These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Long-Term Channel Block Is Required to Inhibit Cellular Transformation by Human Ether-à-Go-Go–Related Gene (hERG1) Potassium Channels  

PubMed Central

Both human ether-à-go-go–related gene (hERG1) and the closely related human ether-à-go-go (hEAG1) channel are aberrantly expressed in a large proportion of human cancers. In the present study, we demonstrate that transfection of hERG1 into mouse fibroblasts is sufficient to induce many features characteristic of malignant transformation. An important finding of this work is that this transformation could be reversed by chronic incubation (for 2–3 weeks) with the hERG channel blocker dofetilide (100 nM), whereas more acute applications (for 1–2 days) were ineffective. The hERG1 expression resulted in a profound loss of cell contact inhibition, multiple layers of overgrowing cells, and high saturation densities. Cells also changed from fibroblast-like to a more spindle-shaped morphology, which was associated with a smaller cell size, a dramatic increase in cell polarization, a reduction in the number of actin stress fibers, and less punctate labeling of focal adhesions. Analysis of single-cell migration and scratch-wound closure clearly demonstrated that hERG1-expressing cells migrated more rapidly than vector-transfected control cells. In contrast to previous studies on hEAG1, there were no increases in rates of proliferation, or loss of growth factor dependency; however, hERG1-expressing cells were capable of substrate-independent growth. Allogeneic transplantation of hERG1-expressing cells into nude mice resulted in an increased incidence of tumors. In contrast to hEAG1, the mechanism of cellular transformation is dependent on ion conduction. Trafficking-deficient and conduction-deficient hERG1 mutants also prevented cellular transformation. These results provide evidence that hERG1 expression is sufficient to induce cellular transformation by a mechanism distinct from hEAG1. The most important conclusion of this study is that selective hERG1 channel blockers have therapeutic potential in the treatment of hERG1-expressing cancers. PMID:24830940

Pier, David M.; Shehatou, George S. G.; Giblett, Susan; Pullar, Christine E.; Trezise, Derek J.; Pritchard, Catrin A.; Challiss, R. A. John

2014-01-01

2

Intragenic Suppression of Trafficking-Defective KCNH2 Channels Associated with Long QT SyndromeS  

E-print Network

Intragenic Suppression of Trafficking-Defective KCNH2 Channels Associated with Long QT Syndrome 25, 2005 ABSTRACT Mutations in the KCNH2 or human ether-a-go-go­related gene- encoded K channel, including defects in intracellular transport (trafficking). Traffick- ing-deficient, or class 2, LQT2

Kamp, Tim

3

Characterization of hERG1 channel role in mouse colorectal carcinogenesis  

PubMed Central

The human ether-à-go-go-related gene (hERG)1 K+ channel is upregulated in human colorectal cancer cells and primary samples. In this study, we examined the role of hERG1 in colorectal carcinogenesis using two mouse models: adenomatous polyposis coli (Apcmin/+) and azoxymethane (AOM)-treated mice. Colonic polyps of Apcmin/+ mice overexpressed mERG1 and their formation was reverted by the hERG1 blocker E4031. AOM was applied to either hERG1-transgenic (TG) mice, which overexpress hERG1 in the mucosa of the large intestine, or wild-type mice. A significant increase of both mucin-depleted foci and polyps in the colon of hERG1-TG mice was detected. Both the intestine of TG mice and colonic polyps of Apcmin/+ showed an upregulation of phospho-Protein Kinase B (pAkt)/vascular endothelial growth factor (VEGF-A) and an increased angiogenesis, which were reverted by treatment with E4031. On the whole, this article assigns a relevant role to hERG1 in the process of in vivo colorectal carcinogenesis. PMID:24403225

Fiore, Antonella; Carraresi, Laura; Morabito, Angela; Polvani, Simone; Fortunato, Angelo; Lastraioli, Elena; Femia, Angelo P; Lorenzo, Emanuele; Caderni, Giovanna; Arcangeli, Annarosa

2013-01-01

4

Stereoselective Inhibition of the hERG1 Potassium Channel  

PubMed Central

A growing number of drugs have been shown to prolong cardiac repolarization, predisposing individuals to life-threatening ventricular arrhythmias known as Torsades de Pointes. Most of these drugs are known to interfere with the human ether à-gogo related gene 1 (hERG1) channel, whose current is one of the main determinants of action potential duration. Prolonged repolarization is reflected by lengthening of the QT interval of the electrocardiogram, as seen in the suitably named drug-induced long QT syndrome. Chirality (presence of an asymmetric atom) is a common feature of marketed drugs, which can therefore exist in at least two enantiomers with distinct three-dimensional structures and possibly distinct biological fates. Both the pharmacokinetic and pharmacodynamic properties can differ between enantiomers, as well as also between individuals who take the drug due to metabolic polymorphisms. Despite the large number of reports about drugs reducing the hERG1 current, potential stereoselective contributions have only been scarcely investigated. In this review, we present a non-exhaustive list of clinically important molecules which display chiral toxicity that may be related to hERG1-blocking properties. We particularly focus on methadone cardiotoxicity, which illustrates the importance of the stereoselective effect of drug chirality as well as individual variations resulting from pharmacogenetics. Furthermore, it seems likely that, during drug development, consideration of chirality in lead optimization and systematic assessment of the hERG1 current block with all enantiomers could contribute to the reduction of the risk of drug-induced LQTS. PMID:21833176

Grilo, Liliana Sintra; Carrupt, Pierre-Alain; Abriel, Hugues

2010-01-01

5

Inhibition of HERG1 K+ channels by the novel second-generation antihistamine mizolastine  

PubMed Central

Ventricular arrhythmias are rare but life-threatening side effects of therapy with the second-generation H1 receptor antagonists terfenadine and astemizole. Blockade of the K+ channels encoded by the Human Ether-à-go-go-Related Gene 1 (HERG1) K+ channels, which is the molecular basis of the cardiac repolarizing current IKr, by prolonging cardiac repolarization, has been recognized as the mechanism underlying the cardiac toxicity of these compounds.In the present study, the potential blocking ability of the novel second-generation H1 receptor antagonist mizolastine of the HERG1 K+ channels heterologously expressed in Xenopus oocytes and in HEK 293 cells or constitutively present in SH-SY5Y human neuroblastoma cells has been examined and compared to that of astemizole.Mizolastine blocked HERG1 K+ channels expressed in Xenopus oocytes with an estimated IC50 of 3.4??M. Mizolastine blockade was characterized by a fast dissociation rate when compared to that of astemizole; when fitted to a monoexponential function, the time constants for drug dissociation from the K+ channel were 72.4±11.9?s for 3??M mizolastine, and 1361±306?s for 1??M astemizole.In human embryonic kidney 293 cells (HEK 293 cells) stably transfected with HERG1 cDNA, extracellular application of mizolastine exerted a dose-related inhibitory action on IHERG1, with an IC50 of 350±76?nM. Furthermore, mizolastine dose-dependently inhibited HERG1 K+ channels constitutively expressed in SH-SY5Y human neuroblastoma clonal cells.The results of the present study suggest that the novel second-generation H1 receptor antagonist mizolastine, in concentrations higher than those achieved in vivo during standard therapy, is able to block in some degree both constitutively and heterologously expressed HERG1 K+ channels, and confirm the heterogeneity of molecules belonging to this therapeutical class with respect to their HERG1-inhibitory action. PMID:11082114

Taglialatela, Maurizio; Pannaccione, Anna; Castaldo, Pasqualina; Giorgio, Giovanna; Annunziato, Lucio

2000-01-01

6

Stoichiometry of altered hERG1 channel gating by small molecule activators  

PubMed Central

Voltage-gated K+ channels are tetramers formed by coassembly of four identical or highly related subunits. All four subunits contribute to formation of the selectivity filter, the narrowest region of the channel pore which determines K+ selective conductance. In some K+ channels, the selectivity filter can undergo a conformational change to reduce K+ flux by a mechanism called C-type inactivation. In human ether-a-go-go–related gene 1 (hERG1) K+ channels, C-type inactivation is allosterically inhibited by ICA-105574, a substituted benzamide. PD-118057, a 2-(phenylamino) benzoic acid, alters selectivity filter gating to enhance open probability of channels. Both compounds bind to a hydrophobic pocket located between adjacent hERG1 subunits. Accordingly, a homotetrameric channel contains four identical activator binding sites. Here we determine the number of binding sites required for maximal drug effect and determine the role of subunit interactions in the modulation of hERG1 gating by these compounds. Concatenated tetramers were constructed to contain a variable number (zero to four) of wild-type and mutant hERG1 subunits, either L646E to inhibit PD-118057 binding or F557L to inhibit ICA-105574 binding. Enhancement of hERG1 channel current magnitude by PD-118057 and attenuated inactivation by ICA-105574 were mediated by cooperative subunit interactions. Maximal effects of the both compounds required the presence of all four binding sites. Understanding how hERG1 agonists allosterically modify channel gating may facilitate mechanism-based drug design of novel agents for treatment of long QT syndrome. PMID:24638994

Wu, Wei; Sachse, Frank B.; Gardner, Alison

2014-01-01

7

Concatenated hERG1 tetramers reveal stoichiometry of altered channel gating by RPR-260243.  

PubMed

Activation of human ether-a-go-go-related gene 1 (hERG1) K(+) channels mediates repolarization of action potentials in cardiomyocytes. RPR-260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid] (RPR) slows deactivation and attenuates inactivation of hERG1 channels. A detailed understanding of the molecular mechanism of hERG1 agonists such as RPR may facilitate the design of more selective and potent compounds for prevention of arrhythmia associated with abnormally prolonged ventricular repolarization. RPR binds to a hydrophobic pocket located between two adjacent hERG1 subunits, and, hence, a homotetrameric channel has four identical RPR binding sites. To investigate the stoichiometry of altered channel gating induced by RPR, we constructed and characterized tetrameric hERG1 concatemers containing a variable number of wild-type subunits and subunits containing a point mutation (L553A) that rendered the channel insensitive to RPR, ostensibly by preventing ligand binding. The slowing of deactivation by RPR was proportional to the number of wild-type subunits incorporated into a concatenated tetrameric channel, and four wild-type subunits were required to achieve maximal slowing of deactivation. In contrast, a single wild-type subunit within a concatenated tetramer was sufficient to achieve half of the maximal RPR-induced shift in the voltage dependence of hERG1 inactivation, and maximal effect was achieved in channels containing three or four wild-type subunits. Together our findings suggest that the allosteric modulation of channel gating involves distinct mechanisms of coupling between drug binding and altered deactivation and inactivation. PMID:25519838

Wu, Wei; Gardner, Alison; Sanguinetti, Michael C

2015-01-01

8

Stoichiometry of altered hERG1 channel gating by small molecule activators.  

PubMed

Voltage-gated K(+) channels are tetramers formed by coassembly of four identical or highly related subunits. All four subunits contribute to formation of the selectivity filter, the narrowest region of the channel pore which determines K(+) selective conductance. In some K(+) channels, the selectivity filter can undergo a conformational change to reduce K(+) flux by a mechanism called C-type inactivation. In human ether-a-go-go-related gene 1 (hERG1) K(+) channels, C-type inactivation is allosterically inhibited by ICA-105574, a substituted benzamide. PD-118057, a 2-(phenylamino) benzoic acid, alters selectivity filter gating to enhance open probability of channels. Both compounds bind to a hydrophobic pocket located between adjacent hERG1 subunits. Accordingly, a homotetrameric channel contains four identical activator binding sites. Here we determine the number of binding sites required for maximal drug effect and determine the role of subunit interactions in the modulation of hERG1 gating by these compounds. Concatenated tetramers were constructed to contain a variable number (zero to four) of wild-type and mutant hERG1 subunits, either L646E to inhibit PD-118057 binding or F557L to inhibit ICA-105574 binding. Enhancement of hERG1 channel current magnitude by PD-118057 and attenuated inactivation by ICA-105574 were mediated by cooperative subunit interactions. Maximal effects of the both compounds required the presence of all four binding sites. Understanding how hERG1 agonists allosterically modify channel gating may facilitate mechanism-based drug design of novel agents for treatment of long QT syndrome. PMID:24638994

Wu, Wei; Sachse, Frank B; Gardner, Alison; Sanguinetti, Michael C

2014-04-01

9

Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2  

PubMed Central

Background Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering?>?90% of cases, are KCNQ1, KCNH2 and SCN5A. Methods We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2. Results Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 “unrelated” families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of?KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis. PMID:24606995

2014-01-01

10

A novel, primate-specific, brain isoform of KCNH2 impacts cortical physiology, cognition, neuronal repolarization and risk for schizophrenia  

PubMed Central

Organized neuronal firing is critical for cortical processing and is disrupted in schizophrenia. Using 5’ RACE in human brain, we identified a primate-specific isoform (3.1) of the K+-channel KCNH2 that modulates neuronal firing. KCNH2-3.1 mRNA levels are comparable to KCNH2-1A in brain, but 1000-fold lower in heart. In schizophrenic hippocampus, KCNH2-3.1 expression is 2.5-fold greater than KCNH2-1A. A meta-analysis of 5 clinical samples (367 families, 1158 unrelated cases, 1704 controls) shows association of SNPs in KCNH2 with schizophrenia. Risk-associated alleles predict lower IQ scores and speed of cognitive processing, altered memory-linked fMRI signals, and increased KCNH2-3.1 expression in post-mortem hippocampus. KCNH2-3.1 lacks a domain critical for slow channel deactivation. Overexpression of KCNH2-3.1 in primary cortical neurons induces a rapidly deactivating K+ current and a high-frequency, non-adapting firing pattern. These results identify a novel KCNH2 channel involved in cortical physiology, cognition, and psychosis, providing a potential new psychotherapeutic drug target. PMID:19412172

Huffaker, Stephen J.; Chen, Jingshan; Nicodemus, Kristin K.; Sambataro, Fabio; Yang, Feng; Mattay, Venkata; Lipska, Barbara K.; Hyde, Thomas M.; Song, Jian; Rujescu, Daniel; Giegling, Ina; Mayilyan, Karine; Proust, Morgan J.; Soghoyan, Armen; Caforio, Grazia; Callicott, Joseph H.; Bertolino, Alessandro; Meyer-Lindenberg, Andreas; Chang, Jay; Ji, Yuanyuan; Egan, Michael F.; Goldberg, Terry E.; Kleinman, Joel E.; Lu, Bai; Weinberger, Daniel R.

2009-01-01

11

Stimulation of hERG1 channel activity promotes a calcium-dependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells  

PubMed Central

Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as marker for poor prognosis in breast cancer, and appears to play a major role in proliferation and therapeutic resistance in several breast cancer cells. Our laboratory has previously reported that stimulation of the hERG1 potassium channel with selective activators led to down-regulation of cyclin E2 in breast cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an ubiquitin-proteasome-dependent degradation of cyclin E2 in multiple breast cancer cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer cells. In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation. This novel function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1 were unaltered by the treatment. Our results reveal a novel mechanism by which hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin E1, and suggest a potential therapeutic use for hERG1 channel activators. PMID:25596745

Perez-Neut, Mathew; Shum, Andrew; Cuevas, Bruce D.; Miller, Richard; Gentile, Saverio

2015-01-01

12

PD-118057 contacts the pore helix of hERG1 channels to attenuate inactivation and enhance K+ conductance  

PubMed Central

Human ether-a-go-go-related gene 1 (hERG1) K+ channels mediate repolarization of cardiac action potentials. Unintended block of hERG1 channels by some drugs can prolong the QT interval and induce arrhythmia. Recently, hERG1 channel agonists were discovered and, based on their mechanisms of action can be classified into two types. RPR260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5 trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid], a type 1 agonist, binds to residues located near the intracellular end of S5 and S6 transmembrane segments and activates hERG1 channels by a dual mechanism of slowed deactivation and attenuated P-type inactivation. As defined here, type 2 agonists such as PD-118057 [2-(4-[2-(3,4-dichloro-phenyl)-ethyl]-phenylamino)-benzoic acid] attenuate inactivation but do not slow deactivation. At 10 ?M, PD-118057 shifted the half-point for inactivation of wild-type hERG1 channels by +19 mV and increased peak outward current by 136%. Scanning mutagenesis and functional characterization of 44 mutant channels expressed in Xenopus oocytes was used to identify the major structural determinants of the binding site for PD-118057. Single mutations of residues in the pore helix (F619) or the S6 segment (L646) of hERG1 eliminated agonist activity. Mutation of a nearby residues in the S6 segment (C643, M645) enhanced drug activity, presumably by reducing steric hindrance for drug binding. Molecular modeling indicates that PD-118057 binds to a hydrophobic pocket formed by L646 of one hERG1 subunit and F619 of an adjacent subunit. We conclude that direct interaction of PD-118057 with the pore helix attenuates fast P-type inactivation and increases open probability of hERG1 channels. PMID:19892732

Perry, Matthew; Sachse, Frank B.; Abbruzzese, Jennifer; Sanguinetti, Michael C.

2009-01-01

13

Keller et al., Characterization of novel KCNH2 mutations in the long QT  

E-print Network

Keller et al., 1 Characterization of novel KCNH2 mutations in the long QT syndrome type 2 Abstract: Background: The Long QT Syndrome (LQTS) is characterized by QTc-prolongation leading to Torsades as "seizure" and Sudden Cardiac Death, and to analyse their impact on the channel function in vitro. Methods

Boyer, Edmond

14

Trafficking Defect and Proteasomal Degradation Contribute to the Phenotype of a Novel KCNH2 Long QT Syndrome Mutation  

PubMed Central

The Kv11.1 (hERG) K+ channel plays a fundamental role in cardiac repolarization. Missense mutations in KCNH2, the gene encoding Kv11.1, cause long QT syndrome (LQTS) and frequently cause channel trafficking-deficiencies. This study characterized the properties of a novel KCNH2 mutation discovered in a LQT2 patient resuscitated from a ventricular fibrillation arrest. Proband genotyping was performed by SSCP and DNA sequencing. The electrophysiological and biochemical properties of the mutant channel were investigated after expression in HEK293 cells. The proband manifested a QTc of 554 ms prior to electrolyte normalization. Mutation analysis revealed an autosomal dominant frameshift mutation at proline 1086 (P1086fs+32X; 3256InsG). Co-immunoprecipitation demonstrated that wild-type Kv11.1 and mutant channels coassemble. Western blot showed that the mutation did not produce mature complex-glycosylated Kv11.1 channels and coexpression resulted in reduced channel maturation. Electrophysiological recordings revealed mutant channel peak currents to be similar to untransfected cells. Co-expression of channels in a 1?1 ratio demonstrated dominant negative suppression of peak Kv11.1 currents. Immunocytochemistry confirmed that mutant channels were not present at the plasma membrane. Mutant channel trafficking rescue was attempted by incubation at reduced temperature or with the pharmacological agents E-4031. These treatments did not significantly increase peak mutant currents or induce the formation of mature complex-glycosylated channels. The proteasomal inhibitor lactacystin increased the protein levels of the mutant channels demonstrating proteasomal degradation, but failed to induce mutant Kv11.1 protein trafficking. Our study demonstrates a novel dominant-negative Kv11.1 mutation, which results in degraded non-functional channels leading to a LQT2 phenotype. PMID:21483829

Mihic, Anton; Chauhan, Vijay S.; Gao, Xiaodong; Oudit, Gavin Y.; Tsushima, Robert G.

2011-01-01

15

Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2.  

PubMed

Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2. The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4-V6 and LQT1 morphology in leads V1-V2. Genomic DNA was isolated from lymphocytes. All exons and intron borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed patch-clamp analysis. In addition, WT or K897T Kv11.1 were also studied by patch clamp. Current-voltage (I-V) relations for V110I showed a significant reduction in both developing and tail current densities compared with WT at potentials >+20 mV (p < 0.05; n = 8 cells, each group), suggesting a reduction in IKs currents. K897T- Kv11.1 channels displayed a significantly reduced tail current density compared with WT-Kv11.1 at potentials >+10 mV. Interestingly, channel availability assessed using a triple-pulse protocol was slightly greater for K897T compared with WT (V0.5 = -53.1 ± 1.13 mV and -60.7 ± 1.15 mV for K897T and WT, respectively; p < 0.05). Comparison of the fully activated I-V revealed no difference in the rectification properties between WT and K897T channels. We report a patient with a loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest that a reduction of both IKr and IKs underlies the combined LQT1 and LQT2 phenotype observed in this patient. PMID:21164565

Cordeiro, Jonathan M; Perez, Guillermo J; Schmitt, Nicole; Pfeiffer, Ryan; Nesterenko, Vladislav V; Burashnikov, Elena; Veltmann, Christian; Borggrefe, Martin; Wolpert, Christian; Schimpf, Rainer; Antzelevitch, Charles

2010-12-01

16

The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and ?,?-ADR Blocker Response in EH Patients in China  

PubMed Central

Background KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. Materials and Methods To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. Results There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P?=?0.010), MAP change (P?=?0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of ?,?-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P?=?0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. Conclusion We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs. PMID:23613831

He, Fazhong; Luo, Jianquan; Luo, Zhiying; Fan, Lan; He, Yijing; Zhu, Dingliang; Gao, Jinping; Deng, Sheng; Wang, Yan; Qian, Yuesheng; Zhou, Honghao; Chen, Xiaoping; Zhang, Wei

2013-01-01

17

Gating and assembly of heteromeric hERG1a/1b channels underlying  

E-print Network

by immunocytochemistry to localize to the same subcellular compartment. These new ¢ndings raise questions as to the role of mutations causing hERG-linked long QT syndrome, approximately 20% of which reside in the hERG1a N potassium channel: structure, function, and long QT syndrome. Wiley, Chichester (Novartis Foundation

Kemnitz, Joseph

18

HERG1 functions as an oncogene in pancreatic cancer and is downregulated by miR-96  

PubMed Central

Pancreatic cancer is an aggressive malignancy with an extremely poor prognosis. The human ether-a-go-go-related potassium channel (HERG1) is a human rapid delayed rectifier, which is involved in many crucial cellular events. In this article, we find that HERG1 expression is dramatically increased both in pancreatic cancer tissues and cell lines, and that increased HERG1 expression is significantly related to the development of pancreatic cancer. HERG1 silencing in pancreatic cancer-derived cell lines PANC-1 and CFPAC-1 strongly inhibits their malignant capacity in vitro as well as tumorigenicity and metastasis in nude mice. In addition, HERG1 is identified as a direct target of miR-96, which is downregulated in pancreatic cancer tissues and cell lines. Ectopic expression of miR-96 represses the HERG1 expression in pancreatic cancer and significantly inhibits malignant behavior of pancreatic cancer cells in vitro and in vivo. Collectively, our findings suggest that miR-96 acts as a tumor suppressor in pancreatic cancer and may therefore serve as a useful therapeutic target for the development of new anticancer therapy. PMID:25071021

Li, Zengliang; Chen, Zheng; Zhang, Wenjie; Wang, Bin; Yang, Li; Xu, Hao; Zhang, Guoxin; Xu, Zekuan

2014-01-01

19

Stromal upregulation of lateral epithelial adhesions: Gene expression analysis of signalling pathways in prostate epithelium  

PubMed Central

Background Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process. Methods Microarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with stromal co-culture compared to without stroma. Two culture models were employed: primary epithelial cells (ten samples) and an epithelial cell line (three experiments). A separate microarray analysis was performed on each model system and then compared to identify tissue-relevant genes in a cell line model. Results TGF beta signalling was significantly ranked for both model systems and in both models the TGF beta signalling gene SOX4 was significantly down regulated. Analysis of all differentially expressed genes to identify genes that were common to both models found several morphology related gene clusters; actin binding (DIAPH2, FHOD3, ABLIM1, TMOD4, MYH10), GTPase activator activity (BCR, MYH10), cytoskeleton (MAP2, MYH10, TMOD4, FHOD3), protein binding (ITGA6, CD44), proteinaceous extracellular matrix (NID2, CILP2), ion channel/ ion transporter activity (CACNA1C, CACNB2, KCNH2, SLC8A1, SLC39A9) and genes associated with developmental pathways (POFUT1, FZD2, HOXA5, IRX2, FGF11, SOX4, SMARCC1). Conclusions In 3D prostate cultures, stromal cells increase lateral epithelial cell adhesions. We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity. PMID:21696611

2011-01-01

20

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.

BEGIN:VCARD VERSION:2.1 FN:Access Excellence N:Excellence; Access REV:2005-03-12 END:VCARD

2005-03-12

21

Long QT Interval in Turner Syndrome – A High Prevalence of LQTS Gene Mutations  

PubMed Central

Objectives QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. Methods Adult women with Turner syndrome (n?=?88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett’s (bQTc) and Hodges’s formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. Results The mean hQTc in women with Turner syndrome (414.0±25.5 ms) compared to controls (390.4±17.8 ms) was prolonged (p<0.001) and did not change over time (416.9±22.6 vs. 415.6±25.5 ms; p?=?0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2±24.8 vs. 407.6±25.5 ms; p?=?0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). Conclusion There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. Clinical Trial Registration NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E. PMID:23936059

Trolle, Christian; Mortensen, Kristian H.; Pedersen, Lisbeth N.; Berglund, Agnethe; Jensen, Henrik K.; Andersen, Niels H.; Gravholt, Claus H.

2013-01-01

22

Species diversity and peptide toxins blocking selectivity of ether-a-go-go-related gene subfamily K+ channels in the central nervous system.  

PubMed

The ether-à-go-go-related gene (erg) K+ channels are known to be crucial for life in Caenorhabditis elegans (mating), Drosophila melanogaster (seizure), and humans (LQT syndrome). The erg genes known to date (erg1, erg2, and erg3) are highly expressed in various areas of the rat and mouse central nervous system (CNS), and ERG channel blockers alter firing accommodation. To assign physiological roles to each isoform, it is necessary to design pharmacological strategies to distinguish individual currents. To this purpose, we have investigated the blocking properties of specific peptide inhibitors of hERG1 channels on the human and rat isoforms. In particular, we have tested ErgTx1 (from the scorpion Centruroides noxious), BeKm-1 (from the scorpion Buthus eupeus), and APETx1 (from the sea anemone Anthopleura elegantissima). Because these peptides had different species-specific effects on the six different channels, we have also carried out a biophysical characterization of hERG2 and hERG3 channels that turned out to be different from the rat homologs. It emerged that APETx1 is exquisitely selective for ERG1 and does not compete with the other two toxins. BeKm-1 discriminates well among the three rat members. ErgTx1 is unable to block hERG2, but blocks rERG2 and has the lowest KD for hERG3. BeKm-1 and ErgTx1 compete for hERG3 but not for rERG2 blockade. Our findings should be helpful for structure-function studies and for novel CNS ERG-specific drug design. PMID:16497878

Restano-Cassulini, Rita; Korolkova, Yuliya V; Diochot, Sylvie; Gurrola, Georgina; Guasti, Leonardo; Possani, Lourival D; Lazdunski, Michel; Grishin, Eugene V; Arcangeli, Annarosa; Wanke, Enzo

2006-05-01

23

Genes and Gene Therapy  

MedlinePLUS

... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

24

hERG subunit composition determines differential drug sensitivity  

PubMed Central

BACKGROUND AND PURPOSE The majority of human ether-a-go-go-related gene (hERG) screens aiming to minimize the risk of drug-induced long QT syndrome have been conducted using heterologous systems expressing the hERG 1a subunit, although both hERG 1a and 1b subunits contribute to the K+ channels producing the repolarizing current IKr. We tested a range of compounds selected for their diversity to determine whether hERG 1a and 1a/1b channels exhibit different sensitivities that may influence safety margins or contribute to a stratified risk analysis. EXPERIMENTAL APPROACH We used the IonWorks™ plate-based electrophysiology device to compare sensitivity of hERG 1a and 1a/1b channels stably expressed in HEK293 cells to 50 compounds previously shown to target hERG channels. Potency was determined as IC50 values (µM) obtained from non-cumulative, eight-point concentration–effect curves of normalized data, fitted to the Hill equation. To minimize possible sources of variability, compound potency was assessed using test plates arranged in alternating columns of cells expressing hERG 1a and 1a/1b. KEY RESULTS Although the potency of most compounds was similar for the two targets, some surprising differences were observed. Fluoxetine (Prozac) was more potent at blocking hERG 1a/1b than 1a channels, yielding a corresponding reduction in the safety margin. In contrast, E-4031 was a more potent blocker of hERG 1a compared with 1a/1b channels, as previously reported, as was dofetilide, another high-affinity blocker. CONCLUSIONS AND IMPLICATIONS The current assays may underestimate the risk of some drugs to cause torsades de pointes arrhythmia, and overestimate the risk of others. PMID:21449979

Abi-Gerges, N; Holkham, H; Jones, EMC; Pollard, CE; Valentin, J-P; Robertson, GA

2011-01-01

25

Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.  

PubMed

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle. The amplitude of ventricular myocyte shortening and the intracellular Ca(2+) transient were unaltered; however, the time-to-peak shortening was prolonged and time-to-half decay of the Ca(2+) transient was shortened in GK myocytes compared with control myocytes. The results of this study demonstrate changes in expression of genes encoding various excitation-contraction coupling proteins that are associated with disturbances in myocyte shortening and intracellular Ca(2+) transport. PMID:22581745

Salem, K A; Adrian, T E; Qureshi, M A; Parekh, K; Oz, M; Howarth, F C

2012-12-01

26

Identification and characterisation of a novel KCNQ1 mutation in a family with Romano–Ward syndrome  

Microsoft Academic Search

Romano–Ward syndrome (RWS), the autosomal dominant form of the congenital long QT syndrome, is characterised by prolongation of the cardiac repolarisation process associated with ventricular tachyarrhythmias of the torsades de pointes type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder.

J. Zehelein; D. Thomas; M. Khalil; A.-B. Wimmer; M. Koenen; M. Licka; K. Wu; J. Kiehn; K. Brockmeier; V. A. W. Kreye; C. A. Karle; H. A. Katus; H. E. Ulmer; W. Schoels

2004-01-01

27

Torsades de pointes following acute myocardial infarction: Evidence for a deadly link with a common genetic variant  

PubMed Central

BACKGROUND Although QT prolongation following myocardial infarction (MI) is generally moderate, cases with marked QT prolongation leading to life-threatening torsades de pointes (TdP) have been described. OBJECTIVE To investigate the genetic substrate of this phenomenon. METHODS We studied 13 patients who developed TdP in the subacute phase of MI (2–11 days) and a group of 133 ethnically matched controls with uncomplicated MI. Long QT syndrome genes and the KCNH2-K897T polymorphism were screened by using denaturing high-performance liquid chromatography plus direct sequencing and a specific TaqMan assay, respectively. RESULTS Two of the 13 patients (15%) who presented with QT prolongation and TdP were found to carry long QT syndrome mutations (KCNH2-R744X and SCN5A-E446K). Nine of the remaining 11 patients (82%) carried the KCNH2-K897T polymorphism, which was present in 35% of the controls (P = .0035). Thus, patients with an acute MI carrying the KCNH2-K897T polymorphism had an 8-fold greater risk of experiencing TdP compared with controls (95% confidence interval = 2–40). CONCLUSIONS Our data suggest that the common K897T polymorphism is associated with an increased risk of TdP developing in the subacute phase of MI. Our findings support the concept that the electrical remodeling associated with this healing phase of MI may unmask a genetic substrate predisposing to a time-limited development of life-threatening arrhythmias. They also provide the first line of evidence in support of the hypothesis that a common polymorphism, previously described as a modifier of the severity of LQTS, may increase the risk of life-threatening arrhythmias in a much more prevalent cardiac disease such as myocardial infarction. PMID:22338672

Crotti, Lia; Hu, Dan; Barajas-Martinez, Hector; De Ferrari, Gaetano M.; Oliva, Antonio; Insolia, Roberto; Pollevick, Guido D.; Dagradi, Federica; Guerchicoff, Alejandra; Greco, Federica; Schwartz, Peter J.; Viskin, Sami; Antzelevitch, Charles

2013-01-01

28

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. PMID:19641145

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

2009-01-01

29

Gene Modifications  

NSDL National Science Digital Library

This animation shows how a gene is constructed to eventually produce a protein in a Bt corn plant. This is the fifth of a series of seven animations that detail the process of crop genetic engineering. To begin at the beginning, see Overview of Crop Genetic Engineering. (To return to the animation previous to this, go to Gene Regions. To go to the next animation, go to Gene Gun.)

30

Gene Therapy  

PubMed Central

Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases. PMID:24372817

Baum, Bruce J

2014-01-01

31

Gene Control  

NSDL National Science Digital Library

The development of creatures that appear to have nothing in common is directed by a surprisingly small number of genes. In this video segment, learn about the power of master control genes. Footage from The Secret of Life: Birth, Sex & Death.

2003-09-26

32

Gene Gun  

NSDL National Science Digital Library

How the gene gun works to transform cells with new DNA. This is thesixth of a series of seven animations that detail the process of cropgenetic engineering. To begin at the beginning, see Overview of Crop Genetic Engineering. (To return to the animation previous to this, go to Gene Modification. To go to the next animation, go to Backcross Breeding.)

33

Gene Identification  

NSDL National Science Digital Library

This module will examine the "Language" of genes and illustrate how basic statistical methods can be applied to the problem of gene prediction. The merger of computational sciences with biology, and the challenges facing BioinFormatics, will also be explored through the use of analysis tools available at the National Center for Biotechnology InFormation (NCBI).

Chuck Daniels

34

Trichoderma genes  

DOEpatents

Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

Foreman, Pamela (Los Altos, CA); Goedegebuur, Frits (Vlaardingen, NL); Van Solingen, Pieter (Naaldwijk, NL); Ward, Michael (San Francisco, CA)

2012-06-19

35

GENE MAPPING  

Technology Transfer Automated Retrieval System (TEKTRAN)

Gene mapping is the science of determining the location of a gene in a species' genome. The genome of most mammalian species is comprised of approximately three billion bases of deoxyribonucleic acid (DNA) contained in 18-35 separate linear molecules (chromosomes). Mammals are diploid organisms so e...

36

Gene Puzzles  

NSDL National Science Digital Library

In this Science NetLinks lesson, students will examine a fictional pedigree and determine which gene is responsible for a given trait. The genetic information for individuals is depicted as a jigsaw puzzle. Without delving into a complicated explanation of the process, the activity in this lesson will help students build an understanding of how offspring inherit genes from their parents.

Science Netlinks

2001-10-20

37

Gene Cloning  

NSDL National Science Digital Library

This interactive activity adapted from the University of Nebraska's Library of Crop Technologies details the steps involved in producing clones of genes that can then be used to transform the characteristics of an organism.

2009-09-08

38

Genes V.  

SciTech Connect

This fifth edition book encompasses a wide range of topics covering 1,272 pages. The book is arranged into nine parts with a total of 36 chapters. These nine parts include Introduction; DNA as a Store of Information; Translation; Constructing Cells; Control of Prokaryotypic Gene Expression; Perpetuation of DNA; Organization of the Eukaryotypic Genome; Eukaryotypic Transcription and RNA Processing; The Dynamic Genome; and Genes in Development.

Lewin, B.

1994-12-31

39

Gene Ontology Driven Classification of Gene  

E-print Network

Gene Ontology Driven Classification of Gene Expression Patterns Claudio Lottaz and Rainer Spang Genetics #12;Overview 23-Jul-02 2 / 17Claudio Lottaz: GO driven classification of gene expression patterns Overview · Introduction · Gene Ontology driven classification of gene expression patterns · Preliminary

Spang, Rainer

40

Attention Genes  

ERIC Educational Resources Information Center

A major problem for developmental science is understanding how the cognitive and emotional networks important in carrying out mental processes can be related to individual differences. The last five years have seen major advances in establishing links between alleles of specific genes and the neural networks underlying aspects of attention. These…

Posner, Michael I.; Rothbart, Mary K.; Sheese, Brad E.

2007-01-01

41

Designer Genes.  

ERIC Educational Resources Information Center

Genetic technologies may soon help fill some of the most important needs of humanity from food to energy to health care. The research of major designer genes companies and reasons why the initial mad rush for biotechnology has slowed are reviewed. (SR)

Miller, Judith; Miller, Mark

1983-01-01

42

Sandro Rusconi Gene transfer  

E-print Network

Program 37 'Somatic Gene Therapy' 2001-today Swiss Natl. Res. Program 50 'Endocrine disruptors' 2002 with other doping, detection Techniques of gene transfer (Gene Therapy) problems and solutions, vectors Somatic Gene Therapy (somatic gene transfer) UNIFR Rusconi 2003 Definition of GT: 'Use genes as drugs

Málaga, Universidad de

43

Gene Expression Mural: Visualizing Gene Expression Databases  

E-print Network

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

44

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.

2013-07-30

45

Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel  

PubMed Central

Ovarian cancer remains the leading cause of death in women with gynecologic malignancies, despite surgical advances and the development of more effective chemotherapeutics. As increasing evidence indicates that clear-cell ovarian cancer may have unique pathogenesis, further understanding of molecular features may enable us to begin to understand the underlying biology and histology-specific information for improved outcomes. To study epigenetics in clear-cell ovarian cancer, fresh frozen tumor DNA (n = 485) was assayed on Illumina Infinium HumanMethylation450 BeadChips. We identified a clear-cell ovarian cancer tumor methylation profile (n = 163) which we validated in two independent replication sets (set 1, n = 163; set 2, n = 159), highlighting 22 CpG loci associated with nine genes (VWA1, FOXP1, FGFRL1, LINC00340, KCNH2, ANK1, ATXN2, NDRG21 and SLC16A11). Nearly all of the differentially methylated CpGs showed a propensity toward hypermethylation among clear-cell cases. Several loci methylation inversely correlated with tumor gene expression, most notably KCNH2 (HERG, a potassium channel) (P = 9.5 × 10?7), indicating epigenetic silencing. In addition, a predicted methylation class mainly represented by the clear-cell cases (20 clear cell out of 23 cases) had improved survival time. Although these analyses included only 30 clear-cell carcinomas, results suggest that loss of expression of KCNH2 (HERG) by methylation could be a good prognostic marker, given that overexpression of the potassium (K+) channel Eag family members promotes increased proliferation and results in poor prognosis. Validation in a bigger cohort of clear-cell tumors of the ovary is warranted. PMID:23571109

Cicek, Mine S.; Koestler, Devin C.; Fridley, Brooke L.; Kalli, Kimberly R.; Armasu, Sebastian M.; Larson, Melissa C.; Wang, Chen; Winham, Stacey J.; Vierkant, Robert A.; Rider, David N.; Block, Matthew S.; Klotzle, Brandy; Konecny, Gottfried; Winterhoff, Boris J.; Hamidi, Habib; Shridhar, Viji; Fan, Jian-Bing; Visscher, Daniel W.; Olson, Janet E.; Hartmann, Lynn C.; Bibikova, Marina; Chien, Jeremy; Cunningham, Julie M.; Goode, Ellen L.

2013-01-01

46

Cardiac Potassium Channel Dysfunction in Sudden Infant Death Syndrome  

PubMed Central

Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5–10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases. Three of the six variants exhibited functional impairments while three were biophysically similar to wild-type channels (KCNH2 variants V279M, R885C, S1040G). When coexpressed with WT-HERG, R273Q and K897T/R954C generated currents resembling the rapid component of the cardiac delayed rectifier current (IKr) but with significantly diminished amplitude. Action potential modeling demonstrated that this level of functional impairment was sufficient to evoke increased action potential duration and pause-dependent early afterdepolarizations. By contrast, KCNQ1-I274V causes a gain-of-function in IKs characterized by increased current density, faster activation, and slower deactivation leading to accumulation of instantaneous current upon repeated stimulation. Action potential simulations using a Markov model of heterozygous I274V-IKs incorporated into the Luo-Rudy (LRd) ventricular cell model demonstrated marked rate-dependent shortening of action potential duration predicting a short QT phenotype. Our results indicate that certain potassium channel mutations associated with SIDS confer overt functional defects consistent with either LQTS or SQTS, and further emphasize the role of congenital arrhythmia susceptibility in this syndrome. PMID:18222468

Rhodes, Troy E.; Abraham, Robert A.; Welch, Richard C.; Vanoye, Carlos G.; Crotti, Lia; Arnestad, Marianne; Insolia, Roberto; Pedrazzini, Matteo; Ferrandi, Chiara; Vege, Ashild; Rognum, Torleiv; Roden, Dan M.; Schwartz, Peter J.; George, Alfred L.

2008-01-01

47

Gene - Gene Interactions Among MCP Genes Polymorphisms in Asthma  

PubMed Central

Purpose Monocyte chemoattractant proteins (MCPs) are important cytokines that involved in cellular activation and releasing of inflammatoy mediators by basophils and eosinophils in allergic disease. Some MCP gene variants implicate in asthma and monoclonal antibody for MCP-3 blocks allergic inflammations in the patients with asthma. Detection of interactions between gene and environment or between genes for complex disease such as asthma is important. We searched for an evidence of genetic effect of single nucleotide polymorphisms (SNPs) of MCP genes as well as gene - gene interactions involved in asthma. Methods Four hundreds asthmatics and four hundreds normal controls were enrolled. Asthma was defined as a positive bronchodilator response or positive methacholine provocation test with compatible clinical symptoms. Seven MCP gene SNPs (2 SNPs in MCP-1, 1 in MCP-2, and 4 in MCP-3) were included. Association analyses between SNP and asthma, and the tests for gene - gene interaction were performed. Results Strong linkage disequilibria were found among 7 MCP gene polymorphisms. There was no SNP that showed a significant association with asthma among 7 SNPs of 3 MCP genes. No haplotype was associated with asthma, either. The combination of MCP1-2518G>A, MCP2+46A>C, and MCP3+563C>T was the best predictive model for asthma as compared to the control in tests for gene - gene interaction. The MCP1-2518G>A and MCP2+46A>C was the second best predictive combination and this had the highest synergistic interaction effect on the subject's status than any other combination of polymorphisms. Complete linkages were not associated with the gene - gene interactions models. Conclusions MCP gene polymorphisms probably interact with each other; thus, these findings may help in developing a possible genetic marker to predict asthma. PMID:24991457

Lee, June-Hyuk

2014-01-01

48

Sandro Rusconi Gene transfer  

E-print Network

Research Program 37 'Somatic Gene Therapy' 2001-today Swiss Natl. Res. Program 50 'Endocrine disruptors, comparison with other doping, detection Techniques of gene transfer (Gene Therapy) problems and solutions getting oldcomp2.mov movie clip deleted Now, let's talk about Somatic Gene Therapy (somatic gene transfer

Málaga, Universidad de

49

Computational Gene Finding  

E-print Network

Computational Gene Finding Dong Xu Digital Biology Laboratory Computer Science Department://digbio.missouri.edu #12; Protein-encoding genes and gene structures Computational models for coding regions;What Is a Gene? Definition: A gene is the nucleotide sequence that stores the information which

Cheng, Jianlin Jack

50

GENES 2000  

NSDL National Science Digital Library

Benjamin Lewin provides this detailed educational site as the online (and continuously updated) version of the printed resource, GENES. Designed as a pilot project "for building an online site that will develop into a general resource for the life sciences, including molecular biology, cell biology, development, immunology, and neurobiology, at levels varying from introductory to advanced," this impressive site is intended to be useful to students at the undergraduate level (or above). First-time users must register (access is free, "at least temporarily") to gain access to chapters; registered users may conduct searches, build references, write notes, highlight specified information, or browse the full resource. Future plans include "better (and faster) searches on the text, searches on figures, identification of new material and recently added references, printing by chapter or by section, more animations, on line tests and problem sets." Content is detailed, well illustrated, and thorough; this looks to be an exceptional resource.

51

Genes and Psoriasis  

MedlinePLUS

... Health Plans For Your Patients Donate Genes and Psoriasis Genes hold the key to understanding how the ... Are some genes linked to specific kinds of psoriasis? At the University of Utah, Drs. Gerald Krueger ...

52

Insert or gene Laboratory Gene transfer vectora  

E-print Network

Insert or gene Laboratory Gene transfer vectora Host rangeb functionc containment leveld MMLV based, CC BSL-2 including neurons TX BSL-2+/BSL-3 Poxvirus based- Broad host range S, E, M, T, DR, MP BSL-2 cells. c General categories of cellular genes and functions: S, structural proteins: actin, myosin, etc

Kay, Mark A.

53

Gene gymnastics  

PubMed Central

Most essential activities in eukaryotic cells are catalyzed by large multiprotein assemblies containing up to ten or more interlocking subunits. The vast majority of these protein complexes are not easily accessible for high resolution studies aimed at unlocking their mechanisms, due to their low cellular abundance and high heterogeneity. Recombinant overproduction can resolve this bottleneck and baculovirus expression vector systems (BEVS) have emerged as particularly powerful tools for the provision of eukaryotic multiprotein complexes in high quality and quantity. Recently, synthetic biology approaches have begun to make their mark in improving existing BEVS reagents by de novo design of streamlined transfer plasmids and by engineering the baculovirus genome. Here we present OmniBac, comprising new custom designed reagents that further facilitate the integration of heterologous genes into the baculovirus genome for multiprotein expression. Based on comparative genome analysis and data mining, we herein present a blueprint to custom design and engineer the entire baculovirus genome for optimized production properties using a bottom-up synthetic biology approach. PMID:23328086

Vijayachandran, Lakshmi S; Thimiri Govinda Raj, Deepak B; Edelweiss, Evelina; Gupta, Kapil; Maier, Josef; Gordeliy, Valentin; Fitzgerald, Daniel J; Berger, Imre

2013-01-01

54

Gene doping: gene delivery for olympic victory  

PubMed Central

With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. PMID:23082866

Gould, David

2013-01-01

55

Clustering gene expression patterns  

Microsoft Academic Search

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

Amir Ben-Dor; Zohar Yakhinit; Zohar Yakhini

1999-01-01

56

Tests for gene clustering  

Microsoft Academic Search

Comparing chromosomal gene order in two or more related species is an important approach to studying the forces that guide genome organization and evolution. Linked clusters of similar genes found in related genomes are often used to support arguments of evolutionary relatedness or functional selection. However, as the gene order and the gene complement of sister genomes diverge progressively due

Dannie Durand; David Sankoff

2002-01-01

57

Corneal gene therapy  

Microsoft Academic Search

Gene therapy to the cornea can potentially correct inherited and acquired diseases of the cornea. Factors that facilitate corneal gene delivery are the accessibility and transparency of the cornea, its stability ex vivo and the immune privilege of the eye. Initial corneal gene delivery studies characterized the relationship between intraocular modes of administration and location of reporter gene expression. The

Eytan A. Klausner; Dan Peer; Robert L. Chapman; Richard F. Multack; Shridhar V. Andurkar

2007-01-01

58

Clustering gene expression data  

E-print Network

CG 1 Clustering gene expression data #12;CG 2 How Gene Expression Data Looks Expression levels, "Raw Data" conditions genes Entries of the Raw Data matrix: · Ratio values · Absolute values · ... · Row = gene's expression pattern · Column = experiment/condition's profile #12;CG 3 Data Preprocessing

Shamir, Ron

59

Differential Gene Rainer Spang  

E-print Network

Differential Gene Expression Rainer Spang Courses in Practical DNA Microarray Analysis #12;Two cell. etc.... For every sample (cell line/patient) we have the expression levels of thousands of genes and the information whether it is A or B #12;Differential gene expression: Which genes are differentially expressed

Spang, Rainer

60

Autism and Genes  

ERIC Educational Resources Information Center

This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

National Institutes of Health, 2005

2005-01-01

61

Life with 6000 Genes  

Microsoft Academic Search

The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275 transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and

A. Gofieau; B. G. Barrell; H. Bussey; R. W. Davis; B. Dujon; H. Feldmann; F. Galibert; J. D. Hoheisel; C. Jacq; M. Johnston; E. J. Louis; H. W. Mewes; Y. Murakami; P. Philippsen; H. Tettelin; S. G. Oliver

1996-01-01

62

Gene doping in sports.  

PubMed

Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement. PMID:15157120

Unal, Mehmet; Ozer Unal, Durisehvar

2004-01-01

63

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome  

PubMed Central

Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type ? subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death. PMID:18464931

Brunner, Michael; Peng, Xuwen; Liu, Gong Xin; Ren, Xiao-Qin; Ziv, Ohad; Choi, Bum-Rak; Mathur, Rajesh; Hajjiri, Mohammed; Odening, Katja E.; Steinberg, Eric; Folco, Eduardo J.; Pringa, Ekatherini; Centracchio, Jason; Macharzina, Roland R.; Donahay, Tammy; Schofield, Lorraine; Rana, Naveed; Kirk, Malcolm; Mitchell, Gary F.; Poppas, Athena; Zehender, Manfred; Koren, Gideon

2008-01-01

64

Human Gene Therapy: Genes without Frontiers?  

ERIC Educational Resources Information Center

Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

Simon, Eric J.

2002-01-01

65

Your Genes, Your Choices  

MedlinePLUS

Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

66

Proto-genes and de novo gene birth  

E-print Network

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. ...

Carvunis, Anne-Ruxandra

67

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

68

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

69

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

70

Gene Regulation by Methylation  

Microsoft Academic Search

Epigenetic gene regulation of specific genes strongly affects clinical outcome of malignant glioma. MGMT is the best studied gene for the connection of promoter methylation and clinical course in glioblastoma. While MGMT promoter methylation analysis currently does not alter treatment of glioblastoma patients, mainly because of a lack of convincing\\u000a therapy to radiotherapy and concomitant administration of alkylating drugs, there

Wolf C. Mueller; Andreas von Deimling

71

Introduction The COMT gene  

E-print Network

Introduction The COMT gene References Dopamine-Related Genetic Influences on Exploratory Decision: The goal of the present work is to explore the role of the prefrontal dopamine gene (COMT) in exploratory.D., Oas-Terpstra, J., Moreno, F. (2009). Prefrontal and Striatal Dopaminergic Genes Predict Individual

Maddox, W. Todd

72

Gene expression heterogeneous  

E-print Network

Magazine R359 Gene expression becomes heterogeneous with age Mehmet Somel1*, Philipp Khaitovich1 for an age-dependent increase in variation in gene expression has yet been found [6­9]. Using eight microarray data sets from different studies in humans and rats, we find that gene expression becomes more

Khaitovich, Philipp

73

Optimization of Heterologous Gene  

E-print Network

Optimization of Heterologous Gene Expression for In Vitro Evolution BioTechniques 30:474-476 (March 2001) Proteins can be evolved in vitro by randomly mutating the corresponding genes, expressing is the development of the high-throughput as- say or "screen". In particular, the wild- type gene should initially

Matsumura, Ichiro

74

Connectionist Approaches for Predicting Mouse Gene Function from Gene Expression  

E-print Network

Connectionist Approaches for Predicting Mouse Gene Function from Gene Expression Emad Andrews. emad@cs.toronto.edu Abstract. Identifying gene function has many useful applications especially in Gene Therapy. Identifying gene function based on gene expression data is much easier in prokaryotes than

Bonner, Anthony

75

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.

76

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.

77

[Imprinted genes in plants].  

PubMed

The expression of imprinted genes is regulated by epigenetic mechanism. In plant endosperm, the allele of imprinted genes is expressed in a pattern of parent-of-origin-dependent. The expression of imprinted genes plays essential roles in the development of embryos and their annexe structures, as well as seed size, reproductive barriers and apomixis. Along with the progress of plant epigenetic research, the exploration of imprinted genes is becoming hotspot in epigenetic research. This review focused on the parental conflict theory about the origin of imprinted genes, and the latest research advances in expression regulation mechanism of plant imprinted genes, using the examples of the important imprinted genes MEA, FIS2, FWA, MPC, and PHE1 in Arabidopsis, and FIEI and FIE2 in maize. PMID:21513148

Zhang, Li-Geng; Yang, Ruo-Fei; Fu, Feng-Ling; Li, Wan-Chen

2010-12-01

78

Oncogenes, genes, and growth factors  

SciTech Connect

This book contains 12 chapters. Some of the chapter titles are: The Epidermal Growth Factor Receptor Gene; Structure and Expression of the Nerve Growth Factor Gene; The Erythropoietin Gene; The Interleukin-2 Gene; The Transferrin Gene; and The Transferrin Receptor Gene.

Guroff, G.

1989-01-01

79

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. 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.; Débarbouillé, 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.

2003-01-01

80

Visualizing differentially expressed genes  

NASA Astrophysics Data System (ADS)

Identification of significantly differentially expressed genes (marker genes) among sample groups is a central issue in microarray analysis. This identification is important to understand the molecular pathway of diseases. Many statistical methods have been proposed to locate marker genes. These methods depend on a cutoff value for selection. A tightfisted cutoff may omit some of the important marker genes, whereas a generous threshold increases the number of false positives. Although robust models for identifying marker genes more accurately is an area of intense research, effective tools for the evaluation of results is often ignored in the literature. Despite the robustness of many of these methods, there is always some probability of false positives. In this paper, we propose a novel approach that exploits parallel coordinates to visualize the gene expression patterns so that one can compare the expression level changes of the marker genes between sample groups and determine whether the selected marker genes are valid. Such visualization is useful to measure the validity of the marker gene selection process as well as to fine tune the parameters of a particular method. A prediction method based on the selected marker genes is used to measure the reliability of our process.

Islam, Atiq U.; Iftekharuddin, Khan M.; Russomanno, David J.

2006-08-01

81

Genes and Disease  

NSDL National Science Digital Library

The National Center for Biotechnology Information of the National Library of Medicine (part of the National Institutes of Health) has posted this webpage, Genes and Disease, which provides information "for some 60 diseases associated with specific genes, and has links to the 1998 Gene Map as well as to PubMed, protein sequences, Online Mendelian Inheritance in Man, and associations related to each disease."

1998-01-01

82

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

83

DNA, Genes and Chromosomes  

NSDL National Science Digital Library

Today you will learn about the parts of DNA and what DNA, genes and chromosomes are. Today you will learn what DNA, genes and chromosomes are and the parts of the DNA molecule. Look at all of the websites, take whatever notes you need to. At the end of the assignment, be able to describle DNA, the parts of DNA, genes and chromosomes. Covers Biology Core Curriculum, ...

Mrs. Fomby

2007-11-07

84

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

2013-08-10

85

Refining discordant gene trees  

PubMed Central

Background Evolutionary studies are complicated by discordance between gene trees and the species tree in which they evolved. Dealing with discordant trees often relies on comparison costs between gene and species trees, including the well-established Robinson-Foulds, gene duplication, and deep coalescence costs. While these costs have provided credible results for binary rooted gene trees, corresponding cost definitions for non-binary unrooted gene trees, which are frequently occurring in practice, are challenged by biological realism. Result We propose a natural extension of the well-established costs for comparing unrooted and non-binary gene trees with rooted binary species trees using a binary refinement model. For the duplication cost we describe an efficient algorithm that is based on a linear time reduction and also computes an optimal rooted binary refinement of the given gene tree. Finally, we show that similar reductions lead to solutions for computing the deep coalescence and the Robinson-Foulds costs. Conclusion Our binary refinement of Robinson-Foulds, gene duplication, and deep coalescence costs for unrooted and non-binary gene trees together with the linear time reductions provided here for computing these costs significantly extends the range of trees that can be incorporated into approaches dealing with discordance. PMID:25434729

2014-01-01

86

'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

87

Testing Groups of Genes Part II: Scoring Gene Ontology Terms  

E-print Network

­ Decorrelating the GO (elim, weight), Alexa et al. (2006) ­ Parent-child approach, Grossmann et al. (2007 the genes of its child ­ a node can contain genes that are not found in the children · a subset of genes that we call significant genes (differentially expressed genes) Goal: · find the nodes from the graph

Spang, Rainer

88

Gene 254 (2000) 253263 www.elsevier.com/locate/gene  

E-print Network

Gene 254 (2000) 253­263 www.elsevier.com/locate/gene The C. elegans gene lin-9,which acts in an Rb The Caenorhabditis elegans gene lin-9 functions in an Rb-related pathway that acts antagonistically to a receptor are multipotent and can adopt either vulval or non- one gene in each pathway is mutated do the cells P3.p

Horvitz, H. Robert

89

Using Gene Expression Noise to Understand Gene Regulation  

E-print Network

REVIEW Using Gene Expression Noise to Understand Gene Regulation Brian Munsky,1 * Gregor Neuert,2 environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been and messenger RNA levels, and they have discovered strong connections between noise and gene regulation

Munsky, Brian

90

Gene 256 (2000) 245252 www.elsevier.com/locate/gene  

E-print Network

Gene 256 (2000) 245­252 www.elsevier.com/locate/gene Redundant and non-functional guide RNA genes in Trypanosoma brucei are a consequence of multiple genes per minicircle Nicholas J. Savill *, Paul G. Higgs classes that contain several functional gRNA genes can be lost from the population via drift and replaced

Schnaufer, Achim

91

Gene 259 (2000) 129138 www.elsevier.com/locate/gene  

E-print Network

Gene 259 (2000) 129­138 www.elsevier.com/locate/gene Evolutionary history of the enolase gene tissue-specific isozymes encoded by three genes: alpha (a), beta (b), and gamma (c) enolase. Limited taxonomic sampling of enolase has obscured the timing of gene duplication events. To help clarify

Hedges, Blair

92

The Gene Ontology (GO) database and informatics Gene Ontology Consortium*  

E-print Network

The Gene Ontology (GO) database and informatics resource Gene Ontology Consortium* GO-EBI, EMBL and Accepted September 12, 2003 ABSTRACT The Gene Ontology (GO) project (http://www. geneontology and cellular biology and are freely available for community use in the annotation of genes, gene products

Botstein, David

93

Gene 252 (2000) 8393 www.elsevier.com/locate/gene  

E-print Network

Gene 252 (2000) 83­93 www.elsevier.com/locate/gene A family of genes with growth factor 45% amino acid identity and 61% similarity to one another. Both genes are preferentially expressed of adults as well as in puparia, while neither gene is expressed during the larval developmental stages

Aksoy, Serap

94

Evolutionary Origin of Orphan Genes  

E-print Network

Evolutionary Origin of Orphan Genes Diethard Tautz, Max-Planck Institute for Evolutionary Biology they turn out to be useful. Orphan genes may have played key roles in generating lineage- specific with a gene family that was known before. Such genes were originally called `orphan' genes (Dujon, 1996

95

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

96

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...

97

The Gene Ontology Consortium  

Microsoft Academic Search

Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied

Michael Ashburner; Catherine A. Ball; Judith A. Blake; David Botstein; Heather Butler; J. Michael Cherry; Allan P. Davis; Kara Dolinski; Selina S. Dwight; Janan T. Eppig; Midori A. Harris; David P. Hill; Laurie Issel-Tarver; Andrew Kasarskis; Suzanna Lewis; John C. Matese; Joel E. Richardson; Martin Ringwald; Gerald M. Rubin; Gavin Sherlock

2000-01-01

98

Antitumor gene therapy  

Microsoft Academic Search

Gene therapy as an anti-tumor strategy is becoming a powerful tool for cytokine delivery to inhibit the growth of many tumors. Several delivery systems are being utilized and designed for the expression of specific genes to achieve a therapeutic result. Liposomes, retroviral vectors, and adenoviral vectors have all been used and eventual clinical application may depend on the type of

C. Cirielli; M. C. Capogrossi; A. Passaniti

1997-01-01

99

What Is a Gene?  

MedlinePLUS

... medicine — so new that scientists are still doing experiments to see if it works. It uses the technology of genetic engineering to treat a disease caused by a gene that has changed in some way. One method being tested is replacing sick genes with healthy ...

100

Gene therapy for newborns  

Microsoft Academic Search

Application of gene therapy to treat genetic and infectious diseases may have several ad- vantages if performed in newborns. Because of the minimal adverse effect of the underlying disease on cells of the newborn, the relatively small size of in- fants, and the large amount of future growth, gene therapy may be more successful in newborns than in older children

DONALD B. KOHN; ROBERTSON PARKMAN

101

Entrez Gene: gene-centered information at NCBI  

Microsoft Academic Search

Entrez Gene (www.ncbi.nlm.nih.gov\\/entrez\\/query. fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to con- tribute gene-specific information or that are sched- uled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference

Donna R. Maglott; James Ostell; Kim D. Pruitt; Tatiana A. Tatusova

2005-01-01

102

GeneEd: Genetics, Education, Discovery  

NSDL National Science Digital Library

The GeneEd website was created by the National Library of Medicine (NLM), the National Human Genome Research Institute (NHGRI), and the National Institutes of Health (NIH) as a helpful resource for the teaching and learning of genetics. On the site, visitors can find labs and experiments, fact sheets, and teacher resources on topics including DNA forensics, genetic conditions, evolution, and biostatistics. First-time visitors will want to start their journey by looking over the Topics tab at the top of the page. There are 40 different thematic areas here consisting of articles, video clips, webcasts, and links to additional quality resources vetted by the GeneEd web team. The Labs & Experiments section includes virtual labs that explore the genetics of different organisms as well as links to resources provided by the Howard Hughes Medical Institute and Cold Spring Harbor Laboratory. Young people may also wish to take a look at the Careers in Genetics section as it features interviews with scientists that will inspire and delight.

103

Genes from scratch – the evolutionary fate of de novo genes  

PubMed Central

Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. PMID:25773713

Schlötterer, Christian

2015-01-01

104

Dopamine genes and ADHD.  

PubMed

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 for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed. PMID:10654656

Swanson, J M; Flodman, P; Kennedy, J; Spence, M A; Moyzis, R; Schuck, S; Murias, M; Moriarity, J; Barr, C; Smith, M; Posner, M

2000-01-01

105

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

106

Genes and Social Behavior  

PubMed Central

What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

2011-01-01

107

Positive Darwinian Selection after Gene Duplication in Primate Ribonuclease Genes  

Microsoft Academic Search

Evolutionary mechanisms of origins of new gene function have been a subject of long-standing debate. Here we report a convincing case in which positive Darwinian selection operated at the molecular level during the evolution of novel function by gene duplication. The genes for eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in primates belong to the ribonuclease gene family, and

Jianzhi Zhang; Helene F. Rosenberg; Masatoshi Nei

1998-01-01

108

Harnessing Gene Expression Networks to Prioritize Candidate Epileptic Encephalopathy Genes  

PubMed Central

We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets. PMID:25014031

Oliver, Karen L.; Lukic, Vesna; Thorne, Natalie P.; Berkovic, Samuel F.; Scheffer, Ingrid E.; Bahlo, Melanie

2014-01-01

109

Gene 237 (1999) 403411 www.elsevier.com/locate/gene  

E-print Network

Gene 237 (1999) 403­411 www.elsevier.com/locate/gene Zwittermicin A biosynthetic cluster Elizabeth cereus. The nucleotide sequence of 2.7 kb of DNA flanking the zwittermicin A self-resistance gene, zma of genes that is involved in zwittermicin A biosynthesis, representing the first biosynthetic pathway

Handelsman, Jo

110

A Gene Scrapbook A Tribute to Gene Loh  

E-print Network

A Gene Scrapbook A Tribute to Gene Loh on the Occasion of His Retirement Feb 22, 2003 #12;The Early of Technology, 1961 #12;The Missing Years Not much is known about Gene's whereabouts between 1961 until his (probably kelp) for transport by sea. #12;Why did Gene leave Cornell? He got tired of shoveling all

111

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

112

Gene 252 (2000) 137145 www.elsevier.com/locate/gene  

E-print Network

Gene 252 (2000) 137­145 www.elsevier.com/locate/gene A HECT domain ubiquitin ligase closely related, and a catalytic HECT domain. A Caenorhabditis elegans gene was cloned encoding a HECT domain protein (CeWWP1 an embryonic lethal phenotype, despite the presence of at least six additional C. elegans genes encoding HECT

Kimble, Judith

113

Inferring gene orders from gene maps using the breakpoint distance  

E-print Network

Inferring gene orders from gene maps using the breakpoint distance Guillaume Blin1 , Eric Blais2- notation of chromosomes as ordered sequences of genes. Unfortunately, different genetic mapping techniques usually give rise to different maps with unequal gene content, and often containing sets of unordered

Paris-Sud XI, Université de

114

Identifying Gene Regulatory Networks from Gene Expression Data  

E-print Network

27 Identifying Gene Regulatory Networks from Gene Expression Data Vladimir Filkov University of California, Davis 27.1 Introduction................................ ........... 27-1 27.2 Gene Networks ............................ ........... 27-2 Definition · Biological Properties · Utility 27.3 Gene Expression: Data and Analysis

Filkov, Vladimir

115

Gene 240 (1999) 4555 www.elsevier.com/locate/gene  

E-print Network

Gene 240 (1999) 45­55 www.elsevier.com/locate/gene Alternative splicing regulates the production by the same gene Annie C.Y. Chang a,1, Bjo¨rn Sohlberg a,1, Laura Trinkle-Mulcahy b, Felix Claverie-Martin a,2 mutations in rne, a gene that encodes Escherichia coli ribonuclease E. NIPP-1 was identified in bovine

Trinkle-Mulcahy, Laura

116

GENE4200/GENE6200 Fall Semester Every Year  

E-print Network

Syllabus GENE4200/GENE6200 Fall Semester Every Year Instructors Richard Meagher and Jeff Bennetzen how much writing 300 words is. Anything longer than this will not be graded in your answer. #12;GENE4200 Honor Credit students and GENE6200 students will be expected to turn in extra written assignments

Arnold, Jonathan

117

Gene 241 (2000) 101105 www.elsevier.com/locate/gene  

E-print Network

Gene 241 (2000) 101­105 www.elsevier.com/locate/gene Interspecific evolution in plant Abstract Several intragenically linked microsatellites have been identified in the floral regulatory genes in the introns of these two genes, suggesting that they are hotspots for microsatellite formation. The sequences

Purugganan, Michael D.

118

Some Genes Are Dominant  

NSDL National Science Digital Library

This interactive activity, adapted from the Dolan DNA Learning Center, illustrates how Gregor Mendel used pure-bred yellow and green peas to show that some genes are dominant and others are recessive.

WGBH Educational Foundation

2007-04-19

119

Gene structure and expression  

SciTech Connect

This book describes the structure of genes in molecular terms and summarizes present knowledge about how their activity is regulated. It covers a range of topics, including a review of the structure and replication of DNA, transcription and translation, prokaryotic and eukaryotic gene organization and expression, retroviruses and oncogenes. The book also includes a chapter on the methodology of DNA manipulation including sections on site-directed mutagenesis, the polymerase chain reaction, reporter genes and restriction fragment length polymorphisms. The hemoglobin gene system and the genetics of the proteins of the immune system are presented in the latter half of the book to show the structure and expression of the most well-studied systems in higher eukaryotes. The final chapter reviews the differences between prokaryotic and the eukaryotic genomes.

Hawkins, J. (London Univ. (United Kingdom))

1990-01-01

120

Microfluidic gene synthesis  

E-print Network

The ability to synthesize custom de novo DNA constructs rapidly, accurately, and inexpensively is highly desired by researchers, as synthetic genes and longer DNA constructs are enabling to numerous powerful applications ...

Kong, David Sun, 1979-

2008-01-01

121

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. PMID:19864470

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

2010-01-01

122

Cystic fibrosis modifier genes.  

PubMed Central

Since the recognition that CFTR genotype was not a good predictor of pulmonary disease severity in CF, several candidate modifier genes have been identified. It is unlikely that a single modifier gene will be found, but more probable that several haplotypes in combination may contribute, which in itself presents a major methodological challenge. The aims of such studies are to increase our understanding of disease pathogenesis, to aid prognosis and ultimately to lead to the development of novel treatments. PMID:16025767

Davies, Jane; Alton, Eric; Griesenbach, Uta

2005-01-01

123

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

124

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

125

Gene Center Munich Genzentrum Mnchen  

E-print Network

Gene Center Munich Genzentrum München Symposium December 1, 2010 'From Genes to Networks ­ Systems:50 ­ 12:50 Prof. Dr. Ulrike Gaul (Alexander von Humboldt Professor, LMU Munich) "Decoding regulatory gene. Patrick Cramer (LMU Munich) "Global mechanisms of gene transcription" 14:30 ­ 15:10 Prof. Dr. Gertrud

Frey, Erwin

126

Gene finding with Hidden Markov  

E-print Network

Gene finding with Hidden Markov models Rachel Brem, Mike Eisen, Lior Pachter #12;Gene Structure 5 to Gene recognition · Homology ­ BLAST, Procrustes, Exonerate · De Novo ­ GRAIL, FGENESH, GENSCAN, Genie, Glimmer, SNAP · Hybrids ­ GenomeScan, Genie · Comparative ­ Rosetta, SLAM, Twinscan #12;Ab-initio gene

Pachter, Lior

127

5____________________________________________________________________________ Gene Regulation in Spermatogenesis  

E-print Network

5____________________________________________________________________________ Gene Regulation Nuclear Receptors C. HeatShock Factors D. Sox E. Plzf F. Dmrt1 G. CAF1 H. Homeobox Genes I. Perspective IV. TestisSpecific Gene Expression and DNA Methylation A. Male Germ Cell­Specific Genes B. SomaticCell Testis

Wilkinson, Miles F.

128

Identifying The Most Significant Genes From Gene Expression Profiles For Sample Classification  

E-print Network

Identifying The Most Significant Genes From Gene Expression Profiles For Sample Classification of gene expression profiles. This generated gene data include complex variations of expression levels with the existing techniques. Keywords: Bioinformatics, Gene Selection, Gene Classification. I. INTRODUCTION The DNA

Al-Mubaid, Hisham

129

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. PMID:24101916

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

2013-01-01

130

GoGene: gene annotation in the fast lane.  

PubMed

High-throughput screens such as microarrays and RNAi screens produce huge amounts of data. They typically result in hundreds of genes, which are often further explored and clustered via enriched GeneOntology terms. The strength of such analyses is that they build on high-quality manual annotations provided with the GeneOntology. However, the weakness is that annotations are restricted to process, function and location and that they do not cover all known genes in model organisms. GoGene addresses this weakness by complementing high-quality manual annotation with high-throughput text mining extracting co-occurrences of genes and ontology terms from literature. GoGene contains over 4,000,000 associations between genes and gene-related terms for 10 model organisms extracted from more than 18,000,000 PubMed entries. It does not cover only process, function and location of genes, but also biomedical categories such as diseases, compounds, techniques and mutations. By bringing it all together, GoGene provides the most recent and most complete facts about genes and can rank them according to novelty and importance. GoGene accepts keywords, gene lists, gene sequences and protein sequences as input and supports search for genes in PubMed, EntrezGene and via BLAST. Since all associations of genes to terms are supported by evidence in the literature, the results are transparent and can be verified by the user. GoGene is available at http://gopubmed.org/gogene. PMID:19465383

Plake, Conrad; Royer, Loic; Winnenburg, Rainer; Hakenberg, Jörg; Schroeder, Michael

2009-07-01

131

Fusion genes in breast cancer  

E-print Network

in breast cancer support the model that there are few commonly mutated genes, and many genes which are mutated much less frequently. Two genes stand out as often mutated in breast cancer across all subtypes: T P53 and PIK3C A. PIK3CA has been reported... distinguish between histologically similar tumours which are molecularly different (Rouzier et al., 2005). Gene expression profiling suggests that the different subtypes of breast cancer vary widely, harbouring different gene alterations and responding...

Batty, Elizabeth

2012-02-07

132

Virus induced gene silencing of Arabidopsis gene homologues in wheat identify genes conferring improved drought tolerance  

Technology Transfer Automated Retrieval System (TEKTRAN)

In a non-model staple crop like wheat, functional validation of potential drought stress responsive genes identified in Arabidopsis could provide gene targets for wheat breeding. Virus induced gene silencing (VIGS) of genes of interest can overcome the inherent problems of polyploidy and limited tra...

133

Gene finding in metatranscriptomic sequences  

PubMed Central

Background Metatranscriptomic sequencing is a highly sensitive bioassay of functional activity in a microbial community, providing complementary information to the metagenomic sequencing of the community. The acquisition of the metatranscriptomic sequences will enable us to refine the annotations of the metagenomes, and to study the gene activities and their regulation in complex microbial communities and their dynamics. Results In this paper, we present TransGeneScan, a software tool for finding genes in assembled transcripts from metatranscriptomic sequences. By incorporating several features of metatranscriptomic sequencing, including strand-specificity, short intergenic regions, and putative antisense transcripts into a Hidden Markov Model, TranGeneScan can predict a sense transcript containing one or multiple genes (in an operon) or an antisense transcript. Conclusion We tested TransGeneScan on a mock metatranscriptomic data set containing three known bacterial genomes. The results showed that TranGeneScan performs better than metagenomic gene finders (MetaGeneMark and FragGeneScan) on predicting protein coding genes in assembled transcripts, and achieves comparable or even higher accuracy than gene finders for microbial genomes (Glimmer and GeneMark). These results imply, with the assistance of metatranscriptomic sequencing, we can obtain a broad and precise picture about the genes (and their functions) in a microbial community. Availability TransGeneScan is available as open-source software on SourceForge at https://sourceforge.net/projects/transgenescan/. PMID:25253067

2014-01-01

134

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

135

Entrez Gene: gene-centered information at NCBI  

Microsoft Academic Search

ABSTRACT Entrez,Gene,(www.ncbi.nlm.nih.gov\\/entrez\\/query. fcgi?db=gene) is NCBI’s database,for gene-specific information.Itdoesnotincludeallknownorpredicted genes; instead,Entrez Gene focuses,on the genomes that have been completely sequenced, that have an active research community to contribute,genespecificinformation,orthatarescheduledforintense sequenceanalysis.Thecontent,of Entrez Gene representstheresultofcurationandautomatedintegration of data,from,NCBI’s Reference,Sequence,project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. The,content (nomenclature,

Donna R. Maglott; James Ostell; Kim D. Pruitt; Tatiana A. Tatusova

2007-01-01

136

Gene therapy in pancreatic cancer  

PubMed Central

Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

2014-01-01

137

XLMR genes: Update 1994  

SciTech Connect

We provide a comprehensive list of all known forms of X-linked mental retardation. It comprises 127 entries, subdivided into 5 categories (syndromes, dominant disorders, and nonspecific mental retardation). Map location of 69 putative loci demonstrates several overlaps, which will only be resolved by more refined mapping or cloning of the respective genes. The ultimate goal of identifying all the genes on the X chromosome whose mutations cause mental retardation will require a concerted effort between clinical and molecular investigators. 74 refs., 2 figs., 5 tabs.

Neri, G.; Chiurazzi, P. [Universita Cattolica del Sacro Cuore, Rome (Italy); Arena, J.F.; Lubs, H.A. [Univ. of Miami School of Medicine, FL (United States)

1994-07-15

138

IBM Research: Blue Gene  

NSDL National Science Digital Library

This is the home page of an IBM research and development project that is designing a supercomputer, called Blue Gene/L, capable of 200 trillion floating point operations per second. According to the Web site, this specification "is larger than the total computing power of the top 500 supercomputers in the world today." Working in collaboration with Lawrence Livermore National Laboratories, IBM expects the project to be completed by 2005. There are a few publications and presentations given about the status of the project and its uses. There is also a fact sheet and several industry links about protein folding, which is the main application of Blue Gene/L.

139

Genes and Vocal Learning  

PubMed Central

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.

2009-01-01

140

Genes2FANs: connecting genes through functional association networks  

PubMed Central

Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in many cancers are mostly connected through PPIs whereas other complex diseases, such as autism and type-2 diabetes, are mostly connected through FANs without PPIs, can guide better strategies for disease gene discovery. Genes2FANs is available at: http://actin.pharm.mssm.edu/genes2FANs. PMID:22748121

2012-01-01

141

[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

142

Gene 240 (1999) 2334 www.elsevier.com/locate/gene  

E-print Network

Gene 240 (1999) 23­34 www.elsevier.com/locate/gene Structure, alternative splicing, and expression of the human RGS9 gene k K. Zhang a,1, K.A. Howes a, W. He b, J.D. Bronson a, M.J. Pettenati c, C.-K. Chen d, K the potential role of the RGS9 gene in human retinal disease, we determined its exon/intron arrangement

Palczewski, Krzysztof

143

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

144

Gene-gene and gene-environment interactions in apolipoprotein L1 gene-associated nephropathy.  

PubMed

Molecular genetics have revolutionized the understanding of susceptibility to the broad spectrum of kidney diseases with light microscopic appearance of FSGS, particularly in populations with recent African ancestry. These disorders include idiopathic FSGS, HIV-associated nephropathy, severe lupus nephritis, sickle cell nephropathy, and the primary kidney disorder focal global glomerulosclerosis, which had historically been ascribed to systemic hypertension. FSGS was once thought to include a multitude of unrelated disorders with similar histologic appearance. However, variation in the apolipoprotein L1 gene locus is now known to account for the vast majority of such cases in African Americans as well as nearly all the excess risk for FSGS and related forms of progressive nondiabetic nephropathy in populations with recent African ancestry, relative to European ancestry. Inheriting two coding apolipoprotein L1 gene nephropathy risk variants is necessary for susceptibility to CKD; however, these variants alone are insufficient to produce disease. This work reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated nephropathy and produce the protean manifestations of this common and complex syndrome. Targeting modifiable second factors will lead to preventive therapies for slowing progression of nondiabetic nephropathy in many patients possessing two apolipoprotein L1 gene risk variants. This model of genetic risk coupled with modifiable second hits will serve as a paradigm applicable to patients with CKD of various etiologies as well as a host of other complex disorders. PMID:24903390

Freedman, Barry I; Skorecki, Karl

2014-11-01

145

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...

146

Gene-Environment Interdependence  

ERIC Educational Resources Information Center

Behavioural genetics was initially concerned with partitioning population variance into that due to genetics and that due to environmental influences. The implication was that the two were separate and it was assumed that gene-environment interactions were usually of so little importance that they could safely be ignored. Theoretical…

Rutter, Michael

2007-01-01

147

Gene Manipulation In Cereals  

Technology Transfer Automated Retrieval System (TEKTRAN)

Aluminum, the most abundant metal on earth, is detrimental to plant growth and agricultural production. There are about 2.5 billion hectares of acid soils high in aluminum around the world. Molecular markers linked to aluminum tolerance gene complexes in rye would be of value in marker-mediated ge...

148

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

149

Naming genes beyond Caenorhabditis  

Technology Transfer Automated Retrieval System (TEKTRAN)

The nomenclature of genes in Caenorhabditis elegans is based on long-standing, successful guidelines established in the late 1970s. Over time these guidelines have matured into a comprehensive, systematic nomenclature that is easy to apply, descriptive and therefore highly informative. Recently, a f...

150

Exploring Genes & Genetic Disorders  

NSDL National Science Digital Library

More and more excellent data continues to be produced by the Human Genome Project, and a number of government organizations have created top-notch educational resources based on this information. The Gene Gateway website was originally produced as a companion to the Human Genome Landmarks poster and has evolved into a "collection of guides and tutorials designed to help students and other novice users get started with some of the resources that make these data available to the public." Here visitors are introduced to various Internet tools that anyone can use to investigate "genetic disorders, chromosomes, genome maps, genes, sequence data, genetic variants, and molecular structures." Visitors can download the Gene Gateway workbook, which contains five activities, complete with screenshots and step-by-step instructions "designed to introduce new users to genetic disorder and bioinformatics resources on the Web". Moving down the homepage, visitors can look into sections such as "Bioinformatics Tools", the "Genetic Disorder Guide", and an outstanding "Chromosome Viewer". The viewer provides a great backdrop for those seeking to understand the physical makeup of human chromosomes. Also, visitors can order a free copy of the wall poster "Human Genome Landmarks: Selected Genes, Traits, and Disorders".

151

SSSR, Environment, and Genes  

ERIC Educational Resources Information Center

Environment and Genes are often found in the titles of my articles, but this is the first and most likely the last of my titles to include SSSR. This article is based on my presidential address at the 10th annual meeting of the Society for the Scientific Study of Reading (SSSR) in Boulder, Colorado (2003), so I begin with some reflection on the…

Olson, Richard K.

2004-01-01

152

Are there anxious genes?  

PubMed Central

Anxiety comprises many clinical descriptions and phenotypes. A genetic predisposition to anxiety is undoubted; however, the nature and extent of that contribution is still unclear. Methods for the genetic analysis of such complex disorders is briefly reviewed, followed by a discussion of the comorbidity of anxiety with other psychiatric disorders and their possible common genetic etiology. Extensive genetic studies of the serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) gene have revealed how variation in gene expression can be correlated with anxiety phenotypes. Complete genome-wide linkage scans for panic disorder (PD) susceptibility genes have suggested a locus on chromosome arm 7p, and association studies have highlighted many candidate genes. A highly significant association between phobias, panic disorder, and a duplication at chromosomal region 15q24-26 is one of the most exciting findings to date. Emerging molecular genetic technologies and the use of increasingly sophisticated animal models of anxiety provide great promise for the future of the field. PMID:22033820

Morris-Rosendahl, Deborah J.

2002-01-01

153

Horizontal Gene Transfer  

NSDL National Science Digital Library

This Citizendium article offers a comprehensive review of horizontal gene transfer (HGT). Topics include main features of HGT in nature, HGT in prokaryotes, HGT in eukaryotes, history and discovery of HGT, and decoding the tree of life from genomes scrambled by HGT. The image-rich text includes a list of related articles, a bibliography and external links of interest.

Citizendium

154

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

155

Clustering Genes Using Gene Expression and Text Literature Data  

Microsoft Academic Search

Clustering of gene expression data is a stan- dard technique used to identify closely related genes. In this paper, we develop a new clustering algorithm, MSC (Multi-Source Clustering), to perform exploratory analysis using two or more diverse sources of data. In particular, we investi- gate the problem of improving the clustering by integrating information obtained from gene ex- pression data

Chengyong Yang; Erliang Zeng; Tao Li; Giri Narasimhan

2005-01-01

156

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...

157

Gene 240 (1999) 247260 www.elsevier.com/locate/gene  

E-print Network

Gene 240 (1999) 247­260 www.elsevier.com/locate/gene Review Uridine insertion/deletion RNA editing-1119 ( 99 ) 00437-0 #12;248 A.M. Este´vez, L. Simpson / Gene 240 (1999) 247­260 adjacent to the basal body of t

Simpson, Larry

158

Eukaryotic Gene Prediction Using GeneMark.hmm-E and GeneMark-ES  

PubMed Central

This unit describes how to use gene finding programs GeneMark.hmm-E and GeneMark-ES for finding protein-coding genes in genomic DNA of eukaryotic genomes. These bioinformatics tools were demonstrated to have state-of-the-art accuracy for many fungal, plant and animal genomes and have been frequently used for gene annotation in novel genomic sequences. Additional advantage of GeneMark-ES is that the problem of algorithm parameterization is solved automatically, with parameters estimated by iterative self-training (unsupervised training). PMID:21901742

Borodovsky, Mark; Lomsadze, Alex

2011-01-01

159

Chapter 15: Disease Gene Prioritization  

PubMed Central

Disease-causing aberrations in the normal function of a gene define that gene as a disease gene. Proving a causal link between a gene and a disease experimentally is expensive and time-consuming. Comprehensive prioritization of candidate genes prior to experimental testing drastically reduces the associated costs. Computational gene prioritization is based on various pieces of correlative evidence that associate each gene with the given disease and suggest possible causal links. A fair amount of this evidence comes from high-throughput experimentation. Thus, well-developed methods are necessary to reliably deal with the quantity of information at hand. Existing gene prioritization techniques already significantly improve the outcomes of targeted experimental studies. Faster and more reliable techniques that account for novel data types are necessary for the development of new diagnostics, treatments, and cure for many diseases. PMID:23633938

Bromberg, Yana

2013-01-01

160

Interactive Fly: Maternally transcribed genes  

NSDL National Science Digital Library

The maternally transcribed genes section of the award-winning and comprehensive site: Interactive fly. It thoroughly discusses genes, tissues, biochemical paths, and developmental processes in the fruit fly, Drosophila.

PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

2006-11-13

161

The Human Gene Mutation Database  

NSDL National Science Digital Library

The Human Gene Mutation Database from the Institute of Medical Genetics at Cardiff provides practical information for researchers, physicians, and genetic counselors. The database is currently undergoing some reorganization, but information can be searched by "disease, gene name, or gene symbol." Search results are well organized and easy to navigate, linking directly to results from external Web databases without requiring that the user perform additional searches. Frequent users may also appreciate the listing of genes recently added to the database.

162

Nanoparticles for retinal gene therapy  

Microsoft Academic Search

Ocular gene therapy is becoming a well-established field. Viral gene therapies for the treatment of Leber’s congentinal amaurosis (LCA) are in clinical trials, and many other gene therapy approaches are being rapidly developed for application to diverse ophthalmic pathologies. Of late, development of non-viral gene therapies has been an area of intense focus and one technology, polymer-compacted DNA nanoparticles, is

Shannon M. Conley; Muna I. Naash

2010-01-01

163

Prediction of disease genes using tissue-specified gene-gene network  

PubMed Central

Background Tissue specificity is an important aspect of many genetic diseases in the context of genetic disorders as the disorder affects only few tissues. Therefore tissue specificity is important in identifying disease-gene associations. Hence this paper seeks to discuss the impact of using tissue specificity in predicting new disease-gene associations and how to use tissue specificity along with phenotype information for a particular disease. Methods In order to find out the impact of using tissue specificity for predicting new disease-gene associations, this study proposes a novel method called tissue-specified genes to construct tissues-specific gene-gene networks for different tissue samples. Subsequently, these networks are used with phenotype details to predict disease genes by using Katz method. The proposed method was compared with three other tissue-specific network construction methods in order to check its effectiveness. Furthermore, to check the possibility of using tissue-specific gene-gene network instead of generic protein-protein network at all time, the results are compared with three other methods. Results In terms of leave-one-out cross validation, calculation of the mean enrichment and ROC curves indicate that the proposed approach outperforms existing network construction methods. Furthermore tissues-specific gene-gene networks make a more positive impact on predicting disease-gene associations than generic protein-protein interaction networks. Conclusions In conclusion by integrating tissue-specific data it enabled prediction of known and unknown disease-gene associations for a particular disease more effectively. Hence it is better to use tissue-specific gene-gene network whenever possible. In addition the proposed method is a better way of constructing tissue-specific gene-gene networks. PMID:25350876

2014-01-01

164

PLANT MORPHOGENESIS AND KNOX GENES  

Technology Transfer Automated Retrieval System (TEKTRAN)

KNOX genes function in plant meristems, which produce leaves and stems. Three recent studies show that the dwarf phenotype, brevipedicellus, is caused by a recessive mutation in a KNOX gene. A fourth study shows that misexpression of KNOX genes leads to novel features that may have selective value....

165

Gene regulation in physiological stress  

Microsoft Academic Search

A range of new tools in molecular biology are now available to allow the comparative biochemist to explore animal responses to environmental stress at multiple levels. In particular, new techniques of gene discovery, such as cDNA array screening, allow broad assessment of the responses of thousands of genes to a stress. This approach frequently identifies genes (and their associated metabolic

Kenneth B. Storey

2004-01-01

166

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

BEGIN:VCARD VERSION:2.1 FN:Bruce Alberts N:Alberts; Bruce REV:2005-04-16 END:VCARD

1998-07-01

167

Gene therapy in the CNS  

Microsoft Academic Search

Gene therapy for neurological disorder is currently an experimental concept. The goals for clinical utilization are the relief of symptoms, slowing of disease progression, and correction of genetic abnormalities. Experimental studies are realizing these goals in the development of gene therapies in animal models. Discoveries of the molecular basis of neurological disease and advances in gene transfer systems have allowed

L C Costantini; J C Bakowska; X O Breakefield; O Isacson

2000-01-01

168

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

169

Mouse Genetics: Determining gene function  

E-print Network

Mouse Genetics: Determining gene function An International Centre for Mouse Genetics Mammalian Genetics Unit #12;Determining gene function · Mutagenesis approaches · Gene-driven, phenotype for Mouse Genetics Mammalian Genetics Unit #12;An International Centre for Mouse Genetics Mammalian Genetics

Goldschmidt, Christina

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

Angiogenic and antiangiogenic gene therapy  

Microsoft Academic Search

Gene therapy is thought to be a promising method for the treatment of various diseases. One gene therapy strategy invloves the manipulations on a process of formation of new vessels, commonly defined as angiogenesis. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovascular and cancer patients, respectively. So far, preclinical and clinical studies are

M Malecki; P Kolsut; R Proczka

2005-01-01

172

Gene Expression-Based Classification  

Microsoft Academic Search

Recently, there has been a growing interest in classification of patient samples based on gene expressions. Here the classification task is made more difficult by the noisy nature of the data, and by the overwhelming number of genes relative to the number of available training samples in the data set. Moreover, many of these genes are irrelevant for classification and

Topon K. Paul; Hitoshi Iba

173

(gene expression) DNA (DNA microarrays).  

E-print Network

µ µ DNA . , µ . , µ . , . µ µµ µ µ (gene expression) . µ, µ µ DNA µ 100%. I. µ , µ [1]. µ µµ µ µ (gene expression. [2] M. K. Deyholos, and D. W. Galbraith, "High- Density Microarrays for Gene Expression Analysis

Athens, University of

174

Coevolution Gene-Language Coevolution  

E-print Network

Coevolution Gene-Language Coevolution Ted Briscoe Computer Laboratory Natural Language, as we have seen, a gradual accumulation of so many genes with effects tending in this direction that the character gradually becomes genetically assimilated (The Evolution of an Evolutionist, p305-6) "Gene

Briscoe, Ted

175

GENE 8940 Genome Analysis Instructor  

E-print Network

GENE 8940 Genome Analysis Instructor: Jessica Kissinger jkissing@uga.edu C210 Life Sciences (AM changes): 15 weeks of classes 1. Aug 24 ­ Introductions ­ Of genes and genomes (DOE) 2. Aug 31 ­ Assembly ­ Genome features & Gene prediction 7. Oct 5 - Annotation and protein motifs ( CDD & PFAM) 8. Oct 12 ­ GO 9

Arnold, Jonathan

176

Gene regulation by nucleosome positioning  

E-print Network

Gene regulation by nucleosome positioning Lu Bai1 and Alexandre V. Morozov2 1 The Rockefeller]. The histone genes and nucleosome structure are extremely well conserved among eukaryotic species. Importantly in gene regulation by affecting the transcriptional compe- tence of various chromatin regions

Morozov, Alexandre V.

177

Deconstructing cell determination: proneural genes  

E-print Network

Deconstructing cell determination: proneural genes and neuronal identity Jean-Franc¸ ois Brunet1 to the relationship between the diversity of neural bHLH genes and the diversity of neuronal phenotypes. This article studies inspired by the established role of ``proneural'' genes in fly neurogenesis, as well

Montpellier II, Université

178

Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome.  

PubMed

Timothy syndrome, long QT syndrome type 8, is highly malignant with ventricular tachyarrhythmia. A 30-month-old boy had sudden cardiac arrest during anesthesia induction before plastic surgery for bilateral cutaneous syndactyly. After successful resuscitation, prolonged QT interval (QTc, 0.58-0.60 sec) and T-wave alternans were found in his electrocardiogram. Starting ?-blocker to prevent further tachycardia and collapse event, then there were no more arrhythmic events. The genes KCNQ1, KCNH2, KCNE1 and 2, and SCN5A were negative for long QT syndrome. The mutation p.Gly406Arg was confirmed in CACNA1C, which maintains L-type calcium channel depolarization in the heart and other systems. PMID:23678275

An, Hyo Soon; Choi, Eun Young; Kwon, Bo Sang; Kim, Gi Beom; Bae, Eun Jung; Noh, Chung Il; Choi, Jung Yun; Park, Sung Sup

2013-05-01

179

Genetics Home Reference: What is gene therapy?  

MedlinePLUS

... Work Mutations and Health Inheritance Consultation Testing Therapy Human Genome Project Genomic Research Next Handbook > Gene Therapy > What is ... offers a list of links to information about genes and gene therapy . Educational resources related to gene therapy are available ...

180

Gene therapy in keratoconus  

PubMed Central

Keratoconus (KC) is the most common ectasia of the cornea and is a common reason for corneal transplant. Therapeutic strategies that can arrest the progression of this disease and modify the underlying pathogenesis are getting more and more popularity among scientists. Cumulating data represent strong evidence of a genetic role in the pathogenesis of KC. Different loci have been identified, and certain mutations have also been mapped for this disease. Moreover, Biophysical properties of the cornea create an appropriate candidate of this tissue for gene therapy. Immune privilege, transparency and ex vivo stability are among these properties. Recent advantage in vectors, besides the ability to modulate the corneal milieu for accepting the target gene for a longer period and fruitful translation, make a big hope for stupendous results reasonable. PMID:25709266

Farjadnia, Mahgol; Naderan, Mohammad; Mohammadpour, Mehrdad

2015-01-01

181

Gene therapy in keratoconus.  

PubMed

Keratoconus (KC) is the most common ectasia of the cornea and is a common reason for corneal transplant. Therapeutic strategies that can arrest the progression of this disease and modify the underlying pathogenesis are getting more and more popularity among scientists. Cumulating data represent strong evidence of a genetic role in the pathogenesis of KC. Different loci have been identified, and certain mutations have also been mapped for this disease. Moreover, Biophysical properties of the cornea create an appropriate candidate of this tissue for gene therapy. Immune privilege, transparency and ex vivo stability are among these properties. Recent advantage in vectors, besides the ability to modulate the corneal milieu for accepting the target gene for a longer period and fruitful translation, make a big hope for stupendous results reasonable. PMID:25709266

Farjadnia, Mahgol; Naderan, Mohammad; Mohammadpour, Mehrdad

2015-01-01

182

Pure genes, pure genius.  

PubMed

The 2012 Albert Lasker Special Achievement Award in Medical Science will be shared by Donald Brown and Tom Maniatis for their scientific work leading to the purification and study of single genes by physical and molecular biological methodologies. Brown and Maniatis are also recognized for their extraordinary commitment and generosity in promoting the careers of young scientists. The impact of these accomplishments has transformed biological and medical science over the past four decades. PMID:22980972

McKnight, Steven L

2012-09-14

183

Canine CD20 gene  

Microsoft Academic Search

The human CD20 antigen, a 35kDa cell surface nonglycosylated hydrophobic phoshpoprotein is expressed consistently on almost all human B-cells, and its monoclonal antibody is used for the therapy on human B-cell lymphoma. In the present study, canine CD20 gene was cloned and sequenced, and the expression of CD20 mRNA was investigated in canine peripheral blood mononuclear cells (PBMCs), and lymph

Rui Kano; Chika Inoiue; Hiromi Okano; Junpei Yamazaki; Tomoko Takahashi; Toshihiro Watari; Mikihiko Tokuriki; Atsuhiko Hasegawa

2005-01-01

184

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

185

Gene Porter Bridwell  

NASA Technical Reports Server (NTRS)

Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

1994-01-01

186

Single Gene Disease Risk  

Microsoft Academic Search

\\u000a The diagnosis of a child with a single gene disorder can take on different meanings for different families. It is not uncommon\\u000a for some families to arrive at a pediatric genetics clinic after months or years of searching for an underlying reason for\\u000a their child’s symptoms. The fact that, through genetic testing, clinicians can put a name to the collection

Tricia See; Cynthia J. Tifft

187

Gene therapy of liver cancer  

PubMed Central

The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/pro-drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition, gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer. PMID:17036377

Hernandez-Alcoceba, Ruben; Sangro, Bruno; Prieto, Jesus

2006-01-01

188

The ethics of gene therapy.  

PubMed

Recent developments have progressed in areas of science that pertain to gene therapy and its ethical implications. This review discusses the current state of therapeutic gene technologies, including stem cell therapies and genetic modification, and identifies ethical issues of concern in relation to the science of gene therapy and its application, including the ethics of embryonic stem cell research and therapeutic cloning, the risks associated with gene therapy, and the ethics of clinical research in developing new therapeutic technologies. Additionally, ethical issues relating to genetic modification itself are considered: the significance of the human genome, the distinction between therapy and enhancement, and concerns regarding gene therapy as a eugenic practice. PMID:17078379

Chan, Sarah; Harris, John

2006-10-01

189

Gene-Gene, Gene-Environment & Multiple Interactions in Colorectal Cancer  

Microsoft Academic Search

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested

FARID E. AHMED

2006-01-01

190

GenomeWide Analysis of Genes, Gene Regulation and Gene Expression  

E-print Network

GenomeWide Analysis of Genes, Gene Regulation and Gene Expression Kathryn Brayer1 , Olivia , Christine Stidley4 and Scott Ness1,5 1 Department of Internal Medicine, Section of Molecular Medicine of Molecular Genetics and Microbiology 4 Department of Internal Medicine, Division of Epidemiology 5 UNM

Maccabe, Barney

191

nanosheets for gene therapy  

NASA Astrophysics Data System (ADS)

A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.

Kou, Zhongyang; Wang, Xin; Yuan, Renshun; Chen, Huabin; Zhi, Qiaoming; Gao, Ling; Wang, Bin; Guo, Zhaoji; Xue, Xiaofeng; Cao, Wei; Guo, Liang

2014-10-01

192

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. PMID:22480730

Evans, C. H.

2012-01-01

193

Genes and Sjögren's Syndrome  

PubMed Central

Sjoögren's syndrome (SS) is a chronic, progressive exocrinopathy characterized by infiltration and proliferation of lymphocytes into affected glands. Although patients are clinically identified through oral and ocular features, the full spectrum of disease encompasses a complex and myriad systemic symptoms. The primary pathophysiology includes concurrent mechanisms of dysregulated innate immunity and adaptive autoimmunity involving cell-mediated and humoral disease processes. Etiology involves environmental and genetic factors; however, large-scale genetic studies have not yet been conducted in SS and the genetic basis for SS is largely unexplored. Although few genetic studies have been completed to date in SS, the overall evidence to support a genetic basis for SS continues to grow. Current data strongly suggest SS is a complex, polygenic disorder likely sharing common genetic determinants with related autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recent advances in SLE and RA provide valuable insight into the potential genetic complexity of SS. This article reviews association studies in various candidate genes for SS completed to date and highlights insights from SS mouse models. Advanced genetic and genomic technologies now are available for assaying gene expression and genetic associations across the entire genome, providing important opportunities to conduct unbiased interrogation of essentially every gene for a role in SS. PMID:18984408

Cobb, Beth L.; Lessard, ChristopherJ.; Harley, John B.; Moser, Kathy L.

2010-01-01

194

Advances in Gene Delivery Systems  

PubMed Central

The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral- and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives. PMID:22200988

Kamimura, Kenya; Suda, Takeshi; Zhang, Guisheng; Liu, Dexi

2011-01-01

195

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

2012-03-15

196

Horizontal gene transfer in choanoflagellates.  

PubMed

Horizontal gene transfer (HGT), also known as lateral gene transfer, results in the rapid acquisition of genes from another organism. HGT has long been known to be a driving force in speciation in prokaryotes, and there is evidence for HGT from symbiotic and infectious bacteria to metazoans, as well as from protists to bacteria. Recently, it has become clear that as many as a 1,000 genes in the genome of the choanoflagellate Monosiga brevicollis may have been acquired by HGT. Interestingly, these genes reportedly come from algae, bacteria, and other choanoflagellate prey. Some of these genes appear to have allowed an ancestral choanoflagellate to exploit nutrient-poor environments and were not passed on to metazoan descendents. However, some of these genes are also found in animal genomes, suggesting that HGT into a common ancestor of choanozoans and animals may have contributed to metazoan evolution. PMID:22997182

Tucker, Richard P

2013-01-01

197

Human disease genes: patterns and predictions  

Microsoft Academic Search

We compared genes at which mutations are known to cause human disease (disease genes) with other human genes (nondisease genes) using a large set of human–rodent alignments to infer evolutionary patterns. Such comparisons may be of use both in predicting disease genes and in understanding the general evolution of human genes. Four features were found to differ significantly between disease

Nick G. C. Smith; Adam Eyre-Walker

2003-01-01

198

Gene-environment dependence creates spurious gene-environment interaction.  

PubMed

Gene-environment interactions have the potential to shed light on biological processes leading to disease and to improve the accuracy of epidemiological risk models. However, relatively few such interactions have yet been confirmed. In part this is because genetic markers such as tag SNPs are usually studied, rather than the causal variants themselves. Previous work has shown that this leads to substantial loss of power and increased sample size when gene and environment are independent. However, dependence between gene and environment can arise in several ways including mediation, pleiotropy, and confounding, and several examples of gene-environment interaction under gene-environment dependence have recently been published. Here we show that under gene-environment dependence, a statistical interaction can be present between a marker and environment even if there is no interaction between the causal variant and the environment. We give simple conditions under which there is no marker-environment interaction and note that they do not hold in general when there is gene-environment dependence. Furthermore, the gene-environment dependence applies to the causal variant and cannot be assessed from marker data. Gene-gene interactions are susceptible to the same problem if two causal variants are in linkage disequilibrium. In addition to existing concerns about mechanistic interpretations, we suggest further caution in reporting interactions for genetic markers. PMID:25152454

Dudbridge, Frank; Fletcher, Olivia

2014-09-01

199

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. PMID:19876378

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

2009-01-01

200

The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function  

PubMed Central

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 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. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist. PMID:20576703

Warde-Farley, David; Donaldson, Sylva L.; Comes, Ovi; Zuberi, Khalid; Badrawi, Rashad; Chao, Pauline; Franz, Max; Grouios, Chris; Kazi, Farzana; Lopes, Christian Tannus; Maitland, Anson; Mostafavi, Sara; Montojo, Jason; Shao, Quentin; Wright, George; Bader, Gary D.; Morris, Quaid

2010-01-01

201

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

DOEpatents

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

Chen, Huei-Mei; Bissell, Mina

2004-06-22

202

Reverse engineering transcriptional gene networks.  

PubMed

The aim of this chapter is a step-by-step guide on how to infer gene networks from gene expression profiles. The definition of a gene network is given in Subheading 1, where the different types of networks are discussed. The chapter then guides the readers through a data-gathering process in order to build a compendium of gene expression profiles from a public repository. Gene expression profiles are then discretized and a statistical relationship between genes, called mutual information (MI), is computed. Gene pairs with insignificant MI scores are then discarded by applying one of the described pruning steps. The retained relationships are then used to build up a Boolean adjacency matrix used as input for a clustering algorithm to divide the network into modules (or communities). The gene network can then be used as a hypothesis generator for discovering gene function and analyzing gene signatures. Some case studies are presented, and an online web-tool called Netview is described. PMID:24233783

Belcastro, Vincenzo; di Bernardo, Diego

2014-01-01

203

Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the Cnidaria.  

PubMed

Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a conserved set of developmental regulatory genes are known to function in patterning the anterior-posterior (AP) axis. This set includes the well-studied Hox cluster genes, and the recently described genes of the ParaHox cluster, which is believed to be the evolutionary sister of the Hox cluster (Brooke et al. 1998). The conserved role of these axial patterning genes in animals as diverse as frogs and flies is believed to reflect an underlying homology (i.e., all bilaterians derive from a common ancestor which possessed an AP axis and the developmental mechanisms responsible for patterning the axis). However, the origin and early evolution of Hox genes and ParaHox genes remain obscure. Repeated attempts have been made to reconstruct the early evolution of Hox genes by analyzing data from the triphoblastic animals, the Bilateria (Schubert et al. 1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive due to a lack of sufficient information from outgroup taxa such as the phylum Cnidaria (corals, hydras, jellyfishes, and sea anemones). In combination with outgroup taxa, another potential source of information about Hox origins is outgroup genes (e.g., the genes of the ParaHox cluster). In this article, we present cDNA sequences of two Hox-like genes (anthox2 and anthox6) from the sea anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (= Cnox2) is homologous to the GSX class of ParaHox genes, and anthox6 is homologous to the anterior class of Hox genes. Therefore, the origin of Hox genes and ParaHox genes occurred prior to the evolutionary split between the Cnidaria and the Bilateria and predated the evolution of the anterior-posterior axis of bilaterian animals. Our analysis also suggests that the central Hox class was invented in the bilaterian lineage, subsequent to their split from the Cnidaria. PMID:11324016

Finnerty, J R; Martindale, M Q

1999-01-01

204

Aberrant Gene Expression in Humans  

PubMed Central

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

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

2015-01-01

205

Gene Trap Insertion Into a Novel Gene Expressed During Mouse Limb Development  

E-print Network

Gene Trap Insertion Into a Novel Gene Expressed During Mouse Limb Development ANDRE´ PIRES¨ttingen, Germany ABSTRACT Gene trapping is a useful method to identify new genes involved in development. Here we describe the spatiotemporal expression of a gene identified in a gene-trap screen. This gene is first

Pires da Silva, Andre

206

Gene: a gene-centered information resource at NCBI.  

PubMed

The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP. PMID:25355515

Brown, Garth R; Hem, Vichet; Katz, Kenneth S; Ovetsky, Michael; Wallin, Craig; Ermolaeva, Olga; Tolstoy, Igor; Tatusova, Tatiana; Pruitt, Kim D; Maglott, Donna R; Murphy, Terence D

2015-01-01

207

Gene: a gene-centered information resource at NCBI  

PubMed Central

The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP. PMID:25355515

Brown, Garth R.; Hem, Vichet; Katz, Kenneth S.; Ovetsky, Michael; Wallin, Craig; Ermolaeva, Olga; Tolstoy, Igor; Tatusova, Tatiana; Pruitt, Kim D.; Maglott, Donna R.; Murphy, Terence D.

2015-01-01

208

Measuring gene interactions.  

PubMed

Measurement is the assignment of numbers to reality, and valid measurement requires that these numbers represent relevant aspects of reality. I discuss epistatic gene interactions from a measurement-theoretical perspective and argue that the standard measurements of epistasis in classical quantitative genetics have failed to capture aspects of epistasis that are relevant to selection dynamics and adaptation. Instead, the use of statistically motivated measurements such as epistatic variance components has led to the misconception that epistasis is dynamically inert. Here, I review work showing that patterns of epistasis may have profound effects on evolutionary dynamics and discuss how these patterns can be measured. PMID:25403530

Hansen, Thomas F

2015-01-01

209

[Progress in gene synthesis technology].  

PubMed

Gene synthesis is the most fundamental and widely used technique in biological research. The synthesis of DNA encoding regulatory elements, genes, pathways and entire genomes provides powerful ways to both test biological hypotheses and harness biology for our use. The emerging field of synthetic biology is generating insatiable demands for synthetic genes. And the past couple of years witnessed exciting new developments in microchip-based gene synthesis technologies. This review discusses the current methods of chemical DNA synthesis and gene assembly, as well as the latest engineering tools, technologies and trends which could potentially lead to breakthroughs in the development of accurate, low-cost and high-throughput gene synthesis technology. These new technologies are leading the field of synthetic biology to a higher level. PMID:24364345

Feng, Miao; Wang, Lu; Tian, Jingdong

2013-08-01

210

Gene targeting with retroviral vectors  

SciTech Connect

The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

Ellis, J.; Bernstein, A. (Toronto Univ., ON (Canada))

1989-04-01

211

Generalist genes and learning disabilities.  

PubMed

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 common learning disabilities are largely the same genes responsible for normal variation in learning abilities. Second, genes that affect any aspect of a learning disability affect other aspects of the disability. Third, genes that affect one learning disability are also likely to affect other learning disabilities. These quantitative genetic findings have far-reaching implications for molecular genetics and neuroscience as well as psychology. PMID:16060804

Plomin, Robert; Kovas, Yulia

2005-07-01

212

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

213

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

214

ed gene constructs Caged cyclofen  

E-print Network

k-ras IRES mCherry ed gene constructs Caged cyclofen Sequestered CRE-E CRE-ERT ubi ubi ubi CRE k-ras IRES k-ras IRES mCherry Transgenic/transfected gene constructs Caged cyclofen Sequestered CRE-ERT ubi/transfected gene constructs Caged cyclofen Sequestered CRE-ERT Active CRE-ERT ubi CRE-ERT CRE-ERT CRE-ERT LASERACTI

215

XLMR genes: Update 1996  

SciTech Connect

A current list of all known forms of X-linked mental retardation (XLMR) and a slightly revised classification are presented. The number of known disorders has not increased because 6 disorders have been combined based on new molecular data or on clinical grounds and only 6 newly described XLMR disorders have been reported. Of the current 105 XLMR disorders, 34 have been mapped, and 18 disorders and 1 non-specific XLMR (FRAXE) have been cloned. The number of families with nonspecific XLMR with a LOD score of {ge}2.0 has more than doubled, with 42 (including FRAXE) now being known. A summary of the localization of presumed nonspecific mental retardation (MR) genes from well-studied X-chromosomal translocations and deletions is also included. Only 10-12 nonoverlapping loci are required to explain all localizations of non-specific MR from both approaches. These new trends mark the beginning of a significantly improved understanding of the role of genes on the X chromosome in producing MR. Continued close collaboration between clinical and molecular investigators will be required to complete the process. 105 refs., 2 figs., 6 tabs.

Lubs, H.A.; Tranebjaerg, L. [Univ. Hospital of Tromso (Norway)] [Univ. Hospital of Tromso (Norway); Arena, J.F. [Univ. of Miami School of Medicine, FL (United States)] [and others] [Univ. of Miami School of Medicine, FL (United States); and others

1996-07-12

216

Show Me the Genes  

NSDL National Science Digital Library

By this point in the unit, students have learned all the necessary information and conceptualized a design for how an optical biosensor could be used to detect a target strand of DNA associated with a cancer-causing gene as their solution to the unit's challenge question. Now student groups act as engineers again, using a poster format to communicate and prove the validity of the design. Successful posters include a description of refraction, explanations of refraction in a thin film, and the factors that can alter the interference pattern of a thin film. The posters culminate with an explanation of what is expected to be seen in a biosensing device of this type if it were coupled to a target molecule, proven with a specific example and illustrated with drawings and diagrams throughout. All the poster elements combine to prove the accuracy and viability of this method of gene detection. Together with its associated lesson, this activity functions as part of the summative assessment for this unit.

VU Bioengineering RET Program,

217

Conotoxin Gene Superfamilies  

PubMed Central

Conotoxins are the peptidic components of the venoms of marine cone snails (genus Conus). They are remarkably diverse in terms of structure and function. Unique potency and selectivity profiles for a range of neuronal targets have made several conotoxins valuable as research tools, drug leads and even therapeutics, and has resulted in a concerted and increasing drive to identify and characterise new conotoxins. Conotoxins are translated from mRNA as peptide precursors, and cDNA sequencing is now the primary method for identification of new conotoxin sequences. As a result, gene superfamily, a classification based on precursor signal peptide identity, has become the most convenient method of conotoxin classification. Here we review each of the described conotoxin gene superfamilies, with a focus on the structural and functional diversity present in each. This review is intended to serve as a practical guide to conotoxin superfamilies and to facilitate interpretation of the increasing number of conotoxin precursor sequences being identified by targeted-cDNA sequencing and more recently high-throughput transcriptome sequencing. PMID:25522317

Robinson, Samuel D.; Norton, Raymond S.

2014-01-01

218

Genes and childhood leukemia.  

PubMed

Leukemia is a heterogeneous hematologic malignancy originating from a multipotent hematopoietic stem cell. It ranks among the commonest cancers in childhood and is characterized by excessive proliferation and differentiation block. The process of leukemogenesis is governed by genetic changes at both the cytogenetic and molecular level. According to numerous analyses, a large spectrum of mutations and rearrangements underlying the disease affect essential cellular transduction pathways, genes ensuring proper course of hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators. Common lesions include translocations to T cell receptor (TCR) loci in T-lineage acute lymphoblastic leukemia (T-ALL), mutations of transcription factors regulating B-lineage development and cell maturation in B-lineage acute lymphoblastic leukemia (B-ALL) (PAX5, TCF3, EBF1, etc.), aberrational disruption of genes coding for transcription factors and coactivators in acute myeloid leukemia (AML) (e.g. CBF) or BCR-ABL1 fusion and activation of multiple kinases in chronic myeloid leukemia (CML). These alterations severely impair cell function. Broadening knowledge of the genetic background gives an insight into the pathobiology of a disease and allows for a better understanding of it. An appropriate investigation of genomic events yields diagnostic, prognostic and therapeutic implications. Broadening knowledge of the pathogenesis of leukemia seems to be a promising contribution to precise stratification of patients, reducing the toxicity and adverse effects caused by medical intervention, treatment personalization and introduction of targeted therapy accessible to a wide range of patients. PMID:25748621

K?sy, Julita; Januszkiewicz-Lewandowska, Danuta

2015-01-01

219

Endothelin-1 gene regulation  

PubMed Central

Over two decades of research have demonstrated that the peptide hormone endothelin-1 (ET-1) plays multiple, complex roles in cardiovascular, neural, pulmonary, reproductive, and renal physiology. Differential and tissue-specific production of ET-1 must be tightly regulated in order to preserve these biologically diverse actions. The primary mechanism thought to control ET-1 bioavailability is the rate of transcription from the ET-1 gene (edn1). Studies conducted on a variety of cell types have identified key transcription factors that govern edn1 expression. With few exceptions, the cis-acting elements bound by these factors have been mapped in the edn1 regulatory region. Recent evidence has revealed new roles for some factors originally believed to regulate edn1 in a tissue or hormone-specific manner. In addition, other mechanisms involved in epigenetic regulation and mRNA stability have emerged as important processes for regulated edn1 expression. The goal of this review is to provide a comprehensive overview of the specific factors and signaling systems that govern edn1 activity at the molecular level.—Stow, L. R., Jacobs, M. E., Wingo, C. S., Cain, B. D. Endothelin-1 gene regulation. PMID:20837776

Stow, Lisa R.; Jacobs, Mollie E.; Wingo, Charles S.; Cain, Brian D.

2011-01-01

220

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

1998-07-01

221

Evolutionary Genomics of Gene Expression  

NASA Astrophysics Data System (ADS)

The study of evolution at the molecular level has focused primarily on changes in gene (protein) sequences overtime [1]. Of course, phenotype is influenced not only by the sequence of genes but also by their expression patterns, i.e., the amplitude, timing, and spatial distribution of transcription. Thus, changes in gene expression are quite likely to be equally as important as sequence changes in evolution; indeed, the significance of gene expression divergence to the evolutionary process has been recognized for some time [2-4]. However, gene expression data have only recently accumulated to the levels needed for systematic evolutionary studies. This has been due to the application of new high-throughput techniques that measure gene expression levels for thousands of genes simultaneously [5-7], as well as the development of database resources needed to handle such data [8-10]. The availability of these expression data, together with the long standing interest in the evolutionary significance of gene expression, has stimulated numerous recent studies on gene expression divergence.

Jordan, I. King; Mariñno-Ramírez, Leonardo

222

Selector Genes, Polymorphisms, and Evolution  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Evolution has been thought to act on small changes in the characteristics of organisms coded by genes called realizator genes. D. Tautz explains how a new result in this issue of Science by Gibson and Hogness (p. 200) shows that this may not always be true. A small phenotypic variation in Drosophila (sensitivity to ether), apparent only under environmental stress, turns out to be coded by a polymorphism in a selector gene, Ultrabithorax, a member of a class of genes that specifies whole body parts and anatomical regions.

Diethard Tautz (Zoologisches Institut der Universität München; )

1996-01-12

223

Reduced Rates of Gene Loss, Gene Silencing, and Gene Mutation in Dnmt1Deficient Embryonic Stem Cells  

Microsoft Academic Search

Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribu- tion of each of these different pathways varies among tumor suppressor genes and by cancer type. The factors that influence the relative utilization of gene inactivation pathways are poorly understood. In this

MATILDA F. CHAN; RENEE VAN AMERONGEN; TARLOCHAN NIJJAR; EDWIN CUPPEN; PETER A. JONES; PETER W. LAIRD

2001-01-01

224

Notung: Dating Gene Duplications using Gene Family Trees Kevin Chen,  

E-print Network

from other ge- nomic rearrangments, such as transpositions and reversals, in that the time organism with 6000 genes [6], while mice have an estimated 50,000 - 100,000 genes [27]. How did this order duplication followed by differentiation of se- quence and function through mutation is posited to be a primary

Farach-Colton, Martin

225

Grammatical evolution decision trees for detecting gene-gene interactions  

Microsoft Academic Search

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

Alison A Motsinger-Reif; Sushamna Deodhar; Stacey J Winham; Nicholas E Hardison

2010-01-01

226

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...

227

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

228

Widespread Gene Conversion of Alpha-2-Fucosyltransferase Genes in Mammals  

E-print Network

Widespread Gene Conversion of Alpha-2-Fucosyltransferase Genes in Mammals Joana Abrantes Æ David access at Springerlink.com Abstract The alpha-2-fucosyltransferases (a2FTs) are enzymes involved. The biologic meaning of this observation may be related to functional constraints. Keywords Fucosyltransferases

Posada, David

229

Gene expression profiles in skeletal muscle after gene electrotransfer  

Microsoft Academic Search

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

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

2007-01-01

230

Linkage Analysis of Candidate Genes and Gene-Gene Interactions in Chinese Hypertensive Sib Pairs  

Microsoft Academic Search

Previous studies of hypertension in humans and experimental animal models have identified a number of candidate genes that have since been implicated as possibly contributing to essential hypertension. Among them are the genes encoding angiotensinogen, renin, the b- and g-subunits of the epithelial sodium channel (b\\/g-ENaC), a-adducin, and kallikrein (KLK). To examine the role of possible contribution of these genes

Tianhua Niu; Xiping Xu; Heather J. Cordell; John Rogus; Yusheng Zhou; Zhian Fang; Klaus Lindpaintner

2009-01-01

231

Sorghum gene expression modulated by water deficit and cold stress  

E-print Network

deficit and cold stress, respectively. Up-regulated genes included previously identified stressinduced genes such as early drought-induced gene, dehydrin, late embryogenesis abundant gene, glycin and proline-rich gene, and water stress-inducible genes...

Lim, Sanghyun

2007-04-25

232

Gene duplication and gene conversion in class II MHC genes of New Zealand robins (Petroicidae).  

PubMed

In contrast to mammals, the evolution of MHC genes in birds appears to be characterized by high rates of gene duplication and concerted evolution. To further our understanding of the evolution of passerine MHC genes, we have isolated class II B sequences from two species of New Zealand robins, the South Island robin (Petroica australis australis), and the endangered Chatham Island black robin (Petroica traversi). Using an RT-PCR based approach we isolated four transcribed class II B MHC sequences from the black robin, and eight sequences from the South Island robin. RFLP analysis indicated that all class II B loci were contained within a single linkage group. Analysis of 3'-untranslated region sequences enabled putative orthologous loci to be identified in the two species, and indicated that multiple rounds of gene duplication have occurred within the MHC of New Zealand robins. The orthologous relationships are not retained within the coding region of the gene, instead the sequences group within species. A number of putative gene conversion events were identified across the length of our sequences that may account for this. Exon 2 sequences are highly diverse and appear to have diverged under balancing selection. It is also possible that gene conversion involving short stretches of sequence within exon 2 adds to this diversity. Our study is the first report of putative orthologous MHC loci in passerines, and provides further evidence for the importance of gene duplication and gene conversion in the evolution of the passerine MHC. PMID:15138734

Miller, Hilary C; Lambert, David M

2004-06-01

233

Modeling gene and genome duplications in eukaryotes  

E-print Network

) were among the first to investigate the overall degree of gene duplication and gene loss in completelyModeling gene and genome duplications in eukaryotes Steven Maere*, Stefanie De Bodt*, Jeroen Raes sequences has revealed that gene duplication has been rampant. Moreover, next to a continuous mode of gene

Gent, Universiteit

234

MRI-guided gene therapy Xiaoming Yanga  

E-print Network

Minireview MRI-guided gene therapy Xiaoming Yanga , Ergin Atalara,b,* a Department of Radiology gene expression. This review summarizes the current status of MRI- guided gene therapy. Ã? 2006 resonance imaging; MRI-guided therapy; Gene therapy 1. Introduction Gene therapy is an exciting frontier

Atalar, Ergin

235

Inferring species trees from gene duplication episodes  

Microsoft Academic Search

Gene tree parsimony, which infers a species tree that implies the fewest gene duplications across a collection of gene trees, is a method for inferring phylogenetic trees from paralogous genes. However, it assumes that all duplications are independent, and therefore, it does not account for large-scale gene duplication events like whole genome duplications. We describe two methods to infer species

J. Gordon Burleigh; Mukul S. Bansal; Oliver Eulenstein; Todd J. Vision

2010-01-01

236

Current strategies in cancer gene therapy  

Microsoft Academic Search

Cancer gene therapy is the most studied application of gene therapy. Many genetic alterations are involved in the transformation of a normal cell into a neoplastic one. The two main gene groups involved in cancer development are oncogenes and tumor suppressor genes. While the latter eliminates cancerous cells via apoptosis, the former enhances cell proliferation. Therefore, apoptotic genes and anti-oncogenes

Anas El-Aneed

2004-01-01

237

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

238

Copyright and gene technology.  

PubMed

The rapid growth of gene technology and its commercialisation raises concerns for scientific researchers and research institutions wishing to place information in the public domain. This article examines whether copyright laws in the United States, United Kingdom and Australia provide any protection for genetically modified DNA, proteins, and genetically modified organisms, in contrast with any copyright protection extending to a record of the lettering of a sequence representing a series of nucleotides of modified DNA or the amino acids comprising a protein. Whilst it is arguable that protection may be available in the United States and the United Kingdom, it is submitted that it would be difficult to persuade a court in Australia that genetically modified DNA and genetically modified organisms directly constitute "literary" or "artistic" works. PMID:12242888

Coke, Sue

2002-08-01

239

In planta gene targeting  

PubMed Central

The development of designed site-specific endonucleases boosted the establishment of gene targeting (GT) techniques in a row of different species. However, the methods described in plants require a highly efficient transformation and regeneration procedure and, therefore, can be applied to very few species. Here, we describe a highly efficient GT system that is suitable for all transformable plants regardless of transformation efficiency. Efficient in planta GT was achieved in Arabidopsis thaliana by expression of a site-specific endonuclease that not only cuts within the target but also the chromosomal transgenic donor, leading to an excised targeting vector. Progeny clonal for the targeted allele could be obtained directly by harvesting seeds. Targeted events could be identified up to approximately once per 100 seeds depending on the target donor combination. Molecular analysis demonstrated that, in almost all events, homologous recombination occurred at both ends of the break. No ectopic integration of the GT vector was found. PMID:22529367

Fauser, Friedrich; Roth, Nadine; Pacher, Michael; Ilg, Gabriele; Sánchez-Fernández, Rocío; Biesgen, Christian; Puchta, Holger

2012-01-01

240

See the Genes  

NSDL National Science Digital Library

Through this concluding lesson and its associated activity, students experience one valuable and often overlooked skill of successful scientists and engineers—communicating your work and ideas. They explore the importance of scientific communication, including the basic, essential elements of communicating new information to the public and pitfalls to avoid. In the associated activity, student groups create posters depicting their solutions to the unit's challenge question—accurate, efficient methods for detecting cancer-causing genes using optical biosensors—which includes providing a specific example with relevant equations. Students are also individually assessed on their understanding of refraction via a short quiz. This lesson and its associated activity conclude the unit and serve as the culminating Go Public phase of the Legacy Cycle, providing unit review and summative assessment.

VU Bioengineering RET Program,

241

Method for cloning genes  

SciTech Connect

This patent describes a recombinant cloning vehicle comprising an inserted human gene, the improvement wherein the cloning vehicle is isolated from a recombinant clone which is isolated and identified by a process comprising the steps of: (a) effecting cDNA synthesis on a mixture of mRNAs containing a target mRNA coding for a major hisitocompatibility antigen, and isolating the resultant cDNA mixture; (b) inserting the resultant cDNA into recombinant cloning vehicles, and transforming hosts with the vehicles; and (c) separating the transformants and isolating and identifying a recombinant clone containing a DNA segment which is homologous over at least a portion thereof to at least one oligonucleotide probe specific for the DNA segment.

Weissman, S.M.; Pereira, D.; Sood, A.

1988-04-19

242

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. PMID:17444812

Bachmanov, Alexander A.; Beauchamp, Gary K.

2009-01-01

243

Pompe disease gene therapy  

PubMed Central

Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disability. In early-onset severe cases, the natural history is characteristically cardiorespiratory failure and death in the first year of life. Since the advent of enzyme replacement therapy (ERT), the clinical outcomes have improved. However, it has become apparent that a new natural history is being defined in which some patients have substantial improvement following ERT, while others develop chronic disability reminiscent of the late-onset disease. In order to improve on the current clinical outcomes in Pompe patients with diminished clinical response to ERT, we sought to address the cause and potential for the treatment of disease manifestations which are not amenable to ERT. In this review, we will focus on the preclinical studies that are relevant to the development of a gene therapy strategy for Pompe disease, and have led to the first clinical trial of recombinant adeno-associated virus-mediated gene-based therapy for Pompe disease. We will cover the preliminary laboratory studies and rationale for a clinical trial, which is based on the treatment of the high rate of respiratory failure in the early-onset patients receiving ERT. PMID:21518733

Byrne, Barry J.; Falk, Darin J.; Pacak, Christina A.; Nayak, Sushrusha; Herzog, Roland W.; Elder, Melissa E.; Collins, Shelley W.; Conlon, Thomas J.; Clement, Nathalie; Cleaver, Brian D.; Cloutier, Denise A.; Porvasnik, Stacy L.; Islam, Saleem; Elmallah, Mai K.; Martin, Anatole; Smith, Barbara K.; Fuller, David D.; Lawson, Lee Ann; Mah, Cathryn S.

2011-01-01

244

Gene therapy on the move  

PubMed Central

The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

2013-01-01

245

Natural selection on gene expression  

Microsoft Academic Search

Changes in genetic regulation contribute to adaptations in natural populations and influence susceptibility to human diseases. Despite their potential phenotypic importance, the selective pressures acting on regulatory processes in general and gene expression levels in particular are largely unknown. Studies in model organisms suggest that the expression levels of most genes evolve under stabilizing selection, although a few are consistent

Yoav Gilad; Alicia Oshlack; Scott A. Rifkin

2006-01-01

246

Generalist Genes and Learning Disabilities  

ERIC Educational Resources Information Center

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…

Plomin, Robert; Kovas, Yulia

2005-01-01

247

Uncovering trends in gene naming  

PubMed Central

We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov’s dogs). We hope this analysis provides clues to better steer gene naming in the future. PMID:18254929

Seringhaus, Michael R; Cayting, Philip D; Gerstein, Mark B

2008-01-01

248

Gene transfer technology in aquaculture  

Microsoft Academic Search

The gene transfer technique, transgenesis, has permitted the transfer of genes from one organism to another to create new lineages of organisms with improvement in traits important to aquaculture. Genetically modified organisms (GMOs), therefore, hold promise for producing genetic improvements, such as enhanced growth rate, increased production and efficiency, disease resistance and expanded ecological ranges. The basic procedure to generate

J. A. Levy; L. F. Marins; A. Sanchez

2000-01-01

249

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. PMID:21906307

2011-01-01

250

Gene therapy on the move.  

PubMed

The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

2013-11-01

251

Gene therapy for cystic fibrosis.  

PubMed

Following the cloning of the cystic fibrosis (CF) gene, in vitro studies rapidly established the feasibility of gene therapy for this disease. Unlike ex vivo approaches that have been utilized for other genetic diseases such as adenosine deaminase deficiency, gene therapy for CF will likely require direct in vivo delivery of gene transfer vectors to the airways of patients with CF. Hence, major research efforts have been directed at the development of efficient gene transfer vectors that are safe for use in human subjects. Several vectors have now emerged from the laboratory for evaluation in clinical safety and efficacy trials in the United States and in the United Kingdom. Adenovirus-mediated gene transfer has been utilized for initial clinical safety and efficacy trials in the United States, while liposome-mediated gene transfer has been chosen for initial clinical safety and efficacy trials in the United Kingdom. The rationale and laboratory studies are reviewed leading to initial clinical safety and efficacy trials. Also reviewed are the currently available vectors for potential use in clinical studies, their advantages and disadvantages, and the promises and pitfalls of current gene therapy efforts for CF in the United States focusing on adenovirus vectors in current clinical trials. PMID:7842818

Johnson, L G

1995-02-01

252

Using Genes to Guide Prescriptions  

MedlinePLUS

... Science > Using Genes to Guide Prescriptions Inside Life Science View All Articles | Inside Life Science Home Page Using Genes to Guide Prescriptions By ... to Zoloft: Ways Medicines Work This Inside Life Science article also appears on LiveScience . Learn about related ...

253

Animal Body Plans: Homeobox Genes  

NSDL National Science Digital Library

The homeobox genes that define the basic body plan of mice and fruit flies are illustrated in this graphic from The Human Evolution Coloring Book by Adrienne Zihlman. The accompanying article describes how these genes act as molecular architects in all animal species.

WGBH Educational Foundation

2003-09-26

254

From genes to genome biology  

SciTech Connect

This article describes a change in the approach to mapping genomes, from looking at one gene at a time, to other approaches. Strategies include everything from lab techniques to computer programs designed to analyze whole batches of genes at once. Also included is a update on the work on the human genome.

Pennisi, E.

1996-06-21

255

Progress toward Human Gene Therapy  

Microsoft Academic Search

Current therapies for most human genetic diseases are inadequate. In response to the need for effective treatments, modern molecular genetics is providing tools for an unprecedented new approach to disease treatment through an attack directly on mutant genes. Recent results with several target organs and gene transfer techniques have led to broad medical and scientific acceptance of the feasibility of

Theodore Friedmann

1989-01-01

256

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

257

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

258

Method of controlling gene expression  

DOEpatents

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

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

1991-12-03

259

Susceptibility Genes in Thyroid Autoimmunity  

PubMed Central

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity. PMID:15712599

Ban, Yoshiyuki; Tomer, Yaron

2005-01-01

260

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

2011-12-01

261

Nanoparticles for Retinal Gene Therapy  

PubMed Central

Ocular gene therapy is becoming a well-established field. Viral gene therapies for the treatment of Leber’s congentinal amaurosis (LCA) are in clinical trials, and many other gene therapy approaches are being rapidly developed for application to diverse ophthalmic pathologies. Of late, development of non-viral gene therapies has been an area of intense focus and one technology, polymer-compacted DNA nanoparticles, is especially promising. However, development of pharmaceutically and clinically viable therapeutics depends not only on having an effective and safe vector but also on a practical treatment strategy. Inherited retinal pathologies are caused by mutations in over 220 genes, some of which contain over 200 individual disease-causing mutations, which are individually very rare. This review will focus on both the progress and future of nanoparticles and also on what will be required to make them relevant ocular pharmaceutics. PMID:20452457

Conley, Shannon M.; Naash, Muna I.

2010-01-01

262

[Transcriptional control of ciliary genes].  

PubMed

Cilia are found in many eukaryotic species and share a common microtubule architecture that can nonetheless show very diverse features within one animal. The genesis of cilia and their diversity require the expression of different specific genes. At least two classes of transcription factors are involved in ciliogenesis: the RFX family, essential for the assembly of most cilia and the FOXJ1 transcription factors that are key regulators of motile cilia assembly. These two different families of transcription factors have both specific and common target genes and they can also cooperate for the formation of cilia. In collaboration with cell type specific factors, they also contribute to the specialisation of cilia. As a consequence, the identification of RFX and FOXJ1 target genes has emerged as an efficient strategy to identify novel ciliary genes, and in particular genes potentially implicated in ciliopathies. PMID:25388578

Vieillard, Jennifer; Jerber, Julie; Durand, Bénédicte

2014-11-01

263

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. PMID:19339170

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

2009-01-01

264

Regulation of Neuronal Gene Expression  

NASA Astrophysics Data System (ADS)

Humans as multicellular organisms contain a variety of different cell types where each cell population must fulfill a distinct function in the interest of the whole organism. The molecular basis for the variations in morphology, biochemistry, molecular biology, and function of the various cell types is the cell-type specific expression of genes. These genes encode proteins necessary for executing the specialized functions of each cell type within an organism. We describe here a regulatory mechanism for the expression of neuronal genes. The zinc finger protein REST binds to the regulatory region of many neuronal genes and represses neuronal gene expression in nonneuronal tissues. A negative regulatory mechanism, involving a transcriptional repressor, seems to play an important role in establishing the neuronal phenotype.

Thiel, Gerald; Lietz, Michael; Leichter, Michael

265

Gene therapy for retinal diseases.  

PubMed

Gene therapy has a growing research potential particularly in the field of ophthalmic and retinal diseases owing to three main characteristics of the eye; accessibility in terms of injections and surgical interventions, its immune-privileged status facilitating the accommodation to the antigenicity of a viral vector, and tight blood-ocular barriers which save other organs from unwanted contamination. Gene therapy has tremendous potential for different ocular diseases. In fact, the perspective of gene therapy in the field of eye research does not confine to exclusive monogenic ophthalmic problems and it has the potential to include gene based pharmacotherapies for non-monogenic problems such as age related macular disease and diabetic retinopathy. The present article has focused on how gene transfer into the eye has been developed and used to treat retinal disorders with no available therapy at present. PMID:25709778

Samiy, Nasrollah

2014-01-01

266

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

267

Reference gene screening for analyzing gene expression across goat tissue.  

PubMed

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

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

2013-12-01

268

Gene expression analysis identifies global gene dosage sensitivity in cancer.  

PubMed

Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying this method to 16,172 patient-derived tumor samples, we replicated many loci with aberrant copy numbers and identified recurrently disrupted genes in genomically unstable cancers. PMID:25581432

Fehrmann, Rudolf S N; Karjalainen, Juha M; Krajewska, Ma?gorzata; Westra, Harm-Jan; Maloney, David; Simeonov, Anton; Pers, Tune H; Hirschhorn, Joel N; Jansen, Ritsert C; Schultes, Erik A; van Haagen, Herman H H B M; de Vries, Elisabeth G E; Te Meerman, Gerard J; Wijmenga, Cisca; van Vugt, Marcel A T M; Franke, Lude

2015-02-01

269

Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue  

PubMed Central

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

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

2013-01-01

270

Analysis of Multiple Association Studies Provides Evidence of an Expression QTL Hub in Gene-Gene  

E-print Network

report an analysis of gene-gene interactions affecting HDL cholesterol (HDL-C) levels in a candidate geneAnalysis of Multiple Association Studies Provides Evidence of an Expression QTL Hub in Gene SNPs involved in another, well-replicated gene-gene interaction underlying HDL-C levels. To further

Keinan, Alon

271

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

E-print Network

A Gene Recommender Algorithm to Identify Coexpressed Genes in C. elegans Art B. Owen,1,4 Josh 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

Stuart, Josh

272

Gene and Enhancer Trap Tagging of Vascular-Expressed Genes in Poplar Trees  

E-print Network

Gene and Enhancer Trap Tagging of Vascular-Expressed Genes in Poplar Trees Andrew Groover*, Joseph, New York 11724 (R.M.) We report a gene discovery system for poplar trees based on gene and enhancer traps. Gene and enhancer trap vectors carrying the b-glucuronidase (GUS) reporter gene were inserted

273

Gene Help: Integrated Access to Genes of Genomes in the Reference Sequence Collection  

E-print Network

Gene Help: Integrated Access to Genes of Genomes in the Reference Sequence Collection Garth Brown Craig Wallin Tatiana Tatusova Kim Pruitt Terence Murphy Donna Maglott Introduction Gene supplies gene. Unique identifiers are assigned to genes with defining sequences, genes with known map positions

Levin, Judith G.

274

The gene map of the rabbit III. ? and ? casein gene synteny  

E-print Network

Note The gene map of the rabbit III. ? and ? casein gene synteny M. DALENS, J. GELLIN LN the gene map of the rabbit using DNA probes which allow us to investigate non-expressed genes. We have characterized an a and (i casein gene synteny and have found that neither the a andcasein genes nor the whey

Paris-Sud XI, Université de

275

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

E-print Network

Neural networks approaches for discovering the learnable correlation between gene function and gene Keywords: Gene function prediction Self organizing maps (SOM) Multilayer perceptrons (MLP) Gene expression Neural networks a b s t r a c t Identifying gene function has many useful applications. Identifying gene

Morris, Quaid

276

BBF RFC 101: Logic Gene Module Standard  

E-print Network

This Request for Comments (RFC) describes a new framework for standardize logic gene relations among gene circuits. Each type of logic module in gene circuit can be summarized in a standard device in electronics. In this ...

Wang, Lingjue

2013-11-01

277

Selecting Relevant Genes with a Spectral Approach  

E-print Network

Array technologies have made it possible to record simultaneously the expression pattern of thousands of genes. A fundamental problem in the analysis of gene expression data is the identification of highly relevant genes ...

Wolf, Lior

2004-01-27

278

Selecting Relevant Genes with a Spectral Approach  

E-print Network

Array technologies have made it possible to record simultaneouslythe expression pattern of thousands of genes. A fundamental problemin the analysis of gene expression data is the identification ofhighly relevant genes that ...

Wolf, Lior

2004-01-27

279

Development and Assessment of Gene Therapies for  

E-print Network

eyes caused by RPE65 mutations: Prerequisite for human gene therapyThe eye is an attractive organ for targeted gene therapy aseye is transparent, it is simple to image and conduct intraocular injections. In addition, gene therapy

Kolstad, Kathleen Durgin

2009-01-01

280

Gene conversion in the rice genome  

E-print Network

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...

Xu, Shuqing; Clark, Terry; Zheng, Hongkun; Vang, SÃ ¸ ren; Li, Ruiqiang; Wong, Gane Ka-Shu; Wang, Jun; Zheng, Xiaoguang

2008-02-25

281

Personalized Medicine: Matching Treatments to Your Genes  

MedlinePLUS

... disclaimer . Subscribe Personalized Medicine Matching Treatments to Your Genes You’re one of a kind. It’s not ... personalized medicine begins with the unique set of genes you inherited from your parents. Genes are stretches ...

282

Gene Duplication and Ectopic Gene Conversion in Drosophila  

PubMed Central

The evolutionary impact of gene duplication events has been a theme of Drosophila genetics dating back to the Morgan School. While considerable attention has been placed on the genetic novelties that duplicates are capable of introducing, and the role that positive selection plays in their early stages of duplicate evolution, much less attention has been given to the potential consequences of ectopic (non-allelic) gene conversion on these evolutionary processes. In this paper we consider the historical origins of ectopic gene conversion models and present a synthesis of the current Drosophila data in light of several primary questions in the field. PMID:24710141

Arguello, J. Roman; Connallon, Tim

2011-01-01

283

Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins.  

PubMed

Understanding the genetic architecture of gene expression is an intermediate step in understanding the genetic architecture of complex diseases. RNA sequencing technologies have improved the quantification of gene expression and allow measurement of allele-specific expression (ASE). ASE is hypothesized to result from the direct effect of cis regulatory variants, but a proper estimation of the causes of ASE has not been performed thus far. In this study, we take advantage of a sample of twins to measure the relative contributions of genetic and environmental effects to ASE, and we find substantial effects from gene × gene (G×G) and gene × environment (G×E) interactions. We propose a model where ASE requires genetic variability in cis, a difference in the sequence of both alleles, but where the magnitude of the ASE effect depends on trans genetic and environmental factors that interact with the cis genetic variants. PMID:25436857

Buil, Alfonso; Brown, Andrew Anand; Lappalainen, Tuuli; Viñuela, Ana; Davies, Matthew N; Zheng, Hou-Feng; Richards, J Brent; Glass, Daniel; Small, Kerrin S; Durbin, Richard; Spector, Timothy D; Dermitzakis, Emmanouil T

2015-01-01

284

Consistency of Sequence-Based Gene Clusters  

NASA Astrophysics Data System (ADS)

In comparative genomics, various combinatorial models can be used to specify gene clusters - groups of genes that are co-located in a set of genomes. Several approaches have been proposed to reconstruct putative ancestral gene clusters based on the gene order of contemporary species. One prevalent and natural reconstruction criterion is consistency: For a set of reconstructed gene clusters, there should exist a gene order that comprises all given clusters.

Wittler, Roland; Stoye, Jens

285

GENES IN SPORT AND DOPING  

PubMed Central

Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation, erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques. PMID:24744482

Kaliszewski, P.; Majorczyk, E.; Zembro?-?acny, A.

2013-01-01

286

Gene regulation: From biophysics to evolutionary genetics  

E-print Network

Gene regulation: From biophysics to evolutionary genetics Michael Lässig Institute for Theoretical interactions Multiple binding sites allow for complex regulation of individual genes in higher organisms

Lässig, Michael

287

COMPARISON OF THE METHYL REDUCTASE GENES AND GENE PRODUCTS  

EPA Science Inventory

The DNA sequences encoding component C of methyl coenzyme M reductase (mcr genes) in Methanothermus fervidus, Methanobacterium thermoautotrophicum, Methanococcus vannielii, and Methanosarcina barkeri have been published. omparisons of transcription initiation and termination site...

288

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

289

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

290

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. There are many activities on the site, and each is broken down into six categories of analysis, "Genes", "Biochemicals", "Cells", "Brain Anatomy", "Cognition", and "Environment". 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. There are several "stops" on the line, and each allows the visitor to learn about the key areas of bipolar disorder research. Scrolling over the stops opens up a small window with a blurb about the content to view. The blurb also shows whether the content is a video, an application, animation, etc. Visitors wishing to see all the research available, should click on the network map, which is the screen behind the smaller "subway line" page. 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. "Teacher Pages," "Student Worksheets", and "Test Items" are offered in PDF form.

291

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

292

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. PMID:15488140

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

293

Genes, Economics, and Happiness *  

PubMed Central

We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being. PMID:24349601

De Neve, Jan-Emmanuel; Christakis, Nicholas A.; Fowler, James H.; Frey, Bruno S.

2012-01-01

294

Gene Delivery to the Airway  

PubMed Central

This unit describes generation of and gene transfer to several commonly used airway models. Isolation and transduction of primary airway epithelial cells are first described. Next, the preparation of polarized airway epithelial monolayers is outlined. Transduction of these polarized cells is also described. Methods are presented for generation of tracheal xenografts as well as both ex vivo and in vivo gene transfer to these xenografts. Finally, a method for in vivo gene delivery to the lungs of rodents is included. Methods for evaluating transgene expression are given in the support protocols. PMID:23853081

Keiser, Nicholas W.; Engelhardt, John F.

2013-01-01

295

Panspermia and horizontal gene transfer  

NASA Astrophysics Data System (ADS)

Evidence that extremophiles are hardy and ubiquitous is helping to make panspermia a respectable theory. But even if life on Earth originally came from space, biologists assume that the subsequent evolution of life is still governed by the darwinian paradigm. In this review we show how panspermia could amend darwinism and point to a cosmic source for, not only extremophiles but, all of life. This version of panspermia can be called "strong panspermia." To support this theory we will discuss recent evidence pertaining to horizontal gene transfer, viruses, genes apparently older than the Earthly evolution of the features they encode, and primate-specific genes without identifiable precursors.

Klyce, Brig

2009-08-01

296

Gene expression and fractionation resistance  

PubMed Central

Background Previous work on whole genome doubling in plants established the importance of gene functional category in provoking or suppressing duplicate gene loss, or fractionation. Other studies, particularly in Paramecium have correlated levels of gene expression with vulnerability or resistance to duplicate loss. Results Here we analyze the simultaneous effect of function category and expression in two plant data sets, rosids and asterids. Conclusion We demonstrate function category and expression level have independent effects, though expression does not play the dominant role it does in Paramecium. PMID:25573431

2014-01-01

297

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

298

Microarray analysis of genes and gene functions in disc degeneration  

PubMed Central

The aim of the present study was to screen differentially expressed genes (DEGs) in human degenerative intervertebral discs (IVDs), and to perform functional analysis on these DEGs. The gene expression profile was downloaded from the Gene Expression Omnibus database (GSE34095)and included six human IVD samples: three degenerative and three non-degenerative. The DEGs between the normal and disease samples were identified using R packages. The online software WebGestalt was used to perform the functional analysis of the DEGs, followed by Osprey software to search for interactions between the DEGs. The Database for Annotation, Visualization and Integrated Discovery was utilized to annotate the DEGs in the interaction network and then the DEGs were uploaded to the Connectivity Map database to search for small molecules. In addition, the active binding sites for the hub genes in the network were obtained, based on the Universal Protein database. By comparing the gene expression profiles of the non-degenerative and degenerative IVDs, the DEGs between the samples were identified. The DEGs were significantly associated with transforming growth factor ? and the extracellular matrix. Matrix metalloproteinase 2 (MMP2) was identified as the hub gene of the interaction network of DEGs. In addition, MMP2 was found to be upregulated in degenerative IVDs. The screened small molecules and the active binding sites of MMP2 may facilitate the development of methods to inhibit overexpression of MMP2. PMID:24396401

TANG, YANCHUN; WANG, SHAOKUN; LIU, YING; WANG, XUYUN

2014-01-01

299

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. PMID:21828248

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

2011-01-01

300

Gene Function Prediction Based on the Gene Ontology Hierarchical Structure  

PubMed Central

The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship. PMID:25192339

Cheng, Liangxi; Lin, Hongfei; Hu, Yuncui; Wang, Jian; Yang, Zhihao

2014-01-01

301

Antivirulence Genes: Insights into Pathogen Evolution through Gene Loss  

PubMed Central

The emergence of new pathogens and the exploitation of novel pathogenic niches by bacteria typically require the horizontal transfer of virulence factors and subsequent adaptation—a “fine-tuning” process—for the successful incorporation of these factors into the microbe's genome. The function of newly acquired virulence factors may be hindered by the expression of genes already present in the bacterium. Occasionally, certain genes must be inactivated or deleted for full expression of the pathogen phenotype to occur. These genes are known as antivirulence genes (AVGs). Originally identified in Shigella, AVGs have improved our understanding of pathogen evolution and provided a novel approach to drug and vaccine development. In this review, we revisit the AVG definition and update the list of known AVGs, which now includes genes from pathogens such as Salmonella, Yersinia pestis, and the virulent Francisella tularensis subspecies. AVGs encompass a wide variety of different roles within the microbe, including genes involved in metabolism, biofilm synthesis, lipopolysaccharide modification, and host vasoconstriction. More recently, the use of one of these AVGs (lpxL) as a potential vaccine candidate highlights the practical application of studying AVG inactivation in microbial pathogens. PMID:23045475

Bliven, Kimberly A.

2012-01-01

302

New Gene Evolution: Little Did We Know  

PubMed Central

Genes are perpetually added to and deleted from genomes during evolution. Thus, it is important to understand how new genes are formed and evolve as critical components of the genetic systems determining the biological diversity of life. Two decades of effort have shed light on the process of new gene origination, and have contributed to an emerging comprehensive picture of how new genes are added to genomes, ranging from the mechanisms that generate new gene structures to the presence of new genes in different organisms to the rates and patterns of new gene origination and the roles of new genes in phenotypic evolution. We review each of these aspects of new gene evolution, summarizing the main evidence for the origination and importance of new genes in evolution. We highlight findings showing that new genes rapidly change existing genetic systems that govern various molecular, cellular and phenotypic functions. PMID:24050177

Long, Manyuan; VanKuren, Nicholas W.; Chen, Sidi; Vibranovski, Maria D.

2014-01-01

303

Gene Therapy for Parkinson's Disease  

PubMed Central

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field. PMID:22619738

Denyer, Rachel; Douglas, Michael R.

2012-01-01

304

Clock genes and female reproduction   

E-print Network

The involvement of clock genes in the temporal regulation of the function and lifespan of the corpus luteum (CL) has not been investigated in detail. Immunohistochemistry and real-time quantitative PCR techniques were used ...

Chen, Cynthia

2009-01-01

305

Statistical mechanics of gene competition   

E-print Network

Statistical mechanics has been applied to a wide range of systems in physics, biology, medicine and even anthropology. This theory has been recently used to model the complex biochemical processes of gene expression and ...

Venegas-Ortiz, Juan; Ortiz, Juan Venegas

2013-11-28

306

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. PMID:20186343

Shin, Yong-Jun; Nourani, Mehrdad

2010-01-01

307

Gene Variants Reduce Opioid Risks  

MedlinePLUS

... reduced severity of neonatal abstinence syndrome (NAS) in newborns who were prenatally exposed to methadone or buprenorphine. ... gene to reduced severity of NAS. Among 86 newborns who were prenatally exposed to buprenorphine or methadone, ...

308

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. PMID:19514890

Venters, Bryan J.; Pugh, B. Franklin

2009-01-01

309

Revisiting Global Gene Expression Analysis  

E-print Network

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

Lovén, Jakob

310

Gene-culture coevolution between cattle milk protein genes and human lactase genes.  

PubMed

Milk from domestic cows has been a valuable food source for over 8,000 years, especially in lactose-tolerant human societies that exploit dairy breeds. We studied geographic patterns of variation in genes encoding the six most important milk proteins in 70 native European cattle breeds. We found substantial geographic coincidence between high diversity in cattle milk genes, locations of the European Neolithic cattle farming sites (>5,000 years ago) and present-day lactose tolerance in Europeans. This suggests a gene-culture coevolution between cattle and humans. PMID:14634648

Beja-Pereira, Albano; Luikart, Gordon; England, Phillip R; Bradley, Daniel G; Jann, Oliver C; Bertorelle, Giorgio; Chamberlain, Andrew T; Nunes, Telmo P; Metodiev, Stoitcho; Ferrand, Nuno; Erhardt, Georg

2003-12-01

311

Gene delivery to dystrophic muscle.  

PubMed

Electroporation is a powerful method for gene delivery to dystrophic muscle in the mdx mouse model of Duchenne muscular dystrophy. Successful transfer of reporter and therapeutic plasmids and antisense oligonucleotides has been demonstrated. However, the efficiency falls with increasing plasmid size. Although it is unlikely that the electrotransfer approach will be useful clinically, it is an important experimental tool, particularly in testing potential immune responses to gene transfer in the absence of vector proteins. PMID:18370219

Wells, Kim E; McMahon, Jill; Foster, Helen; Ferrer, Aurora; Wells, Dominic J

2008-01-01

312

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

313

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

314

NF2 Tumor suppressor gene  

Microsoft Academic Search

The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of multiple tumors of the nervous system,\\u000a either associated with neurofibromatosis 2 or sporadic ones, mainly schwannomas and meningiomas. In order to evaluate the\\u000a role of the NF2 gene in sporadic central nervous system (CNS) tumors, we analyzed NF2 mutations in 26 specimens: 14 meningiomas, 4

Irene Szijan; Daniel Rochefort; Carl Bruder; Ezequiel Surace; Gloria Machiavelli; Viviana Dalamon; Javier Cotignola; Veronica Ferreiro; Alvaro Campero; Armando Basso; Jan P. Dumanski; Guy A. Rouleau

2003-01-01

315

[Genes for extreme violent behaviour?].  

PubMed

A new genetic study focussing on the degree of violence in criminals and using both candidate gene and GWAS approaches finds statistically significant associations of extreme violent behaviour with low activity alleles of monoamine oxydase A (MAOA) and with the CD13 gene. However, the alleles implicated are common in the general population, thus they cannot be causal, and only represent potential indicators of increased risk. PMID:25658738

Jordan, Bertrand

2015-01-01

316

Gene Silencing Therapy Against Cancer  

Microsoft Academic Search

Over the past 25 yr, gene silencing therapy derived from nucleic acid-based molecules has evolved from bench research to clinical\\u000a therapy. The recent discovery of RNA interference (RNAi), a mechanism by which double stranded RNAs mediate sequence-specific\\u000a gene silencing, provided a new tool in the fight against cancer. The application of RNAi technology in basic cancer research\\u000a will facilitate the

Chao-Zhong Song

317

Transgenic Arabidopsis Gene Expression System  

NASA Technical Reports Server (NTRS)

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

Ferl, Robert; Paul, Anna-Lisa

2009-01-01

318

RNA-triggered gene silencing  

Microsoft Academic Search

Double-stranded RNA (dsRNA) has recently been shown to trigger sequence-specific gene silencing in a wide variety of organisms, including nematodes, plants, trypanosomes, fruit flies and planaria; meanwhile an as yet uncharacterized RNA trigger has been shown to induce DNA methylation in several different plant systems. In addition to providing a surprisingly effective set of tools to interfere selectively with gene

Andrew Fire

1999-01-01

319

Glucocorticoids: Effects on Gene Transcription  

Microsoft Academic Search

The major antiinflammatory effects of glucocorticoids appear to be due largely to interaction between the activated glucocorticoid receptor and transcription factors, notably nuclear factor- B( NF-B) and activator protein-1, that mediate the expression of inflamma- tory genes. NF-B switches on inflammatory genes via a process involving recruitment of transcriptional coactivator proteins and changes in chromatin modifications such as histone acetylation.

Ian M. Adcock; Kaz Ito; Peter J. Barnes

2004-01-01

320

[The relationship between mouse fertilization antigen 1 gene and the human counterpart gene].  

PubMed

The cloning of human fertilization antigen 1 gene(FA1) ,the supposed counterpart gene of mouse fertilization antigen 1 gene (FA1),was performed using the PCR and PCR products cloned sequencing methods. The result shows that there might be two mistakes in the mouse FA1 gene open reading frame (ORF),and human OTK27 gene and mouse FA1 gene might be homogeneous genes in the two species. PMID:16135423

Li, Jian-ping; Zhang, Si-zhong; Xia, Qing-jie

2002-07-01

321

Immunoglobulin genes of the turtles.  

PubMed

The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor. PMID:23208582

Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

2013-03-01

322

Autogenous regulation of gene expression.  

PubMed

A new term, autogenous regulation, is used to describe a phenomenon that is not a new discovery but rather is newly appreciated as a mechanism common to a number of systems in both prokaryotic and eukaryotic organisms. In this mechanism the product of a structural gene regulates expression of the operon in which that structural gene resides. In many (perhaps all) cases, the regulatory gene product has several functions, since it may act not only as a regulatory protein but also as an enzyme, structural protein, or antibody, for example. In a few cases, this protein is the multimeric allosteric enzyme that catalyzes the first step of a metabolic pathway, gearing together the two most important mechanisms for controlling the biosynthesis of metabolites in bacterial cells-feedback inhibition and repression. Autogenous regulation may provide a mechanism for amplification of gene expression (84); for severe and prolonged inactivation of gene expression (85); for buffering the response of structural genes to changes in the environment (45, 52); and for maintaining a constant intracellular concentration of a protein, independent of cell size or growth rate (86). Thus, autogenous regulation provides the cell with means for accomplishing a number of different regulatory tasks, each suited to better satisfying the needs of the organism for its survival. PMID:4589900

Goldberger, R F

1974-03-01

323

Genes, Environments, and Behavior 2  

NSDL National Science Digital Library

In this lesson students will study how genetic research on behavior is conducted. Genes, Environment, and Behavior 2 is the second of two lessons about the field called behavioral genetics, in which scientists study the reciprocating influences of genes and environments on behavior, particularly human behavior. Genes, Environment and Behavior 2 introduces students to the various approaches scientists use to explore the interaction of genetic and environmental forces which shape behavior.An important objective of these lessons is to help students overcome the common public misperception that genes can have a direct relationship with behavior; for example, that there may be a "gene for criminality" or a "gene for religiosity." Another common misperception that can be dispelled through these lessons is that the development of an organism is determined solely by genetic factors; this is called genetic determinism. Possibly the most important value of these lessons, therefore, is that they can help students understand why such beliefs are false.These chapters are character-based and have relatively easy context. Provided are quizzes that that are administered after the short readings. These quizzes foster a discussion on each topic in behavior and genetics. Students will also perform a scavenger hunt on a scientific research article for phrases that reference research methods including: family studies, molecular studies, and brain imaging studies.

American Association for the Advancement of Science (; )

2006-04-25

324

Book Review: Plant Gene Expression  

NSDL National Science Digital Library

Whereas many important biological discoveries have been made using plants, subsequent progress in some areas of plant research has fallen behind that in other organisms for which funding and in vitro assays are more readily available. Gene expression is one such field in which importance continues to grow because many potential plant biotechnology–based solutions to global problems depend on regulating the expression of specific genes. Previous limitations to exploring gene expression in plants have been partially mitigated by recent advances in genomics, genetics, and transformation techniques. The book Regulation of Gene Expression in Plants: The Role of Transcript Structure and Processing, edited by Carole L. Bassett, summarizes our current understanding of plant gene expression, with an emphasis on transcriptional and posttranscriptional regulation. The topics covered in six chapters include differences in messenger RNA (mRNA) structure caused by variations in transcription start and polyadenylation sites, alternative splicing, regulation by small RNAs, and mRNA transport and degradation. The chapters vary in depth, quality, and the degree to which the emphasis is placed on plants rather than eukaryotes in general. However, this slim volume is a useful review of gene expression in plants. The question of whether or not all differences in mRNA structure have functional importance remains open.

Alan Rose (University of California Davis; Molecular and Cellular Biology REV)

2007-05-22

325

Use of gene replacement transformation to elucidate gene function in the qa gene cluster of Neurospora crassa.  

PubMed

Gene replacement by transformation, employing selective genetic recombination techniques, has been used to delete or disrupt the qa-x, qa-y and qa-1S genes of the qa gene cluster of Neurospora crassa. The growth characteristics of the strain carrying the deletion of the qa-y gene support earlier evidence that this gene encodes a quinic acid permease. The strain containing the deletion of the qa-1S gene (delta qa-1S) was examined with respect to quinic acid induction and carbon catabolite repression. The delta qa-1S strain exhibits constitutive expression of the qa genes supporting earlier evidence that the qa-1S gene codes for a repressor. Several of the qa genes continued to be expressed at high levels even in the presence of glucose in the delta qa-1S strain, which indicates that transcription of these genes is not being affected directly by a repressor molecule in the presence of glucose. PMID:1533844

Case, M E; Geever, R F; Asch, D K

1992-04-01

326

A reporter gene to analyse the hypermutation of immunoglobulin genes.  

PubMed

The affinity maturation of antibodies is driven by somatic hypermutation which is localized to specific segments of the coding genes. The information available on this process derives from studies in vivo. With the intention of developing new approaches, we have constructed a fusion gene between a kappa chain and a selectable neomycin resistance gene, neor. The neor gene, which includes the SV40 small t intron and polyadenylation site, but not the upstream elements nor its first 12 amino acids, is an in-frame substitution of the FR2-CDR3 fragment of a rearranged V kappa OX1-J kappa 5 gene. Expression of neor activity is therefore dependent on the upstream immunoglobulin sequence. A stop codon was placed in the CDR1 region so that only mutants survive treatment with geneticin sulphate (G418). The effectiveness of the system was tested by transfecting the NS0 myeloma cell line and isolating spontaneous mutants. Neomycin-resistant clones arose at an estimated rate of 1 x 10(-8)/cell division, and over 90% were authentic structural mutants. Unlike the somatic hypermutations, the majority arose by in-frame deletions including the stop codon, although up to 30% involved a point mutation. The reporter gene was then modified by substituting all the sequences downstream of the J kappa 5 with others known to be required for full hypermutation in vivo. Different cell lines were transfected and G418-resistant clones analyzed. No significant increase in the rate of reversion or in the generation of point mutations versus deletions was detected, even using conditioned culture medium. In the presence of azacytidine however, a mutant involving multiple events (single base addition and deletion plus two point mutations) was detected. The reporter gene system therefore seems suitable to test culture conditions and modifications of the host cells aimed at the derivation of an in vitro assay of somatic hypermutation. PMID:7783211

Chui, Y L; Lozano, F; Jarvis, J M; Pannell, R; Milstein, C

1995-06-01

327

A neuro-fuzzy inference system to infer gene-gene interactions based on recognition of microarray gene expression patterns  

Microsoft Academic Search

A neuro-fuzzy inference system that recognizes the expression patterns of genes in microarray gene expression (MGE) data, called GeneCFE-ANFIS, is proposed to infer gene interactions. In this study, three primary features are utilized to extract genes' expression patterns and used as inputs to neuro-fuzzy inference system. The proposed algorithm learns expression patterns from the known genetic interactions, such as the

Cheng-long Chuang; Chung-ming Chen; Grace S. Shieh; Joe-air Jiang

2007-01-01

328

PTCH Gene Mutations in Odontogenic Keratocysts  

Microsoft Academic Search

An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the human homologue of the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The PTCH gene encodes a transmembrane protein that acts

D. C. Barreto; R. S. Gomez; A. E. Bale; W. L. Boson; L. De Marco

2000-01-01

329

Gene Recognition Via Spliced Sequence Alignment  

Microsoft Academic Search

Gene recognition is one of the most important problems in computational molecular biology. Previous attempts to solve this problem were based on statistics, and applications of combinatorial methods for gene recognition were almost unexplored. Recent advances in large-scale cDNA sequencing open a way toward a new approach to gene recognition that uses previously sequenced genes as a clue for recognition

Mikhail S. Gelfand; Andrey A. Mironov; Pavel A. Pevzner

1996-01-01

330

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

331

TREES OF GENES IN POPULATIONS Joseph Felsenstein  

E-print Network

1 TREES OF GENES IN POPULATIONS Joseph Felsenstein Abstract Trees of ancestry of copies of genes appears thin. If each of these thin lines truly contained only one copy of this gene's sequence, we would and more important to evolutionary genetics. #12;4 Trees of genes in populations To explain how population

Borenstein, Elhanan

332

Molecular Evolution of Human Visual Pigment Genes  

Microsoft Academic Search

By comparing the published DNA sequences for (a) the genes encoding the human visual color pigments (red, green, and blue) with (b) the genes encoding human, bovine, and Drosophila rhodopsins, a phylogenetic tree for the mammalian pigment genes has been constructed. This evolutionary tree shows that the common ancestor of the visual color pigment genes diverged first from that of

Shozo Yokoyama; Ruth Yokoyama

1989-01-01

333

Graph ranking for exploratory gene data analysis  

Microsoft Academic Search

BACKGROUND: Microarray technology has made it possible to simultaneously monitor the expression levels of thousands of genes in a single experiment. However, the large number of genes greatly increases the challenges of analyzing, comprehending and interpreting the resulting mass of data. Selecting a subset of important genes is inevitable to address the challenge. Gene selection has been investigated extensively over

Cuilan Gao; Xin Dang; Yixin Chen; Dawn Wilkins

2009-01-01

334

Comparative Gene Prediction in Human and Mouse  

Microsoft Academic Search

The completion of the sequencing of the mouse genome promises to help predict human genes with greater accuracy. While current ab initio gene prediction programs are remarkably sensitive (i.e., they predict at least a fragment of most genes), their specificity is often low, predicting a large number of false-positive genes in the human genome. Sequence conservation at the protein level

Genis Parra; Pankaj Agarwal; Josep F. Abril; Thomas Wiehe; James W. Fickett; Roderic Guigo

2003-01-01

335

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

336

EMF Genes Regulate Arabidopsis Inflorescence Development  

Microsoft Academic Search

Mutations in EMBRYONlC FLOWER (EMF) genes EMFl and EMf2 abolish rosette development, and the mutants pro- duce either a much reduced inflorescence or a transformed flower. These mutant characteristics suggest a repressive effect of EMF activities on reproductive development. To investigate the role of EMf genes in regulating reproductive development, we studied the relationship between EMf genes and the genes

Lingjing Chen; Jin-Chen Cheng; Linda Castle; Renee Sung

1997-01-01

337

Familial aggregation analysis of gene expressions  

PubMed Central

Traditional studies of familial aggregation are aimed at defining the genetic (and non-genetic) causes of a disease from physiological or clinical traits. However, there has been little attempt to use genome-wide gene expressions, the direct phenotypic measures of genes, as the traits to investigate several extended issues regarding the distributions of familially aggregated genes on chromosomes or in functions. In this study we conducted a genome-wide familial aggregation analysis by using the in vitro cell gene expressions of 3300 human autosome genes (Problem 1 data provided to Genetic Analysis Workshop 15) in order to answer three basic genetics questions. First, we investigated how gene expressions aggregate among different types (degrees) of relative pairs. Second, we conducted a bioinformatics analysis of highly familially aggregated genes to see how they are distributed on chromosomes. Third, we performed a gene ontology enrichment test of familially aggregated genes to find evidence to support their functional consensus. The results indicated that 1) gene expressions did aggregate in families, especially between sibs. Of 3300 human genes analyzed, there were a total of 1105 genes with one or more significant (empirical p < 0.05) familial correlation; 2) there were several genomic hot spots where highly familially aggregated genes (e.g., the chromosome 6 HLA genes cluster) were clustered; 3) as we expected, gene ontology enrichment tests revealed that the 1105 genes were aggregating not only in families but also in functional categories. PMID:18466548

Rao, Shao-Qi; Xu, Liang-De; Zhang, Guang-Mei; Li, Xia; Li, Lin; Shen, Gong-Qing; Jiang, Yang; Yang, Yue-Ying; Gong, Bin-Sheng; Jiang, Wei; Zhang, Fan; Xiao, Yun; Wang, Qing K

2007-01-01

338

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

339

Scientists Spot Gene Linked to Tanning 'Addiction'  

MedlinePLUS

... 2015) Friday, January 16, 2015 Related MedlinePlus Pages Genes and Gene Therapy Skin Cancer Sun Exposure THURSDAY, Jan. 15, 2015 ( ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Skin Cancer Sun Exposure Recent Health News Page ...

340

Extracting Knowledge from Dynamics in Gene Expression  

Microsoft Academic Search

Most investigations of coordinated gene expression have focused on year, the focus of the research community is shifting toward identifying correlated expression patterns between genes by examining a functional understanding of the roles of and relationships their normalized static expression levels. In this study, we focus on between different genes. With advances in genetic expres- the dynamics of gene expression

Ben Y. Reis; Atul J. Butte; Isaac S. Kohane

2001-01-01

341

Analysis of Microarray Gene Expression Data  

Microsoft Academic Search

Microarrays provide the biological research community with tremendously rich, sensitive and detailed information on gene expression profiles. Gene expression profiling and gene expression patterns have been found useful for solving a wide variety of important biological and biomedical problems, including the study of metabolic pathways, inference of the functions of unknown genes, diagnosis of diseased states, as well as facilitating

Tuan D. Pham; Christine Wells; Denis I. Crane

2006-01-01

342

Original article Effect of including major gene  

E-print Network

was mostly efficient in the medium and long term when the gene was rare and recessive and in the medium term and to a limited risk of losing it by genetic drift for a rare recessive gene. major gene / QTL / selection / MonteOriginal article Effect of including major gene information in mass selection: a stochastic

Paris-Sud XI, Université de

343

Newer gene editing technologies toward HIV gene therapy.  

PubMed

Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called "Berlin patient" who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

Manjunath, N; Yi, Guohua; Dang, Ying; Shankar, Premlata

2013-11-01

344

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

2012-05-01

345

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

346

Newer Gene Editing Technologies toward HIV Gene Therapy  

PubMed Central

Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

Manjunath, N.; Yi, Guohua; Dang, Ying; Shankar, Premlata

2013-01-01

347

Human aspartic protease genes homologous to progastricsin gene  

SciTech Connect

Two human genomic libraries in lambda-bacteriophages were probed with human progastricsin cDNA and 30 positive clones were identified and isolated. The restriction mapping of the insert DNA of these clones indicated that they could be divided into at least 3 groups based on structural overlaps. Two of the groups have been partially mapped and its restriction enzyme fragments have been probed with 5'- and 3'-region of human progastricsin cDNA. The first group, which will be referred to as GX-1 gene, contained in about 10 kb genomic DNA and probed positive for the progastricsin 3'- and 5'-regions. A 1.3 kb fragment positive in the Southern blot was subcloned in M13 phage and partially sequenced. This structure revealed a 0.2 kb exon with the inferred amino acid sequence homologous to human gastricsin. Since GX-1 gene is positive for both the 5'-and 3'-region of progastricsin it is probably the full length gene of another human aspartic protease with structure very homologous to progastricsin. The clones from a second gene, GX-2, which is about 16 kb represent mainly the 3'-region of progastricsin. Partial nucleotide sequence of presumed exons in GX-2 indicated that it is also homologous to progastricsin. However, the restriction map of GX-2 was very different from GX-1. They speculated that GX-1 and Gx-2 may represent two other genes with exons closely homologous to human progastricsin but more distantly homologous to pepsinogen.

Wang, X.J.; Wong, R.N.S.; Tang, J.

1987-05-01

348

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. PMID:22811949

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

2012-01-01

349

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

350

[Polymeric nanoparticles with therapeutic gene for gene therapy: I. Preparation and in vivo gene transfer study].  

PubMed

VEGF nanoparticle (VEGF-NP) was prepared by a multi-emulsification technique using a biodegradable poly-dl-lactic-co-glycolic (PLGA) as matrix material. The nanoparticles were characterized for size, VEGF loading capacity, and in vitro release. VEGF-NP and naked VEGF plasmid were intramuscularly injected into the ischemia site of the rabbit chronic hindlimb ischemia model and the efficiency of VEGF-NP as gene delivery carrier for gene therapy in animal model was evaluated. Gene therapuetic effect was assessed evaluated by RT-PCR, immunohistochemistry and angiography assay. The average size of VEGF-NP was around 300 nm. The encapsulation efficiency of VEGF was above 96%. Loading amount of VEGF in the nanoparticles was about 4%. In vitro, nanoparticles maintained sustained-release of VEGF for two weeks. Two weeks post gene injection the capillary density in VEGF-NP group (81.22 per mm2) was significantly higher than that in control group (29.54 mm2). RT-PCR results showed greatly higher VEGF expression in VEGF-NP group (31.79au * mm) than that in naked VEGF group (9.15 au * mm). As a carrier system for gene therapy in animal model, VEGF-NP is much better than naked DNA plasmid. The results demonstrate great possibility of using NP carrier in human gene therapy. PMID:16013231

Yang, Jing; Song, Cunxian; Sun, Hongfan; Wu, Li; Tang, Lina; Leng, Xigang; Wang, Pengyan; Xu, Yiyao; Li, Yongjun; Guan, Heng

2005-06-01

351

Genes and Abdominal Aortic Aneurysm  

PubMed Central

Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since first candidate gene studies were published 20 years ago, nearly 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. The studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, if appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called CNTN3 which is located on chromosome 3p12.3. Two follow-up studies, however, could not replicate the association. Two other SNPs, which are located on chromosome 9p21 and 9q33 were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense RNA that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute to AAA pathogenesis. PMID:21146954

Hinterseher, Irene; Tromp, Gerard; Kuivaniemi, Helena

2010-01-01

352

LETTER doi:10.1038/nature11184 Proto-genes and de novo gene birth  

E-print Network

LETTER doi:10.1038/nature11184 Proto-genes and de novo gene birth Anne-Ruxandra Carvunis1 to which functional genes evolve de novo through transitory proto-genes4 generated by widespread-genic sequences togenes.We identify 1,900 candidate proto-genes among S. cerevisiae ORFs and find that denovogene

Thierry-Mieg, Nicolas

353

In silico prioritisation of candidate genes for prokaryotic gene function discovery: an application of phylogenetic profiles  

Microsoft Academic Search

BACKGROUND: In silico candidate gene prioritisation (CGP) aids the discovery of gene functions by ranking genes according to an objective relevance score. While several CGP methods have been described for identifying human disease genes, corresponding methods for prokaryotic gene function discovery are lacking. Here we present two prokaryotic CGP methods, based on phylogenetic profiles, to assist with this task. RESULTS:

Frank P. Y. Lin; Enrico W. Coiera; Ruiting Lan; Vitali Sintchenko

2009-01-01

354

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

NASA Astrophysics Data System (ADS)

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

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

355

Why Is the Correlation between Gene Importance and Gene Evolutionary Rate So Weak?  

E-print Network

that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distributionWhy Is the Correlation between Gene Importance and Gene Evolutionary Rate So Weak? Zhi Wang

Zhang, Jianzhi

356

Coexpression network based on natural variation in human gene expression reveals gene interactions and functions  

Microsoft Academic Search

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene net- works, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting

Renuka R. Nayak; Michael Kearns; Richard S. Spielman; Vivian G. Cheung

2009-01-01

357

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...

358

Microfluidic approaches for gene delivery and gene therapy Jungkyu Kim,a  

E-print Network

Microfluidic approaches for gene delivery and gene therapy Jungkyu Kim,a Inseong Hwang,b Derek for gene delivery and therapy. The micro-scaled environment within microfluidic systems enables precise are producing increased efficiency in gene delivery and promise improved gene therapy results. Introduction Many

Sun, Yu

359

Current status of gene delivery and gene therapy in lacrimal gland using viral vectors  

Microsoft Academic Search

Gene delivery is one of the biggest challenges in the field of gene therapy. It involves the efficient transfer of transgenes into somatic cells for therapeutic purposes. A few major drawbacks in gene delivery include inefficient gene transfer and lack of sustained transgene expression. However, the classical method of using viral vectors for gene transfer has circumvented some of these

Shivaram Selvam; Padmaja B. Thomas; Sarah F. Hamm-Alvarez; Joel E. Schechter; Douglas Stevenson; Austin K. Mircheff; Melvin D. Trousdale

2006-01-01

360

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

Technology Transfer Automated Retrieval System (TEKTRAN)

DNA sequence of the tabD gene within the tabtoxin biosynthetic gene cluster of Pseudomonas syringae (GenBank accession number AY091643). The predicted gene product of the P. syringae tabD gene is a probable aminotransferase, class I and II,pfam00155 (1e-12); most similar to aat-like gene products fr...

361

Sexy Gene Conversions: Locating Gene Conversions on the X-Chromosome  

E-print Network

Sexy Gene Conversions: Locating Gene Conversions on the X-Chromosome Mark J. Lawson1 , Liqing Zhang Gene conversion can have a profound impact on both the short-term and long-term evolution of genes and genomes. Here we examined the gene families that are located on the X-chromosomes of human, chimp, mouse

Zhang, Liqing

362

Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans  

E-print Network

Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans Sabine C:22), which fuses the COL1A1 and PDGF genes. We determined the characteristic gene expression profile of DFSP cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily

Botstein, David

363

Gene tree of the HoxA11 genes in vertebrates illustrating several  

E-print Network

Gene tree of the HoxA11 genes in vertebrates illustrating several whole genome duplications (WGD with all the other vertebrate animals, and many developmental genes with invertebrate animals as well. The Hox genes are one class of toolkit genes that specify body plan features such as limbs and fins

364

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

E-print Network

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

Mukhopadhyay, Asish

365

Virtual Gene: a Gene Selection Algorithm for Sample Classification on Microarray Datasets  

E-print Network

Virtual Gene: a Gene Selection Algorithm for Sample Classification on Microarray Datasets Xian Xu, USA Abstract. Gene Selection is one class of most used data analysis algorithms on microarray dataset. The goal of gene selection algorithms is to filter out a small set of informative genes that best explains

Buffalo, State University of New York

366

Neural Networks Approaches for Discovering the Learnable Correlation between Gene Function and Gene  

E-print Network

Neural Networks Approaches for Discovering the Learnable Correlation between Gene Function and Gene University of Toronto Toronto, ON. emad@cs.toronto.edu Abstract. Identifying gene function has many useful applications. Identifying gene function based on gene expression data is much easier in prokaryotes than

Bonner, Anthony

367

Temporal and spatial expression patterns of canonical clock genes and clock-controlled genes in the  

E-print Network

Temporal and spatial expression patterns of canonical clock genes and clock-controlled genesB)-containing cells is retinorecipient and the cells therein lack rhythmic expression of clock genes and electrical of expression of the canonical clock genes Per1, Per2 and vasopressin mRNA, a clock-controlled gene

Silver, Rae

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

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

370

Conditional Gene Knockout System in Cone Photoreceptors  

Microsoft Academic Search

The generation of gene knockout mice by injection of homologous gene targeted embryonic stem (ES) cells into blastocyst has\\u000a rapidly advanced our knowledge of gene function in mammals. However, knockout of essential genes often causes embryonic or\\u000a neonatal lethality and thus obscures the particular role of genes in a target tissue or in adults. To circumvent this problem\\u000a and disrupt

Yun-Zheng Le; John D. Ash; Muayyad R. Al-Ubaidi; Ying Chen; Jian-Xing Ma; Robert E. Anderson

371

Activities of Human Gene Nomenclature Committee  

SciTech Connect

The objective of this project, shared between NIH and DOE, has been and remains to enable the medical genetics communities to use common names for genes that are discovered by different gene hunting groups, in different species. This effort provides consistent gene nomenclature and approved gene symbols to the community at large. This contributes to a uniform and consistent understanding of genomes, particularly the human as well as functional genomics based on comparisons between homologous genes in related species (human and mice).

NONE

2002-07-16

372

Does inbreeding affect gene expression in birds?  

PubMed

Inbreeding increases homozygosity, exposes genome-wide recessive deleterious alleles and often reduces fitness. The physiological and reproductive consequences of inbreeding may be manifested already during gene regulation, but the degree to which inbreeding influences gene expression is unknown in most organisms, including in birds. To evaluate the pattern of inbreeding-affected gene expression over the genome and in relation to sex, we performed a transcriptome-wide gene expression (10 695 genes) study of brain tissue of 10-day-old inbred and outbred, male and female zebra finches. We found significantly lower gene expression in females compared with males at Z-linked genes, confirming that dosage compensation is incomplete in female birds. However, inbreeding did not affect gene expression at autosomal or sex-linked genes, neither in males nor in females. Analyses of single genes again found a clear sex-biased expression at Z-linked genes, whereas only a single gene was significantly affected by inbreeding. The weak effect of inbreeding on gene expression in zebra finches contrasts to the situation, for example, in Drosophila where inbreeding has been found to influence gene expression more generally and at stress-related genes in particular. PMID:25232028

Hansson, Bengt; Naurin, Sara; Hasselquist, Dennis

2014-09-01

373

Combinatorial methods for gene recognition  

SciTech Connect

The major result of the project is the development of a new approach to gene recognition called spliced alignment algorithm. They have developed an algorithm and implemented a software tool (for both IBM PC and UNIX platforms) which explores all possible exon assemblies in polynomial time and finds the multi-exon structure with the best fit to a related protein. Unlike other existing methods, the algorithm successfully performs exons assemblies even in the case of short exons or exons with unusual codon usage; they also report correct assemblies for the genes with more than 10 exons provided a homologous protein is already known. On a test sample of human genes with known mammalian relatives the average overlap between the predicted and the actual genes was 99%, which is remarkably well as compared to other existing methods. At that, the algorithm absolute correctly reconstructed 87% of genes. The rare discrepancies between the predicted and real axon-intron structures were restricted either to extremely short initial or terminal exons or proved to be results of alternative splicing. Moreover, the algorithm performs reasonably well with non-vertebrate and even prokaryote targets. The spliced alignment software PROCRUSTES has been in extensive use by the academic community since its announcement in August, 1996 via the WWW server (www-hto.usc.edu/software/procrustes) and by biotech companies via the in-house UNIX version.

Pevzner, P.A.

1997-10-29

374

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

2013-01-01

375

Gene Ontology Consortium: going forward  

PubMed Central

The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology. PMID:25428369

2015-01-01

376

Gene methylation in gastric cancer.  

PubMed

Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. PMID:23669186

Qu, Yiping; Dang, Siwen; Hou, Peng

2013-09-23

377

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

2013-12-01

378

Genes, Environments, and Behavior 1  

NSDL National Science Digital Library

Genes, Environment, and Behavior 1 is the first of two lessons about the field called behavioral genetics, in which scientists study the reciprocating influences of genes and environments on behavior, particularly human behavior. It provides students with a clear understanding of how behavior is defined by scientists and an overview of the genetic and environmental forces that interact to shape behavior.In this lesson, students are assigned reading materials from the book Behavioral Genetics: An introduction to how genes and environments interact through development to shape differences in mood, personality, and intelligence, published by AAAS and The Hastings Center. These chapters are character-based and have relatively easy context. Provided are quizzes that that are administered after the short readings. These quizzes foster a discussion on each topic in behavior and genetics. The titles of the chapters in this lesson are: 1) "What is behavioral genetics?", 2) "How do genes work within their environments?", 3) "How do environments impinge upon the genes?"

American Association for the Advancement of Science (; )

2006-04-25

379

Metazoan Gene Families from Metazome  

DOE Data Explorer

Metazome is a joint project of the Department of Energy's Joint Genome Institute and the Center for Integrative Genomics to facilitate comparative genomic studies amongst metazoans. Clusters of orthologous and paralogous genes that represent the modern descendents of ancestral gene sets are constructed at key phylogenetic nodes. These clusters allow easy access to clade specific orthology/paralogy relationships as well as clade specific genes and gene expansions. As of version 2.0.4, Metazome provides access to twenty-four sequenced and annotated metazoan genomes, clustered at nine evolutionarily significant nodes. Where possible, each gene has been annotated with PFAM, KOG, KEGG, and PANTHER assignments, and publicly available annotations from RefSeq, UniProt, Ensembl, and JGI are hyper-linked and searchable. The included organisms (by common name) are: Human, Mouse, Rat, Dog, Opossum, Chicken, Frog, Stickleback, Medaka, Fugu pufferfish; Zebrafish, Seasquirt - savignyi, Seasquirt - intestinalis, Amphioxus, Sea Urchin, Fruitfly, Mosquite, Yellow Fever Mosquito, Silkworm, Red Flour Beetle, Worm, Briggsae Worm, Owl limpet (snail), and Sea anemone. [Copied from Metazome Overview at http://www.metazome.net/Metazome_info.php

380

Gene replacement in Penicillium roqueforti.  

PubMed

Most cheese-making filamentous fungi lack suitable molecular tools to improve their biotechnology potential. Penicillium roqueforti, a species of high industrial importance, would benefit from functional data yielded by molecular genetic approaches. This work provides the first example of gene replacement by homologous recombination in P. roqueforti, demonstrating that knockout experiments can be performed in this fungus. To do so, we improved the existing transformation method to integrate transgenes into P. roqueforti genome. In the meantime, we cloned the PrNiaD gene, which encodes a NADPH-dependent nitrate reductase that reduces nitrate to nitrite. Then, we performed a deletion of the PrNiaD gene from P. roqueforti strain AGO. The ?PrNiaD mutant strain is more resistant to chlorate-containing medium than the wild-type strain, but did not grow on nitrate-containing medium. Because genomic data are now available, we believe that generating selective deletions of candidate genes will be a key step to open the way for a comprehensive exploration of gene function in P. roqueforti. PMID:25315520

Goarin, Anne; Silar, Philippe; Malagnac, Fabienne

2015-05-01

381

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. PMID:23712359

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

2013-01-01

382

Decationized polyplexes for gene delivery.  

PubMed

Gene therapy has received much attention in the field of drug delivery. Synthetic, nonviral gene delivery systems have gained increasing attention as vectors for gene therapy mainly due to a favorable immunogenicity profile and ease of manufacturing as compared to viral vectors. The great majority of these formulations are based on polycationic structures, due to their ability to interact with negatively charged nucleic acids to spontaneously form nanoparticles. In recent years, several polycationic systems have demonstrated high transfection in vitro. However, progress toward clinical applications has been slow, mainly because the cationic nature of these systems leads to intolerable toxicity levels, inappropriate biodistribution and unsatisfactory efficiency in vivo, particularly after systemic administration. Decationized polyplexes are a new class of gene delivery systems that have been developed as an alternative for conventional polycation-based systems. The major innovation introduced by decationized polyplexes is that these systems are based on neutral polymers, without any detrimental effect on the physicochemical stability or encapsulation ability, due to the transient presence of cationic charge and disulfide cross-links between the polymer chains by which the nucleic acids are physically entrapped in the particles. This editorial summarizes the most important features of decationized polyplexes and discusses potential implications for the development of new safe and efficient gene delivery systems. PMID:25425332

Novo, Luís; Mastrobattista, Enrico; van Nostrum, Cornelus F; Lammers, Twan; Hennink, Wim E

2015-04-01

383

Consensus gene regulatory networks: combining multiple microarray gene expression datasets  

NASA Astrophysics Data System (ADS)

In this paper we present a method for modelling gene regulatory networks by forming a consensus Bayesian network model from multiple microarray gene expression datasets. Our method is based on combining Bayesian network graph topologies and does not require any special pre-processing of the datasets, such as re-normalisation. We evaluate our method on a synthetic regulatory network and part of the yeast heat-shock response regulatory network using publicly available yeast microarray datasets. Results are promising; the consensus networks formed provide a broader view of the potential underlying network, obtaining an increased true positive rate over networks constructed from a single data source.

Peeling, Emma; Tucker, Allan

2007-09-01

384

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

PubMed

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. PMID:22110038

Culhane, Aedín C; Schröder, 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

385

Analysis of human genes with protein-protein interaction network for detecting disease genes  

NASA Astrophysics Data System (ADS)

The topological features of disease genes and non-disease genes were widely utilized in disease genes prediction. However, previous studies neglected to exploit essential genes to distinguish disease genes and non-disease genes. Therefore, this paper firstly takes essential genes as reference to analyze the topological properties of human genes with protein-protein interaction network. Empirical results demonstrate that nonessential disease genes are topologically more important and closer to the center of the network than other genes (unknown genes, which are deemed as non-disease genes in disease genes prediction). Although disease genes are closer to essential genes, we find that the influence of disease genes on essential genes is similar with other genes, or even weaker. Further, we generate new topological features according to our findings and validate the effectiveness of combining the additional features for detecting disease genes. In addition, we find that the k-shell index (ks) of protein-protein network follows a power law distribution, and the function of the proteins with the largest ks may deserve further research.

Wu, Shun-yao; Shao, Feng-jing; Sun, Ren-cheng; Sui, Yi; Wang, Ying; Wang, Jin-long

2014-03-01

386

Encapsulation for somatic gene therapy.  

PubMed

With the human genome project approaching its completion date of 2005, gene-based technology will play an increasingly important role in health-care delivery. Non-autologous somatic gene therapy is a novel application in which non-autologous cell lines engineered to secrete a recombinant protein are enclosed within immunoisolation devices and implanted into all patients requiring the same product for therapy. The development of this technology requires a multi-disciplinary effort towards optimization of the biomaterial used to manufacture the implantable devices and selection of the appropriate cell lines for enclosure. The efficacy of this technology is illustrated in the treatment of dwarfism and lysosomal storage disease in murine models. The potential of a safe and cost-effective gene-based delivery method should have wide applications in treating both classical genetic disorders and non-Mendelian diseases. PMID:10415564

Chang, P L

1999-06-18

387

Gene therapy in cardiac arrhythmias.  

PubMed

Gene therapy has progressed from a dream to a bedside reality in quite a few human diseases. From its first application in adenosine deaminase deficiency, through the years, its application has evolved to vascular angiogenesis and cardiac arrhythmias. Gene based biological pacemakers using viral vectors or mesenchymal cells tested in animal models hold much promise. Induction of pacemaker activity within the left bundle branch can provide stable heart rates. Genetic modification of the AV node mimicking beta blockade can be therapeutic in the management of atrial fibrillation. G protein overexpression to modify the AV node also is experimental. Modification and expression of potassium channel genes altering the delayed rectifier potassium currents may permit better management of congenital long QT syndromes. Arrhythmias in a failing heart are due to abnormal calcium cycling. Potential targets for genetic modulation include the sarcoplasmic reticulum calcium pump, calsequestrin and sodium calcium exchanger. Lastly the ethical concerns need to be addressed. PMID:16943902

Praveen, S V; Francis, Johnson; Venugopal, K

2006-01-01

388

Search for Basonuclin Target Genes  

PubMed Central

Basonuclin (Bnc 1) is a transcription factor that has an unusual ability to interact with promoters of both RNA polymerases I and II. The action of basonuclin is mediated through three pairs of evolutionarily conserved zinc fingers, which produce three DNase I footprints on the promoters of rDNA and the basonuclin gene. Using these DNase footprints, we built a computational model for the basonuclin DNA-binding module, which was used to identify in silico potential RNA polymerase II target genes in the human and mouse promoter databases. The target genes of basonuclin show that it regulates the expression of proteins involved in chromatin structure, transcription/DNA-binding, ion-channels, adhesion/cell-cell junction, signal transduction and intracellular transport. Our results suggest that basonuclin, like MYC, may coordinate transcriptional activities among the three RNA polymerases. But basonuclin regulates a distinctive set of pathways, which differ from that regulated by MYC. PMID:16919236

Wang, Junwen; Zhang, Shengliang; Schultz, Richard M.; Tseng, Hung

2006-01-01

389

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. PMID:2644621

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

1989-01-01

390

Modelling Nonstationary Gene Regulatory Processes  

PubMed Central

An important objective in systems biology is to infer gene regulatory networks from postgenomic data, and dynamic Bayesian networks have been widely applied as a popular tool to this end. The standard approach for nondiscretised data is restricted to a linear model and a homogeneous Markov chain. Recently, various generalisations based on changepoint processes and free allocation mixture models have been proposed. The former aim to relax the homogeneity assumption, whereas the latter are more flexible and, in principle, more adequate for modelling nonlinear processes. In our paper, we compare both paradigms and discuss theoretical shortcomings of the latter approach. We show that a model based on the changepoint process yields systematically better results than the free allocation model when inferring nonstationary gene regulatory processes from simulated gene expression time series. We further cross-compare the performance of both models on three biological systems: macrophages challenged with viral infection, circadian regulation in Arabidopsis thaliana, and morphogenesis in Drosophila melanogaster. PMID:20721277

Grzegorcyzk, Marco; Husmeier, Dirk; Rahnenführer, Jörg

2010-01-01

391

Gene Therapy for Bone Engineering  

PubMed Central

Bone has an intrinsic healing capacity that may be exceeded when the fracture gap is too big or unstable. In that moment, osteogenic measures need to be taken by physicians. It is important to combine cells, scaffolds and growth factors, and the correct mechanical conditions. Growth factors are clinically administered as recombinant proteins. They are, however, expensive and needed in high supraphysiological doses. Moreover, their half-life is short when administered to the fracture. Therefore, gene therapy may be an alternative. Cells can constantly produce the protein of interest in the correct folding, with the physiological glycosylation and in the needed amounts. Genes can be delivered in vivo or ex vivo by viral or non-viral methods. Adenovirus is mostly used. For the non-viral methods, hydrogels and recently sonoporation seem to be promising means. This review will give an overview of recent advancements in gene therapy approaches for bone regeneration strategies. PMID:25699253

Balmayor, Elizabeth Rosado; van Griensven, Martijn

2015-01-01

392

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

393

Metagenomics and novel gene discovery  

PubMed Central

Metagenomics provides a means of assessing the total genetic pool of all the microbes in a particular environment, in a culture-independent manner. It has revealed unprecedented diversity in microbial community composition, which is further reflected in the encoded functional diversity of the genomes, a large proportion of which consists of novel genes. Herein, we review both sequence-based and functional metagenomic methods to uncover novel genes and outline some of the associated problems of each type of approach, as well as potential solutions. Furthermore, we discuss the potential for metagenomic biotherapeutic discovery, with a particular focus on the human gut microbiome and finally, we outline how the discovery of novel genes may be used to create bioengineered probiotics. PMID:24317337

Culligan, Eamonn P; Sleator, Roy D; Marchesi, Julian R; Hill, Colin

2014-01-01

394

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

395

Human height genes and cancer.  

PubMed

Body development requires the ability to control cell proliferation and metabolism, together with selective 'invasive' cell migration for organogenesis. These requirements are shared with cancer. Human height-associated loci have been recently identified by genome-wide SNP-association studies. Strikingly, most of the more than 100 genes found associated to height appear linked to neoplastic growth, and impose a higher risk for cancer. Height-associated genes drive the HH/PTCH and BMP/TGF? pathways, with p53, c-Myc, ER?, HNF4A and SMADs as central network nodes. Genetic analysis of body-size-affecting diseases and evidence from genetically-modified animals support this model. The finding that cancer is deeply linked to normal, body-plan master genes may profoundly affect current paradigms on tumor development. PMID:23428607

Tripaldi, Romina; Stuppia, Liborio; Alberti, Saverio

2013-08-01

396

Electroporation-mediated gene delivery.  

PubMed

Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models. PMID:25620008

Young, Jennifer L; Dean, David A

2015-01-01

397

Genome majority vote improves gene predictions.  

PubMed

Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes. Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction. We applied an algorithm using a genome majority vote (GMV) scheme to increase the consistency of gene starts among orthologs. We used a set of validated Escherichia coli genes as a standard to quantify accuracy. Results showed that the GMV algorithm can correct hundreds of gene prediction errors in sets of five or ten genomes while introducing few errors. Using a conservative calculation, we project that GMV would resolve many inconsistencies and errors in publicly available microbial gene maps. Our simple and logical solution provides a notable advance toward accurate gene maps. PMID:22131910

Wall, Michael E; Raghavan, Sindhu; Cohn, Judith D; Dunbar, John

2011-11-01

398

Rapid Concerted Evolution via Gene Conversion at the Drosophila hsp70 Genes  

Microsoft Academic Search

.   We analyzed nucleotide variation in the hsp70 genes of Drosophila melanogaster (five genes) and D. simulans (four genes) to characterize the homogenizing and diversifying roles of gene conversion in their evolution. Gene conversion\\u000a within and between the 87A7 and 87C1 gene clusters homogenize the hsp70 coding regions; in both D. melanogaster and D. simulans, same-cluster paralogues are virtually identical,

Brian R. Bettencourt; Martin E. Feder

2002-01-01

399

Gene therapy for retinal disease  

PubMed Central

Gene therapy strategies for the treatment of inherited retinal diseases have made major advances in recent years. This review focuses on adeno-associated viral (AAV) vector approaches to treat retinal degeneration and thus prevent or delay the onset of blindness. Data from human clinical trials of gene therapy for retinal disease show encouraging signs of safety and efficacy from AAV vectors. Recent progress in enhancing cell-specific targeting and transduction efficiency of the various retinal layers plus the use of AAV-delivered growth factors to augment the therapeutic effect and limit cell death suggest even greater success in future human trials is possible. PMID:23305707

McClements, Michelle E; MacLaren, Robert E

2013-01-01

400

GenePRIMP: Improving Microbial Gene Prediction Quality  

SciTech Connect

Amrita Pati of the DOE Joint Genome Institute's Genome Biology group talks about a computational pipeline that evaluates the accuracy of gene models in genomes and metagenomes at different stages of finishing at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

Pati, Amrita [DOE Joint Genome Institute's Genome Biology group

2009-05-29

401

Selecting Informative Genes from Microarray Dataset by Incorporating Gene Ontology  

E-print Network

profiling [13]. A typical DNA microarray study utilizes several DNA microarray chips on different tis- sue in classifying tumor molecularly with the advent of DNA microarray technologies for large-scale transcriptional samples and generates a numerical array with thousands of rows (genes) and tens of columns (experiments/DNA

Buffalo, State University of New York

402

Identification of genes and gene clusters involved in mycotoxin synthesis  

Technology Transfer Automated Retrieval System (TEKTRAN)

Research methods to identify and characterize genes involved in mycotoxin biosynthetic pathways have evolved considerably over the years. Before whole genome sequences were available (e.g. pre-genomics), work focused primarily on chemistry, biosynthetic mutant strains and molecular analysis of sing...

403

Laser-Based Gene Transfection and Gene Therapy  

Microsoft Academic Search

The plasma membrane of mammalian cells can be transiently permeablized by optical means and exogenous materials or genes can be introduced into the cytoplasm of living cells. Until now, few mechanisms were exploited for the manipulation: laser is directly and tightly focused on the cells for optoinjection, laser-induced stress waves, photochemical internalization, and irradiation of selective cell targeting with light-absorbing

Cui-Ping Yao; Zhen-Xi Zhang; Ramtin Rahmanzadeh; Gereon Huettmann

2008-01-01

404

The frustrated gene: origins of eukaryotic gene expression  

PubMed Central

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

Madhani, Hiten D.

2014-01-01

405

Gene therapy on demand: site specific regulation of gene therapy.  

PubMed

Since 1990 when the first clinical gene therapy trial was conducted, much attention and considerable promise have been given to this form of treatment. Gene therapy has been used with success in patients suffering from severe combined immunodeficiency syndromes (X-SCID and ADA-deficiency), Leber's congenital amaurosis, hemophilia, ?-thalassemia and adrenoleukodystrophy. Last year, the first therapeutic vector (Glybera) for treatment of lipoprotein lipase deficiency has been registered in the European Union. Nevertheless, there are still several numerous issues that need to be improved to make this technique more safe, effective and easily accessible for patients. Introduction of the therapeutic gene to the given cells should provide the level of expression which will restore the production of therapeutic protein to normal values or will provide therapeutic efficacy despite not fully physiological expression. However, in numerous diseases the expression of therapeutic genes has to be kept at certain level for some time, and then might be required to be switched off to be activated again when worsening of the symptoms may aggravate the risk of disease relapse. In such cases the promoters which are regulated by local conditions may be more required. In this article the special emphasis is to discuss the strategies of regulation of gene expression by endogenous stimuli. Particularly, the hypoxia- or miRNA-regulated vectors offer the possibilities of tight but, at the same time, condition-dependent and cell-specific expression. Such means have been already tested in certain pathophysiological conditions. This creates the chance for the translational approaches required for development of effective treatments of so far incurable diseases. PMID:23566848

Jazwa, Agnieszka; Florczyk, Urszula; Jozkowicz, Alicja; Dulak, Jozef

2013-08-10

406

Gene transfer: anything goes in plant mitochondria  

PubMed Central

Parasitic plants and their hosts have proven remarkably adept at exchanging fragments of mitochondrial DNA. Two recent studies provide important mechanistic insights into the pattern, process and consequences of horizontal gene transfer, demonstrating that genes can be transferred in large chunks and that gene conversion between foreign and native genes leads to intragenic mosaicism. A model involving duplicative horizontal gene transfer and differential gene conversion is proposed as a hitherto unrecognized source of genetic diversity. See research article: http://www.biomedcentral.com/1741-7007/8/150 PMID:21176244

2010-01-01

407

The P450 gene superfamily: recommended nomenclature.  

PubMed

A nomenclature for the P450 gene superfamily is proposed based on evolution. Recommendations include Roman numerals for distinct gene families, capital letters for subfamilies, and Arabic numerals for individual genes. An updating of this list, which presently includes 65 entries, will be required every 1-2 years. Assignment of orthologous genes is presently uncertain in some cases--between widely diverged species and especially in the P450II family due to the large number of genes. As more is known, it might become necessary to change some gene assignments that are based on our present knowledge. PMID:3829886

Nebert, D W; Adesnik, M; Coon, M J; Estabrook, R W; Gonzalez, F J; Guengerich, F P; Gunsalus, I C; Johnson, E F; Kemper, B; Levin, W

1987-02-01

408

DNA Methylation and Gene Function  

Microsoft Academic Search

In most higher organisms, DNA is modified after synthesis by the enzymatic conversion of many cytosine residues to 5-methylcytosine. For several years, control of gene activity by DNA methylation has been recognized as a logically attractive possibility, but experimental support has proved elusive. However, there is now reason to believe, from recent studies, that DNA methylation is a key element

Aharon Razin; Arthur D. Riggs

1980-01-01

409

Search for basonuclin target genes  

Microsoft Academic Search

Basonuclin (Bnc 1) is a transcription factor that has an unusual ability to interact with promoters of both RNA polymerases I and II. The action of basonuclin is mediated through three pairs of evolutionarily conserved zinc fingers, which produce three DNase I footprints on the promoters of rDNA and the basonuclin gene. Using these DNase footprints, we built a computational

Junwen Wang; Shengliang Zhang; Richard M. Schultz; Hung Tseng

2006-01-01

410

Circadian gene variants in cancer.  

PubMed

Humans as diurnal beings are active during the day and rest at night. This daily oscillation of behavior and physiology is driven by an endogenous circadian clock not environmental cues. In modern societies, changes in lifestyle have led to a frequent disruption of the endogenous circadian homeostasis leading to increased risk of various diseases including cancer. The clock is operated by the feedback loops of circadian genes and controls daily physiology by coupling cell proliferation and metabolism, DNA damage repair, and apoptosis in peripheral tissues with physical activity, energy homeostasis, immune and neuroendocrine functions at the organismal level. Recent studies have revealed that defects in circadian genes due to targeted gene ablation in animal models or single nucleotide polymorphism, deletion, deregulation and/or epigenetic silencing in humans are closely associated with increased risk of cancer. In addition, disruption of circadian rhythm can disrupt the molecular clock in peripheral tissues in the absence of circadian gene mutations. Circadian disruption has recently been recognized as an independent cancer risk factor. Further study of the mechanism of clock-controlled tumor suppression will have a significant impact on human health by improving the efficiencies of cancer prevention and treatment. PMID:24901356

Kettner, Nicole M; Katchy, Chinenye A; Fu, Loning

2014-06-01

411

Seed Targeted Gene Confinement Strategies  

Technology Transfer Automated Retrieval System (TEKTRAN)

The genetic improvement of plants using biotechnology is now centrally important to agriculture, food security, and the biofuels industry. It is also important to the continued health of the environment as the need for food (on existing arable land) and renewable energy becomes critical. New genes c...

412

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

413

Gene Expression in Trypanosomatid Parasites  

PubMed Central

The parasites Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids. In silico analyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa. PMID:20169133

Martínez-Calvillo, Santiago; Vizuet-de-Rueda, Juan C.; Florencio-Martínez, Luis E.; Manning-Cela, Rebeca G.; Figueroa-Angulo, Elisa E.

2010-01-01

414

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...

415

How can you patent genes?  

PubMed

What accounts for the continued lack of clarity over the legal procedures for the patenting of DNA sequences? The patenting system was built for a "bricks-and-mortar" world rather than an information economy. The fact that genes are both material molecules and informational systems helps explain the difficulty that the patent system is going to continue to have. PMID:12230840

Eisenberg, Rebecca S

2002-01-01

416

RESEARCH COMMUNICATION Targeting genes for  

E-print Network

of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112 USA A procedure; revised version accepted May 3, 1999. The paradigm for targeted germ-line modification of a mammalian into a cloned gene is transferred by homologous recombination to its chromosomal target in a pluripo- tent

Capecchi, Mario R.

417

PERSPECTIVE Candidate Mycobacterium tuberculosis genes  

E-print Network

PERSPECTIVE Candidate Mycobacterium tuberculosis genes targeted by human microRNAs WeiRui Guo1-wu@northwestern.edu (J. Y. Wu), weilp@mail.cbi.pku.edu.cn (L. Wei) Tuberculosis (TB) remains a major health issue in 1882, Mycobacterium tuberculosis (M. tuberculosis), the causative agent for tuberculosis, remains one

Wu, Jane Y.

418

Genes and Surroundings: Teacher's Guide.  

ERIC Educational Resources Information Center

This teacher's guide is intended to be used with "Genes and Surroundings," an activity unit on human and medical genetics for junior high and middle school students. The unit emphasizes variability and diversity in genetics and is organized around five themes: (1) individuality; (2) continuity; (3) variability in relation to others; (4)…

Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.

419

Ocular Gene Therapy: Quo Vadis?  

Microsoft Academic Search

he question of where gene therapy is going has almost as many answers as there are practitioners in the field. Narrowing our focus to diseases of the eye, this diver- sity of opinions does not contract proportionately. Therefore, rather than forecasting the future, it is more useful to assess the field today, including a consideration of where problems re- main

William W. Hauswirth; Laurent Beaufrere

2000-01-01

420

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

421

Interactive Fly: Genes regulating behavior  

NSDL National Science Digital Library

A list and description of Drosophila genes involved in behavior (agression, anaesthesia sensitivity and resistance, circadian rhythms, courtship, convulsive, equilibrium, feeding, ecdysis, geotaxis, gustatory, habituation, learning, hearing, locomotor, olfactory learning, pattern recognition, pain response, seizure, sleep, thermosensory, visual discrimiation, and wing expansion). Links to many papers. A subset of the Interactive Fly collection.

PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

2006-12-18

422

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

423

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

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

Susan Koba with Anne Tweed

2009-05-22

425

Gene-Culture Coevolutionary Games  

ERIC Educational Resources Information Center

Gene-culture interactions have largely been modelled employing population genetic-type models. Moreover, in the most notable application to date, the "interactive" modes have been one way rather than bidirectional. This paper suggests using game theoretic, fully interactive models. Employing the logic utilized in population ecology for coevolution…

Blute, Marion

2006-01-01

426

Orthopedic Gene Therapy in 2008  

Microsoft Academic Search

Orthopedic disorders, although rarely fatal, are the leading cause of morbidity and impose a huge socioeconomic burden. Their prevalence will increase dramatically as populations age and gain weight. Many orthopedic conditions are difficult to treat by conventional means; however, they are good candidates for gene therapy. Clinical trials have already been initiated for arthritis and the aseptic loosening of prosthetic

Christopher H Evans; Steven C Ghivizzani; Paul D Robbins

2009-01-01

427

Concerted gene recruitment in early plant evolution  

PubMed Central

Background Horizontal gene transfer occurs frequently in prokaryotes and unicellular eukaryotes. Anciently acquired genes, if retained among descendants, might significantly affect the long-term evolution of the recipient lineage. However, no systematic studies on the scope of anciently acquired genes and their impact on macroevolution are currently available in eukaryotes. Results Analyses of the genome of the red alga Cyanidioschyzon identified 37 genes that were acquired from non-organellar sources prior to the split of red algae and green plants. Ten of these genes are rarely found in cyanobacteria or have additional plastid-derived homologs in plants. These genes most likely provided new functions, often essential for plant growth and development, to the ancestral plant. Many remaining genes may represent replacements of endogenous homologs with a similar function. Furthermore, over 78% of the anciently acquired genes are related to the biogenesis and functionality of plastids, the defining character of plants. Conclusion Our data suggest that, although ancient horizontal gene transfer events did occur in eukaryotic evolution, the number of acquired genes does not predict the role of horizontal gene transfer in the adaptation of the recipient organism. Our data also show that multiple independently acquired genes are able to generate and optimize key evolutionary novelties in major eukaryotic groups. In light of these findings, we propose and discuss a general mechanism of horizontal gene transfer in the macroevolution of eukaryotes. PMID:18611267

Huang, Jinling; Gogarten, J Peter

2008-01-01

428

Thesaurus-based disambiguation of gene symbols  

PubMed Central

Background Massive text mining of the biological literature holds great promise of relating disparate information and discovering new knowledge. However, disambiguation of gene symbols is a major bottleneck. Results We developed a simple thesaurus-based disambiguation algorithm that can operate with very little training data. The thesaurus comprises the information from five human genetic databases and MeSH. The extent of the homonym problem for human gene symbols is shown to be substantial (33% of the genes in our combined thesaurus had one or more ambiguous symbols), not only because one symbol can refer to multiple genes, but also because a gene symbol can have many non-gene meanings. A test set of 52,529 Medline abstracts, containing 690 ambiguous human gene symbols taken from OMIM, was automatically generated. Overall accuracy of the disambiguation algorithm was up to 92.7% on the test set. Conclusion The ambiguity of human gene symbols is substantial, not only because one symbol may denote multiple genes but particularly because many symbols have other, non-gene meanings. The proposed disambiguation approach resolves most ambiguities in our test set with high accuracy, including the important gene/not a gene decisions. The algorithm is fast and scalable, enabling gene-symbol disambiguation in massive text mining applications. PMID:15958172

Schijvenaars, Bob JA; Mons, Barend; Weeber, Marc; Schuemie, Martijn J; van Mulligen, Erik M; Wain, Hester M; Kors, Jan A

2005-01-01

429

Genomic evidence for adaptation by gene duplication.  

PubMed

Gene duplication is widely believed to facilitate adaptation, but unambiguous evidence for this hypothesis has been found in only a small number of cases. Although gene duplication may increase the fitness of the involved organisms by doubling gene dosage or neofunctionalization, it may also result in a simple division of ancestral functions into daughter genes, which need not promote adaptation. Hence, the general validity of the adaptation by gene duplication hypothesis remains uncertain. Indeed, a genome-scale experiment found similar fitness effects of deleting pairs of duplicate genes and deleting individual singleton genes from the yeast genome, leading to the conclusion that duplication rarely results in adaptation. Here we contend that the above comparison is unfair because of a known duplication bias among genes with different fitness contributions. To rectify this problem, we compare homologous genes from the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. We discover that simultaneously deleting a duplicate gene pair in S. cerevisiae reduces fitness significantly more than deleting their singleton counterpart in S. pombe, revealing post-duplication adaptation. The duplicates-singleton difference in fitness effect is not attributable to a potential increase in gene dose after duplication, suggesting that the adaptation is owing to neofunctionalization, which we find to be explicable by acquisitions of binary protein-protein interactions rather than gene expression changes. These results provide genomic evidence for the role of gene duplication in organismal adaptation and are important for understanding the genetic mechanisms of evolutionary innovation. PMID:24904045

Qian, Wenfeng; Zhang, Jianzhi

2014-08-01

430

Gene Therapy in the Cornea: 2005-present  

PubMed Central

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities have begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer towards establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea. PMID:21967960

Mohan, Rajiv R.; Tovey, Jonathan C.K.; Sharma, Ajay; Tandon, Ashish

2011-01-01

431

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

PubMed Central

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

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

2011-01-01

432

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

PubMed Central

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

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

2012-01-01

433

Common Worldwide Variation Discovered in Human Taste Receptor Genes  

MedlinePLUS

... Taste Receptor Genes Common Worldwide Variation Discovered In Human Taste Receptor Genes Common Worldwide Variation Discovered In Human Taste Receptor Genes Background : Differences in our sense ...

434

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. PMID:23882276

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

2013-01-01

435

Is pituitary gene therapy realistic?  

PubMed

Current therapies for pituitary tumours are moderately successful in many cases but still suffer from significant limitations, with relatively poor long-term rates of endocrine cure from surgery, and long-term hypopituitarism after radiotherapy. Even in the case of the most readily treatable tumours, prolactinomas, medical therapy with dopamine agonists is limited by lack of response or side-effects in up to 10% of patients. This has led to increasing interest in the application of our knowledge of pituitary cell and molecular biology to evaluate the potential of gene therapy. Various vectors are available to facilitate gene delivery, and recombinant adenoviruses have been studied in detail because of their ability to transduce the postmitotic, nondividing cells of the pituitary gland. Various studies with reporter genes such as beta-galactosidase have demonstrated high efficiency and long lasting expression of adenoviral transgenes in cultured pituitary cells in vitro. The feasibility of high level transgene expression has also been shown in vivo, but so far this requires stereotaxic intrapituitary injection to achieve adequate transduction. Ablation of pituitary cells has been demonstrated in cultured cell lines and in subcutaneous tumours in nude mice, though alternative animal models will be required to evaluate efficacy in more slowly proliferating tumours as found in man. Inflammatory responses have been documented in the pituitary gland as in other tissues, and this will require the evaluation of modified vectors to avoid significant adverse effects before human applications can be considered. In summary, gene therapy for pituitary disease is likely to be feasible in the future, but will require careful and extensive evaluation of efficacy and safety, using a variety of possible methods of gene delivery. PMID:11678822

Davis, J R; McNeilly, A S

2001-10-01

436

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.

437

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. PMID:17598924

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

2007-01-01

438

Gene Coexpression Network Analysis as a Source of Functional Annotation for Rice Genes  

PubMed Central

With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa) gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional annotation of those modules. Additionally, the expression patterns of genes across the treatments/conditions of an expression experiment comprise a second form of useful annotation. PMID:21799793

Childs, Kevin L.; Davidson, Rebecca M.; Buell, C. Robin

2011-01-01

439

Horizontal gene transfer in human pathogens  

E-print Network

contributing to the emergence of novel “superbugs”. This review provides update on various mechanisms of horizontal gene transfer and examines how horizontal gene transfer contributes to the evolution of pathogenic bacteria. Special focus is paid to the role...

Juhas, Mario

2013-07-18

440

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

441

Gene silencing: Cosuppression at a distance  

Microsoft Academic Search

When a plant carries a transgenic copy of an endogenous gene, both genes may be silenced. This ‘cosuppression’ can occur not only within individual cells, but also in distant cells through an agent that apparently moves through the plant's phloem.

David R Smyth

1997-01-01

442

Efficient Gene Transfer in Bacterial Cell Chains  

E-print Network

Horizontal gene transfer contributes to evolution and the acquisition of new traits. In bacteria, horizontal gene transfer is often mediated by conjugative genetic elements that transfer directly from cell to cell. Integrative ...

Babic, Ana

443

Enhanced polymeric nanoparticles for gene delivery  

E-print Network

The potential of gene therapy to treat disease and improve human health is tremendous. The failure of viral gene therapy clinical trials due to toxicity, immunogenicity, and carcinogenicity has been tragic and strongly ...

Green, Jordan Jamieson

2007-01-01

444

Genes and Disease: Prader-Willi Syndrome  

MedlinePLUS

... for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for Biotechnology Information (US). ... Center for Biotechnology Information (US). Genes and Disease [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); ...

445

The Evolution of Gene Regulatory Interactions  

NSDL National Science Digital Library

Changes in the timing and level at which genes are expressed are known to play an important role in evolution, but the mechanisms underlying changes in gene expression remain relatively obscure. Until quite recently, evolutionary biologists, like most biologists, tended to study single genes as isolated entities. These studies have added enormously to our understanding of biological evolution. But because gene regulation by its very nature involves interactions between two (or more) genes, researchers have missed a range of evolutionary phenomena that can be observed only at the level of networks of interacting genes. In this article, we consider the change in perspective that genomic technologiesâ??particularly the advent of large-scale platforms for DNA sequencing, genotyping, and measuring gene expressionâ??are bringing to evolutionary biology. We focus specifically on how these technologies can and are being used to increase our understanding of how and why gene expression evolves.

Gregory Wray (Duke University; Department of Biology)

2010-01-04

446

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, ...

447

NIH Researchers Identify OCD Risk Gene  

MedlinePLUS

... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

448

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

449

Gene Trapping Using Gal4 in Zebrafish  

PubMed Central

Large clutch size and external development of optically transparent embryos make zebrafish an exceptional vertebrate model system for in vivo insertional mutagenesis using fluorescent reporters to tag expression of mutated genes. Several laboratories have constructed and tested enhancer- and gene-trap vectors in zebrafish, using fluorescent proteins, Gal4- and lexA- based transcriptional activators as reporters 1-7. These vectors had two potential drawbacks: suboptimal stringency (e.g. lack of ability to differentiate between enhancer- and gene-trap events) and low mutagenicity (e.g. integrations into genes rarely produced null alleles). Gene Breaking Transposon (GBTs) were developed to address these drawbacks 8-10. We have modified one of the first GBT vectors, GBT-R15, for use with Gal4-VP16 as the primary gene trap reporter and added UAS:eGFP as the secondary reporter for direct detection of gene trap events. Application of Gal4-VP16 as the primary gene trap reporter provides two main advantages. First, it increases sensitivity for genes expressed at low expression levels. Second, it enables researchers to use gene trap lines as Gal4 drivers to direct expression of other transgenes in very specific tissues. This is especially pertinent for genes with non-essential or redundant functions, where gene trap integration may not result in overt phenotypes. The disadvantage of using Gal4-VP16 as the primary gene trap reporter is that genes coding for proteins with N-terminal signal sequences are not amenable to trapping, as the resulting Gal4-VP16 fusion proteins are unlikely to be able to enter the nucleus and activate transcription. Importantly, the use of Gal4-VP16 does not pre-select for nuclear proteins: we recovered gene trap mutations in genes encoding proteins which function in the nucleus, the cytoplasm and the plasma membrane. PMID:24121167

Balciuniene, Jorune; Balciunas, Darius

2013-01-01

450

Plant nitrogen regulatory P-PII genes  

DOEpatents

The present invention generally relates to plant nitrogen regulatory PII gene (hereinafter P-PII gene), a gene involved in regulating plant nitrogen metabolism. The invention provides P-PII nucleotide sequences, expression constructs comprising said nucleotide sequences, and host cells and plants having said constructs and, optionally expressing the P-PII gene from said constructs. The invention also provides substantially pure P-PII proteins. The P-PII nucleotide sequences and constructs of the

Coruzzi, Gloria M. (New York, NY); Lam, Hon-Ming (Hong Kong, HK); Hsieh, Ming-Hsiun (Woodside, NY)

2001-01-01

451

Evolutionary Dynamics of Overlapped Genes in Salmonella  

PubMed Central

Presence of overlapping genes (OGs) is a common phenomenon in bacterial genomes. Most frequently, overlapping genes share coding regions with as few as one nucleotide to as many as thousands of nucleotides. Overlapping genes are often co-regulated, transcriptionally and translationally. Overlapping genes are also subject to the whims of evolution, as the gene overlap is known to be disrupted in some species/strains and participating genes are sometimes lost in independent lineages. Therefore, a better understanding of evolutionary patterns and rates of the disruption of overlapping genes is an important component of genome structure and evolution of gene function. In this study, we investigate the fate of ancestrally overlapping genes in complete genomes from 15 contemporary strains of Salmonella species. We find that the fates of overlapping genes inside and outside operons are distinctly different. A larger fraction of overlapping genes inside operons conserves their overlap as compared to gene pairs outside of the operons (average 0.89 vs. 0.83 per genome). However, when overlapping genes in the operons separate, one partner is lost more frequently than in those separated genes outside of operons (average 0.02 vs. 0.01 per genome). We also investigate the fate of a pan set of overlapping genes at the present and ancestral nodes over a phylogenetic tree based on genome sequence data, respectively. We propose that co-regulation plays important roles on the fates of genes. Furthermore, a vast majority of disruptions occurred prior to the common ancestor of all 15 Salmonella strains, which enables us to obtain an estimate of disruptions between Salmonella and E. coli. PMID:24312259

Luo, Yingqin; Battistuzzi, Fabia; Lin, Kui

2013-01-01

452

Polymer Design for Nonviral Gene Delivery  

Microsoft Academic Search

Gene therapy continues to hold promise in treating a variety of inherited and acquired diseases. The great majority of gene\\u000a therapy trials rely on viral vectors for gene transduction because of their high efficiency. Viruses remain the vectors of\\u000a choice in achieving high efficiency of gene transfer in vivo. Viral vectors, however, pose safety concerns unlikely to abate\\u000a in the

Kam W. Leong

453

[Detection of transgenic crop with gene chip].  

PubMed

Some selected available sequences of reporter genes,resistant genes, promoters and terminators are amplified by PCR for the probes of transgenic crop detection gene chip. These probes are arrayed at definite density and printed on the surface of amino-slides by bioRobot MicroGrid II. Results showed that gene chip worked quickly and correctly, when transgenic rice, pawpaw,maize and soybean were applied. PMID:15639876

Huang, Ying-Chun; Sun, Chun-Yun; Feng, Hong; Hu, Xiao-Dong; Yin, Hai-Bin

2003-05-01

454

Function of the DISC1 Gene  

NSDL National Science Digital Library

As a result of the human genome project, we now know largely where our genes are, and what structure they have. The search to uncover each gene's function, on the other hand, is only in its infancy. Functional genomics is an area of research dedicated to studying what protein is produced by a gene, and what happens in the body when it is activated. Understanding gene function is the next major hurdle in genomic research, which holds the key to developing revolutionary therapeutics.

2009-04-14

455

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

456

Switching on the Lights for Gene Therapy  

Microsoft Academic Search

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated

Alexandra Winkeler; Miguel Sena-Esteves; Leonie E. M. Paulis; Hongfeng Li; Yannic Waerzeggers; Benedikt Rückriem; Uwe Himmelreich; Markus Klein; Parisa Monfared; Maria A. Rueger; Michael Heneka; Stefan Vollmar; Mathias Hoehn; Cornel Fraefel; Rudolf Graf; Klaus Wienhard; Wolf D. Heiss; Andreas H. Jacobs; Karen Aboody

2007-01-01

457

Entrez Gene Tutorial NCBI's Entrez Gene provides gene-based information such as  

E-print Network

location, sequence, expression, structure, functional, and homology data. Each record represents a single. In this exercise, we will learn how to obtain information about a human gene such as: - mRNA, genomic, and protein, including bacteria and viruses. The following handout includes the screen shots of Exercise 1. Exercise 1

Levin, Judith G.

458

Bayesian variable selection for hierarchical gene-environment and gene-gene interactions.  

PubMed

We propose a Bayesian hierarchical mixture model framework that allows us to investigate the genetic and environmental effects, gene by gene interactions and gene by environment interactions in the same model. Our approach incorporates the natural hierarchical structure between the main effects and interaction effects into a mixture model, such that our methods tend to remove the irrelevant interaction effects more effectively, resulting in more robust and parsimonious models. We consider both strong and weak hierarchical models. For a strong hierarchical model, both the main effects between interacting factors must be present for the interactions to be considered in the model development, while for a weak hierarchical model, only one of the two main effects is required to be present for the interaction to be evaluated. Our simulation results show that the proposed strong and weak hierarchical mixture models work well in controlling false-positive rates and provide a powerful approach for identifying the predisposing effects and interactions in gene-environment interaction studies, in comparison with the naive model that does not impose this hierarchical constraint in most of the scenarios simulated. We illustrate our approach using data for lung cancer and cutaneous melanoma. PMID:25154630

Liu, Changlu; Ma, Jianzhong; Amos, Christopher I

2015-01-01

459

Infrared lasermediated gene induction in targeted  

E-print Network

a heat shock promoter­driven transgene is required. Most importantly, it enables the induction of geneInfrared laser­mediated gene induction in targeted single cells in vivo Yasuhiro Kamei1 laser­evoked gene operator (IR-LEGO), a microscope system optimized for heating cells without

Cai, Long

460

Confused meanings of life, genes and parents  

Microsoft Academic Search

Questions concerning the moral status of embryos, the validity of new technologies for human reproduction, ownership of one's own genes, gene patenting, privacy and discrimination have all been raised and debated. Although debate is healthy, it is only useful if all participants understand the fundamental biological principles underlying human life, human genes and human parenthood. Many people believe that science

Lee M Silver

2001-01-01

461

Gene Family Evolution across 12 Drosophila Genomes  

Microsoft Academic Search

Comparison of whole genomes has revealed large and frequent changes in the size of gene families. These changes occur because of high rates of both gene gain (via duplication) and loss (via deletion or pseudogenization), as well as the evolution of entirely new genes. Here we use the genomes of 12 fully sequenced Drosophila species to study the gain and

Matthew W. Hahn; Mira V. Han; Sang-Gook Han

2007-01-01

462

Ecdysone-regulated puff genes 2000  

Microsoft Academic Search

The Ashburner model for the hormonal control of polytene chromosome puffing has provided a strong foundation for understanding the basic mechanisms of steroid-regulated gene expression (Cold Spring Harbor Symp. Quant. Biol. 38 (1974) 655). According to this model, the steroid hormone 20-hydroxyecdysone (referred here as ecdysone) directly induces the expression of a small set of early regulatory genes. These genes,

C. S. Thummel

2002-01-01

463

Gene Identification: Classical and Computational Intelligence Approaches  

Microsoft Academic Search

Automatic identification of genes has been an actively researched area of Bioinformatics. Compared to earlier attempts for finding genes, the recent techniques are significantly more accurate and reliable. Many of the current gene finding methods employ computational intelligence techniques that are known to be more robust when dealing with uncertainty and imprecision. In this article, a detailed survey on the

Sanghamitra Bandyopadhyay; Ujjwal Maulik; Debadyuti Roy

2008-01-01

464

Sparse Statistical Modelling in Gene Expression Genomics  

E-print Network

rich data sets are used to provide context and illustration. The first data set arises from a gene1 Sparse Statistical Modelling in Gene Expression Genomics Joe Lucasa , Carlos Carvalhoa , Quanli Wanga,b , Andrea Bildb , Joe Nevinsb and Mike Westa Duke University In: Bayesian Inference for Gene

West, Mike

465

BIOINFORMATICS Comparative Evaluation of Reverse Engineering Gene  

E-print Network

themselves. One of the first seminal papers promoting this approach aimed to learn gene regulatory networksBIOINFORMATICS Comparative Evaluation of Reverse Engineering Gene Regulatory Networks and shortcomings. In the present paper, we compare the accu- racy of reconstructing gene regulatory networks

Babu, M. Madan

466

PROCEEDINGS Open Access Lateral gene transfer, rearrangement,  

E-print Network

Transfers. We examine two datasets of gene trees from a single set of cyanobacteria species. The first setPROCEEDINGS Open Access Lateral gene transfer, rearrangement, reconciliation Murray Patterson1 Abstract Background: Models of ancestral gene order reconstruction have progressively integrated different

Paris-Sud XI, Université de

467

Sparse Statistical Modelling in Gene Expression Genomics  

E-print Network

context and illustration. The first data set arises from a gene expression experiment designed1 Sparse Statistical Modelling in Gene Expression Genomics Joe Lucasa , Carlos Carvalhoa , Quanli central to practical data anal- ysis and inference with increasingly high-dimensional data. Gene ex

West, Mike

468

Development of Biomaterials for Gene Therapy  

Microsoft Academic Search

Novel biocompatible polymeric gene carriers have been examined for their potential in treating various genetic and acquired diseases. The use of polymeric gene carriers may overcome the cur- rent problems associated with viral vectors in safety, immunogenicity, and mutagenesis. However, effective polymer-based gene therapy requires the control of cellular access and uptake, intracel- lular trafficking, and nuclear retention of plasmid

Sang-oh Han; Ram I. Mahato; Yong Kiel Sung; Sung Wan Kim

2000-01-01

469

ADENOVIRAL GENE THERAPY FOR OVARIAN CANCER  

E-print Network

ADENOVIRAL GENE THERAPY FOR OVARIAN CANCER Anna Kanerva Cancer Gene Therapy Group Rational Drug;SUPERVISED BY Docent Akseli Hemminki, M.D., Ph.D. Cancer Gene Therapy Group, Rational Drug Design Program experience is the mysterious. It is the source of all true art and science. Albert Einstein (1879-1955) #12

Hemminki, Akseli

470

Recurrent gene fusions in prostate cancer  

Microsoft Academic Search

The discovery of recurrent gene fusions in a majority of prostate cancers has important clinical and biological implications in the study of common epithelial tumours. Gene fusion and chromosomal rearrangements were previously thought to be primarily the oncogenic mechanism of haematological malignancies and sarcomas. The prostate cancer gene fusions that have been identified thus far are characterized by 5? genomic

Chandan Kumar-Sinha; Scott A. Tomlins; Arul M. Chinnaiyan

2008-01-01

471

Uses of antimicrobial genes from microbial genome  

DOEpatents

We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

Sorek, Rotem; Rubin, Edward M.

2013-08-20

472

Network Topology Reveals Key Cardiovascular Disease Genes  

PubMed Central

The structure of protein-protein interaction (PPI) networks has already been successfully used as a source of new biological information. Even though cardiovascular diseases (CVDs) are a major global cause of death, many CVD genes still await discovery. We explore ways to utilize the structure of the human PPI network to find important genes for CVDs that should be targeted by drugs. The hope is to use the properties of such important genes to predict new ones, which would in turn improve a choice of therapy. We propose a methodology that examines the PPI network wiring around genes involved in CVDs. We use the methodology to identify a subset of CVD-related genes that are statistically significantly enriched in drug targets and “driver genes.” We seek such genes, since driver genes have been proposed to drive onset and progression of a disease. Our identified subset of CVD genes has a large overlap with the Core Diseasome, which has been postulated to be the key to disease formation and hence should be the primary object of therapeutic intervention. This indicates that our methodology identifies “key” genes responsible for CVDs. Thus, we use it to predict new CVD genes and we validate over 70% of our predictions in the literature. Finally, we show that our predicted genes are functionally similar to currently known CVD drug targets, which confirms a potential utility of our methodology towards improving therapy for CVDs. PMID:23977067

Stojkovi?, Neda; Radak, Djordje; Pržulj, Nataša

2013-01-01

473

Genes and chromosomes: control of development  

Microsoft Academic Search

The past decade has witnessed immense progress in research into the molecular basis behind the developmen- tal regulation of genes. Sets of genes functioning under hierarchical control have been identified, evolutionary conserved systems of genes effecting the cell-to-cell transmission of transmembrane signals and assigned a central role in morphogenesis have been intensively studied; the concept of genomic regulatory networks coordinating

Oleg Serov; Irina Serova

2004-01-01

474

Gene therapy in the Cornea: 2005–present  

Microsoft Academic Search

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells\\/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made

Rajiv R. Mohan; Jonathan C. K. Tovey; Ajay Sharma; Ashish Tandon

475

Gene therapy for optic nerve disease  

Microsoft Academic Search

Purpose There has been recent interest in the potential use of gene therapy techniques to treat ocular disease. In this article, we consider the optic nerve diseases that are potentially most amenable to gene therapy.Methods We discuss the recent success of gene transfer experiments in animal models of glaucoma, optic neuritis, Leber's hereditary optic neuropathy (LHON), and optic nerve transection,

K R G Martin; H A Quigley

2004-01-01

476

LSUHSC Gene Therapy Program External Grant Awards  

E-print Network

LSUHSC Gene Therapy Program External Grant Awards FEDERAL AWARDS: $25,422,433 · CFTR expression generated dendritic cells · Adult stem cell mediated gene therapy for cystic fibrosis STATE AWARDS: $15 Center · Lacrimal gland bioinformatics: a neural connection of dry eye and aging · Gene and Stem Cell

477

Gene therapy progress and prospects: the eye  

Microsoft Academic Search

The eye has unique advantages as a target organ for gene therapy of both inherited and acquired ocular disorders and offers a valuable model system for gene therapy. The eye is readily accessible to phenotypic examination and investigation of therapeutic effects in vivo by fundus imaging and electrophysiological techniques. Considerable progress has been made in the development of gene replacement

J W B Bainbridge; M H Tan; R R Ali

2006-01-01

478

Bacteriophages and Diffusion of ?-lactamase Genes  

PubMed Central

We evaluated the presence of various ?-lactamase genes within the bacteriophages in sewage. Results showed the occurrence of phage particles carrying sequences of blaOXA-2, blaPSE-1 or blaPSE-4 and blaPSE-type genes. Phages may contribute to the spread of some ?-lactamase genes. PMID:15207070

Muniesa, Maite; García, Aurora; Miró, Elisenda; Mirelis, Beatriz; Prats, Guillem; Jofre, Juan

2004-01-01

479

Human Lineage-Specific Gene Inactivation  

E-print Network

Human Lineage-Specific Gene Inactivation Wendy E Grus, University of Michigan, Ann Arbor, Michigan vestiges of genes. Inves- tigating genes that were inactivated specifically on the human lineage or within humans can reveal the genetic basis of interspecies differences between humans and chimpanzees

Zhang, Jianzhi

480

Human Lineage-specific Gene Inactivation  

E-print Network

Human Lineage-specific Gene Inactivation Wendy E Grus, University of Michigan, Ann Arbor, Michigan vestiges of genes. Investigating genes that were inactivated specifically on the human lineage can reveal the genetic basis of inter- species differences between humans and chimpanzees and inter

Zhang, Jianzhi

481

VERTEBRATE PHYLOGENOMICS: RECONCILED TREES AND GENE DUPLICATIONS  

E-print Network

VERTEBRATE PHYLOGENOMICS: RECONCILED TREES AND GENE DUPLICATIONS R.D.M. PAGE, J.A. COTTON Division-mail: r.page@bio.gla.ac.uk Ancient gene duplication events have left many traces in vertebrate genomes. Rec- onciled trees represent the differences between gene family trees and the species phylogeny those

Page, Roderic

482

Noncoding RNA Genes Sean R. Eddy  

E-print Network

genes produce functional RNAs instead of encoding proteins. Noncoding RNA genes are surprisingly, and RNAs involved in X dosage compensation. Genome sequences and new algorithms have begun to make are not proteins; instead, they have a very di#11;erent biochemistry. Some of these genes originated before

Eddy, Sean

483

Central Dogma Genome and Gene Structure  

E-print Network

Bioinformatics Allele HIV-1 AZT Resistance Gene Weigang Qiu Chapter 3. Genome Evolution #12;Central Dogma GenomeCentral Dogma Genome and Gene Structure Genome Evolution Bioinformatics Chapter 3. Genome Evolution Weigang Qiu Chapter 3. Genome Evolution #12;Central Dogma Genome and Gene Structure Genome Evolution

Qiu, Weigang

484

A Critical Review of Gene Prediction Software  

E-print Network

. Gene prediction in eukaryotes is somewhat more difficult than in prokaryotes, due in part to the decreased gene density in eukaryotic genomes compared to prokaryotic genomes, and in part to the increased complexity of the "gene unit" in eukaryotes compared to prokaryotes. The structure of a "typical" eukaryotic

485

Aeromonas hydrophila Lateral Flagellar Gene Transcriptional Hierarchy  

PubMed Central

Aeromonas hydrophila AH-3 lateral flagella are not assembled when bacteria grow in liquid media; however, lateral flagellar genes are transcribed. Our results indicate that A. hydrophila lateral flagellar genes are transcribed at three levels (class I to III genes) and share some similarities with, but have many important differences from, genes of Vibrio parahaemolyticus. A. hydrophila lateral flagellum class I gene transcription is ?70 dependent, which is consistent with the fact that lateral flagellum is constitutively transcribed, in contrast to the characteristics of V. parahaemolyticus. The fact that multiple genes are included in class I highlights that lateral flagellar genes are less hierarchically transcribed than polar flagellum genes. The A. hydrophila lafK-fliEJL gene cluster (where the subscript L distinguishes genes for lateral flagella from those for polar flagella) is exclusively from class I and is in V. parahaemolyticus class I and II. Furthermore, the A. hydrophila flgAMNL cluster is not transcribed from the ?54/LafK-dependent promoter and does not contain class II genes. Here, we propose a gene transcriptional hierarchy for the A. hydrophila lateral flagella. PMID:23335410

Wilhelms, Markus; Gonzalez, Victor; Merino, Susana

2013-01-01

486

Discovery of Tumor Suppressor Gene Function.  

ERIC Educational Resources Information Center

This is an update of a 1991 review on tumor suppressor genes written at a time when understanding of how the genes work was limited. A recent major breakthrough in the understanding of the function of tumor suppressor genes is discussed. (LZ)

Oppenheimer, Steven B.

1995-01-01

487

Kinetic Path of Genes Undergoing Selection  

Microsoft Academic Search

As natural populations approach genetic equilibrium, the various genes in the population are capable of assuming intermediate distributions that might not be anticipated from either the rate of the process or the final distribution of the genes. Since it is possible that many populations have not reached genetic equilibrium, the distribution of genes in natural populations may be a reflection

Henry N. Kirkman

1971-01-01

488

Environmental and Behavioral Influences on Gene Activity  

Microsoft Academic Search

The central dogma of molecular biology holds that “information” flows from the genes to the structure of the proteins that the genes bring about through the formula DNA ? RNA ? protein. In this view, a set of master genes activates the DNA necessary to produce the appropriate proteins that the organism needs during development. In contrast to this view,

Gilbert Gottlieb

2000-01-01

489

Jumping Genes: The Transposable DNAs of Bacteria.  

ERIC Educational Resources Information Center

Transposons are transposable elements that carry genes for antibiotic resistance. Provides background information on the structure and organization of these "jumping genes" in bacteria. Also describes the use of transposons in tagging genes and lists pertinent references and resource materials. (DH)

Berg, Claire M.; Berg, Douglas E.

1984-01-01

490

Blue Gene/Q Overview and Update  

E-print Network

Blue Gene®/Q Overview and Update November 2011 #12;Agenda Hardware Architecture George Chiu Sexton #12;© 2011 IBM Corporation IBM System Technology Group 3 Industrial Design BQC DD2.0 Blue Gene/Q 4 Gene/Q #12;© 2011 IBM Corporation IBM System Technology Group Examples of Applications Running on Blue

Kemner, Ken

491

Gene silencing mechanisms in Phytophthora infestans  

E-print Network

Gene silencing mechanisms in Phytophthora infestans Ramesh Raju Vetukuri Faculty of Natural Cover: Confocal images of P.infestans mycelium structure #12;Gene silencing mechanisms in Phytophthora. This thesis focuses on the molecular basis of gene (RNA) silencing in P. infestans and the role it may have

492

Gene regulation, protein networks and disease  

E-print Network

1 Gene regulation, protein networks and disease ­ a computational perspective Ron Shamir School in cancer DEGAS 2 #12;Regulation of Transcription · A gene's ranscription regulation is mainly encoded binding sites (BSs) that are bound by specific proteins called transcription factors (TFs) TFTF Gene 5' 3

Lonardi, Stefano

493

Gene Expression Clustering with Functional Mixture Models  

E-print Network

Gene Expression Clustering with Functional Mixture Models Darya Chudova, Department of Computer measured on a discrete time grid. The model is specifically tailored to gene expression time course data of the model, and apply the proposed approach to the set of cycling genes in yeast. The experiments show

Mjolsness, Eric

494

Gene synthesis by circular assembly amplification  

E-print Network

Gene synthesis by circular assembly amplification Duhee Bang & George M Church Here we report the development of a gene-synthesis technology, circular assembly amplification. In this approach, we first error-rich products, thereby substantially improving gene-synthesis quality. We used this method

Church, George M.

495

Gene Assembly from Chip-Synthesized Oligonucleotides  

E-print Network

Gene Assembly from Chip-Synthesized Oligonucleotides Nikolai Eroshenko,1,5 Sriram Kosuri,2,3,5 Adam off-chip DNA for gene synthesis have failed to scale due to the high error rates, low yields, and high by John Wiley & Sons, Inc. Keywords: oligonucleotide r gene synthesis r nucleic acids r synthetic biology

Church, George M.

496

GENE8970 Fall Semester, 2002 Instructors  

E-print Network

GENE8970 Fall Semester, 2002 Instructors: Michael Bender C418 Life Sciences 542-0529, bender (Enhancer and suppressor screens) Sept. 6 (Bender) Vulval induction in C. elegans (Epistasis and gene order) Genetic tricks in Drosophila (Overexpression analysis, GAL4-UAS systems) Sept. 27 (Manley) Homeobox genes

Arnold, Jonathan

497

Gene ow and geographically structured coevolution  

E-print Network

Gene ¯ow and geographically structured coevolution Scott L. Nuismer1* , John N. Thompson1 and antagonism among communities linked by migration. Inclusion of geographic structure with gene £ow alters structure with gene £ow allows ¢xed mutualisms to be evolutionarily stable within both communities, even

Nuismer, Scott L.

498

Gene Microarray Analysis using Angular Distribution Decomposition  

E-print Network

Gene Microarray Analysis using Angular Distribution Decomposition Karen Lees1 , Stephen Roberts1 of microarray data to group genes with similar expression profiles. The similarity of expres- sion profiles to define the similarity of gene expression patterns. The pairwise comparisons of exper- imental conditions

Roberts, Stephen

499

Gene mapping today: applications to farm animals  

E-print Network

Gene mapping today: applications to farm animals M Gillois Institut National de la Recherche) chromosomes/ gene mapping technologies INTRODUCTION The genetic information contained in mammalian cells it possible to estimate that the mammalian genome may contain fifty thousand structural genes, which may

Paris-Sud XI, Université de

500

Gene duplications, robustness and evolutionary innovations  

E-print Network

Gene duplications, robustness and evolutionary innovations Andreas Wagner1,2,3 Summary Mutational robustness facilitates evolutionary innova- tions. Gene duplications are unique kinds of mutations, in that they generally increase such robustness. The frequent association of gene duplications in regulatory networks

Wagner, Andreas