acid populations of differentiating chicken embryo muscle cells in culture have been examined. Total nucleic acid content per nucleus increased about fivefold in fully developed myotubes as compared to mononucleated myoblasts. The contribution of deoxyribonucleic acid to the total nucleic acid population decreased from 24% in myoblasts to 5% of total nucleic acid in myotubes. Concomitant with the decrement in deoxyribonucleic acid contribution to total nucleic acid was an increase in polyadenylated ribonucleic acid (RNA) content per cell which reached levels in myotubes that were 17-fold higher than those of myoblasts. Specific changes in the RNA population during myogenesis were further investigated by quantitation of the synthetic capacity (messenger RNA levels) per cell for ..cap alpha..- and ..beta..-tropomyosin. Cell-free translation and immunoprecipitation demonstrated an approximately 40-fold increase in messenger RNA levels per nucleus for ..cap alpha..- and ..beta..-tropomyosin after fusion in the terminally differentiated myotubes. Indirect immunofluorescence with affinity-purified tropomyosin antibodies demonstrated the presence of tropomyosin-containing filaments in cells throughout myogenesis. Thus, the tropomyosin genes are constitutively expressed during muscle differentiation through the production of tropomyosin messenger RNA and translation into tropomyosin protein.

  4. Expressing genes do not forget their LINEs: transposable elements and gene expression

    PubMed Central

    Kines, Kristine J.; Belancio, Victoria P.

    2012-01-01

    1. ABSTRACT Historically the accumulated mass of mammalian transposable elements (TEs), particularly those located within gene boundaries, was viewed as a genetic burden potentially detrimental to the genomic landscape. This notion has been strengthened by the discovery that transposable sequences can alter the architecture of the transcriptome, not only through insertion, but also long after the integration process is completed. Insertions previously considered harmless are now known to impact the expression of host genes via modification of the transcript quality or quantity, transcriptional interference, or by the control of pathways that affect the mRNA life-cycle. Conversely, several examples of the evolutionary advantageous impact of TEs on the host gene structure that diversified the cellular transcriptome are reported. TE-induced changes in gene expression can be tissue-or disease-specific, raising the possibility that the impact of TE sequences may vary during development, among normal cell types, and between normal and disease-affected tissues. The understanding of the rules and abundance of TE-interference with gene expression is in its infancy, and its contribution to human disease and/or evolution remains largely unexplored. PMID:22201807

  5. Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes

    Microsoft Academic Search

    Jacques B de Kok; Rian W Roelofs; Belinda A Giesendorf; Jeroen L Pennings; Erwin T Waas; A. B. Feuth; Dorine W Swinkels; Paul N Span

    2005-01-01

    For interpretation of quantitative gene expression measurements in clinical tumor samples, a normalizer is necessary to correct expression data for differences in cellular input, RNA quality, and RT efficiency between samples. In many studies, a single housekeeping gene is used for normalization. However, no unequivocal single reference gene (with proven invariable expression between cells) has been identified yet. As the

  6. Generation of Kidney Transcriptomes Using Serial Analysis of Gene Expression

    Microsoft Academic Search

    Jeffrey R. Schelling; M. Ashraf El-Meanawy; Shrinath Barathan; Tatiana Dodig; Sudha K. Iyengar; John R. Sedor

    2002-01-01

    Chronic renal disease initiation and progression remain incompletely understood. Genomewide expression monitoring should clarify the mechanisms which cause progressive renal disease by determining how clusters of genes coordinately change their activity. Serial analysis of gene expression (SAGE) is a technique of expression profiling which permits simultaneous and quantitative analysis of 9- to 13-bp sequence tags that correspond to unique mRNAs.

  7. A Model for Measurement Error for Gene Expression Arrays

    Microsoft Academic Search

    David M. Rocke; Blythe Durbin

    2001-01-01

    We introduce a model for measurement error in gene expression arrays as a function of the expression level. This model, together with analysis methods, data transformations, and weighting, allows much more precise comparisons of gene expression, and provides guidance for analysis of background, determination of coné dence intervals, and preprocessing data for multivariate analysis.

  8. VISUALIZED ATLAS OF A GENE EXPRESSION DATABANK Jarkko Venna1

    E-print Network

    Kaski, Samuel

    VISUALIZED ATLAS OF A GENE EXPRESSION DATABANK Jarkko Venna1 and Samuel Kaski2,1 1 Neural Networks.kaski}@hut.fi ABSTRACT We construct an atlas of a gene expression databank, to visualize similarity relationships between expression data sets. Such an atlas could be used as an interface to the databank, for users searching

  9. Methods for evaluating gene expression from Affymetrix microarray datasets

    Microsoft Academic Search

    Ning Jiang; Lindsey J. Leach; Xiaohua Hu; Elena Potokina; Tianye Jia; Arnis Druka; Robbie Waugh; Michael J. Kearsey; Zewei W. Luo

    2008-01-01

    BACKGROUND: Affymetrix high density oligonucleotide expression arrays are widely used across all fields of biological research for measuring genome-wide gene expression. An important step in processing oligonucleotide microarray data is to produce a single value for the gene expression level of an RNA transcript using one of a growing number of statistical methods. The challenge for the researcher is to

  10. Serum response factor: toggling between disparate programs of gene expression

    Microsoft Academic Search

    Joseph M. Miano

    2003-01-01

    Serum response factor (SRF) is a widely expressed transcription factor involved in orchestrating disparate programs of gene expression linked to muscle differentiation and cellular growth. Vascular smooth muscle cell (SMC) differentiation, for example, is marked by the coordinate expression of several contractile and cytoskeletal genes regulated directly by SRF through one or more CArG-box elements in the immediate vicinity of

  11. Monoallelic expression of the human FOXP2 speech gene.

    PubMed

    Adegbola, Abidemi A; Cox, Gerald F; Bradshaw, Elizabeth M; Hafler, David A; Gimelbrant, Alexander; Chess, Andrew

    2015-06-01

    The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations. PMID:25422445

  12. Monoallelic expression of the human FOXP2 speech gene

    PubMed Central

    Adegbola, Abidemi A.; Cox, Gerald F.; Bradshaw, Elizabeth M.; Hafler, David A.; Gimelbrant, Alexander; Chess, Andrew

    2015-01-01

    The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations. PMID:25422445

  13. Large scale data mining approach for gene-specific standardization of microarray gene expression data

    Microsoft Academic Search

    Sukjoon Yoon; Young Yang; Jiwon Choi; Jeeweon Seong

    2006-01-01

    Motivation: The identification of the change of gene expression in multifactorial diseases, such as breast cancer is a major goal of DNA microarrayexperiments.Herewepresentanewdataminingstrategyto better analyze the marginal difference in gene expression between microarray samples. The idea is based on the notion that the consid- erationof gene'sbehaviorin a widevarietyof experiments canimprove the statistical reliability on identifying genes with moderate changes between

  14. [The polymorphism of catechol-O-methyltransferase (COMT) and hemochromatosis (HFE) genes in the radiocontaminated regions residents with different chromosome aberration frequency].

    PubMed

    Ivanova, T I; Kondrashova, T V; Krikunova, L I; Smirnova, I A; Shentereva, N I; Sychenkova, N I; Rykova, E V; Zharikova, I A; Khorokhorina, V A; Riabchenko, N I; Zamulaeva, I A

    2010-01-01

    The association between polymorphisms in genes COMT, HFE that takes part in oxidative stress regulation, and chromosome aberration frequency in lymphocytes was assessed in 278 female residents of radiation polluted regions of Central Russia: Bryansk (322 kBk/m2) and Tula Districts (137Cs - 171 kBk/m2). The C187G, G845A genotyping of HFE and G1947A (H/L) of COMT was done by means of polymerase chain reaction-restriction fragment length polymorphism. Studied population was divided into 3 subgroups by level of chromosome aberrations per cell (0-2, 3-4, >5). There was shown statistically significant difference in distribution of COMTand HFE genotypes between the groups. The high frequency of chromosome aberrations (> or = 5%) was associated with homozygotes of the high activity COMT G/G and HFE CC. Heterozygotes for G1947A COMT and C187G HFE reveal negative association with the high frequency of chromosome aberrations and correspond to "resistance factors". PMID:20464957

  15. Coactivators in PPAR-Regulated Gene Expression

    PubMed Central

    Viswakarma, Navin; Jia, Yuzhi; Bai, Liang; Vluggens, Aurore; Borensztajn, Jayme; Xu, Jianming; Reddy, Janardan K.

    2010-01-01

    Peroxisome proliferator-activated receptor (PPAR)?, ? (also known as ?), and ? function as sensors for fatty acids and fatty acid derivatives and control important metabolic pathways involved in the maintenance of energy balance. PPARs also regulate other diverse biological processes such as development, differentiation, inflammation, and neoplasia. In the nucleus, PPARs exist as heterodimers with retinoid X receptor-? bound to DNA with corepressor molecules. Upon ligand activation, PPARs undergo conformational changes that facilitate the dissociation of corepressor molecules and invoke a spatiotemporally orchestrated recruitment of transcription cofactors including coactivators and coactivator-associated proteins. While a given nuclear receptor regulates the expression of a prescribed set of target genes, coactivators are likely to influence the functioning of many regulators and thus affect the transcription of many genes. Evidence suggests that some of the coactivators such as PPAR-binding protein (PBP/PPARBP), thyroid hormone receptor-associated protein 220 (TRAP220), and mediator complex subunit 1 (MED1) may exert a broader influence on the functions of several nuclear receptors and their target genes. Investigations into the role of coactivators in the function of PPARs should strengthen our understanding of the complexities of metabolic diseases associated with energy metabolism. PMID:20814439

  16. Aberration in epigenetic gene regulation in hippocampal neurogenesis by developmental exposure to manganese chloride in mice.

    PubMed

    Wang, Liyun; Shiraki, Ayako; Itahashi, Megu; Akane, Hirotoshi; Abe, Hajime; Mitsumori, Kunitoshi; Shibutani, Makoto

    2013-11-01

    We have shown that maternal manganese (Mn) exposure caused sustained disruption of hippocampal neurogenesis of mouse offspring. To clarify the effects of maternal Mn exposure on epigenetic gene regulation contributing to the sustained disruption of hippocampal neurogenesis, we treated pregnant ICR mice with MnCl? in diet from gestational day 10 through day 21 after delivery on weaning and searched epigenetically downregulated genes by global promoter methylation analysis in the hippocampal dentate gyrus of male offspring on postnatal day (PND) 21 and PND 77. By CpG promoter microarray analysis on PND 21 following 800-ppm Mn exposure, sustained promoter hypermethylation and transcript downregulation through PND 77 were confirmed with Mid1, Atp1a3, and Nr2f1, whereas Pvalb showed a transient hypermethylation only on weaning. The numbers of Pvalb? and ATP1a3? neurons suggestive of ?-aminobutyric acid (GABA)ergic interneurons, Mid1? cells suggestive of late-stage granule cell lineage and GABAergic interneurons, and COUP-TF1? cells suggestive of early-stage granule cell lineage were all reduced on PND 21, and reductions were sustained on PND 77 except for no change in Pvalb? cells. Mid1? cells showed asymmetric distribution with right-side predominance, and Mn exposure abolished it by promoter hypermethylation of the right side. These findings indicate epigenetic mechanisms as mediators, through which Mn exposure modulates neurogenesis involving both granule cell lineage and GABAergic interneurons with long-lasting and stable repercussions. Disruption of asymmetric cellular distribution of Mid1 suggests that higher brain functions specialized in the left or right side of the brain were affected. PMID:23976782

  17. Altered Cell Cycle Gene Expression and Apoptosis in Post-Implantation Dog Parthenotes

    PubMed Central

    Park, Jung Eun; Kim, Min Jung; Ha, Seung Kwon; Hong, So Gun; Oh, Hyun Ju; Kim, Geon A.; Park, Eun Jung; Kang, Jung Taek; Saadeldin, Islam M.; Jang, Goo; Lee, Byeong Chun

    2012-01-01

    Mature oocytes can be parthenogenetically activated by a variety of methods and the resulting embryos are valuable for studies of the respective roles of paternal and maternal genomes in early mammalian development. In the present study, we report the first successful development of parthenogenetic canine embryos to the post-implantation stage. Nine out of ten embryo transfer recipients became pregnant and successful in utero development of canine parthenotes was confirmed. For further evaluation of these parthenotes, their fetal development was compared with artificially inseminated controls and differentially expressed genes (DEGs) were compared using ACP RT-PCR, histological analysis and immunohistochemistry. We found formation of the limb-bud and no obvious differences in histological appearance of the canine parthenote recovered before degeneration occurred; however canine parthenotes were developmentally delayed with different cell cycle regulating-, mitochondria-related and apoptosis-related gene expression patterns compared with controls. In conclusion, our protocols were suitable for activating canine oocytes artificially and supported early fetal development. We demonstrated that the developmental abnormalities in canine parthenotes may result from defective regulation of apoptosis and aberrant gene expression patterns, and provided evidence that canine parthenotes can be a useful tool for screening and for comparative studies of imprinted genes. PMID:22905100

  18. Highthroughput soybean gene expression analysis The changes in the atmosphere are altering gene expression and affecting the interaction

    E-print Network

    DeLucia, Evan H.

    silencing in soybean. A short sequence of targeted plant gene is cloned into the vector. Soybean unifoliate expression and affecting the interaction between plants and pathogens and insects. We are using Affymetrix soybean oligoarrays to analyze changes in the gene expression profile. Affymetrix GeneChip® Soybean Genome

  19. Heterologous Expression of Novobiocin and Clorobiocin Biosynthetic Gene Clusters

    Microsoft Academic Search

    Alessandra S. Eustaquio; Bertolt Gust; Ute Galm; Shu-Ming Li; Keith F. Chater; Lutz Heide

    2005-01-01

    A method was developed for the heterologous expression of biosynthetic gene clusters in different Strepto- myces strains and for the modification of these clusters by single or multiple gene replacements or gene deletions with unprecedented speed and versatility. -Red-mediated homologous recombination was used for genetic modification of the gene clusters, and the attachment site and integrase of phage C31 were

  20. Gene expression network discovery: a pattern based biclustering approach

    Microsoft Academic Search

    Debahuti Mishra; Kailash Shaw; Sashikala Mishra; Amiya Kumar Rath; Milu Acharya

    2011-01-01

    Discovering biologically significant information from gene expression data is now a days playing important role in gene function detection, gene regulation, drug discovery, detecting and predicting the diseases. Many traditional clustering algorithms are present to discover such gene regulations. Such discovered clusters are known as global clusters, which incurs more processing overhead. To overcome such problem, the biclustering approach, also

  1. Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

    PubMed Central

    2011-01-01

    Background Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion. Methods By using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases. Results There were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for ?F1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008). Conclusions The present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL. PMID:21867533

  2. Expression of Cartilage Developmental Genes in Hoxc8- and Hoxd4-Transgenic Mice

    PubMed Central

    Kruger, Claudia; Kappen, Claudia

    2010-01-01

    Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the development of cartilage, the precursor to mature bone. Overexpression of the homeobox transcription factors Hoxc8 and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs), bone morphogenetic proteins (BMPs) and fibroblastic growth factors (FGFs) are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantly expressed in Hoxc8- and/or Hoxd4-transgenic cartilage, we performed quantitative RT-PCR on chondrocytes from Hox-transgenic mice. Gene expression levels of Bmp4, Fgf8, Fgf10, Mmp9, Mmp13, Nos3, Timp3, Wnt3a and Wnt5a were altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4-transgenic chondrocytes, respectively. Notably, Wnt3a expression was elevated in Hoxc8- and reduced in Hoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms, and provide the basis for future studies into the role of these genes and possible interactions in pathogenesis of cartilage defects in Hoxc8- and Hoxd4-transgenic mice. PMID:20126390

  3. Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice.

    PubMed

    Kruger, Claudia; Kappen, Claudia

    2010-01-01

    Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the development of cartilage, the precursor to mature bone. Overexpression of the homeobox transcription factors Hoxc8 and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs), bone morphogenetic proteins (BMPs) and fibroblastic growth factors (FGFs) are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantly expressed in Hoxc8- and/or Hoxd4-transgenic cartilage, we performed quantitative RT-PCR on chondrocytes from Hox-transgenic mice. Gene expression levels of Bmp4, Fgf8, Fgf10, Mmp9, Mmp13, Nos3, Timp3, Wnt3a and Wnt5a were altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4-transgenic chondrocytes, respectively. Notably, Wnt3a expression was elevated in Hoxc8- and reduced in Hoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms, and provide the basis for future studies into the role of these genes and possible interactions in pathogenesis of cartilage defects in Hoxc8- and Hoxd4-transgenic mice. PMID:20126390

  4. OsMADS22, an STMADS11-like MADS-box gene of rice, is expressed in non-vegetative tissues and its ectopic expression induces spikelet meristem indeterminacy.

    PubMed

    Sentoku, Naoki; Kato, Hideki; Kitano, Hidemi; Imai, Ryozo

    2005-03-01

    We report the cDNA sequence and gene expression patterns of OsMADS22, a novel member of the STMADS11-like family of MADS-box genes, from rice. In contrast to previously reported STMADS11-like genes, whose expression is detected in vegetative tissues, OsMADS22 is mainly expressed during embryogenesis and flower development. In situ hybridization analysis revealed that OsMADS22 expression is localized in the L1 layer of embryos and in developing stamen primordia. Ectopic expression of OsMADS22 in transgenic rice plants resulted in aberrant floral morphogenesis, characterized by a disorganized palea, an elongated glume, and a two-floret spikelet. The results are discussed in terms of rice spikelet development and a novel non-vegetative role for a STMADS11-like gene. PMID:15682279

  5. Multiclass Microarray Gene Expression Analysis Based on Mutual Dependency Models

    NASA Astrophysics Data System (ADS)

    Chetty, Girija; Chetty, Madhu

    In this paper a novel feature selection technique based on mutual dependency modelling between genes is proposed for multiclass microarray gene expression classification. Several studies on analysis of gene expression data has shown that the genes (whether or not they belong to the same gene group) get co-expressed via a variety of pathways. Further, a gene may participate in multiple pathways that may or may not be co-active for all samples. It is therefore biologically meaningful to simultaneously divide genes into functional groups and samples into co-active categories. This can be done by modeling gene profiles for multiclass microarray gene data sets based on mutual dependency models, which model complex gene interactions. Most of the current works in multiclass microarray gene expression studies are based on statistical models with little or no consideration of gene interactions. This has led to lack of robustness and overly optimistic estimates of accuracy and noise reduction. In this paper, we propose multivariate analysis techniques which model the mutual dependency between the features and take into account complex interactions for extracting a subset of genes. The two techniques, the cross modal factor analysis (CFA) and canonical correlation analysis(CCA) show a significant reduction in dimensionality and class-prediction error, and improvement in classification accuracy for multiclass microarray gene expression datasets.

  6. Gene Expression Patterns in Bone Following Mechanical Loading

    PubMed Central

    Mantila Roosa, Sara M; Liu, Yunlong; Turner, Charles H

    2011-01-01

    The advent of high-throughput measurements of gene expression and bioinformatics analysis methods offers new ways to study gene expression patterns. The primary goal of this study was to determine the time sequence for gene expression in a bone subjected to mechanical loading during key periods of the bone-formation process, including expression of matrix-related genes, the appearance of active osteoblasts, and bone desensitization. A standard model for bone loading was employed in which the right forelimb was loaded axially for 3 minutes per day, whereas the left forearm served as a nonloaded contralateral control. We evaluated loading-induced gene expression over a time course of 4 hours to 32 days after the first loading session. Six distinct time-dependent patterns of gene expression were identified over the time course and were categorized into three primary clusters: genes upregulated early in the time course, genes upregulated during matrix formation, and genes downregulated during matrix formation. Genes then were grouped based on function and/or signaling pathways. Many gene groups known to be important in loading-induced bone formation were identified within the clusters, including AP-1-related genes in the early-response cluster, matrix-related genes in the upregulated gene clusters, and Wnt/?-catenin signaling pathway inhibitors in the downregulated gene clusters. Several novel gene groups were identified as well, including chemokine-related genes, which were upregulated early but downregulated later in the time course; solute carrier genes, which were both upregulated and downregulated; and muscle-related genes, which were primarily downregulated. © 2011 American Society for Bone and Mineral Research. PMID:20658561

  7. Expressed genes in regenerating rat liver after partial hepatectomy

    PubMed Central

    Xu, Cun-Shuan; Chang, Cui-Fang; Yuan, Jin-Yun; Li, Wen-Qiang; Han, Hong-Peng; Yang, Ke-Jin; Zhao, Li-Feng; Li, Yu-Chang; Zhang, Hui-Yong; Rahman, Salman; Zhang, Jing-Bo

    2005-01-01

    AIM: To reveal the liver regeneration (LR) and its control as well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers. METHODS: Five hundred and fifty-one expressed sequence tags screened by suppression subtractive hybridization were made into an in-house cDNA microarray, and the expressive genes and their expressive profiles in regenerating rat livers were analyzed by microarray and bioinformatics. RESULTS: Three hundred of the analyzed 551 genes were up- or downregulated more than twofolds at one or more time points during LR. Most of the genes were up- or downregulated 2-5 folds, but the highest reached 90 folds of the control. One hundred and thirty-nine of them showed upregulation, 135 displayed downregulation, and up or down expression of 26 genes revealed a dependence on regenerating livers. The genes expressed in 24-h regenerating livers were much more than those in the others. Cluster analysis and generalization analysis showed that there were at least six distinct temporal patterns of gene expression in the regenerating livers, that is, genes were expressed in the immediate early phase, early phase, intermediate phase, early-late phase, late phase, terminal phase. CONCLUSION: In LR, the number of down-regulated genes was almost similar to that of the upregulated genes; the successively altered genes were more than the rapidly transient genes. The temporal patterns of gene expression were similar 2 and 4 h, 12 and 16 h, 48 and 96 h, 72 and 144 h after PH. Microarray combined with suppressive subtractive hybridization can effectively identify the genes related to LR. PMID:15902731

  8. Expression of early developmental genes in vole Microtus rossiaemeridionalis

    Microsoft Academic Search

    M. A. Sorokin; S. P. Medvedev; A. I. Shevchenko; N. M. Slynko; S. M. Zakian

    2010-01-01

    The expression of genes Sox2, Klf4, Myc, Sall4, Gata6, Foxa2, Hnf4a, Cdx2, Esrrb, Hand1 in cell lines, embryos and organs of adult voles Microtus rossiaemeridionalis was studied. High resemblance of the expression patterns of these genes in the organs of adult voles, mice and humans was\\u000a demonstrated. It was established that genes Gata6, Foxa2 and Hnf4a were specifically expressed in

  9. Evaluation of DNA microarray results with quantitative gene expression platforms

    Microsoft Academic Search

    Roger D Canales; Yuling Luo; James C Willey; Bradley Austermiller; Catalin C Barbacioru; Cecilie Boysen; Kathryn Hunkapiller; Roderick V Jensen; Charles R Knight; Kathleen Y Lee; Yunqing Ma; Botoul Maqsodi; Adam Papallo; Elizabeth Herness Peters; Karen Poulter; Patricia L Ruppel; Raymond R Samaha; Leming Shi; Wen Yang; Lu Zhang; Federico M Goodsaid

    2006-01-01

    We have evaluated the performance characteristics of three quantitative gene expression technologies and correlated their expression measurements to those of five commercial microarray platforms, based on the MicroArray Quality Control (MAQC) data set. The limit of detection, assay range, precision, accuracy and fold-change correlations were assessed for 997 TaqMan Gene Expression Assays, 205 Standardized RT (Sta)RT-PCR assays and 244 QuantiGene

  10. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

    PubMed Central

    2010-01-01

    Background Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. Results We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. Conclusion The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes. PMID:21172044

  11. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression.

    PubMed

    Salem, Tamer Z; Zhang, Fengrui; Thiem, Suzanne M

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production. PMID:23131351

  12. Stochastic Resonance Reveals “Pilot Light” Expression in Mammalian Genes

    PubMed Central

    Ptitsyn, Andrey

    2008-01-01

    Background Microarrays are widely used for estimation of expression of thousands of genes in a biological sample. The resolution ability of this method is limited by the background noise. Low expressed genes are detected with insufficient reliability and expression of many genes is never detected at all. Methodology/Principal Findings We have applied the principles of stochastic resonance to detect expression of genes from microarray signals below the background noise level. We report the periodic pattern detected in genes called “Absent” by traditional analysis. The pattern is consistent with expression of the conventionally detected genes and specific to the tissue of origin. This effect is corroborated by the analysis of oscillating gene expression in mouse (M.musculus) and yeast (S. cerevisae). Conclusion/Significance Most genes usually considered silent are in fact expressed at a very low level. Stochastic resonance can be applied to detect changes in expression pattern of low-expressed genes as well as for the validation of the probe performance in microarrays. PMID:18365000

  13. Mitochondrially-targeted expression of a cytoplasmic male sterility-associated orf220 gene causes male sterility in Brassica juncea

    PubMed Central

    2010-01-01

    Background The novel chimeric open reading frame (orf) resulting from the rearrangement of a mitochondrial genome is generally thought to be a causal factor in the occurrence of cytoplasmic male sterility (CMS). Both positive and negative correlations have been found between CMS-associated orfs and the occurrence of CMS when CMS-associated orfs were expressed and targeted at mitochondria. Some orfs cause male sterility or semi-sterility, while some do not. Little is currently known about how mitochondrial factor regulates the expression of the nuclear genes involved in male sterility. The purpose of this study was to investigate the biological function of a candidate CMS-associated orf220 gene, newly isolated from cytoplasmic male-sterile stem mustard, and show how mitochondrial retrograde regulated nuclear gene expression is related to male sterility. Results It was shown that the ORF220 protein can be guided to the mitochondria using the mitochondrial-targeting sequence of the ? subunit of F1-ATPase (atp2-1). Transgenic stem mustard plants expressed the chimeric gene containing the orf220 gene and a mitochondrial-targeting sequence of the ? subunit of F1-ATPase (atp2-1). Transgenic plants were male-sterile, most being unable to produce pollen while some could only produce non-vigorous pollen. The transgenic stem mustard plants also showed aberrant floral development identical to that observed in the CMS stem mustard phenotype. Results obtained from oligooarray analysis showed that some genes related to mitochondrial energy metabolism were down-regulated, indicating a weakening of mitochondrial function in transgenic stem mustard. Some genes related to pollen development were shown to be down-regulated in transgenic stem mustard and the expression of some transcription factor genes was also altered. Conclusion The work presented furthers our understanding of how the mitochondrially-targeted expression of CMS-associated orf220 gene causes male sterility through retrograde regulation of nuclear gene expression in Brassica juncea. PMID:20974011

  14. Aberrations of flat lenses and aplanatic metasurfaces.

    PubMed

    Aieta, Francesco; Genevet, Patrice; Kats, Mikhail; Capasso, Federico

    2013-12-16

    A study of optical aberrations for flat lenses based on phase discontinuities is reported. The wave aberration function and the analytical expression of the aberrations up to the 4th order are derived to describe the performance of both ideal and practical flat lenses. We find that aberration-free focusing is possible under axial illumination but off-axis aberrations appear when the excitation is not normal to the interface. An alternative design for an aplanatic metasurface on a curved substrate is proposed to focus light without coma and spherical aberrations. PMID:24514726

  15. Identifying Drug Active Pathways from Gene Networks Estimated by Gene Expression Data

    Microsoft Academic Search

    Yoshinori Tamada; Seiya Imoto; Kousuke Tashiro; Satoru Kuhara; Satoru Miyano

    2005-01-01

    We present a computational method for identifying genes and their regulatory pathways in?u- enced by a drug, using microarray gene expression data collected by single gene disruptions and drug responses. The automatic identiflcation of such genes and pathways in organisms' cells is an important problem for pharmacogenomics and the tailor-made medication. Our method estimates regulatory relationships between genes as a

  16. Meta-analysis of differentially expressed genes in osteosarcoma based on gene expression data

    PubMed Central

    2014-01-01

    Background To uncover the genes involved in the development of osteosarcoma (OS), we performed a meta-analysis of OS microarray data to identify differentially expressed genes (DEGs) and biological functions associated with gene expression changes between OS and normal control (NC) tissues. Methods We used publicly available GEO datasets of OS to perform a meta-analysis. We performed Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein-Protein interaction (PPI) networks analysis. Results Eight GEO datasets, including 240 samples of OS and 35 samples of controls, were available for the meta-analysis. We identified 979 DEGs across the studies between OS and NC tissues (472 up-regulated and 507 down-regulated). We found GO terms for molecular functions significantly enriched in protein binding (GO: 0005515, P = 3.83E-60) and calcium ion binding (GO: 0005509, P?=?3.79E-13), while for biological processes, the enriched GO terms were cell adhesion (GO:0007155, P?=?2.26E-19) and negative regulation of apoptotic process (GO: 0043066, P?=?3.24E-15), and for cellular component, the enriched GO terms were cytoplasm (GO: 0005737, P?=?9.18E-63) and extracellular region (GO: 0005576, P?=?2.28E-47). The most significant pathway in our KEGG analysis was Focal adhesion (P?=?5.70E-15). Furthermore, ECM-receptor interaction (P?=?1.27E-13) and Cell cycle (P?=?4.53E-11) are found to be highly enriched. PPI network analysis indicated that the significant hub proteins containing PTBP2 (Degree?=?33), RGS4 (Degree?=?15) and FXYD6 (Degree?=?13). Conclusions Our meta-analysis detected DEGs and biological functions associated with gene expression changes between OS and NC tissues, guiding further identification and treatment for OS. PMID:25023069

  17. Gene Expression in Bacillus subtilis Surface Biofilms With and Without

    E-print Network

    Wood, Thomas K.

    Abstract: Five independent DNA microarray experiments were used to study the gene expression profile of a 5 complete sporulation is not necessary for biofilm formation. The expression profiles of these two strains

  18. Gene Expression in the Addicted Brain

    PubMed Central

    Zhou, Zhifeng; Enoch, Mary-Anne; Goldman, David

    2015-01-01

    Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced by addictive agents are dynamic and divergent and range from signal pathway-specific perturbations to widespread molecular and cellular dysregulation that can be measured by “omic” methods and that can be used to identify new pathways. The molecular effects of addiction depend on timing of exposure or withdrawal, the stage of adaptation, the brain region, and the behavioral model, there being many models of addiction. However, the molecular neural adaptations across different drug exposures, conditions, and regions are to some extent shared and can reflect common actions on pathways relevant to addiction. Epigenetic studies of DNA methylation and histone modifications and studies of regulatory RNA networks have been informative for elucidating the mechanisms of transcriptional change in the addicted brain. PMID:25172478

  19. Growth Hormone Receptor Gene Expression in Puberty.

    PubMed

    Pagani, S; Meazza, C; Gertosio, C; Bozzola, E; Bozzola, M

    2015-07-01

    The mechanisms regulating the synergic effect of growth hormone and other hormones during pubertal spurt are not completely clarified. We enrolled 64 females of Caucasian origin and normal height including 22 prepubertal girls, 26 pubertal girls, and 16 adults to evaluate the role of Growth Hormone/Insulin-like growth factor-I axis (GH/IGF-I) during the pubertal period. In these subjects both serum IGF-I and growth hormone binding protein levels, as well as quantitative growth hormone receptor (GHR) gene expression were evaluated in peripheral lymphocytes of all individuals by real-time PCR. Our results showed significantly lower IGF-I levels in women (148±10?ng/ml) and prepubertal girls (166.34±18.85?ng/ml) compared to pubertal girls (441.95±29.42?ng/ml; p<0.0001). Serum GHBP levels were significantly higher in prepubertal (127.02±20.76?ng/ml) compared to pubertal girls (16.63±2.97?ng/ml; p=0.0001) and adult women (19.95±6.65?ng/ml; p=0.0003). We also found higher GHR gene expression levels in pubertal girls [174.73±80.22?ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)] compared with other groups of subjects [women: 42.52±7.66?ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase); prepubertal girls: 58.45±0.18.12?ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)], but the difference did not reach statistical significance. These results suggest that sexual hormones could positively influence GHR action, during the pubertal period, in a dual mode, that is, increasing GHR mRNA production and reducing GHR cleavage leading to GHBP variations. PMID:25602347

  20. Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine

    PubMed Central

    2013-01-01

    Background The purpose of the present study was to retrospectively evaluate whether copy number changes of the genes encoding the ribonucleotide reductase subunit M1 (RRM1) and/or subunit M2B (RRM2B) predict sensitivity to gemcitabine administered in combination with docetaxel compared to single agent docetaxel in advanced breast cancer patients. Methods Primary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering respectively RRM1 at 11p15.5 and a reference probe covering the centromere of chromosome 11 (CEN-11), and RRM2B at 8q22.3 and a reference probe covering the centromere of chromosome 8 (CEN-8). The assays were validated in a material of 60 normal breast samples. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS according to gene status were investigated by subgroup analyses, and the Wald test was applied. All statistical tests were two-sided. Results FISH analysis for both RRM1 and RRM2B was successful in 251 patients. RRM1 and RRM2B aberrations (deletions and amplifications) were observed in 15.9% and 13.6% of patients, respectively. RRM1 aberrations were associated with a decreased OS in the time interval 1.5-7.4 years (hazard ratio = 1.72, 95% confidence interval = 1.05-2.79, P = 0.03). RRM2B aberrations alone or in combination with RRM1 aberrations had no prognostic impact in terms of TTP or OS. RR was not different by gene status. No significant differences were detected in TTP or OS within subgroups according to gene status and chemotherapy regimen. Conclusions This study demonstrated the presence of RRM1 and RRM2B copy number changes in primary breast tumor specimens. Nevertheless, we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients. PMID:24215511

  1. Many body theory of stochastic gene expression

    NASA Astrophysics Data System (ADS)

    Walczak, Aleksandra M.

    The regulation of expression states of genes in cells is a stochastic process. The relatively small numbers of protein molecules of a given type present in the cell and the nonlinear nature of chemical reactions result in behaviours, which are hard to anticipate without an appropriate mathematical development. In this dissertation, I develop theoretical approaches based on methods of statistical physics and many-body theory, in which protein and operator state dynamics are treated stochastically and on an equal footing. This development allows me to study the general principles of how noise arising on different levels of the regulatory system affects the complex collective characteristics of systems observed experimentally. I discuss simple models and approximations, which allow for, at least some, analytical progress in these problems. These have allowed us to understand how the operator state fluctuations may influence the steady state properties and lifetimes of attractors of simple gene systems. I show, that for fast binding and unbinding from the DNA, the operator state may be taken to be in equilibrium for highly cooperative binding, when predicting steady state properties as is traditionally done. Nevertheless, if proteins are produced in bursts, the DNA binding state fluctuations must be taken into account explicitly. Furthermore, even when the steady state probability distributions are weakly influenced by the operator state fluctuations, the escape rate in biologically relevant regimes strongly depends on transcription factor-DNA binding rates.

  2. Partial least squares-based gene expression analysis in preeclampsia.

    PubMed

    Jiang, F; Yang, Y; Li, J; Li, W; Luo, Y; Li, Y; Zhao, H; Wang, X; Yin, G; Wu, G

    2015-01-01

    Preeclampsia is major cause of maternal and fetal morbidity and mortality. Currently, the etiology of preeclampsia is unclear. In this study, we investigated differences in gene expression between preeclampsia patients and controls using partial least squares-based analysis, which is more suitable than routine analysis. Expression profile data were downloaded from the Gene Expression Omnibus database. A total of 503 genes were found to be differentially expressed, including 248 downregulated genes and 255 overexpressed genes. Network analysis identified 5 hub genes, including UBB, PIK3R1, MAPRE1, VEGFA, and ITGB1. Three of these, PIK3R1, VEGFA, and ITGB1, are known to be associated with preeclampsia or preeclampsia-related biological processes. Our findings shed light on expression signatures of preeclampsia patients that can be used as theoretical support in future therapeutic studies. PMID:26125867

  3. Gene amplification and increased expression of the reduced folate carrier in transport elevated K562 cells.

    PubMed

    Wong, S C; Zhang, L; Proefke, S A; Hukku, B; Matherly, L H

    1998-04-01

    The molecular bases for the 6-fold elevated methotrexate transport capacity of K562.4CF cells (Matherly et al., Cancer Res. 51: 3420-3426, 1991) were studied with reduced folate carrier (RFC) cDNA, genomic, and antibody probes. Southern analysis showed that RFC gene copies were increased (approximately 4- to 5-fold) in K562.4CF over wild-type K562 cells. Fluorescence in situ hybridization using a genomic RFC probe confirmed the localization of the RFC gene to the q-arm of chromosome 21. In K562.4CF cells, the frequent loss of a normal copy of chromosome 21 (61% of metaphases) was accompanied by RFC gene amplification and translocations of amplified RFC gene fragments to several (2 to 6) different chromosomal loci not seen in wild-type cells. Particularly intense RFC signals were mapped to homogeneously staining regions in chromosomes 2 and 15. Increased RFC gene copies were accompanied by a similar increase in the major 3.1 kb RFC transcript by northern blotting and an approximately 7-fold elevated level of the broadly migrating (80-95 kDa) RFC protein on a western blot probed with an RFC C-terminal peptide antibody. These results demonstrate that selection of cells with a growth-limiting concentration of reduced folates (0.4 nM of leucovorin) is sufficient to promote chromosomal aberrations, including gene amplification and translocations that result in increased RFC expression and folate transport. PMID:9605439

  4. Indications for distinct pathogenic mechanisms of asbestos and silica through gene expression profiling of the response of lung epithelial cells.

    PubMed

    Perkins, Timothy N; Peeters, Paul M; Shukla, Arti; Arijs, Ingrid; Dragon, Julie; Wouters, Emiel F M; Reynaert, Niki L; Mossman, Brooke T

    2015-03-01

    Occupational and environmental exposures to airborne asbestos and silica are associated with the development of lung fibrosis in the forms of asbestosis and silicosis, respectively. However, both diseases display distinct pathologic presentations, likely associated with differences in gene expression induced by different mineral structures, composition and bio-persistent properties. We hypothesized that effects of mineral exposure in the airway epithelium may dictate deviating molecular events that may explain the different pathologies of asbestosis versus silicosis. Using robust gene expression-profiling in conjunction with in-depth pathway analysis, we assessed early (24 h) alterations in gene expression associated with crocidolite asbestos or cristobalite silica exposures in primary human bronchial epithelial cells (NHBEs). Observations were confirmed in an immortalized line (BEAS-2B) by QRT-PCR and protein assays. Utilization of overall gene expression, unsupervised hierarchical cluster analysis and integrated pathway analysis revealed gene alterations that were common to both minerals or unique to either mineral. Our findings reveal that both minerals had potent effects on genes governing cell adhesion/migration, inflammation, and cellular stress, key features of fibrosis. Asbestos exposure was most specifically associated with aberrant cell proliferation and carcinogenesis, whereas silica exposure was highly associated with additional inflammatory responses, as well as pattern recognition, and fibrogenesis. These findings illustrate the use of gene-profiling as a means to determine early molecular events that may dictate pathological processes induced by exogenous cellular insults. In addition, it is a useful approach for predicting the pathogenicity of potentially harmful materials. PMID:25351596

  5. Kainic acid-induced F-344 rat model of mesial temporal lobe epilepsy: gene expression and canonical pathways.

    PubMed

    Sharma, Alok K; Searfoss, George H; Reams, Rachel Y; Jordan, William H; Snyder, Paul W; Chiang, Alan Y; Jolly, Robert A; Ryan, Timothy P

    2009-10-01

    Mesial temporal lobe epilepsy (MTLE) is a severe neurological condition of unknown pathogenesis for which several animal models have been developed. To obtain a better understanding of the underlying molecular mechanisms and identify potential biomarkers of lesion progression, we used a rat kainic acid (KA) treatment model of MTLE coupled with global gene expression analysis to examine temporal (four hours, days 3, 14, or 28) gene regulation relative to hippocampal histopathological changes. The authors recommend reviewing the companion histopathology paper (Sharma et al. 2008) to get a better understanding of the work presented here. Analysis of filtered gene expression data using Ingenuity Pathways Analysis (Ingenuity Systems, http://www.ingenuity.com) revealed that a number of genes pertaining to neuronal plasticity (RhoA, Rac1, Cdc42, BDNF, and Trk), neurodegeneration (Caspase3, Calpain 1, Bax, a Cytochrome c, and Smac/Diablo), and inflammation/immune-response pathways (TNF-alpha, CCL2, Cox2) were modulated in a temporal fashion after KA treatment. Expression changes for selected genes known to have a role in neuronal plasticity were subsequently validated by quantitative polymerase chain reaction (qPCR). Notably, canonical pathway analysis revealed that a number of genes within the axon guidance signaling canonical pathway were up-regulated from Days 3 to 28, which correlated with aberrant mossy fiber (MF) sprouting observed histologically beginning at Day 6. Importantly, analysis of the gene expression data also identified potential biomarkers for monitoring neurodegeneration (Cox2) and neuronal/synaptic plasticity (Kalrn). PMID:19700661

  6. Inducible Gene Expression in Trypanosomes Mediated by a Prokaryotic Repressor

    Microsoft Academic Search

    Elizabeth Wirtz; Christine Clayton

    1995-01-01

    An inducible expression system was developed for the protozoan parasite Trypanosoma brucei. Transgenic trypanosomes expressing the tetracycline repressor of Escherichia coli exhibited inducer (tetracycline)-dependent expression of chromosomally integrated reporter genes under the control of a procyclic acidic repetitive protein (PARP) promoter bearing a tet operator. Reporter expression could be controlled over a range of four orders of magnitude in response

  7. Pathway level analysis of gene expression using singular value decomposition

    PubMed Central

    Tomfohr, John; Lu, Jun; Kepler, Thomas B

    2005-01-01

    Background A promising direction in the analysis of gene expression focuses on the changes in expression of specific predefined sets of genes that are known in advance to be related (e.g., genes coding for proteins involved in cellular pathways or complexes). Such an analysis can reveal features that are not easily visible from the variations in the individual genes and can lead to a picture of expression that is more biologically transparent and accessible to interpretation. In this article, we present a new method of this kind that operates by quantifying the level of 'activity' of each pathway in different samples. The activity levels, which are derived from singular value decompositions, form the basis for statistical comparisons and other applications. Results We demonstrate our approach using expression data from a study of type 2 diabetes and another of the influence of cigarette smoke on gene expression in airway epithelia. A number of interesting pathways are identified in comparisons between smokers and non-smokers including ones related to nicotine metabolism, mucus production, and glutathione metabolism. A comparison with results from the related approach, 'gene-set enrichment analysis', is also provided. Conclusion Our method offers a flexible basis for identifying differentially expressed pathways from gene expression data. The results of a pathway-based analysis can be complementary to those obtained from one more focused on individual genes. A web program PLAGE (Pathway Level Analysis of Gene Expression) for performing the kinds of analyses described here is accessible at . PMID:16156896

  8. Optimization of transient gene expression system in Gerbera jemosonii petals.

    PubMed

    Hussein, Gihan M; Abu El-Heba, Ghada A; Abdou, Sara M; Abdallah, Naglaa A

    2013-01-01

    Low transformation efficiency and long generation time for production of transgenic Gerbera jemosonii plants leads to vulnerable gene function studies. Thus, transient expression of genes would be an efficient alternative. In this investigation, a transient expression system for gerbera petals based on the Agrobacterium infiltration protocol was developed using the reporter genes ?-glucuronidase (gus) and green florescence protein (gfp). Results revealed the incapability of using the gfp gene as a reporter gene for transient expression study in gerbera flowers due to the detection of green fluorescent color in the non-infiltrated gerbera flower petals. However, the gus reporter gene was successfully utilized for optimizing and obtaining the suitable agroinfiltration system in gerbera flowers. The expression of GUS was detectable after three days of agroinfiltration in gerbera cultivars "Express" and "White Grizzly" with dark pink and white flower colors, respectively. The vacuum agroinfiltration protocol has been applied on the cultivar "Express" for evaluating the transient expression of the two genes involved in the anthocyanin pathway (iris-dfr and petunia-f3' 5'h), which is responsible for the color in flowers. In comparison to the control, transient expression results showed change in the anthocyanin pigment in all infiltrated flowers with color genes. Additionally, blue color was detected in the stigma and pollen grains in the infiltrated flowers. Moreover, blue colors with variant intensities were observed in produced calli during the routine work of stable transformation with f3' 5'h gene. PMID:23552800

  9. Genome wide gene expression in artificially synthesized amphidiploids of Arabidopsis.

    PubMed

    Fujimoto, Ryo; Taylor, Jennifer M; Sasaki, Taku; Kawanabe, Takahiro; Dennis, Elizabeth S

    2011-11-01

    The merging of two different genomes occurs during the formation of amphidiploids, and the merged regulatory networks have the potential to generate a new gene expression pattern. We examined the genome-wide gene expression of two newly synthesized amphidiploids between Arabidopsis thaliana and the related species Arabidopsis lyrata subsp. lyrata and Arabidopsis halleri subsp. gemmifera. 1,137 (4.7%) and 1,316 (5.4%) of probesets showed differential gene expression in A. thaliana-A. halleri and A. thaliana-A. lyrata hybrids respectively, compared to the mid parent value and of these, 489 were in common. Genes that differed in expression between the parental lines tended to have an expression level in both hybrids differing from the mid parent value. In contrast to protein coding genes, there is little differential expression of transposons. Genes in the categories of chloroplast-targeted and response to stress were overrepresented in the non-additively expressed genes in both amphidiploids. As these genes have the potential to contribute directly to the plant phenotype, we suggest that rapid changes of gene expression in amphidiploids might be important for producing greater biomass. PMID:21882042

  10. Decoupling cellular memory from other gene expression characteristics

    NASA Astrophysics Data System (ADS)

    Balazsi, Gabor; Adams, Rhys; Nevozhay, Dmitry

    2010-03-01

    Non-conventional population level gene expression characteristics (such as the noise, cellular memory, skewness, modality, etc.) can have phenotypic impact and can affect cell population fitness independently of the gene expression mean. To study the phenotypic impact of gene expression characteristics other than the mean, they must be decoupled from the mean, and possibly from each other, i.e., two cell populations have to be established with similar means, but different non canonical gene expression characteristics. We study by experiment and mathematical modeling how positive feedback regulation can be used to decouple and adjust the cellular memory independently of the noise and the mean. We describe a state of ``population dynamic bistability'' where the cell population has bistable expression while individual cell lineages do not. Our results have implications for modeling gene expression bimodality and controlling cellular memory in cell populations.

  11. Laser capture microdissection for gene expression analysis.

    PubMed

    Bidarimath, Mallikarjun; Edwards, Andrew K; Tayade, Chandrakant

    2015-01-01

    Laser capture microdissection (LCM) is an excellent and perhaps the only platform to isolate homogeneous cell populations from specific microscopic regions of heterogeneous tissue section, under direct microscopic visualization. The basic operations of the LCM system are based on (a) microscopic visualization of phenotypically identified cells of interest, (b) selective adherence of cells to a melting thermolabile film/membrane using a low-energy infrared laser (IR system) or photovolatization of cells within a selected region (UV system), (c) capturing or catapulting of structurally intact cells from a stained tissue section. RNA/DNA or protein can be extracted from the cell or tissue fragments for downstream applications to quantitatively study gene expression. This method can be applied to many downstream analyses including but not limited to quantitative real-time polymerase chain reaction (PCR), microarray, DNA genotyping, RNA transcript profiling, generation of cDNA library, mass spectrometry analysis, and proteomic discovery.The application of LCM is described here to specifically and reliably obtain a homogeneous cell population in order to extract RNA to study microRNA expression by quantitative real-time PCR. PMID:25308266

  12. Controlling gene expression with the Q repressible binary expression system in Caenorhabditis elegans

    Microsoft Academic Search

    Xing Wei; Christopher J Potter; Liqun Luo; Kang Shen

    2012-01-01

    We established a transcription-based binary gene expression system in Caenorhabditis elegans using the recently developed Q system. This system, derived from genes in Neurospora crassa, uses the transcriptional activator QF to induce the expression of target genes. Activation can be efficiently suppressed by the transcriptional repressor QS, and suppression can be relieved by the nontoxic small molecule quinic acid. We

  13. Aberrant expression of the glycolytic enzymes aldolase B and type II hexokinase in hepatocellular carcinoma are predictive markers for advanced stage, early recurrence and poor prognosis.

    PubMed

    Peng, Shian-Yang; Lai, Po-Lin; Pan, Hung-Wei; Hsiao, Li-Pin; Hsu, Hey-Chi

    2008-04-01

    Cancer cells with a high glycolytic rate have an advantage in tumor growth. Hepatocellular carcinoma (HCC) often exhibits an aberrant expression of glycolytic enzymes, particularly type II hexokinase (HKII) and aldolase B (ALDOB). This study examined the aberrant expression of HKII and ALDOB in 203 surgically resected HCCs. A dramatic down-regulation of ALDOB was found in 116 HCCs (57%), while 43% of HCCs maintained the expression. HKII mRNA was overexpressed in 70 (35%) primary HCCs. The ALDOB down-regulation and HKII overexpression correlated with high-grade (grade II-IV) HCC (all ps<0.0001), portal vein invasion (stage IIIB-IV) (ps<1x10(-6)), early tumor recurrence (ETR) (p<0.001 and p<0.01, respectively) and a lower 5-year survival (p=0.000001 and p=0.0062, respectively). Notably, in stage II HCC which had no vascular invasion, the ALDOB down-regulation was associated with ETR (p<0.05) and a lower 5-year survival (p=0.015). The down-regulation of ALDOB correlated with a high AFP (p=1x10(-8)), whereas the overexpression of HKII, which has two functional motifs for the mutant p53, correlated with the p53 mutation, p<0.01. The three factors (ALDOB down-regulation, HKII overexpression and p53 mutation) not only correlated with tumor progression, but also interacted with one another, leading to a more aggressive HCC with a portal vein invasion and various extent of intrahepatic metastasis by more than four-fold (ps<1x10(-6)) and frequent ETR by more than two-fold (ps<0.0001) compared with HCCs without the events. In conclusion, the aberrant expression of ALDOB and HKII is associated with advanced disease, ETR and poor prognosis, and ALDOB down-regulation in stage II HCC is a predictive marker of ETR and an unfavorable outcome. PMID:18357395

  14. Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture

    PubMed Central

    Satish, Latha; LaFramboise, William A; O'Gorman, David B; Johnson, Sandra; Janto, Benjamin; Gan, Bing Siang; Baratz, Mark E; Hu, Fen Z; Post, J Christopher; Ehrlich, Garth D; Kathju, Sandeep

    2008-01-01

    Dupuytren's contracture (DC) is the most common inherited connective tissue disease of humans and is hypothesized to be associated with aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts are believed to play an important role in the genesis of DC and the fibroproliferation and contraction that are hallmarks of this disease. This study compares the gene expression profiles of fibroblasts isolated from DC patients and controls in an attempt to identify key genes whose regulation might be significantly altered in fibroblasts found within the palmar fascia of Dupuytren's patients. Total RNA isolated from diseased palmar fascia (DC) and normal palmar fascia (obtained during carpal tunnel release; 6 samples per group) was subjected to quantitative analyses using two different microarray platforms (GE Code Link™ and Illumina™) to identify and validate differentially expressed genes. The data obtained was analyzed using The Significance Analysis of Microarrays (SAM) software through which we identified 69 and 40 differentially regulated gene transcripts using the CodeLink™ and Illumina™ platforms, respectively. The CodeLink™ platform identified 18 upregulated and 51 downregulated genes. Using the Illumina™ platform, 40 genes were identified as downregulated, eleven of which were identified by both platforms. Quantitative RT-PCR confirmed the downregulation of three high-interest candidate genes which are all components of the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1) transcript variant D, and type XV collagen alpha 1 chain. Overall, our study has identified a variety of candidate genes that may be involved in the pathophysiology of Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies. PMID:18433489

  15. Effects of G-gene Deletion and Replacement on Rabies Virus Vector Gene Expression

    PubMed Central

    Sato, Sho; Ohara, Shinya; Tsutsui, Ken-Ichiro; Iijima, Toshio

    2015-01-01

    The glycoprotein-gene (G gene) -deleted rabies virus (RV) vector is a powerful tool to examine the function and structure of neural circuits. We previously reported that the deletion of the G gene enhances the transgene expression level of the RV vector. However, the mechanism of this enhancement remains to be clarified. We presume that there are two possible factors for this enhancement. The first factor is the glycoprotein of RV, which shows cytotoxicity; thus, may cause a dysfunction in the translation process of infected cells. The second possible factor is the enhanced expression of the L gene, which encodes viral RNA polymerase. In the RV, it is known that the gene expression level is altered depending on the position of the gene. Since G-gene deletion displaces the L gene in the genome, the expression of the L gene and viral transcription may be enhanced. In this study, we compared the transgene expression level and viral transcription of three recombinant RV vectors. The effect of glycoprotein was examined by comparing the viral gene expression of G-gene-intact RV and G-gene-replaced RV. Despite the fact that the L-gene transcription level of these two RV vectors was similar, the G-gene-replaced RV vector showed higher viral transcription and transgene expression level than the G-gene-intact RV vector. To examine the effect of the position of the L gene, we compared the viral gene expression of the G-gene-deleted RV and G-gene-replaced RV. The G-gene-deleted RV vector showed higher L-gene transcription, viral transcription, and transgene expression level than the G-gene-replaced RV vector. These results indicate that G-gene deletion enhances the transgene expression level through at least two factors, the absence of glycoprotein and enhancement of L-gene expression. These findings enable investigators to design a useful viral vector that shows a controlled desirable transgene expression level in applications. PMID:26023771

  16. Arabidopsis gene expression patterns are altered during spaceflight

    NASA Astrophysics Data System (ADS)

    Paul, Anna-Lisa; Popp, Michael P.; Gurley, William B.; Guy, Charles; Norwood, Kelly L.; Ferl, Robert J.

    The exposure of Arabidopsis thaliana (Arabidopsis) plants to spaceflight environments results in differential gene expression. A 5-day mission on orbiter Columbia in 1999 (STS-93) carried transgenic Arabidopsis plants engineered with a transgene composed of the alcohol dehydrogenase (Adh) gene promoter linked to the ?-Glucuronidase (GUS) reporter gene. The plants were used to evaluate the effects of spaceflight on gene expression patterns initially by using the Adh/GUS transgene to address specifically the possibility that spaceflight induces a hypoxic stress response (Paul, A.L., Daugherty, C.J., Bihn, E.A., Chapman, D.K., Norwood, K.L., Ferl, R.J., 2001. Transgene expression patterns indicate that spaceflight affects stress signal perception and transduction in arabidopsis, Plant Physiol. 126, 613-621). As a follow-on to the reporter gene analysis, we report here the evaluation of genome-wide patterns of native gene expression within Arabidopsis shoots utilizing the Agilent DNA array of 21,000 Arabidopsis genes. As a control for the veracity of the array analyses, a selection of genes was further characterized with quantitative Real-Time RT PCR (ABI - Taqman®). Comparison of the patterns of expression for arrays probed with RNA isolated from plants exposed to spaceflight compared to RNA isolated from ground control plants revealed 182 genes that were differentially expressed in response to the spaceflight mission by more than 4-fold, and of those only 50 genes were expressed at levels chosen to support a conservative change call. None of the genes that are hallmarks of hypoxic stress were induced to this level. However, genes related to heat shock were dramatically induced - but in a pattern and under growth conditions that are not easily explained by elevated temperatures. These gene expression data are discussed in light of current models for plant responses to the spaceflight environment and with regard to potential future spaceflight experiment opportunities.

  17. Gene expression profiling of mouse embryos with microarrays

    PubMed Central

    Sharov, Alexei A.; Piao, Yulan; Ko, Minoru S. H.

    2011-01-01

    Global expression profiling by DNA microarrays provides a snapshot of cell and tissue status and becomes an essential tool in biological and medical sciences. Typical questions that can be addressed by microarray analysis in developmental biology include: (1) to find a set of genes expressed in a specific cell type; (2) to identify genes expressed commonly in multiple cell types; (3) to follow the time-course changes of gene expression patterns; (4) to demonstrate cell’s identity by showing similarities or differences among two or multiple cell types; (5) to find regulatory pathways and/or networks affected by gene manipulations, such as overexpression or repression of gene expression; (6) to find downstream target genes of transcription factors; (7) to find downstream target genes of cell signaling; (8) to examine the effects of environmental manipulation of cells on gene expression patterns; and (9) to find the effects of genetic manipulation in embryos and adults. Here we describe strategies for executing these experiments and monitoring changes of cell state with gene expression microarrays in application to mouse embryology. Both statistical assessment and interpretation of data are discussed. We also present a protocol for performing microarray analysis on a small amount of embryonic materials. PMID:20699157

  18. Metastatic osteosarcoma gene expression differs in vitro and in vivo.

    PubMed

    Lisle, Jennifer W; Choi, Joseph Y; Horton, Jason A; Allen, Matthew J; Damron, Timothy A

    2008-09-01

    An understanding of differential gene expression in highly metastatic osteosarcoma could provide gene targets for treatment of metastases. We compared gene expression profiles of high- (LM7) and low- (LM2) metastatic SaOS2-derived cell lines in an in vitro tissue culture model and examined several differentially regulated genes in vivo in a murine orthotopic xenograft model. We hypothesized an orthotopic inoculation of LM2 and LM7 cells would establish a primary lesion and the gene expression profile of cells grafted in this fashion would resemble the gene expression profile observed in an in vitro model. Thirty-five days after inoculation, animals were euthanized and both tibiae were harvested and rapidly frozen in liquid nitrogen. Human-specific GAPDH mRNA was present in two of four tibias inoculated with LM2 cells and three of four tibias inoculated with LM7 cells. Tibiae displaying the presence of human cells were assayed by semiquantitative reverse transcriptase polymerase chain reaction. We observed poor correspondence of in vitro to in vivo gene expression for either cell line. Accordingly, in vitro osteosarcoma gene expression data must be interpreted with caution until confirmed in vivo. Our orthotopic injection model allowed in vivo study of differential gene expression between these two cell lines but did not show radiographic evidence of an established primary lesion. PMID:18516656

  19. The role of gene expression in ecological speciation

    PubMed Central

    Pavey, Scott A; Collin, Hélène; Nosil, Patrik; Rogers, Sean M

    2010-01-01

    Ecological speciation is the process by which barriers to gene flow between populations evolve due to adaptive divergence via natural selection. A relatively unexplored area in ecological speciation is the role of gene expression. Gene expression may be associated with ecologically important phenotypes not evident from morphology and play a role during colonization of new environments. Here we review two potential roles of gene expression in ecological speciation: (1) its indirect role in facilitating population persistence and (2) its direct role in contributing to genetically based reproductive isolation. We find indirect evidence that gene expression facilitates population persistence, but direct tests are lacking. We also find clear examples of gene expression having effects on phenotypic traits and adaptive genetic divergence, but links to the evolution of reproductive isolation itself remain indirect. Gene expression during adaptive divergence seems to often involve complex genetic architectures controlled by gene networks, regulatory regions, and “eQTL hotspots.” Nonetheless, we review how approaches for isolating the functional mutations contributing to adaptive divergence are proving to be successful. The study of gene expression has promise for increasing our understanding ecological speciation, particularly when integrative approaches are applied. PMID:20860685

  20. GroupRank: rank candidate genes in PPI network by differentially expressed gene groups.

    PubMed

    Wang, Qing; Zhang, Siyi; Pang, Shichao; Zhang, Menghuan; Wang, Bo; Liu, Qi; Li, Jing

    2014-01-01

    Many cell activities are organized as a network, and genes are clustered into co-expressed groups if they have the same or closely related biological function or they are co-regulated. In this study, based on an assumption that a strong candidate disease gene is more likely close to gene groups in which all members coordinately differentially express than individual genes with differential expression, we developed a novel disease gene prioritization method GroupRank by integrating gene co-expression and differential expression information generated from microarray data as well as PPI network. A candidate gene is ranked high using GroupRank if it is differentially expressed in disease and control or is close to differentially co-expressed groups in PPI network. We tested our method on data sets of lung, kidney, leukemia and breast cancer. The results revealed GroupRank could efficiently prioritize disease genes with significantly improved AUC value in comparison to the previous method with no consideration of co-expressed gene groups in PPI network. Moreover, the functional analyses of the major contributing gene group in gene prioritization of kidney cancer verified that our algorithm GroupRank not only ranks disease genes efficiently but also could help us identify and understand possible mechanisms in important physiological and pathological processes of disease. PMID:25330105

  1. Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes

    Microsoft Academic Search

    Ian C. Lawrance; Claudio Fiocchi; Shukti Chakravarti

    2001-01-01

    To elucidate the biological dysregulation underlying two forms of inflammatory bowel disease (IBD), ulcera- tive colitis (UC) and Crohn's disease (CD), we examined global gene expression profiles of inflamed colonic tissue using DNA microarrays. Our results identified several genes with altered expression not previously linked to IBD. In addition to the expected upregulation of various cytokine and chemokine genes, novel

  2. Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data

    Microsoft Academic Search

    Ivan P Gorlov; Jinyoung Byun; Olga Y Gorlova; Ana M Aparicio; Eleni Efstathiou; Christopher J Logothetis

    2009-01-01

    BACKGOUND: The genetic mechanisms of prostate tumorigenesis remain poorly understood, but with the advent of gene expression array capabilities, we can now produce a large amount of data that can be used to explore the molecular and genetic mechanisms of prostate tumorigenesis. METHODS: We conducted a meta-analysis of gene expression data from 18 gene array datasets targeting transition from normal

  3. Global Prediction of Tissue-Specific Gene Expression and Context-Dependent Gene Networks in Caenorhabditis

    E-print Network

    Murphy, Coleen

    Global Prediction of Tissue-Specific Gene Expression and Context-Dependent Gene Networks, United States of America Abstract Tissue-specific gene expression plays a fundamental role in metazoan biology and is an important aspect of many complex diseases. Nevertheless, an organism-wide map of tissue

  4. Digital gene expression tag profiling analysis of the gene expression patterns regulating the early stage of mouse spermatogenesis.

    PubMed

    Zhang, Xiujun; Hao, Lili; Meng, Lijun; Liu, Meiling; Zhao, Lina; Hu, Fen; Ding, Cunbao; Wang, Yang; He, Baoling; Pan, Yuxin; Fang, Wei; Chen, Jing; Hu, Songnian; Jia, Mengchun

    2013-01-01

    Detailed characterization of the gene expression patterns in spermatogonia and primary spermatocytes is critical to understand the processes which occur prior to meiosis during normal spermatogenesis. The genome-wide expression profiles of mouse type B spermatogonia and primary spermatocytes were investigated using the Solexa/Illumina digital gene expression (DGE) system, a tag based high-throughput transcriptome sequencing method, and the developmental processes which occur during early spermatogenesis were systematically analyzed. Gene expression patterns vary significantly between mouse type B spermatogonia and primary spermatocytes. The functional analysis revealed that genes related to junction assembly, regulation of the actin cytoskeleton and pluripotency were most significantly differently expressed. Pathway analysis indicated that the Wnt non-canonical signaling pathway played a central role and interacted with the actin filament organization pathway during the development of spermatogonia. This study provides a foundation for further analysis of the gene expression patterns and signaling pathways which regulate the molecular mechanisms of early spermatogenesis. PMID:23554914

  5. ESPD: a pattern detection model underlying gene expression profiles

    PubMed Central

    Tang, Chun; Zhang, Aidong; Ramanathan, Murali

    2008-01-01

    Motivation DNA arrays permit rapid, large-scale screening for patterns of gene expression and simultaneously yield the expression levels of thousands of genes for samples. The number of samples is usually limited, and such datasets are very sparse in high-dimensional gene space. Furthermore, most of the genes collected may not necessarily be of interest and uncertainty about which genes are relevant makes it difficult to construct an informative gene space. Unsupervised empirical sample pattern discovery and informative genes identification of such sparse high-dimensional datasets present interesting but challenging problems. Results A new model called empirical sample pattern detection (ESPD) is proposed to delineate pattern quality with informative genes. By integrating statistical metrics, data mining and machine learning techniques, this model dynamically measures and manipulates the relationship between samples and genes while conducting an iterative detection of informative space and the empirical pattern. The performance of the proposed method with various array datasets is illustrated. PMID:14751997

  6. Multiclass cancer diagnosis using tumor gene expression signatures

    E-print Network

    Poggio, Tomaso

    to be identified (3). Recently, DNA microarray-based tumor gene expression profiles have been used for cancerMulticlass cancer diagnosis using tumor gene expression signatures Sridhar Ramaswamy* , Pablo, there is a wide spectrum in cancer morphology and many tumors are atypical or lack morphologic features

  7. Multidimensional regulation of gene expression in the C. elegans embryo

    PubMed Central

    Murray, John Isaac; Boyle, Thomas J.; Preston, Elicia; Vafeados, Dionne; Mericle, Barbara; Weisdepp, Peter; Zhao, Zhongying; Bao, Zhirong; Boeck, Max; Waterston, Robert H.

    2012-01-01

    How cells adopt different expression patterns is a fundamental question of developmental biology. We quantitatively measured reporter expression of 127 genes, primarily transcription factors, in every cell and with high temporal resolution in C. elegans embryos. Embryonic cells are highly distinct in their gene expression; expression of the 127 genes studied here can distinguish nearly all pairs of cells, even between cells of the same tissue type. We observed recurrent lineage-regulated expression patterns for many genes in diverse contexts. These patterns are regulated in part by the TCF-LEF transcription factor POP-1. Other genes' reporters exhibited patterns correlated with tissue, position, and left–right asymmetry. Sequential patterns both within tissues and series of sublineages suggest regulatory pathways. Expression patterns often differ between embryonic and larval stages for the same genes, emphasizing the importance of profiling expression in different stages. This work greatly expands the number of genes in each of these categories and provides the first large-scale, digitally based, cellular resolution compendium of gene expression dynamics in live animals. The resulting data sets will be a useful resource for future research. PMID:22508763

  8. Timing Plasmodium Gene Expression with PfBDP1.

    PubMed

    Deitsch, Kirk W

    2015-06-10

    Malaria parasites must express a large contingent of invasion-related genes to propagate within host red blood cells. In this issue of Cell Host & Microbe, Josling et al. (2015) identify a bromodomain protein that serves as a transcriptional activator required to coordinate expression of these genes and enable parasite proliferation. PMID:26067597

  9. Expression of a Bacterial Gene in a Trypanosomatid Protozoan

    Microsoft Academic Search

    Vivian Bellofatto; George A. M. Cross

    1989-01-01

    A simple and reproducible assay for DNA-mediated transfection in the trypanosomatid protozoan Leptomonas seymouri has been developed. The assay is based on expression of the Escherichia coli chloramphenicol acetyl transferase (CAT) gene flanked by Leptomonas DNA fragments that are likely to contain necessary elements for gene expression in trypanosomes. After electroporation of cells in the presence of plasmid DNA, CAT

  10. Time-synchronized Clustering of Gene Expression Trajectories

    E-print Network

    Müller, Hans-Georg

    Time-synchronized Clustering of Gene Expression Trajectories RONG TANG Division of Biostatistics, USA ABSTRACT Current clustering methods are routinely applied to gene expression time course data at different rates, successful clustering in this context requires dealing with varying time and shape patterns

  11. Expression and mapping of anthocyanin biosynthesis genes in carrot

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anthocyanin gene expression has been extensively studied in leaves, fruits and flowers of numerous plants. Little, however, is known about anthocyanin accumulation in roots, or in carrots or other Apiaceae. We quantified expression of six anthocyanin biosynthetic genes (phenylalanine ammonia-lyase (...

  12. GECKO: a complete large-scale gene expression analysis platform

    Microsoft Academic Search

    Joachim Theilhaber; Anatoly Ulyanov; Anish Malanthara; Jack Cole; Dapeng Xu; Robert Nahf; Michael Heuer; Christoph Brockel; Steven Bushnell

    2004-01-01

    Background: Gecko (Gene Expression: Computation and Knowledge Organization) is a complete, high-capacity centralized gene expression analysis system, developed in response to the needs of a distributed user community. Results: Based on a client-server architecture, with a centralized repository of typically many tens of thousands of Affymetrix scans, Gecko includes automatic processing pipelines for uploading data from remote sites, a data

  13. Meteorological Time Series Modeling Using an Adaptive Gene Expression Programming

    E-print Network

    Fernandez, Thomas

    Meteorological Time Series Modeling Using an Adaptive Gene Expression Programming ALINA BRBULESCU of an adaptive evolutionary technique that give promising results for the development of non-linear time series models. Key-Words: time series modeling, gene expression programming, adaptive algorithm, precipitation 1

  14. Clustering of Unevenly Sampled Gene Expression Time-Series Data

    E-print Network

    Rostock, Universität

    Clustering of Unevenly Sampled Gene Expression Time-Series Data C. S. M¨oller-Levet a , F. Klawonn in clustering time-series. However, the shortness of gene expression time-series data limits the use of conventional statistical models and techniques for time-series analysis. To address this problem, this paper

  15. Integrating transcription factor binding site information with gene expression datasets

    Microsoft Academic Search

    Ian B. Jeffery; Stephen F. Madden; Paul A. Mcgettigan; Guy Perrière; Aedín C. Culhane; Desmond G. Higgins

    2007-01-01

    Motivation: Microarrays are widely used to measure gene expression differences between sets of biological samples. Many of these differ- ences will be due to differences in the activities of transcription factors. In principle, these differences can be detected by associating motifs in promoters with differences in gene expression levels between the groups. In practice, this is hard to do. Results:

  16. Challenges in Projecting Clustering Results Across Gene Expression - Profiling Datasets

    Microsoft Academic Search

    Lara Lusa; Lisa M. McShane; James F. Reid; Loris De Cecco; Federico Ambrogi; Elia Biganzoli; Manuela Gariboldi; Marco A. Pierotti

    2007-01-01

    Background Gene expression microarray studies for several types of cancer have been reported to identify previously unknown subtypes of tumors. For breast cancer, a molecular classification consisting of five subtypes based on gene expression microarray data has been proposed. These subtypes have been reported to exist across several breast cancer microarray studies, and they have demonstrated some association with clinical

  17. EST databases as multi-conditional gene expression datasets

    Microsoft Academic Search

    R. m. Ewing; J M Claverie

    2000-01-01

    IntroductionTechniques for monitoring in parallel the expression of 1000s of genes, suchasmicroarrayhybridization, EST generation and SAGE, are providing biologistswith huge amounts of expression information. A notion in common to manystudies is that genes that function in the same pathways are likely to be coexpressedand possibly co-regulated. We subscribe to this \\

  18. ORIGINAL ARTICLE Patterns of Gene Expression in a Scleractinian Coral

    E-print Network

    Palumbi, Stephen

    ORIGINAL ARTICLE Patterns of Gene Expression in a Scleractinian Coral Undergoing Natural Bleaching # Springer Science+Business Media, LLC 2009 Abstract Coral bleaching is a major threat to coral reefs investigation of gene expression in an Indo-Pacific coral species undergoing natural bleaching which involved

  19. A survey of genetic human cortical gene expression

    Microsoft Academic Search

    J Raphael Gibbs; Jennifer A Webster; Kristen Rohrer; Alice Zhao; Lauren Marlowe; Mona Kaleem; Doris Leung; Leslie Bryden; Priti Nath; Victoria L Zismann; Keta Joshipura; Matthew J Huentelman; Diane Hu-Lince; Keith D Coon; David W Craig; John V Pearson; Peter Holmans; Christopher B Heward; Eric M Reiman; Dietrich Stephan; John Hardy; Amanda J Myers

    2007-01-01

    It is widely assumed that genetic differences in gene expression underpin much of the difference among individuals and many of the quantitative traits of interest to geneticists. Despite this, there has been little work on genetic variability in human gene expression and almost none in the human brain, because tools for assessing this genetic variability have not been available. Now,

  20. A Symbolic Approach to Gene Expression Time Series Analysis

    Microsoft Academic Search

    Ivan G. Costa; Francisco De A. T. De Carvalho; Marcílio Carlos Pereira De Souto

    2002-01-01

    In the analysis of gene expression time series, emphasis has been given on the capture of shape similarity (or dissimilarity). A number of proximity functions have been proposed for this task. However, none of them will suitably measure shape similarity (or dissimilarity) with data containing multiple gene expression time series, unless special data handling is made. In this paper, a

  1. Introduction The growing number of genes expressed in similar patterns

    E-print Network

    Oregon, University of

    al., 1998; Weiss et al., 1998). Mouse orthologs belonging respectively to the Nkx, Gsh, and Msx gene Msx genes are expressed at a corresponding stage in the mouse (Satokata and Maas, 1994; Wang et al and Msx families are expressed in similar dorsovental spatial domains of the insect and vertebrate central

  2. Malaria var gene expression: Keeping up with the neighbors

    PubMed Central

    Kim, Kami

    2014-01-01

    Plasmodium falciparum PfEMP1 is a malaria virulence protein whose expression is epigenetically regulated. The parasite’s ability to express exclusively only one of the sixty var genes that encode PfEMP1 is essential for disease pathogenesis. Two recent papers identify key molecular players in determining whether a var gene is active or silenced. PMID:22264506

  3. Identification of Development and Pathogenicity Related Gene in Botrytis cinerea via Digital Gene Expression Profile

    PubMed Central

    Zhao, Bin; Si, He Long; Sun, Zhi Ying; Xu, Zheng; Chen, Zhan; Zhang, Jin lin; Xing, Ji Hong; Dong, Jin Gao

    2015-01-01

    Background: Botrytis cinerea, a haploid Euascomycete fungus that infects numerous crops, has been used as a model system for studying molecular phytopathology. Botrytis cinerea adopts various modes of infection, which are mediated by a number of pathogenicity and virulence-related genes. Many of these genes have not been reported previously. Objectives: This study aimed to investigate development and pathogenicity-related genes between a novel nonpathogenic mutant and the Wild Type (WT) in B. cinerea. Materials and Methods: Digital Gene Expression (DGE) tag profiling can reveal novel genes that may be involved in development and pathogenicity of plant pathogen. A large volume of B. cinerea tag-seq was generated to identify differential expressed genes by the Illumina DGE tag pro?ling technology. Results: A total of 4,182,944 and 4,182,021 clean tags were obtained from the WT and a nonpathogenic mutant stain (BCt89), respectively, and 10,410 differentially expressed genes were identified. In addition, 84 genes were expressed in the WT only while 34 genes were expressed in the mutant only. A total of 664 differentially expressed genes were involved in 91 Kyoto Encyclopedia of Genes and Genome pathways, including signaling and metabolic pathways. Conclusions: Expression levels of 1,426 genes were significantly up-regulated in the mutant compared to WT. Furthermore, 301 genes were down-regulated with False Discovery Rates (FDR) of < 0.001 and absolute value of log2 Ratio of ? 1. PMID:26034553

  4. Lon Protease of Azorhizobium caulinodans ORS571 Is Required for Suppression of reb Gene Expression

    PubMed Central

    Nakajima, Azusa; Tsukada, Shuhei; Siarot, Lowela; Ogawa, Tetsuhiro; Oyaizu, Hiroshi

    2012-01-01

    Bacterial Lon proteases play important roles in a variety of biological processes in addition to housekeeping functions. In this study, we focused on the Lon protease of Azorhizobium caulinodans, which can fix nitrogen both during free-living growth and in stem nodules of the legume Sesbania rostrata. The nitrogen fixation activity of an A. caulinodans lon mutant in the free-living state was not significantly different from that of the wild-type strain. However, the stem nodules formed by the lon mutant showed little or no nitrogen fixation activity. By microscopic analyses, two kinds of host cells were observed in the stem nodules formed by the lon mutant. One type has shrunken host cells containing a high density of bacteria, and the other type has oval or elongated host cells containing a low density or no bacteria. This phenotype is similar to a praR mutant highly expressing the reb genes. Quantitative reverse transcription-PCR analyses revealed that reb genes were also highly expressed in the lon mutant. Furthermore, a lon reb double mutant formed stem nodules showing higher nitrogen fixation activity than the lon mutant, and shrunken host cells were not observed in these stem nodules. These results suggest that Lon protease is required to suppress the expression of the reb genes and that high expression of reb genes in part causes aberrance in the A. caulinodans-S. rostrata symbiosis. In addition to the suppression of reb genes, it was found that Lon protease was involved in the regulation of exopolysaccharide production and autoagglutination of bacterial cells. PMID:22752172

  5. Genomic analysis of metabolic pathway gene expression in mice

    Microsoft Academic Search

    Anatole Ghazalpour; Sudheer Doss; Sonal S Sheth; Leslie A Ingram-Drake; Eric E Schadt; Aldons J Lusis; Thomas A Drake

    2005-01-01

    Background  A segregating population of (C57BL\\/6J × DBA\\/2J)F2 intercross mice was studied for obesity-related traits and for global gene\\u000a expression in liver. Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait and all gene-expression\\u000a data. These data were then used to identify gene sets that are differentially perturbed in lean and obese mice.\\u000a \\u000a \\u000a \\u000a \\u000a Results  We integrated global gene-expression data with

  6. Analysis of gene expression in operons of Streptomyces coelicolor

    Microsoft Academic Search

    Emma Laing; Vassilis Mersinias; Colin P Smith; Simon J Hubbard

    2006-01-01

    Background  Recent studies have shown that microarray-derived gene-expression data are useful for operon prediction. However, it is apparent\\u000a that genes within an operon do not conform to the simple notion that they have equal levels of expression.\\u000a \\u000a \\u000a \\u000a \\u000a Results  To investigate the relative transcript levels of intra-operonic genes, we have used a Z-score approach to normalize the expression\\u000a levels of all genes within

  7. Processed pseudogenes: the ‘fossilized footprints’ of past gene expression

    PubMed Central

    Podlaha, Ondrej; Zhang, Jianzhi

    2009-01-01

    Although our knowledge of the genes and genomes of extinct organisms is improving as a result of progress in sequencing ancient DNA, the transcriptomes of extinct organisms remain inaccessible, owing to the rapid degradation of messenger RNA after death. We provide empirical evidence that gene expression levels in the reproductive tissues of mice and during early mouse development correlate highly with the rate of inherited retroposition: the source of processed pseudogenes in the genome. Thus, processed pseudogenes might serve as fossilized footprints of the expression of their parent genes, shedding light on ancient transcriptomes that could provide significant insights into the evolution of gene expression. PMID:19796837

  8. Gene age predicts the strength of purifying selection acting on gene expression variation in humans.

    PubMed

    Popadin, Konstantin Y; Gutierrez-Arcelus, Maria; Lappalainen, Tuuli; Buil, Alfonso; Steinberg, Julia; Nikolaev, Sergey I; Lukowski, Samuel W; Bazykin, Georgii A; Seplyarskiy, Vladimir B; Ioannidis, Panagiotis; Zdobnov, Evgeny M; Dermitzakis, Emmanouil T; Antonarakis, Stylianos E

    2014-12-01

    Gene expression levels can be subject to selection. We hypothesized that the age of gene origin is associated with expression constraints, given that it affects the level of gene integration into the functional cellular environment. By studying the genetic variation affecting gene expression levels (cis expression quantitative trait loci [cis-eQTLs]) and protein levels (cis protein QTLs [cis-pQTLs]), we determined that young, primate-specific genes are enriched in cis-eQTLs and cis-pQTLs. Compared to cis-eQTLs of old genes originating before the zebrafish divergence, cis-eQTLs of young genes have a higher effect size, are located closer to the transcription start site, are more significant, and tend to influence genes in multiple tissues and populations. These results suggest that the expression constraint of each gene increases throughout its lifespan. We also detected a positive correlation between expression constraints (approximated by cis-eQTL properties) and coding constraints (approximated by Ka/Ks) and observed that this correlation might be driven by gene age. To uncover factors associated with the increase in gene-age-related expression constraints, we demonstrated that gene connectivity, gene involvement in complex regulatory networks, gene haploinsufficiency, and the strength of posttranscriptional regulation increase with gene age. We also observed an increase in heritability of gene expression levels with age, implying a reduction of the environmental component. In summary, we show that gene age shapes key gene properties during evolution and is therefore an important component of genome function. PMID:25480033

  9. Distribution of population-averaged observables in stochastic gene expression.

    PubMed

    Bhattacharyya, Bhaswati; Kalay, Ziya

    2014-01-01

    Observation of phenotypic diversity in a population of genetically identical cells is often linked to the stochastic nature of chemical reactions involved in gene regulatory networks. We investigate the distribution of population-averaged gene expression levels as a function of population, or sample, size for several stochastic gene expression models to find out to what extent population-averaged quantities reflect the underlying mechanism of gene expression. We consider three basic gene regulation networks corresponding to transcription with and without gene state switching and translation. Using analytical expressions for the probability generating function of observables and large deviation theory, we calculate the distribution and first two moments of the population-averaged mRNA and protein levels as a function of model parameters, population size, and number of measurements contained in a data set. We validate our results using stochastic simulations also report exact results on the asymptotic properties of population averages which show qualitative differences among different models. PMID:24580265

  10. Gene expression patterns associated with chicken jejunal development.

    PubMed

    Schokker, Dirkjan; Hoekman, Arjan J W; Smits, Mari A; Rebel, Johanna M J

    2009-11-01

    Jejunal development occurs in a spatio-temporal pattern and is characterized by morphological and functional changes. To investigate jejunal development at the transcriptomic level, we performed microarray studies in 1-21-day-old chickens. Nine gene clusters were identified, each with a specific gene expression pattern. Subsequently, groups of genes with similar functions could be identified. Genes involved in morphological and functional development were highly expressed immediately after hatch with declining expression patterns afterwards. Immunological development can be roughly divided based on expression patterns into three processes over time; first innate response and immigration of immune cells, secondly differentiation and specialization, and thirdly maturation and immune regulation. We conclude that specific gene expression patterns coincide with the immunological, morphological, and functional development as measured by other methods. Our data show that transcriptomic approaches provide more detailed information on the biological processes underlying jejunal development. PMID:19527747

  11. Smoothing Gene Expression Using Biological Networks Yue Fan, Mark Kon

    E-print Network

    Kon, Mark

    Smoothing Gene Expression Using Biological Networks Yue Fan, Mark Kon Dept. of MathematicsLisi Bioinformatics and Systems Biology Boston University Boston, MA Email: kshinuk@bu.edu, delisi@bu.edu Abstract--Gene of genes from small numbers of subjects are used to identify informative biomarkers that may predict

  12. Transient Gene Expression in Intact and Organized Rice Tissues

    Microsoft Academic Search

    Rudy A. Dekeyser; Marianne E. Habets; Marc C. Van Montagu; Allan B. Caplan

    1990-01-01

    Regulated gene expression of chimeric genes has been studied extensively in electroporated protoplasts. The applicability of these assays is limited, however, because protoplasts are not always physiologically identical to the cells from which they are derived. We have developed a procedure to electroporate DNA into intact and organized leaf structures of rice. Optimization of the new gene delivery system mainly

  13. Differential gene expression in the developing mouse ureter

    Microsoft Academic Search

    Eleanor K. L. Mitchell; Darrin F. Taylor; Kyra Woods; Melissa J. Davis; Amy L. Nelson; Rohan D. Teasdale; Sean M. Grimmond; Melissa H. Little; John F. Bertram; Georgina Caruana

    2006-01-01

    In many instances, kidney dysgenesis results as a secondary consequence to defects in the development of the ureter. Through the use of mouse genetics a number of genes associated with such malformations have been identified, however, the cause of many other abnormalities remain unknown. In order to identify novel genes involved in ureter development we compared gene expression in embryonic

  14. Gene expression profile study on osteoinductive effect of natural hydroxyapatite.

    PubMed

    Lü, Xiaoying; Wang, Jiandan; Li, Bin; Zhang, Zhiwei; Zhao, Lifeng

    2014-08-01

    The aim of this study was to investigate the osteoinductive effect of natural hydroxyapatite (NHA). NHA was extracted from pig bones and prepared into disk-like samples. Then, proliferation of mouse bone mesenchymal stem cells (MSCs) cultured on NHA was assessed by the methylthiazoltetrazolium (MTT) assay. Furthermore, microarray technology was applied to obtain the gene expression profiles of MSCs cultured on NHA at 24, 48, and 72 h. The gene expression profile was then comprehensively analyzed by clustering, Gene Ontology (GO), Gene Microarray Pathway Profiler (GenMAPP) and Ingenuity Pathway Analysis (IPA). According to the results of microarray experiment, 8992 differentially expressed genes were obtained. 90 differential expressed genes related to HA osteogenic differentiation were determined by GO analysis. These genes included not only 6 genes related to HA osteogenic differentiation as mentioned in the literatures but also newly discovered 84 genes. Some important signaling pathways (TGF-?, MAPK, Wnt, etc.) were influenced by these genes. Gene interaction networks were obtained by IPA software, in which the scoring values of two networks were highest, and their main functions were related to cell development. The comprehensive analysis of these results indicate that NHA regulate some crucial genes (e.g., Bmp2, Spp1) and then activate some pathways such as TGF-? signaling pathway, and ultimately osteogenic differentiation was induced. PMID:24115491

  15. Daily coordination of cancer growth and circadian clock gene expression

    Microsoft Academic Search

    Shaojin You; Patricia A. Wood; Yin Xiong; Minoru Kobayashi; Jovelyn Du-Quiton; William J. M. Hrushesky

    2005-01-01

    Background.Circadian coordination in mammals is accomplished, in part, by coordinate, rhythmic expression of a series of circadian clock genes in the central clock within the suprachiasmatic nuclei (SCN) of the hypothalamus. These same genes are also rhythmically expressed each day within each peripheral tissue.Methods.We measured tumor size, tumor cell cyclin E protein, tumor cell mitotic index, and circadian clock gene

  16. Transient gene expression in cassava using high-velocity microprojectiles

    Microsoft Academic Search

    Claudine Franche; Didier Bogusz; Christian Schöpke; Claude Fauquet I; Roger N. Beachy

    1991-01-01

    The bacterial gene encoding ß-glucuronidase (GUS) was transiently expressed in cassava leaves following the introduction of the gene by microparticle bombardment. The DNA expression vector used to introduce the reporter gene is a pUC 19 derivative and consisted of a CaMV 35S promoter (P35S), the GUS coding region and 7S polyadenylation region. Several other promoters and regulating sequences were tested

  17. Regulation of KiSS1 gene expression

    Microsoft Academic Search

    Dali Li; Weishi Yu; Mingyao Liu

    2009-01-01

    Kisspeptins are the protein products encoded by KiSS1 gene, an important tumor metastatic suppressor and pivotal master hormone of puberty. Although KiSS1 gene is expressed in both central and peripheral tissues, the molecular mechanisms that determine the temporal and spatial expression of KiSS1 gene are not well understood. This review provides an update on the latest studies and ideas about

  18. Sources of stochasticity in constitutive and autoregulated gene expression

    E-print Network

    Marathe, Rahul; Klumpp, Stefan

    2012-01-01

    Gene expression is inherently noisy as many steps in the read-out of the genetic information are stochastic. To disentangle the effect of different sources of stochasticity in such systems, we consider various models that describe some processes as stochastic and others as deterministic. We review earlier results for unregulated (constitutive) gene expression and present new results for a gene controlled by negative autoregulation with cell growth modeled by linear volume growth.

  19. Keratin gene expression in non-epithelial tissues. Detection with polymerase chain reaction.

    PubMed Central

    Traweek, S. T.; Liu, J.; Battifora, H.

    1993-01-01

    Keratin filament are characteristically present in epithelial cells and tumors, but have also been detected in many normal and neoplastic non-epithelial cell types using immunohistochemical techniques. To investigate the validity of this seemingly aberrant protein expression, we applied the highly sensitive polymerase chain reaction (PCR) technique to study keratin gene expression in a variety of non-epithelial tissues. Total RNA was extracted from nine samples of leiomyosarcoma, four non-Hodgkin's lymphoma, seven normal bone marrows, normal lymph node, normal peripheral blood cells, freshly isolated and cultured endothelial cells, cultured skin fibroblasts, and the myeloid leukemia cell line HL-60. Amplification primers and probes for the three most primitive keratin types (8, 18, and 19) were synthesized using published gene sequences. RNA from the breast carcinoma cell line MCF-7, known to be rich in all three keratins, was used as positive control. Concurrently run actin primers were used to confirm RNA integrity. After an initial cycle with reverse transcriptase, PCR amplification was performed for 30 cycles. Southern blots of the PCR products showed variably intense bands corresponding to keratin 8 and 18 gene products in all samples, offering conclusive evidence of keratin gene expression in cells of both stromal and hematopoietic derivation. However, keratin 19 gene transcription was not nearly so ubiquitous, being detected in normal fibroblasts and endothelial cells, two of four non-Hodgkin's lymphoma and four of nine leiomyosarcoma, but not in normal lymph node, peripheral blood cells, HL-60 cells, or any of the seven normal bone marrows examined. Dilutional experiments showed PCR to be highly sensitive in the detection of keratin 19 gene expression, capable of registering one MCF-7 cell in 10(6) HL-60 cells. These studies show that variable levels of keratin 8 and 18 gene expression may be detected by PCR in a wide variety of non-epithelial tissues, supporting previous immunohistochemical and phylogenetic studies. However, keratin 19 gene expression appears to be more restricted and was not evident in any hematopoietic cells devoid of contaminating stromal elements. These findings suggest a role for PCR in the detection of epithelial micrometastasis in certain sites, particularly bone marrow. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7682761

  20. 369. Development of an Amplifiable Gene Expression System in Lentivirus Vectors

    Microsoft Academic Search

    Kit L. Shaw; Karen Pepper; Denise Petersen; Shundi Ge; Gay Crooks; Donald B. Kohn

    2006-01-01

    In certain applications of gene therapy, regulated (rather than constitutive) gene expression will be crucial for proper function or optimal effect of the delivered gene. Therefore, an important goal of gene therapy is to be able to deliver genes so that they express in a pattern that recapitulates the expression of an endogenous cellular gene. Additionally, regulating transgene expression will

  1. Gene expression analyses identify Narp contribution in the development of L-DOPA-induced dyskinesia.

    PubMed

    Charbonnier-Beaupel, Fanny; Malerbi, Marion; Alcacer, Cristina; Tahiri, Khadija; Carpentier, Wassila; Wang, Chuansong; During, Matthew; Xu, Desheng; Worley, Paul F; Girault, Jean-Antoine; Hervé, Denis; Corvol, Jean-Christophe

    2015-01-01

    In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of L-DOPA-induced dyskinesia (LID). One major hypothesis is that LID results from an aberrant transcriptional program in striatal neurons induced by L-DOPA and triggered by the activation of ERK. To identify these genes, we performed transcriptome analyses in the striatum in 6-hydroxydopamine-lesioned mice. A time course analysis (0-6 h after treatment with L-DOPA) identified an acute signature of 709 genes, among which genes involved in protein phosphatase activity were overrepresented, suggesting a negative feedback on ERK activation by l-DOPA. l-DOPA-dependent deregulation of 28 genes was blocked by pretreatment with SL327, an inhibitor of ERK activation, and 26 genes were found differentially expressed between highly and weakly dyskinetic animals after treatment with L-DOPA. The intersection list identified five genes: FosB, Th, Nptx2, Nedd4l, and Ccrn4l. Nptx2 encodes neuronal pentraxin II (or neuronal activity-regulated pentraxin, Narp), which is involved in the clustering of glutamate receptors. We confirmed increased Nptx2 expression after L-DOPA and its blockade by SL327 using quantitative RT-PCR in independent experiments. Using an escalating L-DOPA dose protocol, LID severity was decreased in Narp knock-out mice compared with their wild-type littermates or after overexpression of a dominant-negative form of Narp in the striatum. In conclusion, we have identified a molecular signature induced by L-DOPA in the dopamine-denervated striatum that is dependent on ERK and associated with LID. Here, we demonstrate the implication of one of these genes, Nptx2, in the development of LID. PMID:25568106

  2. Genome-Wide Patterns of Arabidopsis Gene Expression in Nature

    PubMed Central

    Banta, Joshua; Bhambhra, Naeha; Purugganan, Michael D.

    2012-01-01

    Organisms in the wild are subject to multiple, fluctuating environmental factors, and it is in complex natural environments that genetic regulatory networks actually function and evolve. We assessed genome-wide gene expression patterns in the wild in two natural accessions of the model plant Arabidopsis thaliana and examined the nature of transcriptional variation throughout its life cycle and gene expression correlations with natural environmental fluctuations. We grew plants in a natural field environment and measured genome-wide time-series gene expression from the plant shoot every three days, spanning the seedling to reproductive stages. We find that 15,352 genes were expressed in the A. thaliana shoot in the field, and accession and flowering status (vegetative versus flowering) were strong components of transcriptional variation in this plant. We identified between ?110 and 190 time-varying gene expression clusters in the field, many of which were significantly overrepresented by genes regulated by abiotic and biotic environmental stresses. The two main principal components of vegetative shoot gene expression (PCveg) correlate to temperature and precipitation occurrence in the field. The largest PCveg axes included thermoregulatory genes while the second major PCveg was associated with precipitation and contained drought-responsive genes. By exposing A. thaliana to natural environments in an open field, we provide a framework for further understanding the genetic networks that are deployed in natural environments, and we connect plant molecular genetics in the laboratory to plant organismal ecology in the wild. PMID:22532807

  3. Gene expression atlas at the European bioinformatics institute.

    PubMed

    Kapushesky, Misha; Emam, Ibrahim; Holloway, Ele; Kurnosov, Pavel; Zorin, Andrey; Malone, James; Rustici, Gabriella; Williams, Eleanor; Parkinson, Helen; Brazma, Alvis

    2010-01-01

    The Gene Expression Atlas (http://www.ebi.ac.uk/gxa) is an added-value database providing information about gene expression in different cell types, organism parts, developmental stages, disease states, sample treatments and other biological/experimental conditions. The content of this database derives from curation, re-annotation and statistical analysis of selected data from the ArrayExpress Archive of Functional Genomics Data. A simple interface allows the user to query for differential gene expression either (i) by gene names or attributes such as Gene Ontology terms, or (ii) by biological conditions, e.g. diseases, organism parts or cell types. The gene queries return the conditions where expression has been reported, while condition queries return which genes are reported to be expressed in these conditions. A combination of both query types is possible. The query results are ranked using various statistical measures and by how many independent studies in the database show the particular gene-condition association. Currently, the database contains information about more than 200,000 genes from nine species and almost 4500 biological conditions studied in over 30,000 assays from over 1000 independent studies. PMID:19906730

  4. Magnetic field-controlled gene expression in encapsulated cells

    PubMed Central

    Ortner, Viktoria; Kaspar, Cornelius; Halter, Christian; Töllner, Lars; Mykhaylyk, Olga; Walzer, Johann; Günzburg, Walter H.; Dangerfield, John A.; Hohenadl, Christine; Czerny, Thomas

    2012-01-01

    Cell and gene therapies have an enormous range of potential applications, but as for most other therapies, dosing is a critical issue, which makes regulated gene expression a prerequisite for advanced strategies. Several inducible expression systems have been established, which mainly rely on small molecules as inducers, such as hormones or antibiotics. The application of these inducers is difficult to control and the effects on gene regulation are slow. Here we describe a novel system for induction of gene expression in encapsulated cells. This involves the modification of cells to express potential therapeutic genes under the control of a heat inducible promoter and the co-encapsulation of these cells with magnetic nanoparticles. These nanoparticles produce heat when subjected to an alternating magnetic field; the elevated temperatures in the capsules then induce gene expression. In the present study we define the parameters of such systems and provide proof-of-principle using reporter gene constructs. The fine-tuned heating of nanoparticles in the magnetic field allows regulation of gene expression from the outside over a broad range and within short time. Such a system has great potential for advancement of cell and gene therapy approaches. PMID:22197778

  5. Differential gene expression between Mycobacterium bovis and Mycobacterium tuberculosis

    PubMed Central

    Rehren, Germán; Walters, Shaun; Fontan, Patricia; Smith, Issar; Zárraga, Ana M.

    2007-01-01

    Summary The high sequence identity among the Mycobacterium bovis and Mycobacterium tuberculosis genomes contrasts with the physiological differences reported between these pathogens, suggesting that variations in gene expression may be involved. In this study, microarray hybridization was used to compare the total transcriptome of M. bovis and M. tuberculosis, during the exponential phase of growth. Differential expression was detected in 258 genes, representing a 6% of the total genome. Variable genes were grouped according to functional categories. The main variations were found in genes encoding proteins involved in intermediary metabolism and respiration, cell wall processes, and hypothetical proteins. It is noteworthy that, compared to M. tuberculosis, the expression of a higher number of transcriptional regulators were detected in M. bovis. Likewise, in M. tuberculosis we found a higher expression of the PE/PPE genes, some of which code for cell wall related proteins. Also, in both pathogens we detected the expression of a number of genes not annotated in the M. tuberculosis H37Rv or M. bovis 2122 genomes, but annotated in the M. tuberculosis CDC1551 genome. Our results provide new evidence concerning differences in gene expression between both pathogens, and confirm previous hypotheses inferred from genome comparisons and proteome analysis. This study may shed some new light on our understanding of the mechanisms relating to differences in gene expression and pathogenicity in mycobacteria. PMID:17433778

  6. Differential bacterial gene expression during experimental pneumococcal endophthalmitis.

    PubMed

    Thornton, Justin A; Tullos, Nathan A; Sanders, Melissa E; Ridout, Granger; Wang, Yong-Dong; Taylor, Sidney D; McDaniel, Larry S; Marquart, Mary E

    2015-01-01

    Streptococcus pneumoniae (pneumococcus) is a potential cause of bacterial endophthalmitis in humans that can result in ocular morbidity. We sought to identify pneumococcal genes that are differentially expressed during growth in the vitreous humor of the eye in an experimental endophthalmitis model. Microarray analysis was used to identify genes that were differentially expressed when pneumococci replicated in the vitreous of rabbit eyes as compared with bacteria grown in vitro in Todd Hewitt medium. Array results were verified by quantitative real-time PCR analysis of representative genes. Select genes potentially playing a role in virulence during endophthalmitis were deleted, and mutants were tested for reduced eye pathogenesis and altered adhesion to host cells. Array analysis identified 134 genes that were differentially expressed during endophthalmitis; 112 genes demonstrated increased expression during growth in the eye whereas 22 were downregulated. Real-time analysis verified increased expression of neuraminidase A (NanA; SP1693), neuraminidase B (NanB; SP1687) and serine protease (SP1954), and decreased expression of RlrA (SP0461) and choline transporter (SP1861). Mutation of NanA and NanB had no major effect on pathogenesis. Loss of SP1954 led to increased adherence to host cells. S. pneumoniae enhances and represses the expression of a variety of genes during endophthalmitis. While some of these genes reflect changes in metabolic requirements, some appear to play a role in immune evasion and pathogenesis in the eye. PMID:25791614

  7. Switchable Gene Expression in Escherichia coli Using a Miniaturized Photobioreactor

    PubMed Central

    Kim, Taesung; Lee, Sung Kuk

    2013-01-01

    We present a light-switchable gene expression system for both inducible and switchable control of gene expression at a single cell level in Escherichia coli using a previously constructed light-sensing system. The ? cI repressor gene with an LVA degradation tag was expressed under the control of the ompC promoter on the chromosome. The green fluorescent protein (GFP) gene fused to a ? repressor-repressible promoter was used as a reporter. This light-switchable system allows rapid and reversible induction or repression of expression of the target gene at any desired time. This system also ensures homogenous expression across the entire cell population. We also report the design of a miniaturized photobioreactor to be used in combination with the light-switchable gene expression system. The miniaturized photobioreactor helps to reduce unintended induction of the light receptor due to environmental disturbances and allows precise control over the duration of induction. This system would be a good tool for switchable, homogenous, strong, and highly regulatable expression of target genes over a wide range of induction times. Hence, it could be applied to study gene function, optimize metabolic pathways, and control biological systems both spatially and temporally. PMID:23349683

  8. Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis

    PubMed Central

    Sweiss, Nadera J.; Chen, Edward S.; Moller, David R.; Knox, Kenneth S.; Ma, Shwu-Fan; Wade, Michael S.; Noth, Imre; Machado, Roberto F.; Garcia, Joe G. N.

    2012-01-01

    Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ?20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n?=?39) from healthy controls (n?=?35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n?=?17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis. PMID:22984568

  9. Caenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression

    E-print Network

    van Oudenaarden, Alexander

    of the selec- tor gene mec-3, which is needed, together with unc-86, for the differentiation of the TRNsCaenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression Irini- derstood. For example, mutations in the gene encoding the transcription factor ALR-1 in Caenorhabditis

  10. SRF-dependent gene expression in isolated cardiomyocytes: Regulation of genes involved in cardiac hypertrophy

    Microsoft Academic Search

    Timothy J. Nelson; Robert Balza; Qi Xiao; Ravi P. Misra

    2005-01-01

    Serum response factor (SRF) is a transcription factor required for the regulation of genes important for cardiac structure and function. Notably, the “fetal gene expression profile” that is characteristic of cardiac hypertrophy consists of genes known to be regulated by SRF. Transgenic animal studies suggest that cardiac-specific overexpression of SRF induces this pattern of hypertrophic genes and subsequently causes the

  11. Gene Expression Profile Analysis of Type 2 Diabetic Mouse Liver

    PubMed Central

    Zhang, Fang; Xu, Xiang; Zhang, Yi; Zhou, Ben; He, Zhishui; Zhai, Qiwei

    2013-01-01

    Liver plays a key role in glucose metabolism and homeostasis, and impaired hepatic glucose metabolism contributes to the development of type 2 diabetes. However, the precise gene expression profile of diabetic liver and its association with diabetes and related diseases are yet to be further elucidated. In this study, we detected the gene expression profile by high-throughput sequencing in 9-week-old normal and type 2 diabetic db/db mouse liver. Totally 12132 genes were detected, and 2627 genes were significantly changed in diabetic mouse liver. Biological process analysis showed that the upregulated genes in diabetic mouse liver were mainly enriched in metabolic processes. Surprisingly, the downregulated genes in diabetic mouse liver were mainly enriched in immune-related processes, although all the altered genes were still mainly enriched in metabolic processes. Similarly, KEGG pathway analysis showed that metabolic pathways were the major pathways altered in diabetic mouse liver, and downregulated genes were enriched in immune and cancer pathways. Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased. In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes. Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases. PMID:23469233

  12. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    Microsoft Academic Search

    Charles H. Streuli; Christian Schmidhauser; Nina Bailey; Peter Yurchenco; Amy P. N. Skubitz; Calvin Roskelley; Mina J. Bissell

    1995-01-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells

  13. Soybean kinome: functional classification and gene expression patterns

    PubMed Central

    Liu, Jinyi; Chen, Nana; Grant, Joshua N.; Cheng, Zong-Ming (Max); Stewart, C. Neal; Hewezi, Tarek

    2015-01-01

    The protein kinase (PK) gene family is one of the largest and most highly conserved gene families in plants and plays a role in nearly all biological functions. While a large number of genes have been predicted to encode PKs in soybean, a comprehensive functional classification and global analysis of expression patterns of this large gene family is lacking. In this study, we identified the entire soybean PK repertoire or kinome, which comprised 2166 putative PK genes, representing 4.67% of all soybean protein-coding genes. The soybean kinome was classified into 19 groups, 81 families, and 122 subfamilies. The receptor-like kinase (RLK) group was remarkably large, containing 1418 genes. Collinearity analysis indicated that whole-genome segmental duplication events may have played a key role in the expansion of the soybean kinome, whereas tandem duplications might have contributed to the expansion of specific subfamilies. Gene structure, subcellular localization prediction, and gene expression patterns indicated extensive functional divergence of PK subfamilies. Global gene expression analysis of soybean PK subfamilies revealed tissue- and stress-specific expression patterns, implying regulatory functions over a wide range of developmental and physiological processes. In addition, tissue and stress co-expression network analysis uncovered specific subfamilies with narrow or wide interconnected relationships, indicative of their association with particular or broad signalling pathways, respectively. Taken together, our analyses provide a foundation for further functional studies to reveal the biological and molecular functions of PKs in soybean. PMID:25614662

  14. Skeletal muscle gene expression in space-flown rats.

    PubMed

    Nikawa, Takeshi; Ishidoh, Kazumi; Hirasaka, Katsuya; Ishihara, Ibuki; Ikemoto, Madoka; Kano, Mihoko; Kominami, Eiki; Nonaka, Ikuya; Ogawa, Takayuki; Adams, Gregory R; Baldwin, Kenneth M; Yasui, Natsuo; Kishi, Kyoichi; Takeda, Shin'ichi

    2004-03-01

    Skeletal muscles are vulnerable to marked atrophy under microgravity. This phenomenon is due to the transcriptional alteration of skeletal muscle cells to weightlessness. To further investigate this issue at a subcellular level, we examined the expression of approximately 26,000 gastrocnemius muscle genes in space-flown rats by DNA microarray analysis. Comparison of the changes in gene expression among spaceflight, tail-suspended, and denervated rats revealed that such changes were unique after spaceflight and not just an extension of simulated weightlessness. The microarray data showed two spaceflight-specific gene expression patterns: 1) imbalanced expression of mitochondrial genes with disturbed expression of cytoskeletal molecules, including putative mitochondria-anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein, and 2) up-regulated expression of ubiquitin ligase genes, MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of muscle protein degradation. Distorted expression of cytoskeletal genes during spaceflight resulted in dislocation of the mitochondria in the cell. Several oxidative stress-inducible genes were highly expressed in the muscle of spaceflight rats. We postulate that mitochondrial dislocation during spaceflight has deleterious effects on muscle fibers, leading to atrophy in the form of insufficient energy provision for construction and leakage of reactive oxygen species from the mitochondria. PMID:14715702

  15. Seed-Based Biclustering of Gene Expression Data

    PubMed Central

    An, Jiyuan; Liew, Alan Wee-Chung; Nelson, Colleen C.

    2012-01-01

    Background Accumulated biological research outcomes show that biological functions do not depend on individual genes, but on complex gene networks. Microarray data are widely used to cluster genes according to their expression levels across experimental conditions. However, functionally related genes generally do not show coherent expression across all conditions since any given cellular process is active only under a subset of conditions. Biclustering finds gene clusters that have similar expression levels across a subset of conditions. This paper proposes a seed-based algorithm that identifies coherent genes in an exhaustive, but efficient manner. Methods In order to find the biclusters in a gene expression dataset, we exhaustively select combinations of genes and conditions as seeds to create candidate bicluster tables. The tables have two columns (a) a gene set, and (b) the conditions on which the gene set have dissimilar expression levels to the seed. First, the genes with less than the maximum number of dissimilar conditions are identified and a table of these genes is created. Second, the rows that have the same dissimilar conditions are grouped together. Third, the table is sorted in ascending order based on the number of dissimilar conditions. Finally, beginning with the first row of the table, a test is run repeatedly to determine whether the cardinality of the gene set in the row is greater than the minimum threshold number of genes in a bicluster. If so, a bicluster is outputted and the corresponding row is removed from the table. Repeating this process, all biclusters in the table are systematically identified until the table becomes empty. Conclusions This paper presents a novel biclustering algorithm for the identification of additive biclusters. Since it involves exhaustively testing combinations of genes and conditions, the additive biclusters can be found more readily. PMID:22879981

  16. Deletion of immunoglobulin heavy chain genes from expressed allelic chromosome.

    PubMed

    Yaoita, Y; Honjo, T

    1980-08-28

    We have studied the organization of immunoglobulin heavy-chain genes in a gamma 2b-chain (BALB/c allotype)-producing myeloma BKC F1 # 15 induced in a F1 mouse between C57BL and BALB/c. Southern blot hybridization studies using cloned mu, gamma 1 and gamma 2b-chain genes as probes demonstrate that the mu- and gamma 1-chain genes of the expressed chromosome are deleted while these genes of the unexpressed chromosome are retained. The gamma 2b-chain gene of the expressed allele is rearranged while that gene of the unexpressed allele seems unchanged, as do the gamma 2a-chain genes. These results support the allelic deletion mechanism in heavy-chain class switch and the order of H chain genes. PMID:6774261

  17. Epigenetic mechanisms of gene expression regulation in neurological diseases.

    PubMed

    Gos, Monika

    2013-01-01

    Neurological diseases are a heterogenous group of disorders that are related to alterations in nervous system function. The genetic background of neurological diseases is heterogenous and may include chromosomal aberrations, specific gene mutations and epigenetic defects. This review is aimed at presenting of selected diseases that are associated with different epigenetic alterations. The imprinting defects on chromosome 15 are the cause of Prader-Willi and Angelman syndromes that both are characterized by intellectual disability, developmental delay and specific behavioral phenotype. Besides the imprinting defect, these diseases can also be caused by deletion of chromosome 15 or uniparental disomy. Aberrant epigenetic regulation is also specific for Fragile X syndrome that is caused by expansion of CGG repeats in the FMR1 gene that leads to global methylation of the promoter region and repression of FMR1 transcription. A number of neurological diseases, mainly associated with intellectual impairment, may be caused by mutations in genes encoding proteins involved in epigenetic regulation. The number of such diseases is rapidly growing thanks to the implementation of genomic sequencing for the identification of their molecular causes. One of the best known diseases linked to defects in epigenetic modifiers is Rett syndrome caused by a mutation in the MECP2 gene or its variant - Rett-like syndrome caused by a mutation in CDKL5 or FOXG1 genes. As the epigenetic signature is potentially reversible, much attention is focused on possible therapies with drugs that influence DNA or histone modifications. This is especially important in the case of neurological disorders in which epigenetic changes are observed as the effect of the disease. PMID:23595281

  18. Molecular cloning and expression of the rat angiotensinogen gene

    Microsoft Academic Search

    John S. D. Chan; Albert H. H. Chan; Qin Jiang; Zeng-Rong Nie; Silvana LaChance; Serge Carrière

    1990-01-01

    To identify tissue- and hormonal-specific DNA controlcis-elements in the rat gene, we have constructed fusion genes consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone (hGH) reporter gene and have introduced them into a subclone of rat pancreatic islet tumor cell line (1056A) which expresses the highest level of angiotensinogen

  19. Expression of heat shock protein genes in insect stress responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The heat shock proteins (HSPs) that are abundantly expressed in insects are important modulators of insect survival. Expression of HSP genes in insects is not only developmentally regulated, but also induced by various stressors in order to confer protection against such stressors. The expression o...

  20. For many autosomal genes in diploid organisms, expression is almost

    E-print Network

    , as signals of transient random monoallelic expression from each allele will cancel each other out when to fully deci- pher the mechanistic underpinnings of stable versus transient random monoallelic expressionFor many autosomal genes in diploid organisms, expression is almost exclusively from one allele

  1. Mapping of sex-linked genes onto the genome sequence using various aberrations of the Z chromosome in Bombyx mori

    Microsoft Academic Search

    Tsuguru Fujii; Hiroaki Abe; Susumu Katsuma; Kazuei Mita; Toru Shimada

    2008-01-01

    Many strains of Bombyx mori carry chromosomal aberrations, and they are useful resources for integration between phenotypes and genomic sequences. We compared the molecular structures of three kinds of Z chromosomes, i.e., two strains with chromosome deletions and one strain with translocation involving the Z chromosome. Using polymerase chain reaction markers, we showed that: (1) the Z1 chromosome lacks more

  2. Gene Expression in the Stallion Testes 

    E-print Network

    Laughlin, Andy M.

    2011-08-08

    Understanding the genes that regulate spermatogenesis and steroidogenesis in the testis is critical for enhancement of stallion fertility. Stallion testicular samples were used to identify candidate genes by cDNA microarrays that simultaneously...

  3. Identification of Reference Genes in Human Myelomonocytic Cells for Gene Expression Studies in Altered Gravity

    PubMed Central

    Thiel, Cora S.; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E.

    2015-01-01

    Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes (“housekeeping genes”) are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1?g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity. PMID:25654098

  4. Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

    PubMed

    Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

    2015-01-01

    Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1?g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity. PMID:25654098

  5. The choice of reference genes for assessing gene expression in sugarcane under salinity and drought stresses.

    PubMed

    Guo, Jinlong; Ling, Hui; Wu, Qibin; Xu, Liping; Que, Youxiong

    2014-01-01

    Sugarcane (Saccharum spp. hybrids) is a world-wide cash crop for sugar and biofuel in tropical and subtropical regions and suffers serious losses in cane yield and sugar content under salinity and drought stresses. Although real-time quantitative PCR has a numerous advantage in the expression quantification of stress-related genes for the elaboration of the corresponding molecular mechanism in sugarcane, the variation happened across the process of gene expression quantification should be normalized and monitored by introducing one or several reference genes. To validate suitable reference genes or gene sets for sugarcane gene expression normalization, 13 candidate reference genes have been tested across 12 NaCl- and PEG-treated sugarcane samples for four sugarcane genotypes using four commonly used systematic statistical algorithms termed geNorm, BestKeeper, NormFinder and the deltaCt method. The results demonstrated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and eukaryotic elongation factor 1-alpha (eEF-1a) were identified as suitable reference genes for gene expression normalization under salinity/drought-treatment in sugarcane. Moreover, the expression analyses of SuSK and 6PGDH further validated that a combination of clathrin adaptor complex (CAC) and cullin (CUL) as reference should be better for gene expression normalization. These results can facilitate the future research on gene expression in sugarcane under salinity and drought stresses. PMID:25391499

  6. Exploiting Gene Expression Variation to Capture Gene-Environment Interactions for Disease

    PubMed Central

    Idaghdour, Youssef; Awadalla, Philip

    2013-01-01

    Gene-environment interactions have long been recognized as a fundamental concept in evolutionary, quantitative, and medical genetics. In the genomics era, study of how environment and genome interact to shape gene expression variation is relevant to understanding the genetic architecture of complex phenotypes. While genetic analysis of gene expression variation focused on main effects, little is known about the extent of interaction effects implicating regulatory variants and their consequences on transcriptional variation. Here we survey the current state of the concept of transcriptional gene-environment interactions and discuss its utility for mapping disease phenotypes in light of the insights gained from genome-wide association studies of gene expression. PMID:23755064

  7. The Ribosomal DNA Genes Influence Genome-Wide Gene Expression in Drosophila melanogaster 

    E-print Network

    Paredes Martinez, Lida Silvana

    2012-07-16

    Chromatin structure is a fundamental determinant of eukaryotic gene expression and it is composed of two chromatin environments, euchromatin and heterochromatin. Euchromatin provides an accessible platform for ...

  8. Microarray Analysis of Pneumococcal Gene Expression during Invasive Disease

    PubMed Central

    Orihuela, Carlos J.; Radin, Jana N.; Sublett, Jack E.; Gao, Geli; Kaushal, Deepak; Tuomanen, Elaine I.

    2004-01-01

    Streptococcus pneumoniae is a leading cause of invasive bacterial disease. This is the first study to examine the expression of S. pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research. Total RNA was collected from pneumococci isolated from infected blood, infected cerebrospinal fluid, and bacteria attached to a pharyngeal epithelial cell line in vitro. Microarray analysis of pneumococcal genes expressed in these models identified body site-specific patterns of expression for virulence factors, transporters, transcription factors, translation-associated proteins, metabolism, and genes with unknown function. Contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed by insertion duplication mutagenesis and challenge of mice with the mutants. Finally, we cross-referenced our results with previous studies that used signature-tagged mutagenesis and differential fluorescence induction to identify genes that are potentially required by a broad range of pneumococcal strains for invasive disease. PMID:15385455

  9. Growth Factors and Gene Expression: Fresh Insights from Arrays

    NSDL National Science Digital Library

    Caroline S. Hill (Developmental Signalling Laboratory; REV)

    1999-10-12

    Gene array technology allows researchers to evaluate patterns of gene expression at a genome-wide level. Two recent papers have applied this powerful technique to characterize how gene expression is changed in response to growth factors and mitogens. The studies focus on two important questions concerning specificity in signal transduction. First, are the multiple signaling pathways activated by a single growth factor receptor used to activate gene expression, and if so, do these pathways act combinatorially? Second, how does the initial genetic response of a cell to a signal stimulus relate to the patterns of gene expression that determine that cell's ultimate biological response to the stimulus? Hill and Treisman take a critical look at what these array technology studies tell us concerning these questions and discuss technical issues arising from them.

  10. TDAC: co-expressed gene pattern finding using attribute clustering.

    PubMed

    Rahman, Tahleen A; Bhattacharyya, Dhruba K

    2015-01-01

    A number of clustering methods introduced for analysis of gene expression data for extracting potential relationships among the genes are studied and reported in this paper. An effective unsupervised method (TDAC) is proposed for simultaneous detection of outliers and biologically relevant co-expressed patterns. Effectiveness of TDAC is established in comparison to its other competing algorithms over six publicly available benchmark gene expression datasets in terms of both internal and external validity measures. Main attractions of TDAC are: (a) it does not require discretisation, (b) it is capable of identifying biologically relevant gene co-expressed patterns as well as outlier genes(s), (c) it is cost-effective in terms of time and space, (d) it does not require the number of clusters a priori, and (e) it is free from the restrictions of using any proximity measure. PMID:25667385

  11. Validation of housekeeping genes for gene expression studies in an ice alga Chlamydomonas during freezing acclimation.

    PubMed

    Liu, Chenlin; Wu, Guangting; Huang, Xiaohang; Liu, Shenghao; Cong, Bailin

    2012-05-01

    Antarctic ice alga Chlamydomonas sp. ICE-L can endure extreme low temperature and high salinity stress under freezing conditions. To elucidate the molecular acclimation mechanisms using gene expression analysis, the expression stabilities of ten housekeeping genes of Chlamydomonas sp. ICE-L during freezing stress were analyzed. Some discrepancies were detected in the ranking of the candidate reference genes between geNorm and NormFinder programs, but there was substantial agreement between the groups of genes with the most and the least stable expression. RPL19 was ranked as the best candidate reference genes. Pairwise variation (V) analysis indicated the combination of two reference genes was sufficient for qRT-PCR data normalization under the experimental conditions. Considering the co-regulation between RPL19 and RPL32 (the most stable gene pairs given by geNorm program), we propose that the mean data rendered by RPL19 and GAPDH (the most stable gene pairs given by NormFinder program) be used to normalize gene expression values in Chlamydomonas sp. ICE-L more accurately. The example of FAD3 gene expression calculation demonstrated the importance of selecting an appropriate category and number of reference genes to achieve an accurate and reliable normalization of gene expression during freeze acclimation in Chlamydomonas sp. ICE-L. PMID:22527038

  12. Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

    PubMed

    Perry, Antoinette S; O'Hurley, Gillian; Raheem, Omer A; Brennan, Kevin; Wong, Simon; O'Grady, Anthony; Kennedy, Anne-Marie; Marignol, Laure; Murphy, Therese M; Sullivan, Linda; Barrett, Ciara; Loftus, Barbara; Thornhill, John; Hewitt, Stephen M; Lawler, Mark; Kay, Elaine; Lynch, Thomas; Hollywood, Donal

    2013-04-15

    Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (? 7) and low (? 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (? 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer. PMID:22915211

  13. Differential metal content and gene expression in rat left ventricular hypertrophy due to hypertension and hyperactivity.

    PubMed

    Subramanian, Meenakumari; Hunt, Adam L; Petrucci, Giuseppe A; Chen, Zengyi; Hendley, Edith D; Palmer, Bradley M

    2014-07-01

    The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar-Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction. We hypothesized that cardiac dysfunction in the SHR is uniquely characterized by calcium overload. We measured total cardiac Ca, Cu, Fe, K, Mg and Zn in the four strains. We found elevated Ca and depressed Cu, Mg and Zn with HT, but not unique to SHR. We surmise that HT promotes aberrant regulation of cardiac Ca(2+), Cu(2+), Mg(2+) and Zn(2+), which does not necessarily result in cardiac dysfunction. Interestingly, Cu was elevated in HA strains compared to nonHA counterparts. We then analyzed gene expression as mRNA of Cu-containing proteins, most notably mitochondrial-Cox, Dbh, Lox, Loxl1, Loxl2, Sod1 and Tyr. The gene expression profiles of Lox, Loxl1, Loxl2 and Sod1 were found especially high in the WKHA, which if reflective of protein content could account for the high Cu content in the WKHA. The mRNA of other genes, notably Mb, Fxyd1, Maoa and Maob were also examined. We found that Maoa gene expression and monoamine oxidase-A (MAO-A) protein content were low in the SHR compared to the other strains. The finding that MAO-A protein is low in the SHR and normal in the WKHT and WKHA strains is most consistent with the idea that MAO-A protects against the development of cardiac dysfunction in LVH but not against LVH in these rats. PMID:24629670

  14. Differential metal content and gene expression in rat left ventricular hypertrophy due to hypertension and hyperactivity

    PubMed Central

    Subramanian, Meenakumari; Hunt, Adam L.; Petrucci, Giuseppe A.; Chen, Zengyi; Hendley, Edith D.; Palmer, Bradley M.

    2014-01-01

    The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar-Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction. We hypothesized that cardiac dysfunction in the SHR is uniquely characterized by calcium overload. We measured total cardiac Ca, Cu, Fe, K, Mg and Zn in the four strains. We found elevated Ca and depressed Cu, Mg and Zn with HT, but not unique to SHR. We surmise that HT promotes aberrant regulation of cardiac Ca2+, Cu2+, Mg2+ and Zn2+, which does not necessarily result in cardiac dysfunction. Interestingly, Cu was elevated in HA strains compared to nonHA counterparts. We then analyzed gene expression as mRNA of Cu-containing proteins, most notably mitochondrial-Cox, Dbh, Lox, Loxl1, Loxl2, Sod1 and Tyr. The gene expression profiles of Lox, Loxl1, Loxl2 and Sod1 were found especially high in the WKHA, which if reflective of protein content could account for the high Cu content in the WKHA. The mRNA of other genes, notably Mb, Fxyd1, Maoa and Maob were also examined. We found that Maoa gene expression and monoamine oxidase-A (MAO-A) protein content were low in the SHR compared to the other strains. The finding that MAO-A protein is low in the SHR and normal in the WKHT and WKHA strains is most consistent with the idea that MAO-A protects against the development of cardiac dysfunction in LVH but not against LVH in these rats. PMID:24629670

  15. Expression noise facilitates the evolution of gene regulation.

    PubMed

    Wolf, Luise; Silander, Olin K; van Nimwegen, Erik

    2015-01-01

    Although it is often tacitly assumed that gene regulatory interactions are finely tuned, how accurate gene regulation could evolve from a state without regulation is unclear. Moreover, gene expression noise would seem to impede the evolution of accurate gene regulation, and previous investigations have provided circumstantial evidence that natural selection has acted to lower noise levels. By evolving synthetic Escherichia coli promoters de novo, we here show that, contrary to expectations, promoters exhibit low noise by default. Instead, selection must have acted to increase the noise levels of highly regulated E. coli promoters. We present a general theory of the interplay between gene expression noise and gene regulation that explains these observations. The theory shows that propagation of expression noise from regulators to their targets is not an unwanted side-effect of regulation, but rather acts as a rudimentary form of regulation that facilitates the evolution of more accurate regulation. PMID:26080931

  16. Selection and validation of reference genes for gene expression analysis in apomictic and sexual Cenchrus ciliaris

    PubMed Central

    2013-01-01

    Background Apomixis is a naturally occurring asexual mode of seed reproduction resulting in offspring genetically identical to the maternal plant. Identifying differential gene expression patterns between apomictic and sexual plants is valuable to help deconstruct the trait. Quantitative RT-PCR (qRT-PCR) is a popular method for analyzing gene expression. Normalizing gene expression data using proper reference genes which show stable expression under investigated conditions is critical in qRT-PCR analysis. We used qRT-PCR to validate expression and stability of six potential reference genes (EF1alpha, EIF4A, UBCE, GAPDH, ACT2 and TUBA) in vegetative and reproductive tissues of B-2S and B-12-9 accessions of C. ciliaris. Findings Among tissue types evaluated, EF1alpha showed the highest level of expression while TUBA showed the lowest. When all tissue types were evaluated and compared between genotypes, EIF4A was the most stable reference gene. Gene expression stability for specific ovary stages of B-2S and B-12-9 was also determined. Except for TUBA, all other tested reference genes could be used for any stage-specific ovary tissue normalization, irrespective of the mode of reproduction. Conclusion Our gene expression stability assay using six reference genes, in sexual and apomictic accessions of C. ciliaris, suggests that EIF4A is the most stable gene across all tissue types analyzed. All other tested reference genes, with the exception of TUBA, could be used for gene expression comparison studies between sexual and apomictic ovaries over multiple developmental stages. This reference gene validation data in C. ciliaris will serve as an important base for future apomixis-related transcriptome data validation. PMID:24083672

  17. Development of a Heat-Shock Inducible Gene Expression System in the Red Alga Cyanidioschyzon merolae

    PubMed Central

    Sumiya, Nobuko; Fujiwara, Takayuki; Kobayashi, Yusuke; Misumi, Osami; Miyagishima, Shin-ya

    2014-01-01

    The cell of the unicellular red alga Cyanidioschyzon merolae contains a single chloroplast and mitochondrion, the division of which is tightly synchronized by a light/dark cycle. The genome content is extremely simple, with a low level of genetic redundancy, in photosynthetic eukaryotes. In addition, transient transformation and stable transformation by homologous recombination have been reported. However, for molecular genetic analyses of phenomena that are essential for cellular growth and survival, inducible gene expression/suppression systems are needed. Here, we report the development of a heat-shock inducible gene expression system in C. merolae. CMJ101C, encoding a small heat shock protein, is transcribed only when cells are exposed to an elevated temperature. Using a superfolder GFP as a reporter protein, the 200-bp upstream region of CMJ101C orf was determined to be the optimal promoter for heat-shock induction. The optimal temperature to induce expression is 50°C, at which C. merolae cells are able to proliferate. At least a 30-min heat shock is required for the expression of a protein of interest and a 60-min heat shock yields the maximum level of protein expression. After the heat shock, the mRNA level decreases rapidly. As an example of the system, the expression of a dominant negative form of chloroplast division DRP5B protein, which has a mutation in the GTPase domain, was induced. Expression of the dominant negative DRP5B resulted in the appearance of aberrant-shaped cells in which two daughter chloroplasts and the cells are still connected by a small DRP5B positive tube-like structure. This result suggests that the dominant negative DRP5B inhibited the final scission of the chloroplast division site, but not the earlier stages of division site constriction. It is also suggested that cell cycle progression is not arrested by the impairment of chloroplast division at the final stage. PMID:25337786

  18. Influence of CHIEF pathway genes on gene expression: a pathway approach to functionality

    PubMed Central

    Slattery, Martha L; Lundgreen, Abbie; Mullany, Lila E; Penney, Rosalind B; Wolff, Roger K

    2014-01-01

    Background: Candidate pathway approaches in disease association studies often utilize a tagSNP approach to capture genetic variation. In this paper we assess gene expression patterns with SNPs in genes in the CHIEF pathway to help determine their potential functionality. Methods: Quantitative real-time RT-PCR was run to determine gene expression of 13 genes in normal colon tissue samples from 82 individuals. TagSNP genotype data were obtained from a GoldenGate Illumina multiplex bead array platform. Age, sex, and genetic ancestry adjusted general linear models were used to estimate beta coefficients and p values. Results: Genetic variation in mTOR (1 SNP), NFKB1 (4 SNPs), PRKAG2 (3 SNPs), and TSC2 (1 SNP) significantly influenced their expression. After adjustment for multiple comparisons several associations between pathway genes and expression of other genes were significant. These included AKT1 rs1130214 associated with expression of PDK1; NF?B1 rs13117745 and rs4648110 with STK11 expression; PRKAG2 rs6965771 with expression of NF?B1, PIK3CA, and RPS6KB2; RPS6KB1 rs80711475 with STK11 expression; STK11 rs741765 with PIK3CA and PRKAG2 expression; and TSC2 rs3087631 with AKT1, IkB?B, NF?B1, PDK1, PIK3CA, PRKAG2, and PTEN expression. The higher levels of differential expression were noted for TSC2 rs3087631 (percent difference ranges from 108% to 198% across genes). Many of these SNPs and genes also were associated with colon and rectal cancer risk. Conclusions: Our results suggest that pathway genes may regulate expression of other genes in the pathway. The convergence of these genes in several biological pathways involved in cancer further supports their importance to the carcinogenic process. PMID:24959314

  19. Gene expression changes during retinal development and rod specification

    PubMed Central

    Carrigan, Matthew; Hokamp, Karsten; Farrar, G. Jane

    2015-01-01

    Purpose Retinitis pigmentosa (RP) typically results from individual mutations in any one of >70 genes that cause rod photoreceptor cells to degenerate prematurely, eventually resulting in blindness. Gene therapies targeting individual RP genes have shown efficacy at clinical trial; however, these therapies require the surviving photoreceptor cells to be viable and functional, and may be economically feasible for only the more commonly mutated genes. An alternative potential treatment strategy, particularly for late stage disease, may involve stem cell transplants into the photoreceptor layer of the retina. Rod progenitors from postnatal mouse retinas can be transplanted and can form photoreceptors in recipient adult retinas; optimal numbers of transplantable cells are obtained from postnatal day 3–5 (P3–5) retinas. These cells can also be expanded in culture; however, this results in the loss of photoreceptor potential. Gene expression differences between postnatal retinas, cultured retinal progenitor cells (RPCs), and rod photoreceptor precursors were investigated to identify gene expression patterns involved in the specification of rod photoreceptors. Methods Microarrays were used to investigate differences in gene expression between cultured RPCs that have lost photoreceptor potential, P1 retinas, and fresh P5 retinas that contain significant numbers of transplantable photoreceptors. Additionally, fluorescence-activated cell sorting (FACS) sorted Rho-eGFP-expressing rod photoreceptor precursors were compared with Rho-eGFP-negative cells from the same P5 retinas. Differential expression was confirmed with quantitative polymerase chain reaction (q-PCR). Results Analysis of the microarray data sets, including the use of t-distributed stochastic neighbor embedding (t-SNE) to identify expression pattern neighbors of key photoreceptor specific genes, resulted in the identification of 636 genes differentially regulated during rod specification. Forty-four of these genes when mutated have previously been found to cause retinal disease. Although gene function in other tissues may be known, the retinal function of approximately 61% of the gene list is as yet undetermined. Many of these genes’ promoters contain binding sites for the key photoreceptor transcription factors Crx and Nr2e3; moreover, the genomic clustering of differentially regulated genes appears to be non-random. Conclusions This study aids in understanding gene expression differences between rod photoreceptor progenitors versus cultured RPCs that have lost photoreceptor potential. The results provide insights into rod photoreceptor development and should expedite the development of cell-based treatments for RP. Furthermore, the data set includes a large number of retinopathy genes; less-well-characterized genes within this data set are a resource for those seeking to identify novel retinopathy genes in patients with RP (GEO accession: GSE59201). PMID:25678762

  20. Single-cell gene expression signatures reveal melanoma cell heterogeneity.

    PubMed

    Ennen, M; Keime, C; Kobi, D; Mengus, G; Lipsker, D; Thibault-Carpentier, C; Davidson, I

    2015-06-01

    It is well established that tumours are not homogenous, but comprise cells with differing invasive, proliferative and tumour-initiating potential. A major challenge in cancer research is therefore to develop methods to characterize cell heterogeneity. In melanoma, proliferative and invasive cells are characterized by distinct gene expression profiles and accumulating evidence suggests that cells can alternate between these states through a process called phenotype switching. We have used microfluidic technology to isolate single melanoma cells grown in vitro as monolayers or melanospheres or in vivo as xenografted tumours and analyse the expression profiles of 114 genes that discriminate the proliferative and invasive states by quantitative PCR. Single-cell analysis accurately recapitulates the specific gene expression programmes of melanoma cell lines and defines subpopulations with distinct expression profiles. Cell heterogeneity is augmented when cells are grown as spheres and as xenografted tumours. Correlative analysis identifies gene-regulatory networks and changes in gene expression under different growth conditions. In tumours, subpopulations of cells that express specific invasion and drug resistance markers can be identified amongst which is the pluripotency factor POUF51 (OCT4) whose expression correlates with the tumorigenic potential. We therefore show that single-cell analysis can be used to define and quantify tumour heterogeneity based on detection of cells with specific gene expression profiles. PMID:25132268

  1. Structure and expression of the human FHIT gene in normal and tumor cells.

    PubMed

    Druck, T; Hadaczek, P; Fu, T B; Ohta, M; Siprashvili, Z; Baffa, R; Negrini, M; Kastury, K; Veronese, M L; Rosen, D; Rothstein, J; McCue, P; Cotticelli, M G; Inoue, H; Croce, C M; Huebner, K

    1997-02-01

    The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these genetic landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a major fragile region that includes a viral integration site between exons 4 and 5, and cancer cell homozygous deletions in intron 5) do not necessarily affect coding exons and yet apparently affect expression of the gene product, we examined the FHIT locus and its expression in detail in more than 10 tumor-derived cell lines to clarify mechanisms underlying aberrant expression. We observed some cell lines with apparently continuous large homozygous deletions, which included one or more coding exons; cell lines with discontinuous deletions, some of which included or excluded coding exons; and cell lines that exhibited heterozygous and/or homozygous deletions, by Southern blot analysis for the presence of specific exons. Most of the cell lines that exhibited genomic alterations showed alteration of FHIT transcripts and absence or diminution of Fhit protein. PMID:9012482

  2. Analysis of nuclear reprogramming in cloned miniature pig embryos by expression of Oct-4 and Oct-4 related genes

    SciTech Connect

    Lee, Eugine [Department of Theriogenology and Biotechnololgy, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, So Hyun [Department of Theriogenology and Biotechnololgy, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Sue [Department of Theriogenology and Biotechnololgy, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of)] (and others)

    2006-10-06

    Xenotransplantation is a rapidly expanding field of research and cloned miniature pigs have been considered as a model animal for it. However, the efficiency of somatic cell nuclear transfer (SCNT) is extremely low, with most clones resulting in early lethality and several kinds of aberrant development. A possible explanation for the developmental failure of SCNT embryos is insufficient reprogramming of the somatic cell nucleus by the oocyte. In order to test this, we analyzed the reprogramming capacity of differentiated fibroblast cell nuclei and embryonic germ cell nuclei with Oct-4 and Oct-4 related genes (Ndp5211, Dppa2, Dppa3, and Dppa5), which are important for embryonic development, Hand1 and GATA-4, which are important for placental development, as molecular markers using RT-PCR. The Oct-4 expression level was significantly lower (P < 0.05) in cloned hatched blastocysts derived from fibroblasts and many of fibroblast-derived clones failed to reactivate at least one of the tested genes, while most of the germ cell clones and control embryos correctly expressed these genes. In conclusion, our results suggest that the reprogramming of fibroblast-derived cloned embryos is highly aberrant and this improper reprogramming could be one reason of the early lethality and post-implantation anomalies of somatic cell-derived clones.

  3. Differential Expression of Granulopoiesis Related Genes in Neutrophil Subsets Distinguished by Membrane Expression of CD177

    PubMed Central

    Hu, Nan; Mora-Jensen, Helena; Theilgaard-Mönch, Kim; Doornbos-van der Meer, Berber; Huitema, Minke G.; Stegeman, Coen A.; Heeringa, Peter; Kallenberg, Cees G. M.; Westra, Johanna

    2014-01-01

    Objective Differential gene expression in CD177+ and CD177? neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). Methods Neutrophils were isolated from healthy controls (HC) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177? subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177? subsets in microarray analysis were re-assessed using quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. Results The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177? neutrophils resulted in 14 genes with fold change (fc) >3 difference in expression. Interestingly, 10 of these genes have been reported to change significantly in expression during neutrophil maturation, and most of these genes were granule protein (GP) coding genes. mRNA expression levels measured by RT-PCR of a number of these GP, and of PR3 and MPO were higher in the CD177? neutrophil subset in HC, however, particular granule protein amounts were comparable between CD177+ and CD177? neutrophil subsets. AAV patients had higher amounts of CD177+ neutrophils, but contrary to neutrophils from HC expression of GP-genes was increased, possibly due to activation. Conclusion The neutrophil population can be distinguished by membrane expression of CD177 into subsets that are different in expression of GP mRNA but not in GP protein production. GP gene expression is also elevated in AAV patients, which is not explained by skewed distribution of CD177+ and CD177? subsets but may be associated with neutrophil activation during on-going inflammation. PMID:24926686

  4. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 false Cardiac allograft gene expression profiling test system. 862...Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a) Identification. A cardiac allograft gene expression profiling test system is...

  5. Concordance of gene expression in human protein complexes reveals tissue specificity

    E-print Network

    Concordance of gene expression in human protein complexes reveals tissue specificity and pathology susceptibility gene's tissue involvement was ranked based on coordinated expression with its interaction partners high concordant expression in biologic- ally relevant tissues. Our method identifies novel gene

  6. Skin aging, gene expression and calcium.

    PubMed

    Rinnerthaler, Mark; Streubel, Maria Karolin; Bischof, Johannes; Richter, Klaus

    2015-08-01

    The human epidermis provides a very effective barrier function against chemical, physical and microbial insults from the environment. This is only possible as the epidermis renews itself constantly. Stem cells located at the basal lamina which forms the dermoepidermal junction provide an almost inexhaustible source of keratinocytes which differentiate and die during their journey to the surface where they are shed off as scales. Despite the continuous renewal of the epidermis it nevertheless succumbs to aging as the turnover rate of the keratinocytes is slowing down dramatically. Aging is associated with such hallmarks as thinning of the epidermis, elastosis, loss of melanocytes associated with an increased paleness and lucency of the skin and a decreased barrier function. As the differentiation of keratinocytes is strictly calcium dependent, calcium also plays an important role in the aging epidermis. Just recently it was shown that the epidermal calcium gradient in the skin that facilitates the proliferation of keratinocytes in the stratum basale and enables differentiation in the stratum granulosum is lost in the process of skin aging. In the course of this review we try to explain how this calcium gradient is built up on the one hand and is lost during aging on the other hand. How this disturbed calcium homeostasis is affecting the gene expression in aged skin and is leading to dramatic changes in the composition of the cornified envelope will also be discussed. This loss of the epidermal calcium gradient is not only specific for skin aging but can also be found in skin diseases such as Darier disease, Hailey-Hailey disease, psoriasis and atopic dermatitis, which might be very helpful to get a deeper insight in skin aging. PMID:25262846

  7. Investigation of Gene Regulatory Networks Associated with Autism Spectrum Disorder Based on MiRNA Expression in China

    PubMed Central

    Chen, Zhao; Li, Jiada; Hu, Zhengmao; Qiu, Rong; Zhuang, Wei; Tang, Beisha; Xia, Kun; Jiang, Hong

    2015-01-01

    Autism spectrum disorder (ASD) comprise a group of neurodevelopmental disorders characterized by deficits in social and communication capacities and repetitive behaviors. Increasing neuroscientific evidence indicates that the neuropathology of ASD is widespread and involves epigenetic regulation in the brain. Differentially expressed miRNAs in the peripheral blood from autism patients were identified by high-throughput miRNA microarray analyses. Five of these miRNAs were confirmed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. A search for candidate target genes of the five confirmed miRNAs was performed through a Kyoto encyclopedia of genes and genomes (KEGG) biological pathways and Gene Ontology enrichment analysis of gene function to identify gene regulatory networks. To the best of our knowledge, this study provides the first global miRNA expression profile of ASD in China. The differentially expressed miR-34b may potentially explain the higher percentage of male ASD patients, and the aberrantly expressed miR-103a-3p may contribute to the abnormal ubiquitin-mediated proteolysis observed in ASD. PMID:26061495

  8. Scaling of Gene Expression with Transcription-Factor Fugacity

    NASA Astrophysics Data System (ADS)

    Weinert, Franz M.; Brewster, Robert C.; Rydenfelt, Mattias; Phillips, Rob; Kegel, Willem K.

    2014-12-01

    The proteins associated with gene regulation are often shared between multiple pathways simultaneously. By way of contrast, models in regulatory biology often assume these pathways act independently. We demonstrate a framework for calculating the change in gene expression for the interacting case by decoupling repressor occupancy across the cell from the gene of interest by way of a chemical potential. The details of the interacting regulatory architecture are encompassed in an effective concentration, and thus, a single scaling function describes a collection of gene expression data from diverse regulatory situations and collapses it onto a single master curve.

  9. Scaling of Gene Expression with Transcription-Factor Fugacity

    PubMed Central

    Weinert, Franz M.; Brewster, Robert C.; Rydenfelt, Mattias; Phillips, Rob; Kegel, Willem K.

    2015-01-01

    The proteins associated with gene regulation are often shared between multiple pathways simultaneously. By way of contrast, models in regulatory biology often assume these pathways act independently. We demonstrate a framework for calculating the change in gene expression for the interacting case by decoupling repressor occupancy across the cell from the gene of interest by way of a chemical potential. The details of the interacting regulatory architecture are encompassed in an effective concentration, and thus, a single scaling function describes a collection of gene expression data from diverse regulatory situations and collapses it onto a single master curve. PMID:25554908

  10. PRENATAL EXPRESSION PATTERNS OF GENES ASSOCIATED WITH NEUROPSYCHIATRIC DISORDERS

    PubMed Central

    Birnbaum, Rebecca; Jaffe, Andrew E.; Hyde, Thomas M.; Kleinman, Joel E.; Weinberger, Daniel R.

    2014-01-01

    Objective Neurodevelopmental disorders presumably involve events that occur during brain development. We hypothesized that neuropsychiatric disorders considered to be developmental in etiology are associated with susceptibility genes that are relatively upregulated during fetal life (i.e. differentially expressed). Method We investigated the presence of prenatal expression enrichment of susceptibility genes systematically, as composite gene sets associated with 6 neuropsychiatric disorders in the microarray-based “BrainCloud” dorsolateral prefrontal cortex (DLPFC) transcriptome. Results Using a fetal/post-natal log2 fold change threshold of 0.5, genes associated with syndromic neurodevelopmental disorders (n = 31 genes, p = 3.37×10?3), intellectual disability (n = 88 genes, p = 5.53×10?3), and autism spectrum disorder (n = 242 genes, p = 3.45×10?4) were relatively enriched in prenatal transcript abundance, compared to the overall transcriptome. Genes associated with schizophrenia by GWAS were not preferentially fetal expressed (n = 106 genes, p = 0.46), nor were genes associated with schizophrenia by exome sequencing (n = 212 genes, p = .21), but specific genes within CNV regions associated with schizophrenia were relatively enriched in prenatal transcript abundance, and genes associated with schizophrenia by meta-analysis were functionally enriched for some neurodevelopmental processes. In contrast, genes associated with neurodegenerative disorders were significantly underexpressed during fetal life (n = 46 genes, p = 1.67×10?3). Conclusions We found evidence for relative prenatal enrichment of putative susceptibility genes for syndromic neurodevelopmental disorders, intellectual disability, and autism spectrum disorders. Future transcriptome-level association studies should evaluate regions other than the DLPFC, at other time points, and incorporate further RNA sequencing analyses. PMID:24874100

  11. On Differential Variability of Expression Ratios: Improving Statistical Inference about Gene Expression Changes from Microarray Data

    Microsoft Academic Search

    M. A. Newton; C. M. Kendziorski; C. S. Richmond; Frederick R. Blattner; K. W. Tsui

    2001-01-01

    ABSTRACT We consider the problem of inferring fold changes in gene expression from cDNA microarray data. Standard procedures focus on the ratio of measured è uorescent intensities at each spot on the microarray, but to do so is to ignore the fact that the variation of such ratios is not constant. Estimates of gene expression changes are derived within a

  12. Uncovering differentially expressed pathways with protein interaction and gene expression data

    Microsoft Academic Search

    Yu-Qing Qiu; Shihua Zhang; Xiang-Sun Zhang

    2008-01-01

    The identification of genes and pathways involved in biological processes is a central problem in systems biology. Recent microarray technologies and other high-throughput experi- ments provide information which sheds light on this problem. In this article, we propose a new method to identify differentially expressed pathways via integration of gene expression and inter- actomic data in a sophisticated and efficient

  13. Wilms Tumor Gene ( WT1 ) Expression as a Panleukemic Marker

    Microsoft Academic Search

    Hans D. Menssen; Jan M. Siehl; Eckhard Thiel

    2002-01-01

    The Wilms tumor gene (WT1) is expressed in blasts of patients with acute leukemia, irrespective of lineage, and WT1 nuclear protein is detectable in\\u000a the majority of such blasts. Only very few physiologic hematopoietic progenitors expressWT1, but theWT1 expression level of these progenitors and that of leukemic blasts are comparable. Although not specific for acute hematologic\\u000a malignant diseases, continuousWT1 expression

  14. Reconstruction of gene co-expression network from microarray data using local expression patterns

    PubMed Central

    2014-01-01

    Background Biological networks connect genes, gene products to one another. A network of co-regulated genes may form gene clusters that can encode proteins and take part in common biological processes. A gene co-expression network describes inter-relationships among genes. Existing techniques generally depend on proximity measures based on global similarity to draw the relationship between genes. It has been observed that expression profiles are sharing local similarity rather than global similarity. We propose an expression pattern based method called GeCON to extract Gene CO-expression Network from microarray data. Pair-wise supports are computed for each pair of genes based on changing tendencies and regulation patterns of the gene expression. Gene pairs showing negative or positive co-regulation under a given number of conditions are used to construct such gene co-expression network. We construct co-expression network with signed edges to reflect up- and down-regulation between pairs of genes. Most existing techniques do not emphasize computational efficiency. We exploit a fast correlogram matrix based technique for capturing the support of each gene pair to construct the network. Results We apply GeCON to both real and synthetic gene expression data. We compare our results using the DREAM (Dialogue for Reverse Engineering Assessments and Methods) Challenge data with three well known algorithms, viz., ARACNE, CLR and MRNET. Our method outperforms other algorithms based on in silico regulatory network reconstruction. Experimental results show that GeCON can extract functionally enriched network modules from real expression data. Conclusions In view of the results over several in-silico and real expression datasets, the proposed GeCON shows satisfactory performance in predicting co-expression network in a computationally inexpensive way. We further establish that a simple expression pattern matching is helpful in finding biologically relevant gene network. In future, we aim to introduce an enhanced GeCON to identify Protein-Protein interaction network complexes by incorporating variable density concept. PMID:25079873

  15. Simultaneous tracking of fly movement and gene expression using GFP

    PubMed Central

    Grover, Dhruv; Yang, Junsheng; Tavaré, Simon; Tower, John

    2008-01-01

    Background Green Fluorescent Protein (GFP) is used extensively as a reporter for transgene expression in Drosophila and other organisms. However, GFP has not generally been used as a reporter for circadian patterns of gene expression, and it has not previously been possible to correlate patterns of reporter expression with 3D movement and behavior of transgenic animals. Results We present a video tracking system that allows tissue-specific GFP expression to be quantified and correlated with 3D animal movement in real time. eyeless/Pax6 reporter expression had a 12 hr period that correlated with fly activity levels. hsp70 and hsp22 gene reporters were induced during fly aging in circadian patterns (24 hr and 18 hr periods, respectively), and spiked in the hours preceding and overlapping the death of the animal. The phase of hsp gene reporter expression relative to fly activity levels was different for each fly, and remained the same throughout the life span. Conclusion These experiments demonstrate that GFP can readily be used to assay longitudinally fly movement and tissue-specific patterns of gene expression. The hsp22-GFP and hsp70-GFP expression patterns were found to reflect accurately the endogenous gene expression patterns, including induction during aging and circadian periodicity. The combination of these new tracking methods with the hsp-GFP reporters revealed additional information, including a spike in hsp22 and hsp70 reporter expression preceding death, and an intriguing fly-to-fly variability in the phase of hsp70 and hsp22 reporter expression patterns. These methods allow specific temporal patterns of gene expression to be correlated with temporal patterns of animal activity, behavior and mortality. PMID:19087237

  16. Gene expression profiling of Drosophila tracheal fusion cells.

    PubMed

    Chandran, Rachana R; Iordanou, Ekaterini; Ajja, Crystal; Wille, Michael; Jiang, Lan

    2014-07-01

    The Drosophila trachea is a premier genetic system to investigate the fundamental mechanisms of tubular organ formation. Tracheal fusion cells lead the branch fusion process to form an interconnected tubular network. Therefore, fusion cells in the Drosophila trachea will be an excellent model to study branch fusion in mammalian tubular organs, such as kidneys and blood vessels. The fusion process is a dynamic cellular process involving cell migration, adhesion, vesicle trafficking, cytoskeleton rearrangement, and membrane fusion. To understand how these cellular events are coordinated, we initiated the critical step to assemble a gene expression profile of fusion cells. For this study, we analyzed the expression of 234 potential tracheal-expressed genes in fusion cells during fusion cell development. 143 Tracheal genes were found to encode transcription factors, signal proteins, cytoskeleton and matrix proteins, transporters, and proteins with unknown function. These genes were divided into four subgroups based on their levels of expression in fusion cells compared to neighboring non-fusion cells revealed by in situ hybridization: (1) genes that have relative high abundance in fusion cells, (2) genes that are dynamically expressed in fusion cells, (3) genes that have relative low abundance in fusion cells, and (4) genes that are expressed at similar levels in fusion cells and non-fusion tracheal cells. This study identifies the expression profile of fusion cells and hypothetically suggests genes which are necessary for the fusion process and which play roles in distinct stages of fusion, as indicated by the location and timing of expression. These data will provide the basis for a comprehensive understanding of the molecular and cellular mechanisms of branch fusion. PMID:24928808

  17. A gene expression fingerprint of C. elegans embryonic motor neurons

    PubMed Central

    Fox, Rebecca M; Von Stetina, Stephen E; Barlow, Susan J; Shaffer, Christian; Olszewski, Kellen L; Moore, Jason H; Dupuy, Denis; Vidal, Marc; Miller, David M

    2005-01-01

    Background Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. Results Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which ~1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes (537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons. Conclusion We have described a microarray-based method, MAPCeL, for profiling gene expression in specific C. elegans motor neurons and provide evidence that this approach can reveal candidate genes for key roles in the differentiation and function of these cells. These methods can now be applied to generate a gene expression map of the C. elegans nervous system. PMID:15780142