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1

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

2

Long-term channel block is required to inhibit cellular transformation by human ether-à-go-go-related gene (hERG1) potassium channels.  

PubMed

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; Mitcheson, John S

2014-08-01

3

HERG1 currents in native K562 leukemic cells.  

PubMed

The human ether-a-go-go related gene (HERG1) K+ channel is expressed in neoplastic cells, in which it was proposed to play a role in proliferation, differentiation and/or apoptosis. K562 cells (a chronic myeloid leukemic human cell line) express both the full-length (herg1a) and the N-terminally truncated (herg1b) isoforms of the gene, and this was confirmed with Western blots and coimmunoprecipitation experiments. Whole-cell currents were studied with a tail protocol. Seventy-eight percent of cells showed a HERG1-like current: repolarization to voltages negative to -40 mV produced a transient peak inward tail current, characteristic of HERG1 channels. Cells were exposed to a HERG-specific channel blocker, E4031. Half-maximal inhibitory concentration (IC50) of the blocker was 4.69 nM: The kinetics of the HERG1 current in K562 cells resembled the rapid component of the native cardiac delayed rectifier current, known to be conducted by heterotetrameric HERG1 channels. Fast and slow deactivation time constants at -120 mV were 27.5 and 239.5 ms, respectively. Our results in K562 cells suggest the assembling of heterotetrameric channels, with some parameters being dominated by one of the isoforms and other parameters being intermediate. Hydrogen peroxide was shown to increase HERG1a K+ current in heterologous expression systems, which constitutes an apoptotic signal. However, we found that K562 HERG1 whole-cell currents were not activated by H2O2. PMID:17763876

Cavarra, María S; del Mónaco, Silvana M; Assef, Yanina A; Ibarra, Cristina; Kotsias, Basilio A

2007-10-01

4

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

5

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

E-print Network

and auditory induced syncope interpreted as "seizure" and Sudden Cardiac Death. The biochemical data revealed-expressed with the WT. We concluded that "seizure" must be likely due to cardiac syncope as a consequence of mutation was to screen KCNH2 for mutations in patients with LQTS2 on the ECG and auditory induced syncope interpreted

Boyer, Edmond

6

LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current  

PubMed Central

Aims KCNE1 encodes an auxiliary subunit of cardiac potassium channels. Loss-of-function variations in this gene have been associated with the LQT5 form of the long QT syndrome (LQTS), secondary to reduction of IKs current. We present a case in which a D85N rare polymorphism in KCNE1 is associated with an LQT2 phenotype. Methods and results An 11-year old competitive athlete presented with mild bradycardia and a QTc interval of 470 ms. An LQT2 phenotype, consisting of low-voltage bifid T waves, was evident in the right precordial electrocardiogram leads. During the tachycardia phase following adenosine, QTc increased to 620 ms. Genetic analysis revealed a rare heterozygous polymorphism in KCNE1 predicting the substitution of asparagine for aspartic acid at position 85 of minK (D85N). Patch clamp experiments showed that KCNE1-D85N, when co-expressed with KCNH2 in TSA201 cells, significantly reduced IKr. Homozygous co-expression of the mutant with KCNH2 reduced IKr tail current by 85%, whereas heterozygous co-expression reduced the current by 52%, demonstrating for the first time a dominant-negative effect of D85N to reduce IKr. Co-expression of the mutant with KCNQ1, either homozygously or heterozygously, produced no change in IKs. Conclusions Our results suggest that a rare polymorphism KCNE1-D85N underlies the development of an LQT2 phenotype in this young athlete by interacting with KCNH2 to cause a dominant-negative effect to reduce IKr. Our data provide further evidence in support of the promiscuity of potassium channel ? subunits in modulating the function of multiple potassium channels leading to a diversity of clinical phenotypes. PMID:21712262

Nof, Eyal; Barajas-Martinez, Hector; Eldar, Michael; Urrutia, Janire; Caceres, Gabriel; Rosenfeld, Gail; Bar-Lev, David; Feinberg, Micha; Burashnikov, Elena; Casis, Oscar; Hu, Dan; Glikson, Michael; Antzelevitch, Charles

2011-01-01

7

hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer  

PubMed Central

Angiogenesis is a potential target for cancer therapy. We identified a novel signaling pathway that sustains angiogenesis and progression in colorectal cancer (CRC). This pathway is triggered by ?1 integrin-mediated adhesion and leads to VEGF-A secretion. The effect is modulated by the human ether-à-go-go related gene 1 (hERG1) K+ channel. hERG1 recruits and activates PI3K and Akt. This in turn increases the Hypoxia Inducible Factor (HIF)-dependent transcription of VEGF-A and other tumour progression genes. This signaling pathway has novel features in that the integrin- and hERG1-dependent activation of HIF (i) is triggered in normoxia, especially after CRC cells have experienced a hypoxic stage, (ii) involves NF-kB and (iii) is counteracted by an active p53. Blocking hERG1 switches this pathway off also in vivo, by inhibiting cell growth, angiogenesis and metastatic spread. This suggests that non-cardiotoxic anti-hERG1 drugs might be a fruitful therapeutic strategy to prevent the failure of anti-VEGF therapy. PMID:24270902

Crociani, Olivia; Zanieri, Francesca; Pillozzi, Serena; Lastraioli, Elena; Stefanini, Matteo; Fiore, Antonella; Fortunato, Angelo; D'Amico, Massimo; Masselli, Marika; De Lorenzo, Emanuele; Gasparoli, Luca; Chiu, Martina; Bussolati, Ovidio; Becchetti, Andrea; Arcangeli, Annarosa

2013-01-01

8

Elevated Heart Rate Triggers Action Potential Alternans and Sudden Death. Translational Study of a Homozygous KCNH2 Mutation  

PubMed Central

Background Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed “human HERG knockout” and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. Methods and Results Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q) in the index patient (QTc ?506 ms with notched T waves). Parents were I° cousins – both heterozygous for the mutation and clinically unremarkable (QTc ?447 ms, father and ?396 ms, mother). Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD) compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. Conclusion Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates. PMID:25140878

Marschall, Christoph; Takac, Ina; Brandes, Ralf P.; Kotzot, Dieter; Girmatsion, Zenawit; Hohnloser, Stefan H.; Ehrlich, Joachim R.

2014-01-01

9

Cooperative subunit interactions mediate fast C-type inactivation of hERG1 K+ channels.  

PubMed

At depolarized membrane potentials, the conductance of some voltage-gated K(+) channels is reduced by C-type inactivation. This gating process is voltage independent in Kv1 and involves a conformational change in the selectivity filter that is mediated by cooperative subunit interactions. C-type inactivation in hERG1 K(+) channels is voltage-dependent, much faster in onset and greatly attenuates currents at positive potentials. Here we investigate the potential role of subunit interactions in C-type inactivation of hERG1 channels. Point mutations in hERG1 known to eliminate (G628C/S631C), inhibit (S620T or S631A) or enhance (T618A or M645C) C-type inactivation were introduced into subunits that were combined with wild-type subunits to form concatenated tetrameric channels with defined subunit composition and stoichiometry. Channels were heterologously expressed in Xenopus oocytes and the two-microelectrode voltage clamp was used to measure the kinetics and steady-state properties of inactivation of whole cell currents. The effect of S631A or T618A mutations on inactivation was a graded function of the number of mutant subunits within a concatenated tetramer as predicted by a sequential model of cooperative subunit interactions, whereas M645C subunits increased the rate of inactivation of concatemers, as predicted for subunits that act independently of one another. For mutations located within the inactivation gate proper (S620T or G628C/S631C), the presence of a single subunit in a concatenated hERG1 tetramer disrupted gating to the same extent as that observed for mutant homotetramers. Together, our findings indicate that the final step of C-type inactivation of hERG1 channels involves a concerted, all-or-none cooperative interaction between all four subunits, and that probing the mechanisms of channel gating with concatenated heterotypic channels should be interpreted with care, as conclusions regarding the nature of subunit interactions may depend on the specific mutation used to probe the gating process. PMID:25063820

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

2014-10-15

10

Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum  

PubMed Central

KCNH2 encodes Kv11.1 and underlies the rapidly activating delayed rectifier K+ current (IKr) in the heart. Loss-of-function KCNH2 mutations cause the type 2 long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channels. Drugs that bind to Kv11.1 and block IKr (e.g., E-4031) can act as pharmacological chaperones to increase the trafficking and functional expression for most LQT2 channels (pharmacological correction). We previously showed that LQT2 channels are selectively stored in a microtubule-dependent compartment within the endoplasmic reticulum (ER). We tested the hypothesis that pharmacological correction promotes the trafficking of LQT2 channels stored in this compartment. Confocal analyses of cells expressing the trafficking-deficient LQT2 channel G601S showed that the microtubule-dependent ER compartment is the transitional ER. Experiments with E-4031 and the protein synthesis inhibitor cycloheximide suggested that pharmacological correction promotes the trafficking of G601S stored in this compartment. Treating cells in E-4031 or ranolazine (a drug that blocks IKr and has a short half-life) for 30 min was sufficient to cause pharmacological correction. Moreover, the increased functional expression of G601S persisted 4–5 h after drug washout. Coexpression studies with a dominant-negative form of Rab11B, a small GTPase that regulates Kv11.1 trafficking, prevented the pharmacological correction of G601S trafficking from the transitional ER. These data suggest that pharmacological correction quickly increases the trafficking of LQT2 channels stored in the transitional ER via a Rab11B-dependent pathway, and we conclude that the pharmacological chaperone activity of drugs like ranolazine might have therapeutic potential. PMID:23864605

Smith, Jennifer L.; Reloj, Allison R.; Nataraj, Parvathi S.; Bartos, Daniel C.; Schroder, Elizabeth A.; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Anderson, Corey L.; January, Craig T.

2013-01-01

11

Expression and significance of HERG (KCNH2) potassium channels in the regulation of MDA-MB-435S melanoma cell proliferation and migration.  

PubMed

The human ether-a-go-go related gene (HERG) potassium channel has elicited intense scientific interest due to its role in cardiac repolarization and its association with arrhythmia and sudden cardiac death. Increasing evidence indicates the involvement of HERG channels in the pathophysiology of cancer. In the present study we investigated the expression of HERG protein in MDA-MB-435S melanoma cells, and its importance in regulating cell proliferation and migration. Our results showed that HERG was expressed on protein and mRNA levels in MDA-MB-435S melanoma cells. In these cells blockade of HERG channels with the HERG blockers E 4301 or cisapride attenuated both proliferation and migration of the cells. Activation of HERG with PD118057 stimulated cell migration. Furthermore, HERG small interfering (si) RNA attenuated the proliferation and migration of the cells. Incubation of MDA-MB-435S cells with E 4301 decreased the phosphorylation of mitogen-activated protein (MAP) kinase and the expression of the c-fos transcription factor. In control experiments, overexpression of HERG channels in HEK-293 cells dramatically increased the proliferation and migration of the cells and blocking HERG in these cells attenuated both proliferation and migration. Our results indicate that MDA-MB-435S cells express HERG channels and blockade of HERG results in the attenuation of both proliferation and migration by a mechanism dependent, at least in part, on an inhibition of the MAP kinase/c-fos pathway. PMID:19765650

Afrasiabi, Emad; Hietamäki, Marika; Viitanen, Tero; Sukumaran, Pramod; Bergelin, Nina; Törnquist, Kid

2010-01-01

12

LQTS gene LOVD database.  

PubMed

The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians. PMID:20809527

Zhang, Tao; Moss, Arthur; Cong, Peikuan; Pan, Min; Chang, Bingxi; Zheng, Liangrong; Fang, Quan; Zareba, Wojciech; Robinson, Jennifer; Lin, Changsong; Li, Zhongxiang; Wei, Junfang; Zeng, Qiang; Qi, Ming

2010-11-01

13

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

14

Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays  

PubMed Central

Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-? (TNF-?), which activates both inflammation and NF-?B-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-?M arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes. PMID:21776218

Mo, Jinyao; Xia, Yajuan; Wade, Timothy J.; DeMarini, David M.; Davidson, Mercy; Mumford, Judy

2011-01-01

15

Genes  

NSDL National Science Digital Library

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

Excellence, Access

2005-03-12

16

Long QT Syndrome-Associated Mutations in Intrauterine Fetal Death  

PubMed Central

Importance Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. Objective To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. Design, Setting, and Patients In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. Main Outcomes and Measures Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. Results The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2[1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation (33.2-week male) exhibited a loss of function consistent with in utero LQTS type 2. In addition, 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases) that conferred in vitro electrophysiological characteristics consistent with potentially proarrhythmic phenotypes. Conclusions and Relevance In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in 3 cases (3.3%) and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8%). These preliminary findings may provide insights into mechanisms of some cases of stillbirth. PMID:23571586

Crotti, Lia; Tester, David J.; White, Wendy M.; Bartos, Daniel C.; Insolia, Roberto; Besana, Alessandra; Kunic, Jennifer D.; Will, Melissa L.; Velasco, Ellyn J.; Bair, Jennifer J.; Ghidoni, Alice; Cetin, Irene; Van Dyke, Daniel L.; Wick, Myra J.; Brost, Brian; Delisle, Brian P.; Facchinetti, Fabio; George, Alfred L.; Schwartz, Peter J.; Ackerman, Michael J.

2013-01-01

17

Prevalence of arrhythmia-associated gene mutations and risk of sudden cardiac death in the Finnish population  

PubMed Central

Background Sudden cardiac death (SCD) remains a major cause of death in Western Countries. It has a heritable component, but previous molecular studies have mainly focused on common genetic variants. We studied the prevalence, clinical phenotypes, and risk of SCD presented by ten rare mutations previously associated with arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, or catecholaminergic polymorphic ventricular tachycardia. Methods The occurrence of ten arrhythmia-associated mutations was determined in four large prospective population cohorts (FINRISK 1992, 1997, 2002, and Health 2000, n = 28,465) and two series of forensic autopsies (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 825). Follow-up data was collected from national registries. Results The ten mutations showed a combined prevalence of 79 per 10,000 individuals in Finland and six of them showed remarkable geographic clustering. Of a total of 715 SCD cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W. Conclusions Arrhythmia-associated mutations are prevalent in the general Finnish population but do not seem to present a major risk factor for SCD, at least during a mean of 10-year follow-up of a random adult population sample. PMID:23651034

Lahtinen, Annukka M.; Havulinna, Aki S.; Noseworthy, Peter A.; Jula, Antti; Karhunen, Pekka J.; Perola, Markus; Newton-Cheh, Christopher; Salomaa, Veikko; Kontula, Kimmo

2013-01-01

18

Rehabilitating drug-induced long-QT promoters: In-silico design of hERG-neutral cisapride analogues with retained pharmacological activity  

PubMed Central

Background The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart’s action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus “rehabilitation” studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. Methods In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound’s cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. Results We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. Conclusions An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1. PMID:24606761

2014-01-01

19

Correlation of genetic etiology with response to ?-adrenergic blockade among symptomatic patients with familial long-QT syndrome  

Microsoft Academic Search

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death.\\u000a ?-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic\\u000a relief; however the remaining 20% do not respond well.

Toshio Itoh; Kenjiro Kikuchi; Yasuhisa Odagawa; Shigeo Takata; Katsusuke Yano; Shintaro Okada; Noriyuki Haneda; Satoshi Ogawa; Osami Nakano; Yosuke Kawahara; Hideaki Kasai; Toshio Nakayama; Tatsuya Fukutomi; Harumizu Sakurada; Akihiko Shimizu; Yoshio Yazaki; Ryozo Nagai; Yusuke Nakamura; Toshihiro Tanaka

2001-01-01

20

Gene Cloning  

NSDL National Science Digital Library

This lesson covers the utilization of gene cloning to isolate and copy a specific gene of interest. The transformation of bacteria with plasmids containing antibiotic resistance genes to make gene libraries and the selection of bacteria colonies that contain the specific gene of interest are described.

21

Gene Positioning  

PubMed Central

Eukaryotic gene expression is an intricate multistep process, regulated within the cell nucleus through the activation or repression of RNA synthesis, processing, cytoplasmic export, and translation into protein. The major regulators of gene expression are chromatin remodeling and transcription machineries that are locally recruited to genes. However, enzymatic activities that act on genes are not ubiquitously distributed throughout the nucleoplasm, but limited to specific and spatially defined foci that promote preferred higher-order chromatin arrangements. The positioning of genes within the nuclear landscape relative to specific functional landmarks plays an important role in gene regulation and disease. PMID:20484389

Ferrai, Carmelo; de Castro, Ines Jesus; Lavitas, Liron; Chotalia, Mita; Pombo, Ana

2010-01-01

22

Gene Concepts, Gene Talk, and Gene Patents  

E-print Network

concepts have exerted strong effects on institutions such as medicine, the biotechnology industry, politics, and the law. A particularly rich example of this is the interplay between gene concepts and patent law. Over the last century, biology has...

Torrance, Andrew W.

2010-01-01

23

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.

Foundation, Wgbh E.

2003-09-26

24

Gene Cloning  

NSDL National Science Digital Library

A basic depiction of the steps in gene cloning. This is the third 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 DNA and DNA Extraction. To go to the next animation, go to Gene Regions.)

25

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).

Daniels, Chuck

26

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

27

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

28

Gene doping.  

PubMed

Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping. PMID:16572366

Haisma, H J; de Hon, O

2006-04-01

29

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

30

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

31

Systemic Gene Delivery for Muscle Gene Therapy  

Microsoft Academic Search

\\u000a The muscular dystrophies (MDs) are a heterogeneous group of monogenetic disorders that affect striated muscles, often throughout\\u000a the body. A promising approach to treating the MDs is to use gene therapy to replace, repair, or modify expression of the\\u000a mutant gene. Accomplishing such a goal requires that gene expression cassettes, which comprise a gene regulatory element driving\\u000a expression of an

Dilip Garikipati; Jeffrey S. Chamberlain

32

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

33

Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes  

PubMed Central

Aims Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS. Methods and results We produced LQTS-type 2 (LQT2) hiPSC cardiomyocytes carrying a KCNH2 c.G1681A mutation in a IKr ion-channel pore, which caused impaired glycosylation and channel transport to cell surface. Allele-specific RNA interference (RNAi) directed towards the mutated KCNH2 mRNA caused knockdown, while leaving the wild-type mRNA unaffected. Electrophysiological analysis of patient-derived LQT2 hiPSC cardiomyocytes treated with mutation-specific siRNAs showed normalized action potential durations (APDs) and K+ currents with the concurrent rescue of spontaneous and drug-induced arrhythmias (presented as early-afterdepolarizations). Conclusions These findings provide in vitro evidence that allele-specific RNAi can rescue diseased phenotype in LQTS cardiomyocytes. This is a potentially novel route for the treatment of many autosomal-dominant-negative disorders, including those of the heart. PMID:23470493

Matsa, Elena; Dixon, James E.; Medway, Christopher; Georgiou, Orestis; Patel, Minal J.; Morgan, Kevin; Kemp, Paul J.; Staniforth, Andrew; Mellor, Ian; Denning, Chris

2014-01-01

34

Zebrafish model for human long QT syndrome  

PubMed Central

Long QT syndrome (LQTS) is a disorder of ventricular repolarization that predisposes affected individuals to lethal cardiac arrhythmias. To date, an appropriate animal model of inherited LQTS does not exist. The zebrafish is a powerful vertebrate model used to dissect molecular pathways of cardiovascular development and disease. Because fundamental electrical properties of the zebrafish heart are remarkably similar to those of the human heart, the zebrafish may be an appropriate model for studying human inherited arrhythmias. Here we describe the molecular, cellular, and electrophysiological basis of a zebrafish mutant characterized by ventricular asystole. Genetic mapping and direct sequencing identify the affected gene as kcnh2, which encodes the channel responsible for the rapidly activating delayed rectifier K+ current (IKr). We show that complete loss of functional IKr in embryonic hearts leads to ventricular cell membrane depolarization, inability to generate action potentials (APs), and disrupted calcium release. A small hyperpolarizing current restores spontaneous APs, implying wild-type function of other ionic currents critical for AP generation. Heterozygous fish manifest overt cellular and electrocardiographic evidence for delayed ventricular repolarization. Our findings provide insight into the pathogenesis of homozygous kcnh2 mutations and expand the use of zebrafish mutants as a model system to study human arrhythmias. PMID:17592134

Arnaout, Rima; Ferrer, Tania; Huisken, Jan; Spitzer, Kenneth; Stainier, Didier Y. R.; Tristani-Firouzi, Martin; Chi, Neil C.

2007-01-01

35

Gene–environment interdependence  

Microsoft Academic Search

The modern understanding of genetic influences, of environmental effects, of mental disorder, and of heritabilities is noted. The practical utility of finding susceptibility genes with a very small effect is questioned. The empirical findings and implications of developmental perturbations, epigenetics, gene–environment correlations and interactions are then discussed. It is noted that the genes involved in gene–environment interactions may be concerned

Michael Rutter

2012-01-01

36

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

37

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

38

GeneCards  

NSDL National Science Digital Library

The Weizmann Institute of Science provides GeneCards, a database of "human genes, their products and their involvement in diseases." GeneCards contains concise information on the functions of "all human genes with an approved symbol" (e.g., genes named according to the Human Gene Nomenclature Committee), in addition to "selected others" -- collectively representing over 9,600 genes. The database is searchable, and its most current version (Version 2.14) features a new navigation support system (the "Guidance System") that facilitates information retrieval. Typical information on each Gene Card includes Synonyms, Chromosomal location, Proteins, Sequences, Similar genes in other organisms, Disorders & Mutations, Medical News, Research Articles, and Additional Sources of Information on the WWW. The GeneCards database is of particular use in the context of functional genomics and proteomics.

39

Novel gene delivery systems  

PubMed Central

Gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions, and genetic disorders. Application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Several nonviral and viral gene transfer methods have been developed. Even though the viral agents have a high transferring efficiency, they are difficult to handle due to their toxicity. To overcome the safety problems of the viral counterpart, several nonviral in vitro and in vivo gene delivery systems are developed. Out of these, the most promising and latest systems include polymer-based nonviral gene carriers, dendrimers, and physical means like electroporation, microinjection, etc., Shunning of possible immunogenicity and toxicity, and the feasibility of repeated administration are some of the merits of nonviral gene delivery systems over viral gene delivery. An ideal nonviral gene carrying system should possess all these merits without any compromise to its gene transferring efficiency. The viral gene delivery systems include lytic and nonlytic vectors for drug delivery. Inspite of its toxicity they are still preferred because of their long term expression, stability, and integrity. This review explores the recent developments and relevancy of the novel gene delivery systems in gene therapy. PMID:23799200

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

2013-01-01

40

Airway Mucin Genes and Gene Products  

Microsoft Academic Search

\\u000a \\u000a MUC genes and their MUC gene products have been the subject of several reviews in the last few years [1-4] as expected in a field where the molec­ular tools to address fundamental and disease-related questions are becom­ing available.\\u000a A description and analysis of human mucin genes MUC\\/through MUC7 and of porcine canine murine rat and bovine mucin geneswere published in

Mary Callaghan Rose; Sandra J. Gendler

41

Speciation genes in plants  

PubMed Central

Background Analyses of speciation genesgenes that contribute to the cessation of gene flow between populations – can offer clues regarding the ecological settings, evolutionary forces and molecular mechanisms that drive the divergence of populations and species. This review discusses the identities and attributes of genes that contribute to reproductive isolation (RI) in plants, compares them with animal speciation genes and investigates what these genes can tell us about speciation. Scope Forty-one candidate speciation genes were identified in the plant literature. Of these, seven contributed to pre-pollination RI, one to post-pollination, prezygotic RI, eight to hybrid inviability, and 25 to hybrid sterility. Genes, gene families and genetic pathways that were frequently found to underlie the evolution of RI in different plant groups include the anthocyanin pathway and its regulators (pollinator isolation), S RNase-SI genes (unilateral incompatibility), disease resistance genes (hybrid necrosis), chimeric mitochondrial genes (cytoplasmic male sterility), and pentatricopeptide repeat family genes (cytoplasmic male sterility). Conclusions The most surprising conclusion from this review is that identities of genes underlying both prezygotic and postzygotic RI are often predictable in a broad sense from the phenotype of the reproductive barrier. Regulatory changes (both cis and trans) dominate the evolution of pre-pollination RI in plants, whereas a mix of regulatory mutations and changes in protein-coding genes underlie intrinsic postzygotic barriers. Also, loss-of-function mutations and copy number variation frequently contribute to RI. Although direct evidence of positive selection on speciation genes is surprisingly scarce in plants, analyses of gene family evolution, along with theoretical considerations, imply an important role for diversifying selection and genetic conflict in the evolution of RI. Unlike in animals, however, most candidate speciation genes in plants exhibit intraspecific polymorphism, consistent with an important role for stochastic forces and/or balancing selection in development of RI in plants. PMID:20576737

Rieseberg, Loren H.; Blackman, Benjamin K.

2010-01-01

42

From Gene Networks to Gene Function  

PubMed Central

We propose a novel method to identify functionally related genes based on comparisons of neighborhoods in gene networks. This method does not rely on gene sequence or protein structure homologies, and it can be applied to any organism and a wide variety of experimental data sets. The character of the predicted gene relationships depends on the underlying networks;they concern biological processes rather than the molecular function. We used the method to analyze gene networks derived from genome-wide chromatin immunoprecipitation experiments, a large-scale gene deletion study, and from the genomic positions of consensus binding sites for transcription factors of the yeast Saccharomyces cerevisiae. We identified 816 functional relationships between 159 genes and show that these relationships correspond to protein–protein interactions, co-occurrence in the same protein complexes, and/or co-occurrence in abstracts of scientific articles. Our results suggest functions for seven previously uncharacterized yeast genes: KIN3 and YMR269W may be involved in biological processes related to cell growth and/or maintenance, whereas IES6, YEL008W, YEL033W, YHL029C, YMR010W, and YMR031W-A are likely to have metabolic functions. PMID:14656964

Schlitt, Thomas; Palin, Kimmo; Rung, Johan; Dietmann, Sabine; Lappe, Michael; Ukkonen, Esko; Brazma, Alvis

2003-01-01

43

Autosomal dominant genes (image)  

MedlinePLUS

In the case of autosomal dominant genes, a single abnormal gene on one of the autosomal chromosomes (one of the first 22 "non-sex" chromosomes) from either parent can cause the disease. One of the parents ...

44

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 ...

45

Computational Gene Finding  

E-print Network

fibrosis Huntington's disease Haemophilia Phenylketonuria Alzheimer disease Adult onset diabetes related isoforms (Epp CD, Nature, 389: 537). #12;Monogenic Diseases Common Diseases Infections Cystic Cancer Cardiovascular disease Depression Influenza Hepatitis AIDS Environment Genes Gene and Disease

Cheng, Jianlin Jack

46

Myocardial gene therapy  

NASA Astrophysics Data System (ADS)

Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.

Isner, Jeffrey M.

2002-01-01

47

Gene therapy for arthritis  

Microsoft Academic Search

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

Florence Apparailly; Paul Peter Tak; Christian Jorgensen

48

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

49

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

50

Myocardial gene therapy  

Microsoft Academic Search

Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis

Jeffrey M. Isner

2002-01-01

51

Noncoding RNA genes  

Microsoft Academic Search

Some genes produce RNAs that are functional instead of encoding proteins. Noncoding RNA genes are surprisingly numerous. Recently, active research areas include small nucleolar RNAs, antisense riboregulator RNAs, and RNAs involved in X-dosage compensation. Genome sequences and new algorithms have begun to make systematic computational screens for noncoding RNA genes possible.

Sean R. Eddy

1999-01-01

52

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.

53

Connectionist Approaches for Predicting Mouse Gene Function from Gene Expression  

E-print Network

Therapy. Identifying gene function based on gene expression data is much easier in prokaryotes than ways, especially in Gene Therapy [5]. Identifying gene function in prokaryotes is much easier thanConnectionist Approaches for Predicting Mouse Gene Function from Gene Expression Emad Andrews

Bonner, Anthony

54

Gene therapy review.  

PubMed

The use of genes to treat disease, more commonly known as gene therapy, is a valid and promising tool to manage and treat diseases that conventional drug therapies cannot cure. Gene therapy holds the potential to control a wide range of diseases, including cystic fibrosis, heart disease, diabetes, cancer, and blood diseases. This review assesses the current status of gene therapy, highlighting therapeutic methodologies and applications, terminology, and imaging strategies. This article presents an overview of roadblocks associated with each therapeutic methodology, along with some of the scientific, social, and ethical issues associated with gene therapy. PMID:25391667

Moss, Joseph Anthony

2014-11-01

55

Gene hunting in autoinflammation  

PubMed Central

Steady progress in our understanding of the genetic basis of autoinflammatory diseases has been made over the past 16 years. Since the discovery of the familial Mediterranean fever gene MEFV (also known as marenostrin) in 1997, 18 other genes responsible for monogenic autoinflammatory diseases have been identified to date. The discovery of these genes was made through the utilisation of many genetic mapping techniques, including next generation sequencing platforms. This review article clearly describes the gene hunting approaches, methods of data analysis and the technological platforms used, which has relevance to all those working within the field of gene discovery for Mendelian disorders. PMID:24070009

2013-01-01

56

UniGene  

NSDL National Science Digital Library

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

1997-01-01

57

The gap gene network  

PubMed Central

Gap genes are involved in segment determination during the early development of the fruit fly Drosophila melanogaster as well as in other insects. This review attempts to synthesize the current knowledge of the gap gene network through a comprehensive survey of the experimental literature. I focus on genetic and molecular evidence, which provides us with an almost-complete picture of the regulatory interactions responsible for trunk gap gene expression. I discuss the regulatory mechanisms involved, and highlight the remaining ambiguities and gaps in the evidence. This is followed by a brief discussion of molecular regulatory mechanisms for transcriptional regulation, as well as precision and size-regulation provided by the system. Finally, I discuss evidence on the evolution of gap gene expression from species other than Drosophila. My survey concludes that studies of the gap gene system continue to reveal interesting and important new insights into the role of gene regulatory networks in development and evolution. PMID:20927566

2010-01-01

58

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, ...

Fomby, Mrs.

2007-11-07

59

Gene finding strategies  

Microsoft Academic Search

Both linkage and association methods have been used to localise and identify genes related to behaviour and other complex traits. The linkage approach (parametric or non-parametric) can be used for whole genome screens to localise genes of unknown function. The parametric linkage approach is very effective for locating single-gene disorders and is usually based on large family pedigrees. The non-parametric

Jacqueline M. Vink; D. I. Boomsma

2002-01-01

60

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

61

Gene therapy for arthritis  

PubMed Central

Arthritis is among the leading causes of disability in the developed world. There remains no cure for this disease and the current treatments are only modestly effective at slowing the disease's progression and providing symptomatic relief. The clinical effectiveness of current treatment regimens has been limited by short half-lives of the drugs and the requirement for repeated systemic administration. Utilizing gene transfer approaches for the treatment of arthritis may overcome some of the obstacles associated with current treatment strategies. The present review examines recent developments in gene therapy for arthritis. Delivery strategies, gene transfer vectors, candidate genes, and safety are also discussed. PMID:18176779

Traister, Russell S.

2008-01-01

62

Genes Involved in Atherosclerosis  

Microsoft Academic Search

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

Johanna Laukkanen; Seppo Ylä-Herttuala

2002-01-01

63

Smart Genes, Stupid Science.  

ERIC Educational Resources Information Center

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

Randerson, Sherman; Mahadeva, Madhu N.

1983-01-01

64

One gene's shattering effects.  

PubMed

A new study shows that three independent mutations in the Sh1 gene, which encodes a YABBY transcription factor, gave rise to the non-shattering seed phenotype in domesticated sorghum. This same gene may have also had a role in the domestication of other cereals, including maize and rice. PMID:22641204

Olsen, Kenneth M

2012-06-01

65

Chromatin Structure Regulates Gene  

Microsoft Academic Search

Homology-directed repair is a powerful mechanism for maintaining and altering genomic structure. We asked how chromatin structure contributes to the use of homologous sequences as donors for repair using the chicken B cell line DT40 as a model. In DT40, immunoglobulin genes undergo regulated sequence diversification by gene conversion templated by pseudogene donors. We found that the immunoglobulin Vk pseudogene

Conversion W. Jason Cummings; Munehisa Yabuki; Ellen C. Ordinario; David W. Bednarski; Simon Quay; Nancy Maizels

66

Sandro Rusconi Gene transfer  

E-print Network

distrophy Obesity Artherosclerosis Alzheimer Parkinson 's Drug Abuse Homosexuality Familial Breast Cancer-05 President Union of Swiss Societies for Experimental Biology (USGEB) movie clip deleted Essential concepts GENE OK FUNCTION OK DNA GENE Protein FUNCTION(s) sport boxe 01.mov movie clip deleted #12;Not only

Málaga, Universidad de

67

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...

68

Making a Gene Library  

NSDL National Science Digital Library

This animation shows how to make a colony of new DNA in order to locate a specific gene of interest. This is the third of four animations detailing the gene cloning process. To begin at the beginning, choose Making a Recombinant Plasmid. (The animation prior to this one is Bacteria Transformation. The animation just after this one is Screening a DNA Library.)

69

Gene Expression Mural: Visualizing Gene Expression Databases  

E-print Network

Steele, Yuying Tian, Chris North Department of Computer Science Virginia Tech, Blacksburg, VA 24061 north@cs.vt.edu Abstract The Gene Expression Mural is a tool designed for managing the vast amount of information produced are displayed for each chromosome on the screen for users to directly view and compare data across experiments

70

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.

71

A gene expression screen.  

PubMed Central

A gene expression screen identifies mRNAs that differ in abundance between two mRNA mixtures by a subtractive hybridization method. The two mRNA populations are converted to double-stranded cDNAs, fragmented, and ligated to linkers for polymerase chain reaction (PCR) amplification. The multiple cDNA fragments isolated from any given gene can be treated as alleles in a genetic screen. Probability analysis of the frequency with which multiple alleles are found provides an estimation of the total number of up- and down-regulated genes. We have applied this method to genes that are differentially expressed in amphibian tadpole tail tissue in the first 24 hr after thyroid hormone treatment, which ultimately induces tail resorption. We estimate that there are about 30 up-regulated genes; 16 have been isolated. Images PMID:1722336

Wang, Z; Brown, D D

1991-01-01

72

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

73

Identification of gene regulatory networks by strategic gene disruptions and gene overexpressions  

Microsoft Academic Search

A hot research topic in Genome Science is toanalyze the interactions between genes by systematicgene disruptions and gene overexpressions.This paper analyzes the problem of identifyinga gene regulatory network from data obtainedby multiple gene disruptions and overexpressionsin regard to the number of experimentsand the complexity of experiments. An experimentconsists of a parallel gene disruptions andoverexpressions and the complexity of an experimentis

Tatsuya Akutsu; Satoru Kuhara; Osamu Maruyama; Satoru Miyano

1998-01-01

74

Bispecific Antibodies and Gene Therapy  

Microsoft Academic Search

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

Dirk M. Nettelbeck

75

CARTaGENE Project  

Cancer.gov

Launched in October 2009, the CARTaGENE project is the largest prospective longitudinal cohort of Québec. CARTaGENE's distinguishing features are that it is a quantitative prospective cohort that has deeply phenotyped 20,000 individuals aged 40-69, the age most individuals will develop chronic disease. 37,000 individuals will be enrolled by 2014. It is an open-access infrastructure enabling researchers to investigate the genetic, environmental, and lifestyle determinants of disease in the French Canadian population. CARTaGENE has collected whole blood for DNA from 30,000 individuals.

76

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

77

The fragmented gene.  

PubMed

While once almost synonymous, there is an increasing gap between the expanding definition of what constitutes a gene and the conservative and narrowly defined terms code or coding, which for a long time, almost exclusively constituted the open reading frame. Much confusion results from this disparity, especially in light of the plethora of noncoding RNAs (more correctly termed "non-protein-coding RNAs") that usually are encoded and transcribed by their own genes. A simple solution would be to adopt Ed Trifonov's less constrained definition of a code as any sequence pattern that can have a biological function. Such consideration favors not only a more complex view of the gene as an entity composed of many more or less conserved subgenic modules, but also a concept of modular evolution of genes and entire genomes. PMID:19845638

Brosius, Jürgen

2009-10-01

78

Genes underlying altruism.  

PubMed

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

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

2013-01-01

79

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

80

Introduction to Gene Therapy  

Microsoft Academic Search

Gene therapy is broadly defined as the delivery or transferof genetic material to target cells for therapeutic purposes. Elucidation of the molecular bases of inherited diseases as\\u000a well as acquired diseases, such as cancer, allows for the possibility of therapeutic interventions at the molecular level.\\u000a The therapeutic benefits may be achieved by, interfering with gene function, restoring lost function, or

Ayman Al-Hendy; Salama A. Salama

81

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

82

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

83

Evidence for homosexuality gene  

SciTech Connect

A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

Pool, R.

1993-07-16

84

GeneClinics  

PubMed Central

GeneClinics is an online genetic information resource consisting of descriptions of specific inherited disorders (“disease profiles”) as well as information on the role of genetic testing in the diagnosis, management, and genetic counseling of patients with these inherited conditions. GeneClinics is intended to promote the use of genetic services in medical care and personal decision making by providing health care practitioners and patients with information on genetic testing for specific inherited disorders. GeneClinics is implemented as an object-oriented database containing a combination of data and semistructured text that is rendered as HTML for publishing a given “disease profile” on the Web. Content is acquired from authors via templates, converted to an XML document reflecting the underlying database schema (with tagging of embedded data), and then loaded into the database and subjected to peer review. The initial implementation of a production system and the first phase of population of the GeneClinics database content are complete. Further expansion of the content to cover more disease, significant scaling up of rate of content creation, and evaluation redesign are under way. The ultimate goal is to have an entry in GeneClinics for each entry in the GeneTests directory of medical genetics laboratories—that is, for each disease for which clinical genetic testing is available. PMID:10833163

Tarczy-Hornoch, Peter; Shannon, Paul; Baskin, Patty; Espeseth, Miriam; Pagon, Roberta A.

2000-01-01

85

Sudden Cardiac Arrest during Anesthesia in a 30-Month-Old Boy with Syndactyly: A Case of Genetically Proven Timothy Syndrome  

PubMed Central

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; Noh, Chung Il; Choi, Jung Yun; Park, Sung Sup

2013-01-01

86

Mytilus edulis Histone Gene Clusters Containing Only H1 Genes  

Microsoft Academic Search

.   We isolated five different phage clones containing histone gene clusters with up to five H1 genes per phage clone from a\\u000a Mytilus edulis genomic library. Among these H1 genes, nine gene types coding for five different H1 proteins have been identified. All H1\\u000a histone genes were located on repetitive restriction fragments with only slightly different sizes. The H1 coding

Birgit Drabent; Jae-Sun Kim; Werner Albig; Eva Prats; Luis Cornudella; Detlef Doenecke

1999-01-01

87

How old is my gene?  

PubMed Central

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

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

2013-01-01

88

Drug-induced torsades de pointes: the evolving role of pharmacogenetics.  

PubMed

Drug-induced torsades de pointes (TdP) is a rare, but potentially lethal, unwanted effect of drugs, including many commonly prescribed noncardiac drugs. Despite its low frequency, drug-induced TdP has generated a great deal of angst among physicians and pharmaceutical companies as well as tragedy, albeit rare, among patients. Although in retrospect many patients who died suddenly as a result of drug-induced TdP had identifiable risk factors, prediction in individual cases remains problematic. Over the past decade, tremendous progress has been made with respect to elucidating the fundamental pathogenic mechanisms that underlie drug-induced TdP. The vast majority of drugs associated with "QT liability" and the potential for drug-induced TdP, including all of the drugs removed from the market because of this side effect, are "HERG (human ether-á-go-go-related gene) blockers." These drugs inhibit the KCNH2-encoded HERG potassium channel, which is one of the critical repolarizing forces involved in the exquisite orchestration of the heart's action potential. Consequently, myocyte repolarization is potentially delayed as evidenced by prolongation of the QT interval, thus providing the substrate for drug-induced TdP. Rare mutations in KCNH2 provide the pathogenic substrate for type 2 congenital long QT syndrome (LQTS), thus placing this cardiac potassium channel squarely in the intersection between congenital LQTS (the "Rosetta stone" of the heritable channelopathies) and acquired LQTS (drug-induced TdP). In addition, common polymorphisms residing in the LQTS-causing channel genes may confer heightened arrhythmogenic susceptibility and contribute to the makings of a vulnerable host. This review focuses on the present strategy of identifying "at-risk compounds" and the potential future strategy involving pharmacogenetics to pinpoint "at-risk hosts" in an effort to curb this rare, unintended, but potentially life-threatening side effect. PMID:16253929

Fitzgerald, Patrick T; Ackerman, Michael J

2005-11-01

89

Eukaryotic Genes Involved in Adult Lifespan Regulation.  

National Technical Information Service (NTIS)

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

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

2005-01-01

90

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

91

The locust foraging gene.  

PubMed

Our knowledge of how genes act on the nervous system in response to the environment to generate behavioral plasticity is limited. A number of recent advancements in this area concern food-related behaviors and a specific gene family called foraging (for), which encodes a cGMP-dependent protein kinase (PKG). The desert locust (Schistocerca gregaria) is notorious for its destructive feeding and long-term migratory behavior. Locust phase polyphenism is an extreme example of environmentally induced behavioral plasticity. In response to changes in population density, locusts dramatically alter their behavior, from solitary and relatively sedentary behavior to active aggregation and swarming. Very little is known about the molecular and genetic basis of this striking behavioral phenomenon. Here we initiated studies into the locust for gene by identifying, cloning, and studying expression of the gene in the locust brain. We determined the phylogenetic relationships between the locust PKG and other known PKG proteins in insects. FOR expression was found to be confined to neurons of the anterior midline of the brain, the pars intercerebralis. Our results suggest that differences in PKG enzyme activity are correlated to well-established phase-related behavioral differences. These results lay the groundwork for functional studies of the locust for gene and its possible relations to locust phase polyphenism. PMID:20422718

Lucas, C; Kornfein, R; Chakaborty-Chatterjee, M; Schonfeld, J; Geva, N; Sokolowski, M B; Ayali, A

2010-05-01

92

On sports and genes.  

PubMed

Our genes influence our athletic ability. However, the causal genetic factors and mechanisms, and the extent of their effects, remain largely elusive. Many studies investigate this association between specific genes and athletic performance. Such studies have increased in number over the past few years, as recent developments and patents in DNA sequencing have made large amounts of sequencing data available for such analysis. In this paper, we consider four of the most intensively studied genes in relation to athletic ability: angiotensin I-converting enzyme, alpha-actinin 3, peroxismose proliferator-activator receptor alpha and nitric oxide synthase 3. We investigate the connection between genotype and athletic phenotype in the context of these four genes in various sport fields and across different ethnicities and genders. We do an extensive literature survey on these genes and the polymorphisms (single nucleotide polymorphisms or indels) found to be associated with athletic performance. We also present, for each of these polymorphisms, the allele frequencies in the different ethnicities reported in the pilot phase of the 1000 Genomes Project - arguably the largest human genome-sequencing endeavor to date. We discuss the considerable success, and significant drawbacks, of past research along these lines, and propose interesting directions for future research. PMID:22762737

Zilberman-Schapira, Gili; Chen, Jieming; Gerstein, Mark

2012-12-01

93

Saporin suicide gene therapy.  

PubMed

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

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

2009-01-01

94

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

95

Avian tropomyosin gene expression.  

PubMed Central

Sequence analysis of overlapping fragments from a quail genomic library has revealed a tropomyosin gene consisting of 13 exons spaced over about 18 kilobase pairs of DNA. Skeletal muscle and smooth muscle transcripts share the same 5' untranslated sequence and may initiate from the same promoter. However, the regions encoding amino acids 39-80 and 258-284 are specific to each muscle type. The two sets of exons encoding these regions undergo mutually exclusive alternative splicing in a tissue-specific manner as determined by Northern blots and S1-nuclease protection. Similarly, the 3' ends of the transcripts are different in skeletal muscle and smooth muscle, and each contains two polyadenylation signals which appear to be utilized in vivo. The avian alpha-tropomyosin gene is not expressed in cardiac muscle. The sequence of the gene shows great homology with other muscle-specific tropomyosins and includes a region homologous to the amino terminus of nonmuscle tropomyosins. Images PMID:2701936

Lindquester, G J; Flach, J E; Fleenor, D E; Hickman, K H; Devlin, R B

1989-01-01

96

Characterizing gene family evolution  

PubMed Central

Gene families are widely used in comparative genomics, molecular evolution, and in systematics. However, they are constructed in different manners, their data analyzed and interpreted differently, with different underlying assumptions, leading to sometimes divergent conclusions. In systematics, concepts like monophyly and the dichotomy between homoplasy and homology have been central to the analysis of phylogenies. We critique the traditional use of such concepts as applied to gene families and give examples of incorrect inferences they may lead to. Operational definitions that have emerged within functional genomics are contrasted with the common formal definitions derived from systematics. Lastly, we question the utility of layers of homology and the meaning of homology at the character state level in the context of sequence evolution. From this, we move forward to present an idealized strategy for characterizing gene family evolution for both systematic and functional purposes, including recent methodological improvements. PMID:19461954

Liberles, David A.

2008-01-01

97

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

98

Gene Network Biological Validity Based on Gene-Gene Interaction Relevance  

PubMed Central

In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown. PMID:25295303

Gomez-Vela, Francisco; Diaz-Diaz, Norberto

2014-01-01

99

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.

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

2014-01-01

100

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".

101

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

102

Resistance gene capture  

Microsoft Academic Search

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

Dean A Rowe-Magnus; Didier Mazel

1999-01-01

103

Genes and Psoriasis  

MedlinePLUS

... are some possible genetic changes that could explain why psoriasis/psoriatic arthritis occurs. It is known that some people are more likely to have psoriasis than others, and this "susceptibility" may lie in the genes themselves. Scientists have now identified ...

104

Gene expression data preprocessing  

Microsoft Academic Search

Summary: We present an interactive web tool for prepro- cessing microarray gene expression data. It analyses the data, suggests the most appropriate transformations and proceeds with them after user agreement. The normal preprocessing steps include scale transformations, man- agement of missing values, replicate handling, flat pattern filtering and pattern standardization and they are required before performing any pattern analysis. The

Javier Herrero; Ramón Díaz-uriarte; Joaquín Dopazo

2003-01-01

105

Engineering prokaryotic gene circuits  

PubMed Central

Engineering of synthetic gene circuits is a rapidly growing discipline, currently dominated by prokaryotic transcription networks, which can be easily rearranged or rewired to give different output behaviours. In this review, we examine both a rational and a combinatorial design of such networks and discuss progress on using in vitro evolution techniques to obtain functional systems. Moving beyond pure transcription networks, more and more networks are being implemented at the level of RNA, taking advantage of mechanisms of translational control and aptamer–small molecule complex formation. Unlike gene expression systems, metabolic components are generally not as interconnectable in any combination, and so engineering of metabolic circuits is a particularly challenging field. Nonetheless, metabolic engineering has immense potential to provide useful biosynthesis tools for biotechnology applications. Finally, although prokaryotes are mostly studied as single cell systems, cell–cell communication networks are now being developed that result in spatial pattern formation in multicellular prokaryote colonies. This represents a crossover with multicellular organisms, showing that prokaryotic systems have the potential to tackle questions traditionally associated with developmental biology. Overall, the current advances in synthetic gene synthesis, ultra-high-throughput DNA sequencing and computation are synergizing to drive synthetic gene network design at an unprecedented pace. PMID:19016883

Michalodimitrakis, Konstantinos; Isalan, Mark

2009-01-01

106

Reactivating Tumor Suppressor Genes  

Cancer.gov

This is the first clinical trial to test the combination of a drug called 5-fluoro-2'-deoxycytidine (FdCyd) and tetrahydrouridine (THU) in humans. Researchers are interested in establishing the maximum tolerated dose and determining how this regimen affects the activity of certain tumor suppressor genes in patients with advanced solid tumors.

107

Resistance gene capture.  

PubMed

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

Rowe-Magnus, D A; Mazel, D

1999-10-01

108

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

109

Sandro Rusconi Gene transfer  

E-print Network

Alzheimer Parkinson 's Drug Abuse Homosexuality Familial Breast Cancer Lung Cancer Sporadic Breast Cancer of Swiss Societies for Experimental Biology (USGEB) movie clip deleted #12;Essential concepts on 'molecular OK DNA GENE Protein FUNCTION(s) movie clip deleted #12;Not only the genome determines the health

Málaga, Universidad de

110

Ancient horizontal gene transfer  

Microsoft Academic Search

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

James R. Brown

2003-01-01

111

Human gene therapy.  

PubMed

Human gene therapy is a procedure that is being used in an attempt to treat genetic and other diseases. Eleven clinical protocols are under way at the present time, each with scientific and clinical objectives. Human genetic engineering raises unique safety, social, and ethical concerns. PMID:1589762

Anderson, W F

1992-05-01

112

Evolutionary Similarity Among Genes  

Microsoft Academic Search

An evolutionary history of a set of organisms is a family tree, or topology, with branches of various lengths between vertices that describe how closely the organisms are related to each other. We consider the K evolutionary histories of K genes from a set of N organisms. Evolutionary similarity (ES) occurs when the branching patterns and relative branch lengths in

Marc A. Suchard; Robert E. Weiss; Janet S. Sinsheimer; Karin S. Dorman; Megha Patel; Edward R. B. McCabe

2003-01-01

113

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

114

Tests for gene clustering Dannie Durand  

E-print Network

scale rearrangements, horizontal gene transfer, gene duplica- tion and gene loss, it becomes and loss and horizontal gene transfer result in changes in gene complement, while gene order is disruptedTests for gene clustering Dannie Durand Department of Biological Sciences, Carnegie Mellon

Durand, Dannie

115

ToppGene Suite for gene list enrichment analysis and candidate gene prioritization  

PubMed Central

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

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

2009-01-01

116

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

PubMed

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

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

2009-07-01

117

Gene-based approach to human gene-phenotype correlations  

PubMed Central

Elucidating the genetic basis of human phenotypes is a major goal of contemporary geneticists. Logically, two fundamental and contrasting approaches are available, one that begins with a phenotype and concludes with the identification of a responsible gene or genes; the other that begins with a gene and works toward identifying one or more phenotypes resulting from allelic variation of it. This paper provides a conceptual overview of phenotype-based vs. gene-based procedures with emphasis on gene-based methods. A key feature of a gene-based approach is that laboratory effort first is devoted to developing an assay for mutations in the gene under regard; the assay then is applied to the evaluation of large numbers of unrelated individuals with a variety of phenotypes that are deemed potentially resulting from alleles at the gene. No effort is directed toward chromosomally mapping the loci responsible for the phenotypes scanned. Example is made of my laboratory’s successful use of a gene-based approach to identify genes causing hereditary diseases of the retina such as retinitis pigmentosa. Reductions in the cost and improvements in the speed of scanning individuals for DNA sequence anomalies may make a gene-based approach an efficient alternative to phenotype-based approaches to correlating genes with phenotypes. PMID:9342372

Dryja, Thaddeus P.

1997-01-01

118

Problems in gene clustering based on gene expression data  

Microsoft Academic Search

In this work, we assess the suitability of cluster analysis for the gene grouping problem confronted with microarray data. Gene clustering is the exercise of grouping genes based on attributes, which are generally the expression levels over a number of conditions or subpopulations. The hope is that similarity with respect to expression is often indicative of similarity with respect to

Jenny Bryan

2004-01-01

119

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...

120

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

121

Genes and Genome Systems (Program Description)  

NSF Publications Database

... Cellular Biosciences Genes and Genome Systems Description The Genes and Genome Systems Cluster ... are the processes that mediate and regulate gene expression, such as chromatin structure, epigenetic ...

122

Interactive Fly: Genes involved in Malpighian Tubules  

NSDL National Science Digital Library

A list and description of Drosophila genes involved in malpigian tubule formation, highlighting transcription factors, ATPase genes, and surface protein genes. A subset of the Interactive Fly collection.

PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

2006-12-14

123

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

124

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

125

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

1998-07-01

126

Gene Therapy and Cardiovascular Diseases  

Microsoft Academic Search

Gene therapy is a promising new field in modern medicine and holds great potential for the treatment of cardiovascular diseases.\\u000a This chapter will discuss the principles and methods of gene-based therapy and the use of gene transfer in research and in\\u000a treatment of cardiovascular diseases.

Yi Chu; Neal L. Weintraub; Donald D. Heistad

127

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

128

Globin genes on the move.  

PubMed

Recent data published in BMC Biology from the globin gene clusters in platypus, together with data from other species, show that beta-globin genes transposed from one chromosomal location to another. This resolves some controversies about vertebrate globin gene evolution but ignites new ones. PMID:19040770

Hardison, Ross C

2008-01-01

129

Simulating Gene Expression using Netlogo  

NSDL National Science Digital Library

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

Steven Brewer (University of Massachusetts;); Allen Koop (Grand Valley State University;); Patrick Ehrman (Institue for Systems Biology;)

2004-06-12

130

Myc Cancer Gene  

NSDL National Science Digital Library

This Web site, offered through Johns Hopkins University School of Medicine and Johns Hopkins Health System, aims to "provide a hub for the integration of information on Myc target genes, the role of Myc in human cancers, and proteins that interact with the Myc transcription factors." Users will find a well-organized collection of resources relating to Myc, such as an extensive set of links to PubMed articles, related databases, and some original data. The Web site's introduction provides a very readable explanation of Myc gene function and its role in tumor formation. Researchers working with Myc are encouraged to submit data to the site, which also offers a Myc-related listserve for convenient email updates.

131

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

132

DNA Gene Chip Explanation  

NSDL National Science Digital Library

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

Dr. Melton (Howard Hughes Medical Institute;)

2007-03-31

133

Clock genes and sleep  

Microsoft Academic Search

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

Dominic Landgraf; Anton Shostak; Henrik Oster

134

Radioprotective gene therapy.  

PubMed

Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. We have developed the technology for radioprotective gene therapy using the transgene for the antioxidant manganese superoxide dismutase, delivered to specific target organs (lung, esophagus, oral cavity, oropharynx, and bladder) using gene transfer vectors including plasmid/liposomes (PL) and adenovirus. Irradiation protection by MnSOD transgene overexpression at the cellular level has been demonstrated to be localized to the mitochondrial membrane. Using MnSOD transgene constructs lacking the mitochondrial localization leader sequence, and in other experiments attaching this localization signal to otherwise non-radioprotective cytoplasmic Cu/ZnSOD, mitochondrial localization has been demonstrated to be critical to protection. Organ specific injection of MnSOD-PL prior to irradiation demonstrates transgene expression for 48-72 hours, and an associated decrease in ionizing irradiation-induced expression of inflammatory cytokine mRNA and protein. Significant reduction of organ specific tissue injury has been demonstrated in several organ systems in rodent models. Application of MnSOD-PL gene therapy in the setting of fractionated chemo-radiotherapy is being tested in clinical trials for prevention of esophagitis during treatment of non-small cell carcinoma of the lung, and in prevention of mucositis during combination therapy of carcinomas of the head and neck. Encouraging results in pre-clinical models suggest that radioprotective gene therapy may facilitate dose escalation protocols to allow increases in the therapeutic ratio of cancer radiotherapy. PMID:12762478

Greenberger, J S; Epperly, M W; Gretton, J; Jefferson, M; Nie, S; Bernarding, M; Kagan, V; Guo, H L

2003-06-01

135

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

136

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

137

Gene delivery to bone.  

PubMed

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

2012-09-01

138

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

139

Genes, disease and medicine.  

PubMed

1. Information and technologies derived from genomic research are beginning to revolutionize the study of disease. It is now being predicted that the human genome sequencing project will be more than 90% complete by the end of this decade and that most of the major genes involved in common diseases will have been identified by that time. Correlations between genetic mutations, disease susceptibility, and adverse reactions to drugs are already being established and it seems inevitable that this will lead to the development of novel therapies accurately targeted at subsets of patients most likely to show a favourable response. 2. Targeted therapies present a significant challenge to the pharmaceutical industry because the potential market for such drugs is likely to be smaller than for current 'phenotypic' treatments. However, application of molecular genetic technologies may allow parallel reductions in development costs since it should be more straightforward to demonstrate efficacy and safety in accurately selected patient groups, reducing the requirement for large clinical trials. 3. Gene-based diagnostics have the potential to radically improve medical practice, and progress in genetic testing technology has been impressive. Yet there is growing concern that commercial and other pressures may result in genetic testing being made widely available before the biological consequences of mutations in disease susceptibility genes are fully understood and before the legal, ethical and psychological consequences of testing have been fully debated. PMID:8971423

Dykes, C W

1996-12-01

140

Retinal dystrophies and gene therapy.  

PubMed

Retinal dystrophies are inherited disorders of photoreceptor and retinal pigment epithelial function that may result in severe visual impairment. Advances in molecular genetics have helped identify many of the gene defects responsible, and progress in gene transfer technology has enabled therapeutic strategies to be developed and applied. The first human clinical trials of gene therapy for RPE65 associated retinal dystrophy have shown promising initial results and have helped prepare the way for further trials of gene therapy for inherited retinal disorders. The results of these trials will provide further insight into the safety and efficacy of gene therapy for a range of currently untreatable and debilitating eye disorders. PMID:22080959

Sundaram, Venki; Moore, Anthony T; Ali, Robin R; Bainbridge, James W

2012-05-01

141

Gene network analysis and design  

NASA Astrophysics Data System (ADS)

Gene networks are composed of many different interacting genes and gene products (RNAs and proteins). They can be thought of as switching regions in n-dimensional space or as mass-balanced signaling networks. Both approaches allow for describing gene networks with the limited quantitative or even qualitative data available. We show how these approaches can be used in modeling the apoptosis gene network that has a vital role in tumor development. The open question is whether engineering changes to this network could be used as a possible cancer treatment.

Berryman, Matthew J.; Allison, Andrew; Abbott, Derek

2005-02-01

142

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

143

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

144

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

145

Chromosomal localisation of a Y specific growth gene(s).  

PubMed Central

Although a Y specific growth gene(s) has been postulated in the Yq11 region, the precise location has not been determined. To localise the growth gene(s), we correlated genotype with stature in 13 Japanese and four European non-mosaic adult male patients with a partial Yq deletion. Fourteen patients preserving the region between DYS11 and DYS246 did not have short stature (11 Japanese, 165-180 cm; three Europeans, 165-173 cm) whereas the remaining three patients with the region deleted had short stature (two Japanese, both 159 cm; one European, 157 cm). The results suggest that the region defined by DYS11 at interval 5C and by DYS246 at interval 5D may be the critical region for the Y specific growth gene(s). Images PMID:7562976

Ogata, T; Tomita, K; Hida, A; Matsuo, N; Nakahori, Y; Nakagome, Y

1995-01-01

146

Broker Genes in Human Disease  

PubMed Central

Genes that underlie human disease are important subjects of systems biology research. In the present study, we demonstrate that Mendelian and complex disease genes have distinct and consistent protein–protein interaction (PPI) properties. We show that five different network properties can be reduced to two independent metrics when applied to the human PPI network. These two metrics largely coincide with the degree (number of connections) and the clustering coefficient (the number of connections among the neighbors of a particular protein). We demonstrate that disease genes have simultaneously unusually high degree and unusually low clustering coefficient. Such genes can be described as brokers in that they connect many proteins that would not be connected otherwise. We show that these results are robust to the effect of gene age and inspection bias variation. Notably, genes identified in genome-wide association study (GWAS) have network patterns that are almost indistinguishable from the network patterns of nondisease genes and significantly different from the network patterns of complex disease genes identified through non-GWAS means. This suggests either that GWAS focused on a distinct set of diseases associated with an unusual set of genes or that mapping of GWAS-identified single nucleotide polymorphisms onto the causally affected neighboring genes is error prone. PMID:20937604

Cai, James J.; Borenstein, Elhanan; Petrov, Dmitri A.

2010-01-01

147

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

148

Viral Vectors for Gene Transfer: Current Status of Gene Therapeutics  

Microsoft Academic Search

\\u000a Gene therapy for the correction of inherited or acquired disease has gained increasing importance in recent years. Successful\\u000a treatment of children suffering from severe combined immunodeficiency (SCID) was achieved using retrovirus vectors for gene\\u000a transfer. Encouraging improvements of vision were reported in a genetic eye disorder (LCA) leading to early childhood blindness.\\u000a Adeno-associated virus (AAV) vectors were used for gene

Regine Heilbronn; Stefan Weger

149

GeneTrail - advanced gene set enrichment analysis  

Microsoft Academic Search

We present a comprehensive and efficient gene set analysis tool, called 'GeneTrail' that offers a rich functionality and is easy to use. Our web-based application facilitates the statistical evaluation of high-throughput genomic or proteomic data sets with respect to enrichment of functional categories. GeneTrail covers a wide variety of biological cate- gories and pathways, among others KEGG, TRANSPATH, TRANSFAC, and

Christina Backes; Andreas Keller; Jan Kuentzer; Benny Kneissl; Nicole Comtesse; Yasser A. Elnakady; Rolf Müller; Eckart Meese; Hans-peter Lenhof

2007-01-01

150

Bayesian assignment of gene ontology terms to gene expression experiments  

PubMed Central

Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

Sykacek, P.

2012-01-01

151

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

152

GENE LOOPS ENHANCE TRANSCRIPTIONAL DIRECTIONALITY  

PubMed Central

Eukaryotic genomes are extensively transcribed, forming both messenger (m) and noncoding (nc) RNAs. ncRNAs made by RNA polymerase II (Pol II) often initiate from bidirectional promoters (nucleosome-depleted chromatin) that synthesise mRNA and ncRNA in opposite directions. We demonstrate that actively transcribed mRNA encoding genes by adopting a gene loop conformation, restrict divergent transcription of ncRNAs. Since gene loop formation depends on a protein factor (Ssu72) that co-associates with both promoter and terminator, its inactivation leads to increased synthesis of promoter-associated divergent ncRNAs, referred to as Ssu72 restricted transcripts (SRT). Similarly, inactivation of individual gene loops by gene mutation enhances SRT synthesis. We demonstrate that gene loop conformation enforces transcriptional directionality on otherwise bidirectional promoters. PMID:23019609

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

2012-01-01

153

Gene loops enhance transcriptional directionality.  

PubMed

Eukaryotic genomes are extensively transcribed, forming both messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). ncRNAs made by RNA polymerase II often initiate from bidirectional promoters (nucleosome-depleted chromatin) that synthesize mRNA and ncRNA in opposite directions. We demonstrate that, by adopting a gene-loop conformation, actively transcribed mRNA encoding genes restrict divergent transcription of ncRNAs. Because gene-loop formation depends on a protein factor (Ssu72) that coassociates with both the promoter and the terminator, the inactivation of Ssu72 leads to increased synthesis of promoter-associated divergent ncRNAs, referred to as Ssu72-restricted transcripts (SRTs). Similarly, inactivation of individual gene loops by gene mutation enhances SRT synthesis. We demonstrate that gene-loop conformation enforces transcriptional directionality on otherwise bidirectional promoters. PMID:23019609

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

2012-11-01

154

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

155

Analysis of shuffled gene libraries.  

PubMed

In vitro recombination of homologous genes (family shuffling) has been proposed as an effective search strategy for laboratory evolution of genes and proteins. Few data are available, however, on the composition of shuffled gene libraries, from which one could assess the efficiency of recombination and optimize protocols. Here, probe hybridization is used in a macroarray format to analyze chimeric DNA libraries created by DNA shuffling. Characterization of hundreds of shuffled genes encoding dioxygenases has elucidated important biases in the shuffling reaction. As expected, crossovers are favored in regions of high sequence identity. A sequence-based model of homologous recombination that captures this observed bias was formulated using the experimental results. The chimeric genes were found to show biases in the incorporation of sequences from certain parents, even before selection. Statistically different patterns of parental incorporation in genes expressing functional proteins can help to identify key sequence-function relationships. PMID:11866523

Joern, John M; Meinhold, Peter; Arnold, Frances H

2002-02-22

156

Gene therapy in heart failure.  

PubMed

The treatment of heart failure (HF) may be entering a new era with clinical trials currently assessing the value of gene therapy as a novel therapeutic strategy. If these trials demonstrate efficacy then a new avenue of potential treatments could become available to the clinicians treating HF. In principle, gene therapy allows us to directly target the underlying molecular abnormalities seen in the failing myocyte. In this review we discuss the fundamentals of gene therapy and the challenges of delivering it to patients with HF. The molecular abnormalities underlying HF are discussed along with potential targets for gene therapy, focusing on SERCA2a. We discuss the laboratory and early clinical evidence for the benefit of SERCA2a gene therapy in HF. Finally, we discuss the ongoing clinical trials of SERCA2a gene therapy and possible future directions for this treatment. (Circ J 2014; 78: 2577-2587). PMID:25327883

Hayward, Carl; Patel, Hitesh; Lyon, Alexander

2014-10-24

157

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

158

The Perils of Gene Patents  

PubMed Central

I argue here that gene patents, and patented genetic tests based on them, are a very bad idea. First, I discuss whether genes can reasonably be the subject of patents in the first place; I maintain that the answer is no. Second, I explain how gene patents interfere with scientific progress, slowing down the development of new cures and treatments for genetic diseases. PMID:22609909

Salzberg, SL

2013-01-01

159

Understanding Cancer Series: Gene Testing  

Cancer.gov

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

160

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

PubMed Central

The mammalian circadian system controls various physiology processes and behavior responses by regulating thousands of circadian genes with rhythmic expressions. In this study, we redefined circadian-regulated genes based on published results in the mouse liver and compared them with other gene groups defined relative to circadian regulations, especially the non-circadian-regulated genes expressed in liver at multiple molecular levels from gene position to protein expression based on integrative analyses of different datasets from the literature. Based on the intra-tissue analysis, the liver circadian genes or LCGs show unique features when compared to other gene groups. First, LCGs in general have less neighboring genes and larger in both genomic and 3?-UTR lengths but shorter in CDS (coding sequence) lengths. Second, LCGs have higher mRNA and protein abundance, higher temporal expression variations, and shorter mRNA half-life. Third, more than 60% of LCGs form major co-expression clusters centered in four temporal windows: dawn, day, dusk, and night. In addition, larger and smaller LCGs are found mainly expressed in the day and night temporal windows, respectively, and we believe that LCGs are well-partitioned into the gene expression regulatory network that takes advantage of gene size, expression constraint, and chromosomal architecture. Based on inter-tissue analysis, more than half of LCGs are ubiquitously expressed in multiple tissues but only show rhythmical expression in one or limited number of tissues. LCGs show at least three-fold lower expression variations across the temporal windows than those among different tissues, and this observation suggests that temporal expression variations regulated by the circadian system is relatively subtle as compared with the tissue expression variations formed during development. Taken together, we suggest that the circadian system selects gene parameters in a cost effective way to improve tissue-specific functions by adapting temporal variations from the environment over evolutionary time scales. PMID:23071677

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

2012-01-01

161

Importance of Combinatorial Gene Control  

NSDL National Science Digital Library

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

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

1998-07-01

162

RNAi induced gene silencing in crop improvement  

Microsoft Academic Search

The RNA silencing is one of the innovative and efficient molecular biology tools to harness the down-regulation of expression\\u000a of gene(s) specifically. To accomplish such selective modification of gene expression of a particular trait, homology dependent\\u000a gene silencing uses a stunning variety of gene silencing viz. co-suppression, post-transcriptional gene silencing, virus-induced\\u000a gene silencing etc. This family of diverse molecular phenomena

Subodh Kumar Sinha

2010-01-01

163

Gene- and evidence-based candidate gene selection for schizophrenia and gene feature analysis  

PubMed Central

Summary Objective Schizophrenia is a chronic psychiatric disorder that affects about 1% of the population globally. A tremendous amount of effort has been expended in the past decade, including more than 2400 association studies, to identify genes influencing susceptibility to the disorder. However, few genes or markers have been reliably replicated. The wealth of this information calls for an integration of gene association data, evidence based gene ranking, and follow-up replication in large sample. The objective of this study is to develop and evaluate evidence based gene ranking methods and to examine the features of top-ranking candidate genes for schizophrenia. Methods We proposed a gene-based approach for selecting and prioritizing candidate genes by combining odds ratios (ORs) of multiple markers in each association study and then combining ORs in multiple studies of a gene. We named it combination-combination OR method (CCOR). CCOR is similar to our recently published method, which first selects the largest OR of the markers in each study and then combines these ORs in multiple studies (i.e., selection-combination OR method, SCOR), but differs in selecting representative OR in each study. Features of top-ranking genes were examined by gene ontology terms and gene expression in tissues. Results Our evaluation suggested that the SCOR method overall outperforms the CCOR method. Using the SCOR, a list of 75 top-ranking genes was selected for schizophrenia candidate genes (SZGenes). We found that SZGenes had strong correlation with neuro-related functional terms and were highly expressed in brain-related tissues. Conclusion The scientific landscape for schizophrenia genetics and other complex disease studies is expected to change dramatically in the next a few years, thus, the gene-based combined OR method is useful in candidate gene selection for follow-up association studies and in further artificial intelligence in medicine. This method for prioritization of candidate genes can be applied to other complex diseases such as depression, anxiety, nicotine dependence, alcohol dependence, and cardiovascular diseases. PMID:19944577

Sun, Jingchun; Han, Leng; Zhao, Zhongming

2009-01-01

164

UConn Behavioral Gene Bank The UConn Behavioral Gene Bank  

E-print Network

illness? Mental illnesses include disorders such as schizophrenia, bipolar disorder, depression, anxiety affected by these disorders as well. What is a Gene Bank? Information and tissue samples such as blood to establish a Gene Bank to support research to find causes of illnesses or behavioral disorders. Participation

Oliver, Douglas L.

165

Bioinformatic analysis for exploring relationships between genes and gene products  

Microsoft Academic Search

To carry out their specific roles in the cell, genes and gene products often work together in groups, forming many relationships among themselves and with other molecules. Such relationships include physical protein-protein interaction relationships, regulatory relationships, metabolic relationships, genetic relationships, and much more. With advances in science and technology, some high throughput technologies have been developed to simultaneously detect tens

Erliang Zeng

2008-01-01

166

A Gene Scrapbook A Tribute to Gene Loh  

E-print Network

. #12;De-classified Photo from Cornell Files Subject is known to have fathered children sometime during, spreading the Gospel of the Great Pumpkin to the Children of Alice Springs, Australia #12;Gene in Japan Gene spent some time vacationing at KEK in Japan measuring fluorescence yield from an electron beam

167

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

168

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

169

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 engineersâcommunicating 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 questionâaccurate, efficient methods for detecting cancer-causing genes using optical biosensorsâwhich 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

170

Neofunctionalization of Duplicated Genes Under the Pressure of Gene Conversion  

PubMed Central

Neofunctionalization occurs when a neofunctionalized allele is fixed in one of duplicated genes. This is a simple fixation process if duplicated genes accumulate mutations independently. However, the process is very complicated when duplicated genes undergo concerted evolution by gene conversion. Our simulations demonstrate that the process could be described with three distinct stages. First, a newly arisen neofunctionalized allele increases in frequency by selection, but gene conversion prevents its complete fixation. These two factors (selection and gene conversion) that work in opposite directions create an equilibrium, and the time during which the frequency of the neofunctionalized allele drifts around the equilibrium value is called the temporal equilibrium stage. During this temporal equilibrium stage, it is possible that gene conversion is inactivated by mutations, which allow the complete fixation of the neofunctionalized allele. And then, permanent neofunctionalization is achieved. This article develops basic population genetics theories on the process to permanent neofunctionalization under the pressure of gene conversion. We obtain the probability and time that the frequency of a newly arisen neofunctionalized allele reaches the equilibrium value. It is also found that during the temporal equilibrium stage, selection exhibits strong signature in the divergence in the DNA sequences between the duplicated genes. The spatial distribution of the divergence likely has a peak around the site targeted by selection. We provide an analytical expression of the pattern of divergence and apply it to the human red- and green-opsin genes. The theoretical prediction well fits the data when we assume that selection is operating for the two amino acid differences in exon 5, which are believed to account for the major part of the functional difference between the red and green opsins. PMID:18245342

Teshima, Kosuke M.; Innan, Hideki

2008-01-01

171

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

172

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

173

Introduction: Genes, cognition and neuropsychiatry  

Microsoft Academic Search

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

Brita Elvevåg; Daniel R. Weinberger

2009-01-01

174

Gene therapy in heart disease  

Microsoft Academic Search

Application of gene therapy to the field of cardiovascular disorders has been the subject of intensive work over the recent period. Gene therapy for cardiovascular disorders is now fast developing with most therapies being devoted to the consequences (ischemia) rather than the causes of atherosclerotic diseases. Recent human clinical trials have shown that injection of naked DNA encoding vascular endothelial

E Teiger; I Deprez; V Fataccioli; S Champagne; J. L Dubois-Randé; M Eloit; S Adnot

2001-01-01

175

Cancer gene discovery goes mobile.  

PubMed

A new study describes a tool, Lentihop, for somatic insertional mutagenesis in human cells and uses this system in combination with cancer genome data to define new genes and pathways involved in sarcoma development. Gene discovery in this way suggests that we are far from a complete catalog of cancer drivers. PMID:25162801

van der Weyden, Louise; Ranzani, Marco; Adams, David J

2014-09-01

176

Horizontal gene transfer and phylogenetics  

Microsoft Academic Search

The initial analysis of complete genomes has suggested that horizontal gene transfer events are very frequent between microorganisms. This could potentially render the inference, and even the concept itself, of the organismal phylogeny impossible. However, a coherent phylogenetic pattern has recently emerged from an analysis of about a hundred genes, the so-called ‘core’, strongly suggesting that it is possible to

Hervé Philippe; Christophe J Douady

2003-01-01

177

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

178

Chromatin Structure Regulates Gene Conversion  

Microsoft Academic Search

Homology-directed repair is a powerful mechanism for maintaining and altering genomic structure. We asked how chromatin structure contributes to the use of homologous sequences as donors for repair using the chicken B cell line DT40 as a model. In DT40, immunoglobulin genes undergo regulated sequence diversification by gene conversion templated by pseudogene donors. We found that the immunoglobulin V? pseudogene

W. Jason Cummings; Munehisa Yabuki; Ellen C Ordinario; David W Bednarski; Simon Quay; Nancy Maizels

2007-01-01

179

Gene and Stem Cell Therapy  

Microsoft Academic Search

Gene and stem cell therapy are being developed as novel treatments for cystic fibrosis (CF). In gene therapy, the therapeutic nucleic acid is delivered to terminally differentiated epithelial cells in the airways. While technically less demanding, this approach has the drawback that therapy must be continually re-administered because of target cell turnover. Direct airway administration is also faced with powerful

A. Boyd

2006-01-01

180

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

181

Systems Biophysics of Gene Expression  

E-print Network

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

Jose M. G. Vilar; Leonor Saiz

2013-07-03

182

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

183

Gene regulation by growth hormone  

PubMed Central

Since the somatomedin hypothesis of growth hormone (GH) action was first formulated more than 50 years ago, the key roles of both GH and insulin-like growth factor-I (IGF-I) in human growth have been extended to include important effects on tissue maintenance and repair. More recent observations have revealed that this pathway has a negative side, as it has been implicated as a potential contributor to the development of several human cancers and has been linked to diminished lifespan in experimental animals. This brief review focuses on fundamental aspects of gene regulation by GH, as long-term hormonal effects all require changes in gene expression. Topics to be discussed include GH-stimulated signal transduction pathways, mechanisms of gene activation and gene repression by GH, and an analysis of control of IGF-I gene transcription by the GH-stimulated transcription factor, signal transducer and activator of transcription (Stat)5b. PMID:19626342

Chia, Dennis J.

2014-01-01

184

[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

185

Models, algorithms, and programs for phylogeny reconciliation Keywords: phylogeny; gene duplication, loss, horizontal gene transfer;  

E-print Network

, loss, horizontal gene transfer; parsimony; probability; reconciliation. 1. Institut des Sciences de l. Keywords: phylogeny; gene duplication, loss, horizontal gene transfer; parsimony; probability. Among them, gene duplication, transfer and loss are especially important to identify and differentiate

Paris-Sud XI, Université de

186

Networks of Gene Sharing among 329 Proteobacterial Genomes Reveal Differences in Lateral Gene Transfer  

E-print Network

transfer in proteobacteria is frequently mediated by conjugation. Key words: horizontal gene transfer, microbial evolution, symbionts. Introduction Lateral gene transfer (LGT or horizontal gene transfer gene transfer (LGT) is an important mechanism of natural variation among prokaryotes. Over the full

Ulm, Universität

187

Genes and gene networks implicated in aggression related behaviour.  

PubMed

Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour. PMID:25142712

Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

2014-10-01

188

Genetic ancestry modifies pharmacogenetic gene-gene interaction for asthma  

PubMed Central

Objective A recent admixture mapping analysis identified interleukin 6 (IL6) and IL6 receptor (IL6R) as candidate genes for inflammatory diseases. In the airways during allergic inflammation, IL6 signaling controls the production of proinflammatory and anti-inflammatory factors. In addition, albuterol, a commonly prescribed asthma therapy, has been shown to influence IL6 gene expression. Therefore, we reasoned that interactions between the IL6 and IL6R genes might be associated with bronchodilator drug responsiveness to albuterol in asthmatic patients. Methods Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls. Both family-based association tests and linear regression models were used to assess the association between individual SNPs and haplotypes with bronchodilator response. Gene–gene interactions were tested by using multiple linear regression analyses. Results No single SNP was consistently associated with drug response in all the three populations. However, on the gene level, we found a consistent IL6 and IL6R pharmacogenetic interaction in the three populations. This pharmacogenetic gene–gene interaction was contextual and dependent upon ancestry (racial background). This interaction resulted in higher drug response to albuterol in Latinos, but lower drug response in African-Americans. Herein, we show that there is an effect modification by ancestry on bronchodilator responsiveness to albuterol. Conclusion Genetic variants in the IL6 and IL6R genes act synergistically to modify the bronchodilator drug responsiveness in asthma and this pharmacogenetic interaction is modified by the genetic ancestry. PMID:19503017

Corvol, Harriet; De Giacomo, Anthony; Eng, Celeste; Seibold, Max; Ziv, Elad; Chapela, Rocio; Rodriguez-Santana, Jose R.; Rodriguez-Cintron, William; Thyne, Shannon; Watson, H. Geoffrey; Meade, Kelley; LeNoir, Michael; Avila, Pedro C.; Choudhry, Shweta; Burchard, Esteban Gonz!lez

2009-01-01

189

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

190

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

PubMed Central

Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD. Methods: The effect of gene/gene and gene/environment interaction related to late onset Alzheimer Disease (LOAD) was investigated in 153 subjects with LOAD and 302 gender matched controls enrolled in the Personalized Medicine Research Project, a population-based bio-repository. Genetic risk factors examined included APOE, ACE, OLR1,and CYP46 genes, and environmental factors included smoking, total cholesterol, LDL, HDL, triglycerides, C-reactive protein, blood pressure, statin use, and body mass index. Results: The mean age of the cases was 78.2 years and the mean age of the controls was 87.2 years. APOE4 was significantly associated with LOAD (OR=3.55, 95%CL=1.70, 7.45). Cases were significantly more likely to have ever smoked cigarettes during their life (49.3% versus 38.4%, p=0.03). The highest recorded blood pressure and pulse pressure measurements were significantly higher in the controls than the cases (all P<0.005). Although not statistically significant in this pilot study, the relationship of the following factors was associated in opposite directions with LOAD based on the presence of an APOE4 allele: obesity at the age of 50, ACE, OLR1, and CYP46. Conclusions: These pilot data suggest that gene/gene and gene/environment interactions may be important in LOAD, with APOE, a known risk factor for LOAD, affecting the relationship of ACE and OLR1 to LOAD. Replication with a larger sample size and in other racial/ethnic groups is warranted and the allele and risk factor frequencies will assist in choosing an appropriate sample size for a definitive study. PMID:20682755

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

2011-01-01

191

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

E-print Network

-Gene Interaction Network Affecting HDL Cholesterol Levels Li Ma1� , Christie Ballantyne2 , Ariel Brautbar2 report an analysis of gene-gene interactions affecting HDL cholesterol (HDL-C) levels in a candidate gene Hub in Gene-Gene Interaction Network Affecting HDL Cholesterol Levels. PLoS ONE 9(3): e92469. doi:10

Keinan, Alon

192

Detecting Highways of Horizontal Gene Transfer  

E-print Network

In a horizontal gene transfer (HGT) event, a gene is transferred between two species that do not have an ancestor-descendant relationship. Typically, no more than a few genes are horizontally transferred between any two ...

Bansal, Mukul S.

193

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

194

Gene Research Yields Insights into Ebola Virus  

MedlinePLUS

... please enable JavaScript. Gene Research Yields Insights Into Ebola Virus Strain tied to West Africa outbreak has ... 2014) Thursday, August 28, 2014 Related MedlinePlus Pages Ebola Genes and Gene Therapy THURSDAY, Aug. 28, 2014 ( ...

195

Genes and COPD  

PubMed Central

SYNOPSIS The marked variability in individual susceptibility to the detrimental effects of smoking on lung function and findings suggest a significant genetic contribution to COPD, which has been demonstrated in several studies. The only known genetic risk factor for COPD, severe alpha 1 antitrypsin (AAT) deficiency, explains only 1–2% of cases of this disease. Screening for severe AAT should be conducted in all cases of COPD. Intravenous augmentation therapy should be combined with currently recommended treatment modalities for COPD when treating patients with COPD due to severe AAT deficiency. There is considerable interest in identifying susceptibility genes for COPD unrelated to severe AAT deficiency, as this could greatly enhance current efforts to prevent, diagnose and treat this disease by yielding novel insights into its pathogenesis. Genome-wide association studies (GWAS) of COPD and its intermediate phenotypes (e.g., lung function measures) have identified novel susceptibility loci for COPD. Some of these susceptibility loci may also influence lung function in the general population (e.g., HHIP and FAM13A), while others may affect not only COPD but other diseases related to smoking behavior (e.g., CHRNA3/CHRNA5). Although much work remains to be done, recent advances and the implementation of novel approaches to study COPD genetics (e.g., sequencing) and epigenetics are promising, and could have a profound impact on COPD management. PMID:22793939

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

2012-01-01

196

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 !

BEGIN:VCARD VERSION:2.1 FN:Richard Benz N:Benz;Richard ORG:Wickliffe High School REV:2005-04-12 END:VCARD

1994-07-30

197

Nonadditive gene expression in polyploids.  

PubMed

Allopolyploidy involves hybridization and duplication of divergent parental genomes and provides new avenues for gene expression. The expression levels of duplicated genes in polyploids can show deviation from parental additivity (the arithmetic average of the parental expression levels). Nonadditive expression has been widely observed in diverse polyploids and comprises at least three possible scenarios: (a) The total gene expression level in a polyploid is similar to that of one of its parents (expression-level dominance); (b) total gene expression is lower or higher than in both parents (transgressive expression); and (c) the relative contribution of the parental copies (homeologs) to the total gene expression is unequal (homeolog expression bias). Several factors may result in expression nonadditivity in polyploids, including maternal-paternal influence, gene dosage balance, cis- and/or trans-regulatory networks, and epigenetic regulation. As our understanding of nonadditive gene expression in polyploids remains limited, a new generation of investigators should explore additional phenomena (i.e., alternative splicing) and use other high-throughput "omics" technologies to measure the impact of nonadditive expression on phenotype, proteome, and metabolome. PMID:25421600

Yoo, Mi-Jeong; Liu, Xiaoxian; Pires, J Chris; Soltis, Pamela S; Soltis, Douglas E

2014-11-23

198

Electro-acupuncture-mediated gene transfer  

Microsoft Academic Search

Gene transfer is one of the key techniques in gene therapy application. Unfortunately, it seems that by now, there still exists\\u000a no approach with simplicity, easiness, efficiency and safety. A novel method for gene delivery, electreacupuncture needle-mediated\\u000a gene transfer which combined the Chinese traditional acupuncture with modem gene introduction, was developed. With acupuncture\\u000a needle carrying exogenous gene into muscle after

Jifeng Zhang; Yangjun Qin; Aihua Fu; Jian Tang; Guanghui Chen; Dong Cai; Jisheng Han

1998-01-01

199

Ovarian interleukin-1-induced gene expression: privileged genes threshold theory.  

PubMed

Interleukin (IL)-1, an established mediator of inflammation, is also a mediator of ovulation (a cyclic inflammatory-like process). We have shown that IL-1 beta induces the in vitro expression of genes believed to play important role in ovulation (IL-1 beta itself, its receptors, IL-1 beta receptor antagonist, glucose transporters 1 and 3, secretory and cytosolic phospholipase A(2), prostaglandin endoperoxide synthase 1 and 2). These experiments suggest that the target genes are turned on over a relatively narrow IL-1 beta dose range. Moreover, IL-1 induces gene expression in what appears to be a hierarchical manner. We hypothesize that IL-1 induces a host of ovulation-associated genes, in a manner that is not only dose-dependent, but also obeys a certain hierarchical order, serving as 'check gates' in securing successful ovulation. PMID:11863390

Kol, S; Kehat, I; Adashi, E Y

2002-01-01

200

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...

201

Human copy number polymorphic genes  

PubMed Central

Recent large-scale genomic studies within human populations have identified numerous genomic regions as copy number variant (CNV). As these CNV regions often overlap coding regions of the genome, large lists of potentially copy number polymorphic genes have been produced that are candidates for disease association. Most of the current data regarding normal genic variation, however, has been generated using BAC or SNP microarrays, which lack precision especially with respect to exons. To address this, we assessed 2,790 candidate CNV genes defined from available studies in nine well-characterized HapMap individuals by designing a customized oligonucleotide microarray targeted specifically to exons. Using exon array comparative genomic hybridization (aCGH), we detected 255 (9%) of the candidates as true CNVs including 134 with evidence of variation over the entire gene. Individuals differed in copy number from the control by an average of 100 gene loci. Both partial- and whole-gene CNVs were strongly associated with segmental duplications (55 and 71%, respectively) as well as regions of positive selection. We confirmed 37% of the whole-gene CNVs using the fosmid end sequence pair (ESP) structural variation map for these same individuals. If we modify the end sequence pair mapping strategy to include low-sequence identity ESPs (98–99.5%) and ESPs with an everted orientation, we can capture 82% of the missed genes leading to more complete ascertainment of structural variation within duplicated genes. Our results indicate that segmental duplications are the source of the majority of full-length copy number polymorphic genes, most of the variant genes are organized as tandem duplications, and a significant fraction of these genes will represent paralogs with levels of sequence diversity beyond thresholds of allelic variation. In addition, these data provide a targeted set of CNV genes enriched for regions likely to be associated with human phenotypic differences due to copy number changes and present a source of copy number responsive oligonucleotide probes for future association studies. PMID:19287160

Bailey, J.A.; Kidd, J.M.; Eichler, E.E.

2009-01-01

202

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.

2014-01-01

203

Capillary electrophoresis of gene mutation.  

PubMed

This chapter illustrates the usefulness of capillary electrophoresis (CE) for the detection of gene mutation, i.e., point mutation, methylation, and microsatellite analysis. In order to provide a general description of the main results and challenges in the field, some relevant applications and reviews on CE of gene mutation are tabulated. Furthermore, some detailed experimental procedures are shown. Several CE methods of gene mutation detection were developed including the following: (1) single-strand conformation polymorphism with capillary electrophoresis; (2) SNaPshot analysis; (3) constant denaturant capillary electrophoresis; (4) microsatellite analysis; and (5) methylation analysis. PMID:18392579

Xu, Guowang; Shi, Xianzhe; Zhao, Chunxia; Yuan, Kailong; Weng, Qianfeng; Gao, Peng; Tian, Jing

2008-01-01

204

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

205

Human FOX gene family (Review).  

PubMed

Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25.3), and FOXF1-FOXC2-FOXL1 (16q24.1) loci are FOX gene clusters within the human genome. Members of FOX subfamilies A-G, I-L and Q were grouped into class 1 FOX proteins, while members of FOX subfamilies H and M-P were grouped into class 2 FOX proteins. C-terminal basic region within the FOX domain was the common feature of class 1 FOX proteins. FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. FOXA1 gene is amplified and over-expressed in esophageal and lung cancer. FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. Deregulation of FOX family genes leads to congenital disorders, diabetes mellitus, or carcinogenesis. Expression profiles, genetic alterations and epigenetic changes of FOX family genes as well as binding proteins and target genes of FOX family transcription factors should be comprehensively investigated to develop novel therapeutics and preventives for human diseases. PMID:15492844

Katoh, Masuko; Katoh, Masaru

2004-11-01

206

The REX Gene of Bacteriophage ? Is Really Two Genes  

PubMed Central

Complementation tests among previously isolated rex- mutants of bacteriophage ? reveal that the mutants comprise two complementation groups, designated rexA and rexB. Because rexB- mutants complement prm- mutants, but rexA- mutants do not, it appears that the rexA gene is coordinately controlled with the cI (repressor) gene under the direction of the PRM promoter, but that some other promoter is capable of directing the expression of rexB. PMID:6217105

Matz, Karen; Schmandt, Margaret; Gussin, Gary N.

1982-01-01

207

A comparison of the methyl reductase genes and gene products.  

PubMed

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. Comparisons of transcription initiation and termination sites and of the amino acid sequences of the mcr gene products are presented. Structural features conserved within the amino acid sequences are identified and a comparison of methyl reductase with other disulfide bond synthesizing enzymes is presented. PMID:2720489

Weil, C F; Sherf, B A; Reeve, J N

1989-01-01

208

Mutagenesis of diploid mammalian genes by gene entrapment  

Microsoft Academic Search

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

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

2006-01-01

209

Perspectives of gene combinations in phenotype presentation  

PubMed Central

Cells exhibit a variety of phenotypes in different stages and diseases. Although several markers for cellular phenotypes have been identified, gene combinations denoting cellular phenotypes have not been completely elucidated. Recent advances in gene analysis have revealed that various gene expression patterns are observed in each cell species and status. In this review, the perspectives of gene combinations in cellular phenotype presentation are discussed. Gene expression profiles change during cellular processes, such as cell proliferation, cell differentiation, and cell death. In addition, epigenetic regulation increases the complexity of the gene expression profile. The role of gene combinations and panels of gene combinations in each cellular condition are also discussed. PMID:23951387

Tanabe, Shihori

2013-01-01

210

GeneSigDB--a curated database of gene expression signatures  

PubMed Central

The primary objective of most gene expression studies is the identification of one or more gene signatures; lists of genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands of experimentally derived gene signatures are published, their potential value to the community is limited by their computational inaccessibility. Gene signatures are embedded in published article figures, tables or in supplementary materials, and are frequently presented using non-standard gene or probeset nomenclature. We present GeneSigDB (http://compbio.dfci.harvard.edu/genesigdb) a manually curated database of gene expression signatures. GeneSigDB release 1.0 focuses on cancer and stem cells gene signatures and was constructed from more than 850 publications from which we manually transcribed 575 gene signatures. Most gene signatures (n = 560) were successfully mapped to the genome to extract standardized lists of EnsEMBL gene identifiers. GeneSigDB provides the original gene signature, the standardized gene list and a fully traceable gene mapping history for each gene from the original transcribed data table through to the standardized list of genes. The GeneSigDB web portal is easy to search, allows users to compare their own gene list to those in the database, and download gene signatures in most common gene identifier formats. PMID:19934259

Culhane, Aedin C.; Schwarzl, Thomas; Sultana, Razvan; Picard, Kermshlise C.; Picard, Shaita C.; Lu, Tim H.; Franklin, Katherine R.; French, Simon J.; Papenhausen, Gerald; Correll, Mick; Quackenbush, John

2010-01-01

211

GeneSigDB--a curated database of gene expression signatures.  

PubMed

The primary objective of most gene expression studies is the identification of one or more gene signatures; lists of genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands of experimentally derived gene signatures are published, their potential value to the community is limited by their computational inaccessibility. Gene signatures are embedded in published article figures, tables or in supplementary materials, and are frequently presented using non-standard gene or probeset nomenclature. We present GeneSigDB (http://compbio.dfci.harvard.edu/genesigdb) a manually curated database of gene expression signatures. GeneSigDB release 1.0 focuses on cancer and stem cells gene signatures and was constructed from more than 850 publications from which we manually transcribed 575 gene signatures. Most gene signatures (n = 560) were successfully mapped to the genome to extract standardized lists of EnsEMBL gene identifiers. GeneSigDB provides the original gene signature, the standardized gene list and a fully traceable gene mapping history for each gene from the original transcribed data table through to the standardized list of genes. The GeneSigDB web portal is easy to search, allows users to compare their own gene list to those in the database, and download gene signatures in most common gene identifier formats. PMID:19934259

Culhane, Aedín C; Schwarzl, Thomas; Sultana, Razvan; Picard, Kermshlise C; Picard, Shaita C; Lu, Tim H; Franklin, Katherine R; French, Simon J; Papenhausen, Gerald; Correll, Mick; Quackenbush, John

2010-01-01

212

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

213

Systems Biophysics of Gene Expression  

E-print Network

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

Vilar, Jose M G

2013-01-01

214

Gene Cernan on Apollo 17  

NASA Video Gallery

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

215

Control of beta globin genes.  

PubMed

The developmental changes in expression of the beta like genes from embryonic to adult stages of human life are controlled at least partially at the level of the promoter sequences of these genes and their binding factors, and competition for promoter specific interactions with the locus control region (LCR). In recent years, the control of beta globin genes has also been investigated at the level of chromatin structure involving the chemical modification of histones and their remodelling by DNA dependent ATPases (SMARCA) containing protein complexes. The role of intergenic RNA is also being investigated with renewed interest. Although a wealth of information on the structure/function relationship of the LCR and globin promoters has been gathered over more than two decades, the fundamental nature of the control of these genes at the molecular level is still not completely understood. In the following pages, we intend to briefly describe the progress made in the field and discuss future directions. PMID:17910027

Mahajan, Milind C; Karmakar, Subhradip; Weissman, Sherman M

2007-11-01

216

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

217

Candidate genes in eating disorders.  

PubMed

Environmental influences, as well as biological and genetic factors influence risk for eating disorders. Family and twin studies have shown that eating disorders are familial and suggest the influence of genetic factors on their etiology. Positive associations have been observed for some candidate genes that have been studied (such as 5HT2A receptor gene); however, the field has been plagued by nonreplications. In this paper we review the extant association studies of eating disorders. PMID:12769810

Tozzi, Federica; Bulik, Cynthia M

2003-02-01

218

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

219

Adenoviral vectors for gene therapy  

Microsoft Academic Search

Vectors based on human adenovirus serotypes 2 (Ad2) and 5 (Ad5) of species C possess a number of features that have favored\\u000a their widespread employment for gene delivery both in?vitro and in?vivo. However, the use of recombinant Ad2- and Ad5-based\\u000a vectors for gene therapy also suffers from a number of disadvantages. These vectors possess the tropism of the parental viruses,

Joanne T. Douglas

2007-01-01

220

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

221

Gene Therapy for Erectile Dysfunction  

Microsoft Academic Search

Our current understanding of the underlying mechanisms of erectile dysfunction suggests that gene therapy will become a therapeutic\\u000a treatment in the near future. Over the past decade, erectile dysfunction has been ameliorated in animal models using viral-and\\u000a plasmid-based vectors. Genes that stimulate smooth muscle cell relaxation, such as neuronal, inducible, and endothelial nitric\\u000a oxide synthase, or that inhibit smooth muscle

Thomas R. Magee; Jacob Rajfer; Nestor F. Gonzalez-Cadavid

222

Predicting Gene Expression from Sequence  

Microsoft Academic Search

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

Michael A. Beer; Saeed Tavazoie

2004-01-01

223

Fusion genes in breast cancer  

E-print Network

Fusion genes in breast cancer Elizabeth M. Batty Clare College, University of Cambridge A dissertation submitted to the University of Cambridge in candidature for the degree of Doctor of Philosophy November 2010 ii... is the outcome of work done in collaboration except where specifically indicated in the text. It has not been submitted whole or in part for any other qualification at any other University. iii Summary Fusion genes in breast cancer Elizabeth Batty...

Batty, Elizabeth

2012-02-07

224

DNA methylation and gene expression.  

PubMed Central

A large body of evidence demonstrates that DNA methylation plays a role in gene regulation in animal cells. Not only is there a correlation between gene transcription and undermethylation, but also transfection experiments clearly show that the presence of methyl moieties inhibits gene expression in vivo. Furthermore, gene activation can be induced by treatment of cells with 5-azacytidine, a potent demethylating agent. Methylation appears to influence gene expression by affecting the interactions with DNA of both chromatin proteins and specific transcription factors. Although methylation patterns are very stable in somatic cells, the early embryo is characterized by large alterations in DNA modification. New methodologies are now becoming available for studying methylation at this stage and in the germ line. During development, tissue-specific genes undergo demethylation in their tissue of expression. In tissue culture cells this process is highly specific and appears to involve an active mechanism which takes place in the absence of DNA replication. The X chromosome undergoes inactivation during development; this is accompanied by de novo methylation, which appears necessary to stably maintain its silent state. As opposed to the programmed changes in DNA methylation which occur in vivo, immortalized tissue culture cells demonstrate alterations in DNA modification which take place over a long time scale and which appear to be the result of selective pressures present during the growth of these cells in culture. PMID:1943996

Razin, A; Cedar, H

1991-01-01

225

Hydrogels for Lentiviral Gene Delivery  

PubMed Central

Introduction Gene delivery from hydrogel biomaterials provides a fundamental tool for a variety of clinical applications including regenerative medicine, gene therapy for inherited disorders and drug delivery. The high water content and mild gelation conditions of hydrogels support their use for gene delivery by preserving activity of lentiviral vectors and acting to shield vectors from any host immune response. Areas Covered Strategies to control lentiviral entrapment within and retention/release from hydrogels are reviewed. We discuss the ability of hydrogel design parameters to control the transgene expression profile and the capacity of hydrogels to protect vectors from (and even modulate) the host immune response. Expert Opinion Delivery of genetic vectors from scaffolds provides a unique opportunity to capitalize on the potential synergy between the biomaterial design for cell processes and gene delivery. Hydrogel properties can be tuned to directly control the events that determine the tissue response to controlled gene delivery, which include the extent of cell infiltration, preservation of vector activity and vector retention. While some design parameters have been identified, numerous opportunities for investigation are available in order to develop a complete model relating the biomaterial properties and host response to gene delivery. PMID:23347508

Seidlits, Stephanie K.; Gower, R. Michael; Shepard, Jaclyn A.; Shea, Lonnie D.

2013-01-01

226

Gene Therapy in Heart Failure  

PubMed Central

With increasing knowledge of basic molecular mechanisms governing the development of heart failure (HF), the possibility of specifically targeting key pathological players is evolving. Technology allowing for efficient in vivo transduction of myocardial tissue with long-term expression of a transgene enables translation of basic mechanistic knowledge into potential gene therapy approaches. Gene therapy in HF is in its infancy clinically with the predominant amount of experience being from animal models. Nevertheless, this challenging and promising field is gaining momentum as recent preclinical studies in larger animals have been carried out and, importantly, there are 2 newly initiated phase I clinical trials for HF gene therapy. To put it simply, 2 parameters are needed for achieving success with HF gene therapy: (1) clearly identified detrimental/beneficial molecular targets; and (2) the means to manipulate these targets at a molecular level in a sufficient number of cardiac cells. However, several obstacles do exist on our way to efficient and safe gene transfer to human myocardium. Some of these obstacles are discussed in this review; however, it primarily focuses on the molecular target systems that have been subjected to intense investigation over the last decade in an attempt to make gene therapy for human HF a reality. PMID:18566312

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

2008-01-01

227

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

228

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

229

Shared gene expression in distinct neurons expressing common selector genes  

PubMed Central

Expression of the mec-3/unc-86 selector gene complex induces the differentiation of the touch receptor neurons (TRNs) of Caenorhabditis elegans. These genes are also expressed in another set of embryonically derived mechanosensory neurons, the FLP neurons, but these cells do not share obvious TRN traits or proteins. We have identified ?300 genes in each cell type that are up-regulated at least threefold using DNA microarrays. Twenty-three percent of these genes are up-regulated in both cells. Surprisingly, some of the common genes had previously been identified as TRN-specific. Although the FLP neurons contain low amounts of the mRNAs for these TRN genes, they do not have detectable proteins. These results suggest that transcription control is relatively inexact but that these apparent errors of transcription are tolerated and do not alter cell fate. Previous studies showed that loss of the EGL-44 and EGL-46 transcription factors cause the FLP neurons to acquire TRN-like traits. Here, we show that similar changes occur (e.g., the expression of both the TRN mRNAs and proteins) when the FLP neurons ectopically express the auxiliary transcription factor ALR-1 (Aristaless related), which ensures, but does not direct, TRN differentiation. Thus, the FLP neurons can acquire a TRN-like fate but use multiple levels of regulation to ensure they do not. Our data indicate that expression of common master regulators in different cell types can result in inappropriate expression of effector genes. This misexpression makes these cells vulnerable to influences that could cause them to acquire alternative fates. PMID:22087002

Topalidou, Irini; Chalfie, Martin

2011-01-01

230

Evolution of MADS-Box Gene Induction by FLO\\/LFY Genes  

Microsoft Academic Search

.   Some MADS-box genes function as floral homeotic genes. The Arabidopsis LFY gene is a positive regulator of floral homeotic genes, and homologs of the FLO\\/LFY gene family in other angiosperms and gymnosperms are likely to have a similar function. To investigate the origin of the\\u000a floral homeotic gene regulatory cascade involving the FLO\\/LFY gene, FLO\\/LFY homologs were cloned from

Saiko Himi; Ryosuke Sano; Tomoaki Nishiyama; Takako Tanahashi; Masahiro Kato; Kunihiko Ueda; Mitsuyasu Hasebe

2001-01-01

231

[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

232

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function  

E-print Network

, we will explore the functions and roles of plastid encoded genes in metabolism and their evolutionary take place in plastids, including synthesis of starch, fatty acids, pigments and amino acids (reviewed

dePamphilis, Claude

233

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

234

Genome-Wide Comparative Gene Family Classification  

PubMed Central

Correct classification of genes into gene families is important for understanding gene function and evolution. Although gene families of many species have been resolved both computationally and experimentally with high accuracy, gene family classification in most newly sequenced genomes has not been done with the same high standard. This project has been designed to develop a strategy to effectively and accurately classify gene families across genomes. We first examine and compare the performance of computer programs developed for automated gene family classification. We demonstrate that some programs, including the hierarchical average-linkage clustering algorithm MC-UPGMA and the popular Markov clustering algorithm TRIBE-MCL, can reconstruct manual curation of gene families accurately. However, their performance is highly sensitive to parameter setting, i.e. different gene families require different program parameters for correct resolution. To circumvent the problem of parameterization, we have developed a comparative strategy for gene family classification. This strategy takes advantage of existing curated gene families of reference species to find suitable parameters for classifying genes in related genomes. To demonstrate the effectiveness of this novel strategy, we use TRIBE-MCL to classify chemosensory and ABC transporter gene families in C. elegans and its four sister species. We conclude that fully automated programs can establish biologically accurate gene families if parameterized accordingly. Comparative gene family classification finds optimal parameters automatically, thus allowing rapid insights into gene families of newly sequenced species. PMID:20976221

Frech, Christian; Chen, Nansheng

2010-01-01

235

Horizontal gene transfer in eukaryotic evolution  

Microsoft Academic Search

Horizontal gene transfer (HGT; also known as lateral gene transfer) has had an important role in eukaryotic genome evolution, but its importance is often overshadowed by the greater prevalence and our more advanced understanding of gene transfer in prokaryotes. Recurrent endosymbioses and the generally poor sampling of most nuclear genes from diverse lineages have also complicated the search for transferred

Jeffrey D. Palmer; Patrick J. Keeling

2008-01-01

236

Horizontal gene transfer, genome innovation and evolution  

Microsoft Academic Search

To what extent is the tree of life the best representation of the evolutionary history of microorganisms? Recent work has shown that, among sets of prokaryotic genomes in which most homologous genes show extremely low sequence divergence, gene content can vary enormously, implying that those genes that are variably present or absent are frequently horizontally transferred. Traditionally, successful horizontal gene

J. Peter Gogarten; Jeffrey P. Townsend

2005-01-01

237

Massive Horizontal Gene Transfer in Bdelloid Rotifers  

Microsoft Academic Search

Horizontal gene transfer in metazoans has been documented in only a few species and is usually associated with endosymbiosis or parasitism. By contrast, in bdelloid rotifers we found many genes that appear to have originated in bacteria, fungi, and plants, concentrated in telomeric regions along with diverse mobile genetic elements. Bdelloid proximal gene-rich regions, however, appeared to lack foreign genes,

Eugene A. Gladyshev; Matthew S. Meselson; Irina R. Arkhipova

2008-01-01

238

Modulation of Gene Expression Made Easy  

Microsoft Academic Search

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

Christian Solem; Peter Ruhdal Jensen

2002-01-01

239

Comparative genomic analysis of prion genes  

Microsoft Academic Search

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

Marko Premzl; Vera Gamulin

2007-01-01

240

What is Gene Therapy? Rafael Yez  

E-print Network

What is Gene Therapy? Rafael Yáñez rafael.yanez@rhul.ac.uk Rare Disease Day @ Royal Holloway 28th therapy strategies: "random" integration transgene transgene * #12;Gene Therapy successes;Gene therapy strategies: episomal vectors transgene transgene * #12;DNA repair #12;Gene therapy

Royal Holloway, University of London

241

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

242

Gene therapy for human hemoglobinopathies.  

PubMed

Gene transfer of human globin genes into human pluripotent stem cells via viral vectors may soon be realized. The high level of globin gene expression believed to be required for the treatment of severe hemoglobinopathies necessitated the inclusion of cis-acting sequences (LCR). Retroviral vectors containing the LCR elements are prone to rearrangement, low titer, and poor expression. Inclusion of a "minilocus" containing four HS sites linked to a globin gene resulted in higher expression in transplanted mice, but rearrangement of the provirus still occurs, and it is unclear what significance these experiments have with regard to human marrow stem cell transduction. Recombinant AAV is among the newest of genetic transfer vectors. This once obscure virus possesses unique properties that distinguish it from all other vectors. Its major advantage is the lack of pathogenicity in humans. Wild-type AAV has the unusual ability to selectively integrate into the mammalian genome at a specific region, thus reducing the concern for genomic disruption and insertional mutagenesis. The ability of AAV to carry regulatory elements without interference from the viral template may enable greater control of transferred gene expression. Disadvantages currently include the inferior packaging systems which yield low numbers of recombinant virions which are contaminated with wild-type adenovirus. The small AAV genome that can be packaged (approximately 5 kb) rules out its use for transfer of larger genes. Recombinant AAV viruses do not appear to demonstrate the same site-specific genomic integration as wild-type viruses. Elucidation of the mechanism of site-specific integration should prove useful in the development of safe vectors for gene transfer as well as provide insight into the nature of DNA recombination in humans. PMID:8234372

Walsh, C E; Liu, J M; Miller, J L; Nienhuis, A W; Samulski, R J

1993-12-01

243

Hox gene dysregulation in acute myeloid leukemia.  

PubMed

In humans, class I homeobox genes (HOX genes) are distributed in four clusters. Upstream regulators include transcriptional activators and members of the CDX family of transcription factors. HOX genes encode proteins and need cofactor interactions, to increase their specificity and selectivity. HOX genes contribute to the organization and regulation of hematopoiesis by controlling the balance between proliferation and differentiation. Changes in HOX gene expression can be associated with chromosomal rearrangements generating fusion genes, such as those involving MLL and NUP98, or molecular defects, such as mutations in NPM1 and CEBPA for example. Several miRNAs are involved in the control of HOX gene expression and their expression correlates with HOX gene dysregulation. HOX genes dysregulation is a dominant mechanism of leukemic transformation. A better knowledge of their target genes and the mechanisms by which their dysregulated expression contributes to leukemogenesis could lead to the development of new drugs. PMID:24559452

De Braekeleer, Etienne; Douet-Guilbert, Nathalie; Basinko, Audrey; Le Bris, Marie-Josée; Morel, Frédéric; De Braekeleer, Marc

2014-02-01

244

Integrating heterogeneous gene expression data for gene regulatory network modelling.  

PubMed

Gene regulatory networks (GRNs) are complex biological systems that have a large impact on protein levels, so that discovering network interactions is a major objective of systems biology. Quantitative GRN models have been inferred, to date, from time series measurements of gene expression, but at small scale, and with limited application to real data. Time series experiments are typically short (number of time points of the order of ten), whereas regulatory networks can be very large (containing hundreds of genes). This creates an under-determination problem, which negatively influences the results of any inferential algorithm. Presented here is an integrative approach to model inference, which has not been previously discussed to the authors' knowledge. Multiple heterogeneous expression time series are used to infer the same model, and results are shown to be more robust to noise and parameter perturbation. Additionally, a wavelet analysis shows that these models display limited noise over-fitting within the individual datasets. PMID:21948152

Sîrbu, Alina; Ruskin, Heather J; Crane, Martin

2012-06-01

245

Concepts of Marker Genes for Plants  

Microsoft Academic Search

\\u000a Marker genes, more exactly named selectable marker genes, are absolutely essential for the production of transgenic plants.\\u000a They are required to identify, to “mark” the introduced genes and finally to enable the selective growth of transformed cells.\\u000a These marker genes are co-transformed with the gene of interest (GOI); they are linked to the GOI and therefore remain in\\u000a the transformed

Josef Kraus

246

Review of Weighted Gene Coexpression Network Analysis  

Microsoft Academic Search

\\u000a We survey key concepts of weighted gene coexpression network analysis (WGCNA), also known as weighted correlation network\\u000a analysis, and related data analysis strategies. We describe the construction of a weighted gene coexpression network from\\u000a gene expression data, identification of network modules and integration of external data such as gene ontology information\\u000a and clinical phenotype data. We review Differential Weighted Gene

Tova Fuller; Peter Langfelder; Angela Presson; Steve Horvath

247

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

248

Evolutionary Dynamics of Oncogenes and Tumor Suppressor Genes: Higher Intensities of Purifying Selection than Other Genes  

Microsoft Academic Search

Oncogenes and tumor suppressor genes (hereafter referred to as ''cancer genes'') result in cancer when they experience substitutions that prevent or distort their normal function. We examined evolutionary pressures acting on cancer genes and other classes of disease-related genes and compared our results to analyses of genes without known association to disease. We compared synonymous and nonsynonymous substitution rates in

Michael A. Thomas; Benjamin Weston; Moltu Joseph; Wenhua Wu; Anton Nekrutenko; Peter J. Tonellato

2003-01-01

249

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

250

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

E-print Network

in many ways, especially in Gene Therapy [18]. Identifying gene function in prokaryotes is much easierNeural 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

Bonner, Anthony

251

Towards an accurate identification of mosaic genes and partial horizontal gene transfers  

E-print Network

Towards an accurate identification of mosaic genes and partial horizontal gene transfers Alix Boc). An effective identification of mosaic genes and detection of corresponding partial horizontal gene transfers- itional) horizontal gene transfers detected by any HGT inferring method. While working on a full- genome

Makarenkov, Vladimir

252

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

253

Ontogeny of erythroid gene expression  

PubMed Central

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

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

2013-01-01

254

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

255

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

256

Systems biophysics of gene expression.  

PubMed

Gene expression is a process central to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges to the use of traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses. PMID:23790365

Vilar, Jose M G; Saiz, Leonor

2013-06-18

257

Duplicated fie Genes in Maize  

PubMed Central

Two maize genes with predicted translational similarity to the Arabidopsis FIE (Fertilization-Independent Endosperm) protein, a repressor of endosperm development in the absence of fertilization, were cloned and analyzed. Genomic sequences of fie1 and fie2 show significant homology within coding regions but none within introns or 5? upstream. The fie1 gene is expressed exclusively in the endosperm of developing kernels starting at ?6 days after pollination. fie1 is an imprinted gene showing no detectable expression of the paternally derived fie1 allele during kernel development. Conversely, fie2 is expressed in the embryo sac before pollination. After pollination, its expression persists, predominantly in the embryo and at lower levels in the endosperm. The paternal fie2 allele is not expressed early in kernel development, but its transcription is activated at 5 days after pollination. fie2 is likely to be a functional ortholog of the Arabidopsis FIE gene, whereas fie1 has evolved a distinct function. The maize FIE2 and sorghum FIE proteins form a monophyletic group, sharing a closer relationship to each other than to the FIE1 protein, suggesting that maize fie genes originated from two different ancestral genomes. PMID:12566582

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

2003-01-01

258

Gene Therapy for Pituitary Tumors  

PubMed Central

Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas. PMID:16457646

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

2009-01-01

259

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

260

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

261

Gene Expression Studies in Mosquitoes  

PubMed Central

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

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

2009-01-01

262

Horizontal gene transfer in plants  

Microsoft Academic Search

Abstract Horizontal,gene,transfer,(HGT) has,played,a major,role in bacterial,evolution,and,is fairly common,in certain unicellular eukaryotes. However, the prevalence and importance,of HGT in the,evolution,of multicellular eukaryotes,remain,unclear.,Recent,studies,indicate that plant,mitochondrial,genomes,are unusually,active in HGT relative,to,all other,organellar,and,nuclear genomes,of multicellular,eukaryotes.,Although,little about the mechanisms of plant HGT is known, several studies,have,implicated,parasitic,plants,as both,donors and,recipients,of,mitochondrial,genes.,Most,cases uncovered,thus,far have,involved,a single,transferred gene per species; however, recent work has uncovered a,case,of massive,HGT in Amborella,trichopoda,in- volving,acquisition,of at least

A. O. Richardson; J. D. Palmer

2006-01-01

263

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

264

Gene therapy for Fabry disease.  

PubMed

Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha-galactosidase A (alpha-Gal A). Lack of this lysosomal hydrolase results in the accumulation of galactose-terminal glycosphingolipids in a number of tissues, including vascular endothelial cells. Premature death is predominantly associated with vascular conditions of the heart, kidneys and brain. Historically, treatment has largely been palliative. Alternative treatments for many lysosomal storage diseases have been developed, including allogeneic organ and bone marrow transplantation, enzyme replacement therapy, and gene therapy. Significant clinical risks still exist with allogeneic transplantations. Alpha-Gal A enzyme replacement therapy has been implemented in clinical trials. This approach has been effective but may have limitations for long-term systemic or cost-effective correction. As an alternative, gene therapy approaches, involving a variety of gene delivery systems, have been pursued for the amelioration of Fabry disease. Fabry disease is a compelling disorder for gene therapy, as target cells are readily accessible and relatively low levels of enzyme correction may suffice to reduce storage. Importantly, metabolic cooperativity effects are also manifested in Fabry disease, wherein corrected cells secrete alpha-Gal A that can correct bystander cells. In addition, a broad therapeutic window probably exists, and mouse models of Fabry disease have been generated to assist studies. As an example, in vitro and in vivo studies using alpha-Gal A-transduced haematopoietic cells from Fabry mice have demonstrated enzymatic correction of recipient cells and dissemination of alpha-Gal A upon transplantation, leading to reduced lipid storage in a number of clinically relevant organs. This corrective enzymatic effect has recently been shown to be even further enhanced upon pre-selection of therapeutically transduced cells prior to transplantation. This review will briefly detail current gene delivery methods and summarize results to date in the context of gene therapy for Fabry disease. PMID:11758676

Siatskas, C; Medin, J A

2001-01-01

265

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

266

Gene therapy in clinical medicine  

PubMed Central

Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. Interest in this therapeutic modality is based on the potential for treatment and cure of some of the most malignant and devastating diseases affecting humans. Over the next decade, the relevance of gene therapy to medical practices will increase and it will become important for physicians to understand the basic principles and strategies that underlie the therapeutic intervention. This report reviews the history, basic strategies, tools, and several current clinical paradigms for application. PMID:15466989

Selkirk, S

2004-01-01

267

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

268

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

269

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

E-print Network

gene of E. coli, which encodes an essentialtide(s); ORF, open reading frame; PAC, P1 artificial; Protein expression from ARD-1 cDNA in E. coli resultsSDS, sodium dodecyl sulfate; snRNP, small nuclear Abstract ARD-1 is an endoribonuclease identified initially as the product of a human cDNA that complements

Trinkle-Mulcahy, Laura

270

Gene2Oligo: oligonucleotide design for in vitro gene synthesis  

PubMed Central

There is substantial interest in implementing a bioinformatics tool that allows the design of oligonucleotides to support the development of in vitro gene synthesis. Current protocols to make long synthetic DNA molecules rely on the in vitro assembly of a set of short oligonucleotides, either by ligase chain reaction (LCR) or by assembly PCR. Ideally, such oligonucleotides should represent both strands of the final DNA molecule. They should be adjacent on the same strand and overlap the complementary oligonucleotides from the second strand to ensure good hybridization during assembly. This implies that the thermodynamic properties of each oligonucleotide have to be consistent across the set. Furthermore, any given oligonucleotide has to be totally specific to its target to avoid the creation of incorrectly assembled sequences. We have developed Gene2Oligo (http://berry.engin.umich.edu/gene2oligo/), a web-based tool that divides a long input DNA sequence into a set of adjacent oligonucleotides representing both DNA strands. The length of the oligonucleotides is dynamically optimized to ensure both the specificity and the uniform melting temperatures necessary for in vitro gene synthesis. We have successfully designed and used a set of oligonucleotides to synthesize the Saccharomyces cerevisiae cytochrome b5 by using both LCR and assembly PCR. PMID:15215375

Rouillard, Jean-Marie; Lee, Woonghee; Truan, Gilles; Gao, Xiaolian; Zhou, Xiaochuan; Gulari, Erdogan

2004-01-01

271

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

E-print Network

cereus. The nucleotide sequence of 2.7 kb of DNA flanking the zwittermicin A self-resistance gene, zmaR, from B. cereus UW85 revealed three open reading frames (ORFs). Of these ORFs, two had sequence A is an aminopolyol antibiotic produced by B. cereus and B. thuringiensis (Stabb et al., 1994; He Zwittermicin

Handelsman, Jo

272

Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish  

Microsoft Academic Search

We have generated several hundred lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation. Since many tumor suppressor genes are recessive lethals, we screened our colony for lines that display early mortality and\\/or gross evidence of tumors. We identified 12 lines with elevated cancer incidence. Fish from these lines develop malignant peripheral nerve sheath tumors, and

Adam Amsterdam; Kirsten C Sadler; Kevin Lai; Sarah Farrington; Roderick T Bronson; Jacqueline A Lees; Nancy Hopkins

2004-01-01

273

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

E-print Network

found in the trout and are presumed to be the result of a genome duplication event. © 2000 Elsevier of vertebrates: Chiloscyllium punctatum (shark), Amia calva (bowfin), Salmo trutta (trout), Latimeria chalumnae-Koyanagi et al., 2000). Broad taxonomic sampling enhances any evolutionary Gene and genome duplications

Hedges, Blair

274

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

275

Vertebrate protamine gene evolution I. Sequence alignments and gene structure  

Microsoft Academic Search

Summary The availability of the amino acid sequence for nine different mammalian P1 family protamines and the revised amino acid sequence of the chicken protamine galline (Oliva and Dixon 1989) reveals a much close relationship between mammalian and avian protamines than was previously thought (Nakano et al. 1976). Dot matrix analysis of all protamine genes for which genomic DNA or

Rafael Oliva; Gordon H. Dixon

1990-01-01

276

Global gene disruption in human cells to assign genes to phenotypes  

E-print Network

Insertional mutagenesis in a haploid background can disrupt gene function[superscript 1]. We extend our earlier work by using a retroviral gene-trap vector to generate insertions in >98% of the genes expressed in a human ...

Ploegh, Hidde

277

Using co-expression to redefine functional gene sets for gene set enrichment analysis  

E-print Network

Manually curated gene sets related to a biological function often contain genes that are not tightly co-regulated transcriptionally. which obscures the evidence of coordinated differential expression of these gene sets in ...

Kodysh, Yuliya

2007-01-01

278

Essential genes of a minimal bacterium  

PubMed Central

Mycoplasma genitalium has the smallest genome of any organism that can be grown in pure culture. It has a minimal metabolism and little genomic redundancy. Consequently, its genome is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. Using global transposon mutagenesis, we isolated and characterized gene disruption mutants for 100 different nonessential protein-coding genes. None of the 43 RNA-coding genes were disrupted. Herein, we identify 382 of the 482 M. genitalium protein-coding genes as essential, plus five sets of disrupted genes that encode proteins with potentially redundant essential functions, such as phosphate transport. Genes encoding proteins of unknown function constitute 28% of the essential protein-coding genes set. Disruption of some genes accelerated M. genitalium growth. PMID:16407165

Glass, John I.; Assad-Garcia, Nacyra; Alperovich, Nina; Yooseph, Shibu; Lewis, Matthew R.; Maruf, Mahir; Hutchison, Clyde A.; Smith, Hamilton O.; Venter, J. Craig

2006-01-01

279

Concerted evolution of human amylase genes  

SciTech Connect

Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, the authors have identified two pancreatic amylase gene and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, duplications, gene conversion, and unequal crossover events have resulted in a very high level of sequence similarity among human amylase gene copies. To identify sequence elements involved in tissue-specific expression and hormonal regulation, the promoter regions of the human amylase genes were sequenced and compared with those of the corresponding mouse genes. The promoters of the human and mouse pancreatic amylase genes are highly homologous between nucleotide - 160 and the cap site. Two sequence elements througth to influence pancreas-specific expression of the rodent genes are present in the human genes. In contrast, similarity in the 5' lanking sequences of the salivary amylase genes is limited to several short sequence elements whose positions and orientations differ in the two species. Some of these sequence elements are also associated with other parotid-specific genes and may be involved in their tissue-specific expression. A glucocorticoid response element and a general enhancer element are closely associated in several of the amylase promoters.

Gumucio, D.L.; Wiebauer, K.; Caldwell, R.M.; Samuelson, L.C.; Meisler, M.H.

1988-03-01

280

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

Microsoft Academic Search

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

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

2001-01-01

281

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

282

The Callipyge gene of sheep  

Microsoft Academic Search

The callipyge locus is characterized by a novel form of nonmendelian inheritance, referred to as polar overdominance. Acquiring a molecular understanding of this novel biological phenomenon will contribute to the understanding of complex traits, including those in the human. The proposed strategy to clone the callipyge gene is one of positional candidate cloning. This strategy aims at exploiting (a) the

N. E. Cockett; S. Berghams; M. C. Beckers; T. L. Shay; S. P. Jackson; G. D. Snowder; M. Georges

1997-01-01

283

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

284

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.

285

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

286

Molecular Genetics: Proteins and Genes  

NSDL National Science Digital Library

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

Tweed, Susan K.

2009-05-22

287

Targetability of Human Disease Genes  

Microsoft Academic Search

The availability of complete genome sequences and the wealth of large-scale biological datasets provide an un- precedented opportunity to elucidate the genetic basis of human diseases. Therapeutically relevant targets should be both 'druggable' and 'disease modifying'. In this review we examine the application of computational biology towards the ex- ploration of druggability, targetability and evolutionary conservation of human disease genes.

Meena K. Sakharkar; Kishore R. Sakharkar

288

Deconstructing cell determination: proneural genes  

E-print Network

atonal provides the competence to form chordotonal organs (a type of internal sense organs the difference between scute-dependent and atonal-dependent organs. One such gene is cut, which is expressed in achaete and scute- dependent organs, but not in atonal-dependent organs, and which is responsible

Montpellier II, Université

289

Enzyme evolution beyond gene duplication  

PubMed Central

Understanding the evolution of enzyme function after gene duplication has been a major goal of molecular biologists, biochemists and evolutionary biologists alike, for almost half a century. In contrast, the impact that horizontal gene transfer (HGT) has had on the evolution of enzyme specialization and the assembly of metabolic networks has just started to being investigated. Traditionally, evolutionary studies of enzymes have been limited to either the function of enzymes in vitro, or to sequence variability at the population level, where in almost all cases the starting conceptual framework embraces gene duplication as the mechanism responsible for the appearance of genetic redundancy. Very recently, we merged comparative phylogenomics, detection of selection signals, enzyme kinetics, X-ray crystallography and computational molecular dynamics, to characterize the sub-functionalization process of an amino acid biosynthetic enzyme prompted by an episode of HGT in bacteria. Some of the evolutionary implications of these functional studies, including a proposed model of enzyme specialization independent of gene duplication, are developed in this commentary. PMID:24251070

Noda-Garcia, Lianet; Barona-Gomez, Francisco

2013-01-01

290

Reverse engineering gene regulatory networks  

Microsoft Academic Search

Statistical models for reverse engineering gene regulatory networks are surveyed in this article. To provide readers with a system-level view of the modeling issues in this research, a graphical modeling framework is proposed. This framework serves as the scaffolding on which the review of different models can be systematically assembled. Based on the framework, we review many existing models for

Yufei Huang; Isabel M. Tienda-Luna; Yufeng Wang

2009-01-01

291

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

292

Horizontal gene transfer in chromalveolates  

Microsoft Academic Search

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

Tetyana Nosenko; Debashish Bhattacharya

2007-01-01

293

Genes and Syndromic Hearing Loss.  

ERIC Educational Resources Information Center

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

Keats, Bronya J. B.

2002-01-01

294

RESEARCH COMMUNICATION Targeting genes for  

E-print Network

in turn used to generate chimeric mice. In these chimeras, somatic cells derived from the ES cells embryo-derived stem (ES) cell. Cells containing the modification are placed in an embryonic environmentRESEARCH COMMUNICATION Targeting genes for self-excision in the germ line Michaeline Bunting,1

Capecchi, Mario R.

295

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

296

Hevea gene pool for breeding  

Microsoft Academic Search

The conservation and utilization of allied gene resources is vital for the improvement of crop species. Rubber has been an undeniably beneficial commodity for the past 100 years. Progress in yield improvement over 70 years resulted in primary and hybrid clones with exceptional yielding abilities. The extension of Hevea to marginal areas necessitated breeding of new clones with resistance to

P. M. Priyadarshan; P. de S. Goncalves

2003-01-01

297

Third Edition, Gene Fusion System  

E-print Network

Third Edition, Revision 2 18-1123-20 GST Gene Fusion System #12;PROTEIN DATA BANK ADVISORY NOTICE Library of Medicine, and the United States Department of Energy under Contract No. DE-AC02- 76CH00016. Any, the National Institutes of Health, the Department of Energy, the U.S. Government, BNL or its Operator

Lai, Zhi-Chun

298

Gene selection and classification of microarray data using random forest  

Microsoft Academic Search

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

Ramón Díaz-uriarte; Sara Alvarez De Andrés

2006-01-01

299

Immune response genes in uveitis.  

PubMed

Uveitis is defined as an intraocular inflammation induced by different etiologies. Though the precise pathogenesis is still unknown, accumulating evidence shows that both innate and adaptive immune responses may be predominant mechanisms involved in the development of uveitis. Toll-like receptors have been shown to be expressed in the human eye and play an important role in infectious uveitis. The NOD proteins, expressed mainly in the cytosol by APCs, recognize the products of bacteria and participate in the development of uveitis. HLA genes have been associated with some uveitis entities, including acute anterior uveitis (HLA-B27), Behcet disease (HLA-B51), birdshot retinochoroidopathy (HLA-A29), Vogt-Koyanagi-Harada syndrome (HLA-DR4), sarcoidosis, sympathetic ophthalmia, juvenile idiopathic arthritis, tubulointerstitial nephritis and uveitis (TINU) syndrome, and pars planitis (HLA-DR15). The exact mechanism whereby certain HLA genes predispose to a certain uveitis entity has not yet been elucidated. In addition, several studies have demonstrate that polymorphisms in certain immune response genes, such as tumor necrosis factor (TNF), MHC class I polypeptide-related sequence A (MICA), interleukin-1 (IL-1), and some chemokines, may contribute to the development of human uveitis. Polymorphisms in the gene coding for the costimulatory molecule known as cytotoxic T-lymphocyte antigen 4 (CTLA-4) were recently found in Chinese patients with VKH syndrome but not in patients with Behcet disease. Further developments in the unraveling of immune response genes may lead to a better understanding of human uveitis and will hopefully allow the development of novel treatment regimes. PMID:19657978

Du, Liping; Kijlstra, Aize; Yang, Peizeng

2009-01-01

300

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

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

2013-01-01

301

Brassinosteroid-Regulated Gene Expression  

PubMed Central

Major brassinosteroid (BR) effects such as BR-induced growth are mediated through genomic pathways because RNA synthesis inhibitors and protein synthesis inhibitors interfere with these processes. A limited number of BR-regulated genes have been identified hitherto. The majority of genes (such as BRU1, CycD3, Lin6, OPR3, and TRIP-1) were identified by comparisons of BR-treated versus control-treated plants. However, altered transcript levels after BR application may not reflect normal physiological events. A complementary approach is the comparison of BR-deficient plants versus wild-type plants. No artificial treatments interfere with endogenous signaling pathways, but a subset of phenotypic alterations of phytohormone-deficient plants most probably is secondary. To identify genes that are subject to direct BR regulation, we analyzed CPD antisense and dwf1-6 (cbb1) mutant plants. Both show a mild phenotype in comparison with BR-deficient mutants such as cpd/cbb3, det2, and dwf4. Plants were grown under two different environments to filter out BR deficiency effects that occur only at certain environmental conditions. Finally, we established expression patterns after BR treatment of wild-type and dwf1-6 (cbb1) plants. Ideally, a BR-regulated gene displays a dose-response relationship in such a way that a gene with decreased transcript levels in BR-deficient plants is BR inducible and vice versa. Expression profile analysis of above ground part of plants was performed by means of Affymetrix Arabidopsis Genome Arrays. PMID:12114578

Mussig, Carsten; Fischer, Sabine; Altmann, Thomas

2002-01-01

302

WNT and FGF gene clusters (review).  

PubMed

Mouse mammary tumor virus (MMTV) is a retrovirus, activating Wnt genes (Wnt1/int-1, Wnt3/int-4, Wnt10b), Fgf genes (Fgf3/int-2, Fgf4, Fgf8) and other genes (Notch4/int-3, Eif3s6/int-6) due to proviral integration. Among 19 WNT genes, WNT3 and WNT14B genes are clustered in human chromosome 17q21, WNT3A and WNT14 in human chromosome 1q42, WNT10A and WNT6 in human chromosome 2q35, and WNT10B and WNT1 in human chromosome 12q13. Among 22 FGF genes, FGF19, FGF4 and FGF3 genes are clustered in human chromosome 11q13, while FGF23 and FGF6 in human chromosome 12p13. WNT and FGF gene clusters are conserved between the human genome and the mouse genome. Activation of mouse Wnt or Fgf genes due to proviral integration of MMTV occurs in 5 out of 13 clustered genes, and in 1 out of 28 solitary genes (p=0.0033), which clearly indicates that mouse Wnt or Fgf gene clusters are recombination hot spots associated with carcinogenesis. Recombination results in retroviral integration as well as in chromosomal translocation, gene amplification and deletion during carcinogenesis. The CCND1-FGF19-FGF4-FGF3 gene cluster in human chromosome 11q13 is amplified in breast cancer, squamous cell carcinoma of head and neck, and bladder tumors, and is also translocated in parathyroid tumors and B-cell lymphoma. WNT gene clusters on human chromosome 1q42, 2q35, 12q13, and 17q21 as well as FGF gene cluster on human chromosome 12p13 might be amplified or translocated in human cancer just like FGF gene cluster on human chromosome 11q13. PMID:12429977

Katoh, Masaru

2002-12-01

303

Differential Gene Expression in Human Cerebrovascular Malformations  

PubMed Central

OBJECTIVE We sought to identify genes with differential expression in cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs), and control superficial temporal arteries (STAs) and to confirm differential expression of genes previously implicated in the pathobiology of these lesions. METHODS Total ribonucleic acid was isolated from four CCM, four AVM, and three STA surgical specimens and used to quantify lesion-specific messenger ribonucleic acid expression levels on human gene arrays. Data were analyzed with the use of two separate methodologies: gene discovery and confirmation analysis. RESULTS The gene discovery method identified 42 genes that were significantly up-regulated and 36 genes that were significantly down-regulated in CCMs as compared with AVMs and STAs (P = 0.006). Similarly, 48 genes were significantly up-regulated and 59 genes were significantly down-regulated in AVMs as compared with CCMs and STAs (P = 0.006). The confirmation analysis showed significant differential expression (P < 0.05) in 11 of 15 genes (angiogenesis factors, receptors, and structural proteins) that previously had been reported to be expressed differentially in CCMs and AVMs in immunohistochemical analysis. CONCLUSION We identify numerous genes that are differentially expressed in CCMs and AVMs and correlate expression with the immunohistochemistry of genes implicated in cerebrovascular malformations. In future efforts, we will aim to confirm candidate genes specifically related to the pathobiology of cerebrovascular malformations and determine their biological systems and mechanistic relevance. PMID:12535382

Shenkar, Robert; Elliott, J. Paul; Diener, Katrina; Gault, Judith; Hu, Ling-Jia; Cohrs, Randall J.; Phang, Tzulip; Hunter, Lawrence; Breeze, Robert E.; Awad, Issam A.

2009-01-01

304

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

305

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

306

Database for exchangeable gene trap clones: pathway and gene ontology analysis of exchangeable gene trap clone mouse lines.  

PubMed

Gene trapping in embryonic stem (ES) cells is a proven method for large-scale random insertional mutagenesis in the mouse genome. We have established an exchangeable gene trap system, in which a reporter gene can be exchanged for any other DNA of interest through Cre/mutant lox-mediated recombination. We isolated trap clones, analyzed trapped genes, and constructed the database for Exchangeable Gene Trap Clones (EGTC) [http://egtc.jp]. The number of registered ES cell lines was 1162 on 31 August 2013. We also established 454 mouse lines from trap ES clones and deposited them in the mouse embryo bank at the Center for Animal Resources and Development, Kumamoto University, Japan. The EGTC database is the most extensive academic resource for gene-trap mouse lines. Because we used a promoter-trap strategy, all trapped genes were expressed in ES cells. To understand the general characteristics of the trapped genes in the EGTC library, we used Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway analysis and found that the EGTC ES clones covered a broad range of pathways. We also used Gene Ontology (GO) classification data provided by Mouse Genome Informatics (MGI) to compare the functional distribution of genes in each GO term between trapped genes in the EGTC mouse lines and total genes annotated in MGI. We found the functional distributions for the trapped genes in the EGTC mouse lines and for the RefSeq genes for the whole mouse genome were similar, indicating that the EGTC mouse lines had trapped a wide range of mouse genes. PMID:24444128

Araki, Masatake; Nakahara, Mai; Muta, Mayumi; Itou, Miharu; Yanai, Chika; Yamazoe, Fumika; Miyake, Mikiko; Morita, Ayaka; Araki, Miyuki; Okamoto, Yoshiyuki; Nakagata, Naomi; Yoshinobu, Kumiko; Yamamura, Ken-ichi; Araki, Kimi

2014-02-01

307

PAX Genes in Cancer; Friends or Foes?  

PubMed Central

PAX genes have been shown to be critically required for the development of specific tissues and organs during embryogenesis. In addition, PAX genes are expressed in a handful of adult tissues where they are thought to play important roles, usually different from those in embryogenesis. A common theme in adult tissues is a requirement for PAX gene expression in adult stem cell maintenance or tissue regeneration. The connections between adult stem cell PAX gene expression and cancer are intriguing, and the literature is replete with examples of PAX gene expression in either situation. Here we systematically review the literature and present an overview of postnatal PAX gene expression in normal and cancerous tissue. We discuss the potential link between PAX gene expression in adult tissue and cancer. In addition, we discuss whether persistent PAX gene expression in cancer is favorable or unfavorable. PMID:22303411

Li, Caiyun G.; Eccles, Michael R.

2012-01-01

308

Gene Conversion in Human Genetic Disease  

PubMed Central

Gene conversion is a specific type of homologous recombination that involves the unidirectional transfer of genetic material from a ‘donor’ sequence to a highly homologous ‘acceptor’. We have recently reviewed the molecular mechanisms underlying gene conversion, explored the key part that this process has played in fashioning extant human genes, and performed a meta-analysis of gene-conversion events known to have caused human genetic disease. Here we shall briefly summarize some of the latest developments in the study of pathogenic gene conversion events, including (i) the emerging idea of minimal efficient sequence homology (MESH) for homologous recombination, (ii) the local DNA sequence features that appear to predispose to gene conversion, (iii) a mechanistic comparison of gene conversion and transient hypermutability, and (iv) recently reported examples of pathogenic gene conversion events. PMID:24710102

Chen, Jian-Min; Ferec, Claude; Cooper, David N.

2010-01-01

309

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

310

Genes and Genome Systems (Program Description)  

NSF Publications Database

... Division of Molecular and Cellular BiosciencesGenes and Genome Systems Cluster CONTACTS Name Email ... Target Date: July 12, 2006 SYNOPSIS The Genes and Genome Systems Cluster supports studies on ...

311

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

312

Horizontal gene transfer in human pathogens  

E-print Network

Horizontal gene transfer has a tremendous impact on the genome plasticity, adaptation and evolution of bacteria. Horizontally transferred mobile genetic elements are involved in the dissemination of antibiotic resistance and virulence genes, thus...

Juhas, Mario

2013-07-18

313

Towards integrative gene functional similarity measurement  

PubMed Central

Background In Gene Ontology, the "Molecular Function" (MF) categorization is a widely used knowledge framework for gene function comparison and prediction. Its structure and annotation provide a convenient way to compare gene functional similarities at the molecular level. The existing gene similarity measures, however, solely rely on one or few aspects of MF without utilizing all the rich information available including structure, annotation, common terms, lowest common parents. Results We introduce a rank-based gene semantic similarity measure called InteGO by synergistically integrating the state-of-the-art gene-to-gene similarity measures. By integrating three GO based seed measures, InteGO significantly improves the performance by about two-fold in all the three species studied (yeast, Arabidopsis and human). Conclusions InteGO is a systematic and novel method to study gene functional associations. The software and description are available at http://www.msu.edu/~jinchen/InteGO. PMID:24564710

2014-01-01

314

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- ...

315

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, ...

316

Gene Expression in the Stallion Testes  

E-print Network

Understanding the genes that regulate spermatogenesis and steroidogenesis in the testis is critical for enhancement of stallion fertility. Stallion testicular samples were used to identify candidate genes by cDNA microarrays that simultaneously...

Laughlin, Andy M.

2011-08-08

317

Bayesian Mixture Modeling of Gene-Environment and Gene-Gene Interactions  

PubMed Central

With the advent of rapid and relatively cheap genotyping technologies there is now the opportunity to attempt to identify gene-environment and gene-gene interactions when the number of genes and environmental factors is potentially large. Unfortunately the dimensionality of the parameter space leads to a computational explosion in the number of possible interactions that may be investigated. The full model that includes all interactions and main effects can be unstable, with wide confidence intervals arising from the large number of estimated parameters. We describe a hierarchical mixture model that allows all interactions to be investigated simultaneously, but assumes the effects come from a mixture prior with two components, one that reflects small null effects and the second for epidemiologically significant effects. Effects from the former are effectively set to zero, hence increasing the power for the detection of real signals. The prior framework is very flexible, which allows substantive information to be incorporated into the analysis. We illustrate the methods first using simulation, and then on data from a case-control study of lung cancer in Central and Eastern Europe. PMID:19492346

Wakefield, Jon; De Vocht, Frank; Hung, Rayjean J.

2009-01-01

318

The yeast ubiquitin genes: a family of natural gene fusions.  

PubMed Central

Ubiquitin is a 76-residue protein highly conserved among eukaryotes. Conjugation of ubiquitin to intracellular proteins mediates their selective degradation in vivo. We describe a family of four ubiquitin-coding loci in the yeast Saccharomyces cerevisiae. UB11, UB12 and UB13 encode hybrid proteins in which ubiquitin is fused to unrelated ('tail') amino acid sequences. The ubiquitin coding elements of UB11 and UB12 are interrupted at identical positions by non-homologous introns. UB11 and UB12 encode identical 52-residue tails, whereas UB13 encodes a different 76-residue tail. The tail amino acid sequences are highly conserved between yeast and mammals. Each tail contains a putative metal-binding, nucleic acid-binding domain of the form Cys-X2-4-Cys-X2-15-Cys-X2-4-Cys, suggesting that these proteins may function by binding to DNA. The fourth gene, UB14, encodes a polyubiquitin precursor protein containing five ubiquitin repeats in a head-to-tail, spacerless arrangement. All four ubiquitin genes are expressed in exponentially growing cells, while in stationary-phase cells the expression of UB11 and UB12 is repressed. The UB14 gene, which is strongly inducible by starvation, high temperatures and other stresses, contains in its upstream region strong homologies to the consensus 'heat shock box' nucleotide sequence. Elsewhere we show that the essential function of the UB14 gene is to provide ubiquitin to cells under stress. Images Fig. 1. Fig. 7. PMID:3038523

Ozkaynak, E; Finley, D; Solomon, M J; Varshavsky, A

1987-01-01

319

Identification of genes responsive to PFOS using gene expression profiling  

Microsoft Academic Search

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

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

2005-01-01

320

Gene-gene interactions in breast cancer susceptibility.  

PubMed

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

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

2012-02-15

321

Gene therapy for Stargardt disease associated with ABCA4 gene.  

PubMed

Mutations in the photoreceptor-specific flippase ABCA4 lead to accumulation of the toxic bisretinoid A2E, resulting in atrophy of the retinal pigment epithelium (RPE) and death of the photoreceptor cells. Many blinding diseases are associated with these mutations including Stargardt's disease (STGD1), cone-rod dystrophy, retinitis pigmentosa (RP), and increased susceptibility to age-related macular degeneration. There are no curative treatments for any of these dsystrophies. While the monogenic nature of many of these conditions makes them amenable to treatment with gene therapy, the ABCA4 cDNA is 6.8 kb and is thus too large for the AAV vectors which have been most successful for other ocular genes. Here we review approaches to ABCA4 gene therapy including treatment with novel AAV vectors, lentiviral vectors, and non-viral compacted DNA nanoparticles. Lentiviral and compacted DNA nanoparticles in particular have a large capacity and have been successful in improving disease phenotypes in the Abca4 (-/-) murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat patients with ABCA4-associated Startgardt's disease (STGD1). As a result of the development of these novel technologies, effective therapies for ABCA4-associated diseases may finally be within reach. PMID:24664763

Han, Zongchao; Conley, Shannon M; Naash, Muna I

2014-01-01

322

Gene Expression Profiles in Murine Influenza Pneumonia  

Microsoft Academic Search

Background: Many in vitro studies have focused on gene expression in influenza-infected leukocytes, lung tissue or cell lines. However, knowledge of in vivo gene expression in these compartments is limited. Methods: To obtain insight into gene expression profiles during influenza infection, we determined the expression of multiple genes by using a newly developed mouse-specific multiplex ligation-dependent probe amplification assay. Results:

Mark C. Dessing; Koenraad F. van der Sluijs; C. Arnold Spek; Tom van der Poll

2009-01-01

323

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

324

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

325

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

326

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

327

Leader genes in osteogenesis: a theoretical study.  

PubMed

Little is still known about the molecular mechanisms involved in the process of osteogenesis. In this paper, the leader genes approach, a new bioinformatics method which has already been experimentally validated, is adopted in order to identify the genes involved in human osteogenesis. Interactions among genes are then calculated and genes are ranked according to their relative importance in this process. In total, 167 genes were identified as being involved in osteogenesis. Genes were divided into 4 groups, according to their main function in the osteogenic processes: skeletal development; cell adhesion and proliferation; ossification; and calcium ion binding. Seven genes were consistently identified as leader genes (i.e. the genes with the greatest importance in osteogenesis), while 14 were found to have slightly less importance (class B genes). It was interesting to notice that the larger part of leader and class B genes belonged to the cell adhesion and proliferation or to the ossification sub-groups. This finding suggested that these two particular sub-processes could play a more important role in osteogenesis. Moreover, among the 7 leader genes, it is interesting to notice that RUNX2, BMP2, SPARC, PTH play a direct role in bone formation, while the 3 other leader genes (VEGF, IL6, FGF2) seem to be more connected with an angiogenetic process. Twenty-nine genes have no known interactions (orphan genes). From these results, it may be possible to plan an ad hoc experimentation, for instance by microarray analyses, focused on leader, class B and orphan genes, with the aim to shed new light on the molecular mechanisms underlying osteogenesis. PMID:22884391

Orlando, Bruno; Giacomelli, Luca; Ricci, Massimiliano; Barone, Antonio; Covani, Ugo

2013-01-01

328

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

Stojkovic, Neda; Radak, Djordje; Przulj, Natasa

2013-01-01

329

Gene Identification in Asthma and Allergy  

Microsoft Academic Search

Asthma and atopy are due to the interaction between genetic and environmental factors. The genetic basis of asthma and atopy is becoming more certain, with the promise of improvements in the diagnosis and treatment of these disorders. A combination of candidate gene and positional cloning studies has already identified several genes which influence allergic disease. These genes predispose in general

Miriam F. Moffatt; William O. C. M. Cookson

1998-01-01

330

New Gene Variants for Prostate Cancer Identified  

MedlinePLUS

... page, please enable JavaScript. New Gene Variants for Prostate Cancer Identified 23 new variants associated with increased risk ... 2014 Related MedlinePlus Pages Genes and Gene Therapy Prostate Cancer MONDAY, Sept. 15, 2014 (HealthDay News) -- An international ...

331

Phylomemetics—Evolutionary Analysis beyond the Gene  

Microsoft Academic Search

Genes are propagated by error-prone copying, and the resulting variation provides the basis for phylogenetic reconstruction of evolutionary relationships. Horizontal gene transfer may be superimposed on a tree-like evolutionary pattern, with some relationships better depicted as networks. The copying of manuscripts by scribes is very similar to the replication of genes, and phylogenetic inference programs can be used directly for

Christopher J. Howe; Heather F. Windram

2011-01-01

332

Organization of Iroquois genes in fish  

Microsoft Academic Search

In mammals, a total of six iroquois (Irx) genes exist, which are organized into two clusters. Here we report on the organization of all iroquois genes present in fish, using zebrafish (Danio rerio) and pufferfish (Fugu rubripes and Tetraodon nigroviridis) as examples. A total of 10 Irx genes were found in pufferfish, and 11 in zebrafish; all but one of

Renate Dildrop; Ulrich Rüther

2004-01-01

333

KEGG: Kyoto Encyclopedia of Genes and Genomes  

Microsoft Academic Search

Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules. The major component of KEGG is the PATHWAY database that consists of graphical dia- grams of biochemical pathways including most of the known metabolic pathways and some of the known regulatory pathways. The pathway

Hiroyuki Ogata; Susumu Goto; Kazushige Sato; Wataru Fujibuchi; Hidemasa Bono; Minoru Kanehisa

1999-01-01

334

Two Classes of Genes in Plants  

Microsoft Academic Search

Two classes of genes were identified in three Gramineae (maize, rice, barley) and six dicots (Arabidopsis, soybean, pea, tobacco, tomato, potato). One class, the GC-rich class, contained genes with no, or few, short introns. In contrast, the GC-poor class contained genes with numerous, long introns. The similarity of the properties of each class, as present in the genomes of maize

Nicolas Carels; Giorgio Bernardi

2000-01-01

335

Preferential liver gene expression with polypropylenimine dendrimers  

Microsoft Academic Search

Previously, the lower generation (DAB 8–generation 2 and DAB 16–generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low

Andreas G. Schatzlein; Bernd H. Zinselmeyer; Adurrahim Elouzi; Christine Dufes; Ya Tsz A. Chim; Clive J. Roberts; Martyn C. Davies; Avril Munro; Alexander I. Gray; Ijeoma F. Uchegbu

2005-01-01

336

The Mouse Gene Expression Database (GXD)  

Microsoft Academic Search

The Gene Expression Database (GXD) is a community resource of gene expression information for the laboratory mouse. By combining the different types of expression data, GXD aims to provide increasingly complete information about the expression profiles of genes in different mouse strains and mutants, thus enabling valuable insights into the molecular networks that underlie normal development and disease. GXD is

Martin Ringwald; Janan T. Eppig; Dale A. Begley; John P. Corradi; Ingeborg J. Mccright; Terry F. Hayamizu; David P. Hill; James A. Kadin; Joel E. Richardson

2001-01-01

337

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

338

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

339

Mining gene expression databases for association rules  

Microsoft Academic Search

Motivation: Global gene expression profiling, both at the transcript level and at the protein level, can be a valuable tool in the understanding of genes, biological networks, and cellular states. As larger and larger gene expression data sets become available, data mining techniques can be applied to identify patterns of interest in the data. As- sociation rules, used widely in

Chad Creighton; Samir Hanash

2003-01-01

340

Gene synthesis by circular assembly amplification  

E-print Network

error-containing DNA10. We developed a one-cycle gene synthesis method that substan- tially improvesGene 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

Church, George M.

341

Genew: the Human Gene Nomenclature Database  

Microsoft Academic Search

Genew, the Human Gene Nomenclature Database, is the only resource that provides data for all human genes which have approved symbols. It is managed by the HUGO Gene Nomenclature Committee (HGNC) as a confidential database, containing over 16 000 records, 80% of which are represented on the Web by searchable text files. The data in Genew are highly curated by

Hester M. Wain; Michael J. Lush; Fabrice Ducluzeau; Sue Povey

2002-01-01

342

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

343

EXPERIMENTAL Differential Gene Expression between Juvenile  

E-print Network

Genes Play a Role in the Regeneration of Membranous Bone Derrick C. Wan, M.D. Oliver O. Aalami, M markers (Runx2/Cbfa1, Itm2a, and FGFR-1), and the growth factor Ptn were among other genes with greater expression in juvenile dura mater. Markers of osteoclasts (Acp5, MMP9, Ctsk) and the multiple candidate gene

Derynck, Rik

344

Repetitive sequence environment distinguishes housekeeping genes  

PubMed Central

Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. We further show that isochore membership does not distinguish housekeeping genes from tissue-specific genes and that repetitive sequence environment distinguishes housekeeping genes from tissue-specific genes in every isochore. The distinct repetitive sequence environment, in combination with other previously published sequence properties of housekeeping genes, were used to develop a method of predicting housekeeping genes on the basis of DNA sequence alone. Using expression across tissue types as a measure of success, we demonstrate that repetitive sequence environment is by far the most important sequence feature identified to date for distinguishing housekeeping genes. PMID:17141428

Eller, C. Daniel; Regelson, Moira; Merriman, Barry; Nelson, Stan; Horvath, Steve; Marahrens, York

2007-01-01

345

Progress & Prospects: Gene therapy in aging  

Microsoft Academic Search

Studies performed on various experimental model systems indicate that genetic interventions can increase longevity, even if in a highly protected laboratory condition. Generally, such interventions required partial or complete switching off of the gene and inhibiting the activity of its gene products, which normally have other well-defined roles in metabolic processes. Overexpression of some genes, such as stress response and

S I S Rattan; R Singh

2009-01-01

346

HORIZONTAL GENE TRANSFER BETWEEN CHLOROPLAST GENOMES  

E-print Network

HORIZONTAL GENE TRANSFER BETWEEN CHLOROPLAST GENOMES SENIOR SOPHISTOR PROJECT SUPERVISOR: DR in molecular evolution. The aim of this project was to look for horizontal gene transfer between chloroplast for inconruencies with the species tree. Incongruencies were found which are suggestive of horizontal gene transfer

McLysaght, Aoife

347

Horizontal Gene Transfer in Microbial Genome Evolution  

Microsoft Academic Search

Horizontal gene transfer is the collective name for processes that permit the exchange of DNA among organisms of different species. Only recently has it been recognized as a significant contribution to inter-organismal gene exchange. Traditionally, it was thought that microorganisms evolved clonally, passing genes from mother to daughter cells with little or no exchange of DNA among diverse species. Studies

Ravi Jain; Maria C. Rivera; Jonathan E. Moore; James A. Lake

2002-01-01

348

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

349

The evolutionary origin of orphan genes  

Microsoft Academic Search

Gene evolution has long been thought to be primarily driven by duplication and rearrangement mechanisms. However, every evolutionary lineage harbours orphan genes that lack homologues in other lineages and whose evolutionary origin is only poorly understood. Orphan genes might arise from duplication and rearrangement processes followed by fast divergence; however, de novo evolution out of non-coding genomic regions is emerging

Tomislav Domazet-Lošo; Diethard Tautz

2011-01-01

350

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

351

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

352

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

353

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

354

Hox genes in the echiuroid Urechis unicinctus  

Microsoft Academic Search

An echiuroid species, Urechis unicinctus, was surveyed for Hox genes using polymerase chain reaction with homeobox-specific degenerate primers. We identified nine distinct homeodomain-containing gene fragments. These nine fragments were classified by comparative analysis. This analysis revealed that this echiuroid possessed at least three Hox genes from the anterior group, five from the central group, and one from the posterior group.

Sung-Jin Cho; Dae-Hee Lee; Hyuk-Jae Kwon; Soon Cheol Park; Kil-Sang Shin; Chi Hyun Ahn

2006-01-01

355

Gene targeting in adult rhesus macaque fibroblasts  

Microsoft Academic Search

BACKGROUND: Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT) has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in

Daniel T Meehan; Mary Ann Zink; Melissa Mahlen; Marilu Nelson; Warren G Sanger; Shoukhrat M Mitalipov; Don P Wolf; Michel M Ouellette; Robert B Norgren Jr

2008-01-01

356

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

357

Predicting Gene Function From Patterns of Annotation  

E-print Network

Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA The Gene Ontology Ontology Consortium (Gene Ontology Consortium 2000) provides a standardized vocabulary for the annotation experimentally. A variety of approaches for predicting Gene Ontology (GO) attributes have been attempted. Natural

Roth, Frederick

358

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

359

YABBY Polarity Genes Mediate the Repression of KNOX Homeobox Genes in Arabidopsis  

Microsoft Academic Search

The YABBY ( YAB ) genes specify abaxial cell fate in lateral organs in Arabidopsis. Loss-of-function mutants in two early-expressing YAB genes, FILAMENTOUS FLOWER ( FIL ) and YAB3 , do not exhibit vegetative phenotypes as a result of redundancy. Mutations in these genes result in the derepression of the KNOX homeobox genes SHOOTMERISTEM- LESS ( STM ), BREVIPEDICELLUS ,

Mande K. Kumaran; John L. Bowman; Venkatesan Sundaresan

2002-01-01

360

Inheritance of two foreign genes co-introduced into Petunia hybrida by direct gene transfer  

Microsoft Academic Search

In previous work, transformedPetunia hybrida plants were obtained by direct gene transfer, using two different genes on separate plasmids (NPT II gene and a cDNA of PEPC from green sorghum leaves). In this study, we have analysed the sexual transmission of the acquired genes by genetic crossing analysis of 2 of the transgenic petunias. The ploïdies of the two clones

Denis Tagu; Catherine Bergounioux; Claudette Perennes; Pierre Gadal

1990-01-01

361

Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function  

Microsoft Academic Search

BACKGROUND: PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence,

Chao Di; Wenying Xu; Zhen Su; Joshua S Yuan

2010-01-01

362

'Gene shaving' as a method for identifying distinct sets of genes with similar expression patterns  

Microsoft Academic Search

BACKGROUND: Large gene expression studies, such as those conducted using DNA arrays, often provide millions of different pieces of data. To address the problem of analyzing such data, we describe a statistical method, which we have called 'gene shaving'. The method identifies subsets of genes with coherent expression patterns and large variation across conditions. Gene shaving differs from hierarchical clustering

Trevor Hastie; Robert Tibshirani; Michael B. Eisen; Ash Alizadeh; Ronald Levy; Louis Staudt; Wing C. Chan; David Botstein; Patrick Brown

2000-01-01

363

Horizontal Gene Transfer in Cyanobacterial Signature Genes Shailaja Yerrapragada, Janet L. Siefert, and George E. Fox  

E-print Network

Chapter 20 Horizontal Gene Transfer in Cyanobacterial Signature Genes Shailaja Yerrapragada, Janet candidates for HGT among closely related cyanobacterial strains. Key words: Horizontal gene transfer.), Horizontal Gene Transfer: Genomes in Flux, vol. 532 C Humana Press, a part of Springer Science+Business Media

Fox, George

364

Multiple Yeast Genes, Including Paf1 Complex Genes, Affect Telomere Length via Telomerase RNA Abundance  

Microsoft Academic Search

Telomere length is a quantitative trait affected by more than 273 genes in Saccharomyces cerevisiae (1, 9, 12). To put this number into perspective, genes representing nearly 5% of the 6,000-gene yeast genome (15) influence telomeres. Some of these genes directly impact telomere homeostasis, either by contributing to the activity of the telomerase enzyme or by affecting the physical state

Amy D. Mozdy; Elaine R. Podell; Thomas R. Cech

2008-01-01

365

Indexing TNF-? gene expression using a gene-targeted reporter cell line  

Microsoft Academic Search

BACKGROUND: Current cell-based drug screening technologies utilize randomly integrated reporter genes to index transcriptional activity of an endogenous gene of interest. In this context, reporter expression is controlled by known genetic elements that may only partially capture gene regulation and by unknown features of chromatin specific to the integration site. As an alternative technology, we applied highly efficient gene-targeting with

Ziying Yan; Diana Lei-Butters; John F Engelhardt; Gregory H Leno

2009-01-01

366

Occurrence and Expression of Gene Transfer Agent Genes in Marine Bacterioplankton  

Microsoft Academic Search

Genes with homology to the transduction-like gene transfer agent (GTA) were observed in genome sequences of three cultured members of the marine Roseobacter clade. A broader search for homologs for this host- controlled virus-like gene transfer system identified likely GTA systems in cultured Alphaproteobacteria, and particularly in marine bacterioplankton representatives. Expression of GTA genes and extracellular release of GTA particles

Erin J. Biers; Kui Wang; Catherine Pennington; Robert Belas; Feng Chen; Mary Ann Moran

2008-01-01

367

Gene Expression Omnibus: NCBI gene expression and hybridization array data repository  

Microsoft Academic Search

The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data. GEO provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-throughput gene expression and genomic hybridization experiments. GEO is not intended to replace in house gene expres- sion databases

Ron Edgar; Michael Domrachev; Alex E. Lash

2002-01-01

368

Parent genes of retrotransposition-generated gene duplicates in Drosophila melanogaster have distinct expression profiles  

Microsoft Academic Search

Genes arising by retrotransposition are always different from their parent genes from the outset. In addition, the cDNA must insert into a region that allows expression or it will become a processed pseudogene. We sought to determine whether this class of gene duplication differs from other gene duplications based on functional criteria. Using amino acid sequences from Drosophila melanogaster, we

Morgan G. I. Langille; Denise V. Clark

2007-01-01

369

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

Microsoft Academic Search

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

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

1990-01-01

370

Regulatable Gene Expression Systems for Gene Therapy Applications: Progress and Future Challenges  

Microsoft Academic Search

Gene therapy aims to revert diseased phenotypes by the use of both viral and nonviral gene delivery systems. Substantial progress has been made in making gene transfer vehicles more efficient, less toxic, and nonimmunogenic and in allowing long-term transgene expression. One of the key issues in successfully implementing gene therapies in the clinical setting is to be able to regulate

Shyam Goverdhana; Mariana Puntel; Weidong Xiong; Jeffrey Zirger; Carlos Barcia; James Curtin; Eric Soffer; Sonali Mondkar; Gwendalyn King; Jinwei Hu; S. A. Sciascia; M. Candolfi; D. S. Greengold; P. R. Lowenstein; M. G. Castro

2005-01-01

371

Phenotypic deconstruction of gene circuitry  

PubMed Central

It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space. PMID:23822506

Lomnitz, Jason G.; Savageau, Michael A.

2013-01-01

372

Routes to Binary Gene Expression  

E-print Network

Systems biology approaches combining theoretical modeling with experiments have been singularly successful in uncovering novel features of cellular phenomena. One such feature is that of binary gene expression in which the expression level is either low or high, i.e., digital in nature. This gives rise to two distinct subpopulations in a population of genetically identical cells. The fraction of cells in the high expression state is raised as the strength of the inducing signal is increased indicating that the response is not graded. In this review, we discuss the possible origins of binary gene expression with emphasis on three principal mechanisms: purely stochastic, positive feedback-based and emergent bistability. In the latter case, two stable expression states are obtained due to an autoregulatory positive feedback loop in protein synthesis along with cell growth retardation by the proteins synthesized. The theoretical foundations of the observed phenomena are described in each case.

Indrani Bose

2012-07-30

373

Nickel and Epigenetic Gene Silencing  

PubMed Central

Insoluble nickel compounds are well-established human carcinogens. Occupational exposure to these compounds leads to increased incidence of lung and nasal cancer in nickel refinery workers. Apart from its weak mutagenic activity and hypoxia mimicking effect there is mounting experimental evidence indicating that epigenetic alteration plays an important role in nickel-induced carcinogenesis. Multiple epigenetic mechanisms have been identified to mediate nickel-induced gene silencing. Nickel ion is able to induce heterochromatinization by binding to DNA-histone complexes and initiating chromatin condensation. The enzymes required for establishing or removing epigenetic marks can be targeted by nickel, leading to altered DNA methylation and histone modification landscapes. The current review will focus on the epigenetic changes that contribute to nickel-induced gene silencing. PMID:24705264

Sun, Hong; Shamy, Magdy; Costa, Max

2013-01-01

374

Gene Therapy for Primary Immunodeficiencies  

PubMed Central

Abstract For over 40 years, primary immunodeficiencies (PIDs) have featured prominently in the development and refinement of human allogeneic hematopoietic stem cell transplantation. More recently, ex vivo somatic gene therapy using autologous cells has provided remarkable evidence of clinical efficacy in patients without HLA-matched stem cell donors and in whom toxicity of allogeneic procedures is likely to be high. Together with improved preclinical models, a wealth of information has accumulated that has allowed development of safer, more sophisticated technologies and protocols that are applicable to a much broader range of diseases. In this review we summarize the status of these gene therapy trials and discuss the emerging application of similar strategies to other PIDs. PMID:22691036

Rivat, Christine; Santilli, Giorgia; Gaspar, H. Bobby

2012-01-01

375

Adaptive Models for Gene Networks  

PubMed Central

Biological systems are often treated as time-invariant by computational models that use fixed parameter values. In this study, we demonstrate that the behavior of the p53-MDM2 gene network in individual cells can be tracked using adaptive filtering algorithms and the resulting time-variant models can approximate experimental measurements more accurately than time-invariant models. Adaptive models with time-variant parameters can help reduce modeling complexity and can more realistically represent biological systems. PMID:22359614

Shin, Yong-Jun; Sayed, Ali H.; Shen, Xiling

2012-01-01

376

The insect SNMP gene family.  

PubMed

SNMPs are membrane proteins observed to associate with chemosensory neurons in insects; in Drosophila melanogaster, SNMP1 has been shown to be essential for the detection of the pheromone cis-vaccenyl acetate (CVA). SNMPs are one of three insect gene clades related to the human fatty acid transporter CD36. We previously characterized the CD36 gene family in 4 insect Orders that effectively cover the Holometabola, or some 80% of known insect species and the 300 million years of evolution since this lineage emerged: Lepidoptera (e.g. Bombyx mori, Antheraea polyphemus, Manduca sexta, Heliothis virescens, Helicoverpa assulta, Helicoverpa armigera, Mamestra brassicae); Diptera (D. melanogaster, Drosophila pseudoobscura, Aedes aegypti, Anopheles gambiae, Culex pipiens quinquefasciatus); Hymenoptera (Apis mellifera); and Coleoptera (Tribolium castaneum). This previous study suggested a complex topography within the SNMP clade including a strongly supported SNMP1 sub-clade plus additional SNMP genes. To further resolve the SNMP clade here, we used cDNA sequences of SNMP1 and SNMP2 from various Lepidoptera species, D. melanogaster and Ae. aegypti, as well as BAC derived genomic sequences from Ae. aegypti as models for proposing corrected sequences of orthologues in the D. pseudoobscura and An. gambiae genomes, and for identifying orthologues in the B. mori and C. pipiens q. genomes. We then used these sequences to analyze the SNMP clade of the insect CD36 gene family, supporting the existence of two well supported sub-clades, SNMP1 and SNMP2, throughout the dipteran and lepidopteran lineages, and plausibly throughout the Holometabola and across a broad evolutionary time scale. We present indirect evidence based on evolutionary selection (dN/dS) that the dipteran SNMPs are expressed as functional proteins. We observed expansions of the SNMP1 sub-clade in C. pipiens q. and T. castaneum suggesting that the SNMP1s may have an expanded functional role in these species. PMID:19364529

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

2009-07-01

377

Transgenic plants with cyanobacterial genes  

Microsoft Academic Search

Over the years, cyanobacteria have been regarded as ideal model systems for studying fundamental biochemical processes like\\u000a oxygenic photosynthesis and carbon and nitrogen assimilation. Additionally, they have been used as human foods, sources for\\u000a vitamins, proteins, fine chemicals, and bioactive compounds. Aiming to increase plant productivity as well as nutritional\\u000a values, cyanobacterial genes involved in carbon metabolism, fatty acid biosynthesis,

Youn-Il Park; Sang-Bong Choi; Jang R. Liu

2009-01-01

378

Regulation of Genes by Light  

Microsoft Academic Search

Our current understanding of light-dependent regulation of gene expression in purple bacteria is summarized. Most of the regulatory\\u000a systems utilize photoreceptor proteins that transmit a light-dependent signal to different downstream components to control\\u000a a wide variety of physiological responses. The photoreceptors identified so far are (bacterio)phytochrome, sensory rhodopsin,\\u000a phototropin-related proteins, BLUF domain proteins, cryptochrome, and photoactive yellow protein. They use

Gabriele Klug; Shinji Masuda

379

Identification of cancer-associated gene clusters and genes via clustering penalization  

PubMed Central

Identification of genes associated with cancer development and progression using microarray data is challenging because of the high dimensionality and cluster structure of gene expressions. Here the clusters are composed of multiple genes with coordinated biological functions and/or correlated expressions. In this article, we first propose a hybrid approach for clustering gene expressions. The hybrid approach uses both pathological pathway information and correlations of gene expressions. We propose using the group bridge, a novel clustering penalization approach, for analysis of cancer microarray data. The group bridge approach explicitly accounts for the cluster structure of gene expressions, and is capable of selecting gene clusters and genes within those selected clusters that are associated with cancer. We also develop an iterative algorithm for computing the group bridge estimator. Analysis of three cancer microarray datasets shows that the proposed approach can identify biologically meaningful gene clusters and genes within those identified clusters. PMID:20057914

Ma, Shuangge; Huang, Jian; Shen, Shihao

2009-01-01

380

Horizontal gene transfer in chromalveolates  

PubMed Central

Background Horizontal gene transfer (HGT), the non-genealogical transfer of genetic material between different organisms, is considered a potentially important mechanism of genome evolution in eukaryotes. Using phylogenomic analyses of expressed sequence tag (EST) data generated from a clonal cell line of a free living dinoflagellate alga Karenia brevis, we investigated the impact of HGT on genome evolution in unicellular chromalveolate protists. Results We identified 16 proteins that have originated in chromalveolates through ancient HGTs before the divergence of the genera Karenia and Karlodinium and one protein that was derived through a more recent HGT. Detailed analysis of the phylogeny and distribution of identified proteins demonstrates that eight have resulted from independent HGTs in several eukaryotic lineages. Conclusion Recurring intra- and interdomain gene exchange provides an important source of genetic novelty not only in parasitic taxa as previously demonstrated but as we show here, also in free-living protists. Investigating the tempo and mode of evolution of horizontally transferred genes in protists will therefore advance our understanding of mechanisms of adaptation in eukaryotes. PMID:17894863

Nosenko, Tetyana; Bhattacharya, Debashish

2007-01-01

381

Posttranscriptional gene silencing in nuclei  

PubMed Central

In plants, small interfering RNAs (siRNAs) with sequence homology to transcribed regions of genes can guide the sequence-specific degradation of corresponding mRNAs, leading to posttranscriptional gene silencing (PTGS). The current consensus is that siRNA-mediated PTGS occurs primarily in the cytoplasm where target mRNAs are localized and translated into proteins. However, expression of an inverted-repeat double-stranded RNA corresponding to the soybean FAD2-1A desaturase intron is sufficient to silence FAD2-1, implicating nuclear precursor mRNA (pre-mRNA) rather than cytosolic mRNA as the target of PTGS. Silencing FAD2-1 using intronic or 3?-UTR sequences does not affect transcription rates of the target genes but results in the strong reduction of target transcript levels in the nucleus. Moreover, siRNAs corresponding to pre-mRNA–specific sequences accumulate in the nucleus. In Arabidopsis, we find that two enzymes involved in PTGS, Dicer-like 4 and RNA-dependent RNA polymerase 6, are localized in the nucleus. Collectively, these results demonstrate that siRNA-directed RNA degradation can take place in the nucleus, suggesting the need for a more complex view of the subcellular compartmentation of PTGS in plants. PMID:21173264

Hoffer, Paul; Ivashuta, Sergey; Pontes, Olga; Vitins, Alexa; Pikaard, Craig; Mroczka, Andrew; Wagner, Nicholas; Voelker, Toni

2011-01-01

382

Uncovering legumain genes in rice.  

PubMed

Legumains are Asn specific cysteine proteases physiologically related to the biosynthesis of vacuolar components, degradation of storage proteins and programmed cell death. The present work identifies and characterizes the genic family of legumains in rice (Oryza sativa), which comprises five different loci. Rice legumains (OsaLegs) were ubiquitously detected in all plant tissues analyzed. However, phylogenetic analyses and gene expression studies demonstrated greater association of OsaLeg2 and OsaLeg3 to seed-related legumains, whereas OsaLeg1, 4 and 5 would act as vegetative-related proteases. Additionally, OsaLeg1 mRNA is strongly induced in senescent leaves. All rice legumain genes respond in different ways to environmental conditions such as wounding, salt and abscisic acid treatments. Mainly, wounding is capable of inducing all the four expressed genes OsaLeg1, 2, 3 and 4. Alternative splicing isoforms, with potential to generate pre-activated OsaLeg1 and OsaLeg2 nonvacuolar enzymes under different environmental situations were also observed. PMID:24388520

Christoff, Ana Paula; Turchetto-Zolet, Andreia Carina; Margis, Rogerio

2014-02-01

383

Mutations in cardiovascular connexin genes.  

PubMed

Connexins (Cxs) form a family of transmembrane proteins comprising 21 members in humans. Cxs differ in their expression patterns, biophysical properties and ability to combine into homomeric or heteromeric gap junction channels between neighbouring cells. The permeation of ions and small metabolites through gap junction channels or hemichannels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. Among others, Cx37, Cx40, Cx43, Cx45 and Cx47 are found in heart, blood and lymphatic vessels. Mutations or polymorphisms in the genes coding for these Cxs have not only been implicated in cardiovascular pathologies but also in a variety of other disorders. While mutations in Cx43 are mostly linked to oculodentodigital dysplasia, Cx47 mutations are associated with Pelizaeus-Merzbacher-like disease and lymphoedema. Cx40 mutations are principally linked to atrial fibrillation. Mutations in Cx37 have not yet been described, but polymorphisms in the Cx37 gene have been implicated in the development of arterial disease. This review addresses current knowledge on gene mutations in cardiovascular Cxs systematically and links them to alterations in channel properties and disease. PMID:24966059

Molica, Filippo; Meens, Merlijn J P; Morel, Sandrine; Kwak, Brenda R

2014-09-01

384

Functional Genes and Proteins of Clonorchis sinensis  

PubMed Central

During the past several decades, researches on parasite genetics have progressed from biochemical and serodiagnostic studies to protein chemistry, molecular biology, and functional gene studies. Nowadays, bioinformatics, genomics, and proteomics approaches are being applied by Korean parasitology researchers. As for Clonorchis sinensis, investigations have been carried out to identify its functional genes using forward and reverse genetic approaches and to characterize the biochemical and biological properties of its gene products. The authors review the proteins of cloned genes, which include antigenic proteins, physiologic and metabolic enzymes, and the gene expression profile of Clonorchis sinensis. PMID:19885336

Kim, Tae Im; Na, Byoung-Kuk

2009-01-01

385

[Gene expression profiling in human thyroid tumors].  

PubMed

Our work aims at defining by microarray gene expression profiles in different thyroid tumors: hyperfunctioning autonomous adenomas, and sporadic and post-Chernobyl papillary cancers. Gene expression analysis in hyperfunctioning autonomous adenomas allowed us to identify genes involved in various physiological processes of the thyroid. Concerning papillary cancers, gene expression profiling in post-Chernobyl and sporadic papillary carcinomas could not identify a specific gene expression signature allowing to distinguish both tumors although such a signature exists for autonomous adenomas and carcinomas. This suggests that both cancers represent the same disease, and that there is unlikely to be a molecular signature for radiation-induced thyroid cancer. PMID:16035626

Maenhaut, C

2004-01-01

386

Gene doping: of mice and men.  

PubMed

Gene doping is the newest threat to the spirit of fair play in sports. Its concept stemmed out from legitimate gene therapy trials, but anti-doping authorities fear that they now may be facing a form of doping that is virtually undetectable and extremely appealing to athletes. This paper presents studies that generated mouse models with outstanding physical performance, by manipulating genes such as insulin-like growth factor 1 (IGF-1) or phosphoenolpyruvate carboxykinase (PEPCK), which are likely to be targeted for gene doping. The potential transition from super mice to super athletes will also be discussed, in addition to possible strategies for detection of gene doping. PMID:19272337

Azzazy, Hassan M E; Mansour, Mai M H; Christenson, Robert H

2009-04-01

387

University of Washington: GeneTests  

NSDL National Science Digital Library

This GeneTests website "is a publicly funded medical genetics information resource for physicians, other healthcare providers, and researchers, available at no cost to all interested persons." The GeneTests site features _Gene Reviews_, an online publication of expert-authored disease reviews. The site also offers international directories of genetic testing laboratories and genetics and prenatal diagnosis clinics. Some new site features include Expanded Molecular Genetics in _Gene Reviews_, and Printable Resources. The site also offers usage statistics and is currently posting 4,603 daily hits for _Gene Reviews_ and an impressive 16,536 daily hits for their Laboratory Directory.

388

GENETICS OF LONG QT SYNDROME  

PubMed Central

Long QT syndrome (LQTS) is a potentially life-threatening cardiac arrhythmia characterized by delayed myocardial repolarization that produces QT prolongation and increased risk for torsades des pointes (TdP)-triggered syncope, seizures, and sudden cardiac death (SCD) in an otherwise healthy young individual with a structurally normal heart. Currently, there are three major LQTS genes (KCNQ1, KCNH2, and SCN5A) that account for approximately 75% of the disorder. For the major LQTS genotypes, genotype-phenotype correlations have yielded gene-specific arrhythmogenic triggers, electrocardiogram (ECG) patterns, response to therapies, and intragenic and increasingly mutation-specific risk stratification. The 10 minor LQTS-susceptibility genes collectively account for less than 5% of LQTS cases. In addition, three atypical LQTS or multisystem syndromic disorders that have been associated with QT prolongation have been described, including ankyrin-B syndrome, Anderson-Tawil syndrome (ATS), and Timothy syndrome (TS). Genetic testing for LQTS is recommended in patients with either a strong clinical index of suspicion or persistent QT prolongation despite their asymptomatic state. However, genetic test results must be interpreted carefully. PMID:24932360

2014-01-01

389

Incomplete gene structure prediction with almost 100% specificity  

E-print Network

The goals of gene prediction using computational approaches are to determine gene location and the corresponding functionality of the coding region. A subset of gene prediction is the gene structure prediction problem, which is to define the exon...

Chin, See Loong

2004-09-30

390

Reconstruction of a Functional Human Gene Network, with an Application for Prioritizing Positional Candidate Genes  

PubMed Central

Most common genetic disorders have a complex inheritance and may result from variants in many genes, each contributing only weak effects to the disease. Pinpointing these disease genes within the myriad of susceptibility loci identified in linkage studies is difficult because these loci may contain hundreds of genes. However, in any disorder, most of the disease genes will be involved in only a few different molecular pathways. If we know something about the relationships between the genes, we can assess whether some genes (which may reside in different loci) functionally interact with each other, indicating a joint basis for the disease etiology. There are various repositories of information on pathway relationships. To consolidate this information, we developed a functional human gene network that integrates information on genes and the functional relationships between genes, based on data from the Kyoto Encyclopedia of Genes and Genomes, the Biomolecular Interaction Network Database, Reactome, the Human Protein Reference Database, the Gene Ontology database, predicted protein-protein interactions, human yeast two-hybrid interactions, and microarray coexpressions. We applied this network to interrelate positional candidate genes from different disease loci and then tested 96 heritable disorders for which the Online Mendelian Inheritance in Man database reported at least three disease genes. Artificial susceptibility loci, each containing 100 genes, were constructed around each disease gene, and we used the network to rank these genes on the basis of their functional interactions. By following up the top five genes per artificial locus, we were able to detect at least one known disease gene in 54% of the loci studied, representing a 2.8-fold increase over random selection. This suggests that our method can significantly reduce the cost and effort of pinpointing true disease genes in analyses of disorders for which numerous loci have been reported but for which most of the genes are unknown. PMID:16685651

Franke, Lude; Bakel, Harm van; Fokkens, Like; de Jong, Edwin D.; Egmont-Petersen, Michael; Wijmenga, Cisca

2006-01-01

391

Mytilus edulis Core Histone Genes Are Organized in Two Clusters Devoid of Linker Histone Genes  

Microsoft Academic Search

  Abstract\\u000a \\u000a Comparison of histone gene cluster arrangements in several species has revealed a broad spectrum of histone gene patterns.\\u000a To elucidate the core histone gene organization in a mollusk, we have analyzed a Mytilus edulis genomic library and have isolated eight phage clones containing core histone genes. Analysis of insert DNA revealed that\\u000a the core histone genes are arranged as

Werner Albig; Ursula Warthorst; Birgit Drabent; Eva Prats; Luis Cornudella; Detlef Doenecke

2003-01-01

392

Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function  

PubMed Central

Background PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. Results The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. Conclusion PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out to dissect the PHB gene function. The conserved gene evolution indicated that the study in the model species can be translated to human and mammalian studies. PMID:20946606

2010-01-01

393

Integrating Various Resources for Gene Name Normalization  

PubMed Central

The recognition and normalization of gene mentions in biomedical literature are crucial steps in biomedical text mining. We present a system for extracting gene names from biomedical literature and normalizing them to gene identifiers in databases. The system consists of four major components: gene name recognition, entity mapping, disambiguation and filtering. The first component is a gene name recognizer based on dictionary matching and semi-supervised learning, which utilizes the co-occurrence information of a large amount of unlabeled MEDLINE abstracts to enhance feature representation of gene named entities. In the stage of entity mapping, we combine the strategies of exact match and approximate match to establish linkage between gene names in the context and the EntrezGene database. For the gene names that map to more than one database identifiers, we develop a disambiguation method based on semantic similarity derived from the Gene Ontology and MEDLINE abstracts. To remove the noise produced in the previous steps, we design a filtering method based on the confidence scores in the dictionary used for NER. The system is able to adjust the trade-off between precision and recall based on the result of filtering. It achieves an F-measure of 83% (precision: 82.5% recall: 83.5%) on BioCreative II Gene Normalization (GN) dataset, which is comparable to the current state-of-the-art. PMID:22984434

Hu, Yuncui; Li, Yanpeng; Lin, Hongfei; Yang, Zhihao; Cheng, Liangxi

2012-01-01

394

DNA methylation and evolution of duplicate genes  

PubMed Central

The evolutionary mechanisms underlying duplicate gene maintenance and divergence remain highly debated. Epigenetic modifications, such as DNA methylation, may contribute to duplicate gene evolution by facilitating tissue-specific regulation. However, the role of epigenetic divergence on duplicate gene evolution remains little understood. Here we show, using comprehensive data across 10 diverse human tissues, that DNA methylation plays critical roles in several aspects of duplicate gene evolution. We first demonstrate that duplicate genes are initially heavily methylated, before gradually losing DNA methylation as they age. Within each pair, DNA methylation divergence between duplicate partners increases with evolutionary age. Importantly, tissue-specific DNA methylation of duplicates correlates with tissue-specific expression, implicating DNA methylation as a causative factor for functional divergence of duplicate genes. These patterns are apparent in promoters but not in gene bodies, in accord with the complex relationship between gene-body DNA methylation and transcription. Remarkably, many duplicate gene pairs exhibit consistent division of DNA methylation across multiple, divergent tissues: For the majority (73%) of duplicate gene pairs, one partner is always hypermethylated compared with the other. This is indicative of a common underlying determinant of DNA methylation. The division of DNA methylation is also consistent with their chromatin accessibility profiles. Moreover, at least two sequence motifs known to interact with the Sp1 transcription factor mark promoters of more hypomethylated duplicate partners. These results demonstrate critical roles of DNA methylation, as well as complex interaction between genome and epigenome, on duplicate gene evolution. PMID:24711408

Keller, Thomas E.; Yi, Soojin V.

2014-01-01

395

Biomarker Discovery Using Statistically Significant Gene Sets  

PubMed Central

Abstract Analysis of large gene expression data sets in the presence and absence of a phenotype can lead to the selection of a group of genes serving as biomarkers jointly predicting the phenotype. Among gene selection methods, filter methods derived from ranked individual genes have been widely used in existing products for diagnosis and prognosis. Univariate filter approaches selecting genes individually, although computationally efficient, often ignore gene interactions inherent in the biological data. On the other hand, multivariate approaches selecting gene subsets are known to have a higher risk of selecting spurious gene subsets due to the overfitting of the vast number of gene subsets evaluated. Here we propose a framework of statistical significance tests for multivariate feature selection that can reduce the risk of selecting spurious gene subsets. Using three existing data sets, we show that our proposed approach is an essential step to identify such a gene set that is generated by a significant interaction of its members, even improving classification performance when compared to established approaches. This technique can be applied for the discovery of robust biomarkers for medical diagnosis. PMID:21457009

Kim, Hoon; Watkinson, John

2011-01-01

396

Gene therapy--why can it fail?  

PubMed

The success of reductionism in medicine has enabled the experimental expression of individual genes in complex living systems. The promise of gene therapy, permanent reversal or amelioration of disease symptoms without dependence on a long-lasting intake of drugs, has come within reach because of these conceptual and technical advances in molecular biology. However, there have been setbacks posing serious questions for the medical community. The incidents came at a time when technical advances in the manipulation of DNA had led to wide-spread testing of gene based therapies. In fact, the major limiting factor of this approach had been perceived to be gene delivery rather than toxicity. Here we discuss the hypothesis that knowledge of DNA sequences for relevant genes alone will not be sufficient to allow this promise to come to fruition, unless additional factors are recognized and addressed. The physiologic consequences of gene expression depend on gene dosage, transcriptional regulation by promoters, posttranscriptional editing, and interdependence among gene products, all of which vary among cells. The success of gene therapy will depend, in part, on insight into the factors summarized here, very much like successful drug therapy has depended on an understanding of the manifold influences of pharmacokinetics and pharmacodynamics. In principle, these considerations apply to all transfections, gene disruptions, and transgenic approaches and to potential clinical applications derived from them. Gaining insight and control over those factors may allow gene therapy to live up to current expectations. PMID:23484673

Weber, Georg F

2013-05-01

397

Biological Gene Delivery Vehicles: Beyond Viral Vectors  

PubMed Central

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Seow, Yiqi; Wood, Matthew J

2009-01-01

398

Gene Therapy for ALI/ARDS  

PubMed Central

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by acute respiratory failure and are associated with diverse disorders, such as pulmonary edema, pneumonia, sepsis, trauma, shock and lung contusion. Gene therapy is a potentially powerful approach to treat a variety of diseases related to ALI/ARDS. Numerous viral and non-viral methods for gene delivery to the lung have been developed, although pulmonary architecture and immune activation represent barriers to successful gene transfer. In this review, recent advances in the development of more efficient viral and non-viral gene transfer systems are discussed. In addition, the current status of gene therapy applied to ALI/ARDS-associated pulmonary diseases is reviewed. With the development of more efficient gene therapy vectors, gene therapy is a promising strategy for clinical application in the not too distant future. PMID:21742224

Lin, Xin; Dean, David A

2012-01-01

399

Predicting patient survival from longitudinal gene expression.  

PubMed

Characterizing dynamic gene expression pattern and predicting patient outcome is now significant and will be of more interest in the future with large scale clinical investigation of microarrays. However, there is currently no method that has been developed for prediction of patient outcome using longitudinal gene expression, where gene expression of patients is being monitored across time. Here, we propose a novel prediction approach for patient survival time that makes use of time course structure of gene expression. This method is applied to a burn study. The genes involved in the final predictors are enriched in the inflammatory response and immune system related pathways. Moreover, our method is consistently better than prediction methods using individual time point gene expression or simply pooling gene expression from each time point. PMID:21126232

Zhang, Yuping; Tibshirani, Robert J; Davis, Ronald W

2010-01-01

400

Apolipoprotein gene involved in lipid metabolism  

DOEpatents

Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

Rubin, Edward (Berkeley, CA); Pennacchio, Len A. (Sebastopol, CA)

2007-07-03

401

Lineage-Specific Expansion of IFIT Gene Family: An Insight into Coevolution with IFN Gene Family  

PubMed Central

In mammals, IFIT (Interferon [IFN]-induced proteins with Tetratricopeptide Repeat [TPR] motifs) family genes are involved in many cellular and viral processes, which are tightly related to mammalian IFN response. However, little is known about non-mammalian IFIT genes. In the present study, IFIT genes are identified in the genome databases from the jawed vertebrates including the cartilaginous elephant shark but not from non-vertebrates such as lancelet, sea squirt and acorn worm, suggesting that IFIT gene family originates from a vertebrate ancestor about 450 million years ago. IFIT family genes show conserved gene structure and gene arrangements. Phylogenetic analyses reveal that this gene family has expanded through lineage-specific and species-specific gene duplication. Interestingly, IFN gene family seem to share a common ancestor and a similar evolutionary mechanism; the function link of IFIT genes to IFN response is present early since the origin of both gene families, as evidenced by the finding that zebrafish IFIT genes are upregulated by fish IFNs, poly(I:C) and two transcription factors IRF3/IRF7, likely via the IFN-stimulated response elements (ISRE) within the promoters of vertebrate IFIT family genes. These coevolution features creates functional association of both family genes to fulfill a common biological process, which is likely selected by viral infection during evolution of vertebrates. Our results are helpful for understanding of evolution of vertebrate IFN system. PMID:23818968

Liu, Ying; Zhang, Yi-Bing; Liu, Ting-Kai; Gui, Jian-Fang

2013-01-01

402

GeneTack database: genes with frameshifts in prokaryotic genomes and eukaryotic mRNA sequences  

PubMed Central

Database annotations of prokaryotic genomes and eukaryotic mRNA sequences pay relatively low attention to frame transitions that disrupt protein-coding genes. Frame transitions (frameshifts) could be caused by sequencing errors or indel mutations inside protein-coding regions. Other observed frameshifts are related to recoding events (that evolved to control expression of some genes). Earlier, we have developed an algorithm and software program GeneTack for ab initio frameshift finding in intronless genes. Here, we describe a database (freely available at http://topaz.gatech.edu/GeneTack/db.html) containing genes with frameshifts (fs-genes) predicted by GeneTack. The database includes 206?991 fs-genes from 1106 complete prokaryotic genomes and 45?295 frameshifts predicted in mRNA sequences from 100 eukaryotic genomes. The whole set of fs-genes was grouped into clusters based on sequence similarity between fs-proteins (conceptually translated fs-genes), conservation of the frameshift position and frameshift direction (?1, +1). The fs-genes can be retrieved by similarity search to a given query sequence via a web interface, by fs-gene cluster browsing, etc. Clusters of fs-genes are characterized with respect to their likely origin, such as pseudogenization, phase variation, etc. The largest clusters contain fs-genes with programed frameshifts (related to recoding events). PMID:23161689

Antonov, Ivan; Baranov, Pavel; Borodovsky, Mark

2013-01-01

403

GeneTack database: genes with frameshifts in prokaryotic genomes and eukaryotic mRNA sequences.  

PubMed

Database annotations of prokaryotic genomes and eukaryotic mRNA sequences pay relatively low attention to frame transitions that disrupt protein-coding genes. Frame transitions (frameshifts) could be caused by sequencing errors or indel mutations inside protein-coding regions. Other observed frameshifts are related to recoding events (that evolved to control expression of some genes). Earlier, we have developed an algorithm and software program GeneTack for ab initio frameshift finding in intronless genes. Here, we describe a database (freely available at http://topaz.gatech.edu/GeneTack/db.html) containing genes with frameshifts (fs-genes) predicted by GeneTack. The database includes 206?991 fs-genes from 1106 complete prokaryotic genomes and 45?295 frameshifts predicted in mRNA sequences from 100 eukaryotic genomes. The whole set of fs-genes was grouped into clusters based on sequence similarity between fs-proteins (conceptually translated fs-genes), conservation of the frameshift position and frameshift direction (-1, +1). The fs-genes can be retrieved by similarity search to a given query sequence via a web interface, by fs-gene cluster browsing, etc. Clusters of fs-genes are characterized with respect to their likely origin, such as pseudogenization, phase variation, etc. The largest clusters contain fs-genes with programed frameshifts (related to recoding events). PMID:23161689

Antonov, Ivan; Baranov, Pavel; Borodovsky, Mark

2013-01-01

404

A Mixture Model Approach in Gene-Gene and Gene-Environmental Interactions for Binary Phenotypes  

PubMed Central

Summary In translational research, a genetic association study of a binary outcome has a two-fold aim: test whether genetic/environmental variables or their combinations are associated with a clinical phenotype; and determine how those combinations are grouped to predict the phenotype (i.e. which combinations have a similarly distributed phenotype, and which ones have differently distributed phenotypes). The second part of this aim has high clinical appeal, because it can directly facilitate clinical decisions. Although traditional logistic regression can detect gene-gene or gene-environmental interaction effects on binary phenotypes, they cannot decisively determine how genotype combinations are grouped to predict the phenotype. Our proposed mixture model approach is valuable in this context. It concurrently detects main and interaction effects of genetic and environmental variables through a likelihood ratio test (LRT), and conducts phenotype cluster analysis based on genetic and environmental variable combinations. The theoretical distribution of the proposed mixture model’s likelihood ratio test is robust not only to small sample size, but also to unequal sample size in various genotype and environmental subgroups. Hypothesis testing through a likelihood ratio test results in a fast algorithm for p-value calculations. Extensive simulation studies demonstrate that mixture model, overall test in logistic regression, and Monte Carlo based logic regression constantly possess the best power to detect multi-way gene/environmental combinations. The mixture model approach has the highest recovery probability to recover the true partition in the simulation studies. Its applications are exemplified in interim data analyses for two cancer studies. PMID:18991114

Li, Lang; Yu, Menggang; Jason, Robarge D.; Shen, Changyu; Azzouz, Faouzi; McLeod, Howard L.; Borges-Gonzales, Silvana; Nguyen, Anne; Skaar, Todd; Desta, Zeruesenay; Sweeney, Christopher J.; Flockhart, David A

2009-01-01

405

Upregulation of imprinted genes in mice  

PubMed Central

Imprinted genes are expressed monoallelically because one of the two copies is silenced epigentically in a parent-of-origin pattern. This pattern of expression is controlled by differential marking of parental alleles by DNA methylation and chromatin modifications, including both suppressive and permissive histone acetylation and methylation. Suppressive histone modifications mark silenced alleles of imprinted genes, while permissive histone modifications mark the active alleles, suggesting the possibility that imprinted genes would show upregulation in gene expression. However, it is currently unknown whether imprinted genes show such upregulation. To address this question in mice, we estimated the intensity of expression of 59 genes relative to the rest of the genome by analyzing microarray data. Expression levels of 24 genes were validated using quantitative real-time PCR (qPCR). Expression of imprinted genes was found to be upreguled in various adult and embryonic mouse tissues. Consistent with their functions in growth and development, imprinted genes were found to be highly expressed in extraembryonic tissues and progressively upregulated during early embryonic development. In conclusion, upregulation of imprinted genes found in this study is similar to the dosage compensation (twofold upregulation) recently reported for X-linked genes. It has been proposed that the twofold upregulation of X-linked genes has been coupled with low transcriptional variation (noise) which could lead to deleterious effects on the organism. Results of this study suggest a general need for imprinted genes in the mouse to be upregulated to certain levels in order to avoid deleterious effects of variation in gene expression. PMID:20168089

Zaitoun, Ismail; Downs, Karen M.; Rosa, Guilherme J.M.; Khatib, Hasan

2011-01-01

406

Gene therapy: Biological pacemaker created by gene transfer  

NASA Astrophysics Data System (ADS)

The pacemaker cells of the heart initiate the heartbeat, sustain the circulation, and dictate the rate and rhythm of cardiac contraction. Circulatory collapse ensues when these specialized cells are damaged by disease, a situation that currently necessitates the implantation of an electronic pacemaker. Here we report the use of viral gene transfer to convert quiescent heart-muscle cells into pacemaker cells, and the successful generation of spontaneous, rhythmic electrical activity in the ventricle in vivo. Our results indicate that genetically engineered pacemakers could be developed as a possible alternative to implantable electronic devices.

Miake, Junichiro; Marbán, Eduardo; Nuss, H. Bradley

2002-09-01

407

GRank: a middleware search engine for ranking genes by relevance to given genes  

PubMed Central

Background Biologists may need to know the set of genes that are semantically related to a given set of genes. For instance, a biologist may need to know the set of genes related to another set of genes known to be involved in a specific disease. Some works use the concept of gene clustering in order to identify semantically related genes. Others propose tools that return the set of genes that are semantically related to a given set of genes. Most of these gene similarity measures determine the semantic similarities among the genes based solely on the proximity to each other of the GO terms annotating the genes, while overlook the structural dependencies among these GO terms, which may lead to low recall and precision of results. Results We propose in this paper a search engine called GRank, which overcomes the limitations of the current gene similarity measures outlined above as follows. It employs the concept of existence dependency to determine the structural dependencies among the GO terms annotating a given set of gene. After determining the set of genes that are semantically related to input genes, GRank would use microarray experiment to rank these genes based on their degree of relativity to the input genes. We evaluated GRank experimentally and compared it with a comparable gene prediction tool called DynGO, which retrieves the genes and gene products that are relatives of input genes. Results showed marked improvement. Conclusions The experimental results demonstrated that GRank overcomes the limitations of current gene similarity measures. We attribute this performance to GRank’s use of existence dependency concept for determining the semantic relationships among gene annotations. The recall and precision values for two benchmarking datasets showed that GRank outperforms DynGO tool, which does not employ the concept of existence dependency. The demo of GRank using 11000 KEGG yeast genes and a Gene Expression Omnibus (GEO) microarray file named “GSM34635.pad” is available at: http://ecesrvr.kustar.ac.ae:8080/ (click on the link labelled Gene Ontology 2). PMID:23957362

2013-01-01

408

SHORT COMMUNICATION Adaptive eukaryote-to-eukaryote lateral gene transfer  

E-print Network

: endosymbiotic gene transfer (EGT) and lateral or horizontal gene transfer (LGT or HGT). The transfer of genesSHORT COMMUNICATION Adaptive eukaryote-to-eukaryote lateral gene transfer: stress-related genes, gene duplication and recombination, the transfer of genetic material between unrelated species is now

Nedelcu, Aurora M.

409

Predicted Highly Expressed Genes of Diverse Prokaryotic Genomes  

Microsoft Academic Search

Our approach in predicting gene expression levels relates to codon usage differences among gene classes. In prokaryotic genomes, genes that deviate strongly in codon usage from the average gene but are sufficiently similar in codon usage to ribosomal protein genes, to translation and transcription processing factors, and to chaperone-degradation proteins are predicted highly expressed (PHX). By these criteria, PHX genes

SAMUEL KARLIN; JAN MRAZEK

2000-01-01

410

Functional-Network-Based Gene Set Analysis Using Gene-Ontology  

PubMed Central

To account for the functional non-equivalence among a set of genes within a biological pathway when performing gene set analysis, we introduce GOGANPA, a network-based gene set analysis method, which up-weights genes with functions relevant to the gene set of interest. The genes are weighted according to its degree within a genome-scale functional network constructed using the functional annotations available from the gene ontology database. By benchmarking GOGANPA using a well-studied P53 data set and three breast cancer data sets, we will demonstrate the power and reproducibility of our proposed method over traditional unweighted approaches and a competing network-based approach that involves a complex integrated network. GOGANPA’s sole reliance on gene ontology further allows GOGANPA to be widely applicable to the analysis of any gene-ontology-annotated genome. PMID:23418449

Chang, Billy; Kustra, Rafal; Tian, Weidong

2013-01-01

411

Identification of nitrogen-fixing genes and gene clusters from metagenomic library of acid mine drainage.  

PubMed

Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community. PMID:24498417

Dai, Zhimin; Guo, Xue; Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan

2014-01-01

412

Computing gene expression data with a knowledge-based gene clustering approach  

PubMed Central

Computational analysis methods for gene expression data gathered in microarray experiments can be used to identify the functions of previously unstudied genes. While obtaining the expression data is not a difficult task, interpreting and extracting the information from the datasets is challenging. In this study, a knowledge-based approach which identifies and saves important functional genes before filtering based on variability and fold change differences was utilized to study light regulation. Two clustering methods were used to cluster the filtered datasets, and clusters containing a key light regulatory gene were located. The common genes to both of these clusters were identified, and the genes in the common cluster were ranked based on their coexpression to the key gene. This process was repeated for 11 key genes in 3 treatment combinations. The initial filtering method reduced the dataset size from 22,814 probes to an average of 1134 genes, and the resulting common cluster lists contained an average of only 14 genes. These common cluster lists scored higher gene enrichment scores than two individual clustering methods. In addition, the filtering method increased the proportion of light responsive genes in the dataset from 1.8% to 15.2%, and the cluster lists increased this proportion to 18.4%. The relatively short length of these common cluster lists compared to gene groups generated through typical clustering methods or coexpression networks narrows the search for novel functional genes while increasing the likelihood that they are biologically relevant. PMID:21968910

Rosa, Bruce A.; Oh, Sookyung; Montgomery, Beronda L.; Chen, Jin; Qin, Wensheng

2010-01-01

413

[Laminopathies: one gene, several diseases].  

PubMed

Lamins A and C, encoded by the LMNA gene, are nuclear proteins expressed in all post-mitotic cells. Together with B-type lamins, they form a meshwork of proteins beneath the inner nuclear membrane, the lamina, in connection with the cytoskeleton. Lamins A/C also interact with chromatin and numerous proteins, including transcription factors. Mutations in LMNA are responsible for more than ten different disorders, commonly called "laminopathies". These diseases affect tissues in a specific (striated muscle, adipose tissue, peripheral nerve) or in a systemic manner (premature ageing syndromes). This wide spectrum of phenotypes is associated to a wide variety of mutations. This large clinical and genetic heterogeneity, unique to the LMNA gene, makes genotype-phenotype relations particularly difficult to establish. However, correlations have been obtained in several cases. Hence, LMNA mutations identified in premature ageing syndromes lead to the accumulation of immature proteins with a toxic effect for cells. Mutations in laminopathies of the adipose tissue mainly localize in the Ig-like domain of the proteins, potentially affecting the interaction with the SREBP-1 transcription factor. In laminopathies of the striated muscles, the mutations are spread throughout the gene. These mutations are thought to induce structural modifications of the proteins, thereby affecting their polymerization into nuclear lamina. Such defect would lead to a mechanical weakness of the nuclear lamina and of the cells, particularly in striated muscles continuously stretching. The exploration of pathophysiological mechanisms of LMNA mutations largely benefits from the numerous mouse models created, which have been widely used to analyze affected molecular pathways and to test putative therapeutic treatments. PMID:21982404

Bertrand, Anne T; Chikhaoui, Khadija; Ben Yaou, Rabah; Bonne, Gisèle

2011-01-01

414

Sequence analysis of porothramycin biosynthetic gene cluster.  

PubMed

The biosynthetic gene cluster of porothramycin, a sequence-selective DNA alkylating compound, was identified in the genome of producing strain Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A 39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high similarity with homologous genes from biosynthetic gene cluster of closely related pyrrolobenzodiazepine (PBD) compound anthramycin. However, considering the structures of both compounds, the number of differences in the gene composition of compared biosynthetic gene clusters was unexpectedly high, indicating participation of alternative enzymes in biosynthesis of both porothramycin precursors, anthranilate, and branched L-proline derivative. Based on the sequence analysis of putative NRPS modules Por20 and Por21, we suppose that in porothramycin biosynthesis, the methylation of anthranilate unit occurs prior to the condensation reaction, while modifications of branched proline derivative, oxidation, and dimethylation of the side chain occur on already condensed PBD core. Corresponding two specific methyltransferase encoding genes por26 and por25 were identified in the porothramycin gene cluster. Surprisingly, also methyltransferase gene por18 homologous to orf19 from anthramycin biosynthesis was detected in porothramycin gene cluster even though the appropriate biosynthetic step is missing, as suggested by ultra high-performance liquid chromatography-diode array detection-mass spectrometry (UHPLC-DAD-MS) analysis of the product in the S. albus culture broth. PMID:25128200

Najmanova, Lucie; Ulanova, Dana; Jelinkova, Marketa; Kamenik, Zdenek; Kettnerova, Eliska; Koberska, Marketa; Gazak, Radek; Radojevic, Bojana; Janata, Jiri

2014-11-01

415

Structure of the gene for uteroferrin.  

PubMed

The published structure of the gene for uteroferrin differs from that of the human and mouse tartrate-resistant acid phosphatase (TRAP) genes. Polymerase chain reaction using genomic DNA as template and primers designed from exon 2 of the porcine uteroferrin gene amplified a product containing two previously undescribed introns. Because of these discrepancies, we cloned an EcoRI fragment from a porcine genomic BAC library containing the uteroferrin gene, and the region containing the uteroferrin gene was completely sequenced. The uteroferrin gene spanned 2.5 kb and contained five exons, which is similar to the structure previously reported for human and mouse TRAP genes but different from the published structure of the uteroferrin gene. Southern blotting of porcine genomic DNA digested with a variety of enzymes was consistent with the sequence that we obtained. The most likely explanation for the differing results is that the previously reported structure for the uteroferrin gene was the result of artifactual elimination of introns 2 and 3 by bacteria and artifactual recombination of the region upstream of the transcription start site of this gene. PMID:11098218

Vallet, J L; Fahrenkrug, S C

2000-11-01

416

Differential gene expression during multistage carcinogenesis.  

PubMed Central

The use of the mouse skin multistage model of carcinogenesis has aided our understanding of critical target genes in chemical carcinogenesis. The mutagenic activation of the Harvey-ras proto-oncogene has been found to be an early event associated with the initiation of mouse skin tumors by the polycyclic aromatic hydrocarbon 7,12 dimethylbenz[alpha]anthracene and the pure initiator ethyl carbamate (urethane). In contrast to chemical initiation of mouse skin tumors, ionizing radiation-initiated malignant skin tumors have been shown to possess distinct non-ras transforming gene(s). Differential screening of cDNA libraries made from chemically initiated malignant skin tumors has been used to identify a number of cellular gene transcripts that are overexpressed during mouse skin tumor progression. These differentially expressed genes include beta-actin, ubiquitin, a hyperproliferative keratin (K6), a gene whose product is a member of a fatty acid or lipid-binding protein family, and a gene called transin or stromelysin. The overexpression of the stromelysin gene, which encodes a metalloproteinase that degrades proteins in the basement membrane, is hypothesized to play a functional role in malignant tumor cell invasion and metastasis. We believe that the cloning, identification, and characterization of gene sequences that are differentially expressed during tumor progression could lead to the discovery of gene products that either play functional roles in skin tumor progression or in the maintenance of various progressive tumor phenotypes. PMID:1773801

Bowden, G T; Krieg, P

1991-01-01

417

IL26 gene inactivation in Equidae.  

PubMed

Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution. PMID:23808390

Shakhsi-Niaei, M; Drögemüller, M; Jagannathan, V; Gerber, V; Leeb, T

2013-12-01

418

Human DNA repair and recombination genes  

SciTech Connect

Several genes involved in mammalian DNA repair pathways were identified by complementation analysis and chromosomal mapping based on hybrid cells. Eight complementation groups of rodent mutants defective in the repair of uv radiation damage are now identified. At least seven of these genes are probably essential for repair and at least six of them control the incision step. The many genes required for repair of DNA cross-linking damage show overlap with those involved in the repair of uv damage, but some of these genes appear to be unique for cross-link repair. Two genes residing on human chromosome 19 were cloned from genomic transformants using a cosmid vector, and near full-length cDNA clones of each gene were isolated and sequenced. Gene ERCC2 efficiently corrects the defect in CHO UV5, a nucleotide excision repair mutant. Gene XRCC1 normalizes repair of strand breaks and the excessive sister chromatid exchange in CHO mutant EM9. ERCC2 shows a remarkable /approximately/52% overall homology at both the amino acid and nucleotide levels with the yeast RAD3 gene. Evidence based on mutation induction frequencies suggests that ERCC2, like RAD3, might also be an essential gene for viability. 100 refs., 4 tabs.

Thompson, L.H.; Weber, C.A.; Jones, N.J.

1988-09-01

419

Detection of EPO gene doping in blood.  

PubMed

Gene doping--or the abuse of gene therapy--will continue to threaten the sports world. History has shown that progress in medical research is likely to be abused in order to enhance human performance. In this review, we critically discuss the progress and the risks associated with the field of erythropoietin (EPO) gene therapy and its applicability to EPO gene doping. We present typical vector systems that are employed in ex vivo and in vivo gene therapy trials. Due to associated risks, gene doping is not a feasible alternative to conventional EPO or blood doping at this time. Nevertheless, it is well described that about half of the elite athlete population is in principle willing to risk its health to gain a competitive advantage. This includes the use of technologies that lack safety approval. Sophisticated detection approaches are a prerequisite for prevention of unapproved and uncontrolled use of gene therapy technology. In this review, we present current detection approaches for EPO gene doping, with a focus on blood-based direct and indirect approaches. Gene doping is detectable in principle, and recent DNA-based detection strategies enable long-term detection of transgenic DNA (tDNA) following in vivo gene transfer. PMID:22508654

Neuberger, Elmo W I; Jurkiewicz, Magdalena; Moser, Dirk A; Simon, Perikles

2012-11-01

420

Skeletal muscle specific genes networks in cattle  

PubMed Central

While physiological differences across skeletal muscles have been described, the differential gene expression underlying them and the discovery of how they interact to perform specific biological processes are largely to be elucidated. The purpose of the present study was, firstly, to profile by cDNA microarrays the differential gene expression between two skeletal muscle types, Psoas major (PM) and Flexor digitorum (FD), in beef cattle and then to interpret the results in the context of a bovine gene coexpression network, detecting possible changes in connectivity across the skeletal muscle system. Eighty four genes were differentially expressed (DE) between muscles. Approximately 54% encoded metabolic enzymes and structural-contractile proteins. DE genes were involved in similar processes and functions, but the proportion of genes in each category varied within each muscle. A correlation matrix was obtained for 61 out of the 84 DE genes from a gene coexpression network. Different groups of coexpression were observed, the largest one having 28 metabolic and contractile genes, up-regulated in PM, and mainly encoding fast-glycolytic fibre structural components and glycolytic enzymes. In FD, genes related to cell support seemed to constitute its identity feature and did not positively correlate to the rest of DE genes in FD. Moreover, changes in connectivity for some DE genes were observed in the different gene ontologies. Our results confirm the existence of a muscle dependent transcription and coexpression pattern and suggest the necessity of integrating different muscle types to perform comprehensive networks for the transcriptional landscape of bovine skeletal muscle. Electronic supplementary material The online version of this article (doi:10.1007/s10142-010-0175-2) contains supplementary material, which is available to authorized users. PMID:20524025

Rueda, Julia; Carabano, Maria J.; Reverter, Antonio; McWilliam, Sean; Gonzalez, Carmen; Diaz, Clara

2010-01-01

421

Application of multidisciplinary analysis to gene expression.  

SciTech Connect

Molecular analysis of cancer, at the genomic level, could lead to individualized patient diagnostics and treatments. The developments to follow will signal a significant paradigm shift in the clinical management of human cancer. Despite our initial hopes, however, it seems that simple analysis of microarray data cannot elucidate clinically significant gene functions and mechanisms. Extracting biological information from microarray data requires a complicated path involving multidisciplinary teams of biomedical researchers, computer scientists, mathematicians, statisticians, and computational linguists. The integration of the diverse outputs of each team is the limiting factor in the progress to discover candidate genes and pathways associated with the molecular biology of cancer. Specifically, one must deal with sets of significant genes identified by each method and extract whatever useful information may be found by comparing these different gene lists. Here we present our experience with such comparisons, and share methods developed in the analysis of an infant leukemia cohort studied on Affymetrix HG-U95A arrays. In particular, spatial gene clustering, hyper-dimensional projections, and computational linguistics were used to compare different gene lists. In spatial gene clustering, different gene lists are grouped together and visualized on a three-dimensional expression map, where genes with similar expressions are co-located. In another approach, projections from gene expression space onto a sphere clarify how groups of genes can jointly have more predictive power than groups of individually selected genes. Finally, online literature is automatically rearranged to present information about genes common to multiple groups, or to contrast the differences between the lists. The combination of these methods has improved our understanding of infant leukemia. While the complicated reality of the biology dashed our initial, optimistic hopes for simple answers from microarrays, we have made progress by combining very different analytic approaches.

Wang, Xuefel (University of New Mexico, Albuquerque, NM); Kang, Huining (University of New Mexico, Albuquerque, NM); Fields, Chris (New Mexico State University, Las Cruces, NM); Cowie, Jim R. (New Mexico State University, Las Cruces, NM); Davidson, George S.; Haaland, David Michael; Sibirtsev, Valeriy (New Mexico State University, Las Cruces, NM); Mosquera-Caro, Monica P. (University of New Mexico, Albuquerque, NM); Xu, Yuexian (University of New Mexico, Albuquerque, NM); Martin, Shawn Bryan; Helman, Paul (University of New Mexico, Albuquerque, NM); Andries, Erik (University of New Mexico, Albuquerque, NM); Ar, Kerem (University of New Mexico, Albuquerque, NM); Potter, Jeffrey (University of New Mexico, Albuquerque, NM); Willman, Cheryl L. (University of New Mexico, Albuquerque, NM); Murphy, Maurice H. (University of New Mexico, Albuquerque, NM)

2004-01-01

422

Selection of Phototransduction Genes in Homo sapiens  

PubMed Central

Purpose. We investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level. Methods. SNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively. Results. Six of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes. Conclusions. There is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies. PMID:23868983

Christopher, Mark; Scheetz, Todd E.; Mullins, Robert F.; Abramoff, Michael D.

2013-01-01

423

Antagonistic functional duality of cancer genes.  

PubMed

Cancer evolution is a stochastic process both at the genome and gene levels. Most of tumors contain multiple genetic subclones, evolving in either succession or in parallel, either in a linear or branching manner, with heterogeneous genome and gene alterations, extensively rewired signaling networks, and addicted to multiple oncogenes easily switching with each other during cancer progression and medical intervention. Hundreds of discovered cancer genes are classified according to whether they function in a dominant (oncogenes) or recessive (tumor suppressor genes) manner in a cancer cell. However, there are many cancer "gene-chameleons", which behave distinctly in opposite way in the different experimental settings showing antagonistic duality. In contrast to the widely accepted view that mutant NADP(+)-dependent isocitrate dehydrogenases 1/2 (IDH1/2) and associated metabolite 2-hydroxyglutarate (R)-enantiomer are intrinsically "the drivers" of tumourigenesis, mutant IDH1/2 inhibited, promoted or had no effect on cell proliferation, growth and tumorigenicity in diverse experiments. Similar behavior was evidenced for dozens of cancer genes. Gene function is dependent on genetic network, which is defined by the genome context. The overall changes in karyotype can result in alterations of the role and function of the same genes and pathways. The diverse cell lines and tumor samples have been used in experiments for proving gene tumor promoting/suppressive activity. They all display heterogeneous individual karyotypes and disturbed signaling networks. Consequently, the effect and function of gene under investigation can be opposite and versatile in cells with different genomes that may explain antagonistic duality of cancer genes and the cell type- or the cellular genetic/context-dependent response to the same protein. Antagonistic duality of cancer genes might contribute to failure of chemotherapy. Instructive examples of unexpected activity of cancer genes and "paradoxical" effects of different anticancer drugs depending on the cellular genetic context/signaling network are discussed. PMID:23933273

Stepanenko, A A; Vassetzky, Y S; Kavsan, V M

2013-10-25

424

QB1 - Stochastic Gene Regulation  

SciTech Connect

Summaries of this presentation are: (1) Stochastic fluctuations or 'noise' is present in the cell - Random motion and competition between reactants, Low copy, quantization of reactants, Upstream processes; (2) Fluctuations may be very important - Cell-to-cell variability, Cell fate decisions (switches), Signal amplification or damping, stochastic resonances; and (3) Some tools are available to mode these - Kinetic Monte Carlo simulations (SSA and variants), Moment approximation methods, Finite State Projection. We will see how modeling these reactions can tell us more about the underlying processes of gene regulation.

Munsky, Brian [Los Alamos National Laboratory

2012-07-23

425

Gene variants influence insulin production  

Cancer.gov

A new analytical tool has found three previously unknown gene variants relevant to diabetes, and researchers say it also may be useful in unraveling other complex diseases like obesity and cancer. In research published online December 23 in Nature Genetics, scientists say the relatively rare genetic variants influence insulin production,a finding that could offer new clues about the genetic factors behind diabetes. The study included participants from the University of North Carolina School of Medicine (home to the Lineberger Comprehensive Cancer Center), the University of Michigan (home to the University of Michigan Comprehensive Cancer Center), and the University of Eastern Finland.

426

Gene Ontology annotations and resources.  

PubMed

The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources. PMID:23161678

Blake, J A; Dolan, M; Drabkin, H; Hill, D P; Li, Ni; Sitnikov, D; Bridges, S; Burgess, S; Buza, T; McCarthy, F; Peddinti, D; Pillai, L; Carbon, S; Dietze, H; Ireland, A; Lewis, S E; Mungall, C J; Gaudet, P; Chrisholm, R L; Fey, P; Kibbe, W A; Basu, S; Siegele, D A; McIntosh, B K; Renfro, D P; Zweifel, A E; Hu, J C; Brown, N H; Tweedie, S; Alam-Faruque, Y; Apweiler, R; Auchinchloss, A; Axelsen, K; Bely, B; Blatter, M -C; Bonilla, C; Bouguerleret, L; Boutet, E; Breuza, L; Bridge, A; Chan, W M; Chavali, G; Coudert, E; Dimmer, E; Estreicher, A; Famiglietti, L; Feuermann, M; Gos, A; Gruaz-Gumowski, N; Hieta, R; Hinz, C; Hulo, C; Huntley, R; James, J; Jungo, F; Keller, G; Laiho, K; Legge, D; Lemercier, P; Lieberherr, D; Magrane, M; Martin, M J; Masson, P; Mutowo-Muellenet, P; O'Donovan, C; Pedruzzi, I; Pichler, K; Poggioli, D; Porras Millán, P; Poux, S; Rivoire, C; Roechert, B; Sawford, T; Schneider, M; Stutz, A; Sundaram, S; Tognolli, M; Xenarios, I; Foulgar, R; Lomax, J; Roncaglia, P; Khodiyar, V K; Lovering, R C; Talmud, P J; Chibucos, M; Giglio, M Gwinn; Chang, H -Y; Hunter, S; McAnulla, C; Mitchell, A; Sangrador, A; Stephan, R; Harris, M A; Oliver, S G; Rutherford, K; Wood, V; Bahler, J; Lock, A; Kersey, P J; McDowall, D M; Staines, D M; Dwinell, M; Shimoyama, M; Laulederkind, S; Hayman, T; Wang, S -J; Petri, V; Lowry, T; D'Eustachio, P; Matthews, L; Balakrishnan, R; Binkley, G; Cherry, J M; Costanzo, M C; Dwight, S S; Engel, S R; Fisk, D G; Hitz, B C; Hong, E L; Karra, K; Miyasato, S R; Nash, R S; Park, J; Skrzypek, M S; Weng, S; Wong, E D; Berardini, T Z; Huala, E; Mi, H; Thomas, P D; Chan, J; Kishore, R; Sternberg, P; Van Auken, K; Howe, D; Westerfield, M

2013-01-01

427

Race, genes and preterm delivery.  

PubMed Central

High rates of preterm delivery (PTD) among African Americans are the leading cause of excess infant mortality among African Americans. Failure to fully explain racial disparity in PTD has led to speculation that genetic factors might contribute to this disparity. Current evidence suggests that genetic factors contribute to PTD, but this does not imply that genetic factors contribute to racial disparity in PTD. Environmental factors clearly contribute to PTD. Many of these factors acting over a women's life prior to pregnancy disproportionately affect African Americans and contribute significantly to racial disparity in PTD. Thus, inferring genetic contribution to racial disparity in PTD by attempting to control for environmental factors measured at a single point in time is flawed. There is emerging evidence of gene-environment interactions for PTD, some of which disproportionately affect African Americans. There is also evidence of racial differences in the prevalence of polymorphisms potentially related to PTD. However, to date there is no direct evidence that these differences contribute significantly to racial disparity in PTD. Given the complexity of polygenic conditions such as PTD, the possibility of any single gene contributing substantially to racial disparity in PTD seems remote. PMID:16334498

Fiscella, Kevin

2005-01-01

428

Gene networks and liar paradoxes  

PubMed Central

Network motifs are small patterns of connections, found over-represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ‘on’ it tends towards ‘off’ – and vice versa. Here, we argue that such self-opposition, if considered dimensionlessly, is analogous to the liar paradox: ‘This statement is false’. When ‘true’ it implies ‘false’ – and vice versa. Such logical constructs have provided philosophical consternation for over 2000 years. Extending the analogy, other network topologies give strikingly varying outputs over different dimensions. For example, the motif ‘A activates B and A. B inhibits A’ can give switches or oscillators with time only, or can lead to Turing-type patterns with both space and time (spots, stripes or waves). It is argued here that the dimensionless form reduces to a variant of ‘The following statement is true. The preceding statement is false’. Thus, merely having a static topological description of a gene network can lead to a liar paradox. Network diagrams are only snapshots of dynamic biological processes and apparent paradoxes can reveal important biological mechanisms that are far from paradoxical when considered explicitly in time and space. PMID:19722183

Isalan, Mark

2009-01-01

429

Genes That Bias Mendelian Segregation  

PubMed Central

Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion. PMID:24830502

Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

2014-01-01

430

Heteroplasmy and organelle gene dynamics.  

PubMed Central

This study assesses factors that influence the rates of change of organelle gene diversity and the maintenance of heteroplasmy. Losses of organelle gene diversity within individuals via vegetative segregation during ontogeny are paramount to resultant spatial and temporal patterns. Steady-state losses of organelle variation from the zygote to the gametes are determined by the effective number of organelles, which will be approximately equal to the number of intracellular organelles if random segregation prevails. Both rapid increases in organelle number after zygote formation and reductions at germ lines will reduce variation within individuals. Terminal reductions in organelles must be to very low copy numbers (<5) for substantial losses in variation to occur rapidly. Nonrandom clonal expansion and vegetative segregation during gametogenesis may be effective in reducing genetic variation in gametes. If organelles are uniparentally inherited, the asymptotic expectations for effective numbers of gametes and spatial differentiation will be identical for homoplasmic and heteroplasmic conditions. The rate of attainment of asymptote for heteroplasmic organelles, however, is governed by the rate of loss of variation during ontogeny. With sex-biased dispersal, the effective number of gametes is maximized when the proportional contributions of the sex having the higher dispersal rate are low. PMID:9799281

Chesser, R K

1998-01-01

431

The MHC class I genes of zebrafish.  

PubMed

Major histocompatibility complex (MHC) molecules play a central role in the immune response and in the recognition of non-self. Found in all jawed vertebrate species, including zebrafish and other teleosts, MHC genes are considered the most polymorphic of all genes. In this review we focus on the multi-faceted diversity of zebrafish MHC class I genes, which are classified into three sequence lineages: U, Z, and L. We examine the polygenic, polymorphic, and haplotypic diversity of the zebrafish MHC class I genes, discussing known and postulated functional differences between the different class I lineages. In addition, we provide the first comprehensive nomenclature for the L lineage genes in zebrafish, encompassing at least 15 genes, and characterize their sequence properties. Finally, we discuss how recent findings have shed new light on the remarkably diverse MHC loci of this species. PMID:24631581

Dirscherl, Hayley; McConnell, Sean C; Yoder, Jeffrey A; de Jong, Jill L O

2014-09-01

432

HLA Immune Function Genes in Autism  

PubMed Central

The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects. PMID:22928105

Torres, Anthony R.; Westover, Jonna B.; Rosenspire, Allen J.

2012-01-01

433

Estimation and Testing of Gene Expression Heterosis  

PubMed Central

Heterosis, also known as the hybrid vigor, occurs when the mean phenotype of hybrid off-spring is superior to that of its two inbred parents. The heterosis phenomenon is extensively utilized in agriculture though the molecular basis is still unknown. In an effort to understand phenotypic heterosis at the molecular level, researchers have begun to compare expression levels of thousands of genes between parental inbred lines and their hybrid offspring to search for evidence of gene expression heterosis. Standard statistical approaches for separately analyzing expression data for each gene can produce biased and highly variable estimates and unreliable tests of heterosis. To address these shortcomings, we develop a hierarchical model to borrow information across genes. Using our modeling framework, we derive empirical Bayes estimators and an inference strategy to identify gene expression heterosis. Simulation results show that our proposed method outperforms the more traditional strategy used to detect gene expression heterosis. This article has supplementary material online.

Liu, Peng; Nettleton, Dan

2014-01-01

434

Regulation of the human TRAIL gene  

PubMed Central

TRAIL is a member of the TNF superfamily that induces tumor-selective cell death by engaging the pro-apoptotic death receptors DR4 and DR5. The antitumor potential of the TRAIL pathway has been targeted by several therapeutic approaches including recombinant TRAIL and TRAIL-receptor agonist antibodies among others. Interest in sensitizing tumor cells to TRAIL-mediated apoptosis has driven investigations of TRAIL-receptor gene regulation, though regulation of the TRAIL gene has been less studied. Physiologically, TRAIL serves as a pro-apoptotic effector molecule in the immune surveillance of cancer that is conditionally expressed by immune cells upon stimulation via an interferon-response element that was identified in early studies of the TRAIL gene promoter. Here, we map the TRAIL gene promoter and review studies of TRAIL gene regulation that involve several modalities of gene regulation including transcription factors, epigenetics, single-nucleotide polymorphisms and functionally distinct isoforms. PMID:22892844

Allen, Joshua E.; El-Deiry, Wafik S.

2012-01-01

435

Homeobox genes expressed during echinoderm arm regeneration.  

PubMed

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

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

2014-04-01

436

In Vivo Noninvasive Imaging for Gene Therapy  

PubMed Central

Gene therapy is reaching a stage where some clinical benefits have been demonstrated on patients involved in phase I/II clinical trials. However, in many cases, the clinical benefit is hardly measurable and progress in the improvement of gene therapy formulations is hampered by the lack of objective clinical endpoints to measure transgene delivery and to quantitate transgene expression. However, these endpoints rely almost exclusively on the analysis of biopsies by molecular and histopathological methods. These methods provide only a limited picture of the situation. Therefore, there is a need for a technology that would allow precise, spacio-temporal measurement of gene expression on a whole body scale upon administration of the gene delivery vector. In the field of gene therapy, a considerable effort is being invested in the development of noninvasive imaging of gene expression and this review presents the various strategies currently being developed. PMID:12721514

2003-01-01

437

Gene therapy for carcinoma of the breast  

PubMed Central

In view of the limited success of available treatment modalities for breast cancer, alternative and complementary strategies need to be developed. The delineation of the molecular basis of breast cancer provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches for carcinoma of the breast have been developed. These approaches can be divided into six broad categories: (1) mutation compensation, (2) molecular chemotherapy, (3) proapoptotic gene therapy, (4) antiangiogenic gene therapy, (5) genetic immunopotentiation, and (6) genetic modulation of resistance/sensitivity. Clinical trials for breast cancer have been initiated to evaluate safety, toxicity, and efficacy. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified and advances in vector design are realized, gene therapy will play an increasing role in clinical breast cancer treatment. PMID:16410823

Stoff-Khalili, MA; Dall, P; Curiel, DT

2007-01-01

438

Semantic Particularity Measure for Functional Characterization of Gene Sets Using Gene Ontology  

PubMed Central

Background Genetic and genomic data analyses are outputting large sets of genes. Functional comparison of these gene sets is a key part of the analysis, as it identifies their shared functions, and the functions that distinguish each set. The Gene Ontology (GO) initiative provides a unified reference for analyzing the genes molecular functions, biological processes and cellular components. Numerous semantic similarity measures have been developed to systematically quantify the weight of the GO terms shared by two genes. We studied how gene set comparisons can be improved by considering gene set particularity in addition to gene set similarity. Results We propose a new approach to compute gene set particularities based on the information conveyed by GO terms. A GO term informativeness can be computed using either its information content based on the term frequency in a corpus, or a function of the term's distance to the root. We defined the semantic particularity of a set of GO terms Sg1 compared to another set of GO terms Sg2. We combined our particularity measure with a similarity measure to compare gene sets. We demonstrated that the combination of semantic similarity and semantic particularity measures was able to identify genes with particular functions from among similar genes. This differentiation was not recognized using only a semantic similarity measure. Conclusion Semantic particularity should be used in conjunction with semantic similarity to perform functional analysis of GO-annotated gene sets. The principle is generalizable to other ontologies. PMID:24489737

Bettembourg, Charles; Diot, Christian; Dameron, Olivier

2014-01-01

439

Origin and Ascendancy of a Chimeric Fusion Gene: The ?/?-Globin Gene of Paenungulate Mammals  

PubMed Central

The ?-globin gene (HBD) of eutherian mammals exhibits a propensity for recombinational exchange with the closely linked ?-globin gene (HBB) and has been independently converted by the HBB gene in multiple lineages. Here we report the presence of a chimeric ?/? fusion gene in the African elephant (Loxodonta africana) that was created by unequal crossing-over between misaligned HBD and HBB paralogs. The recombinant chromosome that harbors the ?/? fusion gene in elephants is structurally similar to the “anti-Lepore” duplication mutant of humans (the reciprocal exchange product of the hemoglobin Lepore deletion mutant). However, the situation in the African elephant is unique in that the chimeric ?/? fusion gene supplanted the parental HBB gene and is therefore solely responsible for synthesizing the ?-chain subunits of adult hemoglobin. A phylogenetic survey of ?-like globin genes in afrotherian and xenarthran mammals revealed that the origin of the chimeric ?/? fusion gene and the concomitant inactivation of the HBB gene predated the radiation of “Paenungulata,” a clade of afrotherian mammals that includes three orders: Proboscidea (elephants), Sirenia (dugongs and manatees), and Hyracoidea (hyraxes). The reduced fitness of the human Hb Lepore deletion mutant helps to explain why independently derived ?/? fusion genes (which occur on an anti-Lepore chromosome) have been fixed in a number of mammalian lineages, whereas the reciprocal ?/? fusion gene (which occurs on a Lepore chromosome) has yet to be documented in any nonhuman mammal. This illustrates how the evolutionary fates of chimeric fusion genes can be strongly influenced by their recombinational mode of origin. PMID:19332641

Opazo, Juan C.; Sloan, Angela M.; Campbell, Kevin L.

2009-01-01

440

Stable gene transfer and tissue-specific expression of a human globin gene using adenoviral vectors.  

PubMed Central

Helper-free double recombinant adenoviruses containing a genomic human globin gene and the neomycin resistance gene (neoR) have been constructed. The inserted globin and neoR genes are stable and transcription of two human globin genes (beta and a hybrid gamma-beta gene) is correctly initiated at the respective globin promoter during lytic infection in 293 cells. The neoR gene driven by the SV40 early promoter confers G418 resistance to human fibroblasts and K562 human erythro-leukemia cells transformed with these viruses. Most neoR clones contain the entire recombinant viral genome, including the inserted globin gene, integrated into their chromosomes. Normally, K562 cells express their gamma but not their beta globin genes. The transferred human beta globin gene was not expressed in either K562 cells or fibroblasts. However, the hybrid gamma-beta globin gene was expressed in all K562 clones that contained the gene whereas gamma-beta mRNA was barely detectable in the fibroblasts. This demonstrates tissue-specific expression of the adenovirus-transferred globin gene. Furthermore, the two transferred genes, globin and neoR, which are situated more than 20 kb apart in the viral genome appear to be independently regulated. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:3780679

Karlsson, S; Van Doren, K; Schweiger, S G; Nienhuis, A W; Gluzman, Y

1986-01-01

441

Divergence of Gene Body DNA Methylation and Evolution of Plant Duplicate Genes  

PubMed Central

It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes. PMID:25310342

Wang, Jun; Marowsky, Nicholas C.; Fan, Chuanzhu

2014-01-01

442

Sexy gene conversions: locating gene conversions on the X-chromosome.  

PubMed

Gene conversion can have a profound impact on both the short- and long-term evolution of genes and genomes. Here, we examined the gene families that are located on the X-chromosomes of human (Homo sapiens), chimpanzee (Pan troglodytes), mouse (Mus musculus) and rat (Rattus norvegicus) for evidence of gene conversion. We identified seven gene families (WD repeat protein family, Ferritin Heavy Chain family, RAS-related Protein RAB-40 family, Diphosphoinositol polyphosphate phosphohydrolase family, Transcription Elongation Factor A family, LDOC1-related family, Zinc Finger Protein ZIC, and GLI family) that show evidence of gene conversion. Through phylogenetic analyses and synteny evidence, we show that gene conversion has played an important role in the evolution of these gene families and that gene conversion has occurred independently in both primates and rodents. Comparing the results with those of two gene conversion prediction programs (GENECONV and Partimatrix), we found that both GENECONV and Partimatrix have very high false negative rates (i.e. failed to predict gene conversions), which leads to many undetected gene conversions. The combination of phylogenetic analyses with physical synteny evidence exhibits high resolution in the detection of gene conversions. PMID:19487239

Lawson, Mark J; Zhang, Liqing

2009-08-01

443

Finding an Gene on the Chromosome Map  

NSDL National Science Digital Library

In this activity, students use a pedigree and jigsaw puzzles to explore how scientists use genetic information from a family to identify a gene associated with a genetic disorder. Students will learn that all humans have the same genes, arranged in the same order along the twenty-three pairs of chromosomes. They will also discover how an alteration in the DNA sequence of a gene may cause a genetic disorder.

Utah, The U.

2004-01-01

444

The Human Gene Mutation Database: 2008 update  

Microsoft Academic Search

The Human Gene Mutation Database (HGMD®) is a comprehensive core collection of germline mutations in nuclear genes that underlie or are associated with human inherited\\u000a disease. Here, we summarize the history of the database and its current resources. By December 2008, the database contained\\u000a over 85,000 different lesions detected in 3,253 different genes, with new entries currently accumulating at a

Peter D Stenson; Matthew Mort; Edward V Ball; Katy Howells; Andrew D Phillips; Nick ST Thomas; David N Cooper

2009-01-01

445

Genie---Gene Finding in Drosophila melanogaster  

Microsoft Academic Search

A hidden Markov model-based gene-finding system called Genie was applied to the genomic Adh region in Drosophila melanogaster as a part of the Genome Annotation Assessment Project (GASP). Predictions from three versions of the Genie gene-finding system were submitted, one based on statistical properties of coding genes, a second included EST alignment information, and a third that integrated protein sequence

Martin G. Reese; David Kulp; Hari Tammana; David Haussler

2000-01-01

446

Regulation of KSHV Lytic Gene Expression  

Microsoft Academic Search

The life cycle of KSHV, latency versus lytic replication, is mainly determined at the transcriptional regulation level. A\\u000a viral immediate-early gene product, replication and transcription activator (RTA), has been identified as the molecular switch\\u000a for initiation of the lytic gene expression program from latency. Here we review progress on two key questions: how RTA gene\\u000a expression is controlled by viral

H. Deng; Y. Liang; R. Sun

447

Methods for monitoring multiple gene expression  

DOEpatents

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

Berka, Randy; Bachkirova, Elena; Rey, Michael

2013-10-01

448

Evolution of trappin genes in mammals  

PubMed Central

Background Trappin is a multifunctional host-defense peptide that has antiproteolytic, antiinflammatory, and antimicrobial activities. The numbers and compositions of trappin paralogs vary among mammalian species: human and sheep have a single trappin-2 gene; mouse and rat have no trappin gene; pig and cow have multiple trappin genes; and guinea pig has a trappin gene and two other derivativegenes. Independent duplications of trappin genes in pig and cow were observed recently after the species were separated. To determine whether these trappin gene duplications are restricted only to certain mammalian lineages, we analyzed recently-developed genome databases for the presence of duplicate trappin genes. Results The database analyses revealed that: 1) duplicated trappin multigenes were found recently in the nine-banded armadillo; 2) duplicated two trappin genes had been found in the Afrotherian species (elephant, tenrec, and hyrax) since ancient days; 3) a single trappin-2 gene was found in various eutherians species; and 4) no typical trappin gene has been found in chicken, zebra finch, and opossum. Bayesian analysis estimated the date of the duplication of trappin genes in the Afrotheria, guinea pig, armadillo, cow, and pig to be 244, 35, 11, 13, and 3 million-years ago, respectively. The coding regions of trappin multigenes of almadillo, bovine, and pig evolved much faster than the noncoding exons, introns, and the flanking regions, showing that these genes have undergone accelerated evolution, and positive Darwinian selection was observed in pig-specific trappin paralogs. Conclusion These results suggest that trappin is an eutherian-specific molecule and eutherian genomes have the potential to form trappin multigenes. PMID:20113469

2010-01-01

449

Methods for monitoring multiple gene expression  

DOEpatents

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

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

2012-05-01

450

Translational regulation of rotavirus gene expression.  

PubMed

Rotavirus mRNAs are transcribed from 11 genomic dsRNA segments within a subviral particle. The mRNAs are extruded into the cytoplasm where they serve as mRNA for protein synthesis and as templates for packaging and replication into dsRNA. The molecular steps in the replication pathway that regulate the levels of viral gene expression are not well defined. We have investigated potential mechanisms of regulation of rotavirus gene expression by functional evaluation of two differentially expressed viral mRNAs. NSP1 (gene 5) and VP6 (gene 6) are expressed early in infection, and VP6 is expressed in excess over NSP1. We formulated the hypothesis that the amounts of NSP1 and VP6 were regulated by the translational efficiencies of the respective mRNAs. We measured the levels of gene 5 and gene 6 mRNA and showed that they were not significantly different, and protein analysis indicated no difference in stability of NSP1 compared with VP6. Polyribosome analysis showed that the majority of gene 6 mRNA was present on large polysomes. In contrast, sedimentation of more than half of the gene 5 mRNA was subpolysomal. The change in distribution of gene 5 mRNA in polyribosome gradients in response to treatment with low concentrations of cycloheximide suggested that gene 5 is a poor translation initiation template compared with gene 6 mRNA. These data define a regulatory mechanism for the difference in amounts of VP6 and NSP1 and provide evidence for post-transcriptional control of rotavirus gene expression mediated by the translational efficiency of individual viral mRNAs. PMID:12560571

Mitzel, Dana N; Weisend, Carla M; White, Michael W; Hardy, Michele E

2003-02-01

451

Genes and (Common) Pathways Underlying Drug Addiction  

Microsoft Academic Search

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or

Chuan-Yun Li; Xizeng Mao; Liping Wei

2008-01-01