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1

Xeroderma Pigmentosum p48 Gene Enhances Global Genomic Repair and Suppresses UV-Induced Mutagenesis  

Microsoft Academic Search

UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs)

Jean Y Tang; Byung Joon Hwang; James M Ford; Philip C Hanawalt; Gilbert Chu

2000-01-01

2

cDNA and genomic cloning and expression of the P48 monocytic differentiation/activation factor, a Mycoplasma fermentans gene product.  

PubMed Central

P48 is a 48 kDa monocytic differentiation/activation factor previously purified from the conditioned medium of the Reh human pre-B cell leukaemia cell line. It induces growth arrest and differentiation of HL-60 human promyelocytic leukaemia cells along the monocytic pathway and the production of the cytokines interleukin 1, tumour necrosis factor-alpha and interleukin 6 in human monocytes and monocytic cell lines. The cDNA for P48 was cloned from Reh cellular RNA using 3' reverse amplification of cDNA ends. Southern blot probing with P48 cDNA revealed hybridization with DNA from Reh and Molt-4 cells, but not with DNA from human peripheral blood mononuclear cells. Subsequent studies using PCR and Southern analysis revealed P48 sequences in DNA isolated from Mycoplasma fermentans but not M. hominis, M.iowae, M.synoviae or M.lypophilum. Although initial studies using Mycoplasma culture and hybridization techniques had failed to reveal Mycoplasma infection in our Reh and Molt-4 cell lines, subsequent PCR studies using Mycoplasma genus-specific rRNA primrs revealed Mycoplasma sequences in these cell lines. Using the P48 cDNA probe, we isolated a genomic clone from M. fermentans DNA which was found to be 98.5% identical with the P48 cDNA clone, and the deduced amino acid sequence agreed with N-terminal microsequencing data for P48 protein purified from the Reh cell line conditioned medium. The 5' end of the gene has a number of consensus sequences characteristic of prokaryotic genes, and the deduced amino acid sequence has a number of features suggesting that P48 is a lipoprotein. The P48 cDNA was expressed in pMAL in Escherichia coli, and the 60 kDa expressed fusion protein was found to react with anti-P48 antibodies on Western blots. This is consistent with a pMAL fusion protein representing the sum of the 42 kDa maltose-binding protein and 18 kDa of P48 recombinant protein, suggesting that native P48 has significant post-translational modification. Consistent with this, Northern blot studies revealed a single 1 kb transcript. The recombinant fusion protein was found to possess anti-proliferative activity against HL-60 cells, and antibodies against recombinant P48 were found to block the biological activity of native P48 isolated from conditioned medium. These studies demonstrate that P48, a molecule with immunomodulatory and haematopoietic differentiation activities, is derived from M. fermentans or a closely related species. P48 may be important in the pathophysiology of Mycoplasma infections and may be useful in dissecting the mechanisms involved in mammalian haematopoietic cell differentiation, immune function and cytokine biosynthesis.

Hall, R E; Agarwal, S; Kestler, D P; Cobb, J A; Goldstein, K M; Chang, N S

1996-01-01

3

cDNA and genomic cloning and expression of the P48 monocytic differentiation/activation factor, a Mycoplasma fermentans gene product.  

PubMed

P48 is a 48 kDa monocytic differentiation/activation factor previously purified from the conditioned medium of the Reh human pre-B cell leukaemia cell line. It induces growth arrest and differentiation of HL-60 human promyelocytic leukaemia cells along the monocytic pathway and the production of the cytokines interleukin 1, tumour necrosis factor-alpha and interleukin 6 in human monocytes and monocytic cell lines. The cDNA for P48 was cloned from Reh cellular RNA using 3' reverse amplification of cDNA ends. Southern blot probing with P48 cDNA revealed hybridization with DNA from Reh and Molt-4 cells, but not with DNA from human peripheral blood mononuclear cells. Subsequent studies using PCR and Southern analysis revealed P48 sequences in DNA isolated from Mycoplasma fermentans but not M. hominis, M.iowae, M.synoviae or M.lypophilum. Although initial studies using Mycoplasma culture and hybridization techniques had failed to reveal Mycoplasma infection in our Reh and Molt-4 cell lines, subsequent PCR studies using Mycoplasma genus-specific rRNA primrs revealed Mycoplasma sequences in these cell lines. Using the P48 cDNA probe, we isolated a genomic clone from M. fermentans DNA which was found to be 98.5% identical with the P48 cDNA clone, and the deduced amino acid sequence agreed with N-terminal microsequencing data for P48 protein purified from the Reh cell line conditioned medium. The 5' end of the gene has a number of consensus sequences characteristic of prokaryotic genes, and the deduced amino acid sequence has a number of features suggesting that P48 is a lipoprotein. The P48 cDNA was expressed in pMAL in Escherichia coli, and the 60 kDa expressed fusion protein was found to react with anti-P48 antibodies on Western blots. This is consistent with a pMAL fusion protein representing the sum of the 42 kDa maltose-binding protein and 18 kDa of P48 recombinant protein, suggesting that native P48 has significant post-translational modification. Consistent with this, Northern blot studies revealed a single 1 kb transcript. The recombinant fusion protein was found to possess anti-proliferative activity against HL-60 cells, and antibodies against recombinant P48 were found to block the biological activity of native P48 isolated from conditioned medium. These studies demonstrate that P48, a molecule with immunomodulatory and haematopoietic differentiation activities, is derived from M. fermentans or a closely related species. P48 may be important in the pathophysiology of Mycoplasma infections and may be useful in dissecting the mechanisms involved in mammalian haematopoietic cell differentiation, immune function and cytokine biosynthesis. PMID:8921000

Hall, R E; Agarwal, S; Kestler, D P; Cobb, J A; Goldstein, K M; Chang, N S

1996-11-01

4

The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts  

Microsoft Academic Search

The tumor suppressor protein p53 functions in many cellular responses to UV-induced DNA damage, including activating the global nucleotide excision repair (NER) pathway. A potential mechanism for the effect on NER is through the ability of p53 to transcriptionally regulate genes that are directly involved in NER. DDB2 is one such gene that is regulated by p53 at both the

Maureen E. Fitch; Irina V. Cross; Stephanie J. Turner; Shanthi Adimoolam; Cindy X. Lin; Kevin G. Williams; James M. Ford

2003-01-01

5

Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein  

SciTech Connect

DDB is a damage-specific DNA binding protein whose binding activity is absent from a minority of cell strains from individuals with xeroderma pigmentosum Group E, a human hereditary disease characterized by defective nucleotide excision DNA repair and an increased incidence of skin cancer. The binding activity from HeLa cells is associated with polypeptides of M{sub r} 124,000 and 41,000 as determined by SDS-polyacrylamide gels. This report describes the isolation of full-length human cDNAs encoding each polypeptide of DDB. The predicted peptide molecular masses based on open reading frames are 127,000 and 48,000. When expressed in an in vitro rabbit reticulocyte system, the p48 subunit migrates with an M{sub r} of 41 kDa on SDS-polyacrylamide gels, similarly to the peptide purified from HeLa cells. There is no significant homology between the derived p48 peptide sequence and any proteins in current databases, and the derived peptide sequence of p127 has homology only with the monkey DDB p127 (98% nucleotide identity and only one conserved amino acid substitution). Using a fluorescence in situ hybridization technique, the DDB p127 locus (DDB1) was assigned to the chromosomal location 11q12-q13, and the DDB p48 locus (DDB2) to 11p11-p12. 34 refs., 3 figs., 1 tab.

Dualan, R.; Brody, T.; Keeney, S. [Univ. of California, Berkeley, CA (United States)] [and others

1995-09-01

6

Establishing an in vivo p48ZnF bioluminescence mouse brain imaging model.  

PubMed

p48ZnF is a C3H1 zinc finger domain-containing protein that is involved in the control of gene transcription and translation. In the present study a novel transgenic p48ZnF mouse model is described that is useful for in vivo brain imaging using luciferase as bioluminescence-mediating reporter gene. Yeast two-hybrid screening and western blot analyses revealed Drg1 (developmentally regulated GTP binding protein 1) and Pcbp1 (poly (rC)-binding protein 1) as p48ZnF-associated proteins. Interestingly, p48ZnF' cellular location of action depends on the cell's differentiation status: nuclear in proliferating cells and cytoplasmic in differentiated neurons. PMID:23470633

Heese, Klaus

2013-03-05

7

p/CAF modulates the activity of the transcription factor p48/Ptf1a involved in pancreatic acinar differentiation.  

PubMed

p48, also called Ptf1a (pancreas-specific transcription factor 1a), is a tissue-restricted bHLH (basic helix loop helix) transcription factor which is critical for pancreatic commitment during development and for the activation and maintenance of the acinar differentiation programme in the exocrine pancreas. High-level expression of exocrine digestive enzymes, a hallmark of mature acinar cells, depends largely on the trimeric complex PTF1, formed by p48, RBP-L (recombination signal-binding protein 1-like) and a class A bHLH protein. In addition, p48 induces cell-cycle exit by controlling G(1)/S-phase progression. However, the mechanisms that mediate PTF1-dependent gene activation are poorly understood. In the present study, we report that p48 increases transcription through two activation domains located in its N-terminal region by recruiting transcriptional co-activators. The histone acetyltransferase cofactor p/CAF {p300/CBP [CREB (cAMP-response-element-binding protein)-binding protein]-associated factor} interacts with p48 in acinar cells in vivo and is associated with the promoter region of acinar genes targeted by the PTF1 complex. p/CAF potentiates PTF1 transcriptional activity by enhancing selectively the p48 transactivation activity. p/CAF promotes the nuclear accumulation of p48 and its in vivo acetylation in Lys(200). The K200R mutation abolishes the transcriptional activity of p48, as well as its capacity to functionally co-operate with RBP-L to ensure effective PTF1-driven transcription, indicating that p/CAF-mediated acetylation of p48 is required for the full transcriptional activity of PTF1. In contrast, p/CAF did not co-operate with p48 in its growth regulatory effects. These results support a critical and selective role of p/CAF in PTF1-dependent gene activation during acinar differentiation. PMID:18834332

Rodolosse, Annie; Campos, Maria-Luisa; Rooman, Ilse; Lichtenstein, Mathieu; Real, Francisco X

2009-03-01

8

The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix protein.  

PubMed Central

We report the isolation of cDNA for the p48 DNA-binding subunit of the heterooligomeric transcription factor PTF1. A sequence analysis of the cDNA demonstrates that p48 is a new member of the family of basic helix-loop-helix (bHLH) transcription factors. The p48 bHLH domain shows striking amino acid sequence similarity with the bHLH domain of proteins that act as developmental regulators, including the twist gene product, myogenic factors and proteins involved in hematopoietic differentiation. We show that reduced p48 synthesis correlates with a diminished expression of genes encoding exocrine pancreas-specific functions. The synthesis of p48 mRNAs, and therefore also the protein, is restricted to cells of the exocrine pancreas in the adult and to the pancreatic primordium in the embryo. Thus the pancreas-specific DNA-binding activity of PTF1 originates from the synthesis of at least one cell-specific component rather than from a cell-specific assembly of more widely distributed proteins. Images

Krapp, A; Knofler, M; Frutiger, S; Hughes, G J; Hagenbuchle, O; Wellauer, P K

1996-01-01

9

P48-Triggered transmembrane signaling transduction of human monocytes: mobilization of calcium ion and activation of protein kinase C (PKC)  

Microsoft Academic Search

P48 is a cytokine which induces monocyte differentiation and the induction of cytotoxic activity. In this study, the signal transduction events involved in the stimulation of monocytes with the membrane form of P48 (mP48) were investigated. Monocyte stimulation with mP48 was found to involve the mobilization of intracellular calcium (Ca2+) and the activation and translocation of PKC from the cytosol

ZL Chang; Re Hall

1995-01-01

10

Interactions between hairy/enhancer of split-related proteins and the pancreatic transcription factor Ptf1-p48 modulate function of the PTF1 transcriptional complex.  

PubMed

In the developing pancreas, the onset of exocrine differentiation is driven by the activity of the PTF1 (pancreas transcription factor 1) transcriptional complex, which is comprised of the class II bHLH (basic helix-loop-helix) protein, Ptf1-p48 [also known as Ptf1a (pancreas specific transcription factor 1a)], and a class I E-box binding partner. Activity of the PTF1 complex is normally inhibited by the Notch signalling pathway, a process mediated by Notch effector proteins in the HES (Hairy/Enhancer of Split) family of bHLH transcriptional repressors. In the present study, we show that this inhibitory effect occurs through direct interaction between HES family members and Ptf1-p48. The HES family members Hey1 (hairy/enhancer-of-split related with YRPW motif 1) and Hey2 co-immunoprecipitate with Ptf1-p48, and Ptf1-p48 binding by Hes1 is also evident in yeast two-hybrid and GST (glutathione S-transferase) pull-down assays. The ability of Hes1 to interact with Ptf1-p48 resides within a fragment comprised of the bHLH, Orange and C-terminal domains, and does not require the N-terminal or WRPW elements. The ability of truncated versions of Hes1 to bind Ptf1-p48 correlates with their ability to down-regulate the activity of the PTF1 transcriptional complex, defining Ptf1-p48 binding as the most likely mechanism by which Notch effector proteins delay exocrine pancreatic differentiation. PMID:16201968

Ghosh, Bidyut; Leach, Steven D

2006-02-01

11

Epitope analysis of PPAR? monoclonal antibody P?48.34A and its application for screening PPAR? ligands  

Microsoft Academic Search

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that directly modulate gene expression by binding to specific ligands. It has been established that PPAR? ligands play an essential role in obesity, diabetes, and inflammation. Recently, a great deal of research has focused on the screening of PPAR? ligands. In this study, both a human peroxisome proliferator-activated receptors ?2 (PPAR?2) recombinant protein

Hae-Sook Lee; Min-Chul Cho; Tae-Woong Baek; Yong-Kyung Choe; Jong-Wan Kim; Jin-Tae Hong; Pyung-Keun Myung; Sang-Gi Paik; Do-Young Yoon

2005-01-01

12

Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL-KrasG12D/+ mice.  

PubMed

Pancreatic cancer is the one of most common causes of cancer deaths and has the worst prognosis. Clinical observational studies suggest that statins may reduce the risk of pancreatic cancer. The chemopreventive efficacy of the statin atorvastatin (Lipitor(®)) and the role of the phosphatidyl-inositol 3-kinase (PI3/AKT) signaling pathway were evaluated for the progression of pancreatic intraepithelial neoplasms (PanINs) to pancreatic ductal adenocarcinoma (PDAC) in conditional p48(Cre/+) -LSL-Kras(G12D/+) transgenic mice. Six-week-old male p48(Cre/+) -LSL-Kras(G12D/+) (20/group) mice were fed AIN-76A diets containing 0, 200 and 400 ppm atorvastatin for 35 weeks. At termination, pancreata were evaluated histopathologically for PanINs and PDAC, and for various PI3/AKT signaling markers, and inflammatory cytokines, by immunohistochemistry/immunohistoflourscence, ELISA, Western blotting and/or reverse transcription-PCR methods. Control diet-fed mice showed 85% incidence of PDAC; whereas, mice fed with atorvastatin showed PDAC incidence of 65 and 35%, respectively (p < 0.0001). Similarly, significant suppression of PanIN-3 (22.6%) was observed in mice fed 400 ppm atorvastatin. Importantly, pancreata from atorvastatin-treated mice were ?68% free from ductal lesions. Furthermore, pancreas of mice administered with atorvastatin had significantly reduced expressions levels of PCNA, p2X7, p-ERK, RhoA, cyclin D1, survivin, Akt, pAKT, ?-catenin, cyclin E, cdK2 and caveolin-1. Also, atorvastatin-treated mice had shown dose-dependent suppression of inflammatory cytokines and a significant increase in tunnel-positive cells, p21 and PARP expression levels in pancreas. Atorvastatin significantly delays the progression of PanIN-1 and -2 lesions to PanIN-3 and PDAC by modulating PI3/AKT signal molecules in a preclinical model, suggesting potential clinical benefits of statins for high-risk pancreatic cancer patients. PMID:22287227

Mohammed, Altaf; Qian, Li; Janakiram, Naveena B; Lightfoot, Stan; Steele, Vernon E; Rao, Chinthalapally V

2012-03-14

13

Genes  

NSDL National Science Digital Library

Illustration of the placement of genes in a chromosome. A gene can be defined as a region of DNA that controls a hereditary characteristic. It usually corresponds to a sequence used in the production of a specific protein or RNA. A gene carries biological information in a form that must be copied and transmitted from each cell to all its progeny. This includes the entire functional unit: coding DNA sequences, non-coding regulatory DNA sequences, and introns. Genes can be as short as 1000 base pairs or as long as several hundred thousand base pairs. It can even be carried by more than one chromosome. The estimate for the number of genes in humans has decreased as our knowledge has increased. As of 2001, humans are thought to have between 30,000 and 40,000 genes.

Excellence, Access

2005-03-12

14

The consistency of the data for neutron fission averaged cross-sections of threshold reactions: a study on the cross-section of 46Ti(n,p)46Sc, 47Ti(n,p)47Sc, 48Ti(n,p)48Sc and 64Zn(n,p)64Cu reactions.  

PubMed

The consistency of the published values for fission averaged cross-sections of threshold reactions induced in a nuclear reactor is analyzed. The influence of the literature data involved in the determination of these cross-sections is discussed. Renormalizations based on cross-sections value for the standard reactions, isotopic abundances of the precursors and radiation emission probabilities of the radionuclide under study and the monitor, are applied to the evaluation of the cross-sections for the reactions: (46)Ti(n,p)(46)Sc; (47)Ti(n,p)(47)Sc; (48)Ti(n,p)(48)Sc; and (64)Zn(n,p)(64)Cu. PMID:23583886

Cohen, I M; Fornaciari Iljadica, M C; Furnari, J C; Alí Santoro, M C

2013-03-14

15

Gene Switch  

NSDL National Science Digital Library

Regulatory "switches" are found upstream from a gene. Regulatory molecules bind to the switches and recruit RNA polymerase to bind to the gene's promoter region, increasing the transcription of the gene into messenger RNA.

Howard Hughes Medical Institute (Howard Hughes Medical Institute;)

2008-04-09

16

Gene transfer and gene therapy  

Microsoft Academic Search

This book reports the progress in gene transfer that has been made in various species, from Drosophila to higher mammals, including illustrative examples of germline gene transfer and tissue-specific somatic gene regulation in the mouse. Important new information regarding developmental control of gene transcription includes the delineation of distal elements, both cis and trans, controlling specific gene regulation. The book

A. L. Beaudet; R. Mulligan; I. M. Verma

1988-01-01

17

Gene transfer and gene therapy  

SciTech Connect

This book reports the progress in gene transfer that has been made in various species, from Drosophila to higher mammals, including illustrative examples of germline gene transfer and tissue-specific somatic gene regulation in the mouse. Important new information regarding developmental control of gene transcription includes the delineation of distal elements, both cis and trans, controlling specific gene regulation. The book also offers an overview of vectors for gene transfer, including retroviral vectors and new retroviral packaging cell lines designed to minimize production of replication-competent virus.

Beaudet, A.L.; Mulligan, R.; Verma, I.M.

1988-01-01

18

Gene Therapy  

Microsoft Academic Search

\\u000a Technological developments in gene isolation and DNA sequencing have been important factors contributing to the knowledge\\u000a of the genes associated with numerous diseases. This information has been critical for enhancing our understanding of the\\u000a genetic basis of disease and the role that specific genes play in human phys

Arianna Malgieri; Paola Spitalieri; Giuseppe Novelli; Federica C. Sangiuolo

19

Gene therapy  

Microsoft Academic Search

Gene therapy is not yet possible, but may become feasible soon, particularly for well understood gene defects. Although treatment of a patient raises no ethical problems once it can be done well, changing the genes of an early embryo is more difficult, controversial and unlikely to be required clinically.

Bob Williamson

1982-01-01

20

Gene doping.  

PubMed

Gene doping abuses the legitimate approach of gene therapy. While gene therapy aims to correct genetic disorders by introducing a foreign gene to replace an existing faulty one or by manipulating existing gene(s) to achieve a therapeutic benefit, gene doping employs the same concepts to bestow performance advantages on athletes over their competitors. Recent developments in genetic engineering have contributed significantly to the progress of gene therapy research and currently numerous clinical trials are underway. Some athletes and their staff are probably watching this progress closely. Any gene that plays a role in muscle development, oxygen delivery to tissues, neuromuscular coordination, or even pain control is considered a candidate for gene dopers. Unfortunately, detecting gene doping is technically very difficult because the transgenic proteins expressed by the introduced genes are similar to their endogenous counterparts. Researchers today are racing the clock because assuring the continued integrity of sports competition depends on their ability to develop effective detection strategies in preparation for the 2012 Olympics, which may mark the appearance of genetically modified athletes. PMID:20020377

Azzazy, Hassan M E

2010-01-01

21

Gene Therapy  

PubMed Central

Gene therapy is defined as the treatment of disease by transfer of genetic material into cells. This review will explore methods available for gene transfer as well as current and potential applications for craniofacial regeneration, with emphasis on future development and design. Though non-viral gene delivery methods are limited by low gene transfer efficiency, they benefit from relative safety, low immunogenicity, ease of manufacture, and lack of DNA insert size limitation. In contrast, viral vectors are nature’s gene delivery machines that can be optimized to allow for tissue-specific targeting, site-specific chromosomal integration, and efficient long-term infection of dividing and non-dividing cells. In contrast to traditional replacement gene therapy, craniofacial regeneration seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and replace tissues in vivo.

Scheller, E.L.; Krebsbach, P.H.

2009-01-01

22

Expression of an auxin- and cytokinin-regulated gene in cambial region in Zinnia  

SciTech Connect

The expression patterns of a cDNA clone, p48h-10, of an auxin-induced gene were examined in isolated mesophyll cells of Zinnia and in the organs of Zinnia plants. In the isolated mesophyll cells, the mRNA accumulates in 48 hr of culture with 1-naphthaleneacetic acid alone. Because the first cell division occurs before 36 hr of culture, the gene probably is not involved in cell division. Benzyladenine does not induce expression of this gene, but the combination of 1-naphthaleneacetic acid and benzyladenine induces the mRNA accumulation about 24 hr earlier than does 1-naphthaleneacetic acid alone. Tissue print hybridization shows that the mRNA is present predominantly in the cambial region in stems, leaves, and roots and in the vascular bundles in flower buds but does not occur in the apical regions of shoot or root. The characteristics of the gene expression, including auxin- and cytokinin-regulated induction and cambial region localization, encourage the authors to suggest that the gene is involved in the early process of vascular differentiation.

Ye, Z.H.; Varner, J.E. (Washington Univ., St. Louis, MO (United States))

1994-07-05

23

Gene Therapy  

Microsoft Academic Search

Severe genetic disorders are potentially correctable by the addition of a normal gene into tissues. Although the technical problems involving integration, stable expression, and insertional damage to the treated cell are not yet fully solved, enough scientific progress has already been made to consider somatic cell gene therapy acceptable from both the ethical and scientific viewpoints. The resolutions to problems

Arie Drugan; Orlando J. Miller; Mark I. Evans

1987-01-01

24

Gene Therapy  

NSDL National Science Digital Library

This learning resource is a guide for teachers of sciences in helping students to learn about Gene therapy. This lesson uses multiple activities, which engage students in learning about current genetic research and the ethical implications of this research.

Scientific American Frontiers (;)

2007-09-26

25

Gene Therapy.  

National Technical Information Service (NTIS)

Blood cells are used as cellular vehicles for gene transfer. In one embodiment, the invention is directed to a method of enhancing the therapeutic effects of blood cells. For example, there is provided a method of enhancing the therapeutic effects of bloo...

W. F. Anderson R. M. Blaese S. A. Rosenberg

1989-01-01

26

Vulnerability genes or plasticity genes?  

PubMed Central

The classic diathesis–stress framework, which views some individuals as particularly vulnerable to adversity, informs virtually all psychiatric research on behavior–gene–environment (G × E) interaction. An alternative framework of ‘differential susceptibility' is proposed, one which regards those most susceptible to adversity because of their genetic make up as simultaneously most likely to benefit from supportive or enriching experiences—or even just the absence of adversity. Recent G × E findings consistent with this perspective and involving monoamine oxidase-A, 5-HTTLPR (5-hydroxytryptamine-linked polymorphic region polymorphism) and dopamine receptor D4 (DRD4) are reviewed for illustrative purposes. Results considered suggest that putative ‘vulnerability genes' or ‘risk alleles' might, at times, be more appropriately conceptualized as ‘plasticity genes', because they seem to make individuals more susceptible to environmental influences—for better and for worse.

Belsky, J; Jonassaint, C; Pluess, M; Stanton, M; Brummett, B; Williams, R

2009-01-01

27

Gene Chip Technology for Determining Memory Genes.  

National Technical Information Service (NTIS)

The present invention relates to methods of identifying genes involved in memory formation. This is accomplished by performing a gene chip identification of those genes expressed during transcription-dependent memory formation but not during transcription...

J. Mous J. I. Dubnau M. Davis T. P. Tully U. Certa

2005-01-01

28

Vulnerability genes or plasticity genes?  

Microsoft Academic Search

The classic diathesis–stress framework, which views some individuals as particularly vulnerable to adversity, informs virtually all psychiatric research on behavior–gene–environment (G × E) interaction. An alternative framework of ‘differential susceptibility’ is proposed, one which regards those most susceptible to adversity because of their genetic make up as simultaneously most likely to benefit from supportive or enriching experiences—or even just the

J Belsky; C Jonassaint; M Pluess; M Stanton; B Brummett; R Williams

2009-01-01

29

Good Genes and Bad Genes  

Microsoft Academic Search

\\u000a In popular biographies, Elvis Presley appears as a genetic construct, driven by his genes to his unlikely destiny. He has\\u000a succeeded, the story goes, because of his genetic heritage — and failed because of his family’s history of inbreeding. Elaine\\u000a Dundy, for example, attributes Presley’s success to the qualities of will, ambition, and fantasy passed down to him from his

Dorothy Nelkin; M. Susan Lindee

30

Gene Switches  

NSDL National Science Digital Library

In this activity, learners explore how genetic switches function and the role of genetic switches in the process of evolution. To make these concepts less abstract and more understandable, learners first view a series of video clips and animations from the HHMI DVD (or online) "Evolution: Constant Change and Common Threads." Then, learners construct a model of a gene switch using craft materials or FridgiGears (magnetic gears). This activity can be done as a demonstration, a student inquiry activity, or a combination of the two.

Colvard, Mary

2010-01-01

31

The Mouse DNA Polymerase a-Primase Subunit p48 Mediates Species-Specific Replication of Polyomavirus DNA In Vitro  

Microsoft Academic Search

Mouse cell extracts support vigorous replication of polyomavirus (Py) DNA in vitro, while human cell extracts do not. However, the addition of purified mouse DNA polymerase a-primase to human cell extracts renders them permissive for Py DNA replication, suggesting that mouse polymerase a-primase determines the species specificity of Py DNA replication. We set out to identify the subunit of mouse

ANDREA BRUCKNER; FRANZ STADLBAUER; LINDA A. GUARINO; ANTJE BRUNAHL; CHRISTINE SCHNEIDER; CHRISTOPH REHFUESS; CAROL PRIVES; ELLEN FANNING; ANDHEINZ-PETER NASHEUER

32

Transcription of interferon stimulated genes in response to Porcine rubulavirus infection in vitro  

PubMed Central

Porcine rubulavirus (PoRV) is an emerging virus causing meningo-encephalitis and reproductive failures in pigs. Little is known about the pathogenesis and immune evasion of this virus; therefore research on the mechanisms underlying tissue damage during infection is essential. To explore these mechanisms, the effect of PoRV on the transcription of interferon (IFN) pathway members was analyzed in vitro by semi-quantitative RT-PCR. Ten TCID50 of PoRV stimulated transcription of IFN?, IFN?, STAT1, STAT2, p48 and OAS genes in neuroblastoma cells, whereas infection with 100 TCID50 did not stimulate transcription levels more than non-infected cells. When the cells were primed with IFN?, infection with 1 TCDI50 of PoRV sufficed to stimulate the transcription of the same genes, but 10 and 100 TCID50 did not modify the transcription level of those genes as compared with non-infected and primed controls. MxA gene transcription was observed only when the cells were primed with IFN? and stimulated with 10 TCID50, whereas 100 TCID50 of PoRV did not modify the MxA transcription level as compared to non-infected and primed cells. Our results show that PoRV replication at low titers stimulates the expression of IFN-responsive genes in neuroblastoma cells, and suggest that replication of PoRV at higher titers inhibits the transcription of several members of the IFN pathway. These findings may contribute to the understanding of the pathogenesis of PoRV.

Flores-Ocelotl, Maria del Rosario; Rosas-Murrieta, Nora Hilda; Vallejo-Ruiz, Veronica; Reyes-Leyva, Julio; Herrera-Camacho, Irma; Santos-Lopez, Gerardo

2011-01-01

33

A Truncated Form of the Human CAF-1 p150 Subunit Impairs the Maintenance of Transcriptional Gene Silencing in Mammalian Cells  

PubMed Central

Chromatin assembly factor 1 (CAF-1) is a protein complex formed of three subunits, p150, p60, and p48, conserved from the yeast Saccharomyces cerevisiae to humans, which can promote nucleosome assembly onto newly replicated DNA. In S. cerevisiae, deletion of the genes encoding any of the three CAF-1 subunits (cac? mutants), although nonlethal, results in a silencing defect of genes packaged into heterochromatin. Here we report on a mammalian cell model that we devised to monitor gene silencing and its reversal in a quantitative manner. This model relies on the use of a cell line stably transfected with a reporter gene in a silenced state. Reversal of reporter gene silencing was achieved upon treatment of the cells with 5-azacytidine, which resulted in the demethylation of the reporter gene copies. We show that expression of a cDNA for the human p150 CAF-1 subunit harboring 5? truncations, but not that of a cDNA encoding the full-length p150 CAF-1 subunit, increases by more than 500-fold the frequency at which transcriptional silencing of the reporter gene copies is reversed in these cells. Reversal of gene silencing is dependent upon expression of a truncated protein, possibly acting as a dominant negative mutant of the wild-type CAF-1, is associated with alterations in chromatin structure as measured by an endonuclease sensitivity assay and is not associated with detectable changes in the methylation status of the silenced genes. These results suggest that the role of CAF-1 in the epigenetic control of gene expression has been conserved between yeast and mammals, despite the lack of DNA methylation in yeast chromatin.

Tchenio, Thierry; Casella, Jean-Francois; Heidmann, Thierry

2001-01-01

34

[WRN gene].  

PubMed

Werner's syndrome is a typical progeroid syndrome with many specific features of aging early in life. Clinical features of Werner's syndrome closely resemble accelerated aging, such as cataract, scleroderma skin, diabetes and tumorigenesis. The causative gene of this syndrome is denoted as WRN, which encodes a homolog of the E. coli RecQ DNA helicase and is located on chromosome 8p2-p11.2. WRN is not only a helicase but also an exonuclease and ATPase. WRN protein plays a key role in genome stability, particularly during DNA replication and telomere metabolism. In this review, we introduce the clinical characteristics of Werner's syndrome and recent topics concerning WRN in comparison with other progeroid syndromes. PMID:19591272

Katsuya, Tomohiro; Morishita, Ryuichi

2009-07-01

35

Essential Bacillus subtilis genes  

Microsoft Academic Search

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively

K. Kobayashi; S. D. Ehrlichb; A. Albertini; G. Amati; K. Asaig Arnaudf; M. Arnaud; K. Asai; S. Ashikaga; S. Aymerich; P. Bessieres; F. Boland; S. C. Brignell; S. Bron; K. Bunai; J. Chapuis; L. C. Christiansen; A. Danchin; M. Débarbouillé; E. Dervyn; E. Deuerling; K. Devine; S. K. Devine; O. Dreesen; J. Errington; S. Fillinger; S. J. Foster; Y. Fujita; A. Galizzi; R. Gardan; C. Eschevins; T. Fukushima; K. Haga; C. R. Harwood; M. Hecker; D. Hosoya; M. F. Hullo; H. Kakeshita; D. Karamata; Y. Kasahara; F. Kawamura; K. Koga; P. Koski; R. Kuwana; D. Imamura; M. Ishimaru; S. Ishikawa; I. Ishio; D. Le Coq; A. Masson; C. Mauël; R. Meima; R. P. Mellado; A. Moir; S. Moriya; E. Nagakawa; H. Nanamiya; S. Nakai; P. Nygaard; M. Ogura; T. Ohanan; M. O'Reilly; M. O'Rourke; Z. Pragai; H. M. Pooley; G. Rapoport; J. P. Rawlins; L. A. Rivas; C. Rivolta; A. Sadaie; Y. Sadaie; M. Sarvas; T. Sato; H. H. Saxild; E. Scanlan; W. Schumann; J. F. Seegers; J. Sekiguchi; A. Sekowska; S. J. Seror; M. Simon; P. Stragier; R. Studer; H. Takamatsu; T. Tanaka; M. Takeuchi; H. B. Thomaides; V. Vagner; J. M. van Dijl; K. Watabe; A. Wipat; H. Yamamoto; M. Yamamoto; Y. Yamamoto; K. Yamane; K. Yata; K. Yoshida; H. Yoshikawa; U. Zuber; N. Ogasawara

2003-01-01

36

Chromatin loops, gene positioning, and gene expression  

PubMed Central

Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the ?- and ?-globin gene loci, the antigen receptor loci, the imprinted H19–Igf2 locus and the Hox gene clusters. Collectively, these studies show that regulatory DNA sequences physically contact genes to control their transcription. Proteins set up the 3D configuration of the genome and we will discuss the roles of the key structural organizers CTCF and cohesin, the nuclear lamina and the transcription machinery. Finally, genes adopt non-random positions in the nuclear interior. We will review studies on gene positioning and propose that cell-specific genome conformations can juxtapose a regulatory sequence on one chromosome to a responsive gene on another chromosome to cause altered gene expression in subpopulations of cells.

Holwerda, Sjoerd; de Laat, Wouter

2012-01-01

37

Gene conversion in steroid 21-hydroxylase genes.  

PubMed Central

The steroid 21-hydroxylase gene, CYP21B, encodes cytochrome P450c21, which mediates 21-hydroxylation. The gene is located about 30 kb downstream from pseudogene CYP21A. The CYP21A gene is homologous to the CYP21B gene but contains some mutations, including a C----T change which leads a termination codon, TAG, in the eighth exon. We found the same change in a mutant CYP21B gene isolated from a patient with 21-hydroxylase deficiency. Furthermore, a reciprocal change--i.e., a T----C change in the eighth exon of the CYP21A gene--was observed in the Japanese population and was associated with the two HLA haplotypes, HLA-B44-DRw13 and HLA-Bw46-DRw8. These changes may be considered the result of gene conversion-like events. Images Figure 1 Figure 3 Figure 5 Figure 6

Urabe, K; Kimura, A; Harada, F; Iwanaga, T; Sasazuki, T

1990-01-01

38

Evolution of homeobox genes.  

PubMed

Many homeobox genes encode transcription factors with regulatory roles in animal and plant development. Homeobox genes are found in almost all eukaryotes, and have diversified into 11 gene classes and over 100 gene families in animal evolution, and 10 to 14 gene classes in plants. The largest group in animals is the ANTP class which includes the well-known Hox genes, plus other genes implicated in development including ParaHox (Cdx, Xlox, Gsx), Evx, Dlx, En, NK4, NK3, Msx, and Nanog. Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes. Expression and functional data suggest that NK, Hox, and ParaHox gene clusters acquired distinct roles in patterning the mesoderm, nervous system, and gut. The PRD class is also diverse and includes Pax2/5/8, Pax3/7, Pax4/6, Gsc, Hesx, Otx, Otp, and Pitx genes. PRD genes are not generally arranged in ancient genomic clusters, although the Dux, Obox, and Rhox gene clusters arose in mammalian evolution as did several non-clustered PRD genes. Tandem duplication and genome duplication expanded the number of homeobox genes, possibly contributing to the evolution of developmental complexity, but homeobox gene loss must not be ignored. Evolutionary changes to homeobox gene expression have also been documented, including Hox gene expression patterns shifting in concert with segmental diversification in vertebrates and crustaceans, and deletion of a Pitx1 gene enhancer in pelvic-reduced sticklebacks. WIREs Dev Biol 2013, 2:31-45. doi: 10.1002/wdev.78 For further resources related to this article, please visit the WIREs website. Conflict of interest: The author declares that he has no conflicts of interest. PMID:23799629

Holland, Peter W H

2012-09-10

39

Clock Genes and Cancer  

Microsoft Academic Search

Period genes ( Per2, Per1) are essential circadian clock genes. They also function as negative growth regulators. Per2 mutant mice show de novo and radiation-induced epithelial hyperplasia, tumors, and an abnormal DNA damage response. Human tumors show Period gene mutations or decreased expression. Other murine clock gene mutations are not associated with a tumor prone phenotype. Shift work and nocturnal

Patricia A. Wood; Xiaoming Yang; William J. M. Hrushesky

2009-01-01

40

Aging: gene silencing or gene activation?  

PubMed

According to the author's theory of gene silencing, the key process in aging involves reduced expression of a number of genes. Silencing of genes has a complex mechanism, which involves methylation of DNA, histone modification and chromatin remodeling. In addition to deacetylation of the histones and methylation of DNA, recently described RNAi mechanism could initiate formation of silenced chromatin. Hypermethylation of the promoter will silence the gene. Genome-wide hypomethylation will induce genomic instability, amplification of oncogenes and also silencing of the genes through RNAi mechanism. Studies by different groups, conducted in yeast, worms, flies and mice, confirmed substantial changes in gene expression in aging. Among them, the most important was silencing of tumor suppressors and other genes involved in the control of cell cycle, apoptosis, detoxification, and cholesterol metabolism. There was also increased expression of the smaller group of oncogenes and other genes which are associated with typical diseases of old age. Caloric restriction normalizes expression of a substantial percentage of these genes. Animal studies confirmed importance of caloric restriction, which decreases signaling through the IGF-1/AKT pathway and expression of gene p53. These studies, however, cannot be directly applied to human aging. It is proposed that age management therapy should attempt to normalize gene expression in the older population to the level typical for young adults. This would require activation of silenced genes and normalization of overexpressed genes. Caloric restriction and exercise are helpful in decreasing the activity of important oncogenes and activation of silenced tumor suppressors, and may have a positive impact, not only on aging, but also on prevention of cancer. Dietary supplements containing phytochemicals should normalize increased expression of oncogenes. Examples are: genistein and EGCG, which effect signaling through the IGF-1/AKT pathway and resveratrol and limonen, which do so through the RAS pathway. A group of amino acid derivatives and organic acids of animal and human origin should activate silenced tumor suppressor genes (Aminocare A10, Aminocare Extra). Among them 3-phenylacetylamino-2, 6-piperidinedione intercalates specifically with DNA and protects sequences of tumor suppressor genes, which are vulnerable to the effects of carcinogens. Phenylacetate activates p53 and p21 through inhibition of methyltransferase and farnesylation of the RAS protein. Phenylbutyrate activates tumor suppressor genes through inhibition of histone deacetylation. Phenylacetylglutamine decreases genomic instability and expression of oncogenes and promotes apoptosis. The application of DNA microarray techniques to human studies should provide more information about differences in gene expression in different age groups and help design more effective age management regimens. PMID:15533642

Burzynski, Stanislaw R

2005-01-01

41

Novel gene delivery systems  

PubMed Central

Gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions, and genetic disorders. Application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Several nonviral and viral gene transfer methods have been developed. Even though the viral agents have a high transferring efficiency, they are difficult to handle due to their toxicity. To overcome the safety problems of the viral counterpart, several nonviral in vitro and in vivo gene delivery systems are developed. Out of these, the most promising and latest systems include polymer-based nonviral gene carriers, dendrimers, and physical means like electroporation, microinjection, etc., Shunning of possible immunogenicity and toxicity, and the feasibility of repeated administration are some of the merits of nonviral gene delivery systems over viral gene delivery. An ideal nonviral gene carrying system should possess all these merits without any compromise to its gene transferring efficiency. The viral gene delivery systems include lytic and nonlytic vectors for drug delivery. Inspite of its toxicity they are still preferred because of their long term expression, stability, and integrity. This review explores the recent developments and relevancy of the novel gene delivery systems in gene therapy.

Manjila, Steffy B; Baby, Jomon N; Bijin, Elambilan N; Constantine, Icey; Pramod, Kannissery; Valsalakumari, Janardhanan

2013-01-01

42

A non-classical ISRE/ISGF3 pathway mediates induction of RANTES gene transcription by type I IFNs.  

PubMed

RANTES (regulated upon activation normal T cell expressed and secreted) is a chemoattractant cytokine important in the generation of inflammatory responses and human immunodeficiency virus resistance. In hematopoietic cells, RANTES is over-expressed by type I interferons (IFN-alpha and IFN-beta). The upstream region of the RANTES gene promoter contains a distal low affinity IFN-stimulated response element (ISRE). Specific mutagenesis in this ISRE-like motif abolished the activation of RANTES transcription by type I IFNs. Examination of the ISRE binding factors strongly suggested that signal transducer and activator of transcription (Stat)-2 and p48/IFN-stimulated gene factor 3gamma (ISGF3gamma) are not required for the induction of RANTES by type I IFNs. The specific requirement of Stat-1 was demonstrated using Stat-1-deficient U3A cells. These results revealed a non-classical ISRE/ISGF3 signal transduction pathway for the induction of RANTES by type I IFNs. PMID:11821046

Cremer, Isabelle; Ghysdael, Jacques; Vieillard, Vincent

2002-01-30

43

Human housekeeping genes, revisited.  

PubMed

Housekeeping genes are involved in basic cell maintenance and, therefore, are expected to maintain constant expression levels in all cells and conditions. Identification of these genes facilitates exposure of the underlying cellular infrastructure and increases understanding of various structural genomic features. In addition, housekeeping genes are instrumental for calibration in many biotechnological applications and genomic studies. Advances in our ability to measure RNA expression have resulted in a gradual increase in the number of identified housekeeping genes. Here, we describe housekeeping gene detection in the era of massive parallel sequencing and RNA-seq. We emphasize the importance of expression at a constant level and provide a list of 3804 human genes that are expressed uniformly across a panel of tissues. Several exceptionally uniform genes are singled out for future experimental use, such as RT-PCR control genes. Finally, we discuss both ways in which current technology can meet some of past obstacles encountered, and several as yet unmet challenges. PMID:23810203

Eisenberg, Eli; Levanon, Erez Y

2013-06-27

44

Gene therapy for arthritis  

Microsoft Academic Search

\\u000a Gene therapy has a potential for effective therapeutic intervention in rheumatoid arthritis (RA). Proof of concept has been\\u000a demonstrated in animal models, either through local gene delivery to the joint space or through systemic gene delivery for\\u000a immune intervention. This chapter reviews how certain clinical applications of gene therapy would be beneficial for RA patients\\u000a and discusses the roadblocks that

Florence Apparailly; Paul Peter Tak; Christian Jorgensen

45

Gene Therapy for Cancer  

Microsoft Academic Search

The basic strategies for gene therapy that have been explored include immunogene therapy such as cytokine gene transfer,\\u000a selective prodrug activation, so-called suicide genes, transfer of a tumor suppressor gene, and inhibition of activated oncogenes\\u000a by antisense mechanisms. Many therapeutic protocols have so far been registered in the office of the Recombinant DNA Advisory\\u000a Committee, NIH, as of June 1999.

Yoshio Gunji; Takenori Ochiai; H. Shimada; H. Matsubara

2000-01-01

46

Gene therapy of cancer  

Microsoft Academic Search

There are several approaches to the gene therapy of cancer. Genes can be introduced into cancer cells to either sensitize\\u000a them for killing by subsequent treatment with drugs, or to normalize their growth. In addition, genes can be added to tumor\\u000a cells to provoke an accentuated immune response against these cells leading to cancer cell death. Alternatively, drug resistance\\u000a genes

Arthur Bank

1995-01-01

47

Gene therapy in surgery  

Microsoft Academic Search

Summary  \\u000a Background: With the increasing body of knowledge in molecular biology, gene transfer respectively gene therapy becomes more and more\\u000a a valid therapeutic option.\\u000a \\u000a \\u000a Methods: This is a critical review of gene therapy protocols for treatment of different types of cancer. Furthermore, the pathophysiological\\u000a mechanism, therapeutically strategies as well as experimental approaches toward gene transfer in septic shock and organ

M. A. Rogy; Julie M. Baumhofer; Britta Beinhauer; H. Brandmeier; P. Eisenburger; U. M. Losert; Ramila Philip

1997-01-01

48

Gene Therapy and Radiation  

Microsoft Academic Search

\\u000a Owing to a low efficiency of gene transfer when delivered systemically, gene therapy may find its greatest utility in the\\u000a clinic when combined with loco-regional cancer treatment such as radiation therapy. Although a variety of gene therapy strategies\\u000a have been combined with radiation in preclinical models, only a handful have been translated into the clinic. Overall, combining\\u000a gene therapy with

Svend O. Freytag; Kenneth N. Barton; Farzan Siddiqui; Mohamed Elshaikh; Hans Stricker; Benjamin Movsas

49

Gene therapies for osteoarthritis  

Microsoft Academic Search

Osteoarthritis (OA) is a major health problem in urgent need of better treatment. Gene therapy offers to meet this need. Of\\u000a the different strategies for using gene therapy in OA, local gene transfer to synovium is in the most advanced stage of development.\\u000a Local gene transfer brings several advantages, including a focused, local therapy that promises greater efficacy with reduced

Christopher H. Evans

2004-01-01

50

Cyanobacterial signature genes  

Microsoft Academic Search

A comparison of 8 cyanobacterial genomes reveals that there are 181 shared genes that do not have obvious orthologs in other\\u000a bacteria. These signature genes define aspects of the genotype that are uniquely cyanobacterial. Approximately 25% of these\\u000a genes have been associated with some function. These signature genes may or may not be involved in photosynthesis but likely\\u000a they will

Kirt A. Martin; Janet L. Siefert; Sailaja Yerrapragada; Yue Lu; Thomas Z. McNeill; Pedro A. Moreno; George M. Weinstock; William R. Widger; George E. Fox

2003-01-01

51

Reading and Generalist Genes  

ERIC Educational Resources Information Center

|Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

2007-01-01

52

Mitomycin biosynthetic gene cluster  

US Patent & Trademark Office Database

The invention provides a biosynthetic gene cluster for mitomycin, for example, a mitomycin biosynthetic cluster from organisms such as Streptomyces, for instance, S. lavendulae, as well as methods of using gene(s) within the cluster to alter antibiotic biosynthesis and to prepare a polyketide synthase.

Sherman; David H. (St. Louis Park, MN); Mao; Yingqing (St. Paul, MN); Varoglu; Mustafa (St. Paul, MN); He; Min (St. Paul, MN); Sheldon; Paul (Fitchburg, WI)

2002-12-17

53

Homeobox Genes and Cancer  

Microsoft Academic Search

Homeobox-containing genes are a family of regulatory genes encoding transcription factors that primarily play a crucial role during development. Several indications suggest their involvement in the control of cell growth and, when dysregulated, in oncogenesis. We will describe the implications, in tumor origin and evolution, of members of the homeobox gene families HOX, EMX, PAX, and MSX as well as

Clemente Cillo; Antonio Faiella; Monica Cantile; Edoardo Boncinelli

1999-01-01

54

Advances in gene technology  

SciTech Connect

This is the record of the 19th Miami Winter Symposium. This event is dedicated to exposing advances in gene technology. Subjects covered in this volume are grouped under the following headings: Control of gene expression; Early determination; Differentiation; Cell surface and tissue interactions; Morphogenesis; and Gene therapy.

Voellmy, R.W. Ahmad, F. Black, S. Burgess, D.R. Rotundo, R. Scott, W.A. Whelan, W.J.

1987-01-01

55

Dopamine genes and ADHD  

Microsoft Academic Search

Family, twin, and adoption studies have documented a strong genetic basis for ADHD\\/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD\\/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which

J. M Swanson; Pamela Flodman; James Kennedy; M. Anne Spence; Robert Moyzis; Sabrina Schuck; Michael Murias; Joan Moriarity; Cathy Barr; Moyra Smith; Michael Posner

2000-01-01

56

FMR1 Gene  

MedlinePLUS

... Interruptions? I Was Just Figuring Out CGG Repeats! Fragile X Infographic Donate | Print FMR1 Gene What Is a ... are, let’s discuss the Fragile X gene… The Fragile X (FMR1) Gene Why Is It Called the FMR1 ...

57

Gene Gateway: Exploring Genes and Genetic Disorders  

NSDL National Science Digital Library

This collection of guides and tutorials is intended to help users take advantage of of online data sources from the Human Genome Project for learning about genetic disorders, genes, and proteins. Resources include the Gene Gateway Workbook, a downloadable tutorial consisting of activities with screenshots and instructions, that helps new users locate and use genetic-disorder and bioinformatics resources on the web. There are also resources for learning about genes and the proteins they encode; tips, tutorials, and terminology for using selected resources in the Genome Database Guide; a guide to nontechnical resources on genetic disorder descriptions and treatments; a human genome landmarks poster; and others.

58

UniGene  

NSDL National Science Digital Library

Created by the National Center for Biotechnology Information, UniGene is "an experimental system for automatically partitioning GenBank sequences into a non-redundant set of gene-oriented clusters." In addition to gene sequences, this Web site also offers thousands of novel expressed sequence tag (EST) sequences, a useful gene discovery resource. Organisms currently cataloged include human, rat, mouse, cow, zebrafish, clawed frog, fruitfly, mosquito, wheat, rice, barley, maize, and cress. Users may also access the Digital Differential Display to compare gene expression fingerprints for cancer cells and their normal counterparts. Other Web site features include query tips, FAQs, and relevant external links.

1997-01-01

59

Understanding Cancer Series: Gene Testing  

MedlinePLUS

... Professionals Cancer Trends Progress Report: 2011/2012 Update Gene Testing Slide Number and Title Genes in the News DNA Chemical Bases in DNA DNA Molecules Gene Subunits DNA->RNA->Protein Different Genes - Different Functions ...

60

Gene therapy in periodontics  

PubMed Central

GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ‘the use of genes as medicine’. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

2013-01-01

61

Essential Bacillus subtilis genes.  

PubMed

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life. PMID:12682299

Kobayashi, K; Ehrlich, S D; Albertini, A; Amati, G; Andersen, K K; Arnaud, M; Asai, K; Ashikaga, S; Aymerich, S; Bessieres, P; Boland, F; Brignell, S C; Bron, S; Bunai, K; Chapuis, J; Christiansen, L C; Danchin, A; Débarbouille, M; Dervyn, E; Deuerling, E; Devine, K; Devine, S K; Dreesen, O; Errington, J; Fillinger, S; Foster, S J; Fujita, Y; Galizzi, A; Gardan, R; Eschevins, C; Fukushima, T; Haga, K; Harwood, C R; Hecker, M; Hosoya, D; Hullo, M F; Kakeshita, H; Karamata, D; Kasahara, Y; Kawamura, F; Koga, K; Koski, P; Kuwana, R; Imamura, D; Ishimaru, M; Ishikawa, S; Ishio, I; Le Coq, D; Masson, A; Mauël, C; Meima, R; Mellado, R P; Moir, A; Moriya, S; Nagakawa, E; Nanamiya, H; Nakai, S; Nygaard, P; Ogura, M; Ohanan, T; O'Reilly, M; O'Rourke, M; Pragai, Z; Pooley, H M; Rapoport, G; Rawlins, J P; Rivas, L A; Rivolta, C; Sadaie, A; Sadaie, Y; Sarvas, M; Sato, T; Saxild, H H; Scanlan, E; Schumann, W; Seegers, J F M L; Sekiguchi, J; Sekowska, A; Séror, S J; Simon, M; Stragier, P; Studer, R; Takamatsu, H; Tanaka, T; Takeuchi, M; Thomaides, H B; Vagner, V; van Dijl, J M; Watabe, K; Wipat, A; Yamamoto, H; Yamamoto, M; Yamamoto, Y; Yamane, K; Yata, K; Yoshida, K; Yoshikawa, H; Zuber, U; Ogasawara, N

2003-04-07

62

Essential Bacillus subtilis genes  

PubMed Central

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among ?4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden–Meyerhof–Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Kobayashi, K.; Ehrlich, S. D.; Albertini, A.; Amati, G.; Andersen, K. K.; Arnaud, M.; Asai, K.; Ashikaga, S.; Aymerich, S.; Bessieres, P.; Boland, F.; Brignell, S. C.; Bron, S.; Bunai, K.; Chapuis, J.; Christiansen, L. C.; Danchin, A.; Debarbouille, M.; Dervyn, E.; Deuerling, E.; Devine, K.; Devine, S. K.; Dreesen, O.; Errington, J.; Fillinger, S.; Foster, S. J.; Fujita, Y.; Galizzi, A.; Gardan, R.; Eschevins, C.; Fukushima, T.; Haga, K.; Harwood, C. R.; Hecker, M.; Hosoya, D.; Hullo, M. F.; Kakeshita, H.; Karamata, D.; Kasahara, Y.; Kawamura, F.; Koga, K.; Koski, P.; Kuwana, R.; Imamura, D.; Ishimaru, M.; Ishikawa, S.; Ishio, I.; Le Coq, D.; Masson, A.; Mauel, C.; Meima, R.; Mellado, R. P.; Moir, A.; Moriya, S.; Nagakawa, E.; Nanamiya, H.; Nakai, S.; Nygaard, P.; Ogura, M.; Ohanan, T.; O'Reilly, M.; O'Rourke, M.; Pragai, Z.; Pooley, H. M.; Rapoport, G.; Rawlins, J. P.; Rivas, L. A.; Rivolta, C.; Sadaie, A.; Sadaie, Y.; Sarvas, M.; Sato, T.; Saxild, H. H.; Scanlan, E.; Schumann, W.; Seegers, J. F. M. L.; Sekiguchi, J.; Sekowska, A.; Seror, S. J.; Simon, M.; Stragier, P.; Studer, R.; Takamatsu, H.; Tanaka, T.; Takeuchi, M.; Thomaides, H. B.; Vagner, V.; van Dijl, J. M.; Watabe, K.; Wipat, A.; Yamamoto, H.; Yamamoto, M.; Yamamoto, Y.; Yamane, K.; Yata, K.; Yoshida, K.; Yoshikawa, H.; Zuber, U.; Ogasawara, N.

2003-01-01

63

Myoadenylate deaminase deficiency caused by alternative splicing due to a novel intronic mutation in the AMPD1 gene.  

PubMed

We have examined two Caucasian brothers with myoadenylate deaminase (AMPD) deficiency who presented with exercise intolerance and muscle cramps. Allele-specific PCR amplification assays demonstrated that the common Q12X (C34T) and P48L (C143T) mutations were not found within their AMPD1 genes. Further analysis revealed that both brothers were compound heterozygotes for a previously reported K287I (A860T) mutation in exon 7 and a novel deletion within intron 2 (IVS2-(4-7)delCTTT). The intronic deletion appears to affect the splicing machinery since characterization of AMPD1 mRNA from skeletal muscle of one brother identified multiple alternatively spliced transcripts resulting in multiple deletions in exon 3, the complete deletion of either exon 3 or exons 3 and 4, and the activation of a cryptic splice site that resulted in an insertion at the 5' end of exon 4. The predominant transcript contains a 51 base deletion at the 5' end of exon 3 that is predicted to produce a functional form of AMPD containing a 17-amino acid residue deletion within its N-terminal region. Analysis of 137 Caucasian normal control patients determined that the K287I mutation is relatively frequent (5.1% carrier frequency), whereas the IVS2-(4-7)delCTTT mutation is rare and not present in 274 chromosomes. PMID:16040263

Isackson, Paul J; Bujnicki, Heather; Harding, Cary O; Vladutiu, Georgirene D

2005-07-22

64

Gene therapy for immunodeficiency  

Microsoft Academic Search

Since the early 1990s, primary immunodeficiency (ID) disorders have played a major role in the development of human gene therapy.\\u000a Adenosine deaminase (ADA) deficiency was the first disease to be treated with a gene therapy approach in humans, and was also\\u000a the first condition for which therapeutic gene transfer into the hematopoietic stem cell has been attempted in the clinical

Fabio Candotti

2001-01-01

65

Gene therapy for restenosis  

Microsoft Academic Search

This review provides an overview of candidate genes that are currently being evaluated for genetic strategies in vascular\\u000a gene therapy. We discuss treatment strategies that have proven efficacious in limiting postinterventional restenosis through\\u000a evaluation with in vivo model systems. The candidate strategies utilize genes that are either cytotoxic, regulate vascular\\u000a smooth muscle cell differentiation or proliferation. In addition, we review

Roy C. Smith; Kenneth Walsh

2000-01-01

66

Osteoarthritis gene therapy  

Microsoft Academic Search

Osteoarthritis (OA) is the Western world's leading cause of disability. It is incurable, costly and responds poorly to treatment. This review discusses strategies for treating OA by gene therapy. As OA affects a limited number of weight-bearing joints and has no major extra-articular manifestations, it is well suited to local, intra-articular gene therapy. Possible intra-articular sites of gene transfer include

CH Evans; JN Gouze; E Gouze; PD Robbins; SC Ghivizzani

2004-01-01

67

History of gene therapy.  

PubMed

Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. PMID:23618815

Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

2013-04-23

68

Gene therapy in surgery  

Microsoft Academic Search

Summary\\u000a Background  With the increasing body of knowledge in molecular biology, gene transfer respectively gene therapy becomes more and more\\u000a a valid therapeutic option.\\u000a \\u000a \\u000a \\u000a Methods  This is a critical review of gene therapy protocols for treatment of different types of cancer. Furthermore, the pathophysiological\\u000a mechanism, therapeutically strategies as well as experimental approaches toward gene transfer in septic shock and organ transplantation\\u000a are

M. A. Rogy; Julie M. Baumhofer; Britta Beinhauer; H. Brandmeier; P. Eisenburger; U. M. Losert; Ramila Philip

1996-01-01

69

'COGNITIVE GENES 'R EVEAL HIGHER CODON COMPLEXITY THAN 'SOMATIC GENES  

Microsoft Academic Search

In this article we want to apply the concept of complexity to the analysis and com- parison of genes. A multitude of genes has been identified coding somatic function. Recently the analysis of mental disorders yielded insights about genes coding cogni- tive functions. According to the theory of evolution they evolved from other genes through mutation. Therefore, 'cognitive genes' and

Christoph S. Herrmann; Wolfgang S. Herrmann

70

Heat-responsive gene expression for gene therapy  

Microsoft Academic Search

Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. By this approach, combination of chemotherapy, radiation or hyperthermia with gene therapy can result in considerable, additive or synergistic improvement of therapeutic efficacy. This concept has been successfully tested in particular for gene therapy

Wolfgang Walther; Ulrike Stein

2009-01-01

71

Hypoxia targeting gene expression for breast cancer gene therapy  

Microsoft Academic Search

Gene therapy is a promising strategy to treat various inherited and acquired diseases. However, targeting gene expression to specific tissue is required to minimize side effects of gene therapy. Hypoxia is present in the microenvironment of solid tumors such as breast tumors. A hypoxic tumor targeting gene expression system has been developed for cancer gene therapy. In hypoxic tissues, hypoxia

Minhyung Lee

2009-01-01

72

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...

73

Genes Involved in Atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a multifactorial disease that involves several genes and proteins. The purpose of this article is to focus on the arterial wall and to review lipoprotein receptors, growth factors, cytokines, chemokines, matrix metalloproteinases, adhesion molecules, and apoptosis genes and their involvement in atherogenesis.

Johanna Laukkanen; Seppo Ylä-Herttuala

2002-01-01

74

XLMR genes: update 2000.  

PubMed

This is the sixth edition of the catalogue of XLMR genes, ie X-linked genes whose malfunctioning causes mental retardation. The cloning era is not yet concluded, actually much remains to be done to account for the 202 XLMR conditions listed in this update. Many of these may eventually prove to be due to mutations in the same gene but the present number of 33 cloned genes falls surely short of the actual total count. It is now clear that even small families or individual patients with cytogenetic rearrangements can be instrumental in pinning down the remaining genes. DNA chip technology will hopefully allow (re)screening large numbers of patients for mutations in candidate genes or testing the expression levels of many candidate genes in informative families. Slowly, our knowledge of the structure and functioning of the proteins encoded by these genes is beginning to cast some light on the biological pathways required for the normal development of intelligence. Correlations between the molecular defects and the phenotypic manifestations are also being established. In order to facilitate the exchange of existing information and to allow its timely update, we prepared the first edition of the XLMR database (available at http://homepages.go.com/~xlmr/home.htm) and invite all colleagues, expert in the field, to contribute with their experience. PMID:11313739

Chiurazzi, P; Hamel, B C; Neri, G

2001-02-01

75

Smart Genes, Stupid Science.  

ERIC Educational Resources Information Center

Because many people still believe that specific, identifiable genes dictate the level of human intelligence and that the number/quality of these genes can be evaluated, presents evidence from human genetics (related to nervous system development) to counter this view. Also disputes erroneous assumptions made in "heritability studies" of human…

Randerson, Sherman; Mahadeva, Madhu N.

1983-01-01

76

TIGR Drosophila Gene Index  

NSDL National Science Digital Library

The Institute for Genomic Resources (TIGR) placed online the Drosophila Gene Index (version 1.1) in 1999. The index is searchable by nucleotide or protein sequence, identifier (TC, ET, EST, GB), tissue, or gene product name. Note that this resource is available free of charge "only to researchers at non-profit institutions using it for non-commercial purposes."

77

Gene Patents and Justice  

Microsoft Academic Search

heredity; they ‘‘specify the proteins that form the units of which homoeostatic devices are composed.’’ 2 New genetic diagnostics and therapies might help us prevent, reduce or possibly even cure certain diseases. By manipulating our genes we may be able to influence our propensity for certain physical, intellectual, psychological or even moral characteristics. The first officially sanctioned human somatic-cell gene-therapy

Colin Farrelly

2007-01-01

78

Gene targeting in plants  

PubMed Central

Although the generation of transgenic plants is now routine, the integration of foreign genetic information has so far been at random sites in the genome. We now present evidence for directed integration into a predicted location in the host plant genome. Protoplasts of transgenic tobacco (Nicotiana tabaccum) plants carrying copies of a partial, non-functional drug-resistance gene in the nuclear DNA were used as recipients for DNA molecules containing the missing part of the gene. Molecular and genetic data confirm the integration of the foreign DNA through homologous recombination within overlapping parts of the protein coding region, resulting in the formation of an active gene in the host chromosome. This approach is referred to as gene targeting. The gene targeting frequency (the number of drug-resistant clones resulting from gene correction compared to the number of resistant clones from parallel experiments with a similar non-interrupted hybrid gene) was 0.5-4.2×10-4. These experiments demonstrate the possibility of producing transgenic plants with desired modifications to a specific nuclear gene. Images

Paszkowski, Jerzy; Baur, Markus; Bogucki, Augustyn; Potrykus, Ingo

1988-01-01

79

The Genes of Watermelon  

Microsoft Academic Search

Watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai) is a major vegetable crop in the world, accounting for 6.8% of the world area devoted to vegetable crops. Wa- termelon is a useful vegetable crop for genetic research because of its small genome size, and the many available gene mutants. The watermelon genes were originally organized and summarized in 1944, and have

Nihat Guner; Todd C. Wehner

2004-01-01

80

Gene promoters dictate histone occupancy within genes.  

PubMed

Spt6 is a transcriptional elongation factor and histone chaperone that reassembles transcribed chromatin. Genome-wide H3 mapping showed that Spt6 preferentially maintains nucleosomes within the first 500 bases of genes and helps define nucleosome-depleted regions in 5' and 3' flanking sequences. In Spt6-depleted cells, H3 loss at 5' ends correlates with reduced pol II density suggesting enhanced transcription elongation. Consistent with its 'Suppressor of Ty' (Spt) phenotype, Spt6 inactivation caused localized H3 eviction over 1-2 nucleosomes at 5' ends of Ty elements. H3 displacement differed between genes driven by promoters with 'open'/DPN and 'closed'/OPN chromatin conformations with similar pol II densities. More eviction occurred on genes with 'closed' promoters, associated with 'noisy' transcription. Moreover, swapping of 'open' and 'closed' promoters showed that they can specify distinct downstream patterns of histone eviction/deposition. These observations suggest a novel function for promoters in dictating histone dynamics within genes possibly through effects on transcriptional bursting or elongation rate. PMID:24013117

Perales, Roberto; Erickson, Benjamin; Zhang, Lian; Kim, Hyunmin; Valiquett, Elan; Bentley, David

2013-09-06

81

Conditional gene targeting for cancer gene therapy  

Microsoft Academic Search

Current treatment of solid tumors is limited by severe adverse effects, resulting in a narrow therapeutic index. Therefore, cancer gene therapy has emerged as a targeted approach that would significantly reduce undesired side effects in normal tissues. This approach requires a clear understanding of the molecular biology of both the malignant clone and the biological vectors that serve as vehicles

Yosef S. Haviv; David T. Curiel

2001-01-01

82

MR REPORTER GENES  

PubMed Central

Non-invasive molecular imaging of dynamic processes has benefited tremendously from the use of reporter genes. These genes encode for proteins that emit light, bind radiolabeled probes or, as covered in this review, modulate magnetic resonance (MR) contrast. Reporter genes play a pivotal role in monitoring cell trafficking, gene replacement therapy, protein-protein interactions, neuronal plasticity and embryonic development. Several strategies exist for generating MR contrast: enzyme-catalyzed chemical modification of metal-based contrast agents or (phosphorus) metabolites, using iron-binding and iron-storage proteins to accumulate iron as contrast agent, and using artificial proteins for imaging based on chemical exchange saturation transfer. MR reporter genes have the advantage that the specific signal can be co-registered with soft tissue anatomy and functional tissue information, and have therefore become an active and growing area of scientific interest.

Gilad, Assaf A.; Ziv, Keren; McMahon, Michael T.; van Zijl, Peter C.M.; Neeman, Michal; Bulte, Jeff W.M.

2009-01-01

83

Autophagy genes in immunity  

PubMed Central

In its classical form, autophagy is a pathway by which cytoplasmic constituents, including intracellular pathogens, are sequestered in a double-membrane–bound autophagosome and delivered to the lysosome for degradation. This pathway has been linked to diverse aspects of innate and adaptive immunity, including pathogen resistance, production of type I interferon, antigen presentation, tolerance and lymphocyte development, as well as the negative regulation of cytokine signaling and inflammation. Most of these links have emerged from studies in which genes encoding molecules involved in autophagy are inactivated in immune effector cells. However, it is not yet known whether all of the critical functions of such genes in immunity represent ‘classical autophagy’ or possible as-yet-undefined autophagolysosome-independent functions of these genes. This review summarizes phenotypes that result from the inactivation of autophagy genes in the immune system and discusses the pleiotropic functions of autophagy genes in immunity.

Virgin, Herbert W; Levine, Beth

2009-01-01

84

Targeted Gene Delivery to Accomplish Gene Therapy for Breast Cancer.  

National Technical Information Service (NTIS)

We are developing methods to derive gene transfer vectors capable of accomplishing targeted gene delivery to metastatic breast cancer cells. In this regard, strategies have been explored to modify adenoviral vectors by altering their binding tropism. Gene...

D. T. Curiel

1998-01-01

85

4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP LOOKING SOUTHWEST. DAM AND SPILLWAY VISIBLE IN BOTTOM OF PHOTO. - Gene Wash Reservoir & Dam, 2 miles west of Parker Dam, Parker Dam, San Bernardino County, CA

86

Cloning Human Chromosome 17 Genes:.  

National Technical Information Service (NTIS)

Our research interest is focused on the development of new strategies to identify genes from chromosome 17. The isolation of genes transcribed from chromosome 17 will provide candidates for the proposed sporadic breast and ovarian cancer genes. We have re...

C. C. Lee

1995-01-01

87

Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha.  

PubMed

We report preliminary characterization of a gene designated beta-R1, which is selectively expressed in response to interferon beta (IFN-beta) compared with IFN-alpha. In human astrocytoma cells, beta-R1 was induced to an equivalent extent by 10 IU/mL IFN-beta or 2500 IU/mL IFN-alpha2. To address the mechanism of this differential response, we analyzed induction of the beta-R1 gene in fibrosarcoma cells and derivative mutant cells lacking components required for signaling by type I IFNs. beta-R1 was readily induced by IFN-beta in the parental 2fTGH cell line, but not by recombinant IFN-alpha2, IFN-alpha Con1, or a mixture of IFN-alpha subtypes. IFN-alpha8 induced beta-R1 weakly. beta-R1 was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, and U6A, which lack, respectively, p48, STAT1, JAK1, and STAT2. U5A cells, which lack the Ifnar 2.2 component of the IFN-alpha and -beta receptor, also failed to express beta-R1. U1A cells are partially responsive to IFN-beta and IFN-alpha8 but lacked beta-R1 expression, indicating that TYK2 protein is essential for induction of this gene. Taken together, these results suggest that the expression of beta-R1 in response to type I IFN requires IFN-stimulated gene factor 3 plus an additional component, which is more efficiently formed on induction by IFN-beta compared with IFN-alpha. PMID:8798467

Rani, M R; Foster, G R; Leung, S; Leaman, D; Stark, G R; Ransohoff, R M

1996-09-13

88

Gene therapy for brain tumors  

Microsoft Academic Search

Gene therapy’ can be defined as the transfer of genetic material into a patient’s cells for therapeutic purposes. To date,\\u000a a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer\\u000a for modulating the immune system, enzyme prodrug (‘suicide gene’) therapy, oncolytic therapy, replacement\\/ therapeutic gene\\u000a transfer, and antisense therapy. For malignant glioma, gene-directed

Kanti Bansal; Herbert H. Engelhard

2000-01-01

89

Bispecific Antibodies and Gene Therapy  

Microsoft Academic Search

\\u000a Gene therapy is the transfer of therapeutic genes, via gene transfer vectors, into patients for therapeutic purposes. Different\\u000a gene therapy strategies are being pursued, including long-term gene correction of monogenetic diseases, eradication of tumor\\u000a cells in cancer patients, or genetic vaccination for infectious diseases. Bispecific antibodies and gene therapy are connected\\u000a in two ways. First, bispecific antibodies are tools of

Dirk M. Nettelbeck

90

TIGR Drosophila Gene Index  

NSDL National Science Digital Library

TIGR, The Institute for Genomic Research, has announced the release of the Drosophila Gene Index (DGI). The Drosophila Gene Index, which may be searched by Nucleotide or Protein Sequence, Identifier (TC, ET, EST, GB) Tissue, cDNA Library Name or cDNA Library Identifier(cat#), or Gene Product Name, contains some 50,500 total sequences (ET, EST, TC, and singletons). Data may be requested free of charge by "researchers at non-profit institutions using it for non-commercial purposes;" instructions are provided on-site.

1999-01-01

91

Human and mouse gene nomenclature.  

PubMed

Standard genetic nomenclature is necessary to help researchers, clinicians, and the public to access data on their genes of interest, and to communicate in a globally understood language of approved gene symbols. In both human and mouse, one unique symbol (acronym/abbreviation) and one name are assigned for each gene. Co-ordination between human and mouse gene nomenclature is a successful endeavor, due in part to the historical interaction between the two nomenclature committee groups. This interaction grew out of the Human Gene Mapping (HGM) Workshops. This appendix discusses development and organization of gene nomenclature, how to find a gene and how to name a new gene. PMID:18428336

Wain, Hester; Povey, Sue; Maltais, Lois

2003-02-01

92

Predicting Gene Ontology Biological Process From Temporal Gene Expression Patterns  

PubMed Central

The aim of the present study was to generate hypotheses on the involvement of uncharacterized genes in biological processes. To this end, supervised learning was used to analyze microarray-derived time-series gene expression data. Our method was objectively evaluated on known genes using cross-validation and provided high-precision Gene Ontology biological process classifications for 211 of the 213 uncharacterized genes in the data set used. In addition, new roles in biological process were hypothesized for known genes. Our method uses biological knowledge expressed by Gene Ontology and generates a rule model associating this knowledge with minimal characteristic features of temporal gene expression profiles. This model allows learning and classification of multiple biological process roles for each gene and can predict participation of genes in a biological process even though the genes of this class exhibit a wide variety of gene expression profiles including inverse coregulation. A considerable number of the hypothesized new roles for known genes were confirmed by literature search. In addition, many biological process roles hypothesized for uncharacterized genes were found to agree with assumptions based on homology information. To our knowledge, a gene classifier of similar scope and functionality has not been reported earlier. [Supplemental material is available online at www.genome.org. All annotations, reclassifications of known genes, and classifications of uncharacterized genes are available online at http://www.lcb.uu.se/?hvidsten/fibroblast.

Laegreid, Astrid; Hvidsten, Torgeir R.; Midelfart, Herman; Komorowski, Jan; Sandvik, Arne K.

2003-01-01

93

Cellular & Gene Therapy Research  

Center for Biologics Evaluation and Research (CBER)

... Tumor Vaccines & Biotechnology. Development of Safe and Effective Tumor Vaccines and Gene Therapy Products Raj Puri, MD, PhD; ... More results from www.fda.gov/biologicsbloodvaccines/scienceresearch/biologicsresearchareas

94

What Is a Gene?  

MedlinePLUS

... 9 years old, and she looks like a basketball player already!" Nancy makes a dash to the ... Huh? Aunt Rita's grandmother? Runs in the family? Basketball? What are they talking about?" Genes (say: jeenz ), ...

95

C4 GENE EXPRESSION.  

PubMed

C4 plants, including maize, Flaveria, amaranth, sorghum, and an amphibious sedge Eleocharis vivipara, have been employed to elucidate the molecular mechanisms and signaling pathways that control C4 photosynthesis gene expression. Current evidence suggests that pre-existing genes were recruited for the C4 pathway after acquiring potent and surprisingly diverse regulatory elements. This review emphasizes recent advances in our understanding of the creation of C4 genes, the activities of the C4 gene promoters consisting of synergistic and combinatorial enhancers and silencers, the use of 5' and 3' untranslated regions for transcriptional and posttranscriptional regulations, and the function of novel transcription factors. The research has also revealed new insights into unique or universal mechanisms underlying cell-type specificity, coordinate nuclear-chloroplast actions, hormonal, metabolic, stress and light responses, and the control of enzymatic activities by phosphorylation and reductive processes. PMID:15012208

Sheen, Jen

1999-06-01

96

Viral Gene Expression Assays  

Center for Biologics Evaluation and Research (CBER)

Text Version... Development of reagents. 9 XMRV gene products (VP62). ... 3 forms of sequence-verified Gateway Entry clones; 4 types of protein expression clones; ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

97

Structure of Methanogen Genes.  

National Technical Information Service (NTIS)

An analysis of the structure and presumed regulatory signals in sequenced methanogen genes is presented. The evidence for polycistronic transcriptional units is extended by inclusion of a DNA sequence, cloned from Methanobrevibacter smithii, which precede...

J. N. Reeve P. T. Hamilton G. S. Beckler C. J. Morris C. H. Clarke

1986-01-01

98

Genes underlying altruism.  

PubMed

William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals. PMID:24132092

Thompson, Graham J; Hurd, Peter L; Crespi, Bernard J

2013-10-16

99

Evolutionary Fingerprinting of Genes  

PubMed Central

Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly or resisting change—an “evolutionary fingerprint” of the gene. Aspects of this evolutionary fingerprint, such as the site-specific ratio of nonsynonymous to synonymous substitution rates (dN/dS), are commonly used to identify genetic features of potential biological interest; however, no framework exists for comparing evolutionary fingerprints between genes. We hypothesize that protein-coding genes with similar protein structure and/or function tend to have similar evolutionary fingerprints and that comparing evolutionary fingerprints can be useful for discovering similarities between genes in a way that is analogous to, but independent of, discovery of similarity via sequence-based comparison tools such as Blast. To test this hypothesis, we develop a novel model of coding sequence evolution that uses a general bivariate discrete parameterization of the evolutionary rates. We show that this approach provides a better fit to the data using a smaller number of parameters than existing models. Next, we use the model to represent evolutionary fingerprints as probability distributions and present a methodology for comparing these distributions in a way that is robust against variations in data set size and divergence. Finally, using sequences of three rapidly evolving RNA viruses (HIV-1, hepatitis C virus, and influenza A virus), we demonstrate that genes within the same functional group tend to have similar evolutionary fingerprints. Our framework provides a sound statistical foundation for efficient inference and comparison of evolutionary rate patterns in arbitrary collections of gene alignments, clustering homologous and nonhomologous genes, and investigation of biological and functional correlates of evolutionary rates.

Kosakovsky Pond, Sergei L.; Scheffler, Konrad; Gravenor, Michael B.; Poon, Art F.Y.; Frost, Simon D.W.

2010-01-01

100

Gene therapy for atherosclerosis  

Microsoft Academic Search

Although considerable progress has been made in the prevention and treatment of atherosclerotic cardiovascular disease, new\\u000a therapeutic strategies are still needed. Atherosclerosis is a systemic disease and represents an attractive target for the\\u000a development of somatic gene transfer intended to modulate systemic factors with the goal of inhibiting disease progression.\\u000a This approach should be differentiated from localized vascular gene delivery

D. J. Rader

1997-01-01

101

Cell and Gene Therapy  

Microsoft Academic Search

\\u000a Cell and Gene therapies are novel additions to the current multimodal approach of chemotherapy, radiation, surgery, and hematopoietic\\u000a stem cell transplant (HSCT) for the treatment of pediatric cancers. The manipulation of genes and the immune system can treat\\u000a cancer and prevent genetic diseases as well as increase the body's ability to receive intense treatment that would be impossible\\u000a otherwise. Humans

Robbie Norville

102

Lynch Syndrome Genes  

Microsoft Academic Search

Since the discovery of the major human genes with DNA mismatch repair (MMR) function in 1993--1995, mutations in four, MSH2, MLH1, MSH6, and PMS2, have been convincingly linked to susceptibility of hereditary nonpolyposis colorectal cancer (HNPCC)\\/Lynch syndrome. Among these, PMS2 mutations are associated with diverse clinical features, including those of the Turcot syndrome. Two additional MMR genes, MLH3 and PMS1,

Päivi Peltomäki

2005-01-01

103

Gene therapy of cancer  

Microsoft Academic Search

Recent advances in the understanding of the molecular pathogenesis of cancer herald breakthroughs in the treatment of this collection of diseases, which are still usually incurable in advanced stages. In particular, there is a high expectation of gene and immunogene therapy. A recent meeting1The 3rd European Conference on Gene Therapy of Cancer was held at Berlin, Germany, on 11–13 September

Farzin Farzaneh; Uwe Trefzer; Wolfram Sterry; Peter Walden

1998-01-01

104

Horizontal gene transfer  

Microsoft Academic Search

This review explores examples of horizontal genetic transfer in eukaryotes and prokaryotes. The best understood of these involves\\u000a various conserved families of transposable elements, but examples of non-transposable-element-based movement of genes or gene\\u000a clusters have also been identified in prokaryotic genomes. A unifying theme is the structural and DNA-sequence homology of\\u000a transposable elements from widely unrelated genomes, suggesting evolutionarily conserved

Viji Krishnapillai

1996-01-01

105

The Bacteriorhodopsin Gene  

Microsoft Academic Search

The bacteriorhodopsin gene has been identified in a 5.3-kilobase restriction endonuclease fragment isolated from Halobacterium halobium DNA, using a cloned cDNA fragment as the probe. Of the 1229 nucleotides whose sequence was determined in the genomic fragment, 786 correspond to the structural gene of bacteriorhodopsin, 360 are upstream from the initiator methionine codon, and 83 are downstream from the COOH

Robert Dunn; John McCoy; Mehmet Simsek; Alokes Majumdar; Simon H. Chang; Uttam L. Rajbhandary; H. Gobind Khorana

1981-01-01

106

5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP PLANT IS AT CENTER WITH ADMINISTRATIVE COMPLEX IN FOREGROUND AND RESIDENTIAL AREA BEYOND PLANT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

107

Identification of four soybean reference genes for gene expression normalization  

Technology Transfer Automated Retrieval System (TEKTRAN)

Gene expression analysis requires the use of reference genes stably expressed independently of specific tissues or environmental conditions. Housekeeping genes (e.g., actin, tubulin, ribosomal, polyubiquitin and elongation factor 1-alpha) are commonly used as reference genes with the assumption tha...

108

Gene–Environment Interaction in Yeast Gene Expression  

Microsoft Academic Search

The effects of genetic variants on phenotypic traits often depend on environmental and physiological conditions, but such gene-environment interactions are poorly understood. Recently developed approaches that treat transcript abundances of thousands of genes as quantitative traits offer the opportunity to broadly characterize the architecture of gene-environment interactions. We examined the genetic and molecular basis of variation in gene expression between

Erin N. Smith; Leonid Kruglyak

2008-01-01

109

Displacement of ?-proteobacterial core genes by horizontally transferred homologous genes  

Microsoft Academic Search

The introduction of novel genes by horizontal gene transfer (HGT) is considered an alternative mechanism for genetic adaptation, leading to diversification and speciation. The goal of this study was to determine which genes that are present in all sequenced ?-proteobacterial genomes were acquired by HGT. In our approach we used BLAST analysis to reduce the number of genes that subsequently

Tom Coenye; Peter Vandamme

2005-01-01

110

Gene delivery systems—gene therapy vectors for cystic fibrosis  

Microsoft Academic Search

Gene delivery systems (GDS) play a central role in the development of gene therapy strategies for Cystic Fibrosis (CF). Further, these systems are important tools in studies with cultured cells and in animal models. In this review, we describe the properties of several viral and synthetic gene delivery systems, and evaluate their possible application in gene therapy of CF. While

Daniel Klink; Dirk Schindelhauer; Andreas Laner; Torry Tucker; Zsuzsanna Bebok; Erik M. Schwiebert; A. Christopher Boyd; Bob J. Scholte

2004-01-01

111

Hox genes and study of Hox genes in crustacean  

NASA Astrophysics Data System (ADS)

Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla. The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

Hou, Lin; Chen, Zhijuan; Xu, Mingyu; Lin, Shengguo; Wang, Lu

2004-12-01

112

GeneCards Version 3: the human gene integrator.  

PubMed

GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database URL: www.genecards.org. PMID:20689021

Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

2010-08-05

113

Vectors for cancer gene therapy  

Microsoft Academic Search

Many viral and non-viral vector systems have now been developed for gene therapy applications. In this article, the pros and cons of these vector systems are discussed in relation to the different cancer gene therapy strategies. The protocols used in cancer gene therapy can be broadly divided into six categories including gene transfer to explanted cells for use as cell-based

J. Zhang; S. J. Russell

1996-01-01

114

Gene transfer into the fungi  

Microsoft Academic Search

A growing body of data suggests that fungi have gained genes by horizontal gene transfer (HGT). This is an exciting result because fungi at first glance represent the most recalcitrantof all organisms to gene transfer, possessing robust cell walls and having lost phagotrophiccapacities because they feed exclusively by osmotrophy. Nonetheless, a number of mechanismshave been implicated in gene transfer including:

Thomas A. Richards; Guy Leonard; Darren M. Soanes; Nicholas J. Talbot

2011-01-01

115

Gene Therapy for Autoimmune Disorders  

Microsoft Academic Search

Although many autoimmune disorders do not have a strong genetic basis, their treatment may nevertheless be improved by gene therapies. Most strategies seek to transfer genes encoding immunomodulatory products that will alter host immune responses in a beneficial manner. Used in this fashion, genes serve as biological delivery vehicles for the products they encode. By this means gene therapy overcomes

C. H. Evans; S. C. Ghivizzani; T. J. Oligino; P. D. Robbins

2000-01-01

116

Molecular targets of gene therapy  

Microsoft Academic Search

Ischemic reperfused heart represents a potential target for gene therapy because gene transfer can represent an alternate pharmacological approach to protect the heart from cellular injury. Gene therapy may be particularly useful to deal with previously unapproachable problems. For myocardial preservation, gene therapy could replace those pharmacological interventions when drugs are delivered locally by sustained release with the help of

Dipak K Das; Richard M Engelman; Nilanjana Maulik; John A Rousou; Joseph E Flack; David W Deaton

1999-01-01

117

How old is my gene?  

PubMed

Gene functions, interactions, disease associations, and ecological distributions are all correlated with gene age. However, it is challenging to estimate the intricate series of evolutionary events leading to a modern-day gene and then to reduce this history to a single age estimate. Focusing on eukaryotic gene families, we introduce a framework that can be used to compare current strategies for quantifying gene age, discuss key differences between these methods, and highlight several common problems. We argue that genes with complex evolutionary histories do not have a single well-defined age. As a result, care must be taken to articulate the goals and assumptions of any analysis that uses gene age estimates. Recent algorithmic advances offer the promise of gene age estimates that are fast, accurate, and consistent across gene families. This will enable a shift to integrated genome-wide analyses of all events in gene evolutionary histories in the near future. PMID:23915718

Capra, John A; Stolzer, Maureen; Durand, Dannie; Pollard, Katherine S

2013-08-01

118

FunGene: the functional gene pipeline and repository  

PubMed Central

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

Fish, Jordan A.; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C. Titus; Tiedje, James M.; Cole, James R.

2013-01-01

119

FunGene: the functional gene pipeline and repository.  

PubMed

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes. PMID:24101916

Fish, Jordan A; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C Titus; Tiedje, James M; Cole, James R

2013-10-01

120

Eukaryotic Genes Involved in Adult Lifespan Regulation.  

National Technical Information Service (NTIS)

The present invention relates to regulation of adult lifespan in eukaryotes. More particularly, the present invention is directed to methods of assaying for genes, gene products, and genes in pathways controlled by such genes and gene products, using RNAi...

A. Dillin A. L. A. Hsu C. Kenyon D. Garigan J. Apfeld

2005-01-01

121

Genetics Home Reference: What is gene therapy?  

MedlinePLUS

... How Genes Work Mutations and Health Inheritance Consultation Testing Therapy Human Genome Project Genomic Research Next Handbook > Gene Therapy > What is gene therapy? Gene therapy is an ... are testing several approaches to gene therapy, including: Replacing a ...

122

Gene expression in bladder tumors  

US Patent & Trademark Office Database

Methods for analyzing tumor cells, particularly bladder tumor cells employ gene expression analysis of samples. Gene expression patterns are formed and compared to reference patterns. Alternatively gene expression patterns are manipulated to exclude genes which are expressed in contaminating cell populations. Another alternative employs subtraction of the expression of genes which are expressed in contaminating cell types. These methods provide improved accuracy as well as alternative basis for analysis from diagnostic and prognostic tools currently available.

2002-01-01

123

Gene Therapy and Immune Senescence  

Microsoft Academic Search

Gene therapy can be classified according to the vector used for gene therapy and the transgene that will be expressed as a\\u000a result of the gene therapy. One consideration for gene therapy is that certain vectors have larger capacities than others\\u000a to incorporate genes. The second consideration is the duration of therapy, which depends upon the immune response after delivery

Jian Chen; Hui-Chen Hsu; John D. Mountz

124

Engineered Gene Circuits  

NASA Astrophysics Data System (ADS)

Uncovering the structure and function of gene regulatory networks has become one of the central challenges of the post-genomic era. Theoretical models of protein-DNA feedback loops and gene regulatory networks have long been proposed, and recently, certain qualitative features of such models have been experimentally corroborated. This talk will focus on model and experimental results that demonstrate how a naturally occurring gene network can be used as a ``parts list'' for synthetic network design. The model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics, and the utility of such a formulation will be demonstrated through the consideration of specific design criteria for several novel genetic devices. Fluctuations originating from small molecule-number effects will be discussed in the context of model predictions, and the experimental validation of these stochastic effects underscores the importance of internal noise in gene expression. Potential biotech applications will be highlighted within the framework of cellular control schemes. Specifically, the coupling of an oscillating cellular process to a synthetic oscillator will be considered, and the resulting model behavior will be analyzed in the context of synchronization. The underlying methodology highlights the utility of engineering-based methods in the design of synthetic gene regulatory networks.

Hasty, Jeff

2003-03-01

125

Saporin suicide gene therapy.  

PubMed

New genes useful in suicide gene therapy are those encoding toxins such as plant ribosome-inactivating proteins (RIPs), which can irreversibly block protein synthesis, triggering apoptotic cell death. Plasmids expressing a cytosolic saporin (SAP) gene from common soapwort (Saponaria officinalis) are generated by placing the region encoding the mature plant toxin under the control of strong viral promoters and may be placed under tumor-specific promoters. The ability of the resulting constructs to inhibit protein synthesis is tested in cultured tumor cells co-transfected with a luciferase reporter gene. SAP expression driven by the cytomegalovirus (CMV) promoter (pCI-SAP) demonstrates that only 10 ng ofplasmid DNA per 1.6 x 10(4) B16 melanoma cells drastically reduces luciferase reporter activity to 18% of that in control cells (1). Direct intratumoral injections are performed in an aggressive melanoma model. B16 melanoma-bearing mice injected with pCI-SAP complexed with lipofectamine or N-(2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) show a noteworthy attenuation in tumor growth, and this effect is significantly augmented by repeated administrations of the DNA complexes. Here, we describe in detail this cost-effective and safe suicide gene approach. PMID:19565907

Zarovni, Natasa; Vago, Riccardo; Fabbrini, Maria Serena

2009-01-01

126

GeneAnnot: Interfacing GeneCards with high-throughput gene expression compendia  

Microsoft Academic Search

The interpretation of microarray expression results often includes extensive efforts to identify and annotate the gene representatives immobilised on the arrays. In this paper we describe the usage of our automatic GeneAnnot system, which links between Affymetrix arrays and the rich human gene annotations available in GeneCards. We explain GeneCards search options and results display; elaborate on the presentation of

Vered Chalifa-caspi; Orit Shmueli; Hila Benjamin-rodrig; Naomi Rosen; Michael Shmoish; Itai Yanai; Ron Ophir; Pavel Kats; Marilyn Safran; Doron Lancet

2003-01-01

127

Genes and vocal learning.  

PubMed

Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in primates, rodents and birds suggests that FoxP2 and other language-related genes are interactors in the neuromolecular networks that underlie subsystems of language, such symbolic understanding, vocal learning and theory of mind. The whole picture will only come together through comparative and integrative study into how the human language singularity evolved. PMID:19913899

White, Stephanie A

2009-11-13

128

Quantifying gene expression.  

PubMed

Identifying those genes that are expressed and at what levels is an essential part of almost any biological inquiry at the cellular level. Techniques such as Northern blot have been in existence for decades to perform this task, but advances in molecular biology and bioinstrumentation have led to the development of a variety of new techniques with a range of sensitivities, throughputs and quantitative capabilities. This review focuses on the latter issue. For several commonly used gene expression techniques, the extent and range of quantitative applicability are reviewed, and approaches for maximizing the accuracy and precision of these measurements are discussed. PMID:12074198

Roth, Charles M

2002-07-01

129

Phospholipid - Driven gene regulation  

PubMed Central

Phospholipids (PLs), well known for their fundamental role in cellular structure, play critical signaling roles via their derivatives and cleavage products acting as second messengers in signaling cascades. Recent work has shown that intact PLs act as signaling molecules in their own right by modulating the activity of nuclear hormone transcription factors responsible for tuning genes involved in metabolism, lipid flux, steroid synthesis and inflammation. As such, PLs have been classified as novel hormones. This review highlights recent work in PL-driven gene regulation with a focus on the unique structural features of phospholipid-sensing transcription factors and what sets them apart from well known soluble phospholipid transporters.

Musille, Paul M.; Kohn, Jeffrey A.; Ortlund, Eric A.

2013-01-01

130

Gene expression in aggressive fibromatosis.  

PubMed

Aggressive fibromatosis represents a group of tumors with heterogeneous patterns of biologic behavior. In this study, gene expression in 12 samples of aggressive fibromatosis, as well as that in samples of normal skeletal muscle and a variety of normal tissues, was determined at Gene Logic Inc (Gaithersburg, MD), with the use of Affymetrix GeneChip U_133 arrays containing approximately 33,000 genes. Gene-expression analysis was performed with the Gene Logic Gene Express software system. Differences in gene expression were quantified as the fold change in gene expression between the sets of fibromatosis tissue and normal skeletal muscle. A set of genes was then identified that was significantly overexpressed in aggressive fibromatosis compared with expression in normal muscle. This set of genes was then further examined for expression in a variety of normal tissues. We identified genes that were selectively overexpressed in aggressive fibromatosis compared with expression in 448 samples comprising 16 different nonneoplastic tissues. In particular, ADAM12, WISP-1, SOX-11, and fibroblast activation protein-alpha were uniquely overexpressed in aggressive fibromatosis compared with expression in normal tissues. In addition, the technique of Eisen clustering identified 2 distinct subgroups of aggressive fibromatosis with regard to gene expression. We conclude that gene-expression patterns may be useful in the further classification of subtypes of aggressive fibromatosis and that such classification could have clinical significance. PMID:14966464

Skubitz, Keith M; Skubitz, Amy P N

2004-02-01

131

[Gene therapy in The Netherlands].  

PubMed

Extensive research is ongoing worldwide on the clinical utility of gene therapy, particularly for the treatment of cancer and genetic disorders. Two gene therapy products have already been approved recently in China. Clinical experience with gene therapy has also been accumulating in the Netherlands: over 200 Dutch patients have now been treated in clinical trials. Published results indicate that gene therapy is generally safe. Gene therapy appears to be effective for some genetic disorders, such as severe combined immune deficiency and haemophilia B. The efficacy of gene therapy, particularly in the treatment of cancer, appears to be limited up till now. PMID:17953170

Schenk-Braat, E A M; van Mierlo, M M K B; Hospers, G A P; Wagemaker, G; Bangma, C H; Kaptein, L C M

2007-09-01

132

Genes and vocal learning  

Microsoft Academic Search

Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in primates, rodents and birds suggests

Stephanie A. White

2010-01-01

133

Resistance gene capture.  

PubMed

Integrons are the primary mechanism for antibiotic-resistance gene capture and dissemination among Gram-negative bacteria. The recent finding of super-integron structures in the genomes of several bacterial species has expanded their role in genome evolution and suggests that they are the source of mobile multi-resistant integrons. PMID:10508722

Rowe-Magnus, D A; Mazel, D

1999-10-01

134

Genes and Vocal Learning  

ERIC Educational Resources Information Center

|Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in…

White, Stephanie A.

2010-01-01

135

Exploitation of gene context  

Microsoft Academic Search

Recently, a number of techniques have been proposed that use completely sequenced genomes for the function prediction of individual proteins encoded therein. They use the fusion of genes, their conserved location in operons or merely their co-occurrence in genomes to predict the existence of functional interactions between the proteins they encode. This type of information complements functional features that are

Martijn Huynen; Berend Snel; Warren Lathe; Peer Bork

2000-01-01

136

Retinoids and Hox genes  

Microsoft Academic Search

The vertebrate embryonic body plan is constructed through the interaction of many de- velopmentally regulated genes that supply cells with the essential positional and functional information they require to migrate to their appropriate destina- tion and generate the proper structures. Some mo- lecular cues involved in patterning the central nervous system, particularly in the hindbrain, are interpreted by the Hox

HEATHER MARSHALL; ALASTAIR MORRISON; MICHELE STUDER; HEIKE POPPERL; ROBB KRUMLAUF

137

Gene Therapy: Ethical Issues  

Microsoft Academic Search

To discern the ethical issues involved incurrent gene therapy research, to explore theproblems inherent in possible future genetherapies, and to encourage debate within thescientific community about ethical questionsrelevant to both, we surveyed American Societyof Human Genetics scientists who engage inhuman genetics research. This study of theopinions of U.S. scientific experts about theethical issues discussed in the literature ongene therapy contributes

Isaac Rabino

2003-01-01

138

Human Gene Therapy  

Microsoft Academic Search

Human gene therapy is a procedure that is being used in an attempt to treat genetic and other diseases. Eleven clinical protocols are under way at the present time, each with scientific and clinical objectives. Human genetic engineering raises unique safety, social, and ethical concerns.

W. French Anderson

1992-01-01

139

Genes affecting tooth morphogenesis.  

PubMed

The development of dentition is a fascinating process that encompasses a complex series of epithelial-mesenchymal interactions involving growth factors, transcription factors, signal receptors and other soluble morphogens. It is not surprising that such a complex process is prone to disturbances and may result in tooth agenesis. Initial discoveries indicating that the homeo-domain protein MSX1 and the paired-domain transcription factor PAX9 are causative genes in tooth morphogenesis were made in mice. Both genes are co-expressed in dental mesenchyme and either one, when homozygously deleted, results in an arrest at an early developmental stage. Previous studies have shown a down regulation of Bmp4 gene expression in Pax9 and Msx1 single mutant mice. Therefore, we chose to explore the molecular relationship between Pax9, Msx1 and Bmp4. In humans, unlike in mice, a heterozygous mutation in either PAX9 or MSX1 suffices to cause tooth agenesis of a predominantly molar or more premolar pattern, respectively. Our laboratory and others have identified several PAX9 and MSX1 mutations in families with non-syndromic forms of autosomal dominant posterior tooth agenesis. We have also identified families with tooth agenesis in whom PAX9 and MSX1 mutations have been excluded opening up the possibilities for the discovery of other genes that contribute to human tooth agenesis. PMID:17973693

Kapadia, H; Mues, G; D'Souza, R

2007-11-01

140

The Human Gene Map  

Microsoft Academic Search

Mapping started exactly 50 years ago when Bell & Haldane (Proc. R. Soc. Lond. 123, 119 (1937)) measured the genetic distance between colour blindness and haemophilia. In their Discussion they wrote `if...an equally close linkage were found between the genes determining blood group membership and that determining Huntington's chorea, we should be able, in many cases, to predict which children

E. B. Robson

1988-01-01

141

Chromatin Structure Gene Expression  

Microsoft Academic Search

It is now well understood that chromatin structure is perturbed in the neighborhood of expressed genes. This is most obvious in the neighborhood of promoters and enhancers, where hypersensitivity to nucleases marks sites that no longer carry canonical nucleosomes, and to which transcription factors bind. To study the relationship between transcription factor binding and the generation of these hypersensitive regions,

Gary Felsenfeld; Joan Boyes; Jay Chung; David Clark; Vasily Studitsky

1996-01-01

142

Gene regulation by riboswitches  

Microsoft Academic Search

Riboswitches are complex folded RNA domains that serve as receptors for specific metabolites. These domains are found in the non-coding portions of various mRNAs, where they control gene expression by harnessing allosteric structural changes that are brought about by metabolite binding. New findings indicate that riboswitches are robust genetic elements that are involved in regulating fundamental metabolic processes in many

Maumita Mandal; Ronald R. Breaker

2004-01-01

143

Gene therapy for arthritis  

Microsoft Academic Search

Rheumatoid arthritis is an autoimmune disease with intra-articular inflammation and synovial hyperplasia that results in progressive degradation of cartilage and bone, in severe cases it causes systemic complications. Recently, biological agents that suppress the activities of proinflammatory cytokines have shown efficacy as antiarthritic drugs, but require frequent administration. Thus, gene transfer approaches are being developed as an alternative approach for

P D Robbins; C H Evans; Y Chernajovsky

2003-01-01

144

GENE EXPRESSION PROFILING  

Technology Transfer Automated Retrieval System (TEKTRAN)

DNA microarray technology is fast becoming a standard tool for gene expression analysis. The laboratory methods and protocols for array construction, processing, and hybridization are well established. Many of the initial plant genome sequencing projects are providing large sets of expressed seque...

145

UBE3A Gene  

NSDL National Science Digital Library

Fang et al. (1999) sequenced the major coding exons of the UBE3A gene in 56 index patients with a clinical diagnosis of Angelman syndrome (105830) and a normal DNA methylation pattern. Disease-causing mutations were identified in 17 of the 56 patients (30%),

2009-04-14

146

Ultrasound mediated gene transfection  

NASA Astrophysics Data System (ADS)

Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.

2002-05-01

147

Gene Therapy for Sarcoma  

Microsoft Academic Search

Soft tissue sarcomas are mesenchymal tumors which respond poorly to systemic therapy. Recent studies suggest a higher response rate with an increased doxorubicin dosage. However, this was parallel with a profound hematotoxicity in 75% of patients. Transfer of the human multidrug resistance 1 (MDR1) gene to normal hematopoietic stem cells and transplantation may significantly reduce the hematotoxicity of anthracyclin-based chemotherapy.

S. Fruehauf; M. R. Veldwijk; S. Berlinghoff; N. Basara; C. Baum; M. Flasshove; S. Hegewisch-Becker; N. Kröger; T. Licht; T. Moritz; U. R. Hengge; W. Jens Zeller; S. Laufs

2002-01-01

148

Gene therapy for PNET  

Microsoft Academic Search

A new era has been reached in cancer therapeutics in which the techniques of molecular biology can be applied to human brain tumors. Ongoing studies are determining the best vector system with which to deliver genes to cells. Choices include the retroviral, adenoviral, and Herpes simplex virus vector systems. The optimum mode of delivering the vector specifically to the tumor

Corey Raffel

1996-01-01

149

Genes, Evolution, and Personality  

Microsoft Academic Search

There is abundant evidence, some of it reviewed in this paper, that personality traits are substantially influenced by the genes. Much remains to be understood about how and why this is the case. We argue that placing the behavior genetics of personality in the context of epidemiology, evolutionary psychology, and neighboring psychological domains such as interests and attitudes should help

Thomas J. Bouchard; John C. Loehlin

2001-01-01

150

Engineering prokaryotic gene circuits  

PubMed Central

Engineering of synthetic gene circuits is a rapidly growing discipline, currently dominated by prokaryotic transcription networks, which can be easily rearranged or rewired to give different output behaviours. In this review, we examine both a rational and a combinatorial design of such networks and discuss progress on using in vitro evolution techniques to obtain functional systems. Moving beyond pure transcription networks, more and more networks are being implemented at the level of RNA, taking advantage of mechanisms of translational control and aptamer–small molecule complex formation. Unlike gene expression systems, metabolic components are generally not as interconnectable in any combination, and so engineering of metabolic circuits is a particularly challenging field. Nonetheless, metabolic engineering has immense potential to provide useful biosynthesis tools for biotechnology applications. Finally, although prokaryotes are mostly studied as single cell systems, cell–cell communication networks are now being developed that result in spatial pattern formation in multicellular prokaryote colonies. This represents a crossover with multicellular organisms, showing that prokaryotic systems have the potential to tackle questions traditionally associated with developmental biology. Overall, the current advances in synthetic gene synthesis, ultra-high-throughput DNA sequencing and computation are synergizing to drive synthetic gene network design at an unprecedented pace.

Michalodimitrakis, Konstantinos; Isalan, Mark

2009-01-01

151

Ancient horizontal gene transfer  

Microsoft Academic Search

The cornerstone of Charles Darwin's theory of evolution is the vertical inheritance of traits from parent to offspring across successive generations. However, molecular evolutionary biologists have shown that extensive horizontal (also known as lateral) gene transfer (HGT) can occur between distantly related species. Comparative sequence analyses of genomes indicates that the universal tree of life might be at risk because

James R. Brown

2003-01-01

152

ToppGene Suite for gene list enrichment analysis and candidate gene prioritization  

PubMed Central

ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based disease candidate gene prioritization uses a fuzzy-based similarity measure to compute the similarity between any two genes based on semantic annotations. The similarity scores from individual features are combined into an overall score using statistical meta-analysis. A P-value of each annotation of a test gene is derived by random sampling of the whole genome. The protein–protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method). We demonstrate the utility of ToppGene Suite using 20 recently reported GWAS-based gene–disease associations (including novel disease genes) representing five diseases. ToppGene ranked 19 of 20 (95%) candidate genes within the top 20%, while ToppNet ranked 12 of 16 (75%) candidate genes among the top 20%.

Chen, Jing; Bardes, Eric E.; Aronow, Bruce J.; Jegga, Anil G.

2009-01-01

153

ToppGene Suite for gene list enrichment analysis and candidate gene prioritization.  

PubMed

ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based disease candidate gene prioritization uses a fuzzy-based similarity measure to compute the similarity between any two genes based on semantic annotations. The similarity scores from individual features are combined into an overall score using statistical meta-analysis. A P-value of each annotation of a test gene is derived by random sampling of the whole genome. The protein-protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method). We demonstrate the utility of ToppGene Suite using 20 recently reported GWAS-based gene-disease associations (including novel disease genes) representing five diseases. ToppGene ranked 19 of 20 (95%) candidate genes within the top 20%, while ToppNet ranked 12 of 16 (75%) candidate genes among the top 20%. PMID:19465376

Chen, Jing; Bardes, Eric E; Aronow, Bruce J; Jegga, Anil G

2009-05-22

154

Industrial scale gene synthesis.  

PubMed

The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery. PMID:21601681

Notka, Frank; Liss, Michael; Wagner, Ralf

2011-01-01

155

Gene set analysis for longitudinal gene expression data  

PubMed Central

Background Gene set analysis (GSA) has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations. Results We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified. Conclusions The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website http://ndinbre.org/programs/bioinformatics.php. Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information) with accession number GSE6085.

2011-01-01

156

Allelic based gene-gene interactions in rheumatoid arthritis  

Microsoft Academic Search

The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel

Jeesun Jung; Joon Jin Song; Deukwoo Kwon

2009-01-01

157

GENE METHYLATION CHANGES IN TUMOR SUPPRESSOR GENES INDUCED BY ARSENIC  

EPA Science Inventory

The choice of a dose-response model used for extrapolation can be influenced by knowledge of mechanism of action. We have already showed that arsenic affects methylation of the human p53 gene promoter. Evidence that genes other than the p53 tumor suppressor gene are affected woul...

158

Gene chips: Array of hope for understanding gene regulation  

Microsoft Academic Search

High density arrays of DNA fragments on a solid surface allow the expression of thousands of genes to be assessed in a single experiment. The development of this ‘gene chip’ technique heralds a new era of studies that promises to provide an integrated view of the expression of all genes of an organism.

Mark Johnston

1998-01-01

159

Gene amelioration demonstrated: the journey of nascent genes in bacteria  

Microsoft Academic Search

Gene amelioration is the hypothesis that genes acquired via lateral gene transfer will, over time, acquire the mo- lecular characteristics of the host genome. Species for which multiple strains have been sequenced permit a demonstration that this hypothesis is correct. We use 7 sequenced genomes of Streptococcus pyogenes and 6 sequenced genomes of Staphylococcus aureus to illustrate the action of

Pradeep Reddy Marri; G. Brian Golding

2008-01-01

160

Proto-genes and de novo gene birth.  

PubMed

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation. PMID:22722833

Carvunis, Anne-Ruxandra; Rolland, Thomas; Wapinski, Ilan; Calderwood, Michael A; Yildirim, Muhammed A; Simonis, Nicolas; Charloteaux, Benoit; Hidalgo, César A; Barbette, Justin; Santhanam, Balaji; Brar, Gloria A; Weissman, Jonathan S; Regev, Aviv; Thierry-Mieg, Nicolas; Cusick, Michael E; Vidal, Marc

2012-07-19

161

Proto-genes and de novo gene birth  

PubMed Central

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo1,2. Processes involving re-organization of pre-existing genes, notably following gene duplication, have been extensively described1,2. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or “non-genic” sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions1,3-6. Here, we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes4 generated by widespread translational activity in non-genic sequences. Testing this model at genome-scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events appear to provide adaptive potential7, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.

Carvunis, Anne-Ruxandra; Rolland, Thomas; Wapinski, Ilan; Calderwood, Michael A.; Yildirim, Muhammed A.; Simonis, Nicolas; Charloteaux, Benoit; Hidalgo, Cesar A.; Barbette, Justin; Santhanam, Balaji; Brar, Gloria A.; Weissman, Jonathan S.; Regev, Aviv; Thierry-Mieg, Nicolas; Cusick, Michael E.; Vidal, Marc

2012-01-01

162

HYBRID TET GENES AND TET GENE NONMENCLATURE - REQUEST FOR OPINION  

Technology Transfer Automated Retrieval System (TEKTRAN)

The naming of tetracycline resistance genes is currently based on the predicted amino acid sequences of proteins encoded by those genes. Amino acid identity of less than or equal to 80% is the cutoff for defining new determinants. This cutoff value was established for previously known tet genes va...

163

Human Gene Therapy. Background Paper.  

National Technical Information Service (NTIS)

The paper focuses on the imminent development of human gene therapy, emphasizing early medical applications. The governmental concerns related to human gene therapy, as for other medical technologies, will include protection of subjects involved in resear...

1984-01-01

164

Genes and human brain evolution  

PubMed Central

Several genes were duplicated during human evolution. It seems that one such duplication gave rise to a gene that may have helped to make human brains bigger and more adaptable than those of our ancestors.

Geschwind, Daniel H.; Konopka, Genevieve

2013-01-01

165

Hematopoietic Stem Cell Gene Therapy  

Microsoft Academic Search

Gene therapy applications that target hematopoietic stem cells (HSCs) offer great potential for the treatment of hematologic\\u000a disease. Despite this promise, clinical success has been limited by poor rates of gene transfer, poor engraftment of modified\\u000a cells, and poor levels of gene expression. We describe here the basic approach used for HSC gene therapy, briefly review some\\u000a of the seminal

David W. Emery; Tamon Nishino; Ken Murata; Michalis Fragkos; George Stamatoyannopoulos

2002-01-01

166

Virus-mediated gene delivery for human gene therapy.  

PubMed

After over 20 years from the first application of gene transfer in humans, gene therapy is now a mature discipline, which has progressively overcome several of the hurdles that prevented clinical success in the early stages of application. So far, the vast majority of gene therapy clinical trials have exploited viral vectors as very efficient nucleic acid delivery vehicles both in vivo and ex vivo. Here we summarize the current status of viral gene transfer for clinical applications, with special emphasis on the molecular properties of the major classes of viral vectors and the information so far obtained from gene therapy clinical trials. PMID:22516095

Giacca, Mauro; Zacchigna, Serena

2012-04-10

167

Generalist Genes and Learning Disabilities  

Microsoft Academic Search

The authors reviewed recent quantitative genetic research on learning disabilities that led to the conclusion that genetic diagnoses differ from traditional diagnoses in that the effects of relevant genes are largely general rather than specific. This research suggests that most genes associated with common learning disabilities—language impairment, reading disability, and mathematics disability—are generalists in 3 ways. First, genes that affect

Robert Plomin; Yulia Kovas

2005-01-01

168

Gene Expression Phenotypes of Atherosclerosis  

Microsoft Academic Search

Objective—Fulfilling the promise of personalized medicine by developing individualized diagnostic and therapeutic strategies for atherosclerosis will depend on a detailed understanding of the genes and gene variants that contribute to disease susceptibility and progression. To that end, our group has developed a nonbiased approach congruent with the multigenic concept of complex diseases by identifying gene expression patterns highly associated with

David Seo; Tao Wang; Holly Dressman; Edward E. Herderick; Edwin S. Iversen; Chunming Dong; Korkut Vata; Carmelo A. Milano; Fabio Rigat; Jennifer Pittman; Joseph R. Nevins; Mike West; Pascal J. Goldschmidt-Clermont

2010-01-01

169

Fast parsers for Entrez Gene  

Microsoft Academic Search

Summary: NCBI completed the transition of its main genome annota- tion database from Locuslink to Entrez Gene in Spring 2005. However, to this date few parsers exist for the Entrez Gene annotation file. Owing to the widespread use of Locuslink and the popularity of Perl programming language in bioinformatics, a publicly available high performance Entrez Gene parser in Perl is

Mingyi Liu; Andrei Grigoriev

2005-01-01

170

Independent Gene Discovery and Testing  

ERIC Educational Resources Information Center

A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

2010-01-01

171

Gene Machine: The Lac Operon  

NSDL National Science Digital Library

Build a gene network! The lac operon is a set of genes which are responsible for the metabolism of lactose in some bacterial cells. Explore the effects of mutations within the lac operon by adding or removing genes from the DNA.

Simulations, Phet I.; Blanco, John; Perkins, Kathy; Podolefsky, Noah; Spiegelman, George; Taylor, Jared

2010-05-01

172

Selecting Genes by Test Statistics  

Microsoft Academic Search

Gene selection is an important issue in analyzing multiclass microarray data. Among many proposed selection methods, the tradi- tional ANOVA F test statistic has been employed to identify informative genes for both class prediction (classification) and discovery problems. However, the F test statistic assumes an equal variance. This assumption may not be realistic for gene expression data. This paper explores

Dechang Chen; Zhenqiu Liu; Xiaobin Ma; Dong Hua

2005-01-01

173

Prospects for Human Gene Therapy  

Microsoft Academic Search

Procedures have now been developed for inserting functional genes into the bone marrow of mice. The most effective delivery system at present uses retroviral-based vectors to transfer a gene into murine bone marrow cells in culture. The genetically altered bone marrow is then implanted into recipient animals. These somatic cell gene therapy techniques are becoming increasingly efficient. Their future application

W. French Anderson

1984-01-01

174

Gene therapy and reproductive medicine  

Microsoft Academic Search

Objective: To review the literature on the principles of gene therapy and its potential application in reproductive medicine.Design: Literature review.Setting: Gene therapy involves transfer of genetic material to target cells using a delivery system, or vector. Attention has primarily focused on viral vectors. Significant problems remain to be overcome including low efficacy of gene transfer, the transient expression of some

John M Stribley; Khurram S Rehman; Hairong Niu; Gregory M Christman

2002-01-01

175

Regulatory Protein Coordinating Gene Expression  

NSDL National Science Digital Library

The action of the glucocorticoid receptor is illustrated. On the left is shown a series of genes, each of which has various gene activator proteins bound to its regulatory region. However, these bound proteins are not sufficient on their own to activate transcription efficiently. On the right is shown the effects of adding an additional gene regulatory protein

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter

1998-07-01

176

Homologous Recombination Based Gene Therapy  

Microsoft Academic Search

Background\\/Aims: Most of the current expression vector based gene therapy protocols fail to achieve clinically significant transgene expression required for treating genetic diseases. Homologous recombination, initially considered to be of limited use for gene therapy because of its low frequency in mammalian cells, has recently emerged as a potential strategy for developing gene therapy. Methods: Six recent studies of homologous

Li-Wen Lai; Yeong-Hau H. Lien

1999-01-01

177

NKL homeobox genes in leukemia.  

PubMed

NK-like (NKL) homeobox genes code for transcription factors, which can act as key regulators in fundamental cellular processes. NKL genes have been implicated in divergent types of cancer. In this review, we summarize the involvement of NKL genes in cancer and leukemia in particular. NKL genes can act as tumor-suppressor genes and as oncogenes, depending on tissue type. Aberrant expression of NKL genes is especially common in T-cell acute lymphoblastic leukemia (T-ALL). In T-ALL, 8 NKL genes have been reported to be highly expressed in specific T-ALL subgroups, and in ~30% of cases, high expression is caused by chromosomal rearrangement of 1 of 5 NKL genes. Most of these NKL genes are normally not expressed in T-cell development. We hypothesize that the NKL genes might share a similar downstream effect that promotes leukemogenesis, possibly due to mimicking a NKL gene that has a physiological role in early hematopoietic development, such as HHEX. All eight NKL genes posses a conserved Eh1 repressor motif, which has an important role in regulating downstream targets in hematopoiesis and possibly in leukemogenesis as well. Identification of a potential common leukemogenic NKL downstream pathway will provide a promising subject for future studies. PMID:22094586

Homminga, I; Pieters, R; Meijerink, J P P

2011-11-18

178

Review: Gene Therapy for Cancer  

Microsoft Academic Search

Gene therapy is a new form of therapeutic intervention with applications in many areas of medical treatment. There are still many technical difficulties to be overcome, but recent advances in the molecular and cellular biology of gene transfer have made it likely that gene therapy will soon start to play an increasing role in clinical practice and particularly in the

Gregory Kouraklis

2000-01-01

179

ARDB - Antibiotic Resistance Genes Database  

Microsoft Academic Search

The treatment of infections is increasingly compro- mised by the ability of bacteria to develop resis- tance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resis- tance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have cre-

Bo Liu; Mihai Pop

2009-01-01

180

Gene therapy in the cornea  

Microsoft Academic Search

Technological advances in the field of gene therapy has prompted more than three hundred phase I and phase II gene-based clinical trials for the treatment of cancer, AIDS, macular degeneration, cardiovascular, and other monogenic diseases. Besides treating diseases, gene transfer technology has been utilized for the development of preventive and therapeutic vaccines for malaria, tuberculosis, hepatitis A, B and C

Rajiv R. Mohan; Ajay Sharma; Marcelo V. Netto; Sunilima Sinha; Steven E. Wilson

2005-01-01

181

Hox Genes and Embryonic Development  

Microsoft Academic Search

The hox genes specify regional differ- ences along the anterior-posterior (A\\/P) axis of the vertebrate embryo. This function appears to reflect an ancestral role of the hox gene complex and is conserved across phyla. During the evolution of vertebrates, this gene complex has been recruited to perform other functions as well, many of which occur later in development. Although mutational

BRUCE A. MORGAN

182

Extracting gene-gene interactions through curve fitting.  

PubMed

This paper presents a simple and novel curve fitting approach for generating simple gene regulatory subnetworks from time series gene expression data. Microarray experiments simultaneously generate massive data sets and help immensely in the large-scale study of gene expression patterns. Initial biclustering reduces the search space in the high-dimensional microarray data. The least-squares error between fitting of gene pairs is minimized to extract a set of gene-gene interactions, involving transcriptional regulation of genes. The higher error values are eliminated to retain only the strong interacting gene pairs in the resultant gene regulatory subnetwork. Next the algorithm is extended to a generalized framework to enhance its capability. The methodology takes care of the higher-order dependencies involving multiple genes co-regulating a single gene, while eliminating the need for user-defined parameters. It has been applied to the time-series Yeast data, and the experimental results biologically validated using standard databases and literature. PMID:22997274

Das, Ranajit; Mitra, Sushmita; Murthy, C A

2012-09-14

183

Human gene mapping.  

PubMed

It is now possible to map the human genome completely with a set of closely linked markers. Over 500 coding genes have been cloned and localized, as have approximately 2000 anonymous DNA fragments, most of which recognize two-allele polymorphisms that are caused by single base changes which alter the recognition site for a restriction enzyme (restriction fragment length polymorphisms). Most human chromosomes have been mapped, with markers in defined order placed approximately 10 map units apart. Chromosomes X and 21 are particularly well mapped, with over 200 probes ordered on X. The strategy during the next few years will encompass moving from a linkage map to a set of overlapping cosmid or phage clones, and finally to a complete sequence of regions of chromosomes and entire chromosomes. A complete sequence of the human genome should transform our understanding of development, the control of gene expression, and the parameters of genetic disease. PMID:3481697

Williamson, R

1987-01-01

184

Genes and genomes  

SciTech Connect

Genes and Genomes provides a well-directed excursion into the realms of modern-day molecular genetics with all the excitement of new discoveries clearly presented to the reader. The first 215 pages of the book present a review of basic genetic concepts that laid the groundwork for the approaches and techniques that have led to an explosion of knowledge in the field of molecular genetics. The second part is an extensive guide to tools and experimental systems that are being used to explore the mysteries of the eukaryotic genome. With these tools in hand, the authors now launch the reader into a 400-page account of current understanding of the anatomy, the expression, and the regulation of eukaryotic genes. The final section of the book is an introduction to more complex biological systems.

Singer, M.; Berg, P.

1990-01-01

185

Estrogen receptor genes  

US Patent & Trademark Office Database

The present invention relates to an estrogen receptor gene, characterized by comprising a nucleotide sequence coding for any one of the following amino acid sequences: (a) the amino acid sequence of SEQ ID NO:1, (b) an amino acid sequence of a protein having an estrogen receptor activity, said amino acid sequence has at least 85% sequence identity with the amino acid sequence of SEQ ID NO:1, (c) an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:2, and (d) an amino acid sequence of a protein having an estrogen receptor activity, said amino acid sequence is encoded by a nucleotide sequence having at least 85% sequence identity with a DNA having the nucleotide sequence of SEQ ID NO:2, and the like. The estrogen receptor gene and the like can be applied to assay systems for evaluating the ability of chemical substances to regulate the estrogen receptor activity.

2008-09-02

186

From SNPs to Genes: Disease Association at the Gene Level  

PubMed Central

Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an important step towards understanding the molecular processes that lead to disease. In order to incorporate prior biological knowledge such as pathways and protein interactions in the analysis of GWAS data it is necessary to derive one measure of association for each gene. We compare three different methods to obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based association data: choosing the test statistic from the most significant SNP; the mean test statistics of all SNPs; and the mean of the top quartile of all test statistics. We demonstrate that the gene-wide test statistics can be controlled for the number of SNPs within each gene and show that all three methods perform considerably better than expected by chance at identifying genes with confirmed associations. By applying each method to GWAS data for Crohn's Disease and Type 1 Diabetes we identified new potential disease genes.

Lehne, Benjamin; Lewis, Cathryn M.; Schlitt, Thomas

2011-01-01

187

Explore IT Gene Hunter  

NSDL National Science Digital Library

In this exploration, we'll take a look at how DNA stores information and how scientists identify what particular genes do. DNA is a very, very long molecule. To find out what a particular piece is for, a person (most often a scientist) must search -- or rather hunt-- for the genetic meaning. At the end, we examine how you can use the DNA code yourself.

Nickle, Todd

2010-06-01

188

Gene Therapy vs Pharmacotherapy  

Microsoft Academic Search

Recent progress in molecular and cellular biology has developed numerous effective cardiovascular drugs. However, there are\\u000a still number of diseases for which no known effective therapy exists, such as peripheral arterial disease, ischemic heart\\u000a disease, restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy. Currently, gene\\u000a therapy is emerging as a potential strategy for the treatment of cardiovascular

Ryuichi Morishita

189

Tumor Suppressor Gene Therapy  

Microsoft Academic Search

\\u000a Recent advances in genetics, molecular biology, and molecular pharmacology have resulted in the development of molecularly\\u000a targeted therapies. Targeting specific molecular pathways essential for the survival of cancer cells would personalize treatment\\u000a with the potential to improve outcome and minimize toxicities. In this chapter, we review gene-based targeted therapies for\\u000a cancer. Discussion focuses on replacement therapies for abnormal p53 function

Jack A. Roth; John Nemunaitis; Lin Ji; Rajagopal Ramesh

190

Gene Expression in Bone  

NASA Astrophysics Data System (ADS)

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:

D'Ambrogio, A.

191

The Menin Gene  

Microsoft Academic Search

\\u000a Multiple endocrine neoplasia type I (MEN-1) is an autosomal dominant syndrome featuring tumors of endocrine origin. Heterozygous\\u000a germline mutations in the MEN-1 tumor suppressor gene predispose MEN-1 patients to tumor development, mainly in parathyroid, pancreatic islet cells, and\\u000a the anterior pituitary gland. Since the MEN-1-encoded protein, menin, is ubiquitously expressed, the endocrine-specific nature\\u000a in MEN-1 patients remains unexplained. This chapter

Hsin-Chieh Jennifer Shen; Steven K. Libutti

192

Clock genes and sleep  

Microsoft Academic Search

In most species—from cyanobacteria to humans—endogenous clocks have evolved that drive 24-h rhythms of behavior and physiology.\\u000a In mammals, these circadian rhythms are regulated by a hierarchical network of cellular oscillators controlled by a set of\\u000a clock genes organized in a system of interlocked transcriptional feedback loops. One of the most prominent outputs of the\\u000a circadian system is the synchronization

Dominic Landgraf; Anton Shostak; Henrik Oster

193

DNA Gene Chip Explanation  

NSDL National Science Digital Library

Dr. Melton describes the process used to extract DNA from a cell and to analyze it on a gene chip. This video presentation is also featured on the DVD Potent Biology: Stem Cells, Cloning, and Regeneration, available free from HHMI. This video is 57 seconds in length, and available in Quicktime (13 MB) and Windows Media (20 MB) formats. All Stem Cell videos are located at: http://www.hhmi.org/biointeractive/stemcells/video.html.

Dr. Melton (Howard Hughes Medical Institute;)

2007-03-31

194

GENE DELIVERY TO BONE  

PubMed Central

Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a substantial pre-clinical literature documenting the successful transfer of genes to bone, and their intraosseous expression. Recombinant vectors derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors, have been used for this purpose. Both ex vivo and in vivo strategies, including gene-activated matrices, have been explored. Ex vivo delivery has often employed mesenchymal stem cells (MSCs), partly because of their ability to differentiate into osteoblasts. MSCs also have the potential to home to bone after systemic administration, which could serve as a useful way to deliver transgenes in a disseminated fashion for the treatment of diseases affecting the whole skeleton, such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic transgenes, particularly those encoding bone morphogenetic proteins, has shown great promise in a number of applications where it is necessary to regenerate bone. These include healing large segmental defects in long bones and the cranium, as well as spinal fusion and treating avascular necrosis.

Evans, C. H.

2012-01-01

195

ToppGene Suite for gene list enrichment analysis and candidate gene prioritization  

Microsoft Academic Search

ToppGene Suite (http:\\/\\/toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annota- tions or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based dis- ease

Jing Chen; Eric E. Bardes; Bruce J. Aronow; Anil G. Jegga

2009-01-01

196

Gene socialization: gene order, GC content and gene silencing in Salmonella  

Microsoft Academic Search

BACKGROUND: Genes of conserved order in bacterial genomes tend to evolve slower than genes whose order is not conserved. In addition, genes with a GC content lower than the GC content of the resident genome are known to be selectively silenced by the histone-like nucleoid structuring protein (H-NS) in Salmonella. RESULTS: In this study, we use a comparative genomics approach

Nikolas Papanikolaou; Kalliopi Trachana; Theodosios Theodosiou; Vasilis J Promponas; Ioannis Iliopoulos

2009-01-01

197

Venom evolution through gene duplications.  

PubMed

Venoms contain highly complex mixtures that typically include hundreds of different components and have evolved independently in a diverse range of animals including platypuses, shrews, snakes, lizards, fishes, echinoderms, spiders, wasps, centipedes, sea snails, cephalopods, jellyfish and sea anemones. Many venom genes evolved through gene duplication. Gene duplication occurs in all domains of life and provides the raw substrate from which novel function arise. In this review, we focus on the role that gene duplication has played in the origin and diversification of venom genes. We outline the selective advantages of venom gene duplicates and the role that selection has played in the retention of these duplicates. We use toxin gene intermediates to help trace the evolution of toxin innovation. We also focus on other genomic processes, such as exon and domain duplications, in venom evolution. Finally, we conclude by focusing on the use of high throughput sequencing technology in understanding venom evolution. PMID:22285376

Wong, Emily S W; Belov, Katherine

2012-01-18

198

The Gene Wiki: community intelligence applied to human gene annotation.  

PubMed

Annotating the function of all human genes is a critical, yet formidable, challenge. Current gene annotation efforts focus on centralized curation resources, but it is increasingly clear that this approach does not scale with the rapid growth of the biomedical literature. The Gene Wiki utilizes an alternative and complementary model based on the principle of community intelligence. Directly integrated within the online encyclopedia, Wikipedia, the goal of this effort is to build a gene-specific review article for every gene in the human genome, where each article is collaboratively written, continuously updated and community reviewed. Previously, we described the creation of Gene Wiki 'stubs' for approximately 9000 human genes. Here, we describe ongoing systematic improvements to these articles to increase their utility. Moreover, we retrospectively examine the community usage and improvement of the Gene Wiki, providing evidence of a critical mass of users and editors. Gene Wiki articles are freely accessible within the Wikipedia web site, and additional links and information are available at http://en.wikipedia.org/wiki/Portal:Gene_Wiki. PMID:19755503

Huss, Jon W; Lindenbaum, Pierre; Martone, Michael; Roberts, Donabel; Pizarro, Angel; Valafar, Faramarz; Hogenesch, John B; Su, Andrew I

2009-09-15

199

Progress in gene targeting and gene therapy for retinitis pigmentosa  

SciTech Connect

Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectors for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.

Farrar, G.J.; Humphries, M.M.; Erven, A. [Trinity College, Dublin (Ireland)] [and others

1994-09-01

200

Gene Circuit Analysis of the Terminal Gap Gene huckebein  

PubMed Central

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.

Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

2009-01-01

201

Gene conversion in the rice genome  

Microsoft Academic Search

BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes increases opportunities for gene conversion. RESULTS: To characterize gene conversion in rice, we have defined 626 multigene families in which

Shuqing Xu; Terry Clark; Hongkun Zheng; Søren Vang; Ruiqiang Li; Gane Ka-Shu Wong; Jun Wang; Xiaoguang Zheng

2008-01-01

202

Regulation probability method for gene selection  

Microsoft Academic Search

This paper proposes a novel method for gene selection. In the method, the gene regulation, an important mechanism of gene activities, is first introduced, and then the probabilities of gene regulation are estimated. These probabilities can be seen as the gene regulation information and can be used for gene selection. The applications to the leukemia dataset and the colon dataset

Hong-qiang Wang; De-shuang Huang

2006-01-01

203

Gene therapy of benign gynecological diseases  

Microsoft Academic Search

Gene therapy is the introduction of genetic material into patient's cells to achieve therapeutic benefit. Advances in molecular biology techniques and better understanding of disease pathogenesis have validated the use of a variety of genes as potential molecular targets for gene therapy based approaches. Gene therapy strategies include: mutation compensation of dysregulated genes; replacement of defective tumor-suppressor genes; inactivation of

Memy H. Hassan; Essam E. Othman; Daniela Hornung; Ayman Al-Hendy

2009-01-01

204

Cardiac Gene Therapy: Optimization of Gene Delivery Techniques In Vivo  

PubMed Central

Abstract Vector-mediated cardiac gene therapy holds tremendous promise as a translatable platform technology for treating many cardiovascular diseases. The ideal technique is one that is efficient and practical, allowing for global cardiac gene expression, while minimizing collateral expression in other organs. Here we survey the available in vivo vector-mediated cardiac gene delivery methods—including transcutaneous, intravascular, intramuscular, and cardiopulmonary bypass techniques—with consideration of the relative merits and deficiencies of each. Review of available techniques suggests that an optimal method for vector-mediated gene delivery to the large animal myocardium would ideally employ retrograde and/or anterograde transcoronary gene delivery,extended vector residence time in the coronary circulation, an increased myocardial transcapillary gradient using physical methods, increased endothelial permeability with pharmacological agents, minimal collateral gene expression by isolation of the cardiac circulation from the systemic, and have low immunogenicity.

Katz, Michael G.; Swain, JaBaris D.; White, Jennifer D.; Low, David; Stedman, Hansell

2010-01-01

205

Using Gene Expression Noise to Understand Gene Regulation  

PubMed Central

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression ‘noise’, has been suggested as a major source of this variability, and its physiological consequences have been topics of intense research for the last decade. Several recent studies have measured variability in protein and mRNA levels, and have discovered strong connections between noise and gene regulation mechanisms. When integrated with discrete stochastic models, measurements of cell-to-cell variability provide a sensitive ‘fingerprint’ with which to explore fundamental questions on gene regulation. In this review, we highlight several studies that used gene expression variability to develop a quantitative understanding of the mechanisms and dynamics of gene regulation.

Munsky, Brian; Neuert, Gregor; van Oudenaarden, Alexander

2012-01-01

206

Genes affecting tooth morphogenesis.  

PubMed

The development of dentition is a fascinating process that encompasses a complex series of epithelial-mesenchymal interactions involving growth factors, transcription factors, signal receptors and other soluble morphogens. It is not surprising that such a complex process is prone to disturbances and may result in tooth agenesis. Initial discoveries indicating that the homeo-domain protein MSX1 and the paired-domain transcription factor PAX9 are causative genes in tooth morphogenesis were made in mice. Both genes are co-expressed in dental mesenchyme and either one, when homozygously deleted, results in an arrest at an early developmental stage. Heterozygous Pax9 or Msx1 mice have normal teeth, however, double heterozygous Pax9/Msx1 mice show a phenotype of arrested tooth development which can be rescued by transgenic expression of Bmp4, a very influential signaling factor in many developmental processes. We have obtained mounting evidence for a partnership between PAX9 and MSX1 within the tooth-specific Bmp4 signaling pathway. In humans, unlike in mice, a heterozygous mutation in either PAX9 or MSX1 suffices to cause tooth agenesis of a predominantly molar or more premolar pattern, respectively. Our laboratory and others have identified several PAX9 and MSX1 mutations in families with non-syndromic forms of autosomal dominant posterior tooth agenesis. We have also identified families with tooth agenesis in whom PAX9 and MSX1 mutations have been excluded opening up the possibilities for the discovery of other genes that contribute to human tooth agenesis. PMID:17651126

Kapadia, H; Mues, G; D'Souza, R

2007-08-01

207

Gene Switches: A Model  

NSDL National Science Digital Library

In this activity, learners explore how genetic switches function and the role of genetic switches in the process of evolution. To make these concepts less abstract and more understandable, learners first view a series of video clips and animations from the HHMI DVD (or online) "Evolution: Constant Change and Common Threads." Then, learners construct a model of a gene switch using craft materials or FridgiGears (magnetic gears). This activity can be done as a demonstration, a student inquiry activity, or a combination of the two.

Colvard, Mary

2010-01-01

208

Genes governing premature ovarian failure.  

PubMed

Premature ovarian failure (POF) is unexplained amenorrhoea (>6 months), increased FSH (>20 IU/l) and LH occurring before 40 years. Several genes are reported as having significance in POF, including genes governing regulation of the hypothalamic-pituitary-ovarian axis, but their role in ovarian physiology is not known. Deletions or translocations in Xq arm have been found to be associated with POF, assuming presence of ovarian-related genes but ovary-related function of these genes is unclear. Several researchers have suggested specific loci on Xq critical region, POF1 and POF2 and genes DIA, FMR1 and FMR2. The understanding of ovarian physiology, its regulation and genes involved is important to explain the causes of POF. Some genes coordinate development of germ cell to primordial stage, e.g. GDF9, BMP15 and NGF, while others regulate development of further stages, such as FSH and LH. Mutation in these genes may lead to female infertility and are likely to be candidate genes for POF. Recently, association between blepharophimosis-ptosis-epicanthus inversus syndrome type 1 and POF has emerged as a possibility. Galactosaemia is also shown to be important in POF due to toxic effects of accumulated galactose or downstream products. Thus, understanding the role of several genes can be used for the appropriate genetic diagnosis, research and in the clinical practice of POF. PMID:20382564

Dixit, Hridesh; Rao, Lakshmi; Padmalatha, Venkata; Raseswari, Turlapati; Kapu, Anil Kumar; Panda, Bineet; Murthy, Kanakavalli; Tosh, Durgadutta; Nallari, Pratibha; Deenadayal, Mamata; Gupta, Nalini; Chakrabarthy, Baidyanath; Singh, Lalji

2010-03-01

209

Gene therapy for ocular diseases  

PubMed Central

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-01-01

210

Radionuclide reporter gene imaging for cardiac gene therapy  

Microsoft Academic Search

Introduction  In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial\\u000a of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under\\u000a evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential\\u000a risks

Masayuki Inubushi; Nagara Tamaki

2007-01-01

211

A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes.  

PubMed

11p15.5 is an important tumor-suppressor gene region, showing loss of heterozygosity in Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. We previously mapped directly by genetic complementation a subtransferable fragment (STF) harboring an embryonal tumor-suppressor gene and spanning about 2.5 Mb. We have now mapped the centromeric end of this STF between D11S988 and D11S12 and its telomeric end between D11S1318 and TH. We have isolated a complete contig of PAC, P1, BAC, and cosmid genomic clones spanning the entire 2.5-Mb region defined by this STF, as well as more than 200 exons from these genomic clones using exon trapping. We have isolated genes in this region by directly screening DNA libraries as well as by database searching for ESTs. Nine of these genes have been reported previously by us and by others. However, the initial mapping of most of those genes was based on FISH or somatic cell hybrid analysis, and here we precisely define their physical location. These genes include RRM1, GOK (D11S4896E), Nup98, CARS, hNAP2 (NAP1L4), p57KIP2 (CDKN1C), KVLQT1 (KCNA9), TAPA-1, and ASCL2. In addition, we have identified several novel genes in this region, three of which, termed TSSC1, TSSC2, and TSSC3, are reported here. TSSC1 shows homology to Rb-associated protein p48 and chromatin assembly factor CAF1, and it is located between GOK and Nup98. TSSC2 is homologous to Caenorhabditis elegans beta-mannosyl transferase, and it lies between Nup98 and CARS. TSSC3 shows homology to mouse TDAG51, which is implicated in FasL-mediated apoptosis, and it is located between hNAP2 and p57KIP2. Thus, these genes may play a role in malignancies that involve this region. PMID:9403053

Hu, R J; Lee, M P; Connors, T D; Johnson, L A; Burn, T C; Su, K; Landes, G M; Feinberg, A P

1997-11-15

212

Bayesian assignment of gene ontology terms to gene expression experiments  

PubMed Central

Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at

Sykacek, P.

2012-01-01

213

Gene regulation of steroidogenesis.  

PubMed

The biosynthesis of various steroid hormones in animal tissues are catalyzed by six forms of cytochrome P450 and two hydroxysteroid dehydrogenases. The tissue-specific expression of these enzymes, which are under the control of the pituitary gland and mainly regulated at the transcriptional level, determines the steroidogenesis of animal tissues. Analysis of the promoter regions of the steroidogenic P450 genes revealed various cis-acting elements, including cAMP-responsive sequences (CRS), Ad4, and GC-rich sequences, which were needed for the tissue-specific and cAMP-dependent expression of the genes. Some of the nuclear protein factors binding to the cis-acting elements were isolated and characterized. A zinc-finger protein binding to Ad4, which was termed Ad4BP or SF-1, seems to be of particular importance in steroidogenesis. Ad4BP was expressed in the cells of the steroidogenic tissues, adrenal gland and gonadal tissues, in the rat fetus prior to the expression of steroidogenic P450s, and remained expressed only in steroidogenic cells in adult animals. Close investigation of the temporal and spacial expression of Ad4BP in the fetal tissues suggested its role in the differentiation of the steroidogenic tissues and the sex determination of the gonadal tissues. PMID:7626452

Omura, T; Morohashi, K

1995-06-01

214

GENE LOOPS ENHANCE TRANSCRIPTIONAL DIRECTIONALITY  

PubMed Central

Eukaryotic genomes are extensively transcribed, forming both messenger (m) and noncoding (nc) RNAs. ncRNAs made by RNA polymerase II (Pol II) often initiate from bidirectional promoters (nucleosome-depleted chromatin) that synthesise mRNA and ncRNA in opposite directions. We demonstrate that actively transcribed mRNA encoding genes by adopting a gene loop conformation, restrict divergent transcription of ncRNAs. Since gene loop formation depends on a protein factor (Ssu72) that co-associates with both promoter and terminator, its inactivation leads to increased synthesis of promoter-associated divergent ncRNAs, referred to as Ssu72 restricted transcripts (SRT). Similarly, inactivation of individual gene loops by gene mutation enhances SRT synthesis. We demonstrate that gene loop conformation enforces transcriptional directionality on otherwise bidirectional promoters.

Tan-Wong, Sue Mei; Zaugg, Judith B.; Camblong, Jurgi; Xu, Zhenyu; Zhang, David W.; Mischo, Hannah E.; Ansari, Aseem Z.; Luscombe, Nicholas M.; Steinmetz, Lars M.; Proudfoot, Nick J.

2012-01-01

215

Genes involved in the control of tumor progression and their possible use for gene therapy  

Microsoft Academic Search

Summary Three major groups of genes may be used for cancer gene therapy: (i ) oncogenes and tumor suppressor genes; ( ii ) genes involved in the control of tumor progression and metastasis; and ( iii ) genes encoding proteins protecting the organism from tumor cells. Each group contains numerous genes, and the discovery of new important genes is an

Georgii P. Georgiev; Sergei L. Kiselev; Evgenii M. Lukanidin

216

Guidebook to the homeobox genes  

SciTech Connect

The homeobox encodes a 60-amino-acid region, the homeodomain, that binds to DNA in the regulatory regions of downstream target genes, to regulate their expression. This guidebook is both an excellent introduction to homeobox genes and a fine reference book for scientists of developmental biology. Three introductory chapters are followed by the bulk of the book, which contains summary descriptions of >300 homeobox genes, as well as extensive references. 14 refs.

Duboule, D. [ed.

1995-10-01

217

Gene Therapy for Chronic Pain  

Microsoft Academic Search

\\u000a Gene therapy shows great potential to assist numerous patients with inadequate relief of inflammatory or neuropathic pain,\\u000a or intractable pain associated with advanced cancer. A brief overview is provided of the methods of gene therapy and of preclinical\\u000a findings in animal models of prolonged inflammatory, neuropathic and cancer pain. Preclinical findings demonstrate no efficacy\\u000a of gene therapy on basal thermal

William R. Lariviere; Doris K. Cope

218

Gene defects in idiopathic epilepsy.  

PubMed

Idiopathic epilepsies are mainly due to genetic factors. In most cases the mode of inheritance is either oligogenic or multifactorial. Only a few rare idiopathic epilepsies are single gene disorders. Monogenic epilepsies offer the chance to identify genes/gene families which might also be involved in the aetiology of common forms of the disease. The genetic basis of two monogenic epilepsies have recently been identified: autosomal dominant nocturnal frontal lobe epilepsy and benign familial neonatal convulsions. PMID:10472657

Steinlein, O K

1999-07-01

219

Understanding Cancer Series: Gene Testing  

Cancer.gov

Lydia Schindler Donna Kerrigan, M.S. Jeanne Kelly Brian Hollen Illustrates what genes are, explains how mutations occur and are identified within genes, and discusses the benefits and limitations of gene testing for cancer and other disorders. These PowerPoint slides are not locked files. You can mix and match slides from different tutorials as you prepare your own lectures. In the Notes section, you will find explanations of the graphics.

220

Gene Therapy Approaches to Immunosuppression  

Microsoft Academic Search

\\u000a Gene therapy is defined as the delivery of genetic material in the form of DNA. Its purpose is to correct a missing or disturbed\\u000a gene function associated with a pathophysiological situation in patients. It is attractive compared to the conventional pharmacological\\u000a therapy, as it can be applied more locally and thus should have fewer side-effects. Somatic gene therapy, the delivery

Reto A. Gadient; Thomas Biihler; Marcel Luyten; N. Rao Movva

221

Local Gene Therapy for Cancer  

Microsoft Academic Search

Cancer is an important problem in public health worldwide. Gene therapy has the potential for improved treatment of cancer\\u000a patients, particularly if used in combination with other, conventional therapies. To date, many strategies of gene therapy\\u000a have been explored, including correction of mutant genes, immunstimulation, prodrug activation, interference of oncogene expression,\\u000a and genetically modified oncolytic viruses. Although the preclinical results

Wolfgang Walther; Ulrike S. Stein; Peter M. Schlag

222

Gene therapy for Parkinson's disease  

Microsoft Academic Search

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors\\u000a inhibiting neurodegenerative processes and neurotransmitter-synthesizing enzymes provides the basis for current gene therapy\\u000a strategies for Parkinson's disease. Genes can be transferred by viral or nonviral vectors. Of the various possible vectors,\\u000a recombinant retroviruses are the most efficient for genetic modification of cells

Philippe Horellou; Jacques Mallet

1997-01-01

223

Gene and Genome Parameters of Mammalian Liver Circadian Genes (LCGs)  

PubMed Central

The mammalian circadian system controls various physiology processes and behavior responses by regulating thousands of circadian genes with rhythmic expressions. In this study, we redefined circadian-regulated genes based on published results in the mouse liver and compared them with other gene groups defined relative to circadian regulations, especially the non-circadian-regulated genes expressed in liver at multiple molecular levels from gene position to protein expression based on integrative analyses of different datasets from the literature. Based on the intra-tissue analysis, the liver circadian genes or LCGs show unique features when compared to other gene groups. First, LCGs in general have less neighboring genes and larger in both genomic and 3?-UTR lengths but shorter in CDS (coding sequence) lengths. Second, LCGs have higher mRNA and protein abundance, higher temporal expression variations, and shorter mRNA half-life. Third, more than 60% of LCGs form major co-expression clusters centered in four temporal windows: dawn, day, dusk, and night. In addition, larger and smaller LCGs are found mainly expressed in the day and night temporal windows, respectively, and we believe that LCGs are well-partitioned into the gene expression regulatory network that takes advantage of gene size, expression constraint, and chromosomal architecture. Based on inter-tissue analysis, more than half of LCGs are ubiquitously expressed in multiple tissues but only show rhythmical expression in one or limited number of tissues. LCGs show at least three-fold lower expression variations across the temporal windows than those among different tissues, and this observation suggests that temporal expression variations regulated by the circadian system is relatively subtle as compared with the tissue expression variations formed during development. Taken together, we suggest that the circadian system selects gene parameters in a cost effective way to improve tissue-specific functions by adapting temporal variations from the environment over evolutionary time scales.

Wu, Gang; Zhu, Jiang; He, Fuhong; Wang, Weiwei; Hu, Songnian; Yu, Jun

2012-01-01

224

A genetic ensemble approach for gene-gene interaction identification  

PubMed Central

Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA) and an ensemble of classifiers (called genetic ensemble). Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP) subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR) and is slightly better than Polymorphism Interaction Analysis (PIA), which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of combining identification results from different algorithms.

2010-01-01

225

Importance of Combinatorial Gene Control  

NSDL National Science Digital Library

A hypothetical scheme illustrating how combinations of a few gene regulatory proteins can generate many different cell types during development. In this simple scheme a "decision" to make a new gene regulatory protein (shown as a numbered circle) is made after each cell division. Repetition of this simple rule enables eight cell types (A through H) to be created using only three different regulatory proteins. Each of these hypothetical cell types would then express different genes, as dictated by the combination of gene regulatory proteins that are present within it.

BEGIN:VCARD VERSION:2.1 FN:Bruce Alberts N:Alberts;Bruce REV:2005-04-16 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Dennis Bray N:Bray;Dennis REV:2005-04-16 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Alexander Johnson N:Johnson;Alexander REV:2005-04-16 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Julian Lewis N:Lewis;Julian REV:2005-04-16 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Martin Raff N:Raff;Martin REV:2005-04-16 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Keith Roberts N:Roberts;Keith REV:2005-04-16 END:VCARD

1998-07-01

226

The coalescent with gene conversion.  

PubMed Central

In this article we develop a coalescent model with intralocus gene conversion. The distribution of the tract length is geometric in concordance with results published in the literature. We derive a simulation scheme and deduce a number of analytical results for this coalescent with gene conversion. We compare patterns of variability in samples simulated according to the coalescent with recombination with similar patterns simulated according to the coalescent with gene conversion alone. Further, an expression for the expected number of topology shifts in a sample of present-day sequences caused by gene conversion events is derived.

Wiuf, C; Hein, J

2000-01-01

227

GeneID in Drosophila  

PubMed Central

GeneID is a program to predict genes in anonymous genomic sequences designed with a hierarchical structure. In the first step, splice sites, and start and stop codons are predicted and scored along the sequence using position weight matrices (PWMs). In the second step, exons are built from the sites. Exons are scored as the sum of the scores of the defining sites, plus the log-likelihood ratio of a Markov model for coding DNA. In the last step, from the set of predicted exons, the gene structure is assembled, maximizing the sum of the scores of the assembled exons. In this paper we describe the obtention of PWMs for sites, and the Markov model of coding DNA in Drosophila melanogaster. We also compare other models of coding DNA with the Markov model. Finally, we present and discuss the results obtained when GeneID is used to predict genes in the Adh region. These results show that the accuracy of GeneID predictions compares currently with that of other existing tools but that GeneID is likely to be more efficient in terms of speed and memory usage. GeneID is available at http://www1.imim.es/?eblanco/GeneId.

Parra, Genis; Blanco, Enrique; Guigo, Roderic

2000-01-01

228

GeneDistiller---Distilling Candidate Genes from Linkage Intervals  

Microsoft Academic Search

BackgroundLinkage studies often yield intervals containing several hundred positional candidate genes. Different manual or automatic approaches exist for the determination of the gene most likely to cause the disease. While the manual search is very flexible and takes advantage of the researchers' background knowledge and intuition, it may be very cumbersome to collect and study the relevant data. Automatic solutions

Dominik Seelow; Jana Marie Schwarz; Markus Schuelke; Philip Awadalla

2008-01-01

229

Gene Therapy Using Gene Fusions for Genetic or Acquired Disorders.  

National Technical Information Service (NTIS)

The invention is related generally to the construction of fusion genes. More particularly, it is related to the construction of a fusion gene comprising a coding sequence for a selectable marker linked by fusion to another coding sequence, the product of ...

I. Pastan M. Gottesman

1988-01-01

230

DIFFERENTIAL GENE EXPRESSION OF PUTATIVE VIRULENCE GENES IN Flavobacterium columnare  

Technology Transfer Automated Retrieval System (TEKTRAN)

A shot-gun genomic library of the Flavobacterium columnare ALG-530 virulent strain has been constructed and more than 3,000 clones have been sequenced to date (800 contigs). Based on sequence identity with putative known virulence genes from related species, seven genes were selected for differentia...

231

Contributions of gene marking to cell and gene therapies.  

PubMed

The first human genetic modification studies used replication-incompetent integrating vector vectors to introduce marker genes into T lymphocytes and subsequently into hematopoietic stem cells. Such studies have provided numerous insights into the biology of hematopoiesis and immune reconstitution and contributed to clinical development of gene and cell therapies. Tracking of hematopoietic reconstitution and analysis of the origin of residual malignant disease after hematopoietic transplantation has been possible via gene marking. Introduction of selectable marker genes has enabled preselection of specific T-cell populations for tumor and viral immunotherapy and reduced the threat of graft-versus-host disease, improving the survival of patients after allogeneic marrow transplantation. Marking studies in humans, murine xenografts, and large animals have helped optimize conditions for gene transfer into CD34(+) hematopoietic progenitors, contributing to the achievement of gene transfer efficiencies sufficient for clinical benefit in several serious genetic diseases such as X-linked severe combined immunodeficiency and adrenoleukodystrophy. When adverse events linked to insertional mutagenesis arose in clinical gene therapy trials for inherited immunodeficiencies, additional animal studies using gene-marking vectors have greatly increased our understanding of genotoxicity. The knowledge gained from these studies is being translated into new vector designs and clinical protocols, which we hope will continue to improve the efficiency, effectiveness and safety of these promising therapeutic approaches. PMID:21261461

Barese, Cecilia N; Dunbar, Cynthia E

2011-05-05

232

Gene expression profiling: can we identify the right target genes?  

Microsoft Academic Search

Gene expression profiling allows the simultaneous monitoring of the transcriptional behaviour of thousands of genes, which may potentially be involved in disease development. Several studies have been performed in idiopathic pulmonary fibrosis (IPF), which aim to define genetic links to the disease in an attempt to improve the current understanding of the underlying pathogenesis of the disease and target pathways

J. E. Loyd

2008-01-01

233

Horizontal gene transfer of toxin genes in Clostridium botulinum  

PubMed Central

Intoxication with the potent botulinum neurotoxin (BoNT) gives rise to the serious paralytic illness botulism. BoNT is part of a complex that consists of the neurotoxin and several associated components, all encoded by the bont gene cluster. This gene cluster has likely been subjected to horizontal gene transfer between different groups of clostridia, which has given rise to the genetically diverse species Clostridium botulinum. C. botulinum is divided into four physiological groups (I–IV), where group I and II cause disease in humans and group III in animals. Analysis of the genomes of group I, II and III has revealed that toxin genes, including the bont cluster, often are plasmid-borne. The genomes analyzed from group III contain an unusually high number of plasmids carrying different toxin genes. Some of these genes are also found in other Clostridium species and some have moved between different plasmids within the same physiological group. This indicates that horizontal transfer of toxin genes is taking place within and between species of Clostridium. The abundance of mobile elements, especially in genomes of group III, is likely connected to accelerated genome plasticity and gene transfer events.

Segerman, Bo

2011-01-01

234

Aphids acquired symbiotic genes via lateral gene transfer  

Microsoft Academic Search

BACKGROUND: Aphids possess bacteriocytes, which are cells specifically differentiated to harbour the obligate mutualist Buchnera aphidicola (?-Proteobacteria). Buchnera has lost many of the genes that appear to be essential for bacterial life. From the bacteriocyte of the pea aphid Acyrthosiphon pisum, we previously identified two clusters of expressed sequence tags that display similarity only to bacterial genes. Southern blot analysis

Naruo Nikoh; Atsushi Nakabachi

2009-01-01

235

Bacteria in gene therapy: bactofection versus alternative gene therapy  

Microsoft Academic Search

Recent advances in gene therapy can be attributed to improvements of gene delivery vectors. New viral and nonviral transport vehicles that considerably increase the efficiency of transfection have been prepared. However, these vectors still have many disadvantages that are difficult to overcome, thus, a new approach is needed. The approach of bacterial delivery could in the future be important for

R Pálffy; R Gardlík; J Hodosy; M Behuliak; P Reško; J Radvánský; P Celec

2006-01-01

236

New genes for boys  

SciTech Connect

Sex is a fascinating topic, particularly at the level of molecular genetics, since it represents a wonderful paradigm for mammalian organ development. Recently, interest in the molecular basis for mammalian sex determination has been heating up as new pieces are added to the jigsaw puzzle of testis development. In mammals, the Y chromosome is male determining and encodes a gene referred to as TDF (testis-determining factor), which induces the indifferent embryonic gonad to develop as a testis. Subsequent male sexual differentiation is largely a consequence of hormonal secretion from the testis. In the absence of the Y chromosome, the testis-determining pathway fails to be initiated, and the embryonic gonad develops as an ovary, resulting in female development. 32 refs.

Sinclair, A.H. [Univ. of Melbourne (Australia)

1995-11-01

237

Taste Receptor Genes  

PubMed Central

In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity.

Bachmanov, Alexander A.; Beauchamp, Gary K.

2009-01-01

238

Genes controlling pancreas ontogeny.  

PubMed

The pancreas develops from two separate and independent endodermal primordia. The molecular events supporting the early morphological changes that give rise to the formation of the dorsal and ventral pancreatic buds result from coordinated responses to extrinsic and intrinsic signals. The extrinsic signals are involved in processes dictating whether progenitor cells remain as immature or as committed precursors. After specification, the sequential activation of transcription factors determines cell autonomously the commitment and differentiation of these progenitors. During pancreas development, the roles of extrinsic and intrinsic signals are variable, depending on the particular competence of each progenitor cell. We summarize in this review the main events, at the level of gene expression, which are involved in the early stages of pancreas development. PMID:18956314

Bonal, Claire; Herrera, Pedro L

2008-01-01

239

Rheumatoid arthritis-associated gene-gene interaction network for rheumatoid arthritis candidate genes  

Microsoft Academic Search

Rheumatoid arthritis (RA, MIM 180300) is a chronic and complex autoimmune disease. Using the North American Rheumatoid Arthritis Consortium (NARAC) data set provided in Genetic Analysis Workshop 16 (GAW16), we used the genotype-trait distortion (GTD) scores and proposed analysis procedures to capture the gene-gene interaction effects of multiple susceptibility gene regions on RA. In this paper, we focused on 27

2009-01-01

240

Jasmonate-Responsive Gene Expression  

Microsoft Academic Search

Jasmonic acid (JA) and its volatile methyl ester (MeJA) belong to a family of lipid-derived signalling molecules that affect many aspects of plant life, including defense against certain pathogens and insects and some developmental processes. JA signal transduction leads to modulation of the expression of primary response genes, the products of which lead to the expression of secondary response genes.

Bea Pauw; Johan Memelink

2004-01-01

241

Transcriptional gene silencing in plants  

Microsoft Academic Search

The review presents current data on molecular genetic mechanisms of suppression of the gene (transgene) expression in plants\\u000a at the transcriptional level. The stages of RNA-directed DNA methylation are discussed in detail. Mutations affecting transcriptional\\u000a gene inactivation without altering nucleotide sequence methylation are described.

T. V. Marenkova; E. V. Deineko

2010-01-01

242

Introduction: Genes, cognition and neuropsychiatry  

Microsoft Academic Search

Numerous genes modulate dopamine and consequently prefrontal cortical function. Some of these genes – notably catechol-O-methyltransferase – have been shown to impact a variety of core cognitive processes that are dependent upon the prefrontal cortex. This demonstration that a single functional polymorphism can contribute so dramatically to individual differences heralds a new era for neuropsychiatry. Although enormous detail remains to

Brita Elvevåg; Daniel R. Weinberger

2009-01-01

243

HOX genes in ovarian cancer  

PubMed Central

The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

2011-01-01

244

Expression of mammalian defensin genes  

Microsoft Academic Search

Antimicrobial peptides are a prevalent mechanism of host defense found throughout na- ture. In mammals, defensins are among the most abundant of these broad-spectrum antibiotics, and are expressed in epithelial and hematopoietic cells. The defensin peptides are especially abundant in neutrophils; however, gene expression is limited to the promyelocyte stage. In epithelial cells, defensin genes are found as both constitutively

Vicki Kaiser; Gill Diamond

2000-01-01

245

Polyene antibiotic biosynthesis gene clusters  

Microsoft Academic Search

Over the past 15 years the biosynthetic gene clusters for numerous bioactive polyketides have been intensively studied and recently this work has been extended to the antifungal polyene macrolides. These compounds consist of large macrolactone rings that have a characteristic series of conjugated double bonds, as well as an exocyclic carboxyl group and an unusual mycosamine sugar. The biosynthetic gene

J. F. Aparicio; P. Caffrey; J. A. Gil; S. B. Zotchev

2003-01-01

246

Gene Therapy in Heart Failure  

Microsoft Academic Search

With increasing knowledge of basic molecular mechanisms governing the development of heart failure (HF), the possibility of specifically targeting key pathological players is evolving. Technology allowing for efficient in vivo transduction of myocardial tissue with long-term expression of a transgene enables translation of basic mechanistic knowledge into potential gene therapy approaches. Gene therapy in HF is in its infancy clinically

Leif Erik Vinge; Philip W. Raake; Walter J. Koch

2010-01-01

247

Gene replacement in parasitic protozoa  

Microsoft Academic Search

TRYPANOSOMATID protozoa frequently cause severe diseases in humans. Many molecules likely to have a role during the infectious cycle have been identified, yet proof of their function is often lacking. We describe studies in Leishmania major of homologous gene targeting, a powerful method for testing gene function in other organisms-. Following introduction of a construct containing dihydrofolate reductase-thymidylate synthase (dhfr-ts)

Angela Cruz; Stephen M. Beverley

1990-01-01

248

Feedback control of gene expression  

Microsoft Academic Search

Although feedback regulation of photosynthesis by carbon metabolites has long been recognized and investigated, its underlying molecular mechanisms remain unclear. The recent discovery that glucose and acetate trigger global repression of maize photosynthetic gene transcription provides the first direct evidence that a fundamental mechanism is used for feedback regulation of photosynthesis in higher plants. The metabolic repression of photosynthetic genes

Jen Sheen

1994-01-01

249

Human Cripto-Related Gene.  

National Technical Information Service (NTIS)

The invention relates, in general, to a human CRIPTO-related gene. In particular, the invention relates to a DNA segment encoding a human CRIPTO-related gene; polypeptides encoded by said DNA segment; recombinant DNA molecules containing the DNA segment; ...

D. Salomom M. Persico

1991-01-01

250

Gene Identification by Shotgun Antisense  

Microsoft Academic Search

Shotgun antisense is a technique to make a random set of mutant cells or organisms in such a way that one can select an interesting mutant and then sequence part of the mutated gene within a day. In addition to the fantastic rapidity with which one can identify the mutated gene, there are more advantages of this technique over other

Richard H. Gomer

1999-01-01

251

Multifunctional nanorods for gene delivery  

NASA Astrophysics Data System (ADS)

The goal of gene therapy is to introduce foreign genes into somatic cells to supplement defective genes or provide additional biological functions, and can be achieved using either viral or synthetic non-viral delivery systems. Compared with viral vectors, synthetic gene-delivery systems, such as liposomes and polymers, offer several advantages including ease of production and reduced risk of cytotoxicity and immunogenicity, but their use has been limited by the relatively low transfection efficiency. This problem mainly stems from the difficulty in controlling their properties at the nanoscale. Synthetic inorganic gene carriers have received limited attention in the gene-therapy community, the only notable example being gold nanoparticles with surface-immobilized DNA applied to intradermal genetic immunization by particle bombardment. Here we present a non-viral gene-delivery system based on multisegment bimetallic nanorods that can simultaneously bind compacted DNA plasmids and targeting ligands in a spatially defined manner. This approach allows precise control of composition, size and multifunctionality of the gene-delivery system. Transfection experiments performed in vitro and in vivo provide promising results that suggest potential in genetic vaccination applications.

Salem, Aliasger K.; Searson, Peter C.; Leong, Kam W.

2003-10-01

252

for Hemophilia B Gene Therapy  

Microsoft Academic Search

Adeno-associated viral (AAV) vector is attracting significant interest for use in gene therapy for genetic diseases, because of its unique and advantageous characteristics, compared to other currently available viral vectors. Eight natural serotypes of AAV have been identified, of which AAV serotype 2 is the one best characterized and most widely used in current gene delivery studies. The application of

HENGJUN CHAO; CHRISTOPHER E. WALSH

253

Gene therapy for prostate cancer  

Microsoft Academic Search

Summary The advent of recombinant DNA technology has sparked the age of molecular medicine. The ability to deliberately recombine pieces of DNA and then transfer these specific genes into diseased cells has revolutionized medical research. In fact, the ability to modify these genes in the living person is now possible. Several innovative approaches are being developed to circumvent the limitations

Mitchell S Steiner; Jeffrey R Gingrich

1999-01-01

254

Progress in cancer gene therapy  

Microsoft Academic Search

The “First International Symposium on Genetic Anticancer Agents,” which took place in Amsterdam on March 8–9, 2000, served as a forum to review the results of preclinical and clinical gene therapy studies for cancer endeavored to date.Despite the fact that gene therapy was initially conceptualized as an approach for inherited genetic disease, it is currently finding its widest employ for

David T Curiel; Winald R Gerritsen; Mark R L Krul

2000-01-01

255

Gene therapy for arterial thrombosis  

Microsoft Academic Search

Conventional antithrombotic treatments with antiplatelet, anticoagulant, or fibrinolytic drugs are not uniformly successful and are associated with hemorrhagic side effects. Thus, new approaches to the prevention and treatment of arterial thrombosis are desirable. The gene transfer approach is particularly attractive because of its unique ability to express an antithrombotic gene at selected sites of the . vessel wall where thrombosis

Giuseppe Vassalli; David A. Dichek

256

Using Genes to Guide Prescriptions  

MedlinePLUS

... made up of biochemical units abbreviated A, T, G and C. Different people might have slightly different versions—or spellings—of genes. Most of these variations have no effect on health. But if a gene codes for a protein that plays a role in how the body ...

257

Gli genes and limb development  

Microsoft Academic Search

During development of the limb Shh plays a key role as a mediator of zone of polarizing activity (ZPA). However, the molecular mechanisms by which Shh directs anterior\\/posterior patterning in the limb remain unknown. Members of the Gli gene family encode zinc-finger transcription factors and represent likely candidates for being regulators of Shh target genes. In this review we would

Thomas Theil; Susanne Kaesler; Lars Grotewold; Jens Böse; Ulrich Rüther

1999-01-01

258

The evolution of disease resistance genes  

Microsoft Academic Search

Several common themes have shaped the evolution of plant disease resistance genes. These include duplication events of progenitor resistance genes and further expansion to create clustered gene families. Variation can arise from both intragenic and intergenic recombination and gene conversion. Recombination has also been implicated in the generation of novel resistance specificities. Resistance gene clusters appear to evolve more rapidly

Todd E. Richter; Pamela C. Ronald

2000-01-01

259

Multiconstrained gene clustering based on generalized projections  

Microsoft Academic Search

Background: Gene clustering for annotating gene functions is one of the fundamental issues in bioinformatics. The best clustering solution is often regularized by multiple constraints such as gene expressions, Gene Ontology (GO) annotations and gene network structures. How to integrate multiple pieces of constraints for an optimal clustering solution still remains an unsolved problem. Results: We propose a novel multiconstrained

Jia Zeng; Shanfeng Zhu; Alan Wee-Chung Liew; Hong Yan

2010-01-01

260

Endocrine Aspects of Cancer Gene Therapy  

Microsoft Academic Search

The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene tar- geting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, in- cluding the possibility to exploit hormone and hormone re- ceptor functions for regulating therapeutic gene expression, the use of endocrine-specific

LUISA BARZON; MARCO BOSCARO; GIORGIO PALU

2010-01-01

261

Dynamic agglomerative clustering of gene expression profiles  

Microsoft Academic Search

The increasing use of microarray technologies is generating a large amount of data that must be processed to extract underlying gene expression patterns. Existing clustering methods could suffer from certain drawbacks. Most methods cannot automatically separate scat- tered, singleton and mini-cluster genes from other genes. Inclusion of these types of genes into regular clustering processes can impede identification of gene

Faming Liang; Naisyin Wang

2007-01-01

262

Nonviral Vectors for Gene Delivery  

NASA Astrophysics Data System (ADS)

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was also explored. Positively charged CPPs were complexed with pDNA or siRNA, which resulted in 'loose' (˜1 micron) particles. These were then condensed into small nanoparticles by using calcium, which formed "soft" crosslinks by interacting with both phosphates on nucleic acids and amines on CPPs. An optimal amount of CaCl2 produced stable, ˜100 nm complexes that exhibited higher transfection efficiency and gene silencing than PEI polyplexes. CPPs also displayed negligible cytotoxicity up to 5 mg/mL. Biophysical studies of the pDNA structure within complexes suggested that pDNA within CPP complexes (condensed with calcium) had similar structure, but enhanced thermal stability compared to PEI complexes. Thus, CPP complexes emerged as simple, attractive candidates for future studies on nonviral gene delivery in vivo.

Baoum, Abdulgader Ahmed

263

New colon cancer gene discovered  

SciTech Connect

A new gene has been discovered, by genetic linkage studies, that predisposes to colon cancer. The gene was discovered by linkage to a microsatellite marker on human chromosome 2. The microsatellite DNA shows a high degree of variation in colon cancers, varying in length from tumor to tumor. The gene may act by destabilizing the genome. Different groups looking at different satellite markers saw thousands of microsatellite instabilities throughout the genome, raising the possibility that the DNA as a whole is not being copied correctly, apparently due to a gene mutation that causes wholesale errors during DNA replication. Researchers hope to use the gene as a screening tool for screening individuals susceptible to colon cancer.

Marx, J.

1993-05-07

264

Delivery systems for gene therapy  

PubMed Central

The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

Mali, Shrikant

2013-01-01

265

Delivery systems for gene therapy.  

PubMed

The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy. PMID:23901186

Mali, Shrikant

2013-01-01

266

Nuclear Neighborhoods and Gene Expression  

PubMed Central

Summary The eukaryotic nucleus is a highly compartmentalized and dynamic environment. Chromosome territories are arranged non-randomly within the nucleus and numerous studies have indicated that a gene’s position in the nucleus can impact its transcriptional activity. Here, we focus on recent advances in our understanding of the influence of specific nuclear neighborhoods on gene expression or repression. Nuclear neighborhoods associated with transcriptional repression include the inner nuclear membrane/nuclear lamina and peri-nucleolar chromatin, whereas neighborhoods surrounding the nuclear pore complex, PML nuclear bodies, and nuclear speckles seem to be transcriptionally permissive. While nuclear position appears to play an important role in gene expression, it is likely to be only one piece of a flexible puzzle that incorporates numerous parameters. We are still at a very early, yet exciting stage in our journey toward deciphering the mechanism(s) that govern the permissiveness of gene expression/repression within different nuclear neighborhoods.

Zhao, Rui; Bodnar, Megan S.; Spector, David L.

2009-01-01

267

Phylogenetic analysis of gene expression.  

PubMed

Phylogenetic analyses of gene expression have great potential for addressing a wide range of questions. These analyses will, for example, identify genes that have evolutionary shifts in expression that are correlated with evolutionary changes in morphological, physiological, and developmental characters of interest. This will provide entirely new opportunities to identify genes related to particular phenotypes. There are, however, 3 key challenges that must be addressed for such studies to realize their potential. First, data on gene expression must be measured from multiple species, some of which may be field-collected, and parameterized in such a way that they can be compared across species. Second, it will be necessary to develop comparative phylogenetic methods suitable for large multidimensional datasets. In most phylogenetic comparative studies to date, the number n of independent observations (independent contrasts) has been greater than the number p of variables (characters). The behavior of comparative methods for these classic problems is now well understood under a wide variety of conditions. In studies of gene expression, and in studies based on other high-throughput tools, the number n of samples is dwarfed by the number p of variables. The estimated covariance matrices will be singular, complicating their analysis and interpretation, and prone to spurious results. Third, new approaches are needed to investigate the expression of the many genes whose phylogenies are not congruent with species phylogenies due to gene loss, gene duplication, and incomplete lineage sorting. Here we outline general considerations of project design for phylogenetic analyses of gene expression and suggest solutions to these three categories of challenges. These topics are relevant to high-throughput phenotypic data well beyond gene expression. PMID:23748631

Dunn, Casey W; Luo, Xi; Wu, Zhijin

2013-06-07

268

Quantitative set analysis for gene expression: a method to quantify gene set differential expression including gene-gene correlations.  

PubMed

Enrichment analysis of gene sets is a popular approach that provides a functional interpretation of genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in a high Type I error. The most widely used test, Gene Set Enrichment Analysis, relies on computationally intensive permutations of sample labels to generate a null distribution that preserves gene-gene correlations. A more recent approach, CAMERA, attempts to correct for these correlations by estimating a variance inflation factor directly from the data. Although these methods generate P-values for detecting gene set activity, they are unable to produce confidence intervals or allow for post hoc comparisons. We have developed a new computational framework for Quantitative Set Analysis of Gene Expression (QuSAGE). QuSAGE accounts for inter-gene correlations, improves the estimation of the variance inflation factor and, rather than evaluating the deviation from a null hypothesis with a P-value, it quantifies gene-set activity with a complete probability density function. From this probability density function, P-values and confidence intervals can be extracted and post hoc analysis can be carried out while maintaining statistical traceability. Compared with Gene Set Enrichment Analysis and CAMERA, QuSAGE exhibits better sensitivity and specificity on real data profiling the response to interferon therapy (in chronic Hepatitis C virus patients) and Influenza A virus infection. QuSAGE is available as an R package, which includes the core functions for the method as well as functions to plot and visualize the results. PMID:23921631

Yaari, Gur; Bolen, Christopher R; Thakar, Juilee; Kleinstein, Steven H

2013-08-05

269

Quantitative set analysis for gene expression: a method to quantify gene set differential expression including gene-gene correlations  

PubMed Central

Enrichment analysis of gene sets is a popular approach that provides a functional interpretation of genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in a high Type I error. The most widely used test, Gene Set Enrichment Analysis, relies on computationally intensive permutations of sample labels to generate a null distribution that preserves gene–gene correlations. A more recent approach, CAMERA, attempts to correct for these correlations by estimating a variance inflation factor directly from the data. Although these methods generate P-values for detecting gene set activity, they are unable to produce confidence intervals or allow for post hoc comparisons. We have developed a new computational framework for Quantitative Set Analysis of Gene Expression (QuSAGE). QuSAGE accounts for inter-gene correlations, improves the estimation of the variance inflation factor and, rather than evaluating the deviation from a null hypothesis with a P-value, it quantifies gene-set activity with a complete probability density function. From this probability density function, P-values and confidence intervals can be extracted and post hoc analysis can be carried out while maintaining statistical traceability. Compared with Gene Set Enrichment Analysis and CAMERA, QuSAGE exhibits better sensitivity and specificity on real data profiling the response to interferon therapy (in chronic Hepatitis C virus patients) and Influenza A virus infection. QuSAGE is available as an R package, which includes the core functions for the method as well as functions to plot and visualize the results.

Yaari, Gur; Bolen, Christopher R.; Thakar, Juilee; Kleinstein, Steven H.

2013-01-01

270

Gene Discovery Methods from Large-Scale Gene Expression Data  

NASA Astrophysics Data System (ADS)

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.

Shimizu, Akifumi; Yano, Kentaro

2010-01-01

271

Biological profiling of gene groups utilizing Gene Ontology.  

PubMed

Increasingly used high throughput experimental techniques, like DNA or protein microarrays give as a result groups of interesting, e.g. differentially regulated genes which require further biological interpretation. With the systematic functional annotation provided by the Gene Ontology the information required to automate the interpretation task is now accessible. However, the determination of statistical significance of a biological process within these groups is still an open question. In answering this question, multiple testing issues must be taken into account to avoid misleading results. Here we present a statistical framework that tests whether functions, processes or locations described in the Gene Ontology are significantly enriched within a group of interesting genes when compared to a reference group. First we define an exact analytical expression for the expected number of false positives that allows us to calculate adjusted p-values to control the false discovery rate. Next, we demonstrate and discuss the capabilities of our approach using publicly available microarray data on cell-cycle regulated genes. Further, we analyze the robustness of our framework with respect to the exact gene group composition and compare the performance with earlier approaches. The software package GOSSIP implements our method and is made freely available at http://gossip.gene-groups.net/. PMID:16362912

Blüthgen, Nils; Brand, Karsten; Cajavec, Branka; Swat, Maciej; Herzel, Hanspeter; Beule, Dieter

2005-01-01

272

[Oxidase gene from sweetpotato].  

PubMed

Polyphenol oxidase is the enzyme responsible for enzymatic browning in sweetpotato that decreases the commercial value of sweetpotato products. Here we reported the cloning and characterization of a new cDNA encoding PPO from sweetpotato, designated as IbPPO (GeneBank accession number: AY822711). The full-length cDNA of IbPPO is 1984 bp with a 1767 bp open reading frame (ORF) encoding a 588 amino acid polypeptide with calculated molecular weight of 65.7 kDa and theoretical pI of 6.28. The coding sequence of IbPPO was also directly amplified from the genomic DNA of sweetpotato that demonstrated that IbPPO was an intron-free gene. The computational comparative analysis revealed that IbPPO showed homology to other PPOs of plant origin and contained a 50 amino acid plastidial transit peptides at its N-terminal and the two conserved CuA and CuB copper-binding motifs in the catalytic region of IbPPO. A highly conserved serine-rich motif was firstly found in the transit peptides of plant PPO enzymes. Then the homology-based structural modeling of IbPPO showed that IbPPO had the typical structure of PPO: the catalytic copper center was accommodated in a central four-helix bundle located in a hydrophobic pocket close to the surface. Finally, the results of the semi-quantitative RT-PCR analysis of IbPPO in different tissues demonstrated that IbPPO could express in all the organs of sweetpotato including: mature leaves, young leaves, the stems of mature leaves (petioles), the storage roots and the veins but at different levels. The highest-level expression of IbPPO was found in veins, followed by storage roots, young leaves and mature leaves; and the lowest-level expression of IbPPO was found in petioles. The present researches will facilitate the development of anti-brown sweetpotato by genetic engineering. PMID:17209428

Liao, Zhihua; Chen, Rong; Chen, Min; Yang, Yijian; Fu, Yufan; Zhang, Qitang; Lan, Xiaozhong

273

GenePRIMP: A GENE PRediction IMprovement Pipeline for Prokaryotic genomes  

SciTech Connect

We present 'gene prediction improvement pipeline' (GenePRIMP; http://geneprimp.jgi-psf.org/), a computational process that performs evidence-based evaluation of gene models in prokaryotic genomes and reports anomalies including inconsistent start sites, missed genes and split genes. We found that manual curation of gene models using the anomaly reports generated by GenePRIMP improved their quality, and demonstrate the applicability of GenePRIMP in improving finishing quality and comparing different genome-sequencing and annotation technologies.

Pati, Amrita; Ivanova, Natalia N.; Mikhailova, Natalia; Ovchinnikova, Galina; Hooper, Sean D.; Lykidis, Athanasios; Kyrpides, Nikos C.

2010-04-01

274

A Pilot Study of Gene/Gene and Gene/Environment Interactions in Alzheimer Disease  

PubMed Central

Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD. Methods: The effect of gene/gene and gene/environment interaction related to late onset Alzheimer Disease (LOAD) was investigated in 153 subjects with LOAD and 302 gender matched controls enrolled in the Personalized Medicine Research Project, a population-based bio-repository. Genetic risk factors examined included APOE, ACE, OLR1,and CYP46 genes, and environmental factors included smoking, total cholesterol, LDL, HDL, triglycerides, C-reactive protein, blood pressure, statin use, and body mass index. Results: The mean age of the cases was 78.2 years and the mean age of the controls was 87.2 years. APOE4 was significantly associated with LOAD (OR=3.55, 95%CL=1.70, 7.45). Cases were significantly more likely to have ever smoked cigarettes during their life (49.3% versus 38.4%, p=0.03). The highest recorded blood pressure and pulse pressure measurements were significantly higher in the controls than the cases (all P<0.005). Although not statistically significant in this pilot study, the relationship of the following factors was associated in opposite directions with LOAD based on the presence of an APOE4 allele: obesity at the age of 50, ACE, OLR1, and CYP46. Conclusions: These pilot data suggest that gene/gene and gene/environment interactions may be important in LOAD, with APOE, a known risk factor for LOAD, affecting the relationship of ACE and OLR1 to LOAD. Replication with a larger sample size and in other racial/ethnic groups is warranted and the allele and risk factor frequencies will assist in choosing an appropriate sample size for a definitive study.

Ghebranious, Nader; Mukesh, Bickol; Giampietro, Philip F.; Glurich, Ingrid; Mickel, Susan F.; Waring, Stephen C.; McCarty, Catherine A.

2011-01-01

275

Regulatable Gene Therapy for Prostate Cancer.  

National Technical Information Service (NTIS)

Regulable gene therapy represents a new strategy to control and amplify efficacy of therapeutic gene. By the research efforts during this first period, two new regulators for inducible therapeutic gene expression have been generated, and an adenoviral con...

X. Ye B. W. O'Malley

2003-01-01

276

Challenges of Translating Gene Expression Microarray Data ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... Low power under stringent multiple testing corrections ? Co-regulation of genes 12 Beyond Gene Lists: ... 14 Gene Expression Profile ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

277

New Batch of Alzheimer's Genes Discovered  

MedlinePLUS

... this page, please enable JavaScript. New Batch of Alzheimer's Genes Discovered Scientists say the finding could double ... Preidt Monday, October 28, 2013 Related MedlinePlus Pages Alzheimer's Disease Genes and Gene Therapy MONDAY, Oct. 28 ( ...

278

Genes and equality.  

PubMed

The way people think about equality as a value will influence how they think genetic interventions should be regulated. In this paper the author uses the taxonomy of equality put forth by Derek Parfit and applies this to the issue of genetic interventions. It is argued that telic egalitarianism is untenable and that deontic egalitarianism collapses into prioritarianism. The priority view maintains that it is morally more important to benefit the people who are worse off. Once this precision has been given to the concerns egalitarians have, a number of diverse issues must be considered before determining what the just regulation of genetic interventions would be. Consideration must be given to the current situation of the least advantaged, the fiscal realities behind genetic interventions, the budget constraints on other social programmes egalitarians believe should receive scarce public funds, and the interconnected nature of genetic information. These considerations might lead egalitarians to abandon what they take to be the obvious policy recommendations for them to endorse regarding the regulation of gene therapies and enhancements. PMID:15574450

Farrelly, C

2004-12-01

279

Genes and COPD  

PubMed Central

SYNOPSIS The marked variability in individual susceptibility to the detrimental effects of smoking on lung function and findings suggest a significant genetic contribution to COPD, which has been demonstrated in several studies. The only known genetic risk factor for COPD, severe alpha 1 antitrypsin (AAT) deficiency, explains only 1–2% of cases of this disease. Screening for severe AAT should be conducted in all cases of COPD. Intravenous augmentation therapy should be combined with currently recommended treatment modalities for COPD when treating patients with COPD due to severe AAT deficiency. There is considerable interest in identifying susceptibility genes for COPD unrelated to severe AAT deficiency, as this could greatly enhance current efforts to prevent, diagnose and treat this disease by yielding novel insights into its pathogenesis. Genome-wide association studies (GWAS) of COPD and its intermediate phenotypes (e.g., lung function measures) have identified novel susceptibility loci for COPD. Some of these susceptibility loci may also influence lung function in the general population (e.g., HHIP and FAM13A), while others may affect not only COPD but other diseases related to smoking behavior (e.g., CHRNA3/CHRNA5). Although much work remains to be done, recent advances and the implementation of novel approaches to study COPD genetics (e.g., sequencing) and epigenetics are promising, and could have a profound impact on COPD management.

Foreman, Marilyn; Campos, Michael; Celedon, Juan C.

2012-01-01

280

Genes to Cognition Online  

NSDL National Science Digital Library

The Dolan DNA Learning Center at Cold Spring Harbor, NY has created this fantastic website to explore neuroscience, and it is focused on cognitive disorders, cognitive processes, and research approaches.àThere are many activities on the site, and each is broken down into six categories of analysis, "Genes", "Biochemicals", "Cells", "Brain Anatomy", "Cognition", and "Environment".à Thus, clicking on "Bipolar Disorder" under the "Disorders" tab at the top of the page, will take the visitor to a "subway line" at the top of the page.à There are several "stops" on the line, and each allows the visitor to learn about the key areas of bipolar disorder research.à Scrolling over the stops opens up a small window with a blurb about the content to view.à The blurb also shows whether the content is a video, an application, animation, etc.à Visitors wishing to see all the research available, should click on the network map, which is the screen behind the smaller "subway line" page.à The "Teacher Feature", under the "Targeted Content" tab, and next to the small model of the brain, offers lessons on such topics as autism, memory, and ethical decision-making.à "Teacher Pages," "Student Worksheets", and "Test Items" are offered in PDF form.

2009-12-18

281

Genes-R-Us  

NSDL National Science Digital Library

Genetics and genetic counseling--- How can the modern student relate to the classic principles of genetics? How about forming a genetic counseling agency with your students and "serve" the entire senior class during their "marriage project" in senior health? Genetic counseling can introduce students to basic genetics, an important interface of the biological sciences and the human condition. Many high schools throughout the U.S. have "marriage" or family living programs in which students are randomly paired early in the school year. They work to plan a wedding, a household budget that includes rent, car bills, food bills, and so on, including a future family. It is this future family that attracted my attention a few years back. The students were randomly given a baby to care for (the baby was either an uncooked egg, or a five pound sack of flour.) This is a perfect time to introduce human genetics to the soon-to-be parents. Hence, GENES-R-US !

Richard Benz (Wickliffe High School REV)

1994-07-30

282

Environment, genes, and cancer  

SciTech Connect

In January, comedian George Burns turned 100 years old. In recent appearances in the media, he still seems sharp as a tack, and is still seen smoking his trademark cigars. Others of us, however, were never very funny, and would die of cancer at age 60 if we continuously smoked cigars or cigarettes. Burns presents a common but perplexing paradox; some people are able to tolerate at least moderate exposure to toxins such as cigarette smoke with little adverse affect, while others develop cancer, emphysema, or heart disease. New studies support the idea that there is an interaction between genes and the environment, and that this interaction may be an important determinant of cancer risk. To understand such risks, it is essential to look at both an individual`s genetic makeup and environmental exposures. Such studies require the collaboration of molecular epidemiologists and molecular biologists. At the NIEHS, Jack A. Taylor, a lead clinical investigator in the Epidemiology Branch, and Douglas A. Bell, an investigator with the Genetic Risk Group of the Laboratory of Biochemical Risk Analysis, have worked together and with other scientists to uncover new information in this area.

Manuel, J.

1996-03-01

283

Melanoma-restricted genes  

PubMed Central

Human metastatic cutaneous melanoma has gained a well deserved reputation for its immune responsiveness. The reason(s) remain(s) unknown. We attempted previously to characterize several variables that may affect the relationship between tumor and host immune cells but, taken one at the time, none yielded a convincing explanation. With explorative purposes, high-throughput technology was applied here to portray transcriptional characteristics unique to metastatic cutaneous melanoma that may or may not be relevant to its immunogenic potential. Several functional signatures could be identified descriptive of immune or other biological functions. In addition, the transcriptional profile of metastatic melanoma was compared with that of primary renal cell cancers (RCC) identifying several genes co-coordinately expressed by the two tumor types. Since RCC is another immune responsive tumor, commonalities between RCC and melanoma may help untangle the enigma of their potential immune responsiveness. This purely descriptive study provides, therefore, a map for the investigation of metastatic melanoma in future clinical trials and at the same time may invite consideration of novel therapeutic targets.

Wang, Ena; Panelli, Monica C; Zavaglia, Katia; Mandruzzato, Susanna; Hu, Nan; Taylor, Phil R; Seliger, Barbara; Zanovello, Paola; Freedman, Ralph S; Marincola, Francesco M

2004-01-01

284

Capturing changes in gene expression dynamics by gene set differential coordination analysis  

Microsoft Academic Search

Analyzing gene expression data at the gene set level greatly improves feature extraction and data interpretation. Currently most efforts in gene set analysis are focused on differential expression analysis — finding gene sets whose genes show first-order relationship with the clinical outcome. However the regulation of the biological system is complex, and much of the change in gene expression dynamics

Tianwei Yu; Yun Bai

285

Developing particle-mediated gene-transfer technology for research into gene therapy of cancer  

Microsoft Academic Search

Gene therapy aims to (1) introduce specific genes into a host to replace defective ones (replacement therapy); (2) suppress expression of certain undesirable genes (antisense therapy); or (3) provide additional biological activities (supplement therapy). Naked DNA and viral or non-viral vectors containing candidate genes for human gene therapy are being actively pursued by researchers in molecular medicine. New gene transfer

Dennis McCabe; W SUN

1996-01-01

286

Duplicated homeobox genes in Xenopus.  

PubMed

Multiple kinds of clones and restriction fragment polymorphisms are frequently encountered when analyzing genes of the tetraploid frog Xenopus laevis. Two types of cDNA clone have been isolated for homeobox gene 2. Analysis of their corresponding genomic clones confirmed the existence of clearly distinct restriction maps; in addition the nearby presence of two additional homeoboxes suggests that this region is homologous to the Hox 2 gene complex of mammals. We asked whether the genetic polymorphism in Xenopus results from increased allelic differences due to tetraploidy or from having duplicated Hox 2 complexes. Using X. laevis/Xenopus borealis interspecies hybrids we show that the two types of X. laevis homeobox gene 2 transcripts result from two different genetic loci. They cannot represent alleles of the same gene because they do not segregate independently in the F1 hybrid progeny. Most other X. laevis homeobox genes studied so far are also found in two versions. Thus X. laevis seems to have two homeobox genes, both of which are expressed, for each one present in mammals or other vertebrates. PMID:2563247

Fritz, A F; Cho, K W; Wright, C V; Jegalian, B G; De Robertis, E M

1989-02-01

287

Improvements in gene therapy technologies.  

PubMed

We have combined hemagglutinating virus of Japan (HVJ; Sendai virus) with liposomes for efficient in vitro and in vivo fusion-mediated gene delivery. The HVJ-liposome was a highly efficient vehicle for the introduction of oligonucleotides into cells in vivo as well as for the transfer of genes <100 kbp without damaging cells. By coupling the Epstein-Barr (EB) virus replicon apparatus with HVJ-liposomes (virosomes), transgene expression was sustained in vitro and in vivo. When we added cationic lipids, the HVJ-cationic liposomes increased gene delivery 100 to 800 times in vitro compared with the conventional anionic virosomes and were also more useful for gene expression in restricted areas of organs and for gene therapy of disseminated cancers. We further discovered that the use of anionic virosomes with a virus-mimicking lipid composition (artificial viral envelope; AVE type) increased transfection efficiency approximately 10 fold in vivo, especially in the heart, liver, kidney, and muscle. Most animal organs were found to be suitable targets for the fusigenic virosomes, and numerous gene therapy strategies using this system were successful in animals. The combination of suicide gene therapy with radiation was very effective for killing hepatomas in a mouse model. Arteriosclerosis obliterans in animal models was cured by the transfer of hepatocyte growth factor. PMID:11690554

Kaneda, Y

2001-01-01

288

GeneID in Drosophila.  

PubMed

GeneID is a program to predict genes in anonymous genomic sequences designed with a hierarchical structure. In the first step, splice sites, and start and stop codons are predicted and scored along the sequence using position weight matrices (PWMs). In the second step, exons are built from the sites. Exons are scored as the sum of the scores of the defining sites, plus the log-likelihood ratio of a Markov model for coding DNA. In the last step, from the set of predicted exons, the gene structure is assembled, maximizing the sum of the scores of the assembled exons. In this paper we describe the obtention of PWMs for sites, and the Markov model of coding DNA in Drosophila melanogaster. We also compare other models of coding DNA with the Markov model. Finally, we present and discuss the results obtained when GeneID is used to predict genes in the Adh region. These results show that the accuracy of GeneID predictions compares currently with that of other existing tools but that GeneID is likely to be more efficient in terms of speed and memory usage. PMID:10779490

Parra, G; Blanco, E; Guigó, R

2000-04-01

289

Gene therapy: here to stay.  

PubMed Central

Advances in biotechnology have brought gene therapy to the forefront of medical research. The feasibility of gene transfer was first demonstrated in experiments using tumour viruses. This led to the development of a variety of viral and nonviral methods for the genetic modification of somatic cells. Two main approaches emerged: in-vivo modification, in which gene transfer vehicles are delivered directly into patients, and ex-vivo manipulation, in which cells from the patient are grown in culture, genetically modified and then returned to the patient. In 1990, shortly after the safety of retrovirus-mediated gene transfer was demonstrated in patients with malignant melanoma, the first clinical trial of gene therapy was initiated for adenosine deaminase deficiency. Since then, the number of clinical protocols initiated worldwide has increased exponentially. Although some clinical trials now in progress are concerned with relatively rare inborn errors of metabolism, most are concerned with more commonly encountered cancers and infectious diseases. Preliminary results suggest that by the turn of the century the dream of treating diseases by replacing or supplementing the products of defective genes or introducing novel therapeutic genes will become a reality.

Dube, I D; Cournoyer, D

1995-01-01

290

Mining gene-chip data  

NASA Astrophysics Data System (ADS)

DNA microarray (``gene chip'') technology has enabled a rapid accumulation of gene-expression data for model organisms such as S. cerevisiae and C. elegans, as well as for H. sapiens, raising the issue of how best to extract information about the gene regulatory networks of these organisms from this data. While basic clustering algorithms have been successful at finding genes that are coregulated for a small, specific set of experimental conditions, these algorithms are less effective when applied to large, varied data sets. One of the major challenges in analyzing the data is the diversity in both size and signal strength of the various transcriptional modules, i.e. sets of coregulated genes along with the sets of conditions for which the genes are strongly coregulated. One method that has proven successful at identifying large and/or strong modules is the Iterative Signature Algorithm (ISA) [1]. A modified version of the ISA algorithm, the Progressive Iterative Signature Algorithm (PISA), is also able to identify smaller, weaker modules by sequentially eliminating transcriptional modules as they are identified. Applying these algorithms to a large set of yeast gene expression data illustrates the strengths and weaknesses of each approach. [1] Bergmann, S., Ihmels, J., and Barkai, N., Phys. Rev. E 67, 031902 (2002).

Kloster, Morten

2005-03-01

291

Direct gene transfer to plants  

PubMed Central

Evidence for direct, gene-mediated stable genetic transformation of plant cells of Nicotiana tabacum is presented. A selectable hybrid gene comprising the protein coding region of the Tn5 aminoglycoside phosphotransferase type II gene under control of cauliflower mosaic virus gene VI expression signals was introduced into plant protoplasts as part of an Escherichia coli plasmid. The gene was stably integrated into plant genomic DNA and constitutively expressed in selected, drug resistant, protoplast-derived cell clones. The mode of integration of the foreign gene into the plant genome resembled that observed for DNA transfection of mammalian cells. Plants regenerated from transformed cell lines were phenotypically normal and fertile, and they maintained and expressed the foreign gene throughout the development of vegetative and generative organs. Microspores, grown in anther culture, developed into resistant and sensitive haploid plantlets. Genetic crossing analysis of one of the transformed plants revealed the presence of one dominant trait for kanamycin resistance segregating in a Mendelian fashion in the F1 generation. ImagesFig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.

Paszkowski, Jerzy; Shillito, Raymond D.; Saul, Michael; Mandak, Vaclav; Hohn, Thomas; Hohn, Barbara; Potrykus, Ingo

1984-01-01

292

Direct gene transfer to plants.  

PubMed

Evidence for direct, gene-mediated stable genetic transformation of plant cells of Nicotiana tabacum is presented. A selectable hybrid gene comprising the protein coding region of the Tn5 aminoglycoside phosphotransferase type II gene under control of cauliflower mosaic virus gene VI expression signals was introduced into plant protoplasts as part of an Escherichia coli plasmid. The gene was stably integrated into plant genomic DNA and constitutively expressed in selected, drug resistant, protoplast-derived cell clones. The mode of integration of the foreign gene into the plant genome resembled that observed for DNA transfection of mammalian cells. Plants regenerated from transformed cell lines were phenotypically normal and fertile, and they maintained and expressed the foreign gene throughout the development of vegetative and generative organs. Microspores, grown in anther culture, developed into resistant and sensitive haploid plantlets. Genetic crossing analysis of one of the transformed plants revealed the presence of one dominant trait for kanamycin resistance segregating in a Mendelian fashion in the F(1) generation. PMID:16453573

Paszkowski, J; Shillito, R D; Saul, M; Mandák, V; Hohn, T; Hohn, B; Potrykus, I

1984-12-01

293

The Role of Electrophoresis in Gene Electrotransfer  

Microsoft Academic Search

Gene electrotransfer is an established method for gene delivery which uses high-voltage pulses to increase the permeability\\u000a of a cell membrane and enables transfer of genes. Poor plasmid mobility in tissues is one of the major barriers for the successful\\u000a use of gene electrotransfer in gene therapy. Therefore, we analyzed the effect of electrophoresis on increasing gene electrotransfer\\u000a efficiency using

M. Pavlin; K. Flisar; M. Kandušer

2010-01-01

294

The Gene Resource Locator: gene locus maps for transcriptome analysis  

PubMed Central

Since the advent of the draft human genome sequence there has been growing interest in transcriptome analysis based on genomic data. The Gene Resource Locator (GRL) assembles gene maps that include information on gene-expression patterns, cis-elements in regulatory regions and alternatively spliced transcripts. The database was constructed using customized software, and currently contains 2.2 million alignments (exon–intron structures). The alignments have been annotated and integrated into a system that encompasses approximately 90 000 EST loci sharing common exons, 8091 alternatively spliced transcript groups, 10 801 expression-profile groups, 8066 candidate regulatory regions in full-length cDNAs, and 1 million SNP loci. We have used Flash technology to build a dynamic web viewer that facilitates browsing through the millions of alignments. All of the information is available through the World Wide Web at the Gene Resource Locator web site (http://grl.gi.k.u-tokyo.ac.jp).

Honkura, Toshihiko; Ogasawara, Jun; Yamada, Tomoyuki; Morishita, Shinichi

2002-01-01

295

Comparison of the Methyl Reductase Genes and Gene Products.  

National Technical Information Service (NTIS)

The DNA sequences encoding component C of methyl coenzyme M reductase (mcr genes) in Methanothermus fervidus, Methanobacterium thermoautotrophicum, ethanococcus vannielii, and Methanosarcina barkeri have been published. Comparisons of transcription initia...

C. F. Weil B. A. Sherf J. N. Reeve

1991-01-01

296

Gene-for-gene resistance in Striga-cowpea associations.  

PubMed

Seven races of Striga gesnerioides parasitic on cowpea, a major food and forage legume in sub-Saharan Africa, have been identified. Race-specific resistance of cowpea to Striga involves a coiled-coil nucleotide binding site leucine-rich repeat domain resistance protein encoded by the RSG3-301 gene. Knockdown of RSG3-301 expression by virus-induced gene silencing in the multirace-resistant cowpea cultivar B301 results in the failure of RSG3-301-silenced plants to mount a hypersensitive response and promotes parasite necrosis when challenged with Striga race SG3, whereas the resistance response to races SG2 and SG5 is unaltered. Our findings indicate that a gene-for-gene resistance mechanism is operating in these unique plant-plant associations. PMID:19713520

Li, Jianxiong; Timko, Michael P

2009-08-28

297

A Gene Recommender Algorithm to Identify Coexpressed Genes in C. elegans  

PubMed Central

One of the most important uses of whole-genome expression data is for the discovery of new genes with similar function to a given list of genes (the query) already known to have closely related function. We have developed an algorithm, called the gene recommender, that ranks genes according to how strongly they correlate with a set of query genes in those experiments for which the query genes are most strongly coregulated. We used the gene recommender to find other genes coexpressed with several sets of query genes, including genes known to function in the retinoblastoma complex. Genetic experiments confirmed that one gene (JC8.6) identified by the gene recommender acts with lin-35 Rb to regulate vulval cell fates, and that another gene (wrm-1) acts antagonistically. We find that the gene recommender returns lists of genes with better precision, for fixed levels of recall, than lists generated using the C. elegans expression topomap.

Owen, Art B.; Stuart, Josh; Mach, Kathy; Villeneuve, Anne M.; Kim, Stuart

2003-01-01

298

Irradiation and fusion gene transfer.  

PubMed

The fusion of human and rodent somatic cells is usually followed by the spontaneous loss of human chromosomes from the hybrid cells (1). The correlation between the presence of a human chromosome retained in the hybrid cell and the presence of a human phenotypic trait is the basis of human gene mapping by somatic cell genetics (2). This method for constructing physical maps has been central to human genetics and has resulted in the chromosomal assignment of several hundred genes (see ref. 3). Unfortunately, subchromosomal gene localization by this approach is limited by the paucity of suitable translocation and deletion chromosomes. PMID:21416347

Goodfellow, P N

1991-01-01

299

Grammatical evolution decision trees for detecting gene-gene interactions  

PubMed Central

Background A fundamental goal of human genetics is the discovery of polymorphisms that predict common, complex diseases. It is hypothesized that complex diseases are due to a myriad of factors including environmental exposures and complex genetic risk models, including gene-gene interactions. Such epistatic models present an important analytical challenge, requiring that methods perform not only statistical modeling, but also variable selection to generate testable genetic model hypotheses. This challenge is amplified by recent advances in genotyping technology, as the number of potential predictor variables is rapidly increasing. Methods Decision trees are a highly successful, easily interpretable data-mining method that are typically optimized with a hierarchical model building approach, which limits their potential to identify interacting effects. To overcome this limitation, we utilize evolutionary computation, specifically grammatical evolution, to build decision trees to detect and model gene-gene interactions. In the current study, we introduce the Grammatical Evolution Decision Trees (GEDT) method and software and evaluate this approach on simulated data representing gene-gene interaction models of a range of effect sizes. We compare the performance of the method to a traditional decision tree algorithm and a random search approach and demonstrate the improved performance of the method to detect purely epistatic interactions. Results The results of our simulations demonstrate that GEDT has high power to detect even very moderate genetic risk models. GEDT has high power to detect interactions with and without main effects. Conclusions GEDT, while still in its initial stages of development, is a promising new approach for identifying gene-gene interactions in genetic association studies.

2010-01-01

300

Auxin-responsive gene expression: genes, promoters and regulatory factors  

Microsoft Academic Search

A molecular approach to investigate auxin signaling in plants has led to the identification of several classes of early\\/primary auxin response genes. Within the promoters of these genes, cis elements that confer auxin respon- siveness (referred to as auxin-response elements or AuxREs) have been defined, and a family of trans-acting transcription factors (auxin-response factors or ARFs) that bind with specificity

Gretchen Hagen; Tom Guilfoyle

2002-01-01

301

Mutagenesis of diploid mammalian genes by gene entrapment  

Microsoft Academic Search

The present study describes a genome-wide method for biallelic mutagenesis in mammalian cells. Novel poly(A) gene trap vectors, which contain features for direct cloning vector-cell fusion transcripts and for post-entrapment genome engineering, were used to generate a library of 979 mutant ES cells. The entrapment mutations generally disrupted gene expression and were readily transmitted through the germline, establishing the library

Qing Lin; Sarah L. Donahue; Tracy Moore-Jarrett; Shang Cao; Anna B. Osipovich; H. E. Ruley

2006-01-01

302

Gene-for-Gene Resistance in Striga-Cowpea Associations  

Microsoft Academic Search

Seven races of Striga gesnerioides parasitic on cowpea, a major food and forage legume in sub-Saharan Africa, have been identified. Race-specific resistance of cowpea to Striga involves a coiled-coil nucleotide binding site leucine-rich repeat domain resistance protein encoded by the RSG3-301 gene. Knockdown of RSG3-301 expression by virus-induced gene silencing in the multirace-resistant cowpea cultivar B301 results in the failure

Jianxiong Li; Michael P. Timko

2009-01-01

303

The melanocortin-1-receptor gene is the major freckle gene  

Microsoft Academic Search

strict definitions. The entire coding sequence of the MC1R gene was analyzed by single-strand conform- ation polymorphism analysis followed by sequence analyses. Carriers of one or two MC1R gene variants had a 3- and 11-fold increased risk of developing ephelides, respectively (both P < 0.0001), whereas the risk of developing severe solar lentigines was increased 1.5- and 2-fold (P =

Maarten Bastiaens; Nelleke Gruis; Wilma Bergman; Rudi Westendorp; Bert-Jan Vermeer; Jan-Nico Bouwes Bavinck

2001-01-01

304

Identifying genes of gene regulatory networks using formal concept analysis.  

PubMed

In order to understand the behavior of a gene regulatory network, it is essential to know the genes that belong to it. Identifying the correct members (e.g., in order to build a model) is a difficult task even for small subnetworks. Usually only few members of a network are known and one needs to guess the missing members based on experience or informed speculation. It is beneficial if one can additionally rely on experimental data to support this guess. In this work we present a new method based on formal concept analysis to detect unknown members of a gene regulatory network from gene expression time series data. We show that formal concept analysis is able to find a list of candidate genes for inclusion into a partially known basic network. This list can then be reduced by a statistical analysis so that the resulting genes interact strongly with the basic network and therefore should be included when modeling the network. The method has been applied to the DNA repair system of Mycobacterium tuberculosis. In this application, our method produces comparable results to an already existing method of component selection while it is applicable to a broader range of problems. PMID:18312149

Gebert, Jutta; Motameny, Susanne; Faigle, Ulrich; Forst, Christian V; Schrader, Rainer

2008-03-01

305

Gene discovery and gene function assignment in filamentous fungi  

PubMed Central

Filamentous fungi are a large group of diverse and economically important microorganisms. Large-scale gene disruption strategies developed in budding yeast are not applicable to these organisms because of their larger genomes and lower rate of targeted integration (TI) during transformation. We developed transposon-arrayed gene knockouts (TAGKO) to discover genes and simultaneously create gene disruption cassettes for subsequent transformation and mutant analysis. Transposons carrying a bacterial and fungal drug resistance marker are used to mutagenize individual cosmids or entire libraries in vitro. Cosmids are annotated by DNA sequence analysis at the transposon insertion sites, and cosmid inserts are liberated to direct insertional mutagenesis events in the genome. Based on saturation analysis of a cosmid insert and insertions in a fungal cosmid library, we show that TAGKO can be used to rapidly identify and mutate genes. We further show that insertions can create alterations in gene expression, and we have used this approach to investigate an amino acid oxidation pathway in two important fungal phytopathogens.

Hamer, Lisbeth; Adachi, Kiichi; Montenegro-Chamorro, Maria V.; Tanzer, Matthew M.; Mahanty, Sanjoy K.; Lo, Clive; Tarpey, Rex W.; Skalchunes, Amy R.; Heiniger, Ryan W.; Frank, Sheryl A.; Darveaux, Blaise A.; Lampe, David J.; Slater, Ted M.; Ramamurthy, Lakshman; DeZwaan, Todd M.; Nelson, Grant H.; Shuster, Jeffrey R.; Woessner, Jeffrey; Hamer, John E.

2001-01-01

306

Candidate genes for panhypopituitarism identified by gene expression profiling  

PubMed Central

Mutations in the transcription factors PROP1 and PIT1 (POU1F1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. The dysmorphology of developing Prop1 mutant pituitaries readily distinguishes them from those of Pit1 mutants and normal mice. This and other features suggest that Prop1 controls the expression of genes besides Pit1 that are important for pituitary cell migration, survival, and differentiation. To identify genes involved in these processes we used microarray analysis of gene expression to compare pituitary RNA from newborn Prop1 and Pit1 mutants and wild-type littermates. Significant differences in gene expression were noted between each mutant and their normal littermates, as well as between Prop1 and Pit1 mutants. Otx2, a gene critical for normal eye and pituitary development in humans and mice, exhibited elevated expression specifically in Prop1 mutant pituitaries. We report the spatial and temporal regulation of Otx2 in normal mice and Prop1 mutants, and the results suggest Otx2 could influence pituitary development by affecting signaling from the ventral diencephalon and regulation of gene expression in Rathke's pouch. The discovery that Otx2 expression is affected by Prop1 deficiency provides support for our hypothesis that identifying molecular differences in mutants will contribute to understanding the molecular mechanisms that control pituitary organogenesis and lead to human pituitary disease.

Mortensen, Amanda H.; MacDonald, James W.; Ghosh, Debashis

2011-01-01

307

Singapore's designer genes.  

PubMed

The overwhelming success of the Singapore government's "Stop at Two" policy, limiting families to 2 children, turned a 1970s fear of overcrowding into a 1980s fear of surplus capacity, underachievement, and economic stagnation. To cope with the 1st signs of population decline, policy makers ironically have begun to advocate a selective undoing of previous population controls. An examination of 1983 fertility levels led to 3 startling conclusions: 1) many couples were not even maintaining replacement level fertility; 2) Chinese Singaporeans, 77% of the population, had a fertility rate of 1.5, the lowest of all; and 3) Malaysian and Indian fertility hovered between 1.9 and 2.1 during the late 1970s. Most of Singapore's miraculous economic development during the past 20 years has been the result of 1 carefully cultivated resource--a highly educated labor force. In 1983, 63% of graduate men married non-graduate women; many well-educated women do not marry and are thus not represented in the next generation. Prime Minister Lee invoked the practice of polygamy to dramatize the continued severity of the population problem. Since 1983, the Singaporean government has promoted a 2-tiered policy to encourage "graduate" marriages and "graduate" offspring. The Graduate Mother policy (unofficially known as the Designer Gene policy) offers a weighty package of incentives for educated mothers to have more children and for uneducated mothers to have fewer. But despite all the perks offered to new groups, the government is primarily concerned with the drop in fertility among Chinese Singaporeans, especially the educated Chinese. PMID:12341238

Cutler, B

1987-08-01

308

Prospects for Human Gene Therapy.  

National Technical Information Service (NTIS)

In this taped lecture Dr. Anderson reviews the currently most promising means for using gene therapy in managing various disease states. He outlines a technique by which genetically modified calls can be used in a specific cancer chemotherapy protocol, an...

1994-01-01

309

The Evolution of Gene Annotation  

PubMed Central

Complete and accurate annotation of gene function is an essential starting point for genome interpretation and a host of systems and synthetic biology endeavors. Detecting errors in existing annotation now has an important new tool.

Kasif, Simon; Steffen, Martin

2010-01-01

310

Epigenetics of ?-globin gene regulation  

PubMed Central

It is widely recognized that the next great challenge in the post-genomic period is to understand how the genome establishes the cell and tissue specific patterns of gene expression that underlie development. The ?-globin genes are among the most extensively studied tissue specific and developmentally regulated genes. The onset of erythropoiesis in precursor cells and the progressive expression of different members of the ?-globin family during development are accompanied by dramatic epigenetic changes in the locus. In this review, we will consider the relationship between histone and DNA modifications and the transcriptional activity of the ?-globin genes, the dynamic changes in epigenetic modifications observed during erythroid development, and the potential these changes hold as new targets for therapy in human disease.

Kiefer, Christine M.; Hou, Chunhui; Little, Jane; Dean, Ann

2008-01-01

311

Glucocorticoid Control of Gene Expression.  

National Technical Information Service (NTIS)

The concept that glucocorticoids function at the nuclear level to control expression of specific genes is discussed. The current views on the mechanism of this control are presented and relevant data from different experimental approaches are reported.

F. T. Kenney S. E. Lane K. L. Lee J. N. Ihle

1975-01-01

312

The mouse aquaporin-1 gene  

SciTech Connect

Members of the aquaporin family of molecular water transporters are expressed in diverse epithelia and in complex developmental patterns. Using a cDNA for mouse Aqp1, the structural gene was isolated and a restriction map was constructed. The 13-kb Aqp1 gene contains four exons with intronic boundaries corresponding to other known aquaporin genes. Transcription begins 67 bp 5{prime} to the translation initiation site and 20 bp 3{prime} from a TATAA consensus sequence. Aqp1 was localized by interspecific mouse backcross mapping to the central region of mouse chromosome 6 syntenic with human chromosome 7p14, where AQP1 had previously been localized. These studies have revealed marked structural similarities between the mouse Aqp1 and the human AQP1 genes, suggesting that further comparative studies may provide molecular insight into genetic regulatory features shared by both species. 21 refs., 3 figs.

Moon, C.; Preston, G.M.; Agre, P. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others

1995-11-20

313

Identification of Alcoholism Susceptibility Genes.  

National Technical Information Service (NTIS)

Genetic epidemiological analysis provides convincing data that a significant portion of the liability for developing alcoholism is inherited. The identity and mechanism by which genes contribute to inherited susceptibility to alcoholism are unknown. If ge...

K. C. Wilhelmsen

2002-01-01

314

Identification of Alcoholism Susceptibility Genes.  

National Technical Information Service (NTIS)

Genetic epidemiological analysis provides convincing data that a significant portion of the liability for developing alcoholism is inherited. The identity and mechanism by which genes contribute to inherited susceptibility to alcoholism are unknown. If ge...

K. C. Wilhelmsen

2003-01-01

315

Gene Cernan on Apollo 17  

NASA Video Gallery

Apollo 17 Commander Gene Cernan recalls fixing a lunar rover problem with duct tape during his December 1972 mission. Cernan's interview was part of the commemoration of NASA's 50th anniversary in 2008.

Jim Wilson

2010-06-30

316

Statecharts for Gene Network Modeling  

PubMed Central

State diagrams (stategraphs) are suitable for describing the behavior of dynamic systems. However, when they are used to model large and complex systems, determining the states and transitions among them can be overwhelming, due to their flat, unstratified structure. In this article, we present the use of statecharts as a novel way of modeling complex gene networks. Statecharts extend conventional state diagrams with features such as nested hierarchy, recursion, and concurrency. These features are commonly utilized in engineering for designing complex systems and can enable us to model complex gene networks in an efficient and systematic way. We modeled five key gene network motifs, simple regulation, autoregulation, feed-forward loop, single-input module, and dense overlapping regulon, using statecharts. Specifically, utilizing nested hierarchy and recursion, we were able to model a complex interlocked feed-forward loop network in a highly structured way, demonstrating the potential of our approach for modeling large and complex gene networks.

Shin, Yong-Jun; Nourani, Mehrdad

2010-01-01

317

Thymidylate Synthase Gene and Metastasis.  

National Technical Information Service (NTIS)

Thymidylate synthase (TYMS) gene amplification was observed in 23% of 31 5-FU resistant liver metastases, while no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplifica...

C. Lengauer K. W. Kinzler L. Diaz T. L. Wang V. Velculescu

2004-01-01

318

How eukaryotic genes are transcribed  

PubMed Central

Summary Regulation of eukaryotic gene expression is far more complex than one might have imagined thirty years ago. However, progress towards understanding gene regulatory mechanisms has been rapid and comprehensive, which has made the integration of detailed observations into broadly connected concepts a challenge. This review attempts to integrate the following concepts: 1) a well-defined organization of nucleosomes and modification states at most genes, 2) regulatory networks of sequence-specific transcription factors, 3) chromatin remodeling coupled to promoter assembly of the general transcription factors and RNA polymerase II, and 4) phosphorylation states of RNA polymerase II coupled to chromatin modification states during transcription. The wealth of new insights arising from the tools of biochemistry, genomics, cell biology, and genetics is providing a remarkable view into the mechanics of gene regulation.

Venters, Bryan J.; Pugh, B. Franklin

2009-01-01

319

Gene modifiers in cystic fibrosis.  

PubMed

Studies of modifier genes in cystic fibrosis (CF) have often been performed in small or narrowly defined populations, leading to conflicting results. In this issue of the JCI, Dorfman et al. demonstrate in a large, population-based study that two previously studied modifier genes, coding for mannose-binding lectin 2 and TGF-beta1, influence pulmonary outcome in pediatric CF patients (see the related article beginning on page 1040). They further show gene-gene interaction between the two, underscoring the complexity of CF lung disease. Their findings provide further impetus to study these molecules and associated signaling pathways in CF. In addition, these findings argue strongly for collecting genotypes of known modifiers prospectively in CF clinical trials as well as in longitudinal studies of infants identified through newborn screening, where the full impact of such modifiers can be defined more precisely. PMID:18292812

Accurso, Frank J; Sontag, Marci K

2008-03-01

320

Genes governing premature ovarian failure  

Microsoft Academic Search

Premature ovarian failure (POF) is unexplained amenorrhoea (>6months), increased FSH (>20IU\\/l) and LH occurring before 40years. Several genes are reported as having significance in POF, including genes governing regulation of the hypothalamic–pituitary–ovarian axis, but their role in ovarian physiology is not known. Deletions or translocations in Xq arm have been found to be associated with POF, assuming presence of ovarian-related

Hridesh Dixit; Lakshmi Rao; Venkata Padmalatha; Turlapati Raseswari; Anil Kumar Kapu; Bineet Panda; Kanakavalli Murthy; Durgadutta Tosh; Pratibha Nallari; Mamata Deenadayal; Nalini Gupta; Baidyanath Chakrabarthy; Lalji Singh

2010-01-01

321

The insect SNMP gene family  

Microsoft Academic Search

SNMPs are membrane proteins observed to associate with chemosensory neurons in insects; in Drosophila melanogaster, SNMP1 has been shown to be essential for the detection of the pheromone cis-vaccenyl acetate (CVA). SNMPs are one of three insect gene clades related to the human fatty acid transporter CD36. We previously characterized the CD36 gene family in 4 insect Orders that effectively

Richard G. Vogt; Natalie E. Miller; Rachel Litvack; Richard A. Fandino; Jackson Sparks; Jon Staples; Robert Friedman; Joseph C. Dickens

2009-01-01

322

Predicting Gene Expression from Sequence  

Microsoft Academic Search

We describe a systematic genome-wide approach for learning the complex combinatorial code underlying gene expression. Our probabilistic approach identifies local DNA-sequence elements and the positional and combinatorial constraints that determine their context-dependent role in transcriptional regulation. The inferred regulatory rules correctly predict expression patterns for 73% of genes in Saccharomyces cerevisiae, utilizing microarray expression data and sequences in the 800

Michael A. Beer; Saeed Tavazoie

2004-01-01

323

The Ethics of Gene Patenting  

Microsoft Academic Search

Is it ethical to patent human genes and gene sequences? Like many questions about what is ethically permissible or impermissible,\\u000a this query has layers of complexity. These include fundamental questions about what should and should not be patentable from\\u000a an ethical perspective, as well as what is or is not patentable under existing patent laws. A second layer of legal

Ruth Macklin

324

Epilepsies with single gene inheritance.  

PubMed

Single gene disorders offer the best opportunity for identification of genetic linkage and of abnormal genes. Epilepsies with single gene inheritance include symptomatic epilepsies where there is associated diffuse brain dysfunction, and idiopathic epilepsies where seizures are the major neurological abnormality. There are over 200 single gene symptomatic epilepsies; most are rare. Gene identification has been achieved in a number of these conditions but these important advances have not yet led to a better understanding of epileptogenesis, because of the associated brain disease. Idiopathic single gene epilepsies include benign familial neonatal convulsions, where genetic linkage to chromosomes 20q and 8q has been found in different families, and benign familial infantile convulsions where linkage is presently unknown. Recently, four autosomal dominant partial epilepsies have been described. In autosomal dominant nocturnal frontal lobe epilepsy a genetic defect in the alpha 4 subunit of the nicotinic acetylcholine receptor was found in one family. This is the first genetic defect described in an idiopathic epilepsy. The other three syndromes are autosomal dominant partial epilepsy with variable foci, autosomal dominant rolandic epilepsy with speech dyspraxia, and familial temporal lobe epilepsy. In the latter condition, linkage to chromosome 10q has been reported in one family, but the genetic defect is unknown. It is likely that other idiopathic single gene epilepsies will be identified. Molecular genetic study of these disorders is likely to lead to discovery of other epilepsy genes. This will lead to an improved understanding of human epileptogenesis with implications for clinical diagnosis, genetic counselling, pharmacological therapy and possibly prevention of epilepsy. PMID:9071484

Berkovic, S F; Scheffer, I E

1997-01-01

325

Marker Genes in Farm Animals  

Microsoft Academic Search

Identification of mutations in genes responsible for traits of interest or in a locus marker for such genes will allow geneticists\\u000a to implement the Marker Assisted Selection (MAS) approach. The main advantages of using genetic criteria for selection is\\u000a that such data can be obtained early in life of animals (e.g.: at birth) and in each sex. When a locus

I. Parmentier; D. Portetelle; C. Bertozzi; V. Haezebroeck; M. Pirard; R. Renaville

326

Gene therapy for prostate cancer  

Microsoft Academic Search

Basic research continues to unravel the molecular complexity of normal and abnormal biologic processes. The development of\\u000a means to affect the expression level of genes that promote or contribute to cellular transformation, invasion, and metastasis\\u000a has spawned the concept of gene therapy. This relatively new field seeks to reverse or suspend the pathologic progression\\u000a of a variety of diseases including

Jeffrey R. Gingrich; Ravi D. Chauhan; Mitchell S. Steiner

2001-01-01

327

A Comeback for Gene Therapy  

NSDL National Science Digital Library

Cartier et al. report another major advanceâÂÂthe successful first clinical testing of an HIV-derived vector in hematopoietic stem cell (HSC)âÂÂbased gene therapy. The procedure was used to treat a severe neurodegenerative disease, X-linked adrenoleukodystrophy (ALD), and the results indicate stable expression of a therapeutic gene in a substantial fraction of patients' hematopoietic cells, as well as clinical benefits.

Luigi Naldini ("Vita Salute San Raffaele" University;)

2009-11-06

328

Gene mapping and cystic fibrosis.  

PubMed

The recent molecular cloning of the gene responsible for cystic fibrosis illustrates the importance of human gene mapping to clinical medicine. Identification of a 3bp detection (delta F508) in the majority of cystic fibrosis patients will result in more accurate DNA-based diagnostic testing in cystic fibrosis families, as well as providing clues to the basic molecular defect and its relationship with alterations of anion transport in cystic fibrosis epithelial cells. PMID:2153339

Barker, P E

1990-01-01

329

Gene-culture shock waves  

NASA Astrophysics Data System (ADS)

A hyperbolic model is presented which generalises Aoki's parabolic system for the combined propagation of a mutant gene together with a cultural innovation. It is shown that this model allows for the propagation of a shock wave and the shock amplitude is calculated numerically. Particular attention is paid to the case where the shock moves into a region where the frequencies of the mutant gene and of the individuals adopting the innovation are zero.

Straughan, B.

2013-11-01

330

Network modelling of gene regulation  

Microsoft Academic Search

Gene regulatory network (GRN) modelling has gained increasing attention in the past decade. Many computational modelling techniques\\u000a have been proposed to facilitate the inference and analysis of GRN. However, there is often confusion about the aim of GRN\\u000a modelling, and how a gene network model can be fully utilised as a tool for systems biology. The aim of the present

Joshua W. K. Ho; Michael A. Charleston

2011-01-01

331

Regulation of insulin gene transcription  

Microsoft Academic Search

.   The mammalian insulin gene is exclusively expressed in the beta cells of the endocrine pancreas. Two decades of intensive\\u000a physiological and biochemical studies have led to the identification of regulatory sequence motifs along the insulin promoter\\u000a and to the isolation of transcription factors which interact to activate gene transcription. The majority of the islet-restricted\\u000a (BETA2, PDX-1, RIP3b1-Act\\/C1) and ubiquitous

D. Melloul; S. Marshak; E. Cerasi

2002-01-01

332

Arthritis gene therapy's first death  

PubMed Central

In July 2007 a subject died while enrolled in an arthritis gene therapy trial. The study was placed on clinical hold while the circumstances surrounding this tragedy were investigated. Early in December 2007 the Food and Drug Administration removed the clinical hold, allowing the study to resume with minor changes to the protocol. In the present article we collate the information we were able to obtain about this clinical trial and discuss it in the wider context of arthritis gene therapy.

Evans, Christopher H; Ghivizzani, Steven C; Robbins, Paul D

2008-01-01

333

Why genes overlap in viruses  

PubMed Central

The genomes of most virus species have overlapping genes—two or more proteins coded for by the same nucleotide sequence. Several explanations have been proposed for the evolution of this phenomenon, and we test these by comparing the amount of gene overlap in all known virus species. We conclude that gene overlap is unlikely to have evolved as a way of compressing the genome in response to the harmful effect of mutation because RNA viruses, despite having generally higher mutation rates, have less gene overlap on average than DNA viruses of comparable genome length. However, we do find a negative relationship between overlap proportion and genome length among viruses with icosahedral capsids, but not among those with other capsid types that we consider easier to enlarge in size. Our interpretation is that a physical constraint on genome length by the capsid has led to gene overlap evolving as a mechanism for producing more proteins from the same genome length. We consider that these patterns cannot be explained by other factors, namely the possible roles of overlap in transcription regulation, generating more divergent proteins and the relationship between gene length and genome length.

Chirico, Nicola; Vianelli, Alberto; Belshaw, Robert

2010-01-01

334

Gene Therapy in Heart Failure  

PubMed Central

With increasing knowledge of basic molecular mechanisms governing the development of heart failure (HF), the possibility of specifically targeting key pathological players is evolving. Technology allowing for efficient in vivo transduction of myocardial tissue with long-term expression of a transgene enables translation of basic mechanistic knowledge into potential gene therapy approaches. Gene therapy in HF is in its infancy clinically with the predominant amount of experience being from animal models. Nevertheless, this challenging and promising field is gaining momentum as recent preclinical studies in larger animals have been carried out and, importantly, there are 2 newly initiated phase I clinical trials for HF gene therapy. To put it simply, 2 parameters are needed for achieving success with HF gene therapy: (1) clearly identified detrimental/beneficial molecular targets; and (2) the means to manipulate these targets at a molecular level in a sufficient number of cardiac cells. However, several obstacles do exist on our way to efficient and safe gene transfer to human myocardium. Some of these obstacles are discussed in this review; however, it primarily focuses on the molecular target systems that have been subjected to intense investigation over the last decade in an attempt to make gene therapy for human HF a reality.

Vinge, Leif Erik; Raake, Philip W.; Koch, Walter J.

2008-01-01

335

Homologous gene replacement in Physarum  

SciTech Connect

The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1 in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.

Burland, T.G. [Univ. of Wisconsin, Madison, WI (United States); Pallotta, D. [Laval Univ., Quebec (Canada)

1995-01-01

336

Gene therapy in status epilepticus.  

PubMed

Gene therapy in human disease has expanded rapidly in recent years with the development of safer and more effective viral vectors, and presents a novel approach to the treatment of epilepsy. Studies in animals models have demonstrated that overexpression of inhibitory peptides can modify seizure threshold, prevent the development of epilepsy, and modify established epilepsy. More recently there has been a flurry of studies using optogenetics in which light-activated channels expressed in neurons can transiently change neuronal excitability on exposure to light, thereby enabling the development of closed loop systems to detect and stop seizure activity. The treatment of status epilepticus presents its own challenges. Because of both the delay in gene expression following transfection and also the necessity of using focal transfection, there are a limited number of situations in which gene therapy can be used in status epilepticus. One such condition is epilepsia partialis continua (EPC). We have used gene therapy in a model of EPC and have shown that we can "cure" the condition. Recent evidence suggesting that gene therapy targeting subcortical regions can modify generalized or more diffuse epilepsies, indicates that the range of situations in status epilepticus in which gene therapy could be used will expand. PMID:24001071

Walker, Matthew C; Schorge, Stephanie; Kullmann, Dimitri M; Wykes, Robert C; Heeroma, Joost H; Mantoan, Laura

2013-09-01

337

Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy  

Microsoft Academic Search

A main issue for further clinical progress of cancer gene therapy is to develop technologies for efficient and specific delivery of therapeutic genes to tumor cells. In this work, we describe a photochemical treatment that substantially improves gene delivery by adenovirus, one of the most efficient gene delivery vectors known. Transduction of two different cell lines was studied by microscopy,

Anders Høgset; Birgit Øvstebø Engesæter; Lina Prasmickaite; Kristian Berg; Øystein Fodstad; Gunhild Mari Mælandsmo

2002-01-01

338

Dual-Tagging Gene Trap of Novel Genes in Drosophila melanogaster  

Microsoft Academic Search

A gene-trap system is established for Drosophila. Unlike the conventional enhancer-trap system, the gene-trap system allows the recovery only of fly lines whose genes are inactivated by a P-element insertion, i.e., mutants. In the gene-trap system, the reporter gene expression reflects precisely the spatial and temporal expression pattern of the trapped gene. Flies in which gene trap occurred are identified

Tamas Lukacsovich; Zoltan Asztalos; Wakae Awano; Kotaro Baba; Shunzo Kondo; Suguri Niwa; Daisuke Yamamoto

339

Aphids acquired symbiotic genes via lateral gene transfer  

PubMed Central

Background Aphids possess bacteriocytes, which are cells specifically differentiated to harbour the obligate mutualist Buchnera aphidicola (?-Proteobacteria). Buchnera has lost many of the genes that appear to be essential for bacterial life. From the bacteriocyte of the pea aphid Acyrthosiphon pisum, we previously identified two clusters of expressed sequence tags that display similarity only to bacterial genes. Southern blot analysis demonstrated that they are encoded in the aphid genome. In this study, in order to assess the possibility of lateral gene transfer, we determined the full-length sequences of these transcripts, and performed detailed structural and phylogenetic analyses. We further examined their expression levels in the bacteriocyte using real-time quantitative RT-PCR. Results Sequence similarity searches demonstrated that these fully sequenced transcripts are significantly similar to the bacterial genes ldcA (product, LD-carboxypeptidase) and rlpA (product, rare lipoprotein A), respectively. Buchnera lacks these genes, whereas many other bacteria, including Escherichia coli, a close relative of Buchnera, possess both ldcA and rlpA. Molecular phylogenetic analysis clearly demonstrated that the aphid ldcA was derived from a rickettsial bacterium closely related to the extant Wolbachia spp. (?-Proteobacteria, Rickettsiales), which are intracellular symbionts of various lineages of arthropods. The evolutionary origin of rlpA was not fully resolved, but it was clearly demonstrated that its double-? ?-barrel domain is of bacterial origin. Real-time quantitative RT-PCR demonstrated that ldcA and rlpA are expressed 11.6 and 154-fold higher in the bacteriocyte than in the whole body, respectively. LdcA is an enzyme required for recycling murein (peptidoglycan), which is a component of the bacterial cell wall. As Buchnera possesses a cell wall composed of murein but lacks ldcA, a high level of expression of the aphid ldcA in the bacteriocyte may be essential to maintain Buchnera. Although the function of RlpA is not well known, conspicuous up-regulation of the aphid rlpA in the bacteriocyte implies that this gene is also essential for Buchnera. Conclusion In this study, we obtained several lines of evidence indicating that aphids acquired genes from bacteria via lateral gene transfer and that these genes are used to maintain the obligately mutualistic bacterium, Buchnera.

Nikoh, Naruo; Nakabachi, Atsushi

2009-01-01

340

Invasion of gene duplication through masking for maladaptive gene flow.  

PubMed

Gene duplication can increase an organism's ability to mask the effect of deleterious alleles present in the population, but this is typically a small effect when the source of the genetic variation is mutation. Migration can introduce orders of magnitude more deleterious alleles per generation and may therefore be an important force acting on the structure of genomes. Using formal analytical methods, we study the invasion of haplotypes containing two copies of the resident allele, assuming that a single-locus equilibrium is already established in a continent-island model of migration. Provided that the immigrant allele can be completely masked by multiple functional gene copies, a new duplication will deterministically spread so long as duplicate haplotypes are, on average, fitter than single-copy haplotypes. When fitness depends on the number of immigrant allele copies and their masking ability then the threshold for invasion depends on the rate of immigration and the rate of recombination between the gene copies. Results from several special cases, including formation of protein dimers and Dobzhansky-Muller incompatibilities, suggest that duplications can invade in a wide range of selection regimes. We hypothesize that duplication in response to gene flow may provide an explanation for the high levels of polymorphism in gene copy number observed in natural populations. PMID:22519789

Yanchukov, Alexey; Proulx, Stephen

2012-02-02

341

The biology of novel animal genes: Mouse APEX gene knockout  

SciTech Connect

This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The controlled breeding of novel genes into mice, including the gene knockout (KO), or conversely by adding back transgenes provide powerful genetic technologies that together suffice to determine in large part the biological role(s) of novel genes. Inbred mouse remains the best understood and most useful mammalian experimental system available for tackling the biology of novel genes. The major mammalian apurinic/apyrimidinic (AP) endonuclease (APE), is involved in a key step in the repair of spontaneous and induced AP sites in DNA. Efficient repair of these lesions is imperative to prevent the stable incorporation of mutations into the cellular genome which may lead to cell death or transformation. Loss or modulation of base excison repair activity in vivo may elevate the spontaneous mutation rate in cells, and may lead to a substantial increase in the incidence of cancer. Despite extensive biochemical analysis, however, the significance of these individual APE functions in vivo has not been elucidated. Mouse embryonic stem (ES) cells heterozygous for a deletion mutation in APE have been generated and whole animals containing the APE mutation have been derived from these ES cells. Animals homozygous for the APE null mutation die early in gestation, underscoring the biological significance of this DNA repair gene.

MacInnes, M.; Altherr, M.R.; Ludwig, D. [Los Alamos National Lab., NM (United States); Pedersen, R.; Mold, C. [Univ. of California, San Francisco, CA (United States)

1997-07-01

342

HIV Resistance Mapped by Gene Researchers  

MedlinePLUS

... Preidt Thursday, October 31, 2013 Related MedlinePlus Pages Genes and Gene Therapy HIV/AIDS THURSDAY, Oct. 31 (HealthDay News) -- Researchers ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy HIV/AIDS Recent Health News Page last updated ...

343

RNA Interference and Antisense Mediated Gene Silencing  

Microsoft Academic Search

Gene silencing by RNA interference (RNAi) and by antisense RNA are powerful tools to interfere with the expression of eukryotic genes. Since the first description of RNAi in 1998, antisense-mediated gene silencing has been considered to have essentially the same mechanism as gene silencing by RNAi. However, while substantial effort has been made to dissect the RNAi pathway, the cellular

Markus Kuhlmann; Blaga Popova; Wolfgang Nellen

344

Prospects for Gene Therapy in Pediatric Neurosurgery  

Microsoft Academic Search

Gene therapy represents a powerful tool for both the study and potential treatment of pediatric neurological diseases. The majority of strategies for brain gene therapy have focused upon the use of modified viruses as vehicles for efficient delivery of genes into cells of the central nervous system. Retroviruses were originally the most popular vehicles for gene transfer outside the brain;

Michael G. Kaplitt; Borimir Darakchiev

1998-01-01

345

Modulation of Gene Expression Made Easy  

Microsoft Academic Search

A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example, overexpression was achieved by introducing an additional gene copy into a phage attachment site on

Christian Solem; Peter Ruhdal Jensen

2002-01-01

346

Think big – giant genes in bacteria  

Microsoft Academic Search

Long genes should be rare in archaea and eubacteria because of the demanding costs of time and resources for protein production. The search in 580 sequenced prokaryotic genomes, however, revealed 0.2% of all genes to be longer than 5 kb (absolute number: 3732 genes). Eighty giant bacterial genes of more than 20 kb in length were identified in 47 taxa

Oleg Reva; Burkhard Tümmler

2008-01-01

347

Comparative genomic analysis of prion genes  

Microsoft Academic Search

BACKGROUND: The homologues of human disease genes are expected to contribute to better understanding of physiological and pathogenic processes. We made use of the present availability of vertebrate genomic sequences, and we have conducted the most comprehensive comparative genomic analysis of the prion protein gene PRNP and its homologues, shadow of prion protein gene SPRN and doppel gene PRND, and

Marko Premzl; Vera Gamulin

2007-01-01

348

Markov process modelling of gene regulation  

Microsoft Academic Search

This paper discusses the mathematical modelling of gene regulation with emphasis on the bottom-up modelling of genetic componentry rather than the reverse-engineering of networks from gene expression data. Reflecting the stochastic nature of gene regulation, the chemical master equation is used as a tool to study Markovian models of networks of gene states between which probabilistic transitions occur. These states

Hilary S. Booth; Conrad J. Burden; Markus Hegland; Lucia Santoso

349

Recombination signature of germline immunoglobulin variable genes  

Microsoft Academic Search

In human and mouse, the germline contains a tandem array of highly homologous variable (V) gene elements which encode part of the antigen-binding region of the antibody protein. During evolution this array apparently arose by gene duplication followed by diversification of duplicated genes via point mutation and recombination. Analysis of germline V gene sequences using a novel algorithm shows that

Georg F Weiller; Harald S Rothenfluh; Paula Zylstra; Lynn M Gay; Holger Averdunk; Edward J Steele; Robert V Blanden

1998-01-01

350

Gene therapy: theoretical and bioethical concepts  

Microsoft Academic Search

Gene therapy holds great promise. Somatic gene therapy has the potential to treat a wide range of disorders, including inherited conditions, cancers, and infectious diseases. Early progress has already been made in the treatment of a range of disorders. Ethical issues surrounding somatic gene therapy are primarily those concerned with safety. Germline gene therapy is theoretically possible but raises serious

Kevin R Smith

2003-01-01

351

Environmentally Induced Gene Silencing in Breast Cancer.  

National Technical Information Service (NTIS)

The main goal of the study was to test the hypothesis that a reduction in gene expression could induce gene silencing (i.e. relatively stable loss of gene expression) in breast cells. Silencing of a variety of tumor suppressor genes plays a major role in ...

M. Turker

2008-01-01

352

Homeobox genes in normal and abnormal vasculogenesis  

Microsoft Academic Search

Homeobox containing genes are a family of transcription factors regulating normal development and controlling primary cellular processes (cell identity, cell division and differentiation) recently enriched by the discovery of their interaction with miRNAs and ncRNAs. Class I human homeobox genes (HOX genes) are characterized by a unique genomic network organization: four compact chromosomal loci where 39 sequence corresponding genes can

M. Cantile; G. Schiavo; L. Terracciano; C. Cillo

2008-01-01

353

Gene Therapy Progress and Prospects: Nonviral vectors  

Microsoft Academic Search

The success of gene therapy is largely dependent on the development of the gene delivery vector. Recently, gene transfection into target cells using naked DNA, which is a simple and safe approach, has been improved by combining several physical techniques, for example, electroporation, gene gun, ultrasound and hydrodynamic pressure. Chemical approaches have been utilized to improve the efficiency and cell

T Niidome; L Huang

2002-01-01

354

Cloned Human Cripto Gene and Applications Thereof.  

National Technical Information Service (NTIS)

'CRIPTO' is a new human gene which has never been previously described. The gene has been isolated, cloned and completely sequenced. The invention is related generally to the isolation and cloning of genes and obtaining products encoded by the gene. More ...

M. Persico D. Solomon

1990-01-01

355

Hox genes in hematopoiesis and leukemogenesis  

Microsoft Academic Search

Gene expression analyses, gene targeting experiments and retroviral overexpression studies in the murine bone marrow transplantation model have provided strong correlative evidence for the involvement of clustered Hox genes in normal hematopoiesis. The data strongly support the hypothesis that the role of Hox genes in normal hematopoiesis is primarily at the level of hematopoietic stem cell function. A large body

B Argiropoulos; R K Humphries

2007-01-01

356

Plant DNA viruses and gene silencing  

Microsoft Academic Search

Gene silencing is a multifaceted phenomenon leading to propagative down-regulation of gene expression. Gene silencing, first observed in plants containing transgenes, can operate both at the transcriptional and post-transcriptional levels. Silencing effects can be triggered by nuclear transgenes and by cytoplasmic RNA viruses, and it can be propagated between these elements and endogenous plant genes that share sequence homology. Although

Simon N. Covey; Nadia S. Al-Kaff

2000-01-01

357

Expression of Bacterial Genes in Plant Cells  

Microsoft Academic Search

Chimeric bacterial genes conferring resistance to aminoglycoside antibiotics have been inserted into the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid and introduced into plant cells by in vitro transformation techniques. The chimeric genes contain the nopaline synthase 5' and 3' regulatory regions joined to the genes for neomycin phosphotransferase type I or type II. The chimeric genes were cloned into an intermediate

Robert T. Fraley; Stephen G. Rogers; Robert B. Horsch; Patricia R. Sanders; Jeffery S. Flick; Steven P. Adams; Michael L. Bittner; Leslie A. Brand; Cynthia L. Fink; Joyce S. Fry; Gerald R. Galluppi; Sarah B. Goldberg; Nancy L. Hoffmann; Sherry C. Woo

1983-01-01

358

Gene Expression after Bacteriophage T7 Infection.  

National Technical Information Service (NTIS)

Bacteriophage T7 and its host, E. coli, have provided a simple system in which to analyze the organization and expression of a viral genome. T7 genes are clustered in three groups in the T7 DNA: early genes, genes involved in DNA metabolism, and genes inv...

F. W. Studier

1975-01-01

359

Design of gene circuits: lessons from bacteria  

Microsoft Academic Search

Researchers are now building synthetic circuits for controlling gene expression and considering practical applications for engineered gene circuits. What can we learn from nature about design principles for gene circuits? A large body of experimental data is now available to test some important theoretical predictions about how gene circuits could be organized, but the data also raise some intriguing new

William S. Hlavacek; Michael A. Savageau; Michael E. Wall

2004-01-01

360

The evolutionary dynamics of eukaryotic gene order  

Microsoft Academic Search

In eukaryotes, unlike in bacteria, gene order has typically been assumed to be random. However, the first statistically rigorous analyses of complete genomes, together with the availability of abundant gene-expression data, have forced a paradigm shift: in every complete eukaryotic genome that has been analysed so far, gene order is not random. It seems that genes that have similar and\\/or

Csaba Pál; Martin J. Lercher; Laurence D. Hurst

2004-01-01

361

Cancer gene therapy: an awkward adolescence  

Microsoft Academic Search

At the Eleventh International Conference on Gene Therapy of Cancer (December 12–14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely targets for gene therapy of cancer. These strategies, including viral and

Michael M Gottesman

2003-01-01

362

Gene Therapy for Restenosis Are We Ready?  

Microsoft Academic Search

The application of gene therapy techniques to the clinical problem of coronary restenosis has generated tremendous attention and enthusiasm. Use of gene transfer technology to prevent a common intractable illness would represent a watershed event for human gene therapy. However, the time is not yet right to initiate gene therapy trials for restenosis. The biology of restenosis is incompletely understood,

Mary Beth DeYoung; David A. Dichek

2010-01-01

363

A census of human cancer genes  

Microsoft Academic Search

A central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis ('cancer genes'). After two decades of searching, how many have been identified and how do they compare to the complete gene set that has been revealed by the human genome sequence? We have conducted a 'census' of cancer genes that indicates

P. Andrew Futreal; Lachlan Coin; Mhairi Marshall; Thomas Down; Timothy Hubbard; Richard Wooster; Nazneen Rahman; Michael R. Stratton

2004-01-01

364

Gene Network Landscape of the Ciliate Tetrahymena thermophila  

Microsoft Academic Search

BackgroundGenome-wide expression data of gene microarrays can be used to infer gene networks. At a cellular level, a gene network provides a picture of the modules in which genes are densely connected, and of the hub genes, which are highly connected with other genes. A gene network is useful to identify the genes involved in the same pathway, in a

Jie Xiong; Dongxia Yuan; Jeffrey S. Fillingham; Jyoti Garg; Xingyi Lu; Yue Chang; Yifan Liu; Chengjie Fu; Ronald E. Pearlman; Wei Miao; Arkady B. Khodursky

2011-01-01

365

Evolution of hemoglobin and its genes.  

PubMed

Insights into the evolution of hemoglobins and their genes are an abundant source of ideas regarding hemoglobin function and regulation of globin gene expression. This article presents the multiple genes and gene families encoding human globins, summarizes major events in the evolution of the hemoglobin gene clusters, and discusses how these studies provide insights into regulation of globin genes. Although the genes in and around the ?-like globin gene complex are relatively stable, the ?-like globin gene clusters are more dynamic, showing evidence of transposition to a new locus and frequent lineage-specific expansions and deletions. The cis-regulatory modules controlling levels and timing of gene expression are a mix of conserved and lineage-specific DNA, perhaps reflecting evolutionary constraint on core regulatory functions shared broadly in mammals and adaptive fine-tuning in different orders of mammals. PMID:23209182

Hardison, Ross C

2012-12-01

366

Novel Genes from Formation to Function  

PubMed Central

The study of the evolution of novel genes generally focuses on the formation of new coding sequences. However, equally important in the evolution of novel functional genes are the formation of regulatory regions that allow the expression of the genes and the effects of the new genes in the organism as well. Herein, we discuss the current knowledge on the evolution of novel functional genes, and we examine in more detail the youngest genes discovered. We examine the existing data on a very recent and rapidly evolving cluster of duplicated genes, the Sdic gene cluster. This cluster of genes is an excellent model for the evolution of novel genes, as it is very recent and may still be in the process of evolving.

Ponce, Rita; Martinsen, Lene; Vicente, Luis M.; Hartl, Daniel L.

2012-01-01

367

Characterization of the mammalian DNA polymerase gene(s) and enzyme(s). Annual progress report  

SciTech Connect

Two Genes for DNA polymerase delta were identified from the wild type Chinese hamster ovary cells. These genes were cloned via RT-PCR from mRNA prepared the Chinese hamster ovary cells using primers specific to conserved sequences of the DNA polymerase {delta} gene. The first gene encodes a PCNA dependent DNA polymerase {delta} gene whereas the second gene encodes a PCNA independent DNA polymerase {delta} gene. Methods were developed to clone these genes in expression vector and host systems. The role of the two genes in DNA replication and repair was determined.

Mishra, N.C.

1995-01-01

368

Population genomics of human gene expression  

Microsoft Academic Search

Genetic variation influences gene expression, and this variation in gene expression can be efficiently mapped to specific genomic regions and variants. Here we have used gene expression profiling of Epstein-Barr virus–transformed lymphoblastoid cell lines of all 270 individuals genotyped in the HapMap Consortium to elucidate the detailed features of genetic variation underlying gene expression variation. We find that gene expression

Barbara E Stranger; Alexandra C Nica; Matthew S Forrest; Antigone Dimas; Christine P Bird; Claude Beazley; Catherine E Ingle; Mark Dunning; Paul Flicek; Daphne Koller; Stephen Montgomery; Simon Tavare ´; Panos Deloukas; Emmanouil T Dermitzakis

2007-01-01

369

Activation of floral homeotic genes in arabidopsis  

SciTech Connect

The identity of floral organs in Arabidopsis thaliana is determined by homeotic genes, which are expressed in specific regions of the developing flower. The initial activation of homeotic genes is accomplished at least in part by the products of two earlier acting genes with overlapping functions. These are the floral meristem-identity genes LEAFY and APETALA1. The requirements of LEAFY and APETALA1 activity vary for different homeotic genes.

Weigel, D.; Meyerowitz, E.M. (California Institute of Technology, Pasadena, CA (United States))

1993-09-24

370

Gene Therapy for Celebral Arterial Diseases  

Microsoft Academic Search

Although there has been steady progress towards cardiovascular gene therapy in humans, gene therapy for cerebrovascular disorders\\u000a is still in its infancy. Several major steps, including gene transfer to cerebral arteries and alteration of gene expression,\\u000a have been taken. There are several promising targets for cerebrovascular gene therapy, such as prevention of cerebral vasospasm\\u000a after subarachnoid hemorrhage, stimulation of formation

Yoshimasa Watanabe; Donald D. Heistad

371

Gene Networks Viewed through Two Models  

Microsoft Academic Search

This paper presents our computational and measurement strategy for investigating gene networks from gene expression data using\\u000a state space model and dynamic Bayesian network model with nonparametric regression. These methods are applied to gene expression\\u000a data based on gene knockdowns and drug responses for generating large global maps of gene regulation which will light up the\\u000a geography where drug target

Satoru Miyano; Rui Yamaguchi; Yoshinori Tamada; Masao Nagasaki; Seiya Imoto

2009-01-01

372

The cps gene cluster of Salmonella strain LT2 includes a second mannose pathway: sequence of two genes and relationship to genes in the rfb gene cluster  

Microsoft Academic Search

We report the presence in Salmonella enterica strain LT2 (serovar thyphimurium) of duplicate genes for two steps in the synthesis of GDP-mannose. The previously known genes, rfbK (phosphomannomutase) and rfbM (mannose-l-phosphate guanyltransferase), are part of the gene cluster for the O antigen. The two new genes, cpsB and cpsG, respectively, are thought to be part of the gene cluster for

Gordon Stevenson; Sang Jun Lee; Lajwant K. Romana; Peter R. Reeves

1991-01-01

373

Homology-dependent Gene Silencing in Paramecium  

Microsoft Academic Search

Microinjection at high copy number of plasmids containing only the coding region of a gene into the Paramecium somatic macronucleus led to a marked reduction in the expression of the corresponding endogenous gene(s). The silencing effect, which is stably maintained throughout vegetative growth, has been observed for all Paramecium genes examined so far: a single-copy gene (ND7), as well as

Francoise Ruiz; Laurence Vayssie; Catherine Klotz; Linda Sperling; Luisa Madeddu

1998-01-01

374

Computational tools for prioritizing candidate genes: boosting disease gene discovery.  

PubMed

At different stages of any research project, molecular biologists need to choose - often somewhat arbitrarily, even after careful statistical data analysis - which genes or proteins to investigate further experimentally and which to leave out because of limited resources. Computational methods that integrate complex, heterogeneous data sets - such as expression data, sequence information, functional annotation and the biomedical literature - allow prioritizing genes for future study in a more informed way. Such methods can substantially increase the yield of downstream studies and are becoming invaluable to researchers. PMID:22751426

Moreau, Yves; Tranchevent, Léon-Charles

2012-07-03

375

Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes  

Microsoft Academic Search

Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then

Nicki Tiffin; Euan Adie; Frances Turner; Han G. Brunner; Marc A. van Driel; Martin Oti; Nuria Lopez-Bigas; Christos Ouzounis; Carolina Perez-Iratxeta; Miguel A. Andrade-Navarro; Adebowale Adeyemo; Mary Elizabeth Patti; Colin A. M. Semple; Winston Hide

2006-01-01

376

Tandem and segmental gene duplication and recombination in the evolution of plant disease resistance genes  

Microsoft Academic Search

NBS-LRR genes are the major class of disease resistance genes in flowering plants, and are arranged as single genes and as clustered loci. The evolution of these genes has been investigated in Arabidopsis thaliana by combining data on their genomic organisation and position in phylogenetic trees. Tandem and segmental duplications distribute and separate NBS-LRR genes in the genome. It is,

Dario Leister

2004-01-01

377

DNA SEQUENCE OF THE YEDK GENE WITHIN THE TABTOXIN BIOSYNTHETIC GENE CLUSTER OF PSEUDOMONAS SYRINGAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The predicted gene product of the P. syringae gene is similar to the yedK gene of Escherichia coli (accession:NP 288392) and the 'Gyfsy-2' prophage in Salmonella typhimiurium (accession: NP 460027). The gene also contains significant identity to similar gene in Pseudomonas syringae pv. pisi (accessi...

378

GOToolBox: functional analysis of gene datasets based on Gene Ontology  

Microsoft Academic Search

We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level

David Martin; Christine Brun; Elisabeth Remy; Pierre Mouren; Denis Thieffry; Bernard Jacq

2004-01-01

379

Ontogeny of erythroid gene expression.  

PubMed

Erythroid ontogeny is characterized by overlapping waves of primitive and definitive erythroid lineages that share many morphologic features during terminal maturation but have marked differences in cell size and globin expression. In the present study, we compared global gene expression in primitive, fetal definitive, and adult definitive erythroid cells at morphologically equivalent stages of maturation purified from embryonic, fetal, and adult mice. Surprisingly, most transcriptional complexity in erythroid precursors is already present by the proerythroblast stage. Transcript levels are markedly modulated during terminal erythroid maturation, but housekeeping genes are not preferentially lost. Although primitive and definitive erythroid lineages share a large set of nonhousekeeping genes, annotation of lineage-restricted genes shows that alternate gene usage occurs within shared functional categories, as exemplified by the selective expression of aquaporins 3 and 8 in primitive erythroblasts and aquaporins 1 and 9 in adult definitive erythroblasts. Consistent with the known functions of Aqp3 and Aqp8 as H2O2 transporters, primitive, but not definitive, erythroblasts preferentially accumulate reactive oxygen species after exogenous H2O2 exposure. We have created a user-friendly Web site (http://www.cbil.upenn.edu/ErythronDB) to make these global expression data readily accessible and amenable to complex search strategies by the scientific community. PMID:23243273

Kingsley, Paul D; Greenfest-Allen, Emily; Frame, Jenna M; Bushnell, Timothy P; Malik, Jeffrey; McGrath, Kathleen E; Stoeckert, Christian J; Palis, James

2012-12-12

380

Melatonin receptor genes in vertebrates.  

PubMed

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-05-27

381

Proneural genes in neocortical development.  

PubMed

Neurons, astrocytes and oligodendrocytes arise from CNS progenitor cells at defined times and locations during development, with transcription factors serving as key determinants of these different neural cell fates. An emerging theme is that the transcription factors that specify CNS cell fates function in a context-dependent manner, regulated by post-translational modifications and epigenetic alterations that partition the genome (and hence target genes) into active or silent domains. Here we profile the critical roles of the proneural genes, which encode basic-helix-loop-helix (bHLH) transcription factors, in specifying neural cell identities in the developing neocortex. In particular, we focus on the proneural genes Neurogenin 1 (Neurog1), Neurog2 and Achaete scute-like 1 (Ascl1), which are each expressed in a distinct fashion in the progenitor cell pools that give rise to all of the neuronal and glial cell types of the mature neocortex. Notably, while the basic functions of these proneural genes have been elucidated, it is becoming increasingly evident that tight regulatory controls dictate when, where and how they function. Current efforts to better understand how proneural gene function is regulated will not only improve our understanding of neocortical development, but are also critical to the future development of regenerative therapies for the treatment of neuronal degeneration or disease. PMID:23999125

Wilkinson, G; Dennis, D; Schuurmans, C

2013-08-30

382

Duplicated fie Genes in Maize  

PubMed Central

Two maize genes with predicted translational similarity to the Arabidopsis FIE (Fertilization-Independent Endosperm) protein, a repressor of endosperm development in the absence of fertilization, were cloned and analyzed. Genomic sequences of fie1 and fie2 show significant homology within coding regions but none within introns or 5? upstream. The fie1 gene is expressed exclusively in the endosperm of developing kernels starting at ?6 days after pollination. fie1 is an imprinted gene showing no detectable expression of the paternally derived fie1 allele during kernel development. Conversely, fie2 is expressed in the embryo sac before pollination. After pollination, its expression persists, predominantly in the embryo and at lower levels in the endosperm. The paternal fie2 allele is not expressed early in kernel development, but its transcription is activated at 5 days after pollination. fie2 is likely to be a functional ortholog of the Arabidopsis FIE gene, whereas fie1 has evolved a distinct function. The maize FIE2 and sorghum FIE proteins form a monophyletic group, sharing a closer relationship to each other than to the FIE1 protein, suggesting that maize fie genes originated from two different ancestral genomes.

Danilevskaya, Olga N.; Hermon, Pedro; Hantke, Sabine; Muszynski, Michael G.; Kollipara, Krishna; Ananiev, Evgueni V.

2003-01-01

383

Gene Therapy for Pituitary Tumors  

PubMed Central

Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas.

Seilicovich, Adriana; Pisera, Daniel; Sciascia, Sandra A.; Candolfi, Marianela; Puntel, Mariana; Xiong, Weidong; Jaita, Gabriela; Castro, Maria G.

2009-01-01

384

Melatonin Receptor Genes in Vertebrates  

PubMed Central

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

Li, Di Yan; Smith, David Glenn; Hardeland, Rudiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-01-01

385

Mining Virulence Genes Using Metagenomics  

PubMed Central

When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

Belda-Ferre, Pedro; Cabrera-Rubio, Raul; Moya, Andres; Mira, Alex

2011-01-01

386

GeneMANIA prediction server 2013 update.  

PubMed

GeneMANIA (http://www.genemania.org) is a flexible user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. GeneMANIA can also be used in a function prediction setting: given a query gene, GeneMANIA finds a small set of genes that are most likely to share function with that gene based on their interactions with it. Enriched Gene Ontology categories among this set can sometimes point to the function of the gene. Seven organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens, Rattus norvegicus and Saccharomyces cerevisiae), and hundreds of data sets have been collected from GEO, BioGRID, IRefIndex and I2D, as well as organism-specific functional genomics data sets. Users can customize their search by selecting specific data sets to query and by uploading their own data sets to analyze. PMID:23794635

Zuberi, Khalid; Franz, Max; Rodriguez, Harold; Montojo, Jason; Lopes, Christian Tannus; Bader, Gary D; Morris, Quaid

2013-07-01

387

Gene expression throughout a vertebrate's embryogenesis  

PubMed Central

Background Describing the patterns of gene expression during embryonic development has broadened our understanding of the processes and patterns that define morphogenesis. Yet gene expression patterns have not been described throughout vertebrate embryogenesis. This study presents statistical analyses of gene expression during all 40 developmental stages in the teleost Fundulus heteroclitus using four biological replicates per stage. Results Patterns of gene expression for 7,000 genes appear to be important as they recapitulate developmental timing. Among the 45% of genes with significant expression differences between pairs of temporally adjacent stages, significant differences in gene expression vary from as few as five to more than 660. Five adjacent stages have disproportionately more significant changes in gene expression (> 200 genes) relative to other stages: four to eight and eight to sixteen cell stages, onset of circulation, pre and post-hatch, and during complete yolk absorption. The fewest differences among adjacent stages occur during gastrulation. Yet, at stage 16, (pre-mid-gastrulation) the largest number of genes has peak expression. This stage has an over representation of genes in oxidative respiration and protein expression (ribosomes, translational genes and proteases). Unexpectedly, among all ribosomal genes, both strong positive and negative correlations occur. Similar correlated patterns of expression occur among all significant genes. Conclusions These data provide statistical support for the temporal dynamics of developmental gene expression during all stages of vertebrate development.

2011-01-01

388

Codon usage in plant genes.  

PubMed Central

We have examined codon bias in 207 plant gene sequences collected from Genbank and the literature. When this sample was further divided into 53 monocot and 154 dicot genes, the pattern of relative use of synonymous codons was shown to differ between these taxonomic groups, primarily in the use of G + C in the degenerate third base. Maize and soybean codon bias were examined separately and followed the monocot and dicot codon usage patterns respectively. Codon preference in ribulose 1,5 bisphosphate and chlorophyll a/b binding protein, two of the most abundant proteins in leaves was investigated. These highly expressed are more restricted in their codon usage than plant genes in general.

Murray, E E; Lotzer, J; Eberle, M

1989-01-01

389

Susceptibility genes in human epilepsy.  

PubMed

Major advances in the identification of genetic loci and genes that predispose individuals to epilepsy have been made in the last several years. Two main themes for human, idiopathic epilepsies are emerging; genetic, or locus heterogeneity is not uncommon, and the discovery that epilepsy susceptibility genes are voltage-gated and ligand-gated ion channels. Knowledge that more than a single genetic locus is responsible for a single seizure type, along with a wide spectrum of disease mutations among families will complicate clinical, diagnostic issues. Disease gene identification, such as the two potassium ion channels (KCNQ2 and KCNQ3) for the two forms of benign familial neonatal seizures (BFNC) and the alpha4 subunit of the nicotinic receptor for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), however, should yield significant advances in drug discoveries. Understanding the primary defect in inherited epilepsies provides for specific protein and pathway targets for potential drug intervention. PMID:10716662

Leppert, M F; Singh, N

1999-01-01

390

[Gene therapy for osteoarticular disorders].  

PubMed

Osteoarticular disorders are the major cause of disability in Europe and North America. It is estimated that rheumatoid arthritis affects 1 % of the population and that more than two third of people over age 55 develop osteoarthritis. Because there are no satisfactory treatments, gene therapy offers a new therapeutic approach. The delivery of cDNA encoding anti-arthritic proteins to articular cells has shown therapeutic efficacy in numerous animal models in vivo. Through the development and the experimental progresses that have been made for both rheumatoid arthritis and osteoarthritis, this review discusses the different gene therapy strategies available today and the safety issues with which they may be associated. Among the different vectors available today, adeno-associated virus seems the best candidate for a direct in vivo gene delivery approach for the treatment of joint disorders. PMID:17349293

Gouze, Jean-Noël; Evans, Christopher H; Ghivizzani, Steven C; Gouze, Elvire

2007-03-01

391

Magnetic Resonance Reporter Gene Imaging  

PubMed Central

Molecular imaging has undergone an explosive advancement in recent years, due to the tremendous research efforts made to understand and visualize biological processes. Molecular imaging by definition assesses cellular and molecular processes in living subjects, with the targets of following metabolic, genomic, and proteomic events. Furthermore, reporter gene imaging plays a central role in this field. Many different approaches have been used to visualize genetic events in living subjects, such as, optical, radionuclide, and magnetic resonance imaging. Compared with the other techniques, magnetic resonance (MR)-based reporter gene imaging has not occupied center stage, despite its superior three-dimensional depictions of anatomical details. In this article, the authors review the principles and applications of various types of MR reporter gene imaging technologies and discuss their advantages and disadvantages.

Lee, Sheen-Woo; Lee, Sang-Hoon; Biswal, Sandip

2012-01-01

392

Gene encoding plant asparagine synthetase  

DOEpatents

The identification and cloning of the gene(s) for plant asparagine synthetase (AS), an important enzyme involved in the formation of asparagine, a major nitrogen transport compound of higher plants is described. Expression vectors constructed with the AS coding sequence may be utilized to produce plant AS; to engineer herbicide resistant plants, salt/drought tolerant plants or pathogen resistant plants; as a dominant selectable marker; or to select for novel herbicides or compounds useful as agents that synchronize plant cells in culture. The promoter for plant AS, which directs high levels of gene expression and is induced in an organ specific manner and by darkness, is also described. The AS promoter may be used to direct the expression of heterologous coding sequences in appropriate hosts.

Coruzzi, Gloria M. (New York, NY); Tsai, Fong-Ying (New York, NY)

1993-10-26

393

Transients in chloroplast gene transcription  

SciTech Connect

Transcriptional regulation of chloroplast genes is demonstrated by Quantitative Polymerase Chain Reaction (qPCR). These genes encode apoproteins of the reaction centres of photosystem I and photosystem II. Their transcription is regulated by changes in wavelength of light selectively absorbed by photosystem I and photosystem II, and therefore by the redox state of an electron carrier located between the two photosystems. Chloroplast transcriptional redox regulation is shown to have greater amplitude, and the kinetics of transcriptional changes are more complex, than suggested by previous experiments using only DNA probes in Northern blot experiments. Redox effects on chloroplast transcription appear to be superimposed on an endogenous rhythm of mRNA abundance. The functional significance of these transients in chloroplast gene transcription is discussed.

Puthiyaveetil, Sujith [School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom); Allen, John F. [School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom)], E-mail: j.f.allen@qmul.ac.uk

2008-04-18

394

GeneSigDB: a manually curated database and resource for analysis of gene expression signatures  

PubMed Central

GeneSigDB (http://www.genesigdb.org or http://compbio.dfci.harvard.edu/genesigdb/) is a database of gene signatures that have been extracted and manually curated from the published literature. It provides a standardized resource of published prognostic, diagnostic and other gene signatures of cancer and related disease to the community so they can compare the predictive power of gene signatures or use these in gene set enrichment analysis. Since GeneSigDB release 1.0, we have expanded from 575 to 3515 gene signatures, which were collected and transcribed from 1604 published articles largely focused on gene expression in cancer, stem cells, immune cells, development and lung disease. We have made substantial upgrades to the GeneSigDB website to improve accessibility and usability, including adding a tag cloud browse function, facetted navigation and a ‘basket’ feature to store genes or gene signatures of interest. Users can analyze GeneSigDB gene signatures, or upload their own gene list, to identify gene signatures with significant gene overlap and results can be viewed on a dynamic editable heatmap that can be downloaded as a publication quality image. All data in GeneSigDB can be downloaded in numerous formats including .gmt file format for gene set enrichment analysis or as a R/Bioconductor data file. GeneSigDB is available from http://www.genesigdb.org.

Culhane, Aedin C.; Schroder, Markus S.; Sultana, Razvan; Picard, Shaita C.; Martinelli, Enzo N.; Kelly, Caroline; Haibe-Kains, Benjamin; Kapushesky, Misha; St Pierre, Anne-Alyssa; Flahive, William; Picard, Kermshlise C.; Gusenleitner, Daniel; Papenhausen, Gerald; O'Connor, Niall; Correll, Mick; Quackenbush, John

2012-01-01

395

Gene therapy for lung cancer.  

PubMed

The advances that have been made over the past decade in the field of gene transfer as well as in the fields of immunology and the molecular biology of tumorigenesis have brought to reality the possibility of using gene transfer as an anti-cancer treatment modality. The published results of clinical trials using this approach to date have been very limited, and a considerable amount of work still needs to be done in order to make this an effective treatment modality. However the developments that have occurred in the past several years indicate that this modality will become efficacious in the foreseeable future. PMID:10750725

Antonia, S J; Sotomayor, E

2000-03-01

396

Drought tolerance genes in rice.  

PubMed

Quantitative trait loci (QTLs) for drought tolerance (DT) can be readily identified in available databases and in this paper, these QTLs were summarized in the form of a consensus map. An in silico strategy was then deployed to mine for candidate genes associated with DT QTLs using rice dbEST and rice genome databases. DT QTLs on rice chromosomes 1, 2, 4, 8, and 9 were selected to test the method. The result showed candidate genes associated with DT could be readily identified. PMID:16552602

Zeng, Huazong; Zhong, Yang; Luo, Lijun

2006-03-22

397

Gene therapy in clinical medicine  

PubMed Central

Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. Interest in this therapeutic modality is based on the potential for treatment and cure of some of the most malignant and devastating diseases affecting humans. Over the next decade, the relevance of gene therapy to medical practices will increase and it will become important for physicians to understand the basic principles and strategies that underlie the therapeutic intervention. This report reviews the history, basic strategies, tools, and several current clinical paradigms for application.

Selkirk, S

2004-01-01

398

GENE THERAPY FOR VENTRICULAR TACHYARRHYTHMIAS  

PubMed Central

Cardiac arrest is the leading cause of death in the United States and other developed countries. Ventricular tachyarrhythmias are the most prominent cause of cardiac arrest, and patients with structural heart disease are at increased risk for these abnormal heart rhythms. Drug and device therapy have important limitations that make them inadequate to meet this challenge. We and others have proposed development of arrhythmia gene therapy as an alternative to current treatment methods. In this review, I discuss the basic mechanisms of ventricular arrhythmias and summarize the literature on the use of gene therapy for ventricular tachyarrhythmias.

Donahue, J. Kevin

2013-01-01

399

RNA interference: From gene silencing to gene-specific therapeutics  

Microsoft Academic Search

In the past 4 years, RNA interference (RNAi) has become widely used as an experimental tool to analyse the function of mammalian genes, both in vitro and in vivo. By harnessing an evolutionary conserved endogenous biological pathway, first identified in plants and lower organisms, double-stranded RNA (dsRNA) reagents are used to bind to and promote the degradation of target RNAs,

Ray K. M. Leung; Paul A. Whittaker

2005-01-01

400

Travelling the world of gene-gene interactions.  

PubMed

Over the last few years, main effect genetic association analysis has proven to be a successful tool to unravel genetic risk components to a variety of complex diseases. In the quest for disease susceptibility factors and the search for the 'missing heritability', supplementary and complementary efforts have been undertaken. These include the inclusion of several genetic inheritance assumptions in model development, the consideration of different sources of information, and the acknowledgement of disease underlying pathways of networks. The search for epistasis or gene-gene interaction effects on traits of interest is marked by an exponential growth, not only in terms of methodological development, but also in terms of practical applications, translation of statistical epistasis to biological epistasis and integration of omics information sources. The current popularity of the field, as well as its attraction to interdisciplinary teams, each making valuable contributions with sometimes rather unique viewpoints, renders it impossible to give an exhaustive review of to-date available approaches for epistasis screening. The purpose of this work is to give a perspective view on a selection of currently active analysis strategies and concerns in the context of epistasis detection, and to provide an eye to the future of gene-gene interaction analysis. PMID:21441561

Steen, Kristel Van

2011-03-26

401

Horizontal gene transfer of stress resistance genes through plasmid transport.  

PubMed

The horizontal gene transfer of plasmid-determined stress tolerance was achieved under lab conditions. Bacterial isolates, Enterobacter cloacae (DGE50) and Escherichia coli (DGE57) were used throughout the study. Samples were collected from contaminated marine water and soil to isolate bacterial strains having tolerance against heavy metals and antimicrobial agents. We have demonstrated plasmid transfer, from Amp(+)Cu(+)Zn(-) strain (DGE50) to Amp(-)Cu(-)Zn(+) strain (DGE57), producing Amp(+)Cu(+)Zn(+) transconjugants (DGE(TC50?57)) and Amp(+)Cu(-)Zn(+) transformants (DGE(TF50?57)). DGE57 did not carry any plasmid, therefore, it can be speculated that zinc tolerance gene in DGE57 is located on chromosome. DGE50 was found to carry three plasmids, out of which two were transferred through conjugation into DGE57, and only one was transferred through transformation. Plasmid transferred through transformation was one out of the two transferred through conjugation. Through the results of transformation it was revealed that the genes of copper and ampicillin tolerance in DGE50 were located on separate plasmids, since only ampicillin tolerance genes were transferred through transformation as a result of one plasmid transfer. By showing transfer of plasmids under lab conditions and monitoring retention of respective phenotype via conjugation and transformation, it is very well demonstrated how multiple stress tolerant strains are generated in nature. PMID:22805823

Shoeb, Erum; Badar, Uzma; Akhter, Jameela; Shams, Hina; Sultana, Maria; Ansari, Maqsood A

2011-09-29

402

A hybrid approach to gene ranking using gene relation networks derived from literature for the identification of disease gene markers.  

PubMed

For the identification of gene markers involved in diseases, microarray expression profiles have been widely used to prioritize genes. In this paper, we propose a novel approach to gene ranking that employs gene relation network derived from literature along with microarray expression scores to calculate ranking statistics of individual genes. In particular, the gene relation network is constructed from literature by applying syntactic analysis and co-occurrence method in a hybrid manner. For evaluation, the proposed method was tested with publicly available prostate cancer data. The result shows that our method is superior to other existing approaches. PMID:23155760

Shin, Miyoung; Lee, Hyungmin; Hong, Munpyo

2012-01-01

403

Role of gene order in developmental control of human gamma- and beta-globin gene expression.  

PubMed

To determine the effect of gene order on globin gene developmental regulation, we produced transgenic mice containing two tandemly arranged gamma- or beta-globin or gamma beta- and beta gamma-globin genes linked to a 2.5-kb cassette containing sequences of the locus control region (LCR). Analysis of constructs containing two identical gamma or beta genes assessed the effect of gene order on globin gene expression, while analysis of constructs containing tandemly arranged gamma and beta genes assessed any additional effects of the trans-acting environment. When two gamma genes were tandemly linked to the LCR, expression from the proximal gamma gene was three- to fourfold higher than expression from the distal gamma gene, and the ratio of proximal to distal gene expression remained unchanged throughout development. Similarly, when two beta genes were tandemly linked to the LCR, the proximal beta gene was predominantly expressed throughout development. These results indicate that proximity to LCR increases gene expression, perhaps by influencing the frequency of interaction between the LCR and globin gene promoters. An arrangement where the gamma gene was proximal and the beta gene distal to the LCR resulted in predominant gamma-gene expression in the embryo. When the order was reversed and the gamma gene was placed distally to the LCR, gamma-gene expression in the embryo was still up to threefold higher than expression of the LCR-proximal beta gene. These findings suggest that the embryonic trans-acting environment interacts preferentially with the gamma genes irrespective of their order or proximity to the LCR. We conclude that promoter competition rather than gene order plays the major role in globin gene switching. PMID:8336720

Peterson, K R; Stamatoyannopoulos, G

1993-08-01

404

A literature network of human genes for high-throughput analysis of gene expression  

Microsoft Academic Search

We have carried out automated extraction of explicit and implicit biomedical knowledge from publicly available gene and text databases to create a gene-to-gene co-citation network for 13,712 named human genes by automated analysis of titles and abstracts in over 10 million MEDLINE records. The associations between genes have been annotated by linking genes to terms from the medical subject heading

Tor-Kristian Jenssen; Astrid Lægreid; Jan Komorowski; Eivind Hovig

2001-01-01

405

Development and Evaluation of Functional Gene Arrays for Detection of Selected Genes in the Environment  

Microsoft Academic Search

To determine the potential of DNA array technology for assessing functional gene diversity and distribution, a prototype microarray was constructed with genes involved in nitrogen cycling: nitrite reductase (nirS and nirK) genes, ammonia mono-oxygenase (amoA) genes, and methane mono-oxygenase (pmoA) genes from pure cultures and those cloned from marine sediments. In experiments using glass slide microarrays, genes possessing less than

LIYOU WU; DOROTHEA K. THOMPSON; GUANGSHAN LI; RICHARD A. HURT; JAMES M. TIEDJE; JIZHONG ZHOU

2001-01-01

406

Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism.  

PubMed

Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied to look for the genes associated with autism and their possible interactions. Single-nucleotide polymorphisms (SNPs) were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35.1; GABRR1 and GABRR2 on 6q15; and GABRA5, GABRB3, and GABRG3 on 15q12. Intronic and/or silent mutation SNPs within each gene were analyzed in 470 white families with autism. Initially, SNPs were used in a family-based study for allelic association analysis--with the pedigree disequilibrium test and the family-based association test--and for genotypic and haplotypic association analysis--with the genotype-pedigree disequilibrium test (geno-PDT), the association in the presence of linkage (APL) test, and the haplotype family-based association test. Next, with the use of five refined independent marker sets, extended multifactor-dimensionality reduction (EMDR) analysis was employed to identify the models with locus joint effects, and interaction was further verified by conditional logistic regression. Significant allelic association was found for markers RS1912960 (in GABRA4; P = .01) and HCV9866022 (in GABRR2; P = .04). The geno-PDT found significant genotypic association for HCV8262334 (in GABRA2), RS1912960 and RS2280073 (in GABRA4), and RS2617503 and RS12187676 (in GABRB2). Consistent with the allelic and genotypic association results, EMDR confirmed the main effect at RS1912960 (in GABRA4). EMDR also identified a significant two-locus gene-gene effect model involving RS1912960 in GABRA4 and RS2351299 in GABRB1. Further support for this two-locus model came from both the multilocus geno-PDT and the APL test, which indicated a common genotype and haplotype combination positively associated with disease. Finally, these results were also consistent with the results from the conditional logistic regression, which confirmed the interaction between GABRA4 and GABRB1 (odds ratio = 2.9 for interaction term; P = .002). Through the convergence of all analyses, we conclude that GABRA4 is involved in the etiology of autism and potentially increases autism risk through interaction with GABRB1. These results support the hypothesis that GABA receptor subunit genes are involved in autism, most likely via complex gene-gene interactions. PMID:16080114

Ma, D Q; Whitehead, P L; Menold, M M; Martin, E R; Ashley-Koch, A E; Mei, H; Ritchie, M D; Delong, G R; Abramson, R K; Wright, H H; Cuccaro, M L; Hussman, J P; Gilbert, J R; Pericak-Vance, M A

2005-07-15

407

Permutation and parametric bootstrap tests for gene--gene and gene--environment interactions  

PubMed Central

Summary Permutation tests are widely used in genomic research as a straightforward way to obtain reliable statistical inference without making strong distributional assumptions. However, in this paper we show that in genetic association studies it is not typically possible to construct exact permutation tests of gene-gene or gene-environment interaction hypotheses. We describe an alternative to the permutation approach in testing for interaction, a parametric bootstrap approach. Using simulations, we compare the finite-sample properties of a few often-used permutation tests and the parametric bootstrap. We consider interactions of an exposure with single and multiple polymorphisms. Finally, we address when permutation tests of interaction will be approximately valid in large samples for specific test statistics.

Buzkova, Petra; Lumley, Thomas; Rice, Kenneth

2010-01-01

408

Genes Contributing to the Development of Alcoholism  

PubMed Central

Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. However, identifying those genes and the specific variations involved is challenging. Researchers have used both case–control and family studies to identify genes related to alcoholism risk. In addition, different strategies such as candidate gene analyses and genome-wide association studies have been used. The strongest effects have been found for specific variants of genes that encode two enzymes involved in alcohol metabolism—alcohol dehydrogenase and aldehyde dehydrogenase. Accumulating evidence indicates that variations in numerous other genes have smaller but measurable effects.

Edenberg, Howard J.

2013-01-01

409

A gene sets approach for identifying prognostic gene signatures for outcome prediction  

PubMed Central

Background Gene expression profiling is a promising approach to better estimate patient prognosis; however, there are still unresolved problems, including little overlap among similarly developed gene sets and poor performance of a developed gene set in other datasets. Results We applied a gene sets approach to develop a prognostic gene set from multiple gene expression datasets. By analyzing 12 independent breast cancer gene expression datasets comprising 1,756 tissues with 2,411 pre-defined gene sets including gene ontology categories and pathways, we found many gene sets that were prognostic in most of the analyzed datasets. Those prognostic gene sets were related to biological processes such as cell cycle and proliferation and had additional prognostic values over conventional clinical parameters such as tumor grade, lymph node status, estrogen receptor (ER) status, and tumor size. We then estimated the prediction accuracy of each gene set by performing external validation using six large datasets and identified a gene set with an average prediction accuracy of 67.55%. Conclusion A gene sets approach is an effective method to develop prognostic gene sets to predict patient outcome and to understand the underlying biology of the developed gene set. Using the gene sets approach we identified many prognostic gene sets in breast cancer.

Kim, Seon-Young; Kim, Yong Sung

2008-01-01

410

Genes, Environment, and Human Behavior.  

ERIC Educational Resources Information Center

|This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

411

Genes and Syndromic Hearing Loss.  

ERIC Educational Resources Information Center

This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

Keats, Bronya J. B.

2002-01-01

412

Genes and premature ovarian failure  

Microsoft Academic Search

Premature ovarian failure (POF) is an heterogeneous syndrome. Among genetic causes, X monosomy as in Turner syndrome or X deletions and translocations are known to be responsible for POF. The genes involved in ovarian function, located on the X chromosome are still unknown. On the other hand, autosomal abnormalities have been identified in POF patients such as mutations of the

Sophie Christin-Maitre; Claudine Vasseur; Philippe Bouchard

1998-01-01

413

Making Your Own Gene Library.  

ERIC Educational Resources Information Center

|Presents an experiment aimed at constructing a genomic library that can be carried out over a week. Helps students learn concepts such as donor and vector DNAs, construction of recombinant DNA, host strain, and experiments in gene cloning more clearly. (PVD)|

Perez-Ortin, Jose E.; Li Del Olmo, Marcel; Matallana, Emilia; Tordera, Vicente

1997-01-01

414

Dock 3 Tumor Suppressor Gene.  

National Technical Information Service (NTIS)

The invention relates to a newly identified tumor suppressor gene, designated DOS (for Deleted in Osteosarcoma and alternatively referred to herein as DOCK 3) which has been cloned from human and mouse cells. The DOS nucleic acid and protein molecules and...

A. McClatchey C. Paulding D. Haber V. Yajnik

2002-01-01

415

Neurogenic genes and vertebrate neurogenesis  

Microsoft Academic Search

The neurogenic genes of the Delta-Notch signalling pathway mediate lateral inhibition - a mechanism that controls cell commitment in many tissues and serves in the developing nervous system to single out cells for a neural fate. Recent work has revealed the outlines of the signal transduction pathway from Notch to the nucleus, has clarified the mechanisms by which lateral inhibition

Julian Lewis

1996-01-01

416

Genes and Syndromic Hearing Loss.  

ERIC Educational Resources Information Center

|This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

Keats, Bronya J. B.

2002-01-01

417

Electroporation microchips for gene transfection  

Microsoft Academic Search

Electroporation (EP) microchips can increase gene transfection rate and cells survival rate. Electroporation is a kind of method in which DNA molecules can be delivered into cells by short electric pulses. Unlike the conventional electroporation device, the EP chips in this paper are loaded with a lower concentration of plasmids, and most cells will not be damaged or lysed by

Yu-Cheng Lin

2005-01-01

418

Horizontal gene transfer in chromalveolates  

Microsoft Academic Search

BACKGROUND: Horizontal gene transfer (HGT), the non-genealogical transfer of genetic material between different organisms, is considered a potentially important mechanism of genome evolution in eukaryotes. Using phylogenomic analyses of expressed sequence tag (EST) data generated from a clonal cell line of a free living dinoflagellate alga Karenia brevis, we investigated the impact of HGT on genome evolution in unicellular chromalveolate

Tetyana Nosenko; Debashish Bhattacharya

2007-01-01

419

Gene expression regulation in trypanosomatids.  

PubMed

Trypanosomatids are protozoan micro-organisms that cause serious health problems in humans and domestic animals. In addition to their medical relevance, these pathogens have novel biological structures and processes. From nuclear DNA transcription to mRNA translation, trypanosomes use unusual mechanisms to control gene expression. For example, transcription by RNAPII (RNA polymerase II) is polycistronic, and only a few transcription initiation sites have been identified so far. The sequences present in the polycistronic units code for proteins having unrelated functions, that is, not involved in a similar metabolic pathway. Owing to these biological constraints, these micro-organisms regulate gene expression mostly by post-transcriptional events. Consequently, the function of proteins that recognize RNA elements preferentially at the 3' UTR (untranslated region) of transcripts is central. It was recently shown that mRNP (messenger ribonucleoprotein) complexes are organized within post-transcriptional operons to co-ordinately regulate gene expression of functionally linked transcripts. In the present chapter we will focus on particular characteristics of gene expression in the so-called TriTryp parasites: Trypanosoma cruzi, Trypanosoma brucei and Leishmania major. PMID:22023440

De Gaudenzi, Javier G; Noé, Griselda; Campo, Vanina A; Frasch, Alberto C; Cassola, Alejandro

2011-01-01

420

Gene dispersal from transgenic crops  

Microsoft Academic Search

The risk of release of genetically modified oilseed rape (Brassica napus) was investigated in relation to interspecific gene flow with hoary mustard (Hirschfeldia incana). Microscopic studies showed polymorphism within the population of hoary mustard for pollen germination on oilseed rape flowers. The transgenic herbicide-resistant and a commercial cultivar of oilseed rape were not different for pollen behaviour and ovule fertilization.

Eric Lefol; Alain Fleury; Henri Darmency

1996-01-01

421

Gene expression regulating blastocyst formation  

Microsoft Academic Search

Development of embryos to the blastocyst stage is a critical event in the early lives of all eutherian mammalian species. Blastocyst formation is essential for implantation and is the principal morphological determinant of embryo quality prior to embryo transfer. The physiological events and roles of specific gene families that regulate blastocyst formation are subjects of intense research. Recent findings have

A. J Watson; M. E Westhusin; P. A De Sousa; D. H Betts; L. C Barcroft

1999-01-01

422

Deciphering gene expression regulatory networks  

Microsoft Academic Search

In the past year, great strides have been made in our understanding of the regulatory networks that control gene expression in the model eukaryote Saccharomyces cerevisiae. The development and use of a number of genomic tools, including genome-wide location and expression analysis, has fueled this progress. In addition, a variety of computational algorithms have been devised to mine genomic sequence

John J Wyrick; Richard A Young

2002-01-01

423

Gene therapy for pancreatitis pain  

Microsoft Academic Search

Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replication defective Herpes (HSV-1, DPE) viral vector construct encoding the human preproenkephalin gene (HSV-Enk), used

K N Westlund

2009-01-01

424

Molecular Genetics: Proteins and Genes  

NSDL National Science Digital Library

In this chapter, the authors focus conceptually on the connection between genotype and phenotype, specifically the role of genes and proteins in that connection. They also consider the importance of proteins to the work of cells and the impact of proteins

Tweed, Susan K.

2009-05-22

425

Finding genes for uterine fibroids  

Microsoft Academic Search

Objective: Uterine leiomyomata (fibroids) are the most common pelvic tumors in women, accounting for approximately one third of hysterectomies in the United States. Although little is known about their etiology, cytogenetic and epidemiologic evidence suggests a strong heritable component to fibroid development. To clarify further the role of genes in the pathogenesis of fibroids, the Center for Uterine Fibroids is

Karen Gross; Cynthia Morton; Elizabeth Stewart

2000-01-01

426

Molecular biology of epilepsy genes.  

PubMed

Multifactorial inheritance is the most important model accounting for the genetic behavior of the common epilepsies. Important to this model is the concept that many cumulative or synergistic risk genes ultimately lead to a threshold effect. Sophisticated molecular testing indicates that the common epilepsies are very polygenic without evidence of any single gene having even a mild-to-modest risk effect. However, enrichment of copy number variants in cohorts of individuals with epilepsy indicates that certain structural changes in the genome can confer significant risk for epilepsy. The mechanisms whereby copy number variants confer this effect are not yet known. The study of epilepsy due to single gene defects however has helped clarify certain seizure mechanisms. For example, discoveries using animal models of SCN1A or ARX mutations implicate a predominant role for interneurons due to disturbed GABAergic function. It is hoped that future genetic and neurobiological studies will provide better insight into how multiple genes contribute to the common epilepsies. PMID:22178301

Williams, Charles A; Battaglia, Agatino

2011-12-09

427

Gene transfer in intact animals  

NASA Astrophysics Data System (ADS)

Resistance to methotrexate was induced in bone marrow cells of mice by transformation in vitro with DNA from a drug-resistant cell line. Transformed cells were injected in vivo and haematopoietic cells expressing resistance were selected by drug treatment of recipients. Transformed cells had elevated levels of dihydrofolate reductase and demonstrated a proliferative advantage over untransformed cells, indicating successful gene transfer.

Cline, M. J.; Stang, H.; Mercola, K.; Morse, L.; Ruprecht, R.; Browne, J.; Salser, W.

1980-04-01

428

Gene therapy for lipid disorders  

Microsoft Academic Search

Lipid disorders are associated with atherosclerotic vascular disease, and therapy is associated with a substantial reduction in cardiovascular events. Current approaches to the treatment of lipid disorders are ineffective in a substantial number of patients. New therapies for refractory hypercholesterolemia, severe hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol are needed: somatic gene therapy is one viable approach. The molecular

Masa-aki Kawashiri; Daniel J Rader

2000-01-01

429

Genes associated to sucrose content  

US Patent & Trademark Office Database

Modern sugarcane cultivars are complex hybrids resulting from crosses among several species of the Saccharum genus. Traditional breeding methods have been extensively employed in different countries along the past decades to develop varieties with increased sucrose yield, and resistant to plagues and diseases. Conventional varietal improvement is, however, limited by the narrow pool of suitable markers. In this sense, molecular genetics is seen as a promising tool to assist in the process of molecular marker identification. The present invention concerns the identification of 348 genes associated with sucrose content in sugarcane plants. The genes were found to be differentially expressed when high sucrose and low sucrose plants and populations of plants were compared and/or when high and low sucrose internodes were compared. The expression data was obtained using cDNA microarray and quantitative PCR technologies. The genes identified can be used to identify, distinguish, characterize and/or develop plants with increased sucrose content. More preferably SEQ ID Nos: 1 to 203 should be useful as molecular markers. SEQ ID Nos: 204 to 228 are given as controls or examples of genes never associated with sucrose content. SEQ ID Nos. 1-203 and SEQ ID Nos. 229 to 373 can be targeted in the development of transgenic or non-transgenic varieties with increased sucrose content.

Souza; Glaucia Mendes (Sao Paulo, BR); Papini-Terzi; Flavia Stal (Sao Paulo, BR); Rocha; Flavia Riso (Sao Paulo, BR); Waclawovsky; Alessandro Jaquiel (Sao Paulo, BR); Vencio; Ricardo Zorzetto Nicollielo (Sao Paulo, BR); Marques; Joselia Oliveira (Sao Paulo, BR); de Maria Felix; Juliana (Campinas, BR); Teixeira; Marcelo Menossi (Campinas, BR); Buckeridge; Marcos (Rua do Matao, BR); Pereira de Souza; Amanda (Rua do Matao, BR); Ulian; Eug nio Cesar (Piracicaba, BR)

2010-06-08

430

CNS Genes Implicated in Relapse  

Microsoft Academic Search

Drug abuse is a condition that impacts not only the individual drug user, but society as a whole. Although prevention of initial drug use is the most effective way to prevent addiction, avoiding relapse is a crucial component of drug addiction recovery. Recent studies suggest that there is a set of genes whose expression is robustly and stably altered following

Kara L. Kuntz-Melcavage; Willard M. Freeman; Kent E. Vrana

2008-01-01

431

Ethics of Gene Therapy Debated.  

ERIC Educational Resources Information Center

Presented are the highlights of a press conference featuring biomedical ethicist LeRoy Walters of Georgetown University and attorney Andrew Kimbrell of the Foundation on Economic Trends. The opposing points of view of these two speakers serve to outline the pros and cons of the gene therapy issue. (CW)

Borman, Stu

1991-01-01

432

Patching genes to fight disease  

SciTech Connect

The National Institutes of Health has approved the first gene therapy experiments, one of which will try to cure cancer by bolstering the immune system. The applications of such therapy are limited, but the potential aid to people with genetic diseases is great.

Holzman, D.

1990-09-03

433

Phytochrome-regulated Gene Expression  

Technology Transfer Automated Retrieval System (TEKTRAN)

Identification of all genes involved in the phytochrome (phy)- mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent compr...

434

Leukaemogenesis: more than mutant genes  

Microsoft Academic Search

Acute leukaemias are characterized by recurring chromosomal aberrations and gene mutations that are crucial to disease pathogenesis. It is now evident that epigenetic modifications, including DNA methylation and histone modifications, substantially contribute to the phenotype of leukaemia cells. An additional layer of epigenetic complexity is the pathogenetic role of microRNAs in leukaemias, and their key role in the transcriptional regulation

Jianjun Chen; Olatoyosi Odenike; Janet D. Rowley

2010-01-01

435

Gene therapy for colorectal cancer  

Microsoft Academic Search

Gene therapy has been developed as a potential novel treatment modality for colorectal cancer. The preclinical data have been promising and several clinical trials are under way for colorectal cancer. Data from many phase 1 trials have proven the safety of the reagents, but have not yet demonstrated significant therapeutic benefit. In order to refine this approach, continuing efforts should

Daniel H Palmer; Ming-Jen Chen; David J Kerr

2002-01-01

436

Genes for reading and spelling  

Microsoft Academic Search

This article reviews research on the behavioral and molecular genetics of reading and, where available, spelling. Recent research is summarized, suggesting that reading and spelling appear to share a common genetic basis, and that dyslexia lies on a genetic continuum with normal variance in reading skill. Research also suggests that while many of the genes involved in reading disorder affect

Timothy C. Bates

2006-01-01

437

Posttranscriptional gene silencing across kingdoms  

Microsoft Academic Search

Post-transcriptional gene silencing (PTGS) as a consequence of the introduction of either transgenes or double-stranded RNA molecules has been found to occur in a number of species. In the past year, studies in different systems have greatly enhanced our understanding of the molecular mechanisms of these phenomena. The ubiquitous presence of PTGS in both the plant and animal kingdoms and

Carlo Cogoni; Giuseppe Macino

2000-01-01

438

Genetics of global gene expression  

Microsoft Academic Search

A new field of genetic analysis of global gene expression has emerged in recent years, driven by the realization that traditional techniques of linkage and association analysis can be applied to thousands of transcript levels measured by microarrays. Genetic dissection of transcript abundance has shed light on the architecture of quantitative traits, provided a new approach for connecting DNA sequence

Matthew V. Rockman; Leonid Kruglyak

2006-01-01

439

Gene selection and classification of microarray data using random forest  

Microsoft Academic Search

Background: Selection of relevant genes for sample classification is a common task in most gene expression studies, where researchers try to identify the smallest possible set of genes that can still achieve good predictive performance (for instance, for future use with diagnostic purposes in clinical practice). Many gene selection approaches use univariate (gene-by-gene) rankings of gene relevance and arbitrary thresholds

Ramón Díaz-uriarte; Sara Alvarez De Andrés

2006-01-01

440

Gene losses during human origins.  

PubMed

Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the "less-is-more" hypothesis). However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the "less-is-more" hypothesis. PMID:16464126

Wang, Xiaoxia; Grus, Wendy E; Zhang, Jianzhi

2006-02-14

441

Vascular gene expression: a hypothesis  

PubMed Central

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.

Martinez-Navarro, Angelica C.; Galvan-Gordillo, Santiago V.; Xoconostle-Cazares, Beatriz; Ruiz-Medrano, Roberto

2013-01-01

442

MGC: a metagenomic gene caller  

PubMed Central

Background Computational gene finding algorithms have proven their robustness in identifying genes in complete genomes. However, metagenomic sequencing has presented new challenges due to the incomplete and fragmented nature of the data. During the last few years, attempts have been made to extract complete and incomplete open reading frames (ORFs) directly from short reads and identify the coding ORFs, bypassing other challenging tasks such as the assembly of the metagenome. Results In this paper we introduce a metagenomics gene caller (MGC) which is an improvement over the state-of-the-art prediction algorithm Orphelia. Orphelia uses a two-stage machine learning approach and computes a model that classifies extracted ORFs from fragmented sequences. We hypothesise and demonstrate evidence that sequences need separate models based on their local GC-content in order to avoid the noise introduced to a single model computed with sequences from the entire GC spectrum. We have also added two amino-acid features based on the benefit of amino-acid usage shown in our previous research. Our algorithm is able to predict genes and translation initiation sites (TIS) more accurately than Orphelia which uses a single model. Conclusions Learning separate models for several pre-defined GC-content regions as opposed to a single model approach improves the performance of the neural network as demonstrated by the experimental results presented in this paper. The inclusion of amino-acid usage features also helps improve the overall accuracy of our algorithm. MGC's improvement sets the ground for further investigation into the use of GC-content to separate data for training models in machine learning based gene finders.

2013-01-01

443

Vascular gene expression: a hypothesis.  

PubMed

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

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

2013-07-17

444

Gene expression profiles in skeletal muscle after gene electrotransfer  

PubMed Central

Background Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 ?s) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. Results Differentially expressed genes were investigated by microarray analysis, and descriptive statistics were performed to evaluate the effects of 1) electroporation, 2) DNA injection, and 3) time after treatment. The biological significance of the results was assessed by gene annotation and supervised cluster analysis. Generally, electroporation caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related with the control muscles. Most interestingly, no changes in the expression of proteins involved in inflammatory responses or muscle regeneration was detected, indicating limited muscle damage and regeneration. Histological analysis revealed structural changes with loss of cell integrity and striation pattern in some fibres after DNA+HV+LV treatment, while HV+LV pulses alone showed preservation of cell integrity. No difference in the force generation capacity was observed in the muscles 2 weeks after DNA electrotransfer. Conclusion The small and transient changes found in the gene expression profiles are of great importance, as this demonstrates that DNA electrotransfer is safe with minor effects on the muscle host cells. These findings are essential for introducing the DNA electrotransfer to muscle for clinical use. Indeed the HV+LV pulse combination used has been optimised to ensure highly efficient and safe DNA electrotransfer.

Hojman, Pernille; Zibert, John R; Gissel, Hanne; Eriksen, Jens; Gehl, Julie

2007-01-01

445

Gene set analysis using variance component tests  

PubMed Central

Background Gene set analyses have become increasingly important in genomic research, as many complex diseases are contributed jointly by alterations of numerous genes. Genes often coordinate together as a functional repertoire, e.g., a biological pathway/network and are highly correlated. However, most of the existing gene set analysis methods do not fully account for the correlation among the genes. Here we propose to tackle this important feature of a gene set to improve statistical power in gene set analyses. Results We propose to model the effects of an independent variable, e.g., exposure/biological status (yes/no), on multiple gene expression values in a gene set using a multivariate linear regression model, where the correlation among the genes is explicitly modeled using a working covariance matrix. We develop TEGS (Test for the Effect of a Gene Set), a variance component test for the gene set effects by assuming a common distribution for regression coefficients in multivariate linear regression models, and calculate the p-values using permutation and a scaled chi-square approximation. We show using simulations that type I error is protected under different choices of working covariance matrices and power is improved as the working covariance approaches the true covariance. The global test is a special case of TEGS when correlation among genes in a gene set is ignored. Using both simulation data and a published diabetes dataset, we show that our test outperforms the commonly used approaches, the global test and gene set enrichment analysis (GSEA). Conclusion We develop a gene set analyses method (TEGS) under the multivariate regression framework, which directly models the interdependence of the expression values in a gene set using a working covariance. TEGS outperforms two widely used methods, GSEA and global test in both simulation and a diabetes microarray data.

2013-01-01

446

Gene family matters: expanding the HGNC resource.  

PubMed

ABSTRACT: The HUGO Gene Nomenclature Committee (HGNC) assigns approved gene symbols to human loci. There are currently over 33,000 approved gene symbols, the majority of which represent protein-coding genes, but we also name other locus types such as non-coding RNAs, pseudogenes and phenotypic loci. Where relevant, the HGNC organise these genes into gene families and groups. The HGNC website http://www.genenames.org/ is an online repository of HGNC-approved gene nomenclature and associated resources for human genes, and includes links to genomic, proteomic and phenotypic information. In addition to this, we also have dedicated gene family web pages and are currently expanding and generating more of these pages using data curated by the HGNC and from information derived from external resources that focus on particular gene families. Here, we review our current online resources with a particular focus on our gene family data, using it to highlight our new Gene Symbol Report and gene family data downloads. PMID:23245209

Daugherty, Louise C; Seal, Ruth L; Wright, Mathew W; Bruford, Elspeth A

2012-07-01

447

Developing strategies for detection of gene doping.  

PubMed

It is feared that the use of gene transfer technology to enhance athletic performance, the practice that has received the term 'gene doping', may soon become a real threat to the world of sport. As recognised by the anti-doping community, gene doping, like doping in any form, undermines principles of fair play in sport and most importantly, involves major health risks to athletes who partake in gene doping. One attraction of gene doping for such athletes and their entourage lies in the apparent difficulty of detecting its use. Since the realisation of the threat of gene doping to sport in 2001, the anti-doping community and scientists from different disciplines concerned with potential misuse of gene therapy technologies for performance enhancement have focused extensive efforts on developing robust methods for gene doping detection which could be used by the World Anti-Doping Agency to monitor athletes and would meet the requirements of a legally defensible test. Here we review the approaches and technologies which are being evaluated for the detection of gene doping, as well as for monitoring the efficacy of legitimate gene therapy, in relation to the detection target, the type of sample required for analysis and detection methods. We examine the accumulated knowledge on responses of the body, at both cellular and systemic levels, to gene transfer and evaluate strategies for gene doping detection based on current knowledge of gene technology, immunology, transcriptomics, proteomics, biochemistry and physiology. PMID:18081214

Baoutina, Anna; Alexander, Ian E; Rasko, John E J; Emslie, Kerry R

2008-01-01

448

Stability and evolution of overlapping genes.  

PubMed

When the same sequence of nucleotides codes for regions of more than one functional polypeptide, this sequence contains overlapping genes. Overlap is most common in rapidly evolving genomes with high mutation rates such as viruses, bacteria, and mitochondria. Overlap is thought to be important as: (1) a means of compressing a maximum amount of information into short sequences of structural genes; and (2) as a mechanism for regulating gene expression through translational coupling of functionally related polypeptides. The stability of overlapping codes is examined in relation to the information cost of overlap and the mutation rate of the genome. The degree of overlap in a given population will tend to become monomorphic. Evolution toward partial overlap of genes is shown to depend on a convex cost function of overlap. Overlap does not evolve when expression of overlapping genes is mutually exclusive and produced by rare mutations to the wild-type genome. Assuming overlap increases coupling between functionally related genes, the conditions favoring overlap are explored in relation to the kinetics of gene activation and decay. Coupling is most effective for genes in which the gene overlapping at its 5' end (leading gene) decays rapidly, while the gene overlapping at the 3' end (induced gene) decays slowly. If gene expression can feedback on itself (autocatalysis), then high rates of activation favor overlap. PMID:10937248

Krakauer, D C

2000-06-01

449

Utility of gene-specific algorithms for predicting pathogenicity of uncertain gene variants.  

PubMed

The rapid advance of gene sequencing technologies has produced an unprecedented rate of discovery of genome variation in humans. A growing number of authoritative clinical repositories archive gene variants and disease phenotypes, yet there are currently many more gene variants that lack clear annotation or disease association. To date, there has been very limited coverage of gene-specific predictors in the literature. Here the evaluation is presented of "gene-specific" predictor models based on a naïve Bayesian classifier for 20 gene-disease datasets, containing 3986 variants with clinically characterized patient conditions. The utility of gene-specific prediction is then compared with "all-gene" generalized prediction and also with existing popular predictors. Gene-specific computational prediction models derived from clinically curated gene variant disease datasets often outperform established generalized algorithms for novel and uncertain gene variants. PMID:22037892

Crockett, David K; Lyon, Elaine; Williams, Marc S; Narus, Scott P; Facelli, Julio C; Mitchell, Joyce A

2011-10-28

450

Wistar Institute study finds multiple 'siblings' from every gene: Alternate gene reading leads to alternate gene products:  

Cancer.gov

A genome-wide survey by researchers at The Wistar Institute shows how our cells create alternate versions of mRNA transcripts by altering how they "read" DNA. Many genes are associated with multiple gene promoters, the researchers say, which is the predominant way multiple variants of a given gene, for example, can be made with the same genetic instructions.

451

Housekeeping Genes and Death Genes in the Penna Aging Model  

NASA Astrophysics Data System (ADS)

The Penna model of aging predicts the accumulation of defective genes expressed after the organism reaches the minimum reproduction age in the genetic pool of the population. The accumulation of defects in the genomes implicates the specific age structure of the modeled populations. Nevertheless, the fraction of defective alleles at loci switched on before the reproduction period does not depend on exact age when precisely they are switched on, it may be just after conception or after birth. We have modeled the mortality of a population in the period before the minimum reproduction age, even before birth, assuming that sets of genes of different size are switched on in different periods of the life span.

Niewczas, E.; Kurdziel, A.; Cebrat, S.

452

Role of gene–gene\\/gene–environment interaction in the etiology of eastern Indian ADHD probands  

Microsoft Academic Search

Associations between attention deficit hyperactivity disorder (ADHD) and genetic polymorphisms in the dopamine receptors, transporter and metabolizing enzymes have been reported in different ethnic groups. Gene variants may affect disease outcome by acting synergistically or antagonistically and thus their combined effect becomes an important aspect to study in the disease etiology. In the present investigation, interaction between ten functional polymorphisms

Manali Das; Aneek Das Bhowmik; Nipa Bhaduri; Kanyakumarika Sarkar; Paramita Ghosh; Swagata Sinha; Anirban Ray; Anindita Chatterjee; Kanchan Mukhopadhyay

2011-01-01

453

Gene Therapy Progress and Prospects: cancer gene therapy using tumour suppressor genes  

Microsoft Academic Search

Targeting tumour suppressor gene pathways is an attractive therapeutic strategy in cancer. Since the first clinical trial took place in 1996, at least 20 other trials have investigated the possibility of restoring p53 function, either alone or in combination with chemotherapy, but with limited success. Other recent clinical trials have sought to harness abnormalities in the p53 pathway to permit

IA McNeish; SJ Bell; NR Lemoine

2004-01-01

454

Potato Genes for Resistance to Late Blight.  

National Technical Information Service (NTIS)

Resistance genes and their encoded proteins from the wild potato, Solanum bulbocastanum, are disclosed. The genes and proteins are useful for conferring disease resistance to plants, particularly solanaceous species such as potato and tomato. In particula...

J. Jiang J. Song J. P. Helgeson S. Austin-Phillips S. K. Naess

2004-01-01

455

PAX Genes in Cancer; Friends or Foes?  

PubMed Central

PAX genes have been shown to be critically required for the development of specific tissues and organs during embryogenesis. In addition, PAX genes are expressed in a handful of adult tissues where they are thought to play important roles, usually different from those in embryogenesis. A common theme in adult tissues is a requirement for PAX gene expression in adult stem cell maintenance or tissue regeneration. The connections between adult stem cell PAX gene expression and cancer are intriguing, and the literature is replete with examples of PAX gene expression in either situation. Here we systematically review the literature and present an overview of postnatal PAX gene expression in normal and cancerous tissue. We discuss the potential link between PAX gene expression in adult tissue and cancer. In addition, we discuss whether persistent PAX gene expression in cancer is favorable or unfavorable.

Li, Caiyun G.; Eccles, Michael R.

2012-01-01

456

Updated Sequence Information for TEM ?-Lactamase Genes  

PubMed Central

The sequences of the promoter regions and of the structural genes for 13 penicillinase, extended-spectrum, and inhibitor-resistant TEM-type ?-lactamases have been determined, and an updated blaTEM gene nomenclature is proposed.

Goussard, Sylvie; Courvalin, Patrice

1999-01-01

457

Gene Linkage and Familial Behavioral Characteristics.  

National Technical Information Service (NTIS)

The identification of genes influencing behavioral traits by relating the pattern of phenotypes in a family to the transmission of marker genes having a known Mendelian pattern of inheritance was studied. Families selected for two or more siblings with pr...

L. R. Weitkamp

1981-01-01

458

NIH Researchers Identify OCD Risk Gene  

MedlinePLUS

... Issues Research News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of ... gene variant that doubles an individual's risk for obsessive-compulsive disorder (OCD). The new functional variant, or allele, is ...

459

In The Genes? Searching for Methuselah  

MedlinePLUS

... Current Issue Past Issues Special Section In The Genes? Searching for Methuselah Past Issues / Winter 2007 Table ... 18 million effort to learn more about the genes, lifestyle or other factors that contribute to long, ...

460

Interactive Fly: Early Zygotic Gene Expression Images  

NSDL National Science Digital Library

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.

PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

2006-12-12

461

Cancer gene therapy targeting cellular apoptosis machinery.  

PubMed

The unraveling of cellular apoptosis machinery provides novel targets for cancer treatment, and gene therapy targeting this suicidal system has been corroborated to cause inflammation-free autonomous elimination of neoplastic cells. The apoptotic machinery can be targeted by introduction of a gene encoding an inducer, mediator or executioner of apoptotic cell death or by inhibition of anti-apoptotic gene expression. Strategies targeting cancer cells, which are achieved by selective gene delivery, specific gene expression or secretion of target proteins via genetic modification of autologous cells, dictate the outcome of apoptosis-based cancer gene therapy. Despite so far limited clinical success, gene therapy targeting the apoptotic machinery has great potential to benefit patients with threatening malignancies provided the availability of efficient and specific gene delivery and administration systems. PMID:22800735

Jia, Lin-Tao; Chen, Si-Yi; Yang, An-Gang

2012-07-15

462

Diacylglycerol Acyltransferase Genes, Proteins, and Uses Thereof.  

National Technical Information Service (NTIS)

The present invention relates to diacylglycerol acyltransferase genes and proteins, and methods of their use. In particular, the invention describes genes and proteins that exhibit both long-chain acyltransferase and acetyltransferase activity. The presen...

A. Milcamps D. A. Pan M. R. Pollard

2004-01-01

463

NewGenesSyndromes060305.pdf  

Cancer.gov

New Cancer Genes and Syndromes Mark H. Greene, M.D. Chief, Clinical Genetics Branch Division of Cancer Epidemiology & Genetics National Cancer Institute Less Familiar Cancer Genes and Syndromes Heterozygous ATM Mutation Carriers • This

464

Lamprey Dlx genes and early vertebrate evolution  

PubMed Central

Gnathostome vertebrates have multiple members of the Dlx family of transcription factors that are expressed during the development of several tissues considered to be vertebrate synapomorphies, including the forebrain, cranial neural crest, placodes, and pharyngeal arches. The Dlx gene family thus presents an ideal system in which to examine the relationship between gene duplication and morphological innovation during vertebrate evolution. Toward this end, we have cloned Dlx genes from the lamprey Petromyzon marinus, an agnathan vertebrate that occupies a critical phylogenetic position between cephalochordates and gnathostomes. We have identified four Dlx genes in P. marinus, whose orthology with gnathostome Dlx genes provides a model for how this gene family evolved in the vertebrate lineage. Differential expression of these lamprey Dlx genes in the forebrain, cranial neural crest, pharyngeal arches, and sensory placodes of lamprey embryos provides insight into the developmental evolution of these structures as well as a model of regulatory evolution after Dlx gene duplication events.

Neidert, Adam H.; Virupannavar, Vikrant; Hooker, Gillian W.; Langeland, James A.

2001-01-01

465

Pichia stipitis genomics, transcriptomics, and gene clusters  

Treesearch

These studies have provided an insight into its central carbon metabolism, ... followed by differentiation in the regulatory and coding regions of the gene. ... gene expression, recombinant DNA, genetic transcription, Pichia stipitis, decay fungi.

466

Gene expression and gene therapy in experimental duodenal ulceration  

Microsoft Academic Search

Gastroduodenal ulceration is still poorly understood and changes in gene expression may provide new mechanistic insights. Previously, we demonstrated that angiogenic growth factors are potent ulcer healing agents, and the synthesis of bFGF, PDGF and VEGF is enhanced early in duodenal ulcer healing. The initial molecular event in duodenal ulceration seems to be the organ-specific early release of ET-1 in

Sandor Szabo; Xiaoming Deng; Tetyana Khomenko; Masashi Yoshida; Martin R Jadus; Zsuzsa Sandor; Zoltan Gombos; Hiroko Matsumoto

2001-01-01

467

Identification of genes responsive to PFOS using gene expression profiling  

Microsoft Academic Search

Perfluorooctane sulfonic acid (PFOS) is widely distributed in the environment including in the tissues of wildlife and humans, however, its mechanism of action remains unclear. Here, the Affymetrix rat genome U34A genechip was used to identify alterations in gene expression due to PFOS exposure. Rat hepatoma cells were treated with PFOS at 2–50mg\\/L (4–100?M) for 96h. Sprague-Dawley rats were orally

Wenyue Hu; Paul D. Jones; Trine Celius; John P. Giesy

2005-01-01

468

Good genes, complementary genes and human mate preferences  

Microsoft Academic Search

The past decade has witnessed a rapidly growing interest in the biological basis of human mate choice. Here we review recent\\u000a studies that demonstrate preferences for traits which might reveal genetic quality to prospective mates, with potential but\\u000a still largely unknown influence on offspring fitness. These include studies assessing visual, olfactory and auditory preferences\\u000a for potential good-gene indicator traits, such

S. Craig Roberts; Anthony C. Little

2008-01-01

469

The Ovalbumin Gene: Cloning of the Natural Gene  

Microsoft Academic Search

The structural ovalbumin DNA sequences are not contiguous and are separated by multiple ``intervening regions'' in native chicken DNA. EcoRI, a restriction endonuclease that does not cleave the structural ovalbumin DNA sequences, digests the natural ovalbumin gene into three distinct fragments of 2.4, 1.8, and 9.5 kilobase pairs in length by cleaving within these ``intervening regions.'' The 2.4-kilobase pair fragment

Savio L. C. Woo; Achilles Dugaiczyk; Ming-Jer Tsai; Eugene C. Lai; James F. Catterall; Bert W. O'Malley

1978-01-01

470

Gene-gene interactions in breast cancer susceptibility.  

PubMed

There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 × 10(-4); ATM and BRCA1, P= 0.01; ATM and BRCA2, P= 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 × 10(-4); CHEK2 and BRCA1, P= 0.01; CHEK2 and BRCA2, P= 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation. PMID:22072393

Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Warren-Perry, Margaret; Hughes, Deborah; Elliott, Anna; Pernet, David; Peock, Susan; Adlard, Julian W; Barwell, Julian; Berg, Jonathan; Brady, Angela F; Brewer, Carole; Brice, Glen; Chapman, Cyril; Cook, Jackie; Davidson, Rosemarie; Donaldson, Alan; Douglas, Fiona; Greenhalgh, Lynn; Henderson, Alex; Izatt, Louise; Kumar, Ajith; Lalloo, Fiona; Miedzybrodzka, Zosia; Morrison, Patrick J; Paterson, Joan; Porteous, Mary; Rogers, Mark T; Shanley, Susan; Walker, Lisa; Ahmed, Munaza; Eccles, Diana; Evans, D Gareth; Donnelly, Peter; Easton, Douglas F; Stratton, Michael R; Rahman, Nazneen

2011-11-09

471

RNA Interference and Antisense Mediated Gene Silencing  

Microsoft Academic Search

Gene silencing by RNA interference (RNAi) and by antisense RNA are powerful tools to interfere with the expression of eukryotic\\u000a genes. Since the first description of RNAi in 1998, antisense-mediated gene silencing has been considered to have essentially\\u000a the same mechanism as gene silencing by RNAi. However, while substantial effort has been made to dissect the RNAi pathway,\\u000a the cellular

Markus Kuhlmann; Blaga Popova; Wolfgang Nellen

472

Mycoplasma gallisepticum rpoA gene cluster  

Microsoft Academic Search

Two conservative gene clusters, the S10 ribosomal protein region and one (of the two) set of rRNA genes, were split in a genome crossover rearrangement event in Mycoplasma gallisepticum. As a result of the rearrangement the major part of the S10 ribosomal protein cluster is located upstream of genes for 23S-5S rRNA (rrn23-5), but the genes infA-rpl36-rps13-rpoA-rpl17 are located immediately

Andrei Skamrov; Eugenia Feoktistova; Maria Goldman; Robert Beabealashvilli

2002-01-01

473

Regulation of the genes involved in nitrification.  

SciTech Connect

OAK-B135 This project focuses on the characterization of the regulation of the genes involved in nitrification in the bacterium Nitrosomonas europaea. The key genes in the nitrification pathway, amo and hao, are present in multiple copies in the genome. The promoters for these genes were identified and characterized. It was shown that there were some differences in the transcriptional regulation of the copies of these genes.

Arp, D.J.; Sayavedra-Soto, L.A.

2003-08-14

474

Leader genes in osteogenesis: a theoretical study.  

PubMed

Little is still known about the molecular mechanisms involved in the process of osteogenesis. In this paper, the leader genes approach, a new bioinformatics method which has already been experimentally validated, is adopted in order to identify the genes involved in human osteogenesis. Interactions among genes are then calculated and genes are ranked according to their relative importance in this process. In total, 167 genes were identified as being involved in osteogenesis. Genes were divided into 4 groups, according to their main function in the osteogenic processes: skeletal development; cell adhesion and proliferation; ossification; and calcium ion binding. Seven genes were consistently identified as leader genes (i.e. the genes with the greatest importance in osteogenesis), while 14 were found to have slightly less importance (class B genes). It was interesting to notice that the larger part of leader and class B genes belonged to the cell adhesion and p