Sample records for gene herg1 kcnh2

  1. Two four-marker haplotypes on 7q36.1 region indicate that the potassium channel gene HERG1 (KCNH2, Kv11.1) is related to schizophrenia: a case control study

    PubMed Central

    2010-01-01

    Background The pathobiology of schizophrenia is still unclear. Its current treatment mainly depends on antipsychotic drugs. A leading adverse effect of these medications is the acquired long QT syndrome, which results from the blockade of cardiac HERG1 channels (human ether-a-go-go-related gene potassium channels 1) by antipsychotic agents. The HERG1 channel is encoded by HERG1 (KCNH2, Kv11.1) gene and is most highly expressed in heart and brain. Genetic variations in HERG1 predispose to acquired long QT syndrome. We hypothesized that the blockade of HERG1 channels by antipsychotics might also be significant for their therapeutic mode of action, indicating a novel mechanism in the pathogenesis of schizophrenia. Methods We genotyped four single nucleotide polymorphisms (SNPs) in 7q36.1 region (two SNPs, rs1805123 and rs3800779, located on HERG1, and two SNPs, rs885684 and rs956642, at the 3'-downstream intergenic region) and then performed single SNP and haplotype association analyses in 84 patients with schizophrenia and 74 healthy controls after the exclusion of individuals having prolonged or shortened QT interval on electrocardiogram. Results Our analyses revealed that both genotype and allele frequencies of rs3800779 (c.307+585G>T) were significantly different between populations (P = 0.023 and P = 0.018, respectively). We also identified that two previously undescribed four-marker haplotypes which are nearly allelic opposite of each other and located in chr7:150225599-150302147bp position encompassing HERG1 were either overrepresented (A-A-A-T, the at-risk haplotype, P = 0.0007) or underrepresented (C-A-C-G, the protective haplotype, P = 0.005) in patients compared to controls. Conclusions Our results indicate that the potassium channel gene HERG1 is related to schizophrenia. Our findings may also implicate the whole family of HERG channels (HERG1, HERG2 and HERG3) in the pathogenesis of psychosis and its treatment. PMID:20507645

  2. Mutation Analysis of KCNQ1, KCNH2 and SCN5A Genes in Taiwanese Long QT Syndrome Patients.

    PubMed

    Chang, Ya-Sian; Yang, Yi-Wen; Lin, Yen-Nien; Lin, Kuo-Hung; Chang, Kuan-Cheng; Chang, Jan-Gowth

    2015-07-13

    Long QT syndrome (LQTS) is a genetic cardiac disease. Gene mutation affects the structure or function of ion channels that are associated with a high risk of sudden death. The goal of this study was to determine the frequency of KCNQ1, KCNH2, and SCN5A mutations in LQTS in a Taiwanese population. Genomic DNA was extracted from peripheral blood samples obtained from 5 patients with LQTS and the family members of 3 LQTS patients. High resolution melting (HRM) analysis and direct DNA sequencing were used to characterize the KCNQ1, KCNH2, and SCN5A genetic variations. HRM analysis was successfully optimized for 14 of the 16 exons of the KCNQ1, 5 of the 15 exons of the KCNH2, and 23 of the 27 exons of the SCN5A. HRM and direct DNA sequencing was applied to the cohort of 5 cases and some of their family. The genetic testing revealed two pathogenic mutations (p.T309I in KCNQ1 and p.R744fs in KCNH2) and all of the mutational frequencies in KCNQ1 and KCNH2 were 20%. In the two patients who carry the pathogenic mutation presenting with recurrent syncope due to ventricular fibrillation, an implantable cardioverter defibrillator was implanted. We also discovered 11 polymorphisms in KCNQ1, 3 in KCNH2, and 5 in SCN5A. Two-fifths of cases (40%) presented with one of the three major LQTS-causing gene mutations. PMID:26118593

  3. Heteromeric Assembly of Human Ether-a`-go-go-related Gene (hERG) 1a/1b Channels Occurs Cotranslationally via

    E-print Network

    Kemnitz, Joseph

    Heteromeric Assembly of Human Ether-a`-go-go-related Gene (hERG) 1a/1b Channels Occurs of the human ether-a`-go-go-related gene (hERG1) encode two subunits, hERG 1a and 1b, which form potassium by the human ether-a`-go-go- related gene (hERG1)2 are important in controlling cardiac excitability, neuronal

  4. herg1b expression as a potential specific marker in pediatric acute myeloid leukemia patients with HERG 897K/K genotype.

    PubMed

    Erdem, Merve; Tekiner, Tugce Ayca; Fejzullahu, Arta; Akan, Gokce; Anak, Sema; Saribeyoglu, Ebru Tugrul; Ozbek, Ugur; Atalar, Fatmahan

    2015-04-01

    Human ether-a-go-go related gene (herg) encoding HERG K(+) channel has been demonstrated in many previous studies with its association to cell cycle progression and growth in tumor cells. The upregulated expression of HERG K+ channels was determined in different tumor types. Furthermore, not only full-length transcript herg1 but also a truncated isoform herg1b was shown to be expressed in cancer cells. In this study, the expression levels of herg1 and herg1b and the impact of K897T mutation on their expressions were investigated in pediatric acute myeloid leukemia (pAML). Expression levels of herg1 and herg1b isoforms were analyzed by quantitative real time polymerase chain reaction (PCR) in pAML patients together with healthy donors, and their expressions were confirmed by western blotting. The 2690 A>C nucleotide variation in KCNH2 gene corresponding to K897T amino acid change was analyzed by PCR followed by restriction enzyme digestion. herg1b overexpression was observed in tumor cells compared to healthy controls (P = .0024). However, herg1 expression was higher in healthy control cells than tumor cells (P = .001). The prevalence of polymorphic allele 897T was 26% in our patient group and 897T carriers showed increased herg1b expression compared to wild-type allele carriers. Our results demonstrate the presence of the increased levels of herg1b expression in pAML. In addition, we report for the first time that, pAML subgroup with HERG 897K/K genotype compared to 897K/T and T/T genotypes express increased levels of herg1b. In conclusion, HERG 897K/K genotype with increased level of herg1b expression might well be a prognostic marker for pAML. PMID:25247487

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

    PubMed Central

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

    2014-01-01

    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

  6. Characterization of hERG1 channel role in mouse colorectal carcinogenesis

    PubMed Central

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

    2013-01-01

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

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

    E-print Network

    Boyer, Edmond

    Keller et al., 1 Characterization of novel KCNH2 mutations in the long QT syndrome type 2 , Stefan Osswald1 , Marijke Brink2 , Eckhard Ficker5 , Mohamed Chahine3 Running title: Characterizing novel leading to a reduction of IKr current and loss of hERG channel function. We identified three novel KCNH2

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

    PubMed Central

    2014-01-01

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

  9. The Link between Inactivation and High-Affinity Block of hERG1 Channels.

    PubMed

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

    2015-06-01

    Block of human ether-à-go-go-related gene 1 (hERG1) K(+) channels by many drugs delays cardiac repolarization, prolongs QT interval, and is associated with an increased risk of cardiac arrhythmia. Preferential block of hERG1 channels in an inactivated state has been assumed because inactivation deficient mutant channels can exhibit dramatically reduced drug sensitivity. Here we reexamine the link between inactivation gating and potency of channel block using concatenated hERG1 tetramers containing a variable number (0-4) of subunits harboring a point mutation (S620T or S631A) that disrupts inactivation. Concatenated hERG1 tetramers containing four wild-type subunits exhibited high-affinity block by cisapride, dofetilide, and MK-499, similar to wild-type channels formed from hERG1 monomers. A single S620T subunit within a tetramer was sufficient to fully disrupt inactivation gating, whereas S631A suppressed inactivation as a graded function of the number of mutant subunits present in a concatenated tetramer. Drug potency was positively correlated to the number of S620T subunits contained within a tetramer but unrelated to mutation-induced disruption of channel inactivation. Introduction of a second point mutation (Y652W) into S620T hERG1 partially rescued drug sensitivity. The potency of cisapride was not altered for tetramers containing 0 to 3 S631A subunits, whereas the potency of dofetilide was a graded function of the number of S631A subunits contained within a tetramer. Together these findings indicate that S620T or S631A substitutions can allosterically disrupt drug binding by a mechanism that is independent of their effects on inactivation gating. PMID:25855787

  10. Stoichiometry of altered hERG1 channel gating by small molecule activators

    PubMed Central

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

    2014-01-01

    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

  11. hERG1 Channel Blockers and Cardiac Arrhythmia

    Microsoft Academic Search

    Michael C. Sanguinetti; Matthew Perry

    \\u000a A prolonged QT interval and increased risk of arrhythmia is a dangerous side effect of several antiarrhythmic agents and noncardiac\\u000a medications. In most clinically relevant cases, drug-induced QT prolongation is caused by a block of the cardiac rapid delayed\\u000a rectifier K+ current (I\\u000a Kr), a current that is conducted by hERG1 channels and is a key determinant of phase 3

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-10-15

    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

  14. Cooperative interactions between R531 and acidic residues in the voltage sensing module of hERG1 channels.

    PubMed

    Piper, David R; Rupp, Jason; Sachse, Frank B; Sanguinetti, Michael C; Tristani-Firouzi, Martin

    2008-01-01

    HERG1 K(+) channels are critical for modulating the duration of the cardiac action potential. The role of hERG1 channels in maintaining electrical stability in the heart derives from their unusual gating properties: slow activation and fast inactivation. HERG1 channel inactivation is intrinsically voltage sensitive and is not coupled to activation in the same way as in the Shaker family of K(+) channels. We recently proposed that the S4 transmembrane domain functions as the primary voltage sensor for hERG1 activation and inactivation and that distinct regions of S4 contribute to each gating process. In this study, we tested the hypothesis that S4 rearrangements underlying activation and inactivation gating may be associated with distinct cooperative interactions between a key residue in the S4 domain (R531) and acidic residues in neighboring regions (S1 - S3 domains) of the voltage sensing module. Using double-mutant cycle analysis, we found that R531 was energetically coupled to all acidic residues in S1-S3 during activation, but was coupled only to acidic residues near the extracellular portion of S2 and S3 (D456, D460 and D509) during inactivation. We propose that hERG1 activation involves a cooperative conformational change involving the entire voltage sensing module, while inactivation may involve a more limited interaction between R531 and D456, D460 and D509. PMID:18209470

  15. Mechanistic Basis for Type 2 Long QT Syndrome Caused by KCNH2 Mutations that Disrupt Conserved Arginine Residue in the Voltage Sensor

    PubMed Central

    McBride, Christie M.; Smith, Ashley M.; Smith, Jennifer L.; Reloj, Allison R.; Velasco, Ellyn J.; Powell, Jonathan; Elayi, Claude S.; Bartos, Daniel C.; Burgess, Don E.

    2013-01-01

    KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (IKr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing IKr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (IKv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients’ genotypes) mostly corrected the changes in IKv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing IKr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease IKr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient. PMID:23546015

  16. An In Vivo Cardiac Assay to Determine the Functional Consequences of Putative Long QT Syndrome Mutations

    PubMed Central

    Jou, Chuanchau J.; Barnett, Spencer M.; Bian, Jian-Tao; Weng, H. Cindy; Sheng, Xiaoming; Tristani-Firouzi, Martin

    2015-01-01

    Rationale Genetic testing for Long QT Syndrome (LQTS) is now a standard and integral component of clinical cardiology. A major obstacle to the interpretation of genetic findings is the lack of robust functional assays to determine the pathogenicity of identified gene variants in a high throughput manner. Objective The goal of this study was to design and test a high throughput in vivo cardiac assay to distinguish between disease-causing and benign KCNH2 (hERG1) variants, using the zebrafish as a model organism. Methods and Results We tested the ability of previously characterized LQTS hERG1 mutations and polymorphisms to restore normal repolarization in the kcnh2-knockdown embryonic zebrafish. The cardiac assay correctly identified a benign variant in 9 of 10 cases (negative predictive value 90%) while correctly identifying a disease-causing variant in 39/39 cases (positive predictive value 100%). Conclusion The in vivo zebrafish cardiac assay approaches the accuracy of the current benchmark in vitro assay for the detection of disease-causing mutations and is far superior in terms of throughput rate. Together with emerging algorithms for interpreting a positive LQTS genetic test, the zebrafish cardiac assay provides an additional tool for the final determination of pathogenicity of gene variants identified in LQTS genetic screening. PMID:23303164

  17. Copy Number Variation Detection through the Utilization of Unique Algorithms in the CNV Tool in NextGENe Software®

    PubMed Central

    Shouyong, N.; Liu, C.S.; McGuigan, John

    2013-01-01

    One of the most important steps in accurate determination of copy number variants using a case-control comparison is normalizing the coverage level between the different projects. NextGENe's CNV tool uses unique methods for this global normalization and also for log2 ratio calculation. The global normalization method is based on the median allele coverage of selected heterozygous positions. After normalization, log2 ratios are calculated by selecting one position in each specified region (based on annotation or amplicon location). The positions are selected if they are adequately representative of the region, and (ideally) if they are heterozygous, so that allele frequency changes can be noted. In this analysis, the tool is used to analyze data from multiple targeted sequencing technologies. A known variant (deletion in the KCNH2 gene) was detected using HaloPlex™ Target Enrichment System Panels. Large chromosomal abnormalities (such as trisomy 21) were detected using Ion AmpliSeq™ Panels.

  18. Common Variants in Cardiac Ion Channel Genes are Associated with Sudden Cardiac Death

    PubMed Central

    Albert, Christine M.; MacRae, Calum A.; Chasman, Daniel I.; VanDenburgh, Martin; Buring, Julie E; Manson, JoAnn E; Cook, Nancy R; Newton-Cheh, Christopher

    2010-01-01

    Background Rare variants in cardiac ion channel genes are associated with sudden cardiac death (SCD) in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to SCD risk at the population level. Methods and Results We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 non-coding SNPs associated with QT interval duration and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched controls of European ancestry enrolled in six prospective cohort studies. After accounting for multiple testing, two SNPs (rs2283222 located in intron 11 in KCNQ1 and rs11720524 located in intron 1 in SCN5A) remained significantly associated with sudden/arrhythmic death (FDR = 0.01 and 0.03 respectively). Each increasing copy of the major T allele of rs2283222 or the major C allele of rs1172052 was associated with an OR = 1.36 (95% CI 1.16-1.60, P=0.0002) and 1.30 (95% CI 1.12-1.51, P=0.0005) respectively. Control for cardiovascular risk factors and/or limiting the analysis to definite SCDs did not significantly alter these relationships. Conclusion In this combined analysis of 6 prospective cohort studies, two common intronic variants in KCNQ1 and SCN5A were associated with SCD in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with non-coding variation in these genes may lead to important insights into predisposition to lethal arrhythmias. PMID:20400777

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

    PubMed Central

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

    2013-01-01

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

  20. Sphingosine 1-phosphate and human ether-a'-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells.

    PubMed

    Asghar, Muhammad Yasir; Viitanen, Tero; Kemppainen, Kati; Törnquist, Kid

    2012-10-01

    Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a'-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P(1-3) receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P(1,3) inhibitor VPC-23019, the S1P(2) inhibitor JTE-013, and the S1P(2) receptor siRNA, we showed that the effect was mediated through S1P(2). Treatment of the cells with the Rho inhibitor C3 transferase abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a nonconducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, downregulating HERG protein with siRNA decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 ATC cells by activating S1P(2) and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein. PMID:22889737

  1. Female predominance and transmission distortion in the long-QT syndrome

    Microsoft Academic Search

    Medea Imboden; Heikki Swan; Isabelle Denjoy; Langen van I. M; Päivi Johanna Latinen-Forsblom; Carlo Napolitano; Véronique Fressart; Guenter Breithardt; Myriam Berthet; Silvia Priori; Bernard Hainque; Arthur Arnold Maria Wilde; Eric Schulze-Bahr; Josué Feingold; Pascale Guicheney

    2006-01-01

    BACKGROUND: Congenital long-QT syndrome is a disorder resulting in ventricular arrhythmias and sudden death. The most common forms of the long-QT syndrome, types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and KCNH2, respectively. Although inheritance of the long-QT syndrome is autosomal dominant, female predominance has often been observed and has been attributed to an increased

  2. Post-mortem review and genetic analysis of sudden unexpected death in epilepsy (SUDEP) cases.

    PubMed

    Tu, Emily; Bagnall, Richard D; Duflou, Johan; Semsarian, Christopher

    2011-03-01

    Sudden unexpected death in epilepsy (SUDEP) is the most frequent epilepsy-related cause of death and is characterized by an absence of any identifiable cause of death at post-mortem, suggesting an underlying arrhythmogenic predisposition. This study sought to identify SUDEP cases in a review of post-mortem records and to undertake genetic studies in key familial long QT syndrome (LQTS) genes. All autopsies performed from 1993-2009 at a forensic centre in Sydney, Australia were reviewed and SUDEP cases identified. DNA was extracted from post-mortem blood and the three most common LQTS genes, ie, KCNQ1, KCNH2 (HERG) and SCN5A, were amplified and analyzed. Sixty-eight SUDEP cases were identified (mean age of 40 ± 16 years). Genetic analysis revealed 6 (13%) non-synonymous (amino acid changing) variants in KCNH2 (n?=?2) and SCN5A (n?=?4), all previously reported in LQTS patients. Specifically, KCNH2 Arg176Trp and SCN5A Pro1090Leu were identified once in SUDEP cases and absent in control alleles. Both DNA variants have been previously identified in the pathogenesis of LQTS. The cause of SUDEP is currently unknown. Our results indicate that investigation of key ion channel genes should be pursued in the investigation of the relationship between epilepsy and sudden death. PMID:20875080

  3. Gene Therapy

    PubMed Central

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

    2009-01-01

    Gene therapy is defined as the treatment of disease by transfer of genetic material into cells. This review will explore methods available for gene transfer as well as current and potential applications for craniofacial regeneration, with emphasis on future development and design. Though non-viral gene delivery methods are limited by low gene transfer efficiency, they benefit from relative safety, low immunogenicity, ease of manufacture, and lack of DNA insert size limitation. In contrast, viral vectors are nature’s gene delivery machines that can be optimized to allow for tissue-specific targeting, site-specific chromosomal integration, and efficient long-term infection of dividing and non-dividing cells. In contrast to traditional replacement gene therapy, craniofacial regeneration seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and replace tissues in vivo. PMID:19641145

  4. Selective acquired long QT syndrome (saLQTS) upon risperidone treatment

    PubMed Central

    2012-01-01

    Background Numerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS). All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially. Case presentation We report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes. Conclusions Our observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective. PMID:23216910

  5. Gene Concepts, Gene Talk, and Gene Patents

    E-print Network

    Torrance, Andrew W.

    2010-01-01

    Since the existence of a discrete unit of heredity was first proposed by Gregor Mendel, scientific concepts of the “gene” have undergone rapid evolution. Beyond obvious epistemic and operational importance to the scientific ...

  6. Gene Therapy

    PubMed Central

    Baum, Bruce J

    2014-01-01

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

  7. Trichoderma genes

    DOEpatents

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

    2012-06-19

    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.

  8. Gene Identification

    NSDL National Science Digital Library

    Chuck Daniels

    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).

  9. Gene Control

    NSDL National Science Digital Library

    WGBH Educational Foundation

    2003-09-26

    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.

  10. Gene Cloning

    NSDL National Science Digital Library

    WGBH Educational Foundation

    2009-12-07

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

  11. Vulnerability genes or plasticity genes?

    PubMed Central

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

    2009-01-01

    The classic diathesis–stress framework, which views some individuals as particularly vulnerable to adversity, informs virtually all psychiatric research on behavior–gene–environment (G × E) interaction. An alternative framework of ‘differential susceptibility' is proposed, one which regards those most susceptible to adversity because of their genetic make up as simultaneously most likely to benefit from supportive or enriching experiences—or even just the absence of adversity. Recent G × E findings consistent with this perspective and involving monoamine oxidase-A, 5-HTTLPR (5-hydroxytryptamine-linked polymorphic region polymorphism) and dopamine receptor D4 (DRD4) are reviewed for illustrative purposes. Results considered suggest that putative ‘vulnerability genes' or ‘risk alleles' might, at times, be more appropriately conceptualized as ‘plasticity genes', because they seem to make individuals more susceptible to environmental influences—for better and for worse. PMID:19455150

  12. Genetic mutation in Korean patients of sudden cardiac arrest as a surrogating marker of idiopathic ventricular arrhythmia.

    PubMed

    Son, Myoung Kyun; Ki, Chang-Seok; Park, Seung-Jung; Huh, June; Kim, June Soo; On, Young Keun

    2013-07-01

    Mutation or common intronic variants in cardiac ion channel genes have been suggested to be associated with sudden cardiac death caused by idiopathic ventricular tachyarrhythmia. This study aimed to find mutations in cardiac ion channel genes of Korean sudden cardiac arrest patients with structurally normal heart and to verify association between common genetic variation in cardiac ion channel and sudden cardiac arrest by idiopathic ventricular tachyarrhythmia in Koreans. Study participants were Korean survivors of sudden cardiac arrest caused by idiopathic ventricular tachycardia or fibrillation. All coding exons of the SCN5A, KCNQ1, and KCNH2 genes were analyzed by Sanger sequencing. Fifteen survivors of sudden cardiac arrest were included. Three male patients had mutations in SCN5A gene and none in KCNQ1 and KCNH2 genes. Intronic variant (rs2283222) in KCNQ1 gene showed significant association with sudden cardiac arrest (OR 4.05). Four male sudden cardiac arrest survivors had intronic variant (rs11720524) in SCN5A gene. None of female survivors of sudden cardiac arrest had SCN5A gene mutations despite similar frequencies of intronic variants between males and females in 55 normal controls. Common intronic variant in KCNQ1 gene is associated with sudden cardiac arrest caused by idiopathic ventricular tachyarrhythmia in Koreans. PMID:23853484

  13. Gene Ontology Driven Classification of Gene

    E-print Network

    Spang, Rainer

    expression patterns Gene Ontology · Structure knowledge about genes · Directed acyclic graph · Represents · No biological knowledge #12;Introduction 23-Jul-02 5 / 17Claudio Lottaz: GO driven classification of gene knowledge on · Molecular function · Bilogical process · Cellular component · Genes are annotated to nodes

  14. Gene Expression Mural: Visualizing Gene Expression Databases

    E-print Network

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

  15. Gene Switches

    NSDL National Science Digital Library

    2013-07-30

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

  16. Short QT syndrome in a boy diagnosed on screening for heart disease.

    PubMed

    Suzuki, Hiroshi; Hoshina, Satoshi; Ozawa, Junichi; Sato, Akinori; Minamino, Tohru; Aizawa, Yoshifusa; Saitoh, Akihiko

    2014-10-01

    We report on an asymptomatic 10-year-old boy who had a short QT interval (corrected QT interval, 260 ms). Short QT syndrome (SQTS) was detected in a school screening program for heart disease and the patient was subsequently diagnosed as having N588K mutation in the KCNH2 gene. Quinidine prolonged the QT interval, but not the QU interval. During treadmill exercise stress test, QT and QU intervals responded differently to heart rate changes, suggesting a mechanoelectrical hypothesis for the origin of the U wave. Although rare, attention should be paid to SQTS, which is associated with potential fatal arrhythmias. PMID:25335996

  17. Essential Bacillus subtilis genes

    Microsoft Academic Search

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

    2003-01-01

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

  18. GENES 2000

    NSDL National Science Digital Library

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

  19. Genes and Psoriasis

    MedlinePLUS

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

  20. Gene function, gene networks and the fate of duplicated genes.

    PubMed

    Shimeld, S M

    1999-10-01

    For both copies of a duplicated gene to become fixed in a population and subsequently maintained, selection must favour individuals with both genes over individuals with one. Here I review and assess some of the proposed ways that gene structure and function might affect the likelihood of both copies acquiring distinct functions and therefore positive selection. In particular I focus on the interacting pathways of genes that make up gene networks, and how these may affect genes duplicated both singly and en masse. Using the Wnt and hedgehog pathways as examples and data from developmental and genome analyses, I show that, while some of these theories may genuinely reflect what has occurred in animal evolution, there are still insufficient data to rigorously assess their relative importance. This, however, is likely to change in the near future. PMID:10597639

  1. Genetic analysis, in silico prediction, and family segregation in long QT syndrome.

    PubMed

    Riuró, Helena; Campuzano, Oscar; Berne, Paola; Arbelo, Elena; Iglesias, Anna; Pérez-Serra, Alexandra; Coll-Vidal, Mònica; Partemi, Sara; Mademont-Soler, Irene; Picó, Ferran; Allegue, Catarina; Oliva, Antonio; Gerstenfeld, Edward; Sarquella-Brugada, Georgia; Castro-Urda, Víctor; Fernández-Lozano, Ignacio; Mont, Lluís; Brugada, Josep; Scornik, Fabiana S; Brugada, Ramon

    2015-01-01

    The heritable cardiovascular disorder long QT syndrome (LQTS), characterized by prolongation of the QT interval on electrocardiogram, carries a high risk of sudden cardiac death. We sought to add new data to the existing knowledge of genetic mutations contributing to LQTS to both expand our understanding of its genetic basis and assess the value of genetic testing in clinical decision-making. Direct sequencing of the five major contributing genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, was performed in a cohort of 115 non-related LQTS patients. Pathogenicity of the variants was analyzed using family segregation, allele frequency from public databases, conservation analysis, and Condel and Provean in silico predictors. Phenotype-genotype correlations were analyzed statistically. Sequencing identified 36 previously described and 18 novel mutations. In 51.3% of the index cases, mutations were found, mostly in KCNQ1, KCNH2, and SCN5A; 5.2% of cases had multiple mutations. Pathogenicity analysis revealed 39 mutations as likely pathogenic, 12 as VUS, and 3 as non-pathogenic. Clinical analysis revealed that 75.6% of patients with QTc?500?ms were genetically confirmed. Our results support the use of genetic testing of KCNQ1, KCNH2, and SCN5A as part of the diagnosis of LQTS and to help identify relatives at risk of SCD. Further, the genetic tools appear more valuable as disease severity increases. However, the identification of genetic variations in the clinical investigation of single patients using bioinformatic tools can produce erroneous conclusions regarding pathogenicity. Therefore segregation studies are key to determining causality. PMID:24667783

  2. Clustering gene expression patterns

    Microsoft Academic Search

    Amir Ben-Dor; Zohar Yakhinit; Zohar Yakhini

    1999-01-01

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

  3. Autism and Genes

    ERIC Educational Resources Information Center

    National Institutes of Health, 2005

    2005-01-01

    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…

  4. Gene–environment interdependence

    Microsoft Academic Search

    Michael Rutter

    2012-01-01

    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

  5. Clustering gene expression data

    E-print Network

    Shamir, Ron

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

  6. Therapeutic gene targeting.

    PubMed

    Yáñez, R J; Porter, A C

    1998-02-01

    Gene targeting is the use of homologous recombination to make defined alterations to the genome. One of the possible outcomes of gene targeting is the accurate correction of genetic defects, and this would make it the ideal method of gene therapy for single gene disorder. While gene targeting has been achieved both in human cell lines and in nontransformed, primary human cells, its low efficiency has been a major limitation to its therapeutic potential. Gene therapy in vivo gene targeting is there for impractical without dramatic improvements in targeting efficiency. Ex vivo approaches might more realistically be considered, but would benefit from progress in the isolation and growth of somatic stem cells and improvements in targeting efficiency. We provide here a brief review of the challenges of gene therapy by gene targeting. This is followed by a critical overview of recent developments in gene targeting techniques, and in our understanding of the underlying processes of homologous and nonhomologous recombination. PMID:9578833

  7. 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.

  8. Aging: gene silencing or gene activation?

    PubMed

    Burzynski, Stanislaw R

    2005-01-01

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

  9. The human ERG1 channel polymorphism, K897T, creates a phosphorylation site that inhibits channel activity.

    PubMed

    Gentile, Saverio; Martin, Negin; Scappini, Erica; Williams, Jason; Erxleben, Christian; Armstrong, David L

    2008-09-23

    Single-nucleotide polymorphisms (SNPs) in the human ether-a-go-go-related gene 1, hERG1, are associated with cardiac arrhythmias. The Kv11.1 channels encoded by hERG1 are also essential for rhythmic excitability of the pituitary, where they are regulated by thyroid hormone through a signal transduction cascade involving the phosphatidylinositol 3-kinase (PI3K) and the Ser/Thr-directed protein phosphatase, PP5. Here, we show that the hERG1 polymorphism at codon 897, which is read as a Thr instead of a Lys, creates a phosphorylation site for the Akt protein kinase on the Kv11.1 channel protein. Consequently, hormonal signaling through the PI3K signaling cascade, which normally stimulates K897 channels through PP5-mediated dephosphorylation, inhibits T897 channels through Akt-mediated phosphorylation. Thus, hormonal regulation of Kv11.1 in humans with the T897 polymorphism is predicted to prolong the QT interval of cardiac myocytes. A systematic bioinformatics search for SNPs in human ion channel genes identified 15 additional candidates for such "phosphorylopathies," which are predicted to create or destroy putative phosphorylation sites. Changes in protein phosphorylation might represent a general mechanism for the interaction of genetic variation and environment on human health. PMID:18791070

  10. The human ERG1 channel polymorphism, K897T, creates a phosphorylation site that inhibits channel activity

    PubMed Central

    Gentile, Saverio; Martin, Negin; Scappini, Erica; Williams, Jason; Erxleben, Christian; Armstrong, David L.

    2008-01-01

    Single-nucleotide polymorphisms (SNPs) in the human ether-a-go-go-related gene 1, hERG1, are associated with cardiac arrhythmias. The Kv11.1 channels encoded by hERG1 are also essential for rhythmic excitability of the pituitary, where they are regulated by thyroid hormone through a signal transduction cascade involving the phosphatidylinositol 3-kinase (PI3K) and the Ser/Thr-directed protein phosphatase, PP5. Here, we show that the hERG1 polymorphism at codon 897, which is read as a Thr instead of a Lys, creates a phosphorylation site for the Akt protein kinase on the Kv11.1 channel protein. Consequently, hormonal signaling through the PI3K signaling cascade, which normally stimulates K897 channels through PP5-mediated dephosphorylation, inhibits T897 channels through Akt-mediated phosphorylation. Thus, hormonal regulation of Kv11.1 in humans with the T897 polymorphism is predicted to prolong the QT interval of cardiac myocytes. A systematic bioinformatics search for SNPs in human ion channel genes identified 15 additional candidates for such “phosphorylopathies,” which are predicted to create or destroy putative phosphorylation sites. Changes in protein phosphorylation might represent a general mechanism for the interaction of genetic variation and environment on human health. PMID:18791070

  11. Airway Mucin Genes and Gene Products

    Microsoft Academic Search

    Mary Callaghan Rose; Sandra J. Gendler

    \\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

  12. Gene symbol precision.

    PubMed

    Bennani-Baiti, Barbara; Bennani-Baiti, Idriss M

    2012-01-10

    Several gene databases, including heavily used ones such as the National Center for Biotechnology Information (NCBI) database, erroneously assign, on occasion, literature references to genes or proteins. These mistakes are mostly due to an overlap in gene aliases, whereby two distinct genes share a pseudonym. This is particularly confusing when the gene products have also biological properties in common, are part of signaling pathways that cross-talk to one another, or are regulated by the same effectors. We present examples spanning several research fields including apoptosis, ubiquitin-dependent degradation, signaling by Notch, Wnt, and small G proteins, transporters of glutathione conjugates of electrophiles, and mitochondrial and ribosomal RNA genes. To solve the problem, we argue in favor of including Entrez gene numbers in papers submitted for publication as unique gene identifiers to allow precise identification of genes and species studied. PMID:22019431

  13. Virtual Gene: Using Correlations Between Genes to Select Informative Genes on Microarray Datasets

    Microsoft Academic Search

    Xian Xu; Aidong Zhang

    2005-01-01

    Gene Selection is one class of most used data analysis algorithms on microarray datasets. The goal of gene selection algorithms is to filter out a small set of informative genes that best explains experimental variations. Traditional gene selection algorithms are mostly single-gene based. Some discriminative scores are calculated and sorted for each gene. Top ranked genes are then se- lected

  14. Bacterial avirulence genes.

    PubMed

    Leach, J E; White, F F

    1996-01-01

    Although more than 30 bacterial avirulence genes have been cloned and characterized, the function of the gene products in the elictitation of resistance is unknown in all cases but one. The product of avrD from Pseudomonas syringae pv. glycinea likely functions indirectly to elicit resistance in soybean, that is, evidence suggests the gene product is an enzyme involved in elicitor production. In most if not all cases, bacterial avirulence gene function is dependent on interactions with the hypersensitive response and pathogenicity (hrp) genes. Many hrp genes are similar to genes involved in delivery of pathogenicity factors in mammalian bacterial pathogens. Thus, analogies between mammalian and plant pathogens may provide needed clues to elucidate how virulence gene products control induction of resistance. PMID:15012539

  15. QT Is Longer in Drug-Free Patients with Schizophrenia Compared with Age-Matched Healthy Subjects

    PubMed Central

    Fujii, Kumiko; Ozeki, Yuji; Okayasu, Hiroaki; Takano, Yumiko; Shinozaki, Takahiro; Hori, Hiroaki; Orui, Masami; Horie, Minoru; Kunugi, Hiroshi; Shimoda, Kazutaka

    2014-01-01

    The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n?=?85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n?=?85) and healthy volunteers (n?=?85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P<0.01). Schizophrenic patients with and without medication had a significantly higher mean heart rate than did the healthy volunteers, with no obvious sex-related differences in the QT interval. The QT interval prolongation may be manifestation of a certain biological feature of schizophrenia. PMID:24887423

  16. Molecular Cell Gene Regulation

    E-print Network

    Collins, James J.

    Molecular Cell Previews Gene Regulation: Hacking the Network on a Sugar High Tom Ellis,1,2 Xiao. The resulting input-function map reveals that gene network regulation follows non-Boolean, and often how its individual parts behave in response to different conditions. In the case of gene networks

  17. Evidence for Homosexuality Gene

    Microsoft Academic Search

    Robert Pool

    1993-01-01

    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

  18. Gene Testing Can Be Flawed

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Genetic Testing Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Genetic Testing About MedlinePlus Site Map FAQs Contact ...

  19. Evolution of Gene Expression after Gene Amplification

    PubMed Central

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

    2015-01-01

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

  20. 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.

  1. Gene hunting in autoinflammation

    PubMed Central

    2013-01-01

    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

  2. Do Housekeeping Genes Exist?

    PubMed Central

    Sun, Bingyun

    2015-01-01

    The searching of human housekeeping (HK) genes has been a long quest since the emergence of transcriptomics, and is instrumental for us to understand the structure of genome and the fundamentals of biological processes. The resolved genes are frequently used in evolution studies and as normalization standards in quantitative gene-expression analysis. Within the past 20 years, more than a dozen HK-gene studies have been conducted, yet none of them sampled human tissues completely. We believe an integration of these results will help remove false positive genes owing to the inadequate sampling. Surprisingly, we only find one common gene across 15 examined HK-gene datasets comprising 187 different tissue and cell types. Our subsequent analyses suggest that it might not be appropriate to rigidly define HK genes as expressed in all tissue types that have diverse developmental, physiological, and pathological states. It might be beneficial to use more robustly identified HK functions for filtering criteria, in which the representing genes can be a subset of genome. These genes are not necessarily the same, and perhaps need not to be the same, everywhere in our body. PMID:25970694

  3. Essential Bacillus subtilis genes.

    PubMed

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

    2003-04-15

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

  4. Essential Bacillus subtilis genes

    PubMed Central

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

    2003-01-01

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

  5. Gene therapy for radioprotection.

    PubMed

    Everett, W H; Curiel, D T

    2015-03-01

    Radiation therapy is a critical component of cancer treatment with over half of patients receiving radiation during their treatment. Despite advances in image-guided therapy and dose fractionation, patients receiving radiation therapy are still at risk for side effects due to off-target radiation damage of normal tissues. To reduce normal tissue damage, researchers have sought radioprotectors, which are agents capable of protecting tissue against radiation by preventing radiation damage from occurring or by decreasing cell death in the presence of radiation damage. Although much early research focused on small-molecule radioprotectors, there has been a growing interest in gene therapy for radioprotection. The amenability of gene therapy vectors to targeting, as well as the flexibility of gene therapy to accomplish ablation or augmentation of biologically relevant genes, makes gene therapy an excellent strategy for radioprotection. Future improvements to vector targeting and delivery should greatly enhance radioprotection through gene therapy. PMID:25721205

  6. Metastasis Suppressor Genes

    PubMed Central

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2014-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinical impact of these genes. PMID:23348381

  7. DNA, Genes and Chromosomes

    NSDL National Science Digital Library

    Mrs. Fomby

    2007-11-07

    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, ...

  8. Genes and Disease

    NSDL National Science Digital Library

    1998-01-01

    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."

  9. Chapter 19: Gene: A Directory of Genes Donna Maglott

    E-print Network

    Levin, Judith G.

    Chapter 19: Gene: A Directory of Genes Donna Maglott Kim Pruitt Tatiana Tatusova Summary A major goal of genomic sequencing projects is to identify and characterize genes. Gene (1) has been genes, serving as a major node in the nexus of genomic map, sequence, expression, protein structure

  10. Mining Phenotypes and Informative Genes from Gene Expression Data

    E-print Network

    Pei, Jian

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

  11. Mouse Genetics: Determining gene function

    E-print Network

    Goldschmidt, Christina

    mutagenesis Phenotype Driven Gene Driven · Gene traps · Gene targeting · Gene driven ENU · RNAi EUCOMM, Europe of offspring for transgenic DNA and expression in tissue X Construction of transgene driven by promoter X · Gene driven ENU · RNAi EUCOMM, Europe European Conditional Mouse Mutagenesis KOMP, US Knock-out Mouse

  12. 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

  13. Smart Genes, Stupid Science.

    ERIC Educational Resources Information Center

    Randerson, Sherman; Mahadeva, Madhu N.

    1983-01-01

    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…

  14. 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...

  15. Human DNA Repair Genes

    Microsoft Academic Search

    Richard D. Wood; Michael Mitchell; John Sgouros; Tomas Lindahl

    2001-01-01

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered

  16. Epigenetics and gene expression

    Microsoft Academic Search

    E R Gibney; C M Nolan

    2010-01-01

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

  17. One Gene, Many Proteins

    Microsoft Academic Search

    NICOLLE H. PACKER; ANDREW A. GOOLEY; MARC R. WILKINS

    The release of the sequence of the human genome in early 2000 generated enormous excitement with the promise of rapid identification of the gene products responsible for cellular function. What has become apparent is that knowledge of the DNA sequence of the gene that is involved in a particular metabolic process is insufficient to predict its function, expression and activity.

  18. The Gene Ontology Consortium

    Microsoft Academic Search

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

    2000-01-01

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

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

    Microsoft Academic Search

    Tatsuya Akutsu; Satoru Kuhara; Osamu Maruyama; Satoru Miyano

    1998-01-01

    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

  20. 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.

  1. Apoptotic Genes in Cancer Therapy

    Microsoft Academic Search

    Bertram Opalka; Alexandra Dickopp; Hans-Christoph Kirch

    2002-01-01

    Induction of apoptosis in malignant cells is a major goal of cancer therapy in general and of certain cancer gene therapy strategies in particular. Numerous apoptosis-regulating genes have been evaluated for this purpose. Besides the most prominent p53 gene others include p16, p21, p27, E2F genes, FHIT, PTEN and CASPASE genes. Recently, the potential for therapy of an adenoviral gene,

  2. Human retinoblastoma gene

    SciTech Connect

    Bookstein, R.; Lee, E.Y.H.P.; Peccei, A.; Lee, W.H. (Dept. of Pathology M-012 and Center for Molecular Genetics, Univ. of California, San Diego, La Jolla, CA (US))

    1989-04-01

    Mutational inactivation of the retinoblastoma (RB) gene is considered a fundamental event in the formation of several types of human cancer. A substantial proportion of RB gene mutations are partial or complete deletions that extend an unknown distance beyond one or both ends of the gene. To provide a framework for measuring the extent of these deletions, the authors have constructed a long-range restriction map of SfiI sites spanning 850 kilobases around the RB gene. This map was applied in a molecular analysis of RB gene deletion in breast cancer cell line MB468. A previous study of this cell line demonstrated deletion of the entire RB gene except for exons 1 and 2. Genomic clones containing the deletion junction were isolated from a library made from MB468 DNA. A probe obtained from the far side of the deletion junction was used to localize and clone the unknown 3' endpoint, demonstrating that the chromosomal mutation in this case was a simple deletion spanning 200 kilobases. Sequence analysis of the deletion junction indicated a conservative deletion with no loss or gain of nucleotides. The deletion endpoints had no sequence homology to each other or to any repetitive sequence family, such as Alu, so the recombination event was illegitimate. Structural analysis of this and other RB gene deletions is important for understanding molecular mechanisms of recessive oncogenesis.

  3. [Is gene technology immoral?].

    PubMed

    Halter, H

    1994-10-01

    Since it came into being in the USA in the early 1970s, gene technology has always been fundamentally controversial, especially in the German-speaking countries. The optimistic--or critical--supporters of gene technology are convinced that, in view of gene technology's not otherwise attainable advantages for human and animal health, for food production and other important aims, it would be ethically unacceptable to restrict to the minimum or even ban it. On the other hand, the radical critics are convinced that gene technology, in view of its anthropologically false starting-point, the questionable interests behind it, and above all its unforeseeable, serious negative implications for mankind and environment, is unacceptable on ethical grounds. Critical reflexion on these polarized arguments must start from the question why precisely gene technology is so controversial, and what are the criteria for ethical assessment. These reflexions presuppose that the prior judgement of gene technology as a technology in the ideological field is rooted in life attitudes, history and nature in general, and this is true not only of gene technology's opponents but also its supporters. It is thus a question of one ideology vs. another. Chief importance here attaches to the mankind-nature relationship and the need to take seriously the fundamental ambivalence of all (!) human action with unforeseeable consequences. The conclusion is that neither to demonize nor to glorify gene technology, as a matter of principle, does justice to its wide and varied positive or negative potential. The ethical assessment of gene technology must be differentiated according to the aims and possible implications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7939540

  4. 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.

  5. A Gene Scrapbook A Tribute to Gene Loh

    E-print Network

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

  6. Neighboring Genes Show Correlated Evolution in Gene Expression

    PubMed Central

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

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

  7. Microfluidic gene synthesis

    E-print Network

    Kong, David Sun, 1979-

    2008-01-01

    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 ...

  8. Clock genes and sleep.

    PubMed

    Landgraf, Dominic; Shostak, Anton; Oster, Henrik

    2012-01-01

    In most species--from cyanobacteria to humans--endogenous clocks have evolved that drive 24-h rhythms of behavior and physiology. In mammals, these circadian rhythms are regulated by a hierarchical network of cellular oscillators controlled by a set of clock genes organized in a system of interlocked transcriptional feedback loops. One of the most prominent outputs of the circadian system is the synchronization of the sleep-wake cycle with external (day-) time. Clock genes also have a strong impact on many other biological functions, such as memory formation, energy metabolism, and immunity. Remarkably, large overlaps exist between clock gene and sleep (loss) mediated effects on these processes. This review summarizes sleep clock gene interactions for these three phenomena, highlighting potential mediators linking sleep and/or clock function to physiological output in an attempt to better understand the complexity of diurnal adaptation and its consequences for health and disease. PMID:21833490

  9. "Bad genes" & criminal responsibility.

    PubMed

    González-Tapia, María Isabel; Obsuth, Ingrid

    2015-01-01

    The genetics of the accused is trying to break into the courts. To date several candidate genes have been put forward and their links to antisocial behavior have been examined and documented with some consistency. In this paper, we focus on the so called "warrior gene", or the low-activity allele of the MAOA gene, which has been most consistently related to human behavior and specifically to violence and antisocial behavior. In preparing this paper we had two objectives. First, to summarize and analyze the current scientific evidence, in order to gain an in depth understanding of the state of the issue and determine whether a dominant line of generally accepted scientific knowledge in this field can be asserted. Second, to derive conclusions and put forward recommendations related to the use of genetic information, specifically the presence of the low-activity genotype of the MAOA gene, in modulation of criminal responsibility in European and US courts. PMID:25708001

  10. Genes underlying altruism.

    PubMed

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

    2013-01-01

    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

  11. Classification of genes based on gene expression analysis

    NASA Astrophysics Data System (ADS)

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

    2008-05-01

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

  12. Gene therapy for atherosclerosis

    Microsoft Academic Search

    D. J. Rader

    1997-01-01

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

  13. Lynch Syndrome Genes

    Microsoft Academic Search

    Päivi Peltomäki

    2005-01-01

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

  14. Enhanced electro-mediated gene delivery using carrier genes

    Microsoft Academic Search

    Jeong Ah Kim; Won Gu Lee; Neon Cheol Jung

    2010-01-01

    Low transfection and expression of target genes has been a problem in gene delivery for clinical therapy. In this study, we present a method for enhancing the transfection efficiency of target genes by electroporation using carrier genes. To evaluate the transfection efficiency, we transfected HeLa cells with luciferase genes (pGL3-control) and then measured the luciferase activity. In our experiments, the

  15. GeneCards Version 3: the human gene integrator.

    PubMed

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

    2010-01-01

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

  16. Evidence for homosexuality gene

    SciTech Connect

    Pool, R.

    1993-07-16

    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.

  17. Susceptibility genes in hypertension.

    PubMed

    Armani, C; Botto, N; Andreassi, M G

    2011-01-01

    Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have revealed the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium Na reabsorption in the distal nephron, with accompanying expansion of extracellular volume. On the contrary in the essential hypertension the underlying pathogenetic mechanism is more complex because of interplay between several 'risk' genes and environmental factors. It is assumed that blood pressure is under the control of a large number of genes each of which has only relatively mild effects. It has therefore been difficult to discover the genes that contribute to blood pressure variation using traditional approaches including candidate gene studies and linkage studies. Recent development of genotyping technology made large scale genome-wide association studies possible. This approach and the study of monogenic forms of hypertension has led to the discovery of novel and robust candidate genes for human essential hypertension, many of which require functional analysis in experimental models. This review summarizes the current findings for candidate genes associated with blood pressure and focuses on recent advances and future potential of pharmacogenetics of hypertension, with the intent to clarify what amount of these investments in basic science research will be delivered into benefits to patients. PMID:21861838

  18. Gene finding in novel genomes

    Microsoft Academic Search

    Ian Korf

    2004-01-01

    Background: Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results: I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that

  19. Vectors for cancer gene therapy

    Microsoft Academic Search

    J. Zhang; S. J. Russell

    1996-01-01

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

  20. Enhanced electro-mediated gene delivery using carrier genes.

    PubMed

    Kim, Jeong Ah; Lee, Won Gu; Jung, Neon Cheol

    2010-06-01

    Low transfection and expression of target genes has been a problem in gene delivery for clinical therapy. In this study, we present a method for enhancing the transfection efficiency of target genes by electroporation using carrier genes. To evaluate the transfection efficiency, we transfected HeLa cells with luciferase genes (pGL3-control) and then measured the luciferase activity. In our experiments, the prokaryotic expression vector pCR2.1 was used as a carrier gene in the electro-mediated gene delivery. The result shows that the luciferase gene can be effectively transferred into the cell membrane with the aid of carrier genes. In the presence of carrier genes, luciferase activities increased two- to three-fold compared with that in the absence of carrier genes. We also investigated the effect of the weight ratio of luciferase genes to carrier genes on transfection efficiency and found no significant relationship between them. Consequently, we believe that carrier genes are potentially beneficial for promoting transfection and expression of target genes in biological applications. PMID:19783228

  1. How old is my gene?

    PubMed Central

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

    2013-01-01

    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

  2. Gene therapy for sarcoma.

    PubMed

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

    2002-01-01

    Soft tissue sarcomas are mesenchymal tumors which respond poorly to systemic therapy. Recent studies suggest a higher response rate with an increased doxorubicin dosage. However, this was parallel with a profound hematotoxicity in 75% of patients. Transfer of the human multidrug resistance 1 (MDR1) gene to normal hematopoietic stem cells and transplantation may significantly reduce the hematotoxicity of anthracyclin-based chemotherapy. To test this concept of supportive gene therapy in advance of a clinical study, we transduced mobilized peripheral blood progenitor cells (PBPC) with the retroviral vector SF91m3 containing the human MDR1 gene, transplanted these cells to immune-deficient mice, allowed 6 weeks for engraftment to occur and treated the animals with MDR1-based chemotherapy. In the MDR1-transduced group the human leukocytes were significantly protected from the toxicity of chemotherapy (p < 0.05). While the gene transfer rate was in the range of 10% and thus comparable to recent clinical trials, the gene expression was 59% of transduced cells and thus significantly higher than previously reported for less-advanced vectors. On the other hand, ifosfamide, a drug which has been used successfully for stem cell mobilization, is active in soft tissue sarcoma. Due to these favorable characteristics sarcoma is an attractive target to test the efficacy of MDR1 gene therapy in a clinical setting. Gene therapeutic strategies may also be used to directly target sarcoma cells, e.g. by transfer of suicide genes. We found that adenoassociated virus 2 (AAV-2) vectors efficiently transduce human HS-1 and HT1080 sarcoma cells (>90%) while other tumor cell lines and primary human PBPC were less susceptible. The thymidine kinase (TK) suicide gene was cloned into an AAV-2 vector and a complete kill of TK-transduced HS-1 and HT1080 cells was observed following exposure to aciclovir or ganciclovir (GCV), while >90% of mock-transduced HS-1 cells survived at these dosages. Transplantation of those sarcoma cells to nonobese diabetic (NOD)/LtSz-severe-combined immunodeficient (scid)/scid (NOD/SCID) mice resulted in a survival of >5 months in the AAV-TK-transduced/GCV-treated group, while the mice in the mock-transduced/GCV-treated group had died after 3 weeks. These data show that soft tissue sarcomas are a particularly suitable model system for the development and clinical testing of new gene therapeutic concepts. PMID:12426490

  3. Down-weighting overlapping genes improves gene set analysis

    PubMed Central

    2012-01-01

    Background The identification of gene sets that are significantly impacted in a given condition based on microarray data is a crucial step in current life science research. Most gene set analysis methods treat genes equally, regardless how specific they are to a given gene set. Results In this work we propose a new gene set analysis method that computes a gene set score as the mean of absolute values of weighted moderated gene t-scores. The gene weights are designed to emphasize the genes appearing in few gene sets, versus genes that appear in many gene sets. We demonstrate the usefulness of the method when analyzing gene sets that correspond to the KEGG pathways, and hence we called our method Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). Unlike most gene set analysis methods which are validated through the analysis of 2-3 data sets followed by a human interpretation of the results, the validation employed here uses 24 different data sets and a completely objective assessment scheme that makes minimal assumptions and eliminates the need for possibly biased human assessments of the analysis results. Conclusions PADOG significantly improves gene set ranking and boosts sensitivity of analysis using information already available in the gene expression profiles and the collection of gene sets to be analyzed. The advantages of PADOG over other existing approaches are shown to be stable to changes in the database of gene sets to be analyzed. PADOG was implemented as an R package available at: http://bioinformaticsprb.med.wayne.edu/PADOG/or http://www.bioconductor.org. PMID:22713124

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Epigenetics--gene silencing.

    PubMed

    Lele, R D

    2009-01-01

    The discovery of the mechanism of RNA interference by ds RNA by Prof. Andrew Fire and Prof. Craig Mello in 1998, gave them the Nobel Prize in 2006. This discovery revealed a new mechanism for gene regulation through "gene silencing" at the transcriptional level (TGS) or at the post-transcriptional level (PTGS), which play a key role in many essential cellular processes. Today dsRNA is used as a powerful tool to experimentally elucidate the function of essentially any gene in a cell. The immense impact of the discovery of RNA interference (RNAi) on biomedical research and its novel medical applications in the future are reviewed in this article, with particular stress on therapeutic applications of radio-labeled antisense oligonucleotides (RASONs) for diagnosis and treatment of various cancers and neurodegenerative diseases by "gene silencing". Antisense oligonucleotides (ASONs) can also modulate alternative splicing which 74% of all human genes undergo. The most effective targeting strategy employs simultaneous blocking SnRNP binding sites and splice junctions. Correction of splicing by ASONs can be used to silence mutations causing aberrant splicing as in thalassemia, Duchenne muscular dystrophy and cystic fibrosis. PMID:19753761

  6. On sports and genes.

    PubMed

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

    2012-12-01

    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

  7. Multidimensional gene search with Genehopper

    PubMed Central

    Munz, Matthias; Tönnies, Sascha; Balke, Wolf-Tilo; Simon, Eric

    2015-01-01

    The high abundance of genetic information enables researchers to gain new insights from the comparison of human genes according to their similarities. However, existing tools that allow the exploration of such gene-to-gene relationships, apply each similarity independently. To make use of multidimensional scoring, we developed a new search engine named Genehopper. It can handle two query types: (i) the typical use case starts with a term-to-gene search, i.e. an optimized full-text search for an anchor gene of interest. The web-interface can handle one or more terms including gene symbols and identifiers of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined, the user can explore its neighborhood by a gene-to-gene search as the weighted sum of nine normalized gene similarities based on sequence homology, protein domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and other features. Each weight can be adjusted by the user, allowing flexible customization of the gene search. All implemented similarities have a low pairwise correlation (max r2 = 0.4) implying a low linear dependency, i.e. any change in a single weight has an effect on the ranking. Thus, we treated them as separate dimensions in the search space. Genehopper is freely available at http://genehopper.ifis.cs.tu-bs.de. PMID:25990726

  8. Multidimensional gene search with Genehopper.

    PubMed

    Munz, Matthias; Tönnies, Sascha; Balke, Wolf-Tilo; Simon, Eric

    2015-07-01

    The high abundance of genetic information enables researchers to gain new insights from the comparison of human genes according to their similarities. However, existing tools that allow the exploration of such gene-to-gene relationships, apply each similarity independently. To make use of multidimensional scoring, we developed a new search engine named Genehopper. It can handle two query types: (i) the typical use case starts with a term-to-gene search, i.e. an optimized full-text search for an anchor gene of interest. The web-interface can handle one or more terms including gene symbols and identifiers of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined, the user can explore its neighborhood by a gene-to-gene search as the weighted sum of nine normalized gene similarities based on sequence homology, protein domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and other features. Each weight can be adjusted by the user, allowing flexible customization of the gene search. All implemented similarities have a low pairwise correlation (max r(2) = 0.4) implying a low linear dependency, i.e. any change in a single weight has an effect on the ranking. Thus, we treated them as separate dimensions in the search space. Genehopper is freely available at http://genehopper.ifis.cs.tu-bs.de. PMID:25990726

  9. Gene therapy in pancreatic cancer

    PubMed Central

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

    2014-01-01

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

  10. Alphaviruses in Gene Therapy

    PubMed Central

    Lundstrom, Kenneth

    2015-01-01

    Alphavirus vectors present an attractive approach for gene therapy applications due to the rapid and simple recombinant virus particle production and their broad range of mammalian host cell transduction. Mainly three types of alphavirus vectors, namely naked RNA, recombinant particles and DNA/RNA layered vectors, have been subjected to preclinical studies with the goal of achieving prophylactic or therapeutic efficacy, particularly in oncology. In this context, immunization with alphavirus vectors has provided protection against challenges with tumor cells. Moreover, alphavirus intratumoral and systemic delivery has demonstrated substantial tumor regression and significant prolonged survival rates in various animal tumor models. Recent discoveries of the strong association of RNA interference and disease have accelerated gene therapy based approaches, where alphavirus-based gene delivery can play an important role. PMID:25961488

  11. Beyond the gene.

    PubMed

    Keller, Evelyn Fox; Harel, David

    2007-01-01

    This paper is a response to the increasing difficulty biologists find in agreeing upon a definition of the gene, and indeed, the increasing disarray in which that concept finds itself. After briefly reviewing these problems, we propose an alternative to both the concept and the word gene-an alternative that, like the gene, is intended to capture the essence of inheritance, but which is both richer and more expressive. It is also clearer in its separation of what the organism statically is (what it tangibly inherits) and what it dynamically does (its functionality and behavior). Our proposal of a genetic functor, or genitor, is a sweeping extension of the classical genotype/phenotype paradigm, yet it appears to be faithful to the findings of contemporary biology, encompassing many of the recently emerging-and surprisingly complex-links between structure and functionality. PMID:18043738

  12. Gene Characterization Index: Assessing the Depth of Gene Annotation

    PubMed Central

    Yusuf, Dimas; Brumm, Jochen; Cheung, Warren; Wahlestedt, Claes; Lenhard, Boris; Wasserman, Wyeth W.

    2008-01-01

    Background We introduce the Gene Characterization Index, a bioinformatics method for scoring the extent to which a protein-encoding gene is functionally described. Inherently a reflection of human perception, the Gene Characterization Index is applied for assessing the characterization status of individual genes, thus serving the advancement of both genome annotation and applied genomics research by rapid and unbiased identification of groups of uncharacterized genes for diverse applications such as directed functional studies and delineation of novel drug targets. Methodology/Principal Findings The scoring procedure is based on a global survey of researchers, who assigned characterization scores from 1 (poor) to 10 (extensive) for a sample of genes based on major online resources. By evaluating the survey as training data, we developed a bioinformatics procedure to assign gene characterization scores to all genes in the human genome. We analyzed snapshots of functional genome annotation over a period of 6 years to assess temporal changes reflected by the increase of the average Gene Characterization Index. Applying the Gene Characterization Index to genes within pharmaceutically relevant classes, we confirmed known drug targets as high-scoring genes and revealed potentially interesting novel targets with low characterization indexes. Removing known drug targets and genes linked to sequence-related patent filings from the entirety of indexed genes, we identified sets of low-scoring genes particularly suited for further experimental investigation. Conclusions/Significance The Gene Characterization Index is intended to serve as a tool to the scientific community and granting agencies for focusing resources and efforts on unexplored areas of the genome. The Gene Characterization Index is available from http://cisreg.ca/gci/. PMID:18213364

  13. IBM Research: Blue Gene

    NSDL National Science Digital Library

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

  14. Entrez Gene: gene-centered information at NCBI.

    PubMed

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2011-01-01

    Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP. PMID:21115458

  15. Entrez Gene: gene-centered information at NCBI.

    PubMed

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2007-01-01

    Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp. PMID:17148475

  16. Analysis of Gene-Gene Interactions Using Gene-Trait Similarity Regression

    PubMed Central

    Wang, Xin; Epstein, Michael P.; Tzeng, Jung-Ying

    2014-01-01

    Objective Gene-Gene interactions (GxG) are important to study because of their extensiveness in biological systems and their potential in explaining missing heritability of complex traits. In this work, we propose a new similarity-based test to assess GxG at gene level, which permits the study of epistasis at biologically functional units with amplified interaction signals. Methods Under the framework of gene-trait similarity regression (SimReg), we propose a gene-based test for detecting gene-gene interactions. SimReg uses a regression model to correlate trait similarity with genotypic similarity across a gene. Unlike existing gene-level methods based on leading principal components (PCs), SimReg summarizes all information on genotypic variation within a gene and can be used to assess the joint/interactive effects of two genes as well as the effect of one gene conditional on another. Results Using simulations and a real data application on warfarin study, we show that the SimReg GxG tests have satisfactory power and robustness under different genetic architecture when compared to existing gene-based interaction tests such as PC analysis or partial least squares (PLS). A genomewide association study with ~20,000 genes may be completed on a parallel computing system in 2 weeks. PMID:24969398

  17. Interactive Fly: Genes involved in Malpighian Tubules

    NSDL National Science Digital Library

    PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

    2006-12-14

    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.

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

    Microsoft Academic Search

    Liping Ji; Kian-lee Tan

    2005-01-01

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

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

    E-print Network

    Botstein, David

    The Gene Ontology (GO) database and informatics resource Gene Ontology Consortium* GO-EBI, EMBL and Accepted September 12, 2003 ABSTRACT The Gene Ontology (GO) project (http://www. geneontology of the integration effort is the development and use of annotation standards such as ontologies (1±4). Ontologies

  20. Gene expression in brain

    SciTech Connect

    Zomzely-Neurath, C.; Walker, W.

    1985-01-01

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

  1. 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".

  2. Horizontal Gene Transfer

    NSDL National Science Digital Library

    Citizendium

    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.

  3. Ultrasound mediated gene transfection

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

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

  4. Inferring Horizontal Gene Transfer

    PubMed Central

    Lassalle, Florent; Dessimoz, Christophe

    2015-01-01

    Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages [1]. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric") methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic") approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events. PMID:26020646

  5. Gene Therapy: Ethical Issues

    Microsoft Academic Search

    Isaac Rabino

    2003-01-01

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

  6. Photoprotection, Photoinhibition, Gene

    E-print Network

    Govindjee "Gov"

    Photoprotection, Photoinhibition, Gene Regulation, and Environment Edited by Barbara Demmig. Photoacclimation: Yin-Yang and the Compromise between Photoinactivation and Photoprotection 14 V and Photoinhibition: A Continuum of Photoprotection 49­64 William W. Adams III, C. Ryan Zarter, Kristine E. Mueh, V

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

    PubMed

    Freedman, Barry I; Skorecki, Karl

    2014-11-01

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

  8. Gene Manipulation In Cereals

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. IBMFS - gene mutations

    Cancer.gov

    A "mutation" is a change in a gene that prevents it from working properly. A "germline" mutation is a change that occurs in the egg or the sperm, or both, and is passed from one parent or both parents to the child.

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

    PubMed Central

    Borodovsky, Mark; Lomsadze, Alex

    2011-01-01

    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

  11. Interactive Fly: Maternally transcribed genes

    NSDL National Science Digital Library

    PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

    2006-11-13

    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.

  12. Nonviral Vectors for Gene Delivery

    E-print Network

    Baoum, Abdulgader Ahmed

    2011-04-26

    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...

  13. Hematopoietic Stem Cell Gene Therapy

    Microsoft Academic Search

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

    2002-01-01

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

  14. Gene targeting in Arabidopsis thaliana

    Microsoft Academic Search

    Ursula Halfter; Peter-Christian Morris; Lothar Willmitzer

    1992-01-01

    Gene targeting of a chromosomally integrated transgene in Arabidopsis thaliana is reported. A chimeric gene consisting of the promoter of the 35S RNA of CaMV, the polyadenylation signal of the octopine synthase gene and the coding region of the bacterial hygromycin phosphotransferase gene (hpt), which was rendered non-functional by deletion of 19 bp, was introduced into the genome of A.

  15. Analyzing tumor gene expression profiles

    Microsoft Academic Search

    Carsten Peterson; Markus Ringner

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

  16. Analyzing tumor gene expression profiles

    Microsoft Academic Search

    Carsten Peterson; Markus Ringnér

    2003-01-01

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

  17. Eukaryotic Gene Prediction Kelli Davies

    E-print Network

    Eukaryotic Gene Prediction Kelli Davies 2009 December 12 Introduction: The advent of large in 1977, that of a small bacteriophage consisting of 11 genes over 5.4kb of DNA. In the bacteriophage, coding genes comprise 95% of the genome.1 Since then, numerous prokaryotic and eukaryotic genomes have

  18. Sox genes find their feet

    Microsoft Academic Search

    Larysa H Pevny; Robin Lovell-Badge

    1997-01-01

    The identification of the mammalian testis-determining factor, SRY, led to the description of a new class of genes encoding transcription factors, the SOX gene family. SOX proteins display properties of both classical transcription factors and architectural components of chromatin. The dynamic and diverse patterns of expression of SOX genes and analysis of mutations in humans, mice and Drosophila suggest that

  19. Is there a mind gene?

    Microsoft Academic Search

    Ajit Narayanan

    Is there a gene or, rather, a set of genes which code for mind? To refine this question further, can all our cognitive processes and states be accounted for mainly or even entirel y in genetic terms? Clearly, environmental factors are important, since a person may have a gene for X which is never triggered because the right environmental conditions

  20. Simulating Gene Expression using Netlogo

    NSDL National Science Digital Library

    Steven Brewer (University of Massachusetts; )

    2004-06-12

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

  1. Independent Gene Discovery and Testing

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  2. Gene Discoveries Could Help Rheumatoid Arthritis Treatment

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Rheumatoid Arthritis About MedlinePlus Site Map FAQs Contact ...

  3. Gene conversion in the rice genome

    E-print Network

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

    2008-02-25

    genome, the large number of duplicated genes increases opportunities for gene conversion. Results: To characterize gene conversion in rice, we have defined 626 multigene families in which 377 gene conversions were detected using the GENECONV program...

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

    Microsoft Academic Search

    FARID E. AHMED

    2006-01-01

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

  5. Brains, genes, and primates.

    PubMed

    Izpisua Belmonte, Juan Carlos; Callaway, Edward M; Caddick, Sarah J; Churchland, Patricia; Feng, Guoping; Homanics, Gregg E; Lee, Kuo-Fen; Leopold, David A; Miller, Cory T; Mitchell, Jude F; Mitalipov, Shoukhrat; Moutri, Alysson R; Movshon, J Anthony; Okano, Hideyuki; Reynolds, John H; Ringach, Dario; Sejnowski, Terrence J; Silva, Afonso C; Strick, Peter L; Wu, Jun; Zhang, Feng

    2015-05-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators, and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive, and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  6. Gene therapy in keratoconus

    PubMed Central

    Farjadnia, Mahgol; Naderan, Mohammad; Mohammadpour, Mehrdad

    2015-01-01

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

  7. 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.

  8. Human disease genes: patterns and predictions

    Microsoft Academic Search

    Nick G. C. Smith; Adam Eyre-Walker

    2003-01-01

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

  9. Gene Therapy and Vaccination

    Microsoft Academic Search

    William J. Bowers; Michelle C. Janelsins; Howard J. Federoff

    Central nervous system (CNS) diseases represent a class of complex disorders for which cures have been largely unmet due to\\u000a the general lack of knowledge regarding underlying pathogenic mechanisms. Gene-based therapies directed at ameliorating neurodegenerative\\u000a diseases exhibit great potential due to rapid scientific advances made regarding delivery modalities, neurosurgical methods,\\u000a neuroimaging, and molecular biological manipulation. Given these breakthroughs, the diseased

  10. Gene Expression in Bone

    NASA Astrophysics Data System (ADS)

    D'Ambrogio, A.

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

  11. Housekeeping genes in prostate tumorigenesis.

    PubMed

    Byun, Jinyoung; Logothetis, Christopher J; Gorlov, Ivan P

    2009-12-01

    Housekeeping (HK) genes are involved in basic cellular functions and tend to be constitutively expressed across various tissues and conditions. A number of studies have analyzed the value of HK genes as an internal standard for assessing gene expression, but the role of HK genes in cancer development has never been specifically addressed. In this study, we sought to evaluate the expression of HK genes during prostate tumorigenesis. We performed a meta-analysis of gene expression during the transition from normal prostate (NP) to localized prostate cancer (LPC) (i.e., NP > LPC) and from localized to metastatic prostate cancer (MPC) (i.e., LPC > MPC). We found that HK genes are more likely to be differentially expressed during prostate tumorigenesis than is the average gene in the human genome, suggesting that prostate tumorigenesis is driven by modulation of the expression of HK genes. Cell-cycle genes and proliferation markers were up-regulated in both NP > LPC and LPC > MPC transitions. We also found that the genes encoding ribosomal proteins were up-regulated in the NP > LPC and down-regulated in the LPC > MPC transition. The expression of heat shock proteins was up-regulated during the LPC > MPC transition, suggesting that in its advanced stages, prostate tumor is under cellular stress. The results of these analyses suggest that during prostate tumorigenesis, there is a period when the tumor is under cellular stress and, therefore, may be the most vulnerable and responsive to treatment. PMID:19551858

  12. Advances in Gene Delivery Systems

    PubMed Central

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

    2011-01-01

    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

  13. Fever, genes, and epilepsy.

    PubMed

    Baulac, Stéphanie; Gourfinkel-An, Isabelle; Nabbout, Rima; Huberfeld, Gilles; Serratosa, Jose; Leguern, Eric; Baulac, Michel

    2004-07-01

    About 13% of patients with epilepsy have a history of febrile seizures (FS). Studies of familial forms suggest a genetic component to the epidemiological link. Indeed, in certain monogenic forms of FS, for which several loci have been reported, some patients develop epilepsy with a higher risk than in the general population. Patients with generalised epilepsy with febrile seizures plus (GEFS+) can have typical and isolated FS, FS lasting more beyond age 6 years, and subsequent afebrile (typically generalised) seizures. Mutations associated with GEFS+ were identified in genes for subunits of the voltage-gated sodium channel and the gamma2 subunit of the ligand-gated GABAA receptor. Screening for these genes in patients with severe myoclonic epilepsy in infancy showed de novo mutations of the alpha1 subunit of the voltage-gated sodium channel. Antecedent FS are commonly observed in temporal-lobe epilepsy (TLE). In sporadic mesial TLE-characterised by the sequence of complex FS in childhood, hippocampal sclerosis, and refractory temporal-lobe seizures-association studies suggested the role of several susceptibility genes. Work on some large pedigrees also suggests that FS and temporal-lobe seizures may have a common genetic basis, whether hippocampus sclerosis is present or not. The molecular defects identified in the genetic associations of FS and epileptic seizures are very attractive models to aid our understanding of epileptogenesis and susceptibility to seizure-provoking factors, especially fever. PMID:15207799

  14. nanosheets for gene therapy

    NASA Astrophysics Data System (ADS)

    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

    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.

  15. Gene-environment dependence creates spurious gene-environment interaction.

    PubMed

    Dudbridge, Frank; Fletcher, Olivia

    2014-09-01

    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

  16. Progress in gene targeting and gene therapy for retinitis pigmentosa

    SciTech Connect

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

    1994-09-01

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

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

    PubMed Central

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

    2009-01-01

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

  18. Using the Gene Ontology Hierarchy when Predicting Gene Function

    E-print Network

    Mostafavi, Sara

    2012-01-01

    The problem of multilabel classification when the labels are related through a hierarchical categorization scheme occurs in many application domains such as computational biology. For example, this problem arises naturally when trying to automatically assign gene function using a controlled vocabularies like Gene Ontology. However, most existing approaches for predicting gene functions solve independent classification problems to predict genes that are involved in a given function category, independently of the rest. Here, we propose two simple methods for incorporating information about the hierarchical nature of the categorization scheme. In the first method, we use information about a gene's previous annotation to set an initial prior on its label. In a second approach, we extend a graph-based semi-supervised learning algorithm for predicting gene function in a hierarchy. We show that we can efficiently solve this problem by solving a linear system of equations. We compare these approaches with a previous ...

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

    DOEpatents

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

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

  20. Endocrine regulation of HOX genes.

    PubMed

    Daftary, Gaurang S; Taylor, Hugh S

    2006-06-01

    Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology. PMID:16632680

  1. Reverse engineering transcriptional gene networks.

    PubMed

    Belcastro, Vincenzo; di Bernardo, Diego

    2014-01-01

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

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

    PubMed

    Finnerty, J R; Martindale, M Q

    1999-01-01

    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

  3. Detecting and visualizing gene fusions.

    PubMed

    Supper, Jochen; Gugenmus, Claudia; Wollnik, Johannes; Drueke, Tanja; Scherf, Matthias; Hahn, Alexander; Grote, Korbinian; Bretschneider, Nancy; Klocke, Bernward; Zinser, Christian; Cartharius, Kerstin; Seifert, Martin

    2013-01-01

    In recent years, gene fusions have gained significant recognition as biomarkers. They can assist treatment decisions, are seldom found in normal tissue and are detectable through Next-generation sequencing (NGS) of the transcriptome (RNA-seq). To transform the data provided by the sequencer into robust gene fusion detection several analysis steps are needed. Usually the first step is to map the sequenced transcript fragments (RNA-seq) to a reference genome. One standard application of this approach is to estimate expression and detect variants within known genes, e.g. SNPs and indels. In case of gene fusions, however, completely novel gene structures have to be detected. Here, we describe the detection of such gene fusion events based on our comprehensive transcript annotation (ElDorado). To demonstrate the utility of our approach, we extract gene fusion candidates from eight breast cancer cell lines, which we compare to experimentally verified gene fusions. We discuss several gene fusion events, like BCAS3-BCAS4 that was only detected in the breast cancer cell line MCF7. As supporting evidence we show that gene fusions occur more frequently in copy number enriched regions (CNV analysis). In addition, we present the Transcriptome Viewer (TViewer) a tool that allows to interactively visualize gene fusions. Finally, we support detected gene fusions through literature mining based annotations and network analyses. In conclusion, we present a platform that allows detecting gene fusions and supporting them through literature knowledge as well as rich visualization capabilities. This enables scientists to better understand molecular processes, biological functions and disease associations, which will ultimately lead to better biomedical knowledge for the development of biomarkers for diagnostics and therapies. PMID:23036331

  4. Aberrant Gene Expression in Humans

    PubMed Central

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

    2015-01-01

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

  5. Gene amelioration demonstrated: the journey of nascent genes in bacteria.

    PubMed

    Marri, Pradeep Reddy; Golding, G Brian

    2008-02-01

    Gene amelioration is the hypothesis that genes acquired via lateral gene transfer will, over time, acquire the molecular characteristics of the host genome. Species for which multiple strains have been sequenced permit a demonstration that this hypothesis is correct. We use 7 sequenced genomes of Streptococcus pyogenes and 6 sequenced genomes of Staphylococcus aureus to illustrate the action of amelioration on these genomes. PMID:18356951

  6. Chromosomal localisation of a pseudoautosomal growth gene(s).

    PubMed Central

    Ogata, T; Petit, C; Rappold, G; Matsuo, N; Matsumoto, T; Goodfellow, P

    1992-01-01

    Although recent molecular studies in patients with sex chromosome aberrations are consistent with a growth gene(s) being present in the pseudoautosomal region (PAR), the precise location has not been determined. In this report, we describe a Japanese boy and his mother with an interstitial deletion in Xp22.3 and review the correlation between genotype and stature in six cases of partial monosomy of the PAR. The results indicate that the region from DXYS20 to DXYS15 is the critical region for the putative growth gene(s). Images PMID:1404292

  7. Entrez Gene: gene-centered information at NCBI.

    PubMed

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2005-01-01

    Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. It does not include all known or predicted genes; instead Entrez Gene focuses on the genomes that have been completely sequenced, that have an active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is updated as new information becomes available. Entrez Gene is a step forward from NCBI's LocusLink, with both a major increase in taxonomic scope and improved access through the many tools associated with NCBI Entrez. PMID:15608257

  8. Gene: a gene-centered information resource at NCBI.

    PubMed

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

    2015-01-01

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

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

    PubMed

    Fitzgerald, Patrick T; Ackerman, Michael J

    2005-11-01

    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

  10. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists.

  11. AMIGene: Annotation of MIcrobial Genes

    Microsoft Academic Search

    Stéphanie Bocs; Stéphane Cruveiller; David Vallenet; Grégory Nuel; Claudine Médigue

    2003-01-01

    AMIGene (Annotation of MIcrobial Genes) is an application for automatically identifying the most likely coding sequences (CDSs) in a large contig or a complete bacterial genome sequence. The first step in AMIGene is dedicated to the construction of Markov models that fit the input genomic data (i.e. the gene model), followed by the combination of well-known gene-finding methods and an

  12. Gene therapy for hematological malignancies

    Microsoft Academic Search

    G. D. Schmidt-Wolf; I. G. H. Schmidt-Wolf

    2003-01-01

    .   Since cancer is the result of genetic mutations, it should be well suited for correction through gene therapy. Hematological\\u000a malignancies in which human gene transfer has been performed are leukemias, lymphomas, graft-versushost disease after allogeneic\\u000a bone marrow transplantation in leukemia, and multiple myeloma. Gene therapy may be used to induce or enhance an antitumor\\u000a immunological reaction, to correct a

  13. GENE THERAPY FOR LUNG NEOPLASMS

    PubMed Central

    Vachani, Anil; Moon, Edmund; Wakeam, Elliot; Haas, Andrew R.; Sterman, Daniel H.; Albelda, Steven M.

    2011-01-01

    SYNOPSIS Both advanced stage lung cancer and malignant pleural mesothelioma are associated with a poor prognosis. Although there have been advances in treatment regimens for both diseases, these have had only a modest effect on their progressive course. Gene therapy for thoracic malignancies represents a novel therapeutic approach and has been evaluated in a number of clinical trials over the last two decades. Strategies have included induction of apoptosis, tumor suppressor gene replacement, suicide gene expression, cytokine based therapy, various vaccination approaches, and adoptive transfer of modified immune cells. This review will consider the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies. PMID:22054892

  14. Selector Genes, Polymorphisms, and Evolution

    NSDL National Science Digital Library

    Diethard Tautz (Zoologisches Institut der Universität München; )

    1996-01-12

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

  15. Show Me the Genes

    NSDL National Science Digital Library

    2014-09-18

    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.

  16. Genes and childhood leukemia.

    PubMed

    K?sy, Julita; Januszkiewicz-Lewandowska, Danuta

    2015-01-01

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

  17. XLMR genes: Update 1996

    SciTech Connect

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

    1996-07-12

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

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

    PubMed Central

    Sun, Jingchun; Han, Leng; Zhao, Zhongming

    2009-01-01

    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

  19. Comparative genomics of metabolic pathways in Mycobacterium species: gene duplication, gene decay and lateral gene transfer.

    PubMed

    Marri, Pradeep Reddy; Bannantine, John P; Golding, Geoffrey B

    2006-11-01

    The genus Mycobacterium comprises significant pathogenic species that infect both humans and animals. One species within this genus, Mycobacterium tuberculosis, is the primary killer of humans resulting from bacterial infections. Five mycobacterial genomes belonging to four different species (M. tuberculosis, Mycobacterium bovis, Mycobacterium leprae and Mycobacterium avium ssp. paratuberculosis) have been sequenced to date and another 14 mycobacterial genomes are at various stages of completion. A comparative analysis of the gene products of key metabolic pathways revealed that the major differences among these species are in the gene products constituting the cell wall and the gene families encoding the acidic glycine-rich (PE/PPE/PGRS) proteins. Mycobacterium leprae has evolved by retaining a minimal gene set for most of the gene families, whereas M. avium ssp. paratuberculosis has acquired some of the virulence factors by lateral gene transfer. PMID:17064286

  20. DIFFERENTIAL GENE EXPRESSION OF PUTATIVE VIRULENCE GENES IN Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. Integrating Gene Ontology and Blast to predict gene functions

    Microsoft Academic Search

    WANG Cheng-gang; MO Zhi-hong

    2007-01-01

    A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by

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

    Microsoft Academic Search

    Emma Peeling; Allan Tucker

    2007-01-01

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

  3. Biological Profiling of Gene Groups utilizing Gene Ontology

    Microsoft Academic Search

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

    2004-01-01

    Increasingly used high throughput experimental techniques, like DNA or protein microarrays give as a result groups of interesting, e.g. differentially regulated genes which require further biological interpretation. With the systematic functional annotation provided by the Gene Ontology the information required to automate the interpretation task is now accessible. However, the determination of statistical significant e.g. molecular functions within these groups

  4. Creating a honey bee consensus gene set

    Microsoft Academic Search

    Christine G Elsik; Aaron J Mackey; Justin T Reese; Natalia V Milshina; David S Roos; George M Weinstock

    2007-01-01

    BACKGROUND: We wished to produce a single reference gene set for honey bee (Apis mellifera). Our motivation was twofold. First, we wished to obtain an improved set of gene models with increased coverage of known genes, while maintaining gene model quality. Second, we wished to provide a single official gene list that the research community could further utilize for consistent

  5. Variability in gene expression underlies incomplete penetrance

    E-print Network

    van Oudenaarden, Alexander

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

  6. Msx homeobox gene family and craniofacial development

    Microsoft Academic Search

    Sylvia ALAPPAT; Zun Yi ZHANG; Yi Ping CHEN

    2003-01-01

    Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the

  7. Global gene expression in Leishmania.

    PubMed

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

    2007-08-01

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

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

    E-print Network

    Palle, Sreenath Reddy

    2011-10-21

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

  9. 5____________________________________________________________________________ Gene Regulation in Spermatogenesis

    E-print Network

    Wilkinson, Miles F.

    in the Testis A. Mechanisms of Androgen Action B. The Androgen Receptor C. Estrogen and the Testis D. TestisSpecific Gene Expression and DNA Methylation A. Male Germ Cell­Specific Genes B. SomaticCell Testis conferred by transcription factors in the testis, particularly those defined in knockout mice. Third, we

  10. 20Engineering Gene Circuits: Foundations

    E-print Network

    You, Lingchong

    [27,28]. As evidenced in the term ``circuit,'' gene circuits are often compared to electrical circuits or repressed. Construction of electrical circuits benefits from a large collection of well-characterized parts20Engineering Gene Circuits: Foundations and Applications Dennis Tu Jiwon Lee Taylan Ozdere Tae Jun

  11. Susceptibility Genes in Thyroid Autoimmunity

    PubMed Central

    Ban, Yoshiyuki; Tomer, Yaron

    2005-01-01

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

  12. Method of controlling gene expression

    DOEpatents

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

    1991-12-03

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

  13. On Meme-Gene Coevolution

    Microsoft Academic Search

    Larry Bull; Owen Holland; Susan Blackmore

    2000-01-01

    In this paper we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is,

  14. Animal Body Plans: Homeobox Genes

    NSDL National Science Digital Library

    WGBH Educational Foundation

    2003-09-26

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

  15. Mining Virulence Genes Using Metagenomics

    Microsoft Academic Search

    Pedro Belda-Ferre; Raúl Cabrera-Rubio; Andrés Moya; Alex Mira; Jack Anthony Gilbert

    2011-01-01

    When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible

  16. Evolutionary Origin of Orphan Genes

    E-print Network

    deoxyribonucleic acid (DNA). This latter process may even occur much more frequently than previously assumed that functional ribonucleic acids (RNAs) and proteins can relatively easilyarise outof randomnucleotidesequences Definition of Orphan Genes While gene families are defined through their presence in diverse evolutionary

  17. Gene Technology in Tissue Engineering

    Microsoft Academic Search

    Xiao-Dan Sun; In-Seop Lee

    2006-01-01

    Scaffold, cells and signaling factors are regarded as the three essential components in tissue engineering. With the development of molecular and cell biology, gene technology is beginning to show a promising position in tissue engineering as it can influence these essential components at DNA-level. By introducing plasmid DNA or genes encoding certain signaling factors (growth factors\\/cytokines) into the cells, required

  18. Posttranscriptional Gene Regulation by Spatial

    E-print Network

    Bedwell, David M.

    Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3 Untranslated Region Andrea B for Posttranscriptional Gene Regualtion by spatial Rearrangement of 3'UTR #12;A Competition between Stimulators Intron Enhances NMD PABC1 Antagonizes the interaction between eRF3 and hUpf1 in vitro #12;A Competition

  19. Generalist Genes and Learning Disabilities

    ERIC Educational Resources Information Center

    Plomin, Robert; Kovas, Yulia

    2005-01-01

    The authors reviewed recent quantitative genetic research on learning disabilities that led to the conclusion that genetic diagnoses differ from traditional diagnoses in that the effects of relevant genes are largely general rather than specific. This research suggests that most genes associated with common learning disabilities--language…

  20. Gene therapy on the move

    PubMed Central

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

    2013-01-01

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

  1. Druggability of human disease genes

    Microsoft Academic Search

    Meena Kishore Sakharkar; Kishore Ramaji Sakharkar; Shazib Pervaiz

    2007-01-01

    The availability of complete genome sequences and the wealth of large-scale biological datasets provide an unprecedented opportunity to elucidate the genetic basis of human diseases. Here we use integrative in silico approaches to provide an accurate description of gene functions to a set of 1737 highly curated disease genes in the human genome. This analysis is the first attempt on

  2. Gene diversity in Indian populations

    Microsoft Academic Search

    A. K. Roychoudhury

    1977-01-01

    Gene frequency data of ten protein and enzyme loci in seven populations of India were collected from the literature. The gene differentiation among seven populations relative to total population was only 0.6%, indicating that the genic variation between populations was small compared to that within them. Using 29 common protein loci, the genetic distances between Indians and three major races

  3. Gli genes and limb development

    Microsoft Academic Search

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

    1999-01-01

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

  4. See the Genes

    NSDL National Science Digital Library

    VU Bioengineering RET Program,

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

  5. Gene therapy for hemophilia

    PubMed Central

    Rogers, Geoffrey L.; Herzog, Roland W.

    2015-01-01

    Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors. PMID:25553466

  6. Taste Receptor Genes

    PubMed Central

    Bachmanov, Alexander A.; Beauchamp, Gary K.

    2009-01-01

    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

  7. Nonviral Vectors for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Baoum, Abdulgader Ahmed

    2011-12-01

    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.

  8. Delivery systems for gene therapy

    PubMed Central

    Mali, Shrikant

    2013-01-01

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

  9. Nanoparticle-Mediated Gene Delivery

    NASA Astrophysics Data System (ADS)

    Jin, Sha; Leach, John C.; Ye, Kaiming

    Nonviral gene delivery has been gaining considerable attention recently. Although the efficacy of DNA transfection, which is a major concern, is low in nonviral vector-mediated gene transfer compared with viral ones, nonviral vectors are relatively easy to prepare, less immunogenic and oncogenic, and have no potential of virus recombination and no limitation on the size of a transferred gene. The ability to incorporate genetic materials such as plasmid DNA, RNA, and siRNA into functionalized nanoparticles with little toxicity demonstrates a new era in pharmacotherapy for delivering genes selectively to tissues and cells. In this chapter, we highlight the basic concepts and applications of nonviral gene delivery using super paramagnetic iron oxide nanoparticles and functionalized silica nanoparticles. The experimental protocols related to these topics are described in the chapter.

  10. Nanoparticles for Retinal Gene Therapy

    PubMed Central

    Conley, Shannon M.; Naash, Muna I.

    2010-01-01

    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

  11. Druggability of human disease genes.

    PubMed

    Sakharkar, Meena Kishore; Sakharkar, Kishore Ramaji; Pervaiz, Shazib

    2007-01-01

    The availability of complete genome sequences and the wealth of large-scale biological datasets provide an unprecedented opportunity to elucidate the genetic basis of human diseases. Here we use integrative in silico approaches to provide an accurate description of gene functions to a set of 1737 highly curated disease genes in the human genome. This analysis is the first attempt on in silico identification of druggable domains within disease genes. We provide information on gene architecture and function, druggability in the context of available drugs, and evolutionary conservation across 38 model eukaryotic genomes. These data could serve as a useful compendium for integrated information on disease genes with the potential for exploring pharmaceutically exploitable targets. Our analyses underscore the utility of large genomic databases for in silico systematic drug target identification in the post-genomic era. PMID:17446117

  12. Gene function prediction with gene interaction networks: a context graph kernel approach

    Microsoft Academic Search

    Xin Li; Hsinchun Chen; Jiexun Li; Zhu Zhang

    2010-01-01

    Predicting gene functions is a challenge for biologists in the postgenomic era. Interactions among genes and their products compose networks that can be used to infer gene functions. Most previous studies adopt a linkage assumption, i.e., they assume that gene interactions indicate functional similarities between connected genes. In this study, we propose to use a gene's context graph, i.e., the

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

    E-print Network

    Levin, Judith G.

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

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

    Microsoft Academic Search

    Seon-Young Kim; Yong Sung Kim

    2008-01-01

    BACKGROUND: Gene expression profiling is a promising approach to better estimate patient prognosis; however, there are still unresolved problems, including little overlap among similarly developed gene sets and poor performance of a developed gene set in other datasets. RESULTS: We applied a gene sets approach to develop a prognostic gene set from multiple gene expression datasets. By analyzing 12 independent

  15. Online Discovery and Refinement of Novel Genes Using GeneScope

    Microsoft Academic Search

    Hasan Jamil Jesmin; J. Jesmin

    2009-01-01

    We present a novel gene finding and validation tool, called GeneScope, which is capable of finding and validat- ing genes declaratively by autonomously integrating hetero- geneous online resources. GeneScope also supports user defined concepts to articulate gene structures, and refine ex- isting concepts toward the discovery of the intended genes. The system relies upon a new string query language called

  16. Detecting Highways of Horizontal Gene Transfer

    E-print Network

    Bansal, Mukul S.

    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 ...

  17. Lecture 7: Gene 26 Nov 2013

    E-print Network

    Shamir, Ron

    Finding in Prokaryotes CG © Ron Shamir 9 #12;CG © Ron Shamir 10 #12;Genes in Prokaryotes · High gene #12;First Order Markov Model · Use two Markov models (similar to CpG islands) to discriminate genes

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

    NASA Astrophysics Data System (ADS)

    Shimizu, Akifumi; Yano, Kentaro

    2010-01-01

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

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

    PubMed

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

    2013-12-01

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

  20. Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios.

    PubMed

    Li, Qing; Kim, Yoonhee; Suktitipat, Bhoom; Hetmanski, Jacqueline B; Marazita, Mary L; Duggal, Priya; Beaty, Terri H; Bailey-Wilson, Joan E

    2015-07-01

    Genome-wide association studies (GWAS) for nonsyndromic cleft lip with or without cleft palate (CL/P) have identified multiple genes as important in the etiology of this common birth defect. We performed a candidate gene/pathway analysis explicitly considering gene-gene (G × G) interaction to further explore the etiology of CL/P. Animal models have shown the WNT signaling pathway plays an important role in mid-facial development, and various genes in this pathway have been associated with nonsyndromic CL/P in previous studies. We propose a combined approach to search for possible G × G interactions using machine learning and regression-based methods to test for interactions between genes in the WNT family, and between these genes and other genes identified by GWAS in case-parent trios. Using this combined approach of regression-based and machine learning methods in CL/P case-parent trios, we found robust evidence of G × G interaction between markers in WNT5B and MAFB (empiric P-values = 0.0076 among Asian trios and P-values = 0.018 among European trios). Additional evidence for epistatic interaction between markers in WNT5A, IRF6, and C1orf107 was seen among Asian trios, and markers in the 8q24 region and WNT5B among European trios. PMID:25663376

  1. Identifying gene-environment and gene-gene interactions using a progressive penalization approach

    PubMed Central

    Zhu, Ruoqing; Zhao, Hongyu; Ma, Shuangge

    2015-01-01

    In genomic studies, identifying important gene-environment and gene-gene interactions is a challenging problem. In this study, we adopt the statistical modeling approach, where interactions are represented by product terms in regression models. For the identification of important interactions, we adopt penalization, which has been used in many genomic studies. Straightforward application of penalization does not respect the “main effect, interaction” hierarchical structure. A few recently proposed methods respect this structure by applying constrained penalization. However, they demand very complicated computational algorithms and can only accommodate a small number of genomic measurements. We propose a computationally fast penalization method that can identify important gene-environment and gene-gene interactions and respect a strong hierarchical structure. The method takes a stagewise approach and progressively expands its optimization domain to account for possible hierarchical interactions. It is applicable to multiple data types and models. A coordinate descent method is utilized to produce the entire regularized solution path. Simulation study demonstrates the superior performance of the proposed method. We analyze a lung cancer prognosis study with gene expression measurements and identify important gene-environment interactions. PMID:24723356

  2. Reverse engineering the ovine gene network under

    E-print Network

    Painter, Kevin

    Reverse engineering the ovine gene network under Psoroptes Ovis infestation. Supervisor: Dr. Pier.....................................................................10 2.2 Reverse Engineering the Gene Regulatory Networks (GRNs

  3. Detecting multivariate differentially expressed genes

    PubMed Central

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

    2007-01-01

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

  4. Genes in sport and doping.

    PubMed

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

    2013-09-01

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

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

    PubMed

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

    2011-01-01

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

  6. 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...

  7. Gene Delivery to the Airway

    PubMed Central

    Keiser, Nicholas W.; Engelhardt, John F.

    2013-01-01

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

  8. Gene Machine: The Lac Operon

    NSDL National Science Digital Library

    The PhET project at the University of Colorado creates "fun, interactive, research-based simulations of physical phenomena." This particular one deals with the lac operon. Build a gene network! The lac operon is a set of genes which are responsible for the metabolism of lactose in some bacterial cells. Explore the effects of mutations within the lac operon by adding or removing genes from the DNA. The simulation is also paired with a user-contirubed Teaching Idea using the simulation in context that can be found near the bottom of the page. The simulation is also available in multiple languages.

  9. Gene Flow and Genetic Differentiation

    PubMed Central

    Spieth, P. T.

    1974-01-01

    A brief analysis is presented for the effects of gene flow upon genetic differentiation within and between populations generated by mutation and drift. Previous results obtained with the "island" model are developed into a form that lends itself to biological interpretation. Attention is focused upon the effective local population size and the ratio of the genetic identity of two genes in different populations to that of two genes in the same population. The biological significance of this ratio, which is independent of population size, is discussed. Similarities between the results of this model and those of the "stepping-stone" model are noted. PMID:4452477

  10. Dimerizer-regulated gene expression.

    PubMed

    Pollock, Roy; Clackson, Tim

    2002-10-01

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

  11. Genomics screens for metastasis genes

    PubMed Central

    Yan, Jinchun; Huang, Qihong

    2014-01-01

    Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367

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

    Microsoft Academic Search

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

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

  13. Tilapia metallothionein genes: PCR-cloning and gene expression studies

    Microsoft Academic Search

    Andrew Pok Lap; Vincent Kwok Lim Lam; King Ming Chan

    2005-01-01

    Genomic PCR reactions were performed to isolate gene sequences of tilapia metallothionein (tiMT) from Oreochromis mossambicus and Oreochromis aureus. Two AP1 binding sites, four metal responsive elements, and a TATA box are the major cis-acting elements identified in the 800-bp 5? flanking region of the tiMTs obtained in this study. The tiMT gene promoter cloned from O. aureus was characterized

  14. OGEE: an online gene essentiality database.

    PubMed

    Chen, Wei-Hua; Minguez, Pablo; Lercher, Martin J; Bork, Peer

    2012-01-01

    OGEE is an Online GEne Essentiality database. Its main purpose is to enhance our understanding of the essentiality of genes. This is achieved by collecting not only experimentally tested essential and non-essential genes, but also associated gene features such as expression profiles, duplication status, conservation across species, evolutionary origins and involvement in embryonic development. We focus on large-scale experiments and complement our data with text-mining results. Genes are organized into data sets according to their sources. Genes with variable essentiality status across data sets are tagged as conditionally essential, highlighting the complex interplay between gene functions and environments. Linked tools allow the user to compare gene essentiality among different gene groups, or compare features of essential genes to non-essential genes, and visualize the results. OGEE is freely available at http://ogeedb.embl.de. PMID:22075992

  15. Genes to Cognition Online

    NSDL National Science Digital Library

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

  16. Genes and COPD

    PubMed Central

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

    2012-01-01

    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

  17. Environment, genes, and cancer

    SciTech Connect

    Manuel, J.

    1996-03-01

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

  18. Genes-R-Us

    NSDL National Science Digital Library

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

    1994-07-30

    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 !

  19. Gene Function Prediction Based on the Gene Ontology Hierarchical Structure

    PubMed Central

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

    2014-01-01

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

  20. Gene function prediction based on the Gene Ontology hierarchical structure.

    PubMed

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

    2014-01-01

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

  1. A forest-based approach to identifying gene and gene–gene interactions

    PubMed Central

    Chen, Xiang; Liu, Ching-Ti; Zhang, Meizhuo; Zhang, Heping

    2007-01-01

    Multiple genes, gene-by-gene interactions, and gene-by-environment interactions are believed to underlie most complex diseases. However, such interactions are difficult to identify. Although there have been recent successes in identifying genetic variants for complex diseases, it still remains difficult to identify gene–gene and gene–environment interactions. To overcome this difficulty, we propose a forest-based approach and a concept of variable importance. The proposed approach is demonstrated by simulation study for its validity and illustrated by a real data analysis for its use. Analyses of both real data and simulated data based on published genetic models show the effectiveness of our approach. For example, our analysis of a published data set on age-related macular degeneration (AMD) not only confirmed a known genetic variant (P value = 2E-6) for AMD, but also revealed an unreported haplotype surrounding single-nucleotide polymorphism (SNP) rs10272438 on chromosome 7 that was significantly associated with AMD (P value = 0.0024). These significance levels are obtained after the consideration for a large number of SNPs. Thus, the importance of this work is twofold: it proposes a powerful and flexible method to identify high-risk haplotypes and their interactions and reveals a potentially protective variant for AMD. PMID:18048322

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

    Microsoft Academic Search

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

    2001-01-01

    .   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

  3. Gene therapy for Parkinson's disease.

    PubMed

    Yasuhara, Takao; Date, Isao

    2009-01-01

    Parkinson's disease is characterized by the degeneration of the nigrostriatal dopaminergic neurons with the manifestation of tremor, rigidity, akinesia, and disturbances of postural reflexes. Medication using L-DOPA and surgeries including deep brain stimulation are the established therapies for Parkinson's disease. Cell therapies are also effective and have rapidly developed with the recent advancement in molecular biological technology including gene transfer. In this review, ex vivo gene therapy using genetically engineered cell transplantation for Parkinson's disease model of animals is described, including catecholamine/neurotrophic factor-secreting cell transplantation with or without encapsulation, as well as in vivo gene therapy using direct injection of viral vector to increase dopamine-production, ameliorate the survival of dopaminergic neurons, correct the deteriorated microenvironment, or normalize genetic abnormality. Furthermore, the future directions for clinical application are described together with recent clinical trials of gene therapy. PMID:20411788

  4. Revisiting Global Gene Expression Analysis

    E-print Network

    Lovén, Jakob

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

  5. Intervention in gene regulatory networks 

    E-print Network

    Choudhary, Ashish

    2006-10-30

    Example . . . . . . . . . . . . . . . . . . . . 12 D. Metastatic Melanoma Application . . . . . . . . . . . . . . 13 E. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . 19 IV THE IMPERFECT INFORMATION CASE . . . . . . . . . . . 20 A. Belief... Vector . . . . . . . . . . . . . . . . . . . . . . . . . . 21 B. Cost to Go Functions . . . . . . . . . . . . . . . . . . . . . 21 C. 3 Gene PBN Example . . . . . . . . . . . . . . . . . . . . 22 D. Metastatic Melanoma Application...

  6. Systems Biophysics of Gene Expression

    E-print Network

    Vilar, Jose M G

    2013-01-01

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

  7. Sleep deprivation and gene expression.

    PubMed

    da Costa Souza, Annie; Ribeiro, Sidarta

    2015-01-01

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

  8. Gene Variants Reduce Opioid Risks

    MedlinePLUS

    ... Prevention Research Training Treatment Research Trends and Statistics Drugs of Abuse Alcohol Amphetamines Bath Salts Club Drugs Cocaine Emerging ... this article APA style citation National Institute on Drug Abuse. Gene Variants Reduce Opioid Risks Retrieved from http:// ...

  9. Combining Hierarchical and Associative Gene Ontology Relations with Textual Evidence in Estimating Gene and Gene Product Similarity

    SciTech Connect

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.; Tratz, Stephen C.; Gregory, Michelle L.

    2007-03-01

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the Gene Ontology, two complementary approaches have emerged where the similarity between two genes or gene products is obtained by comparing Gene Ontology (GO) annotations associated with the genes or gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene subontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene subontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy, and demonstrate that further improvements can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  10. Regulated Genes in Transgenic Plants

    Microsoft Academic Search

    Philip N. Benfey; Nam-Hai Chua

    1989-01-01

    Transgenic plants are an effective system for the study of regulated gene expression. Developmental control of expression can be monitored by assaying different tissues or by assaying a plant at different developmental stages. Analysis of the petunia 5-enolpyruvylshikimate-3-phosphate synthase gene, which is highly expressed in flowers, allowed identification of an upstream region that confers tissue-specific and developmentally regulated expression. The

  11. Transgenic Arabidopsis Gene Expression System

    NASA Technical Reports Server (NTRS)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

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

  12. Gene Polymorphisms in Chronic Periodontitis

    PubMed Central

    Laine, Marja L.; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (R)-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP. PMID:20339487

  13. Annotating genes using textual patterns.

    PubMed

    Cakmak, Ali; Ozsoyoglu, Gultekin

    2007-01-01

    Annotating genes with Gene Ontology (GO) terms is crucial for biologists to characterize the traits of genes in a standardized way. However, manual curation of textual data, the most reliable form of gene annotation by GO terms, requires significant amounts of human effort, is very costly, and cannot catch up with the rate of increase in biomedical publications. In this paper, we present GEANN, a system to automatically infer new GO annotations for genes from biomedical papers based on the evidence support linked to PubMed, a biological literature database of 14 million papers. GEANN (i) extracts from text significant terms and phrases associated with a GO term, (ii) based on the extracted terms, constructs textual extraction patterns with reliability scores for GO terms, (iii) expands the pattern set through "pattern crosswalks", (iv) employs semantic pattern matching, rather than syntactic pattern matching, which allows for the recognition of phrases with close meanings, and (iv) annotates genes based on the "quality" of the matched pattern to the genomic entity occurring in the text. On the average, in our experiments, GEANN has reached to the precision level of 78% at the 57% recall level. PMID:17990494

  14. SMAD genes in juvenile polyposis.

    PubMed

    Roth, S; Sistonen, P; Salovaara, R; Hemminki, A; Loukola, A; Johansson, M; Avizienyte, E; Cleary, K A; Lynch, P; Amos, C I; Kristo, P; Mecklin, J P; Kellokumpu, I; Järvinen, H; Aaltonen, L A

    1999-09-01

    Juvenile polyposis (JP) is a dominantly inherited condition characterized by the development of multiple hamartomatous tumors, juvenile polyps, in the gastrointestinal tract. The aim of this study was to clarify the role of SMAD4 in JP. DNA from four unrelated JP kindreds and three sporadic JP cases was available for mutation screening. Two truncating defects (one in a familial and one in a sporadic case) and one missense change (in a familial case) that was absent in 55 control samples were detected. To study the possibility that germline mutations in other genes encoding different components of the TGF-beta signaling pathway may be present in these JP patients, mutation analyses of the SMAD2, SMAD3, and SMAD7 genes were also performed. No mutations of these genes were detected in any of the patients. Our results confirm that SMAD4 is a gene predisposing to JP and suggest the existence of further JP loci other than the SMAD2, SMAD3, or SMAD7 genes. Genes Chromosomes Cancer 26:54-61, 1999. PMID:10441006

  15. Genes contributing to prion pathogenesis

    PubMed Central

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V.; Lessard, Pierre; Wille, Holger; Tremblay, Patrick; Groth, Darlene F.; Yehiely, Fruma; Korth, Carsten; Moore, Richard C.; Tatzelt, Jörg; Rubenstein, Eric; Boucheix, Claude; Yang, Xiaoping; Stanley, Pamela; Lisanti, Michael P.; Dwek, Raymond A.; Rudd, Pauline M.; Moskovitz, Jackob; Epstein, Charles J.; Cruz, Tracey Dawson; Kuziel, William A.; Maeda, Nobuyo; Sap, Jan; Ashe, Karen Hsiao; Carlson, George A.; Tesseur, Ina; Wyss-Coray, Tony; Mucke, Lennart; Weisgraber, Karl H.; Mahley, Robert W.; Cohen, Fred E.; Prusiner, Stanley B.

    2009-01-01

    SUMMARY Prion diseases are caused by conversion of a normally folded, nonpathogenic isoform of the prion protein (PrPC) to a misfolded, pathogenic isoform (PrPSc). Prion inoculation experiments in mice expressing homologous PrPC molecules on different genetic backgrounds displayed different incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analyzed prion incubation times in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 gene candidates, because their products either colocalize with PrP, are associated with Alzheimer’s disease, are elevated during prion disease, or function in PrP-mediated signaling, PrP glycosylation, or protein maintenance. Whereas some of the candidates tested may have a role in the normal function of PrPC, our data show that many genes previously implicated in prion replication have no discernable effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of amyloid beta (A4) precursor protein (App) or interleukin 1 receptor, type I (Il1r1), and transgenic overexpression of human superoxide dismutase 1 (SOD1) prolonged incubation times by 13%, 16%, and 19%, respectively. PMID:18559949

  16. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

    PubMed

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-05-15

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-?), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-?, resistin and adiponectin in pathogenesis of T2DM. PMID:25987962

  17. Gene therapy in status epilepticus.

    PubMed

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

    2013-09-01

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

  18. Immunoglobulin genes of the turtles.

    PubMed

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

    2013-03-01

    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

  19. Predicting essential genes in fungal genomes

    Microsoft Academic Search

    Michael Seringhaus; Alberto Paccanaro; Anthony Borneman; Michael Snyder; Mark Gerstein

    2006-01-01

    Essential genes are required for an organism's viability, and the ability to identify these genes in pathogens is crucial to directed drug development. Predicting essential genes through computational methods is appealing because it circumvents expensive and difficult experimental screens. Most such prediction is based on homology mapping to experimentally verified essential genes in model organisms. We present here a different

  20. Review article Generating biological models through gene

    E-print Network

    Paris-Sud XI, Université de

    applications in medicine and agricul- ture. New animal models have been created using gene transfer and gene modification of the genome. To create lines of genetically modified animals, gene trans- fer must be achievedReview article Generating biological models through gene transfer to domestic animals LM Houdebine

  1. Practice Note Establishing and managing gene

    E-print Network

    Practice Note Establishing and managing gene conservation units 1FCPN021 Jason Hubert and Joan are called gene conservation units. This Practice Note sets out what you need to do to establish a gene in a way that would make them suitable, but a more formal recognition of a network of gene conservation

  2. A census of human cancer genes

    Microsoft Academic Search

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

    2004-01-01

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

  3. Cancer gene therapy: an awkward adolescence

    Microsoft Academic Search

    Michael M Gottesman

    2003-01-01

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

  4. A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data

    PubMed Central

    Seok, Junhee; Davis, Ronald W.; Xiao, Wenzhong

    2015-01-01

    Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn’t been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge. PMID:25933378

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

    SciTech Connect

    Mishra, N.C.

    1995-01-01

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

  6. Novel gene transfer systems: intelligent gene transfer vectors for gene medicines.

    PubMed

    Nakajima, Toshihiro

    2012-01-01

    Drug delivery systems for gene transfer are called 'vectors'. These systems were originally invented as a delivery system for the transfection in vitro or in vivo. Several vectors are then developed for clinical use of gene medicines and currently some of them are approved as animal drugs. Conventional drug delivery system generally consists of approved (existing) materials to avoid additional pre-clinical or clinical studies. However, current vectors contain novel materials to improve an efficacy of gene medicines. Thus, these vectors have functions more than a mere delivery of active ingredients. For example some vectors have immunological functions such as adjuvants in vaccines. These new types of vectors are called 'intelligent' or 'innovative' vector system', since the concept or strategy for the development is completely different from conventional drug delivery systems. In this article, we described a current status of 'intelligent gene transfer vectors and discussed on the potentials of them. PMID:22762555

  7. Advancement and prospects of tumor gene therapy

    PubMed Central

    Zhang, Chao; Wang, Qing-Tao; Liu, He; Zhang, Zhen-Zhu; Huang, Wen-Lin

    2011-01-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell– and T cell–based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy. PMID:21352695

  8. Evolution of Hemoglobin and Its Genes

    PubMed Central

    Hardison, Ross C.

    2012-01-01

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

  9. Gene therapy of benign gynecological diseases?

    PubMed Central

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

    2015-01-01

    Gene therapy is the introduction of genetic material into patient’s cells to achieve therapeutic benefit. Advances in molecular biology techniques and better understanding of disease pathogenesis have validated the use of a variety of genes as potential molecular targets for gene therapy based approaches. Gene therapy strategies include: mutation compensation of dysregulated genes; replacement of defective tumor-suppressor genes; inactivation of oncogenes; introduction of suicide genes; immunogenic therapy and antiangiogenesis based approaches. Preclinical studies of gene therapy for various gynecological disorders have not only shown to be feasible, but also showed promising results in diseases such as uterine leiomyomas and endometriosis. In recent years, significant improvement in gene transfer technology has led to the development of targetable vectors, which have fewer side-effects without compromising their efficacy. This review provides an update on developing gene therapy approaches to treat common gynecological diseases such as uterine leiomyoma and endometriosis. PMID:19446586

  10. Gene tree of the HoxA11 genes in vertebrates illustrating several

    E-print Network

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

  11. GeneSeqer@PlantGDB: gene structure prediction in plant genomes

    E-print Network

    Brendel, Volker

    GeneSeqer@PlantGDB: gene structure prediction in plant genomes Shannon D. Schlueter1 , Qunfeng Dong, 2003 ABSTRACT The GeneSeqer@PlantGDB Web server (http:// www.plantgdb.org/cgi-bin/GeneSeqer.cgi) provides a gene structure prediction tool tailored for applica- tions to plant genomic sequences

  12. Gene targeting using a promoterless gene trap vector (``targeted trapping'') is an efficient method to

    E-print Network

    McConnell, Susan

    Gene targeting using a promoterless gene trap vector (``targeted trapping'') is an efficient method to mutate a large fraction of genes Roland H. Friedel* , Andrew Plump* , Xiaowei Lu* , Kerri Spilker-Lavigne, July 11, 2005 A powerful tool for postgenomic analysis of mammalian gene function is gene targeting

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

    E-print Network

    Zhang, Liqing

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

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

    E-print Network

    Buffalo, State University of New York

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

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

    E-print Network

    Mukhopadhyay, Asish

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

  16. Evolution of the Glutamine Synthetase Gene, One of the Oldest Existing and Functioning Genes

    Microsoft Academic Search

    Y. Kumada; D. R. Benson; D. Hillemann; T. J. Hosted; D. A. Rochefort; C. J. Thompson; W. Wohlleben; Y. Tateno

    1993-01-01

    We performed molecular phylogenetic analyses of glutamine synthetase (GS) genes in order to investigate their evolutionary history. The analyses were done on 30 DNA sequences of the GS gene which included both prokaryotes and eukaryotes. Two types of GS genes are known at present: the GSI gene found so far only in prokaryotes and the GSII gene found in both

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

    NASA Astrophysics Data System (ADS)

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

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

  18. Improved Algorithms for Finding Gene Teams and Constructing Gene Team Trees

    Microsoft Academic Search

    Biing-Feng Wang; Chien-Hsin Lin

    2011-01-01

    A gene team is a set of genes that appear in two or more species, possibly in a different order yet with the distance between adjacent genes in the team for each chromosome always no more than a certain threshold ? . A gene team tree is a succinct way to represent all gene teams for every possible value of

  19. Identifying Drug Active Pathways from Gene Networks Estimated by Gene Expression Data

    Microsoft Academic Search

    Yoshinori Tamada; Seiya Imoto; Kousuke Tashiro; Satoru Kuhara; Satoru Miyano

    2005-01-01

    We present a computational method for identifying genes and their regulatory pathways in?u- enced by a drug, using microarray gene expression data collected by single gene disruptions and drug responses. The automatic identiflcation of such genes and pathways in organisms' cells is an important problem for pharmacogenomics and the tailor-made medication. Our method estimates regulatory relationships between genes as a

  20. GOToolBox: functional analysis of gene datasets based on Gene Ontology

    Microsoft Academic Search

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

    2004-01-01

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

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

    E-print Network

    Obradovic, Zoran

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

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

    E-print Network

    Obradovic, Zoran

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

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

    E-print Network

    Morris, Quaid

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

  4. [Developments in gene delivery vectors for ocular gene therapy].

    PubMed

    Khabou, Hanen; Dalkara, Deniz

    2015-05-01

    Gene therapy is quickly becoming a reality applicable in the clinic for inherited retinal diseases. Its remarkable success in safety and efficacy, in clinical trials for Leber's congenital amaurosis (LCA) type II generated significant interest and opened up possibilities for a new era of retinal gene therapies. Success in these clinical trials was mainly due to the favorable characteristics of the retina as a target organ. The eye offers several advantages as it is readily accessible and has some degree of immune privilege making it suitable for application of viral vectors. The viral vectors most frequently used for retinal gene delivery are lentivirus, adenovirus and adeno-associated virus (AAV). Here we will discuss the use of these viral vectors in retinal gene delivery with a strong focus on favorable properties of AAV. Thanks to its small size, AAV diffuses well in the inter-neural matrix making it suitable for applications in neural retina. Building on this initial clinical success with LCA II, we have now many opportunities to extend this proof-of-concept to other retinal diseases using AAV as a vector. This article will discuss what are some of the most imminent cellular targets for such therapies and the AAV toolkit that has been built to target these cells successfully. We will also discuss some of the challenges that we face in translating AAV-based gene therapies to the clinic. PMID:26059304

  5. Newer Gene Editing Technologies toward HIV Gene Therapy

    PubMed Central

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

    2013-01-01

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

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

    Microsoft Academic Search

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

    1991-01-01

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

  7. Activities of Human Gene Nomenclature Committee

    SciTech Connect

    NONE

    2002-07-16

    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).

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  9. Gene replacement in Penicillium roqueforti.

    PubMed

    Goarin, Anne; Silar, Philippe; Malagnac, Fabienne

    2015-05-01

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

  10. Melatonin Receptor Genes in Vertebrates

    PubMed Central

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

    2013-01-01

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

  11. Genes, Environments, and Behavior 1

    NSDL National Science Digital Library

    American Association for the Advancement of Science (; )

    2006-04-25

    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?"

  12. Gene methylation in gastric cancer.

    PubMed

    Qu, Yiping; Dang, Siwen; Hou, Peng

    2013-09-23

    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

  13. 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

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

    E-print Network

    Paris-Sud XI, Université de

    Models, algorithms, and programs for phylogeny reconciliation Keywords: phylogeny; gene duplication, loss, horizontal gene transfer; parsimony; probability; reconciliation. 1. Institut des Sciences de l on comparative genomics, especially combinatorial and probabilistic aspects of reconciliations between gene

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

    PubMed Central

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

    2006-01-01

    Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then apply them in concert to the analysis of 9556 positional candidate genes for type 2 diabetes (T2D) and the related trait obesity. We generate and analyse a list of nine primary candidate genes for T2D genes and five for obesity. Two genes, LPL and BCKDHA, are common to these two sets. We also present a set of secondary candidates for T2D (94 genes) and for obesity (116 genes) with 58 genes in common to both diseases. PMID:16757574

  16. Global gene disruption in human cells to assign genes to phenotypes

    E-print Network

    Ploegh, Hidde

    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 ...

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

    Microsoft Academic Search

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

    2001-01-01

    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

  18. Genetic evidence for a novel gene(s) involved in urogenital development on 10q26

    Microsoft Academic Search

    Tsutomu Ogata; Koji Muroya; Isoji Sasagawa; Tomoki Kosho; Keiko Wakui; Satoru Sakazume; Katsumi Ito; Nobutake Matsuo; Hirofumi Ohashi; Toshiro Nagai

    2000-01-01

    Genetic evidence for a novel gene(s) involved in urogenital development on 10q26.BackgroundAlthough the frequent association between distal 10q monosomy and urogenital anomalies suggests the presence of a gene(s) for urogenital development on distal 10q, molecular deletion mapping has not been performed for the putative gene(s). In this study, we examined genotype-phenotype correlations in patients with distal 10q monosomy.MethodsThis study consisted

  19. Metagenomics and novel gene discovery

    PubMed Central

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

    2014-01-01

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

  20. [Virulence gene of H. pylori].

    PubMed

    Sugiyama, T; Mizushima, T; Ishizuka, J; Asaka, M

    2001-02-01

    H. pylori is a well-recognized pathogen that infects up to 50% of humans in the world. H. pylori lives for decades in the hostile environment of the human stomach. H. pylori is closely associated with histologic gastritis, gastric ulceration, duodenal ulceration, gastric cancer and MALT lymphoma. These various clinical outcomes are considered by 1) different virulence, 2) host response, 3) other environmental factors, and their interactions. Since the whole genome was sequenced in 1997, the virulence genes have been investigated in molecular genetic aspects. The cag pathogenicity island (cagPAI) is a complex of virulence genes, which code approximately 30 proteins. The cagPAI acquired by horizontal transfer and is coding for type 4 secretion machinery system. Via this system, many virulence gene products or other interactive proteins are transferred into the host cells. PMID:11218390

  1. Composite nanoparticles for gene delivery.

    PubMed

    Wang, Yuhua; Huang, Leaf

    2014-01-01

    Nanoparticle-mediated gene and siRNA delivery has been an appealing area to gene therapists when they attempt to treat the diseases by manipulating the genetic information in the target cells. However, the advances in materials science could not keep up with the demand for multifunctional nanomaterials to achieve desired delivery efficiency. Researchers have thus taken an alternative approach to incorporate various materials into single composite nanoparticle using different fabrication methods. This approach allows nanoparticles to possess defined nanostructures as well as multiple functionalities to overcome the critical extracellular and intracellular barriers to successful gene delivery. This chapter will highlight the advances of fabrication methods that have the most potential to translate nanoparticles from bench to bedside. Furthermore, a major class of composite nanoparticle-lipid-based composite nanoparticles will be classified based on the components and reviewed in details. PMID:25409605

  2. Gene Expression Studies in Mosquitoes

    PubMed Central

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

    2009-01-01

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

  3. Intervention in gene regulatory networks

    E-print Network

    Choudhary, Ashish

    2006-10-30

    /3,1/3,1/3]. . . . . . . . . . . . . . . . . . . . . . 52 IX Performance of control with pi0=[1/3,1/3,1/3], M = 2. . . . . . . . . 53 X Cluster centers as attractors for the WNT5A network. The good attractors are the ones with the profile of WNT5A gene downreg- ulated. PIRIN is the most significant bit...(MSB) and WNT5A is the least significant bit(LSB) . . . . . . . . . . . . . . . . . . . . . . 54 x LIST OF FIGURES FIGURE Page 1 3 gene BN with P1 = {x1,x2,x3},P2 = {x1,x3} and P3 = {x1} . . . . 4 2 3 Boolean Networks (N1,N2 and N3) over 3 genes...

  4. Gene Therapy in Corneal Transplantation

    PubMed Central

    Qazi, Yureeda; Hamrah, Pedram

    2014-01-01

    Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection. PMID:24138037

  5. Accurate and superaccurate gene mapping.

    PubMed Central

    Lange, K; Kunkel, L; Aldridge, J; Latt, S A

    1985-01-01

    Highly accurate gene mapping techniques need to be developed to clone disease genes with unknown defective products. The classical pedigree method and methods based on cytologically observable chromosome aberrations share definite limits in resolution. We quantify the limits in resolution for the pedigree method. We also discuss a technique for gene localization that exploits the possible presence of minute depletions overlapping the disease locus. One can search for such submicroscopic deletions by aiming random probes at them. We show quantitatively that relatively few probes may suffice to hit a target deletion. Choosing which probes to aim should be guided by pedigree studies and by close examination of relevant cytologically observable translocations and deletions. PMID:2931976

  6. Genome-wide analysis of homeobox genes from Mesobuthus martensii reveals Hox gene duplication in scorpions.

    PubMed

    Di, Zhiyong; Yu, Yao; Wu, Yingliang; Hao, Pei; He, Yawen; Zhao, Huabin; Li, Yixue; Zhao, Guoping; Li, Xuan; Li, Wenxin; Cao, Zhijian

    2015-06-01

    Homeobox genes belong to a large gene group, which encodes the famous DNA-binding homeodomain that plays a key role in development and cellular differentiation during embryogenesis in animals. Here, one hundred forty-nine homeobox genes were identified from the Asian scorpion, Mesobuthus martensii (Chelicerata: Arachnida: Scorpiones: Buthidae) based on our newly assembled genome sequence with approximately 248 × coverage. The identified homeobox genes were categorized into eight classes including 82 families: 67 ANTP class genes, 33 PRD genes, 11 LIM genes, five POU genes, six SINE genes, 14 TALE genes, five CUT genes, two ZF genes and six unclassified genes. Transcriptome data confirmed that more than half of the genes were expressed in adults. The homeobox gene diversity of the eight classes is similar to the previously analyzed Mandibulata arthropods. Interestingly, it is hypothesized that the scorpion M. martensii may have two Hox clusters. The first complete genome-wide analysis of homeobox genes in Chelicerata not only reveals the repertoire of scorpion, arachnid and chelicerate homeobox genes, but also shows some insights into the evolution of arthropod homeobox genes. PMID:25910680

  7. THE JOURNAL OF GENE MEDICINE RESEARCH ARTICLE J Gene Med 2008; 10: 583592.

    E-print Network

    Bristol, University of

    -transduction with the two types of viral vectors provided doxycycline- regulated transgene expression in a neuron gene transfer; tetracycline-regulated gene expression; CNS; lentiviral vectors; doxycycline; cell

  8. Leukemogenesis: More Than Mutant Genes

    PubMed Central

    Chen, Jianjun; Odenike, Olatoyosi; Rowley, Janet D.

    2010-01-01

    Acute leukemias are characterized by recurring chromosomal aberrations and gene mutations which are critical to disease pathogenesis. It is now evident that epigenetic modifications including DNA methylation and histone modifications contribute significantly to the leukemogenic phenotype. An additional layer of epigenetic complexity is the pathogenetic role of microRNAs in leukemias, and their key role in the transcriptional regulation of tumor suppressor genes and oncogenes. The genetic heterogeneity of acute leukemias poses therapeutic challenges, but pharmacologic agents that target components of the epigenetic machinery hold promise as a part of the therapeutic arsenal for this group of diseases. PMID:20029422

  9. JavaGenes Molecular Evolution

    NASA Technical Reports Server (NTRS)

    Lohn, Jason; Smith, David; Frank, Jeremy; Globus, Al; Crawford, James

    2007-01-01

    JavaGenes is a general-purpose, evolutionary software system written in Java. It implements several versions of a genetic algorithm, simulated annealing, stochastic hill climbing, and other search techniques. This software has been used to evolve molecules, atomic force field parameters, digital circuits, Earth Observing Satellite schedules, and antennas. This version differs from version 0.7.28 in that it includes the molecule evolution code and other improvements. Except for the antenna code, JaveGenes is available for NASA Open Source distribution.

  10. UConn Behavioral Gene Bank The UConn Behavioral Gene Bank

    E-print Network

    Oliver, Douglas L.

    , obsessive-compulsive disorder, panic disorder, and addiction. Many mental illnesses run in families to establish a Gene Bank to support research to find causes of illnesses or behavioral disorders. Participation illness? Mental illnesses include disorders such as schizophrenia, bipolar disorder, depression, anxiety

  11. The frustrated gene: origins of eukaryotic gene expression

    PubMed Central

    Madhani, Hiten D.

    2014-01-01

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

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

    PubMed

    Madhani, Hiten D

    2013-11-01

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

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

    E-print Network

    Purugganan, Michael D.

    2000-01-01

    A. sandwicense APETALA1 (ASAP1) and A. sandwicense APETALA3/TM6 (ASAP3/TM6) in 17 species instability is We have isolated the floral regulatory genes A. sandwi- cense APETALA1 (ASAP1) and A. sandwicense Abbreviations: ASAP1, A. sandwicense APETALA1; ASAP3/TM6, APETALA3/TM6 (ASAP3/TM6) from members

  14. GenePRIMP: Improving Microbial Gene Prediction Quality

    SciTech Connect

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

    2009-05-29

    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

  15. The P450 gene superfamily: recommended nomenclature.

    PubMed

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

    1987-02-01

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

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

    PubMed

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

    2013-08-10

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

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

    PubMed Central

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

    2012-01-01

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

  18. Gene family matters: expanding the HGNC resource.

    PubMed

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

    2012-01-01

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

  19. Tuning noise in gene expression

    PubMed Central

    Tyagi, Sanjay

    2015-01-01

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

  20. Seed Targeted Gene Confinement Strategies

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. Orthopedic Gene Therapy in 2008

    Microsoft Academic Search

    Christopher H Evans; Steven C Ghivizzani; Paul D Robbins

    2009-01-01

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

  2. Patching genes to fight disease

    SciTech Connect

    Holzman, D.

    1990-09-03

    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.

  3. CNS Genes Implicated in Relapse

    Microsoft Academic Search

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

    2008-01-01

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

  4. Genes, Environment, and Human Behavior.

    ERIC Educational Resources Information Center

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

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

  5. Gene transfer in intact animals

    NASA Astrophysics Data System (ADS)

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

    1980-04-01

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

  6. Circadian gene variants in cancer

    PubMed Central

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

    2014-01-01

    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

  7. Genes and Syndromic Hearing Loss.

    ERIC Educational Resources Information Center

    Keats, Bronya J. B.

    2002-01-01

    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…

  8. Sperm-mediated gene transfer

    Microsoft Academic Search

    Anthony W. S. Chan; C. Marc Luetjens; Gerald P. Schatten

    2000-01-01

    Since 1989, a new method for the production of transgenic animals has been available, namely sperm- mediated gene transfer (SMGT), based on the intrinsic ability of sperm cells to bind and internalise exogenous DNA molecules and to transfer them into the oocyte at fertilisation. We first described the SMGT procedure in a small animal model, with high efficiency reported in

  9. Reservoirs of Antibiotic Resistance Genes

    Microsoft Academic Search

    Abigail Salyers; Nadja B. Shoemaker

    2006-01-01

    A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating

  10. Targetability of Human Disease Genes

    Microsoft Academic Search

    Meena K. Sakharkar; Kishore R. Sakharkar

    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.

  11. Third Edition, Gene Fusion System

    E-print Network

    Lai, Zhi-Chun

    Cleavage ............................. 19 Detection of GST Fusion Proteins .... 20 17. Measurement of GSTThird Edition, Revision 2 18-1123-20 GST Gene Fusion System #12;PROTEIN DATA BANK ADVISORY NOTICE. Screening pGEX Vectors with PCR ..... 10 Purification of GST Fusion Proteins.. 11 8. Preparation

  12. Polymorphism in regulatory gene sequences

    PubMed Central

    Mitchison, N A

    2001-01-01

    The extensive polymorphism revealed in non-coding gene-regulatory sequences, particularly in the immune system, suggests that this type of genetic variation is functionally and evolutionarily far more important than has been suspected, and provides a lead to new therapeutic strategies. PMID:11178274

  13. GSDM family genes meet autophagy.

    PubMed

    Tamura, Masaru; Shiroishi, Toshihiko

    2015-07-15

    In the previous issue of Biochemical Journal, Shi et al. [(2015) 468, 325-336] report that Gasdermin (Gsdm) family proteins regulate autophagy activity, which is counter-balanced by the opposite functions of well-conserved N- and C-terminal domains of the proteins. The Gsdm family was originally identified as the causative gene of dominant skin mutations exhibiting alopecia. Each member of the Gsdm gene family shows characteristic expression patterns in the epithelium, which is tissue and differentiation stage-specific. Previous phenotype analyses of mutant mice, biochemical analyses of proteins and genome-wide association studies showed that the Gsdm gene family might be involved in epithelial cell development, apoptosis, inflammation, carcinogenesis and immune-related diseases. To date, however, their molecular function(s) remain unclear. Shi et al. found that mutations in the C-terminal domain of Gsdma3, a member of the Gsdm family, induce autophagy. Further studies revealed that the wild-type N-terminal domain has pro-autophagic activity and that the C-terminal domain conversely inhibits this N-terminal function. These opposite functions of the two domains were also observed in other Gsdm family members. Thus, their study provides a new insight into the function of Gsdm genes in epithelial cell lineage, causality of cancers and immune-related diseases including childhood-onset asthma. PMID:26171832

  14. Genes for reading and spelling

    Microsoft Academic Search

    Timothy C. Bates

    2006-01-01

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

  15. Molecular Genetics: Proteins and Genes

    NSDL National Science Digital Library

    Susan Koba with Anne Tweed

    2009-05-22

    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

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

    Microsoft Academic Search

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

    1993-01-01

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

  17. ENHANCING DEPLOYMENT OF GENES FOR BLAST RESISTANCE: OPPORTUNITIES FROM CLONING A RESISTANCE GENE/AVIRULENCE GENE PAIR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pi-ta-mediated resistance in rice controls strains of the rice blast fungus that express avirulent alleles of AVR-Pita in a gene-for-gene manner. Map-based cloning of AVR-Pita identified a gene predicted to encode a neutral zinc metalloprotease. We also cloned Pi-ta, a centromere-linked resistance...

  18. 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- ...

  19. 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, ...

  20. Horizontal gene transfer in human pathogens

    E-print Network

    Juhas, Mario

    2013-07-18

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

  1. Genes, Memes and Demes JAMES R. GRIESEMER

    E-print Network

    Genes, Memes and Demes JAMES R. GRIESEMER Departmentof Philosophy University of California Davis and culture, e.g., that genes are material but "memes" are not, that biological inheritance is Mendelian

  2. Gene Expression in the Stallion Testes 

    E-print Network

    Laughlin, Andy M.

    2011-08-08

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

  3. Clustering analysis for gene expression data

    NASA Astrophysics Data System (ADS)

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

    1999-05-01

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

  4. Energy transduction anchors genes in organelles

    E-print Network

    Allen, John F.

    and heredity, and furthermore, redox chemistry is intrinsically mutagenic. Thus the small, functional genomes is regulated by the function of their gene products. For safe and efficient energy transduction, genes in orga

  5. Impulse Control: Temporal Dynamics in Gene Transcription

    E-print Network

    Yosef, Nir

    Regulatory circuits controlling gene expression constantly rewire to adapt to environmental stimuli, differentiation cues, and disease. We review our current understanding of the temporal dynamics of gene expression in ...

  6. Towards integrative gene functional similarity measurement

    PubMed Central

    2014-01-01

    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

  7. The Evolution of Gene Regulatory Interactions

    NSDL National Science Digital Library

    Gregory Wray (Duke University; Department of Biology)

    2010-01-04

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

  8. Interactive Fly: Early Zygotic Gene Expression Images

    NSDL National Science Digital Library

    PhD Thomas B Brody (NIH Laboratory of Neurochemistry)

    2006-12-12

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

  9. Information Retrieval meets Gene Analysis Hagit Shatkay

    E-print Network

    Shatkay, Hagit

    relationships among genes on a genome-wide scale. Experiments applied to documents discussing yeast genes, such as infection or tumor development, while encouraging desirable ones, such as normal growth and development

  10. INVITED REVIEW Speciation genes in plants

    E-print Network

    Rieseberg, Loren

    ), 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 incompatibility, hybrid necrosis, hybrid sterility, hybrid inviability, hybrid breakdown, cytoplasmic male

  11. Gene therapy for obesity: progress and prospects.

    PubMed

    Gao, Mingming; Liu, Dexi

    2014-06-01

    Advances in understanding the molecular basis of obesity and obesity-associated diseases have made gene therapy a vital approach in coping with this world-wide epidemic. Gene therapy for obesity aims to increase or decrease gene product in favor of lipolysis and energy expenditure, leading toward fat reduction and loss of body weight. It involves successful delivery and expression of therapeutic genes in appropriate cells. The ultimate goal of gene therapy is to restore and maintain energy homeostasis. Here we summarize progress made in recent years in identifying genes responsible for obesity and present examples where the gene therapy approach has been applied to treating or preventing obesity. Discussion on advantages and limitations of gene therapy strategies employed is provided. The intent of this review is to inspire further studies toward the development of new strategies for successful treatment of obesity and obesity-associated diseases. PMID:24979252

  12. Genes and Disease: Prader-Willi Syndrome

    MedlinePLUS

    ... Medicine, National Institutes of Health. National Center for Biotechnology Information (US). Genes and Disease [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show ...

  13. Vascular gene expression: a hypothesis

    PubMed Central

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

    2013-01-01

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

  14. Function of the DISC1 Gene

    NSDL National Science Digital Library

    2009-04-14

    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.

  15. Plant nitrogen regulatory P-PII genes

    DOEpatents

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

    2001-01-01

    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

  16. Promoter proximal pausing on genes in metazoans

    Microsoft Academic Search

    David S. Gilmour

    2009-01-01

    The past two decades of research into transcriptional control of protein-encoding genes in eukaryotes have focused on regulatory\\u000a mechanisms that act by controlling the recruitment of Pol II to a gene’s promoter. Recent genome-wide analyses of the distribution\\u000a of Pol II indicates that Pol II is concentrated in the promoter regions of thousands of genes in human and Drosophila cells.

  17. VERTEBRATE PHYLOGENOMICS: RECONCILED TREES AND GENE DUPLICATIONS

    E-print Network

    Page, Roderic

    VERTEBRATE PHYLOGENOMICS: RECONCILED TREES AND GENE DUPLICATIONS R.D.M. PAGE, J.A. COTTON Division-mail: r.page@bio.gla.ac.uk Ancient gene duplication events have left many traces in vertebrate genomes of vertebrates largely in agreement with other data. We formulate the problem of locating episodes of gene

  18. Prokaryotic Evolution in Light of Gene Transfer

    Microsoft Academic Search

    J. Peter Gogarten; W. Ford Doolittle; Jeffrey G. Lawrence

    2002-01-01

    Accumulating prokaryotic gene and genome sequences reveal that the exchange of genetic information through both homology-dependent recombination and horizontal (lateral) gene transfer (HGT) is far more important, in quantity and quality, than hitherto imagined. The traditional view, that prokaryotic evolution can be understood primarily in terms of clonal divergence and periodic selection, must be augmented to embrace gene exchange as

  19. Human gene therapy and imaging: cardiology

    Microsoft Academic Search

    Joseph C. Wu; Seppo Yla-Herttuala

    2005-01-01

    This review discusses the basics of cardiovascular gene therapy, the results of recent human clinical trials, and the rapid progress in imaging techniques in cardiology. Improved understanding of the molecular and genetic basis of coronary heart disease has made gene therapy a potential new alternative for the treatment of cardiovascular diseases. Experimental studies have established the proof-of-principle that gene transfer

  20. Aeromonas hydrophila Lateral Flagellar Gene Transcriptional Hierarchy

    PubMed Central

    Wilhelms, Markus; Gonzalez, Victor; Merino, Susana

    2013-01-01

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

  1. Gene Expression Profiling in Developing Human Hippocampus

    E-print Network

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

  2. TAGGING OF DISEASE RESISTANCE GENES IN SUGARBEET

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The characterization of genes that confer resistance to diseases important to sugarbeet production has been hampered by a lack of markers associated with these genes. In ongoing collaborative research, we have begun generating molecular genetic markers linked to various disease resistance genes for...

  3. Frequent Alternative Splicing of Human Genes

    Microsoft Academic Search

    Andrey A. Mironov; James Wildon Fickett; Mikhail S. Gelfand

    1999-01-01

    Alternative splicing can produce variant proteins and expression patterns as different as the products of different genes, yet the prevalence of alternative splicing has not been quantified. Here the spliced alignment algorithm was used to make a first inventory of exon-intron structures of known human genes using EST contigs from the TIGR Human Gene Index. The results on any one

  4. Genes: Philosophical analyses put to the test

    Microsoft Academic Search

    Karola Stotz; Paul Griffiths

    2004-01-01

    This paper describes one complete and one ongoing empirical study in which philosophical analyses of the concept of the gene were operationalized and tested against questionnaire data obtained from working biologists to determine whether and when biologists conceive genes in the ways suggested. These studies throw light on how different gene concepts contribute to biological research. Their aim is not

  5. Inductive Logic Programming for Gene Regulation Prediction

    Microsoft Academic Search

    Sebastian Fröhler; Stefan Kramer

    2006-01-01

    One of the central goals in computational and systems biology is to understand the mechanisms of gene transcriptional regulation on a system-wide level. The eorts are often based on high-throughput genomic data of model organisms such as S. cerevisiae. The goal of this work is to learn a model of gene regulation predicting under which conditions genes are up- or

  6. Gene Family Evolution across 12 Drosophila Genomes

    Microsoft Academic Search

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

    2007-01-01

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

  7. Chapter 12 Gene Genealogies Noah A. Rosenberg

    E-print Network

    Rosenberg, Noah

    Chapter 12 ­ Gene Genealogies Noah A. Rosenberg Program in Molecular and Computational Biology can be viewed as the result of mutations on a scaffold of genetic relationships ­ a gene genealogy, migration, species divergence, and changes in population size, an understanding of gene genealogies

  8. INVESTIGATION Gene Genealogies Within a Fixed Pedigree,

    E-print Network

    INVESTIGATION Gene Genealogies Within a Fixed Pedigree, and the Robustness of Kingman's Coalescent, not as a random quantity. Gene genealogical models should describe the outcome of the percolation of genetic provide a surprisingly accurate description of gene genealogies on a fixed pedigree. We study

  9. Gene prioritization through genomic data fusion

    Microsoft Academic Search

    Diether Lambrechts; Sunit Maity; Peter Van Loo; Bert Coessens; Frederik De Smet; Leon-Charles Tranchevent; Bart De Moor; Peter Marynen; Bassem Hassan; Peter Carmeliet; Yves Moreau; Stein Aerts

    2006-01-01

    The identification of genes involved in health and disease remains a challenge. We describe a bioinformatics approach, together with a freely accessible, interactive and flexible software termed Endeavour, to prioritize candidate genes underlying biological processes or diseases, based on their similarity to known genes involved in these phenomena. Unlike previous approaches, ours generates distinct prioritizations for multiple heterogeneous data sources,

  10. Human Lineage-Specific Gene Inactivation

    E-print Network

    Zhang, Jianzhi

    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

  11. Human Lineage-specific Gene Inactivation

    E-print Network

    Zhang, Jianzhi

    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

  12. Problem-Solving Test: Targeted Gene Disruption

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2008-01-01

    Mutational inactivation of a specific gene is the most powerful technique to analyze the biological function of the gene. This approach has been used for a long time in viruses, bacteria, yeast, and fruit fly, but looked quite hopeless in more complex organisms. Targeted inactivation of specific genes (also known as knock-out mutation) in mice is…

  13. Repetitive sequence environment distinguishes housekeeping genes

    PubMed Central

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

    2007-01-01

    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

  14. The evolutionary origin of orphan genes

    Microsoft Academic Search

    Tomislav Domazet-Lošo; Diethard Tautz

    2011-01-01

    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

  15. ADENOVIRAL GENE THERAPY FOR OVARIAN CANCER

    E-print Network

    Hemminki, Akseli

    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

  16. Predicting Housekeeping Genes Based on Fourier Analysis

    Microsoft Academic Search

    Bo Dong; Peng Zhang; Xiaowei Chen; Li Liu; Yunfei Wang; Shunmin He; Runsheng Chen

    2011-01-01

    Housekeeping genes (HKGs) generally have fundamental functions in basic biochemical processes in organisms, and usually have relatively steady expression levels across various tissues. They play an important role in the normalization of microarray technology. Using Fourier analysis we transformed gene expression time-series from a Hela cell cycle gene expression dataset into Fourier spectra, and designed an effective computational method for

  17. Sparse Statistical Modelling in Gene Expression Genomics

    E-print Network

    West, Mike

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

  18. Tissue classification with gene expression profiles

    Microsoft Academic Search

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

    2000-01-01

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

  19. Sparse Statistical Modelling in Gene Expression Genomics

    E-print Network

    West, Mike

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

  20. Current approaches to gene regulatory network modelling

    Microsoft Academic Search

    Thomas Schlitt; Alvis Brazma

    2007-01-01

    Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more

  1. Horizontal Gene Transfer in Microbial Genome Evolution

    Microsoft Academic Search

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

    2002-01-01

    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

  2. Hox genes in digit development and evolution

    Microsoft Academic Search

    József Zákány; Denis Duboule

    1999-01-01

    Homeobox genes located in the 5' part of the HoxA and HoxD complexes are required for proliferation of skeletal progenitor cells of the vertebrate limb. Specific combinations of gene products determine the length of the upper arm (genes belonging to groups 9 and 10), the lower arm (groups 10, 11 and 12) and the digits (groups 11, 12 and 13).

  3. Discovery of Tumor Suppressor Gene Function.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.

    1995-01-01

    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)

  4. Beyond the Gene Evelyn Fox Keller1

    E-print Network

    Harel, David

    is a response to the increasing difficulty biologists find in agreeing upon a definition of the gene, and indeed an alternative to both the concept and the word gene--an alternative that, like the gene, is intended to capture of the classical genotype/phenotype paradigm, yet it appears to be faithful to the findings of contemporary biology

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

    Microsoft Academic Search

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

    1990-01-01

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

  6. Gene identication in bacterial and organellar genomes using GeneScan

    E-print Network

    Ramaswamy, Ram

    Gene identi®cation in bacterial and organellar genomes using GeneScan Ramaswamy Ramakrishnaa, 110 067, India Received 23 June 1998; accepted 13 November 1998 Abstract The performance of the GeneScan algorithm for gene identi®cation has been improved by incorporation of a directed iterative scanning

  7. gene encoding enhanced green fluorescent protein to the repressor gene, and quantify

    E-print Network

    Weeks, Eric R.

    gene encoding enhanced green fluorescent protein to the repressor gene, and quantify of gene expression in the feedback network, compared with the control networks. They also show concentrations of anhydrotetra- cycline--achemicalinhibitorofTetR. In past theoretical studies of gene

  8. Mining Coherent Gene Clusters from Gene-Sample-Time Microarray Data

    E-print Network

    Buffalo, State University of New York

    Mining Coherent Gene Clusters from Gene-Sample-Time Microarray Data Daxin Jiang Jian Pei Murali research and biomedical applications. In this paper, we explore a novel type of gene- sample-time microarray data sets, which records the expres- sion levels of various genes under a set of samples during

  9. Gene loss rate: a probabilistic measure for the conservation of eukaryotic genes

    E-print Network

    Borenstein, Elhanan

    Gene loss rate: a probabilistic measure for the conservation of eukaryotic genes Elhanan Borenstein; Accepted October 2, 2006 ABSTRACT The rate of conservation of a gene in evolution is believed for genes and have shown that they are correlated with several biological characteristics of functional

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

    E-print Network

    Zhang, Jianzhi

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

  11. Estimation of gene induction enables a relevance-based ranking of gene sets

    E-print Network

    Timmer, Jens

    Estimation of gene induction enables a relevance-based ranking of gene sets Kilian Bartholom by microarray experiments, the analysis of sets of genes with a common biological functionality has been shown to be advantageous compared to single gene analyses. Some statistical methods have been proposed to analyse

  12. From Gene to Organismal Phylogeny: Reconciled Trees and the Gene Tree/Species Tree Problem

    E-print Network

    Page, Roderic

    From Gene to Organismal Phylogeny: Reconciled Trees and the Gene Tree/Species Tree Problem Roderic The processes of gene duplication, loss, and lineage sorting can result in incongruence between the phylog- enies of genes and those of species. This incongruence complicates the task of inferring the latter from

  13. Estimation of Gene Induction Enables a Relevance-Based Ranking of Gene Sets

    E-print Network

    Timmer, Jens

    Estimation of Gene Induction Enables a Relevance-Based Ranking of Gene Sets KILIAN BARTHOLOME´,1 produced by microarray ex- periments, the analysis of sets of genes with a common biological functionality has been shown to be advantageous compared to single gene analyses. Some statistical methods have been

  14. Caenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression

    E-print Network

    van Oudenaarden, Alexander

    of the selec- tor gene mec-3, which is needed, together with unc-86, for the differentiation of the TRNsCaenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression Irini- derstood. For example, mutations in the gene encoding the transcription factor ALR-1 in Caenorhabditis

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

    Microsoft Academic Search

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

    2002-01-01

    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 ,

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

    Microsoft Academic Search

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

    2010-01-01

    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,

  17. SRF-dependent gene expression in isolated cardiomyocytes: Regulation of genes involved in cardiac hypertrophy

    Microsoft Academic Search

    Timothy J. Nelson; Robert Balza; Qi Xiao; Ravi P. Misra

    2005-01-01

    Serum response factor (SRF) is a transcription factor required for the regulation of genes important for cardiac structure and function. Notably, the “fetal gene expression profile” that is characteristic of cardiac hypertrophy consists of genes known to be regulated by SRF. Transgenic animal studies suggest that cardiac-specific overexpression of SRF induces this pattern of hypertrophic genes and subsequently causes the

  18. Rabbit calcium-sensing receptor (CASR) gene: chromosome location and evidence for related genes

    Microsoft Academic Search

    P. A. Martin-DeLeon; L. Canaff; R. Korstanje; V. Bhide; M. Selkirk; G. N. Hendy

    1999-01-01

    Diverse cellular functions are regulated by the calcium-sensing receptor, encoded by the CASR gene, which plays an important role in calcium homeostasis. Here we provide the sequence for exon VII of the rabbit CASR gene and show that it is 91% identical to the human gene at the nucleotide level, and 95% identical at the amino acid level. The gene

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

    Microsoft Academic Search

    Sukjoon Yoon; Young Yang; Jiwon Choi; Jeeweon Seong

    2006-01-01

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

  20. Log-linear model-based multifactor dimensionality reduction method to detect gene-gene interactions

    Microsoft Academic Search

    Seung Yeoun Lee; Yujin Chung; Robert C. Elston; Youngchul Kim; Taesung Park

    2007-01-01

    Motivation: The identification and characterization of susceptibility genes that influence the risk of common and complex diseases remains a statistical and computational challenge in genetic association studies. This is partly because the effect of any single genetic variant for a common and complex disease may be dependent on other genetic variants (gene-gene interaction) and environmental factors (gene-environment interaction). To address

  1. Multiscale Bootstrap Analysis of Gene Networks 1 Multiscale Bootstrap Analysis of Gene Networks Based

    E-print Network

    Shimodaira, Hidetoshi

    Multiscale Bootstrap Analysis of Gene Networks 1 Multiscale Bootstrap Analysis of Gene Networks, Ookayama, Meguro, Tokyo 152-8552, Japan Keywords: multiscale bootstrap, AU test, graphical Gaussian model, microarray, gene network 1 Introduction The development of DNA microarray technology has enabled gene

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

    E-print Network

    Bonner, Anthony

    Neural Networks Approaches for Discovering the Learnable Correlation between Gene Function and Gene novel clustering and Neural Network (NN) approaches for predicting mouse gene functions from gene. Our results show that neural networks can be extremely useful in this area. We present the improved

  3. Dragon Gene Start Finder identifies approximate locations of the 5' ends of genes

    Microsoft Academic Search

    Vladimir B. Bajic; Seng Hong Seah

    2003-01-01

    Recognition of gene starts is a difficult and yet unsolved problem. We present a program, Dragon Gene Start Finder (DGSF), which assesses the gene start in mammalian genomes and predicts a region which should overlap with the first exon of the gene or be in its proximity. The program has been rigorously tested on human chromosomes 4, 21 and 22,

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

    PubMed

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

    2015-01-01

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

  5. Diametric gene-dosage effects as windows into neurogenetic architecture

    E-print Network

    Crespi, Bernard J.

    Diametric gene-dosage effects as windows into neurogenetic architecture Bernard Crespi Gene diametric changes in gene dosage influence neurological development and function? Recent studies of transgenic and knockout mouse models, genomic copy-number variants, imprinted- gene expression alterations

  6. Hope to Live to 100? Check Your Genes

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Healthy Aging Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Healthy Aging About MedlinePlus Site Map FAQs Contact ...

  7. Gene Variation Could Spur Longer Smoking, Earlier Cancer

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Lung Cancer Smoking Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Lung Cancer Smoking About MedlinePlus Site Map FAQs ...

  8. Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

    E-print Network

    Ames, Ryan M.; Money, Daniel; Lovell, Simon C.

    2014-06-12

    The complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological ...

  9. Gene duplication and inactivation in the HPRT gene family

    Microsoft Academic Search

    Alaine C. Keebaugh; Robert T. Sullivan; James W. Thomas

    2007-01-01

    Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch–Nyhan disease. The studies described here utilized targeted comparative mapping and sequencing, in conjunction with database searches, to assemble a collection of 53 HPRT1 homologs from 28 vertebrates. Phylogenetic analysis of these homologs revealed that the HPRT gene family expanded as the result

  10. Gene gain and gene loss in streptococcus: is it driven by habitat?

    PubMed

    Marri, Pradeep Reddy; Hao, Weilong; Golding, G Brian

    2006-12-01

    Bacterial genomes can evolve either by gene gain, gene loss, mutating existing genes, and/or by duplication of existing genes. Recent studies have clearly demonstrated that the acquisition of new genes by lateral gene transfer (LGT) is a predominant force in bacterial evolution. To better understand the significance of LGT, we employed a comparative genomics approach to model species-specific and intraspecies gene insertions/deletions (ins/del among 12 sequenced streptococcal genomes using a maximum likelihood method. This study indicates that the rate of gene ins/del is higher on the external branches and varies dramatically for each species. We have analyzed here some of the experimentally characterized species-specific genes that have been acquired by LGT and conclude that at least a portion of these genes have a role in adaptation. PMID:16966682

  11. Role of gene-gene/gene-environment interaction in the etiology of eastern Indian ADHD probands.

    PubMed

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

    2011-03-30

    Associations between attention deficit hyperactivity disorder (ADHD) and genetic polymorphisms in the dopamine receptors, transporter and metabolizing enzymes have been reported in different ethnic groups. Gene variants may affect disease outcome by acting synergistically or antagonistically and thus their combined effect becomes an important aspect to study in the disease etiology. In the present investigation, interaction between ten functional polymorphisms in DRD4, DAT1, MAOA, COMT, and DBH genes were explored in the Indo-Caucasoid population. ADHD cases were recruited based on DSM-IV criteria. Peripheral blood samples were collected from ADHD probands (N=126), their parents (N=233) and controls (N=96) after obtaining informed written consent for participation. Genomic DNA was subjected to PCR based analysis of single nucleotide polymorphisms and variable number of tandem repeats (VNTRs). Data obtained was examined for population as well as family-based association analyses. While case-control analysis revealed higher occurrence of DAT1 intron 8 VNTR 5R allele (P=0.02) in cases, significant preferential transmission of the 7R-T (DRD4 exon3 VNTR-rs1800955) and 3R-T (MAOA-u VNTR-rs6323) haplotypes were noticed from parents to probands (P=0.02 and 0.002 respectively). Gene-gene interaction analysis revealed significant additive effect of DBH rs1108580 and DRD4 rs1800955 with significant main effects of DRD4 exon3 VNTR, DAT1 3'UTR and intron 8 VNTR, MAOA u-VNTR, rs6323, COMT rs4680, rs362204, DBH rs1611115 and rs1108580 thereby pointing towards a strong association of these markers with ADHD. Correlation between gene variants, high ADHD score and low DBH enzymatic activity was also noticed, especially in male probands. From these observations, an impact of the studied sites on the disease etiology could be speculated in this ethnic group. PMID:21216270

  12. Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.

    PubMed

    Millat, G; Chevalier, P; Restier-Miron, L; Da Costa, A; Bouvagnet, P; Kugener, B; Fayol, L; Gonzàlez Armengod, C; Oddou, B; Chanavat, V; Froidefond, E; Perraudin, R; Rousson, R; Rodriguez-Lafrasse, C

    2006-09-01

    Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes. PMID:16922724

  13. Gene–gene interactions in breast cancer susceptibility

    PubMed Central

    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

    2012-01-01

    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

  14. Gene-gene interactions in breast cancer susceptibility.

    PubMed

    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

    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

  15. GeneSeqer add PlantGDB: gene structure prediction in plant genomes

    Microsoft Academic Search

    Shannon D. Schlueter; Qunfeng Dong; Volker Brendel

    2003-01-01

    The GeneSeqer@PlantGDB Web server (http:\\/\\/ www.plantgdb.org\\/cgi-bin\\/GeneSeqer.cgi) provides a gene structure prediction tool tailored for applica- tions to plant genomic sequences. Predictions are based on spliced alignment with source-native ESTs and full-length cDNAs or non-native probes derived from putative homologous genes. The tool is illustrated with applications to refinement of current gene structure annotation and de novo annotation of draft genomic

  16. Functional Identification of a Putative ?-Galactosidase Gene in the Special lac Gene Cluster of Lactobacillus   acidophilus

    Microsoft Academic Search

    Qu Pan; Junmin Zhu; Lina Liu; Yanguang Cong; Fuquan Hu; Jinchuan Li; Xiaoping Yu

    2010-01-01

    The putative ?-galactosidase gene (lacZ) of Lactobacillus acidophilus has a very low degree of homology to the Escherichia coli ?-galactosidase gene (lacZ) and locates in a special lac gene cluster which contains two ?-galactosidase genes. No functional characteristic of the putative ?-galactosidase has been\\u000a described so far. In this study, the lacZ gene of L. acidophilus was hetero-expressed in E. coli and the recombinant

  17. Gene and genome duplications: the impact of dosage-sensitivity on the fate of nuclear genes

    Microsoft Academic Search

    Patrick P. Edger; J. Chris Pires

    2009-01-01

    Whole genome duplications (WGDs) followed by diploidization, which includes gene loss, have been an important recurrent process\\u000a in the evolution of higher eukaryotes. Gene retention is biased to specific functional gene categories during diploidization.\\u000a Dosage-sensitive genes, which include transcription factors, are significantly over-retained following WGDs. By contrast,\\u000a these same functional gene categories exhibit lower retention rates following smaller scale duplications

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

    PubMed Central

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

    2006-01-01

    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

  19. GOToolBox: functional analysis of gene datasets based on Gene Ontology

    PubMed Central

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

    2004-01-01

    We have developed methods and tools based on the Gene Ontology (GO) resource allowing the identification of statistically over- or under-represented terms in a gene dataset; the clustering of functionally related genes within a set; and the retrieval of genes sharing annotations with a query gene. GO annotations can also be constrained to a slim hierarchy or a given level of the ontology. The source codes are available upon request, and distributed under the GPL license. PMID:15575967

  20. 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.

  1. Evolutionary Dynamics of Plant R-Genes

    NSDL National Science Digital Library

    Joy Bergelson (University of Chicago; Department of Ecology and Evolution)

    2001-06-22

    Plant R-genes involved in gene-for-gene interactions with pathogens are expected to undergo coevolutionary arms races in which plant specificity and pathogen virulence continually adapt in response to each other. Lending support to this idea, the solvent-exposed amino acid residues of leucine-rich repeats, a region of R-genes involved in recognizing pathogens, often evolve at unusually fast rates. But within-species polymorphism is also common in R-genes, implying that the adaptive substitution process is not simply one of successive selective sweeps. Here we document these features in available data and discuss them in light of the evolutionary dynamics they likely reflect.

  2. Hematopoietic Stem Cell Expansion and Gene Therapy

    PubMed Central

    Watts, Korashon Lynn; Adair, Jennifer; Kiem, Hans-Peter

    2012-01-01

    Hematopoietic stem cell (HSC) gene therapy remains a highly attractive treatment option for many disorders including hematologic conditions, immunodeficiencies including HIV/AIDS, and other genetic disorders like lysosomal storage diseases, among others. In this review, we discuss the successes, side effects, and limitations of current gene therapy protocols. In addition, we describe the opportunities presented by implementing ex vivo expansion of gene-modified HSCs, as well as summarize the most promising ex vivo expansion techniques currently available. We conclude by discussing how some of the current limitations of HSC gene therapy could be overcome by combining novel HSC expansion strategies with gene therapy. PMID:21999373

  3. Gene myths in public perceptions.

    PubMed

    Svalastog, Anna Lydia

    2012-05-01

    In this article I examine myths in the gene science debate, and their use as a tool in analysis of popular perceptions and public opinion of genetic science and gene technology. In daily language myth means something untrue, though theories of myth present them as carriers of knowledge and truth. I understand myth as a narrative, a cultural construct that aims to describe the world, its origin, and its constituent elements. I compare scholars' usage of myths, considering their implications. I conclude that i) As an analytical tool the concept of myth is too loosely defined, or understood through theories which leave out context, social relations and interaction. This provides limited insight about myths and myth-making in present day society. ii) An updated understanding of myths, including location/context and interaction/process would enrich analysis. PMID:23038860

  4. Gene You: Genetics and Inheritance

    NSDL National Science Digital Library

    How do gene patterns affect our lives? Geneticists learn new things everyday about such matters and young people (and others) can bask in this fascinating knowledge via the Baylor College of Medicine's Gene You project. Funding for the project comes from the Science Education Partnership Award program at the National Institutes of Health and the Robert Wood Johnson Foundation. The content includes a wide variety of genetics and genomics based resources for educators, including complete undergraduate courses, video and slide presentations and related materials. In the Genetics/Genomics courses area, visitors can take four courses, including "Key Advances in Genetics" and "Seminal Experiments in Genetics." Moving along, the Related Video and Slide Presentations area features multimedia explorations of evolutionary theory, cloning and inherited traits. The site also includes Nature News Stories, which includes dozens of relevant news articles culled from Nature News.

  5. Gene therapy for viral hepatitis.

    PubMed

    Gonzalez-Aseguinolaza, Gloria; Crettaz, Julien; Ochoa, Laura; Otano, Itziar; Aldabe, Rafael; Paneda, Astrid

    2006-12-01

    Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models. PMID:17223736

  6. Seasonal Effects on Gene Expression

    PubMed Central

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

    2015-01-01

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

  7. Comparison of Gene Coexpression Profiles and Construction of Conserved Gene Networks to Find Functional Modules

    PubMed Central

    Okamura, Yasunobu; Obayashi, Takeshi; Kinoshita, Kengo

    2015-01-01

    Background Computational approaches toward gene annotation are a formidable challenge, now that many genome sequences have been determined. Each gene has its own function, but complicated cellular functions are achieved by sets of genes. Therefore, sets of genes with strong functional relationships must be identified. For this purpose, the similarities of gene expression patterns and gene sequences have been separately utilized, although the combined information will provide a better solution. Result & Discussion We propose a new method to find functional modules, by comparing gene coexpression profiles among species. A coexpression pattern is represented as a list of coexpressed genes with each guide gene. We compared two coexpression lists, one from a human guide gene and the other from a homologous mouse gene, and defined a measure to evaluate the similarity between the lists. Based on this coexpression similarity, we detected the highly conserved genes, and constructed human gene networks with conserved coexpression between human and mouse. Some of the tightly coupled genes (modules) showed clear functional enrichment, such as immune system and cell cycle, indicating that our method could identify functionally related genes without any prior knowledge. We also found a few functional modules without any annotations, which may be good candidates for novel functional modules. All of the comparisons are available at the http://v1.coxsimdb.info web database. PMID:26147120

  8. Mathematical Morphology applied to Spot Segmentation and Quantification of Gene

    E-print Network

    Hero, Alfred O.

    1 Mathematical Morphology applied to Spot Segmentation and Quantification of Gene Microarray Images for identification of sequence (gene/gene mutation) and determination of gene expression. A typical gene microarray determines the level of gene ex- pression (abundance) in the sample. The massive scale and variability

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

    Microsoft Academic Search

    FAMING LIANG; Texas A

    2008-01-01

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

  10. Growth factor genes as oncogenes

    Microsoft Academic Search

    Ing-Ming Chiu

    1989-01-01

    The oncogenic retroviruses can be divided into two main categories: those that induce neoplasia after a long latent period\\u000a (chronic leukemia viruses) and those that induce neoplasia relatively rapidly (acute transforming viruses). Chronic leukemia\\u000a viruses do not transform cells in tissue culture and contain only the virally encoded genes. By nucleotide sequence comparison,\\u000a it was possible to show that all

  11. The insect SNMP gene family.

    PubMed

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

    2009-07-01

    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

  12. Gene expression in diabetic nephropathy

    Microsoft Academic Search

    Daniela Hohenadel; Fokko J. van der Woude

    2004-01-01

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

  13. Regulation of Genes by Light

    Microsoft Academic Search

    Gabriele Klug; Shinji Masuda

    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

  14. Gene therapy for lung cancer

    Microsoft Academic Search

    Eric B. Haura; Eduardo Sotomayor; Scott J. Antonia

    2003-01-01

    Lung cancer continues to be the largest killer of Americans due to cancer. Although progress has been made, with advances\\u000a in chemotherapy, the majority of patients diagnosed with lung cancer ultimately succumb to the disease. A better understanding\\u000a of the molecular pathogenesis of lung cancer is demonstrating how alterations in oncogenes and tumor suppressor genes control\\u000a lung cancer initiation, growth,

  15. Gene transfer to the vasculature

    Microsoft Academic Search

    Sarah J. George; Andrew H. Baker

    2002-01-01

    Cardiovascular diseases are a major cause of fatality, disability, and economic burden in Western civilization. Although the\\u000a pharmaceutical industry has delivered a plethora of drugs for treatment of diverse cardiovascular complaints, there remain\\u000a many conditions for which pharmacological regimens are either nonexistent or largely ineffective. In contrast, remarkable\\u000a progress has been made in the field of vascular gene transfer in

  16. Targetability of human disease genes.

    PubMed

    Sakharkar, Meena K; Sakharkar, Kishore R

    2007-06-01

    The availability of complete genome sequences and the wealth of large-scale biological datasets provide an unprecedented 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 exploration of druggability, targetability and evolutionary conservation of human disease genes. These analyses could have a tremendous potential for systematic in silico drug target identification in the post-genomic era. PMID:17630928

  17. Gene therapy of multiple sclerosis

    Microsoft Academic Search

    Roberto Furlan; Chiara Maiorino; Alberto Gatta; Francesca Ruffini; Gianvito Martino

    \\u000a Multiple sclerosis (MS) constitutes a difficult challenge for the design of innovative therapies: the aetiology is unknown,\\u000a the pathogenesis only partially understood, and the whole process is multi-focal, chronic, and occurring beyond anatomical\\u000a barriers, making the delivery of potentially therapeutic molecules difficult. Gene therapy, thus, constitutes a realistic\\u000a alternative to ensure prolonged, and site-specific delivery of therapies. Recent advancements in

  18. Evolution of Antennapedia-Class Homeobox Genes

    PubMed Central

    Zhang, J.; Nei, M.

    1996-01-01

    Antennapedia (Antp)-class homeobox genes are involved in the determination of pattern formation along the anterior-posterior axis of the animal embryo. A phylogenetic analysis of Antp-class homeodomains of the nematode, Drosophila, amphioxus, mouse, and human indicates that the 13 cognate group genes of this gene family can be divided into two major groups, i.e., groups I and II. Group I genes can further be divided into subgroups A (cognate groups 1-2), B (cognate group 3), and C (cognate groups 4-8), and group II genes can be divided into subgroups D (cognate groups 9-10) and E (cognate groups 11-13), though this classification is somewhat ambiguous. Evolutionary distances among different amino acid sequences suggest that the divergence between group I and group II genes occurred ~1000 million years (MY) ago, and the five different subgroups were formed by ~600 MY ago, probably before the divergence of Pseudocoelomates (e.g., nematodes) and Coelomates (e.g., insects and chordates). Our results show that the genes that are phylogenetically close are also closely located in the chromosome, suggesting that the colinearity between the gene expression and gene arrangement was generated by successive tandem gene duplications and that the gene arrangement has been maintained by some sort of selection. PMID:8770606

  19. Integrating various resources for gene name normalization.

    PubMed

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

    2012-01-01

    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

  20. Integrating Various Resources for Gene Name Normalization

    PubMed Central

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

    2012-01-01

    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

  1. Progress in Gene Therapy for Prostate Cancer

    PubMed Central

    Ahmed, Kamran A.; Davis, Brian J.; Wilson, Torrence M.; Wiseman, Gregory A.; Federspiel, Mark J.; Morris, John C.

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies. PMID:23181221

  2. Gene therapy for sensorineural hearing loss.

    PubMed

    Chien, Wade W; Monzack, Elyssa L; McDougald, Devin S; Cunningham, Lisa L

    2015-01-01

    Gene therapy is a promising treatment modality that is being explored for several inherited disorders. Multiple human gene therapy clinical trials are currently ongoing, but few are directed at hearing loss. Hearing loss is one of the most prevalent sensory disabilities in the world, and genetics play an important role in the pathophysiology of hearing loss. Gene therapy offers the possibility of restoring hearing by overcoming the functional deficits created by the underlying genetic mutations. In addition, gene therapy could potentially be used to induce hair cell regeneration by delivering genes that are critical to hair cell differentiation into the cochlea. In this review, we examine the promises and challenges of applying gene therapy to the cochlea. We also summarize recent studies that have applied gene therapy to animal models of hearing loss. PMID:25166629

  3. Apolipoprotein gene involved in lipid metabolism

    DOEpatents

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

    2007-07-03

    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.

  4. Posttranscriptional gene silencing in nuclei

    PubMed Central

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

    2011-01-01

    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

  5. Collaborative computing for gene mapping

    SciTech Connect

    Gatewood, J.M.

    1993-12-01

    The authors are investigating mechanisms for utilizing advances in high performance computing and alignment algorithm development which will allow the analysis of newly acquired sequence data in real time and eliminate the global alignments problems associated with existing datasets. The presence of repetitive DNA sequences in the human genome complicates the process of homology comparisons. Three approaches have been used to address this problem. Two of the approaches involve elimination of the repetitive elements either by removing the repetitive element from the query or scoring words due to the repetitive elements poorly or not at all during the alignment process. The approach involves identification of the repetitive element in the query by comparison to a known repeat set prior to comparison to the large database. Any homologies returned which are contained within a previously identified repeat are ignored unless the homology exceeds set quality parameters. The homologies which extend outside the bounds of the repetitive element are reported. Using this approach the repeat is not eliminated from larger homologous units which may exist, and is returned as part of the overall homology result. The method the authors utilize in the laboratory for gene mapping is fluorescent in situ hybridization (FISH). This approach involves labelling a gene segment with a fluorescent molecule and then mixing the labeled gene segment (probe) with chromosomes.

  6. A gene mapping expert system.

    PubMed

    Galland, J; Skolnick, M H

    1990-08-01

    Expert systems are now commonly developed to solve practical problems. Nevertheless, genetics has just begun to benefit from this new technology, since genetic expert systems are extremely rare and often purely experimental. A prototype for risk calculation in pedigrees was developed at the University of Utah, using a commercial frames/rules developmental shell (Intelligence Compiler), which runs on an IBM PC. When small data sets were used, the implementation functioned well, but it could not handle larger data sets. Performance became a major issue, with two possible solutions. The first possibility would have been to port the system to a more powerful machine, and the second would have been to use several different shells or languages, each efficiently representing a specific type of knowledge. Neither of these solutions was applicable in this case. From this experience, we learned that performance, portability, and modifiability were three major requirements for genetic expert systems. To achieve these goals, we implemented the gene mapping expert system GMES: (GMES is unrelated to the gene mapping system, GMS in Lisp combined with a frame/object shell (FROBS). We were able to efficiently represent, control, and optimize a gene mapping experiment, achieving portability by building GMES on top of a C-based version of Common Lisp. Lisp combined with the FROBS expert system shell permitted a declarative representation of each of the components of the experiment, resulting in a transplant specification of the problem within a maintainable system. PMID:2394090

  7. Posttranscriptional gene silencing in nuclei.

    PubMed

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

    2011-01-01

    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

  8. Altered patterns of gene duplication and differential gene gain and loss in fungal pathogens

    PubMed Central

    Powell, Amy J; Conant, Gavin C; Brown, Douglas E; Carbone, Ignazio; Dean, Ralph A

    2008-01-01

    Background Duplication, followed by fixation or random loss of novel genes, contributes to genome evolution. Particular outcomes of duplication events are possibly associated with pathogenic life histories in fungi. To date, differential gene gain and loss have not been studied at genomic scales in fungal pathogens, despite this phenomenon's known importance in virulence in bacteria and viruses. Results To determine if patterns of gene duplication differed between pathogens and non-pathogens, we identified gene families across nine euascomycete and two basidiomycete species. Gene family size distributions were fit to power laws to compare gene duplication trends in pathogens versus non-pathogens. Fungal phytopathogens showed globally altered patterns of gene duplication, as indicated by differences in gene family size distribution. We also identified sixteen examples of gene family expansion and five instances of gene family contraction in pathogenic lineages. Expanded gene families included those predicted to be important in melanin biosynthesis, host cell wall degradation and transport functions. Contracted families included those encoding genes involved in toxin production, genes with oxidoreductase activity, as well as subunits of the vacuolar ATPase complex. Surveys of the functional distribution of gene duplicates indicated that pathogens show enrichment for gene duplicates associated with receptor and hydrolase activities, while euascomycete pathogens appeared to have not only these differences, but also significantly more duplicates associated with regulatory and carbohydrate binding functions. Conclusion Differences in the overall levels of gene duplication in phytopathogenic species versus non-pathogenic relatives implicate gene inventory flux as an important virulence-associated process in fungi. We hypothesize that the observed patterns of gene duplicate enrichment, gene family expansion and contraction reflect adaptation within pathogenic life histories. These adaptations were likely shaped by ancient, as well as contemporary, intimate associations with monocot hosts. PMID:18373860

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

    PubMed

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

    2013-01-01

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

  10. Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks

    PubMed Central

    Priedigkeit, Nolan; Wolfe, Nicholas; Clark, Nathan L.

    2015-01-01

    Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC), is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting “disease map” network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks. PMID:25679399

  11. A portal to gene-centered information from different sources http://www.ncbi.nlm.nih.gov/gene/

    E-print Network

    Levin, Judith G.

    NCBI Gene A portal to gene-centered information from different sources http://www.ncbi.nlm.nih.gov/gene of Health · Department of Health and Human Services NCBI Handout Series | Gene | Last Update December 18, 2013 Contact: info@ncbi.nlm.nih.gov NCBI Gene A portal to gene-centered information from different

  12. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

    Microsoft Academic Search

    Monika Jung; Azizbek Ramankulov; Jan Roigas; Manfred Johannsen; Martin Ringsdorf; Glen Kristiansen; Klaus Jung

    2007-01-01

    BACKGROUND: Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in

  13. Remodelling of a homeobox gene cluster by multiple independent gene reunions in Drosophila.

    PubMed

    Chan, Carolus; Jayasekera, Suvini; Kao, Bryant; Páramo, Moisés; von Grotthuss, Marcin; Ranz, José M

    2015-01-01

    Genome clustering of homeobox genes is often thought to reflect arrangements of tandem gene duplicates maintained by advantageous coordinated gene regulation. Here we analyse the chromosomal organization of the NK homeobox genes, presumed to be part of a single cluster in the Bilaterian ancestor, across 20 arthropods. We find that the ProtoNK cluster was extensively fragmented in some lineages, showing that NK clustering in Drosophila species does not reflect selectively maintained gene arrangements. More importantly, the arrangement of NK and neighbouring genes across the phylogeny supports that, in two instances within the Drosophila genus, some cluster remnants became reunited via large-scale chromosomal rearrangements. Simulated scenarios of chromosome evolution indicate that these reunion events are unlikely unless the genome neighbourhoods harbouring the participating genes tend to colocalize in the nucleus. Our results underscore how mechanisms other than tandem gene duplication can result in paralogous gene clustering during genome evolution. PMID:25739651

  14. Prediction of regulatory gene pairs using dynamic time warping and gene ontology.

    PubMed

    Yang, Andy C; Hsu, Hui-Huang; Lu, Ming-Da; Tseng, Vincent S; Shih, Timothy K

    2014-01-01

    Selecting informative genes is the most important task for data analysis on microarray gene expression data. In this work, we aim at identifying regulatory gene pairs from microarray gene expression data. However, microarray data often contain multiple missing expression values. Missing value imputation is thus needed before further processing for regulatory gene pairs becomes possible. We develop a novel approach to first impute missing values in microarray time series data by combining k-Nearest Neighbour (KNN), Dynamic Time Warping (DTW) and Gene Ontology (GO). After missing values are imputed, we then perform gene regulation prediction based on our proposed DTW-GO distance measurement of gene pairs. Experimental results show that our approach is more accurate when compared with existing missing value imputation methods on real microarray data sets. Furthermore, our approach can also discover more regulatory gene pairs that are known in the literature than other methods. PMID:25796734

  15. Random forests-based differential analysis of gene sets for gene expression data.

    PubMed

    Hsueh, Huey-Miin; Zhou, Da-Wei; Tsai, Chen-An

    2013-04-10

    In DNA microarray studies, gene-set analysis (GSA) has become the focus of gene expression data analysis. GSA utilizes the gene expression profiles of functionally related gene sets in Gene Ontology (GO) categories or priori-defined biological classes to assess the significance of gene sets associated with clinical outcomes or phenotypes. Many statistical approaches have been proposed to determine whether such functionally related gene sets express differentially (enrichment and/or deletion) in variations of phenotypes. However, little attention has been given to the discriminatory power of gene sets and classification of patients. In this study, we propose a method of gene set analysis, in which gene sets are used to develop classifications of patients based on the Random Forest (RF) algorithm. The corresponding empirical p-value of an observed out-of-bag (OOB) error rate of the classifier is introduced to identify differentially expressed gene sets using an adequate resampling method. In addition, we discuss the impacts and correlations of genes within each gene set based on the measures of variable importance in the RF algorithm. Significant classifications are reported and visualized together with the underlying gene sets and their contribution to the phenotypes of interest. Numerical studies using both synthesized data and a series of publicly available gene expression data sets are conducted to evaluate the performance of the proposed methods. Compared with other hypothesis testing approaches, our proposed methods are reliable and successful in identifying enriched gene sets and in discovering the contributions of genes within a gene set. The classification results of identified gene sets can provide an valuable alternative to gene set testing to reveal the unknown, biologically relevant classes of samples or patients. In summary, our proposed method allows one to simultaneously assess the discriminatory ability of gene sets and the importance of genes for interpretation of data in complex biological systems. The classifications of biologically defined gene sets can reveal the underlying interactions of gene sets associated with the phenotypes, and provide an insightful complement to conventional gene set analyses. PMID:23219997

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

    PubMed Central

    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

    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

  17. Functional Analysis of the Molecular Interactions of TATA Box-Containing Genes and Essential Genes

    PubMed Central

    Moon, Jisook

    2015-01-01

    Genes can be divided into TATA-containing genes and TATA-less genes according to the presence of TATA box elements at promoter regions. TATA-containing genes tend to be stress-responsive, whereas many TATA-less genes are known to be related to cell growth or “housekeeping” functions. In a previous study, we demonstrated that there are striking differences among four gene sets defined by the presence of TATA box (TATA-containing) and essentiality (TATA-less) with respect to number of associated transcription factors, amino acid usage, and functional annotation. Extending this research in yeast, we identified KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways that are statistically enriched in TATA-containing or TATA-less genes and evaluated the possibility that the enriched pathways are related to stress or growth as reflected by the individual functions of the genes involved. According to their enrichment for either of these two gene sets, we sorted KEGG pathways into TATA-containing-gene-enriched pathways (TEPs) and essential-gene-enriched pathways (EEPs). As expected, genes in TEPs and EEPs exhibited opposite results in terms of functional category, transcriptional regulation, codon adaptation index, and network properties, suggesting the possibility that the bipolar patterns in these pathways also contribute to the regulation of the stress response and to cell survival. Our findings provide the novel insight that significant enrichment of TATA-binding or TATA-less genes defines pathways as stress-responsive or growth-related. PMID:25789484

  18. Gene age predicts the strength of purifying selection acting on gene expression variation in humans.

    PubMed

    Popadin, Konstantin Y; Gutierrez-Arcelus, Maria; Lappalainen, Tuuli; Buil, Alfonso; Steinberg, Julia; Nikolaev, Sergey I; Lukowski, Samuel W; Bazykin, Georgii A; Seplyarskiy, Vladimir B; Ioannidis, Panagiotis; Zdobnov, Evgeny M; Dermitzakis, Emmanouil T; Antonarakis, Stylianos E

    2014-12-01

    Gene expression levels can be subject to selection. We hypothesized that the age of gene origin is associated with expression constraints, given that it affects the level of gene integration into the functional cellular environment. By studying the genetic variation affecting gene expression levels (cis expression quantitative trait loci [cis-eQTLs]) and protein levels (cis protein QTLs [cis-pQTLs]), we determined that young, primate-specific genes are enriched in cis-eQTLs and cis-pQTLs. Compared to cis-eQTLs of old genes originating before the zebrafish divergence, cis-eQTLs of young genes have a higher effect size, are located closer to the transcription start site, are more significant, and tend to influence genes in multiple tissues and populations. These results suggest that the expression constraint of each gene increases throughout its lifespan. We also detected a positive correlation between expression constraints (approximated by cis-eQTL properties) and coding constraints (approximated by Ka/Ks) and observed that this correlation might be driven by gene age. To uncover factors associated with the increase in gene-age-related expression constraints, we demonstrated that gene connectivity, gene involvement in complex regulatory networks, gene haploinsufficiency, and the strength of posttranscriptional regulation increase with gene age. We also observed an increase in heritability of gene expression levels with age, implying a reduction of the environmental component. In summary, we show that gene age shapes key gene properties during evolution and is therefore an important component of genome function. PMID:25480033

  19. Arabidopsis gene expression patterns during spaceflight

    NASA Astrophysics Data System (ADS)

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

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

  20. Leukemogenic transformation by HOXA cluster genes.

    PubMed

    Bach, Christian; Buhl, Sebastian; Mueller, Dorothée; García-Cuéllar, María-Paz; Maethner, Emanuel; Slany, Robert K

    2010-04-01

    HOX homeobox genes are important regulators of normal and malignant hematopoiesis. Abdominal-type HOXA genes like HOXA9 are highly leukemogenic. However, little is known about transformation by anterior HOXA genes. Here we performed a comprehensive assessment of the oncogenic potential of every HOXA gene in primary hematopoietic cells. With exception of HOXA2 and HOXA5, all HOXA genes caused a block or delay of hematopoietic differentiation and cooperated with Meis1. No evidence for the alleged tumor-suppressor function of HOXA5 could be found. Whereas all active HOXA genes immortalized mixed granulocytic/monocytic populations, HOXA13 preferentially specified monocytoid development. The anterior HOXA genes HOXA1, HOXA4, and HOXA6 transformed cells, generating permanent cell lines, although they did so less potently than HOXA9. Upon transplantation these lines induced myeloproliferation and acute myeloid leukemia in recipient animals. Kinetic studies with inducible HOX derivatives demonstrated that anterior HOXA genes autonomously contributed to cellular transformation. This function was not mediated by endogenous Hoxa9, which was persistently expressed in cells transformed by anterior HOX genes. In summary our results demonstrate a hitherto unexpected role of anterior HOXA genes in hematopoietic malignancy. PMID:20130239

  1. Evolution of the Vertebrate Resistin Gene Family.

    PubMed

    Hu, Qingda; Tan, Huanran; Irwin, David M

    2015-01-01

    Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions. PMID:26076481

  2. Evolution of the Vertebrate Resistin Gene Family

    PubMed Central

    Hu, Qingda; Tan, Huanran; Irwin, David M.

    2015-01-01

    Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions. PMID:26076481

  3. The history of the Mendelian gene.

    PubMed

    Frías L, Daniel

    2007-01-01

    The concept of heredity arose when the ancient philosophers and scientists felt the need to explain the variation and organic evolution phenomena. The ideas about inheritance developed before Mendel were significant in the construction of the Mendelian concept of gene. From Mendelian hereditary principles to molecular genetics there have been many different concepts and also many definitions of gene. In the first corpuscular concept of gene, mutation was quite crucial to explain the different alternative genotype and phenotype expression in the progeny. From the rediscovery of Mendelian Principles to 1961, Morgan's idea that a gene is not divisible by recombination prevailed. Nevertheless it was later demonstrated that there are different units of recombination and mutation within the gene, and in a determinate gene different "functional units" can exist. In 1977, surprisingly, Sharp and Roberts found out that genes are fragmented into "exons" and "introns". At present time, with the discovery of iRNA, non coding RNA, importance of introns, transposable elements, pseudogenes, endogenous viral DNA, repeated DNA, superposed genes, non-transcriptional genes and epigenesis, ancient questions return: what is a gene? where is the program? what is the true role of mutations in the organic evolution? PMID:17592820

  4. RapGene: a fast and accurate strategy for synthetic gene assembly in Escherichia coli.

    PubMed

    Zampini, Massimiliano; Stevens, Pauline Rees; Pachebat, Justin A; Kingston-Smith, Alison; Mur, Luis A J; Hayes, Finbarr

    2015-01-01

    The ability to assemble DNA sequences de novo through efficient and powerful DNA fabrication methods is one of the foundational technologies of synthetic biology. Gene synthesis, in particular, has been considered the main driver for the emergence of this new scientific discipline. Here we describe RapGene, a rapid gene assembly technique which was successfully tested for the synthesis and cloning of both prokaryotic and eukaryotic genes through a ligation independent approach. The method developed in this study is a complete bacterial gene synthesis platform for the quick, accurate and cost effective fabrication and cloning of gene-length sequences that employ the widely used host Escherichia coli. PMID:26062748

  5. RapGene: a fast and accurate strategy for synthetic gene assembly in Escherichia coli

    PubMed Central

    Zampini, Massimiliano; Stevens, Pauline Rees; Pachebat, Justin A.; Kingston-Smith, Alison; Mur, Luis A. J.; Hayes, Finbarr

    2015-01-01

    The ability to assemble DNA sequences de novo through efficient and powerful DNA fabrication methods is one of the foundational technologies of synthetic biology. Gene synthesis, in particular, has been considered the main driver for the emergence of this new scientific discipline. Here we describe RapGene, a rapid gene assembly technique which was successfully tested for the synthesis and cloning of both prokaryotic and eukaryotic genes through a ligation independent approach. The method developed in this study is a complete bacterial gene synthesis platform for the quick, accurate and cost effective fabrication and cloning of gene-length sequences that employ the widely used host Escherichia coli. PMID:26062748

  6. Differential Gene Expression in the Laccase Gene Family from Basidiomycete I-62 (CECT 20197)

    PubMed Central

    Mansur, Mariana; Suárez, Teresa; González, Aldo E.

    1998-01-01

    A family of genes encoding laccases has recently been described for the basidiomycete I-62 (CECT 20197). Transcript levels of genes lcc1, lcc2, and lcc3 were analyzed under four different culture conditions to study their expression patterns. Two of the laccase genes were clearly inducible by veratryl alcohol: the lcc1 gene is inducible in early stages of growth, and the lcc2 gene is also inducible but only when the organism reaches the stationary phase. Transcript levels for the third gene, lcc3, were uninduced by veratryl alcohol and repressed by glucose. PMID:16349507

  7. Effects of G-gene Deletion and Replacement on Rabies Virus Vector Gene Expression

    PubMed Central

    Sato, Sho; Ohara, Shinya; Tsutsui, Ken-Ichiro; Iijima, Toshio

    2015-01-01

    The glycoprotein-gene (G gene) -deleted rabies virus (RV) vector is a powerful tool to examine the function and structure of neural circuits. We previously reported that the deletion of the G gene enhances the transgene expression level of the RV vector. However, the mechanism of this enhancement remains to be clarified. We presume that there are two possible factors for this enhancement. The first factor is the glycoprotein of RV, which shows cytotoxicity; thus, may cause a dysfunction in the translation process of infected cells. The second possible factor is the enhanced expression of the L gene, which encodes viral RNA polymerase. In the RV, it is known that the gene expression level is altered depending on the position of the gene. Since G-gene deletion displaces the L gene in the genome, the expression of the L gene and viral transcription may be enhanced. In this study, we compared the transgene expression level and viral transcription of three recombinant RV vectors. The effect of glycoprotein was examined by comparing the viral gene expression of G-gene-intact RV and G-gene-replaced RV. Despite the fact that the L-gene transcription level of these two RV vectors was similar, the G-gene-replaced RV vector showed higher viral transcription and transgene expression level than the G-gene-intact RV vector. To examine the effect of the position of the L gene, we compared the viral gene expression of the G-gene-deleted RV and G-gene-replaced RV. The G-gene-deleted RV vector showed higher L-gene transcription, viral transcription, and transgene expression level than the G-gene-replaced RV vector. These results indicate that G-gene deletion enhances the transgene expression level through at least two factors, the absence of glycoprotein and enhancement of L-gene expression. These findings enable investigators to design a useful viral vector that shows a controlled desirable transgene expression level in applications. PMID:26023771

  8. Genes

    NSDL National Science Digital Library

    John Smith

    2004-11-29

    Students will explore Genetics. All About Genetics These pages teach you how genetics work. Genetics: Decoding Life What students need to know about genetics Genetic Activities Websites that give you ideas for classroom activities. Comparing Apples and Oranges TRB 5:5 Activity 1 Students will learn differnces in organisms. The Living Corn Necklace TRB 5:5 Activity 2 Students will learn to compare similarities and differnces in a similar organism. Paint's Family Tree TRB 5:5 Activity 3 Students will discover family traits. Mealworms and Earthworms TRB 5:5 Activity 4 Students will learn about ...

  9. Horizontal acquisition of multiple mitochondrial genes from a parasitic plant followed by gene conversion with host mitochondrial genes

    PubMed Central

    2010-01-01

    Background Horizontal gene transfer (HGT) is relatively common in plant mitochondrial genomes but the mechanisms, extent and consequences of transfer remain largely unknown. Previous results indicate that parasitic plants are often involved as either transfer donors or recipients, suggesting that direct contact between parasite and host facilitates genetic transfer among plants. Results In order to uncover the mechanistic details of plant-to-plant HGT, the extent and evolutionary fate of transfer was investigated between two groups: the parasitic genus Cuscuta and a small clade of Plantago species. A broad polymerase chain reaction (PCR) survey of mitochondrial genes revealed that at least three genes (atp1, atp6 and matR) were recently transferred from Cuscuta to Plantago. Quantitative PCR assays show that these three genes have a mitochondrial location in the one species line of Plantago examined. Patterns of sequence evolution suggest that these foreign genes degraded into pseudogenes shortly after transfer and reverse transcription (RT)-PCR analyses demonstrate that none are detectably transcribed. Three cases of gene conversion were detected between native and foreign copies of the atp1 gene. The identical phylogenetic distribution of the three foreign genes within Plantago and the retention of cytidines at ancestral positions of RNA editing indicate that these genes were probably acquired via a single, DNA-mediated transfer event. However, samplings of multiple individuals from two of the three species in the recipient Plantago clade revealed complex and perplexing phylogenetic discrepancies and patterns of sequence divergence for all three of the foreign genes. Conclusions This study reports the best evidence to date that multiple mitochondrial genes can be transferred via a single HGT event and that transfer occurred via a strictly DNA-level intermediate. The discovery of gene conversion between co-resident foreign and native mitochondrial copies suggests that transferred genes may be evolutionarily important in generating mitochondrial genetic diversity. Finally, the complex relationships within each lineage of transferred genes imply a surprisingly complicated history of these genes in Plantago subsequent to their acquisition via HGT and this history probably involves some combination of additional transfers (including intracellular transfer), gene duplication, differential loss and mutation-rate variation. Unravelling this history will probably require sequencing multiple mitochondrial and nuclear genomes from Plantago. See Commentary: http://www.biomedcentral.com/1741-7007/8/147. PMID:21176201

  10. Cross-Ontological Analytics: Combining Associative and Hierarchical Relations in the Gene Ontologies to Assess Gene Product Similarity

    SciTech Connect

    Posse, Christian; Sanfilippo, Antonio P.; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.

    2006-05-28

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the gene ontologies, two complementary approaches have emerged where the similarity between two genes/gene products is obtained by comparing gene ontology (GO) annotations associated with the gene/gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene ontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene ontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy.

  11. Gene flow from transgenic common beans expressing the bar gene.

    PubMed

    Faria, Josias C; Carneiro, Geraldo E S; Aragão, Francisco J L

    2010-01-01

    Gene flow is a common phenomenon even in self-pollinated plant species. With the advent of genetically modified plants this subject has become of the utmost importance due to the need for controlling the spread of transgenes. This study was conducted to determine the occurrence and intensity of outcrossing in transgenic common beans. In order to evaluate the outcross rates, four experiments were conducted in Santo Antonio de Goiás (GO, Brazil) and one in Londrina (PR, Brazil), using transgenic cultivars resistant to the herbicide glufosinate ammonium and their conventional counterparts as recipients of the transgene. Experiments with cv. Olathe Pinto and the transgenic line Olathe M1/4 were conducted in a completely randomized design with ten replications for three years in one location, whereas the experiments with cv. Pérola and the transgenic line Pérola M1/4 were conducted at two locations for one year, with the transgenic cultivar surrounded on all sides by the conventional counterpart. The outcross occurred at a negligible rate of 0.00741% in cv. Pérola, while none was observed (0.0%) in cv. Olathe Pinto. The frequency of gene flow was cultivar dependent and most of the observed outcross was within 2.5 m from the edge of the pollen source. Index terms: Phaseolus vulgaris, outcross, glufosinate ammonium. PMID:21865877

  12. Testing Gene-Gene Interactions in Genome Wide Association Studies

    PubMed Central

    Hu, Jie Kate; Wang, Xianlong; Wang, Pei

    2015-01-01

    Detection of gene-gene interaction has become increasingly popular over the past decade in genome wide association studies (GWAS). Besides traditional logistic regression analysis for detecting interactions between two markers, new methods have been developed in recent years such as comparing linkage disequilibrium (LD) in case and control groups. All these methods form the building blocks of most screening strategies for disease susceptibility loci in GWAS. In this paper, we are interested in comparing the competing methods and providing practical guidelines for selecting appropriate testing methods for interaction in GWAS. We first review a series of existing statistical methods to detect interactions, and then examine different definitions of interactions to gain insight into the theoretical relationship between the existing testing methods. Lastly, we perform extensive simulations to compare powers of various methods to detect either interaction between two markers at two unlinked loci or the overall association allowing for both interaction and main effects. This investigation reveals informative characteristics of various methods that are helpful to GWAS investigators. PMID:24431225

  13. Cancer Genes in Lung Cancer

    PubMed Central

    El-Telbany, Ahmed

    2012-01-01

    Cancer is now known as a disease of genomic alterations. Mutational analysis and genomics profiling in recent years have advanced the field of lung cancer genetics/genomics significantly. It is becoming more accepted now that the identification of genomic alterations in lung cancer can impact therapeutics, especially when the alterations represent “oncogenic drivers” in the processes of tumorigenesis and progression. In this review, we will highlight the key driver oncogenic gene mutations and fusions identified in lung cancer. The review will summarize and report the available demographic and clinicopathological data as well as molecular details behind various lung cancer gene alterations in the context of race. We hope to shed some light into the disparities in the incidence of various genetic mutations among lung cancer patients of different racial backgrounds. As molecularly targeted therapy continues to advance in lung cancer, racial differences in specific genetic/genomic alterations can have an important impact in the choices of therapeutics and in our understanding of the drug sensitivity/resistance profile. The most relevant genes in lung cancer described in this review include the following: EGFR, KRAS, MET, LKB1, BRAF, PIK3CA, ALK, RET, and ROS1. Commonly identified genetic/genomic alterations such as missense or nonsense mutations, small insertions or deletions, alternative splicing, and chromosomal fusion rearrangements were discussed. Relevance in current targeted therapeutic drugs was mentioned when appropriate. We also highlighted various targeted therapeutics that are currently under clinical development, such as the MET inhibitors and antibodies. With the advent of next-generation sequencing, the landscape of genomic alterations in lung cancer is expected to be much transformed and detailed in upcoming years. These genomic landscape differences in the context of racial disparities should be emphasized both in tumorigenesis and in drug sensitivity/resistance. It is hoped that such effort will help to diminish racial disparities in lung cancer outcome in the future. PMID:23264847

  14. Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins.

    PubMed

    Holmes, Roger S; Wright, Matthew W; Laulederkind, Stanley J F; Cox, Laura A; Hosokawa, Masakiyo; Imai, Teruko; Ishibashi, Shun; Lehner, Richard; Miyazaki, Masao; Perkins, Everett J; Potter, Phillip M; Redinbo, Matthew R; Robert, Jacques; Satoh, Tetsuo; Yamashita, Tetsuro; Yan, Bingfan; Yokoi, Tsuyoshi; Zechner, Rudolf; Maltais, Lois J

    2010-10-01

    Mammalian carboxylesterase (CES or Ces) genes encode enzymes that participate in xenobiotic, drug, and lipid metabolism in the body and are members of at least five gene families. Tandem duplications have added more genes for some families, particularly for mouse and rat genomes, which has caused confusion in naming rodent Ces genes. This article describes a new nomenclature system for human, mouse, and rat carboxylesterase genes that identifies homolog gene families and allocates a unique name for each gene. The guidelines of human, mouse, and rat gene nomenclature committees were followed and "CES" (human) and "Ces" (mouse and rat) root symbols were used followed by the family number (e.g., human CES1). Where multiple genes were identified for a family or where a clash occurred with an existing gene name, a letter was added (e.g., human CES4A; mouse and rat Ces1a) that reflected gene relatedness among rodent species (e.g., mouse and rat Ces1a). Pseudogenes were named by adding "P" and a number to the human gene name (e.g., human CES1P1) or by using a new letter followed by ps for mouse and rat Ces pseudogenes (e.g., Ces2d-ps). Gene transcript isoforms were named by adding the GenBank accession ID to the gene symbol (e.g., human CES1_AB119995 or mouse Ces1e_BC019208). This nomenclature improves our understanding of human, mouse, and rat CES/Ces gene families and facilitates research into the structure, function, and evolution of these gene families. It also serves as a model for naming CES genes from other mammalian species. PMID:20931200

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

    PubMed

    Lawson, Mark J; Zhang, Liqing

    2009-08-01

    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

  16. Gorgeous mosaic of mitochondrial genes created by horizontal transfer and gene conversion

    PubMed Central

    Hao, Weilong; Richardson, Aaron O.; Zheng, Yihong; Palmer, Jeffrey D.

    2010-01-01

    The best known outcome of horizontal gene transfer (HGT) is the introduction of novel genes, but other outcomes have been described. When a transferred gene has a homolog in the recipient genome, the native gene may be functionally replaced (and subsequently lost) or partially overwritten by gene conversion with transiently present foreign DNA. Here we report the discovery, in two lineages of plant mitochondrial genes, of novel gene combinations that arose by conversion between coresident native and foreign homologs. These lineages have undergone intricate conversion between native and foreign copies, with conversion occurring repeatedly and differentially over the course of speciation, leading to radiations of mosaic genes involved in respiration and intron splicing. Based on these findings, we develop a model—the duplicative HGT and differential gene conversion model—that integrates HGT and ongoing gene conversion in the context of speciation. Finally, we show that one of these HGT-driven gene-conversional radiations followed two additional types of conversional chimerism, namely, intramitochondrial retroprocessing and interorganellar gene conversion across the 2 billion year divide between mitochondria and chloroplasts. These findings expand our appreciation of HGT and gene conversion as creative evolutionary forces, establish plant mitochondria as a premiere system for studying the evolutionary dynamics of HGT and its genetic reverberations, and recommend careful examination of bacterial and other genomes for similar, likely overlooked phenomena. PMID:21115831

  17. Identification of Development and Pathogenicity Related Gene in Botrytis cinerea via Digital Gene Expression Profile

    PubMed Central

    Zhao, Bin; Si, He Long; Sun, Zhi Ying; Xu, Zheng; Chen, Zhan; Zhang, Jin lin; Xing, Ji Hong; Dong, Jin Gao

    2015-01-01

    Background: Botrytis cinerea, a haploid Euascomycete fungus that infects numerous crops, has been used as a model system for studying molecular phytopathology. Botrytis cinerea adopts various modes of infection, which are mediated by a number of pathogenicity and virulence-related genes. Many of these genes have not been reported previously. Objectives: This study aimed to investigate development and pathogenicity-related genes between a novel nonpathogenic mutant and the Wild Type (WT) in B. cinerea. Materials and Methods: Digital Gene Expression (DGE) tag profiling can reveal novel genes that may be involved in development and pathogenicity of plant pathogen. A large volume of B. cinerea tag-seq was generated to identify differential expressed genes by the Illumina DGE tag pro?ling technology. Results: A total of 4,182,944 and 4,182,021 clean tags were obtained from the WT and a nonpathogenic mutant stain (BCt89), respectively, and 10,410 differentially expressed genes were identified. In addition, 84 genes were expressed in the WT only while 34 genes were expressed in the mutant only. A total of 664 differentially expressed genes were involved in 91 Kyoto Encyclopedia of Genes and Genome pathways, including signaling and metabolic pathways. Conclusions: Expression levels of 1,426 genes were significantly up-regulated in the mutant compared to WT. Furthermore, 301 genes were down-regulated with False Discovery Rates (FDR) of < 0.001 and absolute value of log2 Ratio of ? 1. PMID:26034553

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

    PubMed Central

    Bettembourg, Charles; Diot, Christian; Dameron, Olivier

    2014-01-01

    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

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

    PubMed Central

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

    2009-01-01

    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

  20. Divergence of gene body DNA methylation and evolution of plant duplicate genes.

    PubMed

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

    2014-01-01

    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

  1. Gene flow and bacterial transformation

    SciTech Connect

    Dixon, B.

    1993-07-01

    It is common knowledge that Salmonella which should be removed during the processing of sewage can persist is sewage sludge that is sprayed as agricultural fertilizer. Currently, researchers have found that Salmonella may become nonculturable by conventional means, while remaining viable. The issue raised by this article is the knowledge of lateral gene flow as secure as scientist suppose The author sites several research papers that suggest that intergeneric transformation can and does take place in marine environments such as tropical and subtropical estuaries.

  2. QB1 - Stochastic Gene Regulation

    SciTech Connect

    Munsky, Brian [Los Alamos National Laboratory

    2012-07-23

    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.

  3. Gene therapy for carcinoma of the breast

    PubMed Central

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

    2007-01-01

    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

  4. Non-random sharing of Plantae genes.

    PubMed

    Chan, Cheong Xin; Bhattacharya, Debashish

    2011-05-01

    The power of eukaryote genomics relies strongly on taxon sampling. This point was underlined in a recent analysis of red algal genome evolution in which we tested the Plantae hypothesis that posits the monophyly of red, green (including plants) and glaucophyte algae. The inclusion of novel genome data from two mesophilic red algae enabled us to robustly demonstrate the sisterhood of red and green algae in the tree of life. Perhaps more exciting was the finding that >1,800 putative genes in the unicellular red alga Porphyridium cruentum showed evidence of gene-sharing with diverse lineages of eukaryotes and prokaryotes. Here we assessed the correlation between the putative functions of these shared genes and their susceptibility to transfer. It turns out that genes involved in complex interactive networks such as biological regulation and transcription/translation are less susceptible to endosymbiotic or horizontal gene transfer, when compared to genes with metabolic and transporter functions. PMID:21980581

  5. Homeobox genes expressed during echinoderm arm regeneration.

    PubMed

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

    2014-04-01

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

  6. HLA Immune Function Genes in Autism

    PubMed Central

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

    2012-01-01

    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

  7. Towards Automatic Generation of Gene Summary

    Microsoft Academic Search

    Feng Jin; Minlie Huang; Zhiyong Lu; Xiaoyan Zhu

    2009-01-01

    In this paper we present an extractive system that au- tomatically generates gene summaries from the biomed- ical literature. The proposed text summarization system selects and ranks sentences from multiple MEDLINE abstracts by exploiting gene-specific information and similarity relationships between sentences. We evaluate our system on a large dataset of 7,294 human genes and 187,628 MEDLINE abstracts using Recall-Oriented Understudy

  8. Methods for monitoring multiple gene expression

    DOEpatents

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

    2012-05-01

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

  9. Klotho is a target gene of PPAR-?

    Microsoft Academic Search

    Hong Zhang; Yuanyuan Li; Yanbo Fan; Jing Wu; Beilei Zhao; Youfei Guan; Shu Chien; Nanping Wang

    2008-01-01

    Klotho is an anti-aging gene whose expression is regulated by many stimuli. Here we examined the transcriptional regulation of the klotho gene by peroxisome proliferator-activated receptor-? (PPAR-?). The PPAR-? agonists thiazolidinediones increased both klotho mRNA and protein expression in HEK293 cells and several renal epithelial cell lines. The induction was blocked by PPAR-? antagonists or small-interfering RNA-mediated gene silencing of

  10. Exploring the opioid system by gene knockout

    Microsoft Academic Search

    Brigitte L Kieffer; Claire Gavériaux-Ruff

    2002-01-01

    The endogenous opioid system consists of three opioid peptide precursor genes encoding enkephalins (preproenkephalin, Penk), dynorphins (preprodynorphin, Pdyn) and ?-endorphin (?end), proopiomelanocortin (POMC) and three receptor genes encoding mu-opiod receptor (MOR), delta-opiod receptor (DOR) and kappa-opiod receptor (KOR). In the past years, all six genes have been inactivated in mice by homologous recombination. The analysis of spontaneous behavior in mutant

  11. Awareness and attitudes concerning BRCA gene testing

    Microsoft Academic Search

    Avigyail Mogilner; Marc Otten; John D. Cunningham; Steven T. Brower

    1998-01-01

    Background: The availability of a commercial test for the breast cancer susceptibility genes, BRCA1 and BRCA2, has generated interest in both the medical community and the general public.\\u000aMethods: Patients and family members were approached in the waiting room and asked to fill out an anonymous questionnaire about their awareness of breast cancer genes and breast cancer gene testing, and

  12. Aflatoxin biosynthesis gene clusters and flanking regions

    Microsoft Academic Search

    K. C. Ehrlich; J. Yu; P. J. Cotty

    2005-01-01

    K.C. EHRLICH, J. YU AND P.J. COTTY. 2005. Aims: To compare the biosynthetic gene cluster sequences of the main aflatoxin (AF)-producing Aspergillus species. Methods and Results: Sequencing was on fosmid clones selected by homology to Aspergillus parasiticus sequence. Alignments revealed that gene order is conserved among AF gene clusters of Aspergillus nomius, A. parasiticus, two sclerotial morphotypes of Aspergillus flavus,

  13. Simulated annealing for supervised gene selection

    Microsoft Academic Search

    Maurizio Filippone; Francesco Masulli; Stefano Rovetta

    2011-01-01

    Genomic data, and more generally biomedical data, are often characterized by high dimensionality. An input selection procedure\\u000a can attain the two objectives of highlighting the relevant variables (genes) and possibly improving classification results.\\u000a In this paper, we propose a wrapper approach to gene selection in classification of gene expression data using simulated annealing\\u000a along with supervised classification. The proposed approach

  14. Targeted gene insertion for molecular medicine

    Microsoft Academic Search

    Katrin Voigt; Zsuzsanna Izsvák; Zoltán Ivics

    2008-01-01

    Genomic insertion of a functional gene together with suitable transcriptional regulatory elements is often required for long-term\\u000a therapeutical benefit in gene therapy for several genetic diseases. A variety of integrating vectors for gene delivery exist.\\u000a Some of them exhibit random genomic integration, whereas others have integration preferences based on attributes of the targeted\\u000a site, such as primary DNA sequence and

  15. Properties of developmental gene regulatory networks

    PubMed Central

    Davidson, Eric H.; Levine, Michael S.

    2008-01-01

    The modular components, or subcircuits, of developmental gene regulatory networks (GRNs) execute specific developmental functions, such as the specification of cell identity. We survey examples of such subcircuits and relate their structures to corresponding developmental functions. These relations transcend organisms and genes, as illustrated by the similar structures of the subcircuits controlling the specification of the mesectoderm in the Drosophila embryo and the endomesoderm in the sea urchin, even though the respective subcircuits are composed of nonorthologous regulatory genes. PMID:19104053

  16. A Gene Map of the Human Genome

    Microsoft Academic Search

    G. D. Schuler; M. S. Boguski; E. A. Stewart; L. D. Stein; G. Gyapay; K. Rice; R. E. White; P. Rodriguez-Tome; A. Aggarwal; E. Bajorek; S. Bentolila; B. B. Birren; A. Butler; A. B. Castle; N. Chiannilkulchai; A. Chu; C. Clee; S. Cowles; P. J. R. Day; T. Dibling; I. Dunham; C. East; C. Edwards; J.-B. Fan; N. Fang; C. Fizames; C. Garrett; L. Green; D. Hadley; M. Harris; P. Harrison; S. Brady; A. Hicks; E. Holloway; L. Hui; S. Hussain; C. Louis-Dit-Sully; J. Ma; A. Macgilvery; C. Mader; A. Maratukulam; T. C. Matise; K. B. McKusick; J. Morissette; A. Mungall; D. Muselet; H. C. Nusbaum; D. C. Page; A. Peck; S. Perkins; M. Piercy; F. Qin; J. Quackenbush; S. Ranby; T. Reif; S. Rozen; C. Sanders; J. Silva; D. K. Slonim; C. Soderlund; W.-L. Sun; P. Tabar; T. Thangarajah; N. Vega-Czarny; D. Vollrath; S. Voyticky; T. Wilmer; X. Wu; M. D. Adams; C. Aufiray; N. A. R. Walter; R. Brandon; A. Dehejia; P. N. Goodfellow; R. Houlgatte; J. R. Hudson Jr.; S. E. Ide; K. R. Iorio; W. Y. Lee; N. Seki; T. Nagase; K. Ishikawa; N. Nomura; C. Phillips; M. H. Polymeropoulos; M. Sandusky; K. Schmitt; R. Berry; K. Swanson; R. Torres; J. C. Venter; J. M. Sikela; J. Weissenbach; R. M. Myers; D. R. Cox; M. R. James; D. Bentley; P. Deloukas; E. S. Lander; T. J. Hudson

    1996-01-01

    The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes

  17. A formal theory of the selfish gene.

    PubMed

    Gardner, A; Welch, J J

    2011-08-01

    Adaptation is conventionally regarded as occurring at the level of the individual organism. In contrast, the theory of the selfish gene proposes that it is more correct to view adaptation as occurring at the level of the gene. This view has received much popular attention, yet has enjoyed only limited uptake in the primary research literature. Indeed, the idea of ascribing goals and strategies to genes has been highly controversial. Here, we develop a formal theory of the selfish gene, using optimization theory to capture the analogy of 'gene as fitness-maximizing agent' in mathematical terms. We provide formal justification for this view of adaptation by deriving mathematical correspondences that translate the optimization formalism into dynamical population genetics. We show that in the context of social interactions between genes, it is the gene's inclusive fitness that provides the appropriate maximand. Hence, genic selection can drive the evolution of altruistic genes. Finally, we use the formalism to assess the various criticisms that have been levelled at the theory of the selfish gene, dispelling some and strengthening others. PMID:21605218

  18. [Overlapping genes and antisense transcription in eukaryotes].

    PubMed

    Cherezov, R O; Simonova, O B

    2014-07-01

    Numerous studies showed that overlapping genes are fairly common elements of genome organization, not only in viruses and prokaryotes but also in eukaryotes. At the same time, the regulatory mechanisms of overlapping gene expression, as well as the functional relevance of antisense transcription, are still relatively unknown. This review describes the history of the discovery of regulatory antisense RNAs, the types of gene overlap, and the putative mechanisms of their functioning. In conclusion, the critical views of different authors on the problem of detecting overlapping genes and an evaluation of the level of antisense transcription are presented. PMID:25720133

  19. A gene map of congenital malformations.

    PubMed Central

    Wilkie, A O; Amberger, J S; McKusick, V A

    1994-01-01

    Congenital malformations frequently arise sporadically, making it difficult to determine whether or not they are genetic in aetiology, let alone which gene(s) may be involved. Nevertheless, rapid progress has been made over recent years in the localisation and identification of gene mutations in specific malformations. This review draws from Mendelian inheritance in man (Johns Hopkins University Press, 11th ed, 1994) and the online version (OMIM) to catalogue 139 loci (including 65 specifically identified genes) implicated in congenital malformations. Some of the most interesting recent developments are discussed. PMID:7966186

  20. Aldehyde dehydrogenase gene superfamily: the 2002 update.

    PubMed

    Sophos, Nickolas A; Vasiliou, Vasilis

    2003-02-01

    The aldehyde dehydrogenase (ALDH) superfamily represents a divergently related group of enzymes that metabolize a wide variety of endogenous and exogenous aldehydes. With the advent of megabase genome sequencing, the ALDH superfamily is continuously expanding on many fronts. The presence of ALDH encoding genes in the vast majority of archaeal, eubacterial and eukaryotic genomes supports the notion that these enzymes are important components of metabolic processes in living organisms and that the ALDH superfamily is ancient in origin. As of July 2002, the ALDH superfamily consists of 555 distinct genes: 32 in archaea, 351 in eubacteria, and 172 in eukaryota. Complete sequencing of individual genomes reveals the number of ALDH genes found per organism ranges from 1 to 5 in archaeal species, 1-26 genes in eubacterial species, and 8-17 genes in eukaryotic species. In the human genome, 17 functional genes and 3 pseudogenes have been identified to date. A standardized ALDH gene nomenclature system has been developed based on multiple alignment analysis of eukaryotic ALDH amino acid sequences. Both Human and Mouse Genome Projects have accepted this nomenclature system. In this report, we present a complete listing of all ALDH sequences known to date, along with the evolutionary analysis of the eukaryotic ALDHs. Thus far, the eukaryotic ALDHs comprise 20 gene families. Detailed information on ALDH gene superfamily is also available at http://www.uchsc.edu/sp/sp/alcdbase/aldhcov.html. PMID:12604184