WorldWideScience

Sample records for epsilon-sarcoglycan gene mutations1

  1. No muscle involvement in myoclonus-dystonia caused by epsilon-sarcoglycan gene mutations1

    DEFF Research Database (Denmark)

    Hjermind, L.E.; Vissing, J.; Asmus, F.

    2008-01-01

    homologous and may substitute for one-another in different tissues. We therefore investigated whether mutations in SGCE also cause abnormalities of skeletal and myocardial muscle. Six patients with clinically and genetically verified M-D and no signs of limb-girdle muscular dystrophy were included. Skeletal...... muscle biopsies were obtained from all patients, and endomyocardial muscle biopsy from one of the patients. Morphological and immunohistological investigations were performed and compared with controls. Histological and immunohistological investigations of muscle and clinical assessment of muscle...... strength and mass showed no difference between M-D patients and controls. Our findings indicate that patients with M-D have no signs or symptoms of muscle disease. This suggests a different role of the sarcoglycan complex epsilonbetagammadelta versus alphabetagammadelta complex in humans, as earlier...

  2. Cryptic 7q21 and 9p23 deletions in a patient with apparently balanced de novo reciprocal translocation t(7;9)(q21;p23) associated with a dystonia-plus syndrome: paternal deletion of the epsilon-sarcoglycan (SGCE) gene.

    Science.gov (United States)

    Bonnet, C; Grégoire, M-J; Vibert, M; Raffo, E; Leheup, B; Jonveaux, P

    2008-01-01

    We report on a boy with myoclonus-dystonia (M-D), language delay, and malformative anomalies. Genetic investigations allowed the identification of an apparently balanced de novo reciprocal translocation, t(7;9)(q21;p23). Breakpoint-region mapping using fluorescent in situ hybridization (FISH) analysis of bacterial artificial chromosome (BAC) clone probes identified microdeletions of 3.7 and 5.2 Mb within 7q21 and 9p23 breakpoint regions, respectively. Genotyping with microsatellite markers showed that deletions originated from paternal alleles. The deleted region on chromosome 7q21 includes a large imprinted gene cluster. SGCE and PEG10 are two maternally imprinted genes. SGCE mutations are implicated in M-D. In our case, M-D is due to deletion of the paternal allele of the SGCE gene. PEG10 is strongly expressed in the placenta and is essential for embryo development. Prenatal growth retardation identified in the patient may be due to deletion of the paternal allele of the PEG10 gene. Other genes in the deleted region on chromosome 7 are not imprinted. Nevertheless, a phenotype can be due to haploinsufficiency of these genes. KRIT1 is implicated in familial forms of cerebral cavernous malformations, and COL1A2 may be implicated in very mild forms of osteogenesis imperfecta. The deleted region on chromosome 9 overlaps with the candidate region for monosomy 9p syndrome. The proband shows dysmorphic features compatible with monosomy 9p syndrome, without mental impairment. These results emphasize that the phenotypic abnormalities of apparently balanced de novo translocations can be due to cryptic deletions and that the precise mapping of these aneusomies may improve clinical management.

  3. Distribution and Coexistence of Myoclonus and Dystonia as Clinical Predictors of SGCE Mutation Status: A Pilot Study

    NARCIS (Netherlands)

    Zutt, Rodi; Dijk, Joke M.; Peall, Kathryn J.; Speelman, Hans; Dreissen, Yasmine E. M.; Contarino, Maria Fiorella; Tijssen, Marina A. J.

    2016-01-01

    Myoclonus-dystonia (M-D) is a young onset movement disorder typically involving myoclonus and dystonia of the upper body. A proportion of the cases are caused by mutations to the autosomal dominantly inherited, maternally imprinted, epsilon-sarcoglycan gene (SGCE). Despite several sets of diagnostic

  4. RELN rare variants in myoclonus-dystonia

    NARCIS (Netherlands)

    Groen, Justus L.; Ritz, Katja; Jalalzadeh, Hamid; van der Salm, Sandra M. A.; Jongejan, Aldo; Mook, Olaf R.; Haagmans, Martin A.; Zwinderman, Aeilko H.; Motazacker, Mahdi M.; Hennekam, Raoul C.; Baas, Frank; Tijssen, Marina A. J.

    BACKGROUND: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene. In remaining M-D patients, no genetic factor has been

  5. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  6. Improvement of Isolated Myoclonus Phenotype in Myoclonus Dystonia after Pallidal Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Ritesh Ramdhani

    2016-03-01

    Full Text Available Background: Myoclonus–dystonia is a condition that manifests predominantly as myoclonic jerks with focal dystonia. It is genetically heterogeneous with most mutations in the epsilon sarcoglycan gene (SGCE. In medically refractory cases, deep brain stimulation (DBS has been shown to provide marked sustainable clinical improvement, especially in SGCE-positive patients. We present two patients with myoclonus–dystonia (one SGCE positive and the other SGCE negative who have the isolated myoclonus phenotype and had DBS leads implanted in the bilateral globus pallidus internus (GPi. Methods: We review their longitudinal Unified Myoclonus Rating Scale scores along with their DBS programming parameters and compare them with published cases in the literature. Results: Both patients demonstrated complete amelioration of all aspects of myoclonus within 6–12 months after surgery. The patient with the SGCE-negative mutation responded just as well as the patient who was SGCE positive. High-frequency stimulation (130 Hz with amplitudes greater than 2.5 V provided therapeutic benefit. Discussion: This case series demonstrates that high frequency GPi-DBS is effective in treating isolated myoclonus in myoclonus–dystonia, regardless of the presence of SGCE mutation.

  7. Genes and Gene Therapy

    Science.gov (United States)

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

  8. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  9. Sarcoglycan subcomplex in normal human smooth muscle: an immunohistochemical and molecular study.

    Science.gov (United States)

    Anastasi, Giuseppe; Cutroneo, Giuseppina; Sidoti, Antonina; Santoro, Giuseppe; D'Angelo, Rosalia; Rizzo, Giuseppina; Rinaldi, Carmen; Giacobbe, Oddone; Bramanti, Placido; Navarra, Giuseppe; Amato, Aldo; Favaloro, Angelo

    2005-09-01

    The sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix in adult muscle fibers. Sarcoglycans seem to be functionally and pathologically as important as dystrophin. In the skeletal and cardiac muscle, the sarcoglycan subcomplex is a heterotetrameric unit composed of the transmembrane glycoproteins alpha-, beta-, gamma- and delta-sarcoglycan. A fifth sarcoglycan with significant homology to alpha-sarcoglycan, epsilon-sarcoglycan, has been identified; this sarcoglycan is expressed in both muscle and non-muscle cells. It is hypothesized that epsilon-sarcoglycan might replace alpha-sarcoglycan in smooth muscle, forming a novel sarcoglycan subcomplex consisting of epsilon-, beta-, gamma-, and delta-sarcoglycan. Recently, zeta-sarcoglycan, a novel sarcoglycan highly related to gamma-sarcoglycan and delta-sarcoglycan, has been identified. On this basis, growing evidence suggests that there are two types of sarcoglycan complex; one, in skeletal and cardiac muscle, consisting of alpha-, beta-, gamma- and delta-sarcoglycan; and the other, in smooth muscle, containing beta-, delta-, zeta- and epsilon-sarcoglycan. epsilon-sarcoglycan may be substituted for alpha-sarcoglycan in a subset of striated muscle complexes. Our results, obtained with immunofluorescence semi-quantitative analysis and molecular methods on smooth muscle biopsies of human adult gastroenteric tract, show for the first time that alpha-sarcoglycan fluorescence is also always detectable in smooth muscle, although its staining pattern is lower than epsilon-sarcoglycan. Normal alpha-sarcoglycan staining was detected at times, whereas there was reduced, but clearly detectable staining for epsilon-sarcoglycan. Moreover, gamma-sarcoglycan staining is always detectable in all analyzed biopsies. On the basis of our results, we would be able to hypothesize the existence of a pentameric or, considering zeta-sarcolgycan, a hexameric

  10. gene structure, gene expression

    Indian Academy of Sciences (India)

    Primer 5.0 software. To adjust for RNA quality and diffe- rences in cDNA concentration, we amplified actin as an internal control with the following primers: PtActin-F (5′-TG. AAGGAGAAACTTGCGTAT-3′) and PtActin-R (5′-GCA. CAATGTTACCGTACAGAT-3′). These genes were ampli- fied from first-strand cDNA using ...

  11. Sarcoglycan subcomplex expression in refluxing ureteral endings.

    Science.gov (United States)

    Arena, Salvatore; Favaloro, Angelo; Cutroneo, Giuseppina; Consolo, Angela; Arena, Francesco; Anastasi, Giuseppe; Di Benedetto, Vincenzo

    2008-05-01

    Functional and structural lesions of ureteral endings seem to alter the active valve mechanism of the ureterovesical junction, causing vesicoureteral reflux. The interaction of the dystroglycan complex with components of the extracellular matrix may have an important role in force transmission and sarcolemma protection, and the sarcoglycan complex is an essential component of the muscle membrane located dystroglycan complex. We performed immunofluorescence and molecular analysis on the expression of sarcoglycan complex subunits. A total of 21 specimens of refluxing ureteral endings were obtained during ureteral reimplantation. Six ureteral ends obtained during organ explantation were used as controls. Immunohistochemical analysis and reverse transcriptase polymerase chain reaction evaluation were performed for alpha, beta, gamma, delta and epsilon-sarcoglycan complex. The Spearman test revealed a significant positive correlation between alpha-sarcoglycan complex immunofluorescence intensity and grade of vesicoureteral reflux, while a negative correlation was recorded between epsilon-sarcoglycan complex immunofluorescence intensity and grade of vesicoureteral reflux. Semiquantitative analysis demonstrated a significant grade related impairment of epsilon-sarcoglycan complex coupled with an increased expression of alpha-sarcoglycan complex. This observation suggests that the structural deficiency of the trigonal ureterovesical junction could cause a passive stretching of refluxing urine on the ureter, deranging the multimodular tensegrity architecture of the sarcoglycan subcomplex, or that the sarcoglycan complex could have a key role in the physiopathology of vesicoureteral reflux. In fact, the defect in any of the sarcoglycan complexes results in degeneration of membrane integrity and muscle fiber. An altered configuration of the sarcoglycan complex could explain the structural and functional changes in refluxing ureteral endings. Our observations underline the

  12. Gene Locater

    DEFF Research Database (Denmark)

    Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur

    2012-01-01

    UNLABELLED: Locating genes on a chromosome is important for understanding the gene function and its linkage and recombination. Knowledge of gene positions on chromosomes is necessary for annotation. The study is essential for disease genetics and genomics, among other aspects. Currently available...... software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...

  13. Application of gene detection technique in the antenatal diagnosis of hereditary hearing loss.

    Science.gov (United States)

    Fang, Y; Gu, M-S; Suo, F; Wang, C-X; Liu, X-H; Liu, F-M

    2017-04-01

    Gene chip and gene sequencing techniques were used to detect the main pathogenic genes in pregnant women with hereditary hearing loss. From May 2015 to May 2016, 1080 pregnant in Xuzhou Maternal and Child Health Hospital were enrolled in this study. Women age range was 18 to 40 years. 4 genes and 9 mutation sites, including 4 sites (35delG, 176, 235delC and 299) in GJB2 gene, 2 sites (2168A>G and IVS-7-2A>G) in SLC26A4 (PDS) gene, 2 sites (1494C>T and 1555A>G) in 12s rRNA gene and 1 site (538C>T) in GJB3 gene, were detected using the GeeDom® 9-item hereditary hearing loss gene detection kit. Deafness genes in the husband of the pregnant woman with GJB2 and SLC26A4 positive gene mutations were verified using Sanger sequencing. Fetuses with the same deafness genes as their parents were diagnosed before delivery using amniocentesis. 48 patients (4.45 %) were detected positive for hereditary hearing loss. Most of them (28 cases) were identified with GJB2 gene mutation (1 case with 176 site mutation, 22 cases with 235delC site mutation and 5 cases with 299 site mutation). We had 15 cases of the SLC26A4 gene mutation (3 cases of 2168A>G site mutation and 12 cases of IVS-7-2A>G site mutation), 2 cases of 538C>T site mutation of GJB3 gene and 3 cases of 1555A>G site mutation of 12s rRNA gene. The gene detection technique has a great health-economic significance in screening the main pathogenic genes involved in the hereditary hearing loss.

  14. Trichoderma genes

    Science.gov (United States)

    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.

  15. Gene Therapy

    Science.gov (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  16. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu

    2012-01-01

    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  17. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  18. Screening for MYO15A Gene Mutations in Autosomal Recessive Nonsyndromic, GJB2 Negative Iranian Deaf Population

    Science.gov (United States)

    Fattahi, Zohreh; Shearer, A. Eliot; Babanejad, Mojgan; Bazazzadegan, Niloofar; Almadani, Seyed Navid; Nikzat, Nooshin; Jalalvand, Khadijeh; Arzhangi, Sanaz; Esteghamat, Fatemehsadat; Abtahi, Rezvan; Azadeh, Batool; Smith, Richard J.H.; Kahrizi, Kimia; Najmabadi, Hossein

    2013-01-01

    MYO15A is located at the DFNB3 locus on chromosome 17p11.2, and encodes myosin-XV, an unconventional myosin critical for the formation of stereocilia in hair cells of cochlea. Recessive mutations in this gene lead to profound autosomal recessive nonsyndromic hearing loss (ARNSHL) in humans and the shaker2 (sh2) phenotype in mice. Here, we performed a study on 140 Iranian families in order to determine mutations causing ARNSHL. The families, who were negative for mutations in GJB2, were subjected to linkage analysis. Eight of these families showed linkage to the DFNB3 locus, suggesting a MYO15A mutation frequency of 5.71% in our cohort of Iranian population. Subsequent sequencing of the MYO15A gene led to identification of 7 previously unreported mutations, including 4 missense mutations, 1 nonsense mutation, and 2 deletions in different regions of the myosin-XV protein. PMID:22736430

  19. AcEST: DK962766 [AcEST

    Lifescience Database Archive (English)

    Full Text Available earch results ■■ - Swiss-Prot (release 56.9) Link to BlastX Result : Swiss-Prot sp_hit_id Q9ZTK5 Definition sp|Q9ZTK...ments: (bits) Value sp|Q9ZTK5|DAT_CATRO Deacetylvindoline O-acetyltransferase OS=...n 324A OS=Homo sapiens G... 30 8.6 sp|O70258|SGCE_MOUSE Epsilon-sarcoglycan OS=Mus musculus GN=Sgce... 30 8.6 >sp|Q9ZTK

  20. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    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 approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...

  1. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

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

  2. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as ...

  3. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available Gene regulatory processes lead to differential gene expression and are referred to as epigenetic phenomena; these are ubiquitous processes in the biological world. These reversible heritable changes concern DNA and RNA, their interactions...

  4. Polydactyly and genes

    National Research Council Canada - National Science Library

    Phadke, Shubha R; Sankar, V H

    2010-01-01

    .... A lot of information about genes involved in development is available now. Genetics of hand development and genes involved in polydactyly syndromes is discussed in this article as a prototype to know about genetics of malformations...

  5. Evolution of gene expression after gene amplification.

    Science.gov (United States)

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

    2015-04-24

    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 γ-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 γ-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. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. How Genes Evolve

    Indian Academy of Sciences (India)

    evolutionary history of duplicated genes within a given lineage. The timings of gene duplication events can be inferred ... evolutionary history of the creatures in which various globin genes are found, the timings of the ..... But I cannot find heart to give any part of my life for money-making purposes ... : In 1901, one of the large ...

  7. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  8. Gene therapy in periodontics

    Science.gov (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-01-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ‘the use of genes as medicine’. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone. PMID:23869119

  9. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  10. Modelling prokaryote gene content

    Directory of Open Access Journals (Sweden)

    Edward Susko

    2006-01-01

    Full Text Available The patchy distribution of genes across the prokaryotes may be caused by multiple gene losses or lateral transfer. Probabilistic models of gene gain and loss are needed to distinguish between these possibilities. Existing models allow only single genes to be gained and lost, despite the empirical evidence for multi-gene events. We compare birth-death models (currently the only widely-used models, in which only one gene can be gained or lost at a time to blocks models (allowing gain and loss of multiple genes within a family. We analyze two pairs of genomes: two E. coli strains, and the distantly-related Archaeoglobus fulgidus (archaea and Bacillus subtilis (gram positive bacteria. Blocks models describe the data much better than birth-death models. Our models suggest that lateral transfers of multiple genes from the same family are rare (although transfers of single genes are probably common. For both pairs, the estimated median time that a gene will remain in the genome is not much greater than the time separating the common ancestors of the archaea and bacteria. Deep phylogenetic reconstruction from sequence data will therefore depend on choosing genes likely to remain in the genome for a long time. Phylogenies based on the blocks model are more biologically plausible than phylogenies based on the birth-death model.

  11. Retrieval with gene queries

    Directory of Open Access Journals (Sweden)

    Srinivasan Padmini

    2006-04-01

    Full Text Available Abstract Background Accuracy of document retrieval from MEDLINE for gene queries is crucially important for many applications in bioinformatics. We explore five information retrieval-based methods to rank documents retrieved by PubMed gene queries for the human genome. The aim is to rank relevant documents higher in the retrieved list. We address the special challenges faced due to ambiguity in gene nomenclature: gene terms that refer to multiple genes, gene terms that are also English words, and gene terms that have other biological meanings. Results Our two baseline ranking strategies are quite similar in performance. Two of our three LocusLink-based strategies offer significant improvements. These methods work very well even when there is ambiguity in the gene terms. Our best ranking strategy offers significant improvements on three different kinds of ambiguities over our two baseline strategies (improvements range from 15.9% to 17.7% and 11.7% to 13.3% depending on the baseline. For most genes the best ranking query is one that is built from the LocusLink (now Entrez Gene summary and product information along with the gene names and aliases. For others, the gene names and aliases suffice. We also present an approach that successfully predicts, for a given gene, which of these two ranking queries is more appropriate. Conclusion We explore the effect of different post-retrieval strategies on the ranking of documents returned by PubMed for human gene queries. We have successfully applied some of these strategies to improve the ranking of relevant documents in the retrieved sets. This holds true even when various kinds of ambiguity are encountered. We feel that it would be very useful to apply strategies like ours on PubMed search results as these are not ordered by relevance in any way. This is especially so for queries that retrieve a large number of documents.

  12. Primetime for Learning Genes.

    Science.gov (United States)

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  13. Primetime for Learning Genes

    Directory of Open Access Journals (Sweden)

    Joyce Keifer

    2017-02-01

    Full Text Available Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF, by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli.

  14. Viral gene therapy.

    Science.gov (United States)

    Mancheño-Corvo, P; Martín-Duque, P

    2006-12-01

    Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

  15. Gene manupulations in invertebrates

    OpenAIRE

    Čermáková, Eliška

    2017-01-01

    Gene manipulations in invertebrates are based on the same approches used in vertebrates. The are applied for the development of new genotypes in model species, convenient as model systems of human hereditary diseases etc. Gene manipulations are important as well for practical purposes, which is shown by the example of trangenic mosquitoes. Recently, it has been proved that programmable nucleases can be successfully used in invertebrates. Key words: Gene manipulations, invertebrates, methods, ...

  16. Genes and Social Behavior

    OpenAIRE

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

    2008-01-01

    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence beh...

  17. History of gene therapy.

    Science.gov (United States)

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

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Chromatin loops, gene positioning, and gene expression

    NARCIS (Netherlands)

    Holwerda, S.; de Laat, W.

    2012-01-01

    Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the alpha- and beta-globin

  19. One gene's shattering effects.

    Science.gov (United States)

    Olsen, Kenneth M

    2012-05-29

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

  20. A multi-gene panel study in hereditary breast and ovarian cancer in Colombia.

    Science.gov (United States)

    Cock-Rada, A M; Ossa, C A; Garcia, H I; Gomez, L R

    2018-01-01

    Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene: BRCA1 (7), BRCA2 (8), PALB2 (1), ATM (1), MSH2 (1) and PMS2 (1). The frequency of mutations in BRCA1/2 was 17.6%. One BRCA2 mutation (c.9246dupG) was recurrent in five non-related individuals and is not previously reported in the country. Seventeen mutation-carriers had a diagnosis of breast cancer (median age of diagnosis of 36 years) and two of ovarian cancer. All BRCA1 mutation-carriers with breast cancer had triple negative tumors (median age of diagnosis of 31 years). Variants of unknown significance were reported in 35% of test results. This is the first report of a multi-gene study for hereditary breast and/or ovarian cancer in a Latin American country. We found a high frequency and a wide spectrum of germline mutations in cancer susceptibility genes in Colombian patients, some of which were not previously reported in the country. We observed a very low frequency of known Colombian founder BRCA1/2 mutations (1.2%) and we found mutations in other genes such as PALB2, ATM, MSH2 and PMS2. Our results highlight the importance of performing multi-gene panel testing, including comprehensive BRCA1/2 analysis (full gene sequencing and large rearrangement

  1. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S. M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  2. Gene therapy flexes muscle.

    Science.gov (United States)

    VandenDriessche, Thierry

    2005-09-01

    This commentary highlights the promising results of recent studies in animal models of Duchenne muscular dystrophy and amyotrophic lateral sclerosis that have clearly demonstrated the potential of gene therapy for tackling these diseases. In the absence of effective drugs or other treatments, these advances in gene therapy technology represent the best hope for those patients and families that are blighted by these diseases. Diseases characterized by progressive muscle degeneration are often incurable and affect a relatively large number of individuals. The progressive deterioration of muscle function is like the sword of Damocles that constantly reminds patients suffering from these diseases of their tragic fate, since most of them will eventually die from cardiac or pulmonary dysfunction. Some of these disorders are due to mutations in genes that directly influence the integrity of muscle fibers, such as in Duchenne muscular dystrophy (DMD), a recessive X-linked genetic disease. Others result from a progressive neurodegeneration of the motoneurons that are essential for maintaining muscle function, such as in amyotrophic lateral sclerosis (ALS), also commonly known as Lou Gehrig's disease. The genetic basis of DMD is relatively well understood as it is due to mutations in the dystrophin gene that encodes the cognate sarcolemmal protein. In contrast, the cause of ALS is poorly defined, with the exception of some dominantly inherited familial cases of ALS that are due to gain-of-function mutations in the gene encoding superoxide dismutase (SODG93A). Gene therapy for these disorders has been hampered by the inability to achieve widespread gene transfer. Moreover, since familial ALS is due to a dominant gain-of-function mutation, inhibition of gene expression (rather than gene augmentation) would be required to correct the phenotype, which is particularly challenging. Copyright (c) 2005 John Wiley & Sons, Ltd.

  3. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  4. Gene Therapy for Hemophilia.

    Science.gov (United States)

    Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D

    2017-10-01

    The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Genes underlying altruism.

    Science.gov (United States)

    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.

  6. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  7. Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Yusof Zurkurnai

    2011-03-01

    Full Text Available Abstract Background Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown. We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan. The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements. Results A total of 29 gene sequence variants were reported in 117(76.0% of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation, and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45. The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants. Conclusions Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.

  8. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    National Research Council Canada - National Science Library

    Adegoke, Olufemi

    2003-01-01

    The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

  10. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

  11. Ribosomal genes in focus

    Science.gov (United States)

    Koberna, Karel; Malínský, Jan; Pliss, Artem; Mašata, Martin; Večeřová, Jaromíra; Fialová, Markéta; Bednár, Jan; Raška, Ivan

    2002-01-01

    T he organization of transcriptionally active ribosomal genes in animal cell nucleoli is investigated in this study in order to address the long-standing controversy with regard to the intranucleolar localization of these genes. Detailed analyses of HeLa cell nucleoli include direct localization of ribosomal genes by in situ hybridization and their indirect localization via nascent ribosomal transcript mappings. On the light microscopy (LM) level, ribosomal genes map in 10–40 fluorescence foci per nucleus, and transcription activity is associated with most foci. We demonstrate that each nucleolar focus observed by LM corresponds, on the EM level, to an individual fibrillar center (FC) and surrounding dense fibrillar components (DFCs). The EM data identify the DFC as the nucleolar subcompartment in which rRNA synthesis takes place, consistent with detection of rDNA within the DFC. The highly sensitive method for mapping nascent transcripts in permeabilized cells on ultrastructural level provides intense and unambiguous clustered immunogold signal over the DFC, whereas very little to no label is detected over the FC. This signal is strongly indicative of nascent “Christmas trees” of rRNA associated with individual rDNA genes, sampled on the surface of thin sections. Stereological analysis of the clustered transcription signal further suggests that these Christmas trees may be contorted in space and exhibit a DNA compaction ratio on the order of 4–5.5. PMID:12034768

  12. On sports and genes.

    Science.gov (United States)

    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.

  13. Recombination in immunoglobulin gene loci

    Directory of Open Access Journals (Sweden)

    Komisarenko S. V.

    2009-02-01

    Full Text Available Gene network of the lymphoid cell differentiation coordinates precisely the recombination process in immunoglobulin gene loci. In our opinion, cellular microRNAs can contribute to the allelic exclusion through microRNA-directed DNA methylation and participate in retargeting recombinases activity from the gene loci of heavy immunoglobulin chains to the gene loci of light chains

  14. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  15. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel

    2007-01-01

    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  16. Mechanisms of Horizontal Gene Transfer

    OpenAIRE

    Cafini Barrado, Fabio; Medrano Romero, Verónica; Morikawa, Kazuya

    2017-01-01

    Horizontal gene transfer plays important roles in the evolution of S. aureus, and indeed, a variety of virulence factors and antibiotic resistance genes are embedded in a series of mobile genetic elements. In this chapter, we review the mechanisms of horizontal gene transfer, including recent findings on the natural genetic competence. Then, we consider the transfer of two important antibiotic resistance genes: the methicillin resistance gene, mecA (in Staphylococcal Cassette Chromosome) and ...

  17. Idiomatic (gene) expressions.

    Science.gov (United States)

    Rockman, Matthew V

    2003-05-01

    Hidden among the myriad nucleotide variants that constitute each species' gene pool are a few variants that contribute to phenotypic variation. Many of these differences that make a difference are non-coding cis-regulatory variants, which, unlike coding variants, can only be identified through laborious experimental analysis. Recently, Cowles et al.1 described a screening method that does an end-run around this problem by searching for genes whose cis regulation varies without having to find the polymorphic nucleotides that influence transcription. While we will continue to require a diverse arsenal of experimental methods, this versatile method will speed the identification of functional genetic variation. Copyright 2003 Wiley Periodicals, Inc.

  18. A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome.

    Science.gov (United States)

    Lin, Eugene; Hsu, Sen-Yen

    2009-01-01

    In the study of genomics, it is essential to address gene-gene and gene-environment interactions for describing the complex traits that involves disease-related mechanisms. In this work, our goal is to detect gene-gene and gene-environment interactions resulting from the analysis of chronic fatigue syndrome patients' genetic and demographic factors including SNPs, age, gender and BMI. We employed the dataset that was original to the previous study by the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Research Group. To investigate gene-gene and gene-environment interactions, we implemented a Bayesian based method for identifying significant interactions between factors. Here, we employed a two-stage Bayesian variable selection methodology based on Markov Chain Monte Carlo approaches. By applying our Bayesian based approach, NR3C1 was found in the significant two-locus gene-gene effect model, as well as in the significant two-factor gene-environment effect model. Furthermore, a significant gene-environment interaction was identified between NR3C1 and gender. These results support the hypothesis that NR3C1 and gender may play a role in biological mechanisms associated with chronic fatigue syndrome. We demonstrated that our Bayesian based approach is a promising method to assess the gene-gene and gene-environment interactions in chronic fatigue syndrome patients by using genetic factors, such as SNPs, and demographic factors such as age, gender and BMI.

  19. Neighboring Genes Show Correlated Evolution in Gene Expression

    Science.gov (United States)

    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 (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

  20. Gene Therapy and Children (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Gene Therapy and Children KidsHealth > For Parents > Gene Therapy and ... by a "bad" gene. continue Two Types of Gene Therapy The two forms of gene therapy are: Somatic ...

  1. Ultrasound mediated gene transfection

    Science.gov (United States)

    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.

  2. What is a Gene?

    Indian Academy of Sciences (India)

    His other interests include reading, photography and listening to classical music. The first part of this general article appeared in April 1997. S C Lakhotia. The first part of this article traced the evolution of the concept of a gene from Mendel's times to the middle of this century: starting from the imaginary factors of Mendel, the.

  3. Genes in mammalian reproduction

    Energy Technology Data Exchange (ETDEWEB)

    Gwatkin, R.B.L. [ed.

    1996-11-01

    This is an informative book which deals mainly with genomic imprinting, the role of steroid hormones in development, the expression of a variety of genes during development and the link to hereditary diseases. It is an up-to-date review in a field that is quickly changing and provides valuable basic information and current research trends.

  4. (FIE) gene from soybean

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-04-17

    Apr 17, 2012 ... Harb. Protoc. doi:10.1101/pdb.prot4666. Xu H, Li Y, Yan Y, Wang K, Gao Y, Hu Y (2010). Genome-scale identification of Soybean BURP domain-containing genes and their expression under stress treatments. BMC Plant Biol. 10: 197. Yadegari R, Kinoshita T, Lotan O, Cohen G, Katz A, Choi Y, Nakashima.

  5. Silence of the Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 4. Silence of the Genes - 2006 Nobel Prize in Physiology or Medicine. Utpal Nath Saumitra Das. General Article Volume 12 Issue 4 April 2007 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Silence of the Genes

    Indian Academy of Sciences (India)

    Srimath

    research for several decades (See Resonance, Vol. 12, pp.47–53,. March 2007). RNA interference (RNAi) is a novel mechanism for controlling gene expression. In this mechanism, tiny double-stranded RNA molecules called 'small interfering RNA' (siRNA) degrade cellu- lar mRNA that has sequence similarity with them.

  7. Gene therapy in pancreatic cancer

    Science.gov (United States)

    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

  8. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  9. Using gene expression noise to understand gene regulation

    NARCIS (Netherlands)

    Munsky, B.; Neuert, G.; van Oudenaarden, A.

    2012-01-01

    Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

  10. Gene set analysis for longitudinal gene expression data

    Directory of Open Access Journals (Sweden)

    Piepho Hans-Peter

    2011-07-01

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

  11. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  12. Genes, stress, and depression.

    Science.gov (United States)

    Wurtman, Richard J

    2005-05-01

    A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls

  13. Vertebrate gene predictions and the problem of large genes

    DEFF Research Database (Denmark)

    Wang, Jun; Li, ShengTing; Zhang, Yong

    2003-01-01

    To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistent...

  14. Gene Therapy for Lung Cancer.

    Science.gov (United States)

    Lara-Guerra, Humberto; Roth, Jack A

    2016-01-01

    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein.

  15. Gene therapy in keratoconus

    Directory of Open Access Journals (Sweden)

    Mahgol Farjadnia

    2015-01-01

    Full Text Available 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.

  16. The sulfatase gene family.

    Science.gov (United States)

    Parenti, G; Meroni, G; Ballabio, A

    1997-06-01

    During the past few years, molecular analyses have provided important insights into the biochemistry and genetics of the sulfatase family of enzymes, identifying the molecular bases of inherited diseases caused by sulfatase deficiencies. New members of the sulfatase gene family have been identified in man and other species using a genomic approach. These include the gene encoding arylsulfatase E, which is involved in X-linked recessive chondrodysplasia punctata, a disorder of cartilage and bone development. Another important breakthrough has been the discovery of the biochemical basis of multiple sulfatase deficiency, an autosomal recessive disorder characterized by a severe of all sulfatase activities. These discoveries, together with the resolution of the crystallographic structure of sulfatases, have improved our understanding of the function and evolution of this fascinating family of enzymes.

  17. Brains, Genes and Primates

    Science.gov (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; 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

    2015-01-01

    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

  18. PRRT2 gene mutations

    Science.gov (United States)

    Gardiner, Alice R.; Bhatia, Kailash P.; Stamelou, Maria; Dale, Russell C.; Kurian, Manju A.; Schneider, Susanne A.; Wali, G.M.; Counihan, Tim; Schapira, Anthony H.; Spacey, Sian D.; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A.G.; Raskin, Salmo; Sander, Josemir W.; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M.; Wood, Nicholas W.; Hanna, Michael

    2012-01-01

    ABSTRACT Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. PMID:23077024

  19. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

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

  20. Genealogy and gene trees.

    Science.gov (United States)

    Rasmuson, Marianne

    2008-02-01

    Heredity can be followed in persons or in genes. Persons can be identified only a few generations back, but simplified models indicate that universal ancestors to all now living persons have occurred in the past. Genetic variability can be characterized as variants of DNA sequences. Data are available only from living persons, but from the pattern of variation gene trees can be inferred by means of coalescence models. The merging of lines backwards in time leads to a MRCA (most recent common ancestor). The time and place of living for this inferred person can give insights in human evolutionary history. Demographic processes are incorporated in the model, but since culture and customs are known to influence demography the models used ought to be tested against available genealogy. The Icelandic data base offers a possibility to do so and points to some discrepancies. Mitochondrial DNA and Y chromosome patterns give a rather consistent view of human evolutionary history during the latest 100 000 years but the earlier epochs of human evolution demand gene trees with longer branches. The results of such studies reveal as yet unsolved problems about the sources of our genome.

  1. Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Su

    Full Text Available BACKGROUND: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1, the gene coding interleukin-4 receptor alpha chain (IL4Ra and the gene coding insulin induced gene 2 (INSIG2 on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2, signal transducer and activator of transcription 6 (STAT6. We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.

  2. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  3. Independent Gene Discovery and Testing

    Science.gov (United States)

    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…

  4. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Rapley, Ralph; Aquino de Muro, Marilena

    2002-01-01

    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  5. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin

    2002-01-01

    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  6. Optimal gene partition into operons correlates with gene functional order

    Science.gov (United States)

    Zaslaver, Alon; Mayo, Avi; Ronen, Michal; Alon, Uri

    2006-09-01

    Gene arrangement into operons varies between bacterial species. Genes in a given system can be on one operon in some organisms and on several operons in other organisms. Existing theories explain why genes that work together should be on the same operon, since this allows for advantageous lateral gene transfer and accurate stoichiometry. But what causes the frequent separation into multiple operons of co-regulated genes that act together in a pathway? Here we suggest that separation is due to benefits made possible by differential regulation of each operon. We present a simple mathematical model for the optimal distribution of genes into operons based on a balance of the cost of operons and the benefit of regulation that provides 'just-when-needed' temporal order. The analysis predicts that genes are arranged such that genes on the same operon do not skip functional steps in the pathway. This prediction is supported by genomic data from 137 bacterial genomes. Our work suggests that gene arrangement is not only the result of random historical drift, genome re-arrangement and gene transfer, but has elements that are solutions of an evolutionary optimization problem. Thus gene functional order may be inferred by analyzing the operon structure across different genomes.

  7. Somatic gene therapy for dyslipidemias.

    Science.gov (United States)

    Belalcazar, M; Chan, L

    1999-09-01

    Somatic gene transfer is a valuable tool for the in vivo evaluation of lipoprotein metabolism. It has been used to dissect metabolic pathways, to establish structure-function relationships of various gene products, and to evaluate conventional lipid-lowering and novel therapeutic genes for the treatment of lipoprotein disorders. In this article we review some general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. We highlight some recent advances in adenoviral vector development that make this vector an attractive system for clinical trials.

  8. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie

    2014-01-01

    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapte...... describes how gene therapy may be performed using electric pulses to enhance uptake and expression.......Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapter...

  9. Tumor-suppressing gene therapy.

    Science.gov (United States)

    Fang, Bingliang; Roth, Jack A

    2003-01-01

    Tumor-suppressor genes play pivotal roles in maintaining genome integrity and in regulating cell proliferation, differentiation, and apoptosis. Their loss-of-function mutations are related directly to tumorigenesis. Thus, use of tumor-suppressor genes as anticancer therapeutics has been investigated rigorously in both experimental and clinical researches. Transfer of various tumor-suppressor genes directly to cancer cells has been demonstrated to suppress tumor growth via induction of apoptosis and cell-cycle arrest and, in some cases, with evidence for bystander effects. Various studies also have shown that combination of tumor-suppressor gene therapy with conventional anticancer therapy can yield synergistic therapeutic benefits. Clinical trials with tumor-suppressor genes, especially the p53 gene, have demonstrated that the treatment is well tolerated, and; favorable clinical responses, including a pathologically complete responses, have been observed in a subset of patients with advanced disease or with cancers resistant to conventional therapy. Yet, current gene replacement approaches in cancer gene therapy must be improved if they are to have a broader clinical impact. Efficient systemic gene delivery systems will be required ultimately for treatment of metastatic disease. In this review, we have recently summarized achievements in tumor-suppressor gene therapy with a focus on the p53 gene.

  10. Horizontal gene transfer in choanoflagellates.

    Science.gov (United States)

    Tucker, Richard P

    2013-01-01

    Horizontal gene transfer (HGT), also known as lateral gene transfer, results in the rapid acquisition of genes from another organism. HGT has long been known to be a driving force in speciation in prokaryotes, and there is evidence for HGT from symbiotic and infectious bacteria to metazoans, as well as from protists to bacteria. Recently, it has become clear that as many as a 1,000 genes in the genome of the choanoflagellate Monosiga brevicollis may have been acquired by HGT. Interestingly, these genes reportedly come from algae, bacteria, and other choanoflagellate prey. Some of these genes appear to have allowed an ancestral choanoflagellate to exploit nutrient-poor environments and were not passed on to metazoan descendents. However, some of these genes are also found in animal genomes, suggesting that HGT into a common ancestor of choanozoans and animals may have contributed to metazoan evolution. Copyright © 2012 Wiley Periodicals, Inc.

  11. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract 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 the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2009-09-03

    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. 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. 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.

  14. Gene circuit analysis of the terminal gap gene huckebein.

    Directory of Open Access Journals (Sweden)

    Maksat Ashyraliyev

    2009-10-01

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

  15. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M

    2008-10-01

    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  16. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  17. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

    2015-01-01

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

  18. The infinitely many genes model with horizontal gene transfer

    OpenAIRE

    Baumdicker, Franz; Pfaffelhuber, Peter

    2013-01-01

    The genome of bacterial species is much more flexible than that of eukaryotes. Moreover, the distributed genome hypothesis for bacteria states that the total number of genes present in a bacterial population is greater than the genome of every single individual. The pangenome, i.e. the set of all genes of a bacterial species (or a sample), comprises the core genes which are present in all living individuals, and accessory genes, which are carried only by some individuals. In order to use acce...

  19. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12, a previou......We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  20. Gene therapy for psychiatric disorders.

    Science.gov (United States)

    Gelfand, Yaroslav; Kaplitt, Michael G

    2013-01-01

    Gene therapy has become of increasing interest in clinical neurosurgery with the completion of numerous clinical trials for Parkinson disease, Alzheimer disease, and pediatric genetic disorders. With improved understanding of the dysfunctional circuitry mediating various psychiatric disorders, deep brain stimulation for refractory psychiatric diseases is being increasingly explored in human patients. These factors are likely to facilitate development of gene therapy for psychiatric diseases. Because delivery of gene therapy agents would require the same surgical techniques currently being employed for deep brain stimulation, neurosurgeons are likely to lead the development of this field, as has occurred in other areas of clinical gene therapy for neurologic disorders. We review the current state of gene therapy for psychiatric disorders and focus specifically on particular areas of promising research that may translate into human trials for depression, drug addiction, obsessive-compulsive disorder, and schizophrenia. Issues that are relatively unique to psychiatric gene therapy are also discussed. Copyright © 2013. Published by Elsevier Inc.

  1. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic...... parameter and the genesis and distribution of the gene-level statistics, and illustrate the effects of differential weighting in a real-life example....

  2. A genetic ensemble approach for gene-gene interaction identification

    Directory of Open Access Journals (Sweden)

    Ho Joshua WK

    2010-10-01

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

  3. Gene therapy for hemophilia

    Science.gov (United States)

    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

  4. Introduction: Cancer Gene Networks.

    Science.gov (United States)

    Clarke, Robert

    2017-01-01

    Constructing, evaluating, and interpreting gene networks generally sits within the broader field of systems biology, which continues to emerge rapidly, particular with respect to its application to understanding the complexity of signaling in the context of cancer biology. For the purposes of this volume, we take a broad definition of systems biology. Considering an organism or disease within an organism as a system, systems biology is the study of the integrated and coordinated interactions of the network(s) of genes, their variants both natural and mutated (e.g., polymorphisms, rearrangements, alternate splicing, mutations), their proteins and isoforms, and the organic and inorganic molecules with which they interact, to execute the biochemical reactions (e.g., as enzymes, substrates, products) that reflect the function of that system. Central to systems biology, and perhaps the only approach that can effectively manage the complexity of such systems, is the building of quantitative multiscale predictive models. The predictions of the models can vary substantially depending on the nature of the model and its inputoutput relationships. For example, a model may predict the outcome of a specific molecular reaction(s), a cellular phenotype (e.g., alive, dead, growth arrest, proliferation, and motility), a change in the respective prevalence of cell or subpopulations, a patient or patient subgroup outcome(s). Such models necessarily require computers. Computational modeling can be thought of as using machine learning and related tools to integrate the very high dimensional data generated from modern, high throughput omics technologies including genomics (next generation sequencing), transcriptomics (gene expression microarrays; RNAseq), metabolomics and proteomics (ultra high performance liquid chromatography, mass spectrometry), and "subomic" technologies to study the kinome, methylome, and others. Mathematical modeling can be thought of as the use of ordinary

  5. Pompe disease gene therapy

    Science.gov (United States)

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

    2011-01-01

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

  6. Mutation spectrum of β-globin gene in thalassemia patients at Hasan Sadikin Hospital - West Java Indonesia.

    Science.gov (United States)

    Maskoen, Ani Melani; Rahayu, Nurul S; Reniarti, Lelani; Susanah, Susi; Laksono, Bremmy; Fauziah, Prima Nanda; Zada, Almira; Hidayat, Dadang S

    2017-12-30

    Thalassemia is the most common hereditary haemolytic anemia in Southeast Asia, in which Indonesia is among countries that are at a high risk for thalassemia. It has been reported that mutation in the beta-globin gene is responsible in severe Thalassemia. However, the spectrum of beta-globin gene mutations in Indonesian population varies in different regions . Thus, this study aimed to identify the most prevalent mutation of Thalassemia patients from the Hasan Sadikin Hospital, Bandung, using this as a reference hospital for Thalassemia in West Java. The three most prevalent mutations of beta globin (IVS1nt5, Cd26 (HbE), and IVS1nt1), were conducted in the beginning of this study. Mutations of 291 samples were detected by PCR-RFLP in the Molecular Genetic Laboratory, Faculty of Medicine Universitas Padjadjaran, Bandung. The prevalence of the beta globin gene mutation types were 47.4% IVS1nt5 homozygote, 9.9% compound heterozygote IVS1nt5/HbE, 5.4% compound heterozygote IVS1nt5/IVS1nt1, 1.4% compound heterozygote HbE/IVS1nt1, 1% HbE homozygote, 14.4% Compound heterzygote IVS1nt5/… (no paired mutation), 2.06% compound heterozygote HbE/… (no paired mutation), 1.3% compound heterozygote IVS1nt1/… (no paired mutation), and 7 samples were unidentified. The thalassemia mutation IVS1nt5 homozygote is the most common mutation found in Thalassemia patients at Hasan Sadikin Hospital, Bandung. The samples with unidentified results might carry mutations other than the three that are observed in the present study.

  7. Gene therapy for meningioma : improved gene delivery with targeted adenoviruses

    NARCIS (Netherlands)

    Dirven, CMF; Grill, J; Lamfers, MLM; Van der Valk, P; Leonhart, AM; Van Beusechem, VW; Haisma, HJ; Pinedo, HM; Curiel, DT; Vandertop, WP; Gerritsen, WR

    Object. Due to their surgical inaccessibility or aggressive behavior, some meningiomas cannot be cured with current treatment strategies. Gene therapy is an emerging strategy for the treatment of brain tumors, which the authors investigated to determine whether adenoviruses could be used for gene

  8. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    H. Lin (Honghuang); M. Mueller-Nurasyid; A.V. Smith (Albert Vernon); D.E. Arking (Dan); J. Barnard (John); T.M. Bartz (Traci M.); K.L. Lunetta (Kathryn); K. Lohman (Kurt); M.E. Kleber (Marcus); S.A. Lubitz (Steven); Geelhoed, B. (Bastiaan); S. Trompet (Stella); M.N. Niemeijer (Maartje); T. Kacprowski (Tim); D.I. Chasman (Daniel); Klarin, D. (Derek); M.F. Sinner (Moritz); M. Waldenberger (Melanie); T. Meitinger (Thomas); T.B. Harris (Tamara); L.J. Launer (Lenore); E.Z. Soliman (Elsayed Z.); L. Chen (Lin); J.D. Smith (Jonathan); D.R. van Wagoner (David); Rotter, J.I. (Jerome I.); B.M. Psaty (Bruce); Xie, Z. (Zhijun); A.E. Hendricks (Audrey E.); Ding, J. (Jingzhong); G.E. Delgado (Graciela E.); N. Verweij (Niek); P. van der Harst (Pim); P.W. MacFarlane (Peter); I. Ford (Ian); A. Hofman (Albert); A.G. Uitterlinden (André); J. Heeringa (Jan); O.H. Franco (Oscar); J.A. Kors (Jan); Weiss, S. (Stefan); H. Völzke (Henry); L.M. Rose (Lynda); Natarajan, P. (Pradeep); S. Kathiresan (Sekar); S. Kääb (Stefan); V. Gudnason (Vilmundur); A. Alonso (Alvaro); M.K. Chung (Mina); S.R. Heckbert (Susan); E.J. Benjamin (Emelia); Y. Liu (Yongmei); W. März (Winfried); S.A. Rienstra; J.W. Jukema (Jan Wouter); B.H.Ch. Stricker (Bruno); M. Dörr (Marcus); C.M. Albert (Christine); P.T. Ellinor (Patrick)

    2016-01-01

    textabstractAtrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility.

  9. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    Lin, Honghuang; Mueller-Nurasyid, Martina; Smith, Albert V.; Arking, Dan E.; Barnard, John; Bartz, Traci M.; Lunetta, Kathryn L.; Lohman, Kurt; Kleber, Marcus E.; Lubitz, Steven A.; Geelhoed, Bastiaan; Trompet, Stella; Niemeijer, Maartje N.; Kacprowski, Tim; Chasman, Daniel I.; Klarin, Derek; Sinner, Moritz F.; Waldenberger, Melanie; Meitinger, Thomas; Harris, Tamara B.; Launer, Lenore J.; Soliman, Elsayed Z.; Chen, Lin Y.; Smith, Jonathan D.; Van Wagoner, David R.; Rotter, Jerome I.; Psaty, Bruce M.; Xie, Zhijun; Hendricks, Audrey E.; Ding, Jingzhong; Delgado, Graciela E.; Verweij, Niek; van der Harst, Pim; Macfarlane, Peter W.; Ford, Ian; Hofman, Albert; Uitterlinden, Andre; Heeringa, Jan; Franco, Oscar H.; Kors, Jan A.; Weiss, Stefan; Volzke, Henry; Rose, Lynda M.; Natarajan, Pradeep; Kathiresan, Sekar; Kaab, Stefan; Gudnason, Vilmundur; Alonso, Alvaro; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Liu, Yongmei; Marz, Winfried; Rienstra, Michiel; Jukema, J. Wouter; Stricker, Bruno H.; Dorr, Marcus; Albert, Christine M.; Ellinor, Patrick T.

    2016-01-01

    Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed

  10. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas

    2010-05-01

    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  11. Electro-acupuncture-mediated gene transfer.

    Science.gov (United States)

    Zhang, J; Qin, Y; Fu, A; Tang, J; Chen, G; Cai, D; Han, J

    1998-10-01

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

  12. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  13. Uncovering trends in gene naming

    OpenAIRE

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

    2008-01-01

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

  14. Uncovering trends in gene naming.

    Science.gov (United States)

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

    2008-01-31

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

  15. Gene Synthesis with HG Khorana

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 12. Gene Synthesis with H G Khorana. Marvin H Caruthers. General Article Volume 17 Issue 12 December 2012 pp ... Keywords. Chemical synthesis of genes for yeast alanine tRNA and E. coli supressor tRNA; Khorana's philosophy on science.

  16. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available 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.

  17. On meme--gene coevolution.

    Science.gov (United States)

    Bull, L; Holland, O; Blackmore, S

    2000-01-01

    In this article 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, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability.

  18. Sarcoglycan subcomplex expression in normal human smooth muscle.

    Science.gov (United States)

    Anastasi, Giuseppe; Cutroneo, Giuseppina; Sidoti, Antonina; Rinaldi, Carmen; Bruschetta, Daniele; Rizzo, Giuseppina; D'Angelo, Rosalia; Tarone, Guido; Amato, Aldo; Favaloro, Angelo

    2007-08-01

    The sarcoglycan complex (SGC) is a multimember transmembrane complex interacting with other members of the dystrophin-glycoprotein complex (DGC) to provide a mechanosignaling connection from the cytoskeleton to the extracellular matrix. The SGC consists of four proteins (alpha, beta, gamma, and delta). A fifth sarcoglycan subunit, epsilon-sarcoglycan, shows a wider tissue distribution. Recently, a novel sarcoglycan, the zeta-sarcoglycan, has been identified. All reports about the structure of SGC showed a common assumption of a tetrameric arrangement of sarcoglycans. Addressing this issue, our immunofluorescence and molecular results showed, for the first time, that all sarcoglycans are always detectable in all observed samples. Therefore, one intriguing possibility is the existence of a pentameric or hexameric complex considering zeta-sarcoglycan of SGC, which could present a higher or lower expression of a single sarcoglycan in conformity with muscle type--skeletal, cardiac, or smooth--or also in conformity with the origin of smooth muscle.

  19. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa....... Not is a homeobox containing gene that regulates the formation of the notochord in chordates, while Cdx (caudal) is a ParaHox gene involved in the formation of posterior tissues of various animal phyla. The T. transversa homolog, TtrNot, is expressed in the ectoderm from the beginning of gastrulation until...... formation. TtrNot expression is absent in unfertilized eggs, in embryos prior to gastrulation, and in settled individuals during and after metamorphosis. Comparison with the expression patterns of Not genes in other metazoan phyla suggests an ancestral role for this gene in gastrulation and germ layer...

  20. CNS Genes Implicated in Relapse

    Directory of Open Access Journals (Sweden)

    Willard M. Freeman

    2008-01-01

    Full Text Available 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 drug use and ensuing abstinence. Such stable changes in gene expression correlate with ultrastructural changes in brain as well as alterations in behavior. As persistent molecular changes, these genes may provide targets for the development of therapeutics. Developing a list of well-characterized candidate genes and examining the effect of manipulating these genes will contribute to the ultimate goal of developing effective treatments to prevent relapse to drug use.

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

    Science.gov (United States)

    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.

  2. Gene recognition by combination of several gene-finding programs.

    Science.gov (United States)

    Murakami, K; Takagi, T

    1998-01-01

    A number of programs have been developed to predict the eukaryotic gene structures in DNA sequences. However, gene finding is still a challenging problem. We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2). By HIGHEST-policy combination method or BOUNDARY method, approximate correlation (AC) improved by 3-5% in comparison with the best single gene-finding program. From another viewpoint, OR-based combination of the four programs is the most reliable to know whether a candidate exon overlaps with the real exon or not, although it is less sensitive than GENSCAN for exon-intron boundaries. Our methods can easily be extended to combine other programs. We have developed a server program (Shirokane System) and a client program (GeneScope) to use the methods. GeneScope is available through a WWW site (http://gf.genome.ad.jp/). (katsu,takagi)@ims.u-tokyo.ac.jp

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

    Science.gov (United States)

    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.

  4. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2013-12-01

    Full Text Available 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.

  5. Phylogenetic analysis of gene expression.

    Science.gov (United States)

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

    2013-11-01

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

  6. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Science.gov (United States)

    Zhou, Xiaobo; Wang, Xiaodong; Dougherty, Edward R.

    2004-12-01

    A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  7. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Directory of Open Access Journals (Sweden)

    Wang Xiaodong

    2004-01-01

    Full Text Available A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  8. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  9. Evidence based selection of housekeeping genes

    NARCIS (Netherlands)

    de Jonge, Hendrik J. M.; Fehrmann, Rudolf S. N.; de Bont, Eveline S. J. M.; Hofstra, Robert M. W.; Gerbens, Frans; Kamps, Willem A.; de Vries, Elisabeth G. E.; van der Zee, Ate G. J.; te Meerman, Gerard J.; ter Elst, Arja

    2007-01-01

    For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e. g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental

  10. Human Lacrimal Gland Gene Expression.

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Aakalu

    Full Text Available The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development.We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium.The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described.Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.

  11. GENES IN SPORT AND DOPING

    Science.gov (United States)

    Kaliszewski, P.; Majorczyk, E.; Zembroń-Łacny, A.

    2013-01-01

    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

  12. GENES IN SPORT AND DOPING

    Directory of Open Access Journals (Sweden)

    Andrzej Pokrywka

    2013-06-01

    Full Text Available 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.

  13. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne

    2007-01-01

    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 mus......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

  14. Cloning and selection of reference genes for gene expression ...

    African Journals Online (AJOL)

    Full length mRNA sequences of Ac-β-actin and Ac-gapdh, and partial mRNA sequences of Ac-18SrRNA and Ac-ubiquitin were cloned from pineapple in this study. The four genes were tested as housekeeping genes in three experimental sets. GeNorm and NormFinder analysis revealed that β-actin was the most ...

  15. Gene therapy of cancer by vaccines carrying inserted immunostimulatory genes

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2007-01-01

    Roč. 53, č. 3 (2007), s. 71-73 ISSN 0015-5500 Grant - others:EU-FP6 NoE Clinigene(XE) 018933; Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : gene therapy * immunostimulatory genes * vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.596, year: 2007

  16. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  17. Gene Therapy Approaches to Hemoglobinopathies.

    Science.gov (United States)

    Ferrari, Giuliana; Cavazzana, Marina; Mavilio, Fulvio

    2017-10-01

    Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Panspermia and horizontal gene transfer

    Science.gov (United States)

    Klyce, Brig

    2009-08-01

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

  19. Genomics screens for metastasis genes

    Science.gov (United States)

    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

  20. Recurring dominant-negative mutations in the AVP-NPII gene cause neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Repaske, D.R. [Children`s Hospital Medical Center, Cincinnati, OH (United States); Phillips, J.A.; Krishnamani, M.R.S. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others

    1994-09-01

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a familial form of arginine vasopressin (or antidiuretic hormone) deficiency that is usually manifest in early childhood with polyuria, polydipsia and an antidiuretic response to exogenous vasopressin or its analogs. The phenotype is postulated to arise from gliosis and depletion of the magnocellular neurons that produce vasopressin in the supraoptic and paraventricular nuclei of the hypothalamus. ADNDI is caused by heterozygosity for a variety of mutations in the AVP-NPII gene which encodes vasopressin, its carrier protein (NPII) and a glycoprotein (copeptin) of unknown function. These mutations include: (1) Ala 19{r_arrow}Thr (G279A) in AVP`s signal peptide, (2) Gly 17{r_arrow}Val (G1740T), (3) Pro 24{r_arrow}Leu (C1761T), (4) Gly 57{r_arrow}Ser (G1859A) and (5) del Glu 47({delta}AGG 1824-26), all of which occur in NPII. In characterizing the AVP-NPII mutations in five non-related ADNDI kindreds, we have detected two kindreds having mutation 1 (G279A), two having mutation 3 (C1761T) and one having mutation 4 (G1859A) without any other allelic changes being detected. Two of these recurring mutations (G279A and G1859A) are transitions that occur at CpG dinucleotides while the third (C1761T) does not. Interestingly, families with the same mutations differed in their ethnicity or in their affected AVP-NPII allele`s associated haplotype of closely linked DNA polymorphisms. Our data indicated that at least three of five known AVP-NPII mutations causing ADNDI tend to recur but the mechanisms by which these dominant-negative mutations cause variable or progressive expression of the ADNDI phenotype remain unclear.

  1. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Chicago Learn More Close The American Society of Gene & Cell Therapy ASGCT is the primary membership organization for scientists, ... Therapeutics Official Journal of the American Society of Gene & Cell Therapy Molecular Therapy is the leading journal for gene ...

  2. Gene Expression Analysis of Breast Cancer Progression

    National Research Council Canada - National Science Library

    Gerald, Wiliam L

    2004-01-01

    ... to identify genes, gene expression profiles and molecular pathways associated with metastatic BC we have performed genome-wide gene expression analysis of a large number of breast cancer samples...

  3. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  4. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.

    2016-01-01

    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered...

  5. Sleep deprivation and gene expression.

    Science.gov (United States)

    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.

  6. Gene Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Rachel Denyer

    2012-01-01

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

  7. Deregulated genes in sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric

    2010-01-01

    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....

  8. Gene expression based cancer classification

    OpenAIRE

    Sara Tarek; Reda Abd Elwahab; Mahmoud Shoman

    2017-01-01

    Cancer classification based on molecular level investigation has gained the interest of researches as it provides a systematic, accurate and objective diagnosis for different cancer types. Several recent researches have been studying the problem of cancer classification using data mining methods, machine learning algorithms and statistical methods to reach an efficient analysis for gene expression profiles. Studying the characteristics of thousands of genes simultaneously offered a deep in...

  9. Transgenic Arabidopsis Gene Expression System

    Science.gov (United States)

    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.

  10. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  11. Rice Multi-Gene Analysis

    Indian Academy of Sciences (India)

    gdyang

    Maps of all the intronic MIR genes analyzed using MPSS database in rice. Click here for a legend that explains the icons and colors in the image below. Click here to jump in the page below to the specific gene. osa-MIR159f osa-MIR399i osa-MIR418 osa-MIR437 osa-MIR439b osa-MIR439j osa-MIR440 osa-MIR442.

  12. Degradable Polymers for Gene Delivery

    Science.gov (United States)

    Sunshine, Joel; Bhise, Nupura; Green, Jordan J.

    2014-01-01

    Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure led to significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than Lipofectamine 2000 or polyethylenimine for gene delivery to cancerous fibroblasts or human primary fibroblasts. These materials may be useful for cancer therapeutics and regenerative medicine. PMID:19964958

  13. Cationic Bolaamphiphiles for Gene Delivery

    Science.gov (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  14. ASPM gene expression in medulloblastoma.

    Science.gov (United States)

    Vulcani-Freitas, Tânia M; Saba-Silva, Najsla; Cappellano, Andréa; Cavalheiro, Sérgio; Marie, Sueli K N; Oba-Shinjo, Sueli M; Malheiros, Suzana M F; de Toledo, Sílvia Regina Caminada

    2011-01-01

    Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

  15. Genetics and Disease Expression in the CNGA3 Form of Achromatopsia: Steps on the Path to Gene Therapy.

    Science.gov (United States)

    Zelinger, Lina; Cideciyan, Artur V; Kohl, Susanne; Schwartz, Sharon B; Rosenmann, Ada; Eli, Dalia; Sumaroka, Alexander; Roman, Alejandro J; Luo, Xunda; Brown, Cassondra; Rosin, Boris; Blumenfeld, Anat; Wissinger, Bernd; Jacobson, Samuel G; Banin, Eyal; Sharon, Dror

    2015-05-01

    Achromatopsia (ACHM) is a congenital, autosomal recessive retinal disease that manifests cone dysfunction, reduced visual acuity and color vision, nystagmus, and photoaversion. Five genes are known causes of ACHM. The present study took steps toward performing a trial of gene therapy in ACHM by characterizing the genetics of ACHM in Israel and the Palestinian Territories and analyzing retinal function and structure in CNGA3 ACHM patients from the Israeli-Palestinian population and US patients with other origins. Case series study. Patients with clinically suspected ACHM, cone dysfunction phenotypes, and unaffected family members were included. The protocol was approved by the local institutional review board and informed consent was obtained from all participants. Genetic analyses included homozygosity mapping and exome sequencing. Phenotype was assessed with electroretinography (ERG), optical coherence tomography, psychophysics, and photoaversion testing. Single nucleotide polymorphism microarray, exome analysis, DNA sequence analysis, visual function testing including ERG, and photoaversion. We identified 148 ACHM patients from 57 Israeli and Palestinian families; there were 16 CNGA3 mutations (5 novel) in 41 families and 5 CNGB3 mutations (1 novel) in 8 families. Two CNGA3 founder mutations underlie >50% of cases. These mutations lead to a high ACHM prevalence of ∼1:5000 among Arab-Muslims residing in Jerusalem. Rod ERG abnormalities (in addition to cone dysfunction) were detected in 59% of patients. Retinal structure in CNGA3 ACHM patients revealed persistent but abnormal foveal cones. Under dark- and light-adapted conditions, patients use rod-mediated pathways. Photoaversion was readily demonstrated with transition from the dark to a dim light background. Among Israeli and Palestinian patients, CNGA3 mutations are the leading cause of ACHM. Retinal structural results support the candidacy of CNGA3 ACHM for clinical trials for therapy of cone photoreceptors

  16. New Gene Evolution: Little Did We Know

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

  18. The biology of novel animal genes: Mouse APEX gene knockout

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-07-01

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

  19. Newer Gene Editing Technologies toward HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Premlata Shankar

    2013-11-01

    Full Text Available 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.

  20. Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells

    NARCIS (Netherlands)

    Chan, M.F.; van Amerongen, R.; Nijjar, T.; Cuppen, E.; Jones, P.A.; Laird, P.W.

    2001-01-01

    Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by

  1. PoplarGene: poplar gene network and resource for mining functional information for genes from woody plants.

    Science.gov (United States)

    Liu, Qi; Ding, Changjun; Chu, Yanguang; Chen, Jiafei; Zhang, Weixi; Zhang, Bingyu; Huang, Qinjun; Su, Xiaohua

    2016-08-12

    Poplar is not only an important resource for the production of paper, timber and other wood-based products, but it has also emerged as an ideal model system for studying woody plants. To better understand the biological processes underlying various traits in poplar, e.g., wood development, a comprehensive functional gene interaction network is highly needed. Here, we constructed a genome-wide functional gene network for poplar (covering ~70% of the 41,335 poplar genes) and created the network web service PoplarGene, offering comprehensive functional interactions and extensive poplar gene functional annotations. PoplarGene incorporates two network-based gene prioritization algorithms, neighborhood-based prioritization and context-based prioritization, which can be used to perform gene prioritization in a complementary manner. Furthermore, the co-functional information in PoplarGene can be applied to other woody plant proteomes with high efficiency via orthology transfer. In addition to poplar gene sequences, the webserver also accepts Arabidopsis reference gene as input to guide the search for novel candidate functional genes in PoplarGene. We believe that PoplarGene (http://bioinformatics.caf.ac.cn/PoplarGene and http://124.127.201.25/PoplarGene) will greatly benefit the research community, facilitating studies of poplar and other woody plants.

  2. Combining gene prediction methods to improve metagenomic gene annotation

    Directory of Open Access Journals (Sweden)

    Rosen Gail L

    2011-01-01

    Full Text Available Abstract Background Traditional gene annotation methods rely on characteristics that may not be available in short reads generated from next generation technology, resulting in suboptimal performance for metagenomic (environmental samples. Therefore, in recent years, new programs have been developed that optimize performance on short reads. In this work, we benchmark three metagenomic gene prediction programs and combine their predictions to improve metagenomic read gene annotation. Results We not only analyze the programs' performance at different read-lengths like similar studies, but also separate different types of reads, including intra- and intergenic regions, for analysis. The main deficiencies are in the algorithms' ability to predict non-coding regions and gene edges, resulting in more false-positives and false-negatives than desired. In fact, the specificities of the algorithms are notably worse than the sensitivities. By combining the programs' predictions, we show significant improvement in specificity at minimal cost to sensitivity, resulting in 4% improvement in accuracy for 100 bp reads with ~1% improvement in accuracy for 200 bp reads and above. To correctly annotate the start and stop of the genes, we find that a consensus of all the predictors performs best for shorter read lengths while a unanimous agreement is better for longer read lengths, boosting annotation accuracy by 1-8%. We also demonstrate use of the classifier combinations on a real dataset. Conclusions To optimize the performance for both prediction and annotation accuracies, we conclude that the consensus of all methods (or a majority vote is the best for reads 400 bp and shorter, while using the intersection of GeneMark and Orphelia predictions is the best for reads 500 bp and longer. We demonstrate that most methods predict over 80% coding (including partially coding reads on a real human gut sample sequenced by Illumina technology.

  3. COGNATE: comparative gene annotation characterizer.

    Science.gov (United States)

    Wilbrandt, Jeanne; Misof, Bernhard; Niehuis, Oliver

    2017-07-17

    The comparison of gene and genome structures across species has the potential to reveal major trends of genome evolution. However, such a comparative approach is currently hampered by a lack of standardization (e.g., Elliott TA, Gregory TR, Philos Trans Royal Soc B: Biol Sci 370:20140331, 2015). For example, testing the hypothesis that the total amount of coding sequences is a reliable measure of potential proteome diversity (Wang M, Kurland CG, Caetano-Anollés G, PNAS 108:11954, 2011) requires the application of standardized definitions of coding sequence and genes to create both comparable and comprehensive data sets and corresponding summary statistics. However, such standard definitions either do not exist or are not consistently applied. These circumstances call for a standard at the descriptive level using a minimum of parameters as well as an undeviating use of standardized terms, and for software that infers the required data under these strict definitions. The acquisition of a comprehensive, descriptive, and standardized set of parameters and summary statistics for genome publications and further analyses can thus greatly benefit from the availability of an easy to use standard tool. We developed a new open-source command-line tool, COGNATE (Comparative Gene Annotation Characterizer), which uses a given genome assembly and its annotation of protein-coding genes for a detailed description of the respective gene and genome structure parameters. Additionally, we revised the standard definitions of gene and genome structures and provide the definitions used by COGNATE as a working draft suggestion for further reference. Complete parameter lists and summary statistics are inferred using this set of definitions to allow down-stream analyses and to provide an overview of the genome and gene repertoire characteristics. COGNATE is written in Perl and freely available at the ZFMK homepage ( https://www.zfmk.de/en/COGNATE ) and on github ( https

  4. Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd.

    Science.gov (United States)

    de Feyter, R; Li, P

    2000-06-01

    Ribozymes (catalytic RNAs) can be made to specifically cleave target RNAs that are involved in disease conditions and therefore have potential as therapeutic agents. Gene Shears Pty Ltd is developing hammerhead ribozyme technology for therapy against HIV infection, targeting either the tat gene or the RNA packaging sequence (Psi) of HIV. These ribozymes have been expressed from constructs that were introduced into hematopoietic cells in culture, thereby protecting the cells against viral infection. Two phase I clinical trials are underway to test the safety and feasibility of the approach with the anti-tat ribozyme in human subjects.

  5. [Gene therapy for Parkinson's disease].

    Science.gov (United States)

    Muramatsu, Shin-Ichi

    2012-01-01

    The current clinical trials of gene therapy for Parkinson's disease (PD) are based on three strategies. 1. To restore the local production of dopamine by introducing genes associated with dopamine-synthesizing enzymes into the putamen. 2. To protect nigrostriatal projection by delivering the neurturin gene, a trophic factor for dopaminergic neurons, both in the putamen and the substantia nigra. 3. To modulate the neural activity by transducing the subthalamic nucleus with vectors expressing glutamic acid decarboxylase. A phase I clinical study was initiated in 2007 to determine the safety of intra-putaminal infusion of a recombinant adeno-associated virus (AAV) vector encoding aromatic (L)-amino acid decarboxylase (AADC). All six patients enrolled in the trial showed improvements from baseline in the Unified Parkinson's Disease Rating Scale motor scores in the OFF medication state at 36 months after treatment. Although this trial was a small, open-label study and the use of a non-blinded, uncontrolled analysis limits interpretation, the efficacy outcomes are encouraging and indicate that the AAV vector-mediated gene transfer of AADC may benefit advanced PD patients. A similar approach, delivering AAV vector carrying AADC gene into the putamen ameliorated the symptoms in children with AADC deficiency.

  6. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available 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.

  7. Systems Biophysics of Gene Expression

    Science.gov (United States)

    Vilar, Jose M.G.; Saiz, Leonor

    2013-01-01

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

  8. Control of Renin Gene Expression

    Science.gov (United States)

    Glenn, Sean T.; Jones, Craig A.; Gross, Kenneth W.; Pan, Li

    2015-01-01

    Renin, as part of the renin-angiotensin system, plays a critical role in the regulation of blood pressure, electrolyte homeostasis, mammalian renal development and progression of fibrotic/hypertrophic diseases. Renin gene transcription is subject to complex developmental and tissue-specific regulation. Initial studies using the mouse As4.1 cell line, which has many characteristics of the renin-expressing juxtaglomerular cells of the kidney, have identified a proximal promoter region (−197 to −50 bp) and an enhancer (−2866 to −2625 bp) upstream of the Ren-1c gene, which are critical for renin gene expression. The proximal promoter region contains several transcription factor-binding sites including a binding site for the products of the developmental control genes Hox. The enhancer consists of at least 11 transcription factor-binding sites and is responsive to various signal transduction pathways including cAMP, retinoic acid, endothelin-1, and cytokines, all of which are known to alter renin mRNA levels. Furthermore, in vivo models have validated several of these key components found within the proximal promoter region and the enhancer as well as other key sites necessary for renin gene transcription. PMID:22576577

  9. Molecular Studies on Preproinsulin Gene

    Directory of Open Access Journals (Sweden)

    Sabir Sarah

    2016-01-01

    Full Text Available Insulin plays an important role in maintaining the blood glucose level of the body. The β-cells of pancreas produce insulin in the form of precursor that is preproinsulin. The gene of preproinsulin provides an interesting system for addressing question related to molecular evolution. Recombinant DNA technology has made it possible to isolate and sequence the chromosomal genes coding for unique protein products. Although preproinsulin of various organism has been isolated and cloned, but there is no report from buffalo (Bubalus bubalis that is our major livestock. The genomic DNA of buffalo was isolated using Laura-Lee-Boodram method. The part of preproinsulin gene (596bp and 520bp using BPPI-UPS and bpiful_F as forward and BC1-C as reverse primer was amplified. Cloning of amplified fragments of gene were performed in pCR 2.1 vector. Positive clones were screened on the basis of blue white selection. The band obtained on 596bp and 520bp after colony PCR confirmed the successful cloning of preproinsulin gene in pCR 2.1 vector.

  10. Gene Therapy Applications in Gastroenterology and Hepatology

    Directory of Open Access Journals (Sweden)

    Catherine H Wu

    2000-01-01

    Full Text Available Advantages and disadvantages of viral vectors and nonviral vectors for gene delivery to digestive organs are reviewed. Advances in systems for the introduction of new gene expression are described, including self-deleting retroviral transfer vectors, chimeric viruses and chimeric oligonucleotides. Systems for inhibition of gene expression are discussed, including antisense oligonucleotides, ribozymes and dominant-negative genes.

  11. Evolving chromosomes and gene regulatory networks

    Indian Academy of Sciences (India)

    Aswin

    Many processes change genomes. Koonin and Wolf. 2008. Page 5 .. including horizontal gene transfer. Koonin and Wolf. 2008. Page 6. Horizontal gene transfer. Drastic modification of genetic material. Rapid exploration of ne niches and phenot pes. Page 7. Horizontal gene transfer regulates. New selective forces for gene ...

  12. A Gene Ontology Tutorial in Python.

    Science.gov (United States)

    Vesztrocy, Alex Warwick; Dessimoz, Christophe

    2017-01-01

    This chapter is a tutorial on using Gene Ontology resources in the Python programming language. This entails querying the Gene Ontology graph, retrieving Gene Ontology annotations, performing gene enrichment analyses, and computing basic semantic similarity between GO terms. An interactive version of the tutorial, including solutions, is available at http://gohandbook.org .

  13. How Gene Patents May Inhibit Scientific Research

    Directory of Open Access Journals (Sweden)

    Campo-Engelstein, Lisa

    2015-02-01

    Full Text Available In this paper, we point out three possible ways gene patents could impede scientific research. First, gene patent laws might exacerbate the culture of secrecy ubiquitous in science. Second, gene patents may limit researchers’ ability to study poly or multigenic diseases without access to all genetic etiologies. Third, gene patents could result in a “patent thicket”.

  14. Synthetic promoter libraries- tuning of gene expression

    DEFF Research Database (Denmark)

    Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

    2006-01-01

    The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene ...

  15. Deregulated genes in sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric

    2010-01-01

    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology.......In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....

  16. A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

    Science.gov (United States)

    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.

  17. Gene conversion in the rice genome

    DEFF Research Database (Denmark)

    Xu, Shuqing; Clark, Terry; Zheng, Hongkun

    2008-01-01

    than ten percent. Pseudogenes in the rice genome with low similarity to Arabidopsis genes showed greater likelihood for gene conversion than those with high similarity to Arabidopsis genes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were......BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes......-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P

  18. Evolution of Hemoglobin and Its Genes

    Science.gov (United States)

    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 α-like globin gene complex are relatively stable, the β-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

  19. Metagenomics and novel gene discovery

    Science.gov (United States)

    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. Gene Therapy in Cardiac Arrhythmias

    Directory of Open Access Journals (Sweden)

    Praveen S.V

    2006-04-01

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

  1. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S

    2011-01-01

    as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic...... disease associated with an improper hypertrophic response....

  2. Candidate Gene Identification of Flowering Time Genes in Cotton

    Directory of Open Access Journals (Sweden)

    Corrinne E. Grover

    2015-07-01

    Full Text Available Flowering time control is critically important to all sexually reproducing angiosperms in both natural ecological and agronomic settings. Accordingly, there is much interest in defining the genes involved in the complex flowering-time network and how these respond to natural and artificial selection, the latter often entailing transitions in day-length responses. Here we describe a candidate gene analysis in the cotton genus , which uses homologs from the well-described flowering network to bioinformatically and phylogenetically identify orthologs in the published genome sequence from Ulbr., one of the two model diploid progenitors of the commercially important allopolyploid cottons, L. and L. Presence and patterns of expression were evaluated from 13 aboveground tissues related to flowering for each of the candidate genes using allopolyploid as a model. Furthermore, we use a comparative context to determine copy number variability of each key gene family across 10 published angiosperm genomes. Data suggest a pattern of repeated loss of duplicates following ancient whole-genome doubling events in diverse lineages. The data presented here provide a foundation for understanding both the parallel evolution of day-length neutrality in domesticated cottons and the flowering-time network, in general, in this important crop plant.

  3. Effect Alpha Globlin Gene Deletion And Gamma Globin Gene -158 ...

    African Journals Online (AJOL)

    We studied the Xmn1 polymorphism (C/T) in γ- globin gene position -158 of β- thalassemia as a modulating factor of the disease severity. Presence of the polymorphism was found in two patients and this was not sufficient to explain the diversity of the phenotype encountered. Co-inheritance of alpha thalassaemia as a ...

  4. FunGeneClusterS

    DEFF Research Database (Denmark)

    Vesth, Tammi Camilla; Brandl, Julian; Andersen, Mikael Rørdam

    2016-01-01

    and industrial biotechnology applications. We have previously published a method for accurate prediction of clusters from genome and transcriptome data, which could also suggest cross-chemistry, however, this method was limited both in the number of parameters which could be adjusted as well as in user......Secondary metabolites of fungi are receiving an increasing amount of interest due to their prolific bioactivities and the fact that fungal biosynthesis of secondary metabolites often occurs from co-regulated and co-located gene clusters. This makes the gene clusters attractive for synthetic biology...

  5. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each......%). Fifteen nuclear encoded mitochondrial proteins were all down-regulated in CRC. We identified several chromosomal locations with clusters of either potential oncogenes or potential tumor suppressors. Some of these, such as aminopeptidase N/CD13 and sigma B3 protein on chromosome 15q25, coincided...

  6. Does inbreeding affect gene expression in birds?

    Science.gov (United States)

    Hansson, Bengt; Naurin, Sara; Hasselquist, Dennis

    2014-09-01

    Inbreeding increases homozygosity, exposes genome-wide recessive deleterious alleles and often reduces fitness. The physiological and reproductive consequences of inbreeding may be manifested already during gene regulation, but the degree to which inbreeding influences gene expression is unknown in most organisms, including in birds. To evaluate the pattern of inbreeding-affected gene expression over the genome and in relation to sex, we performed a transcriptome-wide gene expression (10 695 genes) study of brain tissue of 10-day-old inbred and outbred, male and female zebra finches. We found significantly lower gene expression in females compared with males at Z-linked genes, confirming that dosage compensation is incomplete in female birds. However, inbreeding did not affect gene expression at autosomal or sex-linked genes, neither in males nor in females. Analyses of single genes again found a clear sex-biased expression at Z-linked genes, whereas only a single gene was significantly affected by inbreeding. The weak effect of inbreeding on gene expression in zebra finches contrasts to the situation, for example, in Drosophila where inbreeding has been found to influence gene expression more generally and at stress-related genes in particular. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  7. Integrones: los coleccionistas de genes Integrons: gene collectors

    Directory of Open Access Journals (Sweden)

    J. A. Di Conza

    2010-02-01

    Full Text Available Los integrones son estructuras genéticas que han despertado gran interés, debido a que algunos de ellos vehiculizan genes de resistencia a los antimicrobianos. Están formados por un fragmento que codifica una integrasa (intI y, a continuación, una secuencia attI a la que se unen los genes en casetes que codifican diferentes mecanismos de resistencia. Dentro de intI, en su extremo 3´, hay una secuencia promotora Pc a partir de la cual se transcriben los casetes de resistencia integrados, ya que estos genes carecen de promotor. Sin embargo, estos casetes presentan una secuencia específica denominada attC, la cual es reconocida por la integrasa que se une, por recombinación, a la secuencia attI del integrón en la orientación adecuada para su expresión. Los integrones se han clasificado según la secuencia de su integrasa, pero en la actualidad se prefiere clasificarlos según su localización. Se habla, en general, de "integrones móviles" para referirse a aquellos asociados a secuencias de inserción, transposones y/o plásmidos conjugativos, los que en su mayoría median mecanismos de resistencia, y de "superintegrones", de localización cromosómica y con grandes arreglos de genes en casetes. Los integrones móviles de clase 1 son los más abundantes en aislamientos clínicos y suelen estar asociados a transposones del subgrupo Tn21, seguidos por los de clase 2, derivados principalmente de Tn7. Estos elementos no son móviles por sí mismos, pero su asociación con elementos que sí lo son facilita su transferencia horizontal, lo que explica su amplia difusión entre las bacterias. Esta revisión intenta recopilar la información disponible acerca de los integrones móviles descritos en Argentina hasta la fecha.Integrons gained great interest due to their participation in resistance gene recruitment and expression. Their basic structure includes a fragment that encodes an integrase (intI followed by a recognition sequence (attI into

  8. Detecting Sequence Homology at the Gene Cluster Level with MultiGeneBlast

    NARCIS (Netherlands)

    Medema, Marnix H.; Takano, Eriko; Breitling, Rainer; Nowick, Katja

    The genes encoding many biomolecular systems and pathways are genomically organized in operons or gene clusters. With MultiGeneBlast, we provide a user-friendly and effective tool to perform homology searches with operons or gene clusters as basic units, instead of single genes. The

  9. Machine Learning-Based Gene Prioritization Identifies Novel Candidate Risk Genes for Inflammatory Bowel Disease.

    Science.gov (United States)

    Isakov, Ofer; Dotan, Iris; Ben-Shachar, Shay

    2017-09-01

    The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders, associated with genetic, immunologic, and environmental factors. Although hundreds of genes are implicated in IBD etiology, it is likely that additional genes play a role in the disease process. We developed a machine learning-based gene prioritization method to identify novel IBD-risk genes. Known IBD genes were collected from genome-wide association studies and annotated with expression and pathway information. Using these genes, a model was trained to identify IBD-risk genes. A comprehensive list of 16,390 genes was then scored and classified. Immune and inflammatory responses, as well as pathways such as cell adhesion, cytokine-cytokine receptor interaction, and sulfur metabolism were identified to be related to IBD. Scores predicted for IBD genes were significantly higher than those for non-IBD genes (P genes had a high prediction score (>0.8). A literature review of the genes, excluding those used to train the model, identified 67 genes without any publication concerning IBD. These genes represent novel candidate IBD-risk genes, which can be targeted in future studies. Our method successfully differentiated IBD-risk genes from non-IBD genes by using information from expression data and a multitude of gene annotations. Crucial features were defined, and we were able to detect novel candidate risk genes for IBD. These findings may help detect new IBD-risk genes and improve the understanding of IBD pathogenesis.

  10. Interactive visualization of gene regulatory networks with associated gene expression time series data

    NARCIS (Netherlands)

    Westenberg, Michel A.; Hijum, Sacha A.F.T. van; Lulko, Andrzej T.; Kuipers, Oscar P.; Roerdink, Jos B.T.M.; Linsen, L; Hagen, H; Hamann, B

    2008-01-01

    We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

  11. A gene-based information gain method for detecting gene-gene interactions in case-control studies.

    Science.gov (United States)

    Li, Jin; Huang, Dongli; Guo, Maozu; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Zhang, Ruijie; Jiang, Yongshuai; Lv, Hongchao; Wang, Limei

    2015-11-01

    Currently, most methods for detecting gene-gene interactions (GGIs) in genome-wide association studies are divided into SNP-based methods and gene-based methods. Generally, the gene-based methods can be more powerful than SNP-based methods. Some gene-based entropy methods can only capture the linear relationship between genes. We therefore proposed a nonparametric gene-based information gain method (GBIGM) that can capture both linear relationship and nonlinear correlation between genes. Through simulation with different odds ratio, sample size and prevalence rate, GBIGM was shown to be valid and more powerful than classic KCCU method and SNP-based entropy method. In the analysis of data from 17 genes on rheumatoid arthritis, GBIGM was more effective than the other two methods as it obtains fewer significant results, which was important for biological verification. Therefore, GBIGM is a suitable and powerful tool for detecting GGIs in case-control studies.

  12. TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal acute myeloid leukemia patients with NPM1+ and FLT3-ITD - mutations.

    Science.gov (United States)

    Tian, Xiaopeng; Xu, Yang; Yin, Jia; Tian, Hong; Chen, Suning; Wu, Depei; Sun, Aining

    2014-07-01

    Cytogenetically normal acute myeloid leukemia (cn-AML) is a group of heterogeneous diseases. Gene mutations are increasingly used to assess the prognosis of cn-AML patients and guide risk-adapted treatment. In the present study, we analyzed the molecular genetics characteristics of 373 adult cn-AML patients and explored the relationship between TET2 gene mutations or different genetic mutation patterns and prognosis. We found that 16.1 % of patients had TET2 mutations, 31.6 % had FLT3 internal tandem duplications (ITDs), 6.2 % had FLT3 tyrosine kinase domain mutations, 2.4 % had c-KIT mutations, 37.8 % had NPM1 mutations, 11.3 % had WT1 mutations, 5.9 % had RUNX1 mutations, 11.5 % had ASXL1 mutations, 3.8 % had MLL-PTDs, 7.8 % had IDH1 mutations, 7.8 % had NRAS mutations, 12.3 % had IDH2 mutations, 1.6 % had EZH2 mutations, and 14.7 % had DNMT3A mutations, while none had CBL mutations. Gene mutations were detected in 76.94 % (287/373) of all patients. In the NPM1m(+) patients, those with TET2 mutations were associated with a shorter median overall survival (OS) as compared to TET2 wild-type (wt) patients (9.9 vs. 27.0 months, respectively; P = 0.023); Interestingly, the TET2 mutation was identified as an unfavorable prognostic factor and was closely associated with a shorter median OS as compared to TET2-wt (9.5 vs. 32.2 months, respectively; P = 0.013) in the NPM1m(+)/FLT3-ITDm(-) patient group. Thus, identification of TET2 combined with classic NPM1 and FLT3-ITD mutations allowed us to stratify cn-AML into distinct subtypes.

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

    Science.gov (United States)

    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, β-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. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Persistence drives gene clustering in bacterial genomes

    Directory of Open Access Journals (Sweden)

    Rocha Eduardo PC

    2008-01-01

    Full Text Available Abstract Background Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms – persistent genes – and those present in very few organisms – rare genes. Results We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters. Conclusion We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.

  15. Gene-gene and gene-environment interaction on the risk of Parkinson's disease.

    Science.gov (United States)

    Singh, Neeraj Kumar; Banerjee, Basu Dev; Bala, Kiran; Chhillar, Mitrabasu; Chhillar, Neelam

    2014-01-01

    Even with numerous studies the cause of Parkinson's disease (PD) remains elusive. It has been hypothesized that interactions between genetic and environmental factors may play an important role in the pathogenesis of PD. To examine the gene-gene and gene-environment interaction on PD risk with respect to gene polymorphism of cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1), organochlorine pesticides (OCPs) and metals. This study included 70 patients of PD and 100 age-matched controls. The restriction fragment length polymorphism was used for analysis of genetic polymorphism. OCPs and serum metal levels were estimated by using gas chromatography and an autoanalyser respectively. The CYP2D6*4 mt and GSTP1 *B allelic variants were significantly associated with increase in PD risk. We found a statistically significant difference in β -hexachlorocyclohexane (β-HCH), dieldrin, 1,1-dichloro-2,2-bis(pchlorophenyl) ethylene (pp'-DDE) and copper levels between the patients and controls. We found significantly high levels of β-HCH, dieldrin and pp'-DDE in the CYP2D6*4 mt allelic variants, β-HCH and pp'-DDE in the GSTP1*B allelic variants and dieldrin in the GSTP1*C allelic variants when comparing CYP2D6*4 non-mt, GSTP1 non-*B and GSTP1 non-*C allelic variants in patients of PD respectively. This study demonstrates that the CYP2D6*4 and GSTP1 genes may be considered as candidate genes for PD and they may also interact with β- HCH, dieldrin and pp'-DDE to influence the risk for PD.

  16. Genome position and gene amplification

    Czech Academy of Sciences Publication Activity Database

    Jirsová, Pavla; Snijders, A.M.; Kwek, S.; Roydasgupta, R.; Fridlyand, J.; Tokuyasu, T.; Pinkel, D.; Albertson, D. G.

    2007-01-01

    Roč. 8, č. 6 (2007), r120 ISSN 1474-760X Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : gene amplification * array comparative genomic hybridization * oncogene Subject RIV: BO - Biophysics Impact factor: 6.589, year: 2007

  17. Positional cloning of deafness genes

    NARCIS (Netherlands)

    Kremer, H.; Cremers, F.P.M.

    2009-01-01

    The identification of the majority of the known causative genes involved in nonsyndromic sensorineural hearing loss (NSHL) started with linkage analysis as part of a positional cloning procedure. The human and mouse genome projects in combination with technical developments on genotyping,

  18. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

    African Journals Online (AJOL)

    Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with abortion, early embryo loss and recurrent spontaneous abortion in human. However, information on the association between MTHFR polymorphism and cow abortion is scarce. In the present study, the effects of MTHFR ...

  19. (TNNC1) gene in goat

    African Journals Online (AJOL)

    Yomi

    2012-02-23

    Feb 23, 2012 ... that TNNC1 was a 161-amino acid polypeptide that had been highly conserved during evolution. Its ... patterns and evolution of TNNC1 gene in animal. .... Dog. 93.00. 98.76. EM. XM533799.2. Genbank. Oryctolagus cuniculus. Rabbit. 90.74. 99.38. EM. XM002713240.1 Genbank. Mus musculus. Mouse.

  20. Sculpting the Barnyard Gene Pool

    Science.gov (United States)

    Childers, Gina; Wolfe, Kim; Dupree, Alan; Young, Sheila; Caver, Jessica; Quintanilla, Ruby; Thornton, Laura

    2016-01-01

    Project-based learning (PBL) takes student engagement to a higher level through reflective collaboration, inquiry, critical thinking, problem solving, and personal relevance. This article explains how six high school teachers developed an interconnected, interdisciplinary STEM-focused PBL called "Sculpting the Barnyard Gene Pool." The…

  1. Gene expression profile of pulpitis

    Science.gov (United States)

    Galicia, Johnah C.; Henson, Brett R.; Parker, Joel S.; Khan, Asma A.

    2016-01-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the Significance Analysis of Microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (≥30mm on VAS) compared to those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology. PMID:27052691

  2. Gene Expression in Trypanosomatid Parasites

    Directory of Open Access Journals (Sweden)

    Santiago Martínez-Calvillo

    2010-01-01

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

  3. 06 Silence of the Genes

    Indian Academy of Sciences (India)

    Srimath

    April 2007 Volume 12 Number 4. GENERAL ARTICLES. 06 Silence of the Genes. 2006 Nobel Prize in Physiology or Medicine. Utpal Nath and Saumitra Das. 19 Euclid and 'The Elements'. C R Pranesachar. 26 Euclid's Fifth Postulate. Renuka Ravindran. 37 Decoding Reed–Solomon Codes Using Euclid's. Algorithm.

  4. Gene expression profile of pulpitis.

    Science.gov (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A

    2016-06-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

  5. Ethics of Gene Therapy Debated.

    Science.gov (United States)

    Borman, Stu

    1991-01-01

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

  6. Embryos, genes, and birth defects

    National Research Council Canada - National Science Library

    Ferretti, Patrizia

    2006-01-01

    ... Structural anomalies The genesis of chromosome abnormalities Embryo survival The cause of high levels of chromosome abnormality in human embryos Relative parental risks - age, translocations, inversions, gonadal and germinal mosaics 33 33 34 35 36 44 44 45 4 Identification and Analysis of Genes Involved in Congenital Malformation Syndromes Peter J. Scambler Ge...

  7. Patching genes to fight disease

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. The Language of the Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 3. The Language of the Genes Linking the Past and the Future. Amitabh Joshi ... Author Affiliations. Amitabh Joshi1. Animal Behaviour Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bangalore 560 064, India.

  9. Homeobox genes and melatonin synthesis

    DEFF Research Database (Denmark)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based indu......Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a c......AMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX......) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating c...

  10. [Chromosomal rearrangements and fusion genes in carcinoma].

    Science.gov (United States)

    Massard, Christophe; Auger, Nathalie; Lacroix, Ludovic; Bénard, Jean

    2011-12-01

    In the last decades, rarity of chromosomal rearrangements and fusion genes detected in epithelial cancers in using classical karyotyping led to consider these genomic events as specifically restricted to haematological neoplasia and mesenchymal tumors. Today, gene positioning as well as bio-informatics approaches has enabled identifying in carcinoma various fusion genes subsequent to chromosomal translocations, inversions, or deletions. Thus, gene fusion formation appears as a common mechanism in oncology that concerns most of human cancers, independent of original tissue lineage. At a clinical point of view, applications of fusion genes in terms of diagnosis, prognosis and therapeutics can be envisioned. This review will present current knowledge about fusion genes in common carcinoma (prostate, breast, colon). Following a structural and functional description of various fusion genes so far found in human malignant solid tumors, as well as techniques used for their detection, the review will integrate fusion genes in epithelia oncogenesis general scheme. Finally, promising clinical issues of fusion genes will be surveyed.

  11. The combinatorics of overlapping genes.

    Science.gov (United States)

    Lèbre, Sophie; Gascuel, Olivier

    2017-02-21

    Overlapping genes exist in all domains of life and are much more abundant than expected upon their first discovery in the late 1970s. Assuming that the reference gene is read in frame +0, an overlapping gene can be encoded in two reading frames in the sense strand, denoted by +1 and +2, and in three reading frames in the opposite strand, denoted by -0, -1, and -2. This motivated numerous researchers to study the constraints induced by the genetic code on the various overlapping frames, mostly based on information theory. Our focus in this paper is on the constraints induced on two overlapping genes in terms of amino acids, as well as polypeptides. We show that simple linear constraints bind the amino-acid composition of two proteins encoded by overlapping genes. Novel constraints are revealed when polypeptides are considered, and not just single amino acids. For example, in double-coding sequences with an overlapping reading frame -2, each Tyrosine (denoted as Tyr or Y) in the overlapping frame overlaps a Tyrosine in the reference frame +0 (and reciprocally), whereas specific words (e.g. YY) never occur. We thus distinguish between null constraints (YY = 0 in frame -2) and non-null constraints (Y in frame +0 ⇔ Y in frame -2). Our equivalence-based constraints are symmetrical and thus enable the characterization of the joint composition of overlapping proteins. We describe several formal frameworks and a graph algorithm to characterize and compute these constraints. As expected, the degrees of freedom left by these constraints vary drastically among the different overlapping frames. Interestingly, the biological meaning of constraints induced on two overlapping proteins (hydropathy, forbidden di-peptides, expected overlap length …) is also specific to the reading frame. We study the combinatorics of these constraints for overlapping polypeptides of length n, pointing out that, (i) except for frame -2, non-null constraints are deduced from the amino-acid (length

  12. Identification of context-specific gene regulatory networks with GEMULA--Gene Expression Modeling Using LAsso

    NARCIS (Netherlands)

    Geeven, G.; van Kesteren, R.E.; Smit, A.B.; de Gunst, M.C.M.

    2012-01-01

    Motivation: Gene regulatory networks, in which edges between nodes describe interactions between transcriptional regulators and their target genes, determine the coordinated spatiotemporal expression of genes. Especially in higher organisms, context-specific combinatorial regulation by transcription

  13. Gene losses during human origins.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Wang

    2006-03-01

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

  14. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available 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.

  15. Empirical study of supervised gene screening

    Directory of Open Access Journals (Sweden)

    Ma Shuangge

    2006-12-01

    Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

  16. Gene therapy and its implications in Periodontics

    Science.gov (United States)

    Mahale, Swapna; Dani, Nitin; Ansari, Shumaila S.; Kale, Triveni

    2009-01-01

    Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here. PMID:20376232

  17. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  18. Genes from scratch – the evolutionary fate of de novo genes

    Science.gov (United States)

    Schlötterer, Christian

    2015-01-01

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

  19. Identification and functional analysis of light-responsive unique genes and gene family members in rice.

    Directory of Open Access Journals (Sweden)

    Ki-Hong Jung

    2008-08-01

    Full Text Available Functional redundancy limits detailed analysis of genes in many organisms. Here, we report a method to efficiently overcome this obstacle by combining gene expression data with analysis of gene-indexed mutants. Using a rice NSF45K oligo-microarray to compare 2-week-old light- and dark-grown rice leaf tissue, we identified 365 genes that showed significant 8-fold or greater induction in the light relative to dark conditions. We then screened collections of rice T-DNA insertional mutants to identify rice lines with mutations in the strongly light-induced genes. From this analysis, we identified 74 different lines comprising two independent mutant lines for each of 37 light-induced genes. This list was further refined by mining gene expression data to exclude genes that had potential functional redundancy due to co-expressed family members (12 genes and genes that had inconsistent light responses across other publicly available microarray datasets (five genes. We next characterized the phenotypes of rice lines carrying mutations in ten of the remaining candidate genes and then carried out co-expression analysis associated with these genes. This analysis effectively provided candidate functions for two genes of previously unknown function and for one gene not directly linked to the tested biochemical pathways. These data demonstrate the efficiency of combining gene family-based expression profiles with analyses of insertional mutants to identify novel genes and their functions, even among members of multi-gene families.

  20. GenePRIMP: A GENE PRediction IMprovement Pipeline for Prokaryotic genomes

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-01

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

  1. Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing

    Directory of Open Access Journals (Sweden)

    Corti Stefania

    2011-03-01

    Full Text Available Abstract Background Duchenne and Becker Muscular dystrophies (DMD/BMD are allelic disorders caused by mutations in the dystrophin gene, which encodes a sarcolemmal protein responsible for muscle integrity. Deletions and duplications account for approximately 75% of mutations in DMD and 85% in BMD. The implementation of techniques allowing complete gene sequencing has focused attention on small point mutations and other mechanisms underlying complex rearrangements. Methods We selected 47 patients (41 families; 35 DMD, 6 BMD without deletions and duplications in DMD gene (excluded by multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction analysis. This cohort was investigated by systematic direct sequence analysis to study sequence variation. We focused our attention on rare mutational events which were further studied through transcript analysis. Results We identified 40 different nucleotide alterations in DMD gene and their clinical correlates; altogether, 16 mutations were novel. DMD probands carried 9 microinsertions/microdeletions, 19 nonsense mutations, and 7 splice-site mutations. BMD patients carried 2 nonsense mutations, 2 splice-site mutations, 1 missense substitution, and 1 single base insertion. The most frequent stop codon was TGA (n = 10 patients, followed by TAG (n = 7 and TAA (n = 4. We also analyzed the molecular mechanisms of five rare mutational events. They are two frame-shifting mutations in the DMD gene 3'end in BMD and three novel splicing defects: IVS42: c.6118-3C>A, which causes a leaky splice-site; c.9560A>G, which determines a cryptic splice-site activation and c.9564-426 T>G, which creates pseudoexon retention within IVS65. Conclusion The analysis of our patients' sample, carrying point mutations or complex rearrangements in DMD gene, contributes to the knowledge on phenotypic correlations in dystrophinopatic patients and can provide a better understanding of pre-mRNA maturation defects

  2. Thesaurus-based disambiguation of gene symbols.

    Science.gov (United States)

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

    2005-06-16

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

  3. Thesaurus-based disambiguation of gene symbols

    Directory of Open Access Journals (Sweden)

    Wain Hester M

    2005-06-01

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

  4. [Bt gene flow of transgeic cotton].

    Science.gov (United States)

    Shen, F F; Yu, Y J; Zhang, X K; Bi, J J; Yin, C Y

    2001-01-01

    This study was carried out to determine the gene flow of transgenic cotton under Chinese ecological environment. Transgenic cotton GK-12 containing the marker gene NPTII and Bt gene was planted in the 6 x 6 m2 plot, non-transgenic cotton CCRC 12 and Xinmian 13 were planted respectively around them. At varying distances from transgenic cotton, seeds produced by the non-transgenic cotton were collected and screened for marker gene and Bt gene using kanamycine sulphate and Dot-ELISA method. PCR technique was also used in some seeds to screen Bt gene. The result indicated that gene flow was found to be high at 0-6 m, and to decrease with distances; however gene flow occurred up to distance of 36 m from the transgenic cotton plot. Bt gene flow at 3-6 m increased with increasing the diversity of transgenic cotton in the plot, but gene flow increased little at long distance. The gene flow between species was lower than between cultivars at 0-6 m, and occurred at the distance of 72 m from transgenic plot. 72 m buffer zones would serve to limit gene flow of transgenic cotton from small-scale field test. The possibility of escapes of engineered gene to wild relatives of cotton species was also discussed.

  5. Somatic gene therapy for hypertension

    Directory of Open Access Journals (Sweden)

    Phillips M.I.

    2000-01-01

    Full Text Available Gene therapy for hypertension is needed for the next generation of antihypertensive drugs. Current drugs, although effective, have poor compliance, are expensive and short-lasting (hours or one day. Gene therapy offers a way to produce long-lasting antihypertensive effects (weeks, months or years. We are currently using two strategies: a antisense oligodeoxynucleotides (AS-ODN and b antisense DNA delivered in viral vectors to inhibit genes associated with vasoconstrictive properties. It is not necessary to know all the genes involved in hypertension, since many years of experience with drugs show which genes need to be controlled. AS-ODN are short, single-stranded DNA that can be injected in naked form or in liposomes. AS-ODN, targeted to angiotensin type 1 receptors (AT1-R, angiotensinogen (AGT, angiotensin converting enzyme, and ß1-adrenergic receptors effectively reduce hypertension in rat models (SHR, 2K-1C and cold-induced hypertension. A single dose is effective up to one month when delivered with liposomes. No side effects or toxic effects have been detected, and repeated injections can be given. For the vector, adeno-associated virus (AAV is used with a construct to include a CMV promoter, antisense DNA to AGT or AT1-R and a reporter gene. Results in SHR demonstrate reduction and slowing of development of hypertension, with a single dose administration. Left ventricular hypertrophy is also reduced by AAV-AGT-AS treatment. Double transgenic mice (human renin plus human AGT with high angiotensin II causing high blood pressure, treated with AAV-AT1-R-AS, show a normalization of blood pressure for over six months with a single injection of vector. We conclude that ODNs will probably be developed first because they can be treated like drugs for the treatment of hypertension with long-term effects. Viral vector delivery needs more engineering to be certain of its safety, but one day may be used for a very prolonged control of blood pressure.

  6. New Cholesterol Fighting Meds Target Key Gene

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_165942.html New Cholesterol Fighting Meds Target Key Gene Two trials show ... New gene-based therapies appear to significantly decrease cholesterol levels in people, and could even cut down ...

  7. Biodegradable nanoparticles for gene therapy technology

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@mail.ntust.edu.tw; He, Wen-Jie [National Taiwan University of Science and Technology (Taiwan Tech), Graduate Institute of Biomedical Engineering (China); Chiang, Chiao-Hsi [School of Pharmacy, National Defense Medical Center (China); Hong, Po-Da [National Taiwan University of Science and Technology (Taiwan Tech), Graduate Institute of Biomedical Engineering (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [The Hebrew University of Jerusalem, Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Center for Nanoscience and Nanotechnology and The Alex Grass Center for Drug Design and Synthesis (Israel); Ou, Keng-Liang [College of Oral Medicine, Taipei Medical University, Research Center for Biomedical Devices and Prototyping Production (China)

    2013-07-15

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes.

  8. Scientists Spot Genes Behind Crohn's, Ulcerative Colitis

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_166957.html Scientists Spot Genes Behind Crohn's, Ulcerative Colitis Large study finds key ... Researchers say they've come closer to pinpointing genes linked with inflammatory bowel diseases such as Crohn's ...

  9. NIH Researchers Identify OCD Risk Gene

    Science.gov (United States)

    ... 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- ...

  10. Biodegradable nanoparticles for gene therapy technology

    Science.gov (United States)

    Hosseinkhani, Hossein; He, Wen-Jie; Chiang, Chiao-Hsi; Hong, Po-Da; Yu, Dah-Shyong; Domb, Abraham J.; Ou, Keng-Liang

    2013-07-01

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes.

  11. Rounding up sickle cells with gene therapy.

    Science.gov (United States)

    Byrne, Leah

    2017-03-15

    A report of a patient treated with ex vivo lentiviral gene transfer to hematopoietic stem cells shows the promise of gene therapy for sickle cell anemia. Copyright © 2017, American Association for the Advancement of Science.

  12. What Is a Gene? (For Kids)

    Science.gov (United States)

    ... tested is replacing sick genes with healthy ones. Gene therapy trials — where the research is tested on people — and ... THIS TOPIC How to Deal With Hemophilia What's the Right Weight for Me? Do You ...

  13. Genomewide survey and characterization of metacaspase gene ...

    Indian Academy of Sciences (India)

    Oryza sativa). Likai Wang ... Keywords. metacaspases; OsMC gene family; expression profiles; domestication; rice; Oryza sativa. ... The expression profiles of eight OsMC genes were analysed in 27 tissues covering the whole life cycle of rice.

  14. Drugs to awaken a paternal gene

    OpenAIRE

    Beaudet, Arthur L.

    2011-01-01

    Mutations in the maternal copy of the UBE3A gene cause a neurodevelopmental disorder known as Angelman syndrome. Drugs that activate the normally silenced paternal copy of this gene may be of therapeutic value.

  15. RESISTANCE-RELATED GENE TRANSCRIPTION AND ...

    African Journals Online (AJOL)

    jdx

    2014-02-05

    related gene, antioxidant enzyme activity. INTRODUCTION ... oxygen and nitrogen species, through changes in ion flux across the plasma ... A better understanding of the gene network underlying anthracnose resistance in ...

  16. Influence of thiopurine methyltransferase gene polymorphism on ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 96; Issue 6. Influence of thiopurine methyltransferase gene polymorphism on Egyptian children with acute lymphoblastic leukaemia. AZZA A. G. ... thiopurine methyltransferase gene polymorphism; acute lymphoblastic leukaemia; Egyptian children; thiopurine methyltransferase.

  17. Rogue Genes May Cause Some ALS Cases

    Science.gov (United States)

    ... discover other possible genetic triggers and to further define possible non-genetic factors that may play a ... Services. More Health News on Amyotrophic Lateral Sclerosis Genes and Gene Therapy Recent Health News Related MedlinePlus ...

  18. Nickel and Epigenetic Gene Silencing

    Directory of Open Access Journals (Sweden)

    Hong Sun

    2013-10-01

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

  19. Nickel and epigenetic gene silencing.

    Science.gov (United States)

    Sun, Hong; Shamy, Magdy; Costa, Max

    2013-10-25

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

  20. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used...... be obtained using proteome analysis. Chapter 1 and 2 provide the basic theoretical aspects of proteome analysis, its principles, the main techniques involved and their use in the studies of the molecular biology of yeast cells. Chapter 3 presents the methods and tools involved in proteome analysis and used...... to multiple drug resistance in yeast. It analyses the cellular response to the overexpression of the Pdr5p - an ABC transporter protein that is responsible for resistance of yeast cells to several drugs and chemical compounds. It shows that the overexpression of Pdr5p triggers a strong cell stress response...

  1. Gene therapy for lipid disorders

    OpenAIRE

    Rader Daniel J; Kawashiri Masa-aki

    2000-01-01

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

  2. Nickel and Epigenetic Gene Silencing

    OpenAIRE

    Hong Sun; Magdy Shamy; Max Costa

    2013-01-01

    Insoluble nickel compounds are well-established human carcinogens. Occupational exposure to these compounds leads to increased incidence of lung and nasal cancer in nickel refinery workers. Apart from its weak mutagenic activity and hypoxia mimicking effect there is mounting experimental evidence indicating that epigenetic alteration plays an important role in nickel-induced carcinogenesis. Multiple epigenetic mechanisms have been identified to mediate nickel-induced gene silencing. Nickel io...

  3. The Insect SNMP Gene Family

    Science.gov (United States)

    2009-01-01

    chemosensory neurons in insects ; in Drosophila melanogaster, SNMP1 has been shown to be essential for the detection of the pheromone cis- vaccenyl...Elsevier Ltd. All rights reserved. 1. Introduction SNMPs are insect membrane proteins which associate with pheromone sensitive neurons in Lepidoptera and...melanogaster, SNMP1 has been shown to be essential for the detection of the pheromone cisvaccenyl acetate (CVA). SNMPs are one of three insect gene clades

  4. Gene Therapy for Fracture Repair

    Science.gov (United States)

    2007-05-01

    forma - tion and finally remodeling [8]. Fracture callus formation eventually results in the bridging of the fracture and the restoration of skeletal...analysis was performed using ImaGene software (BioDiscovery, El Segundo, CA), that used an internal statistical analysis of the signal intensity of...expression during the normal repair of a simple femur fracture with the elimination of scar tissue from the healing bone. This model does not address

  5. Gene Therapy for Childhood Neurofibromatosis

    Science.gov (United States)

    2014-05-01

    Neurofibromatosis PRINCIPAL INVESTIGATOR: Segal, David J. CONTRACTING ORGANIZATION: University of California, Davis Davis, California...May 2014 4. TITLE AND SUBTITLE Gene Therapy for Childhood Neurofibromatosis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0101 5c...project was to develop an innovative therapy for neurofibromatosis . Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders (1

  6. Expression of evolutionarily novel genes in tumors

    OpenAIRE

    A. P. Kozlov

    2016-01-01

    The evolutionarily novel genes originated through different molecular mechanisms are expressed in tumors. Sometimes the expression of evolutionarily novel genes in tumors is highly specific. Moreover positive selection of many human tumor-related genes in primate lineage suggests their involvement in the origin of new functions beneficial to organisms. It is suggested to consider the expression of evolutionarily young or novel genes in tumors as a new biological phenomenon, a phenomenon of TS...

  7. The gene expression signatures of melanoma progression

    OpenAIRE

    Haqq, Christopher; Nosrati, Mehdi; Sudilovsky, Daniel; Crothers, Julia; Khodabakhsh, Daniel; Pulliam, Brian L.; Federman, Scot; Miller, James R.; Allen, Robert E.; Singer, Mark I.; Leong, Stanley P L; Ljung, Britt-Marie; Sagebiel, Richard W.; Kashani-Sabet, Mohammed

    2005-01-01

    Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser...

  8. Ethics of Cancer Gene Transfer Clinical Research.

    Science.gov (United States)

    Kimmelman, Jonathan

    2015-01-01

    Translation of cancer gene transfer confronts many familiar-and some distinctive-ethical challenges. In what follows, I survey three major ethical dimensions of cancer gene transfer development. Subheading 1 centers on the ethics of planning, designing, and reporting animal studies. Subheading 2 describes basic elements of human subjects protection as pertaining to cancer gene transfer. In Subheading 3, I describe how cancer gene transfer researchers have obligations to downstream consumers of the evidence they produce.

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

    Science.gov (United States)

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

    2011-01-01

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

  10. Gene coexpression network analysis as a source of functional annotation for rice genes.

    Directory of Open Access Journals (Sweden)

    Kevin L Childs

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

  11. Suicide gene therapy of rhabdomyosarcoma.

    Science.gov (United States)

    Konieczny, Paweł; Sułkowski, Maciej; Badyra, Bogna; Kijowski, Jacek; Majka, Marcin

    2017-02-01

    Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and young adulthood. Conventional treatment consisting of surgery, chemotherapy and radiotherapy can be insufficient, as long-term survival chances decrease dramatically when cancer recurrence occurs. Due to this fact, efficient treatment of this cancer is still a demanding issue, thus, novel and innovative therapies have to be considered as a part of combined treatment. In the present study, we present effective suicide gene therapy of rhabdomyosarcoma cell line Rh30 involving herpes simplex thymidine kinase (HSV-TK) and ganciclovir (GCV). Transduction of rhabdomyosarcoma cells using lentiviral vectors allowed efficient introduction of HSV-TK gene. In this study we proved high susceptibility of modified cells to ganciclovir resulting in eradication of cancer cells both in vitro and in vivo. Our data revealed strong gap junctional intercellular communication in examined cell line responsible for elimination of unmodified cells by bystander effect, even if HSV-TK-expressing cells comprise only 20% of cultured cells. Moreover, investigated approach is also efficient in vivo, where complete remission of tumors upon only 14 days of systemic administration of GCV can be observed. Obtained results suggest that HSV-TK suicide gene therapy is very promising concept in future clinical studies concerning rhabdomyosarcoma.

  12. Nongenomic regulation of gene expression.

    Science.gov (United States)

    Iglesias-Platas, Isabel; Monk, David

    2016-08-01

    The purpose of this review is to highlight the recent advances in epigenetic regulation and chromatin biology for a better understanding of gene regulation related to human disease. Alterations to chromatin influence genomic function, including gene transcription. At its most simple level, this involves DNA methylation and posttranscriptional histone modifications. However, recent developments in biochemical and molecular techniques have revealed that transcriptional regulation is far more complex, involving combinations of histone modifications and discriminating transcription factor binding, and long-range chromatin loops with enhancers, to generate a multifaceted code. Here, we describe the most recent advances, culminating in the example of genomic imprinting, the parent-of-origin monoallelic expression that utilizes the majority of these mechanisms to attain one active and one repressed allele. It is becoming increasingly evident that epigenetic mechanisms work in unison to maintain tight control of gene expression and genome function. With the wealth of knowledge gained from recent molecular studies, future goals should focus on the application of this information in deciphering their role in developmental diseases.

  13. Horizontal gene transfer in chromalveolates

    Directory of Open Access Journals (Sweden)

    Bhattacharya Debashish

    2007-09-01

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

  14. Targeted gene flow for conservation.

    Science.gov (United States)

    Kelly, Ella; Phillips, Ben L

    2016-04-01

    Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

  15. DMRT genes in vertebrate gametogenesis.

    Science.gov (United States)

    Zarkower, David

    2013-01-01

    Genes containing the DM domain DNA-binding motif regulate sex determination and sexual differentiation in a broad variety of metazoans, including nematodes, insects, and vertebrates. They can function in primary sex determination or downstream in sexual differentiation, and they can act either throughout the body or in highly restricted cell types. In vertebrates, several DM domain genes--DMRT genes--play critical roles in gonadal differentiation or gametogenesis. DMRT1 has the most prominent role and likely regulates testicular differentiation in all vertebrates. In the mammalian gonad, DMRT1 exerts both intrinsic and extrinsic control of gametogenesis; it is required for germ cell differentiation in males and regulates meiosis in both sexes, and it is required in supporting cells for the establishment and maintenance of male fate in the testis. These varied functions of DMRT1 serve to coordinate gonadal development and function. In other vertebrates, DMRT1 regulates gonadal differentiation, and it also appears to have played a central role in the evolution of new sex-determining mechanisms in at least three vertebrate clades. This chapter focuses on the regulation of vertebrate gametogenesis by DMRT1. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Gene transfer to the cerebellum.

    Science.gov (United States)

    Louboutin, Jean-Pierre; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

    2010-12-01

    There are several diseases for which gene transfer therapy to the cerebellum might be practicable. In these studies, we used recombinant Tag-deleted SV40-derived vectors (rSV40s) to study gene delivery targeting the cerebellum. These vectors transduce neurons and microglia very effectively in vitro and in vivo, and so we tested them to evaluate gene transfer to the cerebellum in vivo. Using a rSV40 vector carrying human immunodeficiency virus (HIV)-Nef with a C-terminal FLAG epitope, we characterized the distribution, duration, and cell types transduced. Rats received test and control vectors by stereotaxic injection into the cerebellum. Transgene expression was assessed 1, 2, and 4 weeks later by immunostaining of serial brain sections. FLAG epitope-expressing cells were seen, at all times after vector administration, principally detected in the Purkinje cells of the cerebellum, identified as immunopositive for calbindin. Occasional microglial cells were tranduced; transgene expression was not detected in astrocytes or oligodendrocytes. No inflammatory or other reaction was detected at any time. Thus, SV40-derived vectors can deliver effective, safe, and durable transgene expression to the cerebellum.

  17. Scintigraphic imaging of HSVtk gene therapy

    NARCIS (Netherlands)

    de Vries, EFJ; Buursma, AR; Hospers, GAP; Mulder, NH; Vaalburg, W

    2002-01-01

    The evolution of molecular biology has enabled the exploration of novel sophisticated gene-directed treating modalities for cancer. Suicide gene therapy - i.e. transfection of a so-called suicide gene that sensitizes target cells towards a prodrug - may offer an attractive approach to treat

  18. Uses of antimicrobial genes from microbial genome

    Science.gov (United States)

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

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

  19. Structure of the murine Thy-1 gene

    NARCIS (Netherlands)

    V. Giguere; K-I. Isobe; F.G. Grosveld (Frank)

    1985-01-01

    textabstractWe have cloned the murine Thy-1.1 (AKR) and Thy-1.2 (Balb/c) genes. The complete exon/intron structure and the nucleotide sequence of the Thy-1.2 gene was determined. The gene contains four exons and three intervening sequences. The complete transcriptional unit gives rise to a tissue

  20. Network topology reveals key cardiovascular disease genes.

    Directory of Open Access Journals (Sweden)

    Anida Sarajlić

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

  1. Transposon based functional characterization of soybean genes

    Science.gov (United States)

    Type II transposable elements that use cut and paste mechanism for jumping from one genomic region to another is ideal in tagging and cloning genes. Precise excision from an insertion site in a mutant gene leads to regaining the wild-type function. Thus, function of a gene can be established based o...

  2. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and ... Polymorphisms in the POMC gene locus are associated with obesity phenotypes. Aim: To ... Keywords: Childhood obesity; POMC gene; Metabolic syndrome ...

  3. Mutation Spectrum of Common Deafness-Causing Genes in Patients with Non-Syndromic Deafness in the Xiamen Area, China.

    Directory of Open Access Journals (Sweden)

    Yi Jiang

    Full Text Available In China, approximately 30,000 babies are born with hearing impairment each year. However, the molecular factors causing congenital hearing impairment in the Xiamen area of Fujian province have not been evaluated. To provide accurate genetic testing and counseling in the Xiamen area, we investigated the molecular etiology of non-syndromic deafness in a deaf population from Xiamen. Unrelated students with hearing impairment (n = 155 who attended Xiamen Special Education School in Fujian Province were recruited for this study. Three common deafness-related genes, GJB2, SLC26A4, and mtDNA12SrRNA, were analyzed using all-exon sequencing. GJB2 mutations were detected in 27.1% (42/155 of the entire cohort. The non-syndromic hearing loss (NSHL hotspot mutations c.109G>A (p.V37I and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not. The allelic frequency of the c.109G>A mutation was 9.03% (28/310, slightly higher than that of c.235delC (8.39%, 26/310, which is the most common GJB2 mutation in most areas of China. The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00. The SLC26A4 mutations were found in 16.77% (26/155 of this cohort. The most common pathogenic allele was c.IVS7-2A>G (6.13%, 19/310, and the second most common was the c.1079C>T (p.A360V mutation (1.94%, 6/310 which has rarely been reported as a hotspot mutation in other studies. The mutation rate of mtDNA12SrRNA in this group was 3.87% (6/155, all being the m.A1555G mutation. These findings show the specificity of the common deaf gene-mutation spectrum in this area. According to this study, there were specific hotspot mutations in Xiamen deaf patients. Comprehensive sequencing analysis of the three common deaf genes can help portray the mutation spectrum and develop optimal testing strategies for deaf patients in this area.

  4. Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

    Science.gov (United States)

    Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

    2015-01-01

    In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

  5. High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei.

    Science.gov (United States)

    Woo, Patrick C Y; Tam, Emily W T; Chong, Ken T K; Cai, James J; Tung, Edward T K; Ngan, Antonio H Y; Lau, Susanna K P; Yuen, Kwok-Yung

    2010-09-01

    Despite the unique phenotypic properties and clinical importance of Penicillium marneffei, the polyketide synthase genes in its genome have never been characterized. Twenty-three putative polyketide synthase genes and two putative polyketide synthase nonribosomal peptide-synthase hybrid genes were identified in the P. marneffei genome, a diversity much higher than found in other pathogenic thermal dimorphic fungi, such as Histoplasma capsulatum (one polyketide synthase gene) and Coccidioides immitis (10 polyketide synthase genes). These genes were evenly distributed on the phylogenetic tree with polyketide synthase genes of Aspergillus and other fungi, indicating that the high diversity was not a result of lineage-specific gene expansion through recent gene duplication. The melanin-biosynthesis gene cluster had gene order and orientations identical to those in the Talaromyces stipitatus (a teleomorph of Penicillium emmonsii) genome. Phylogenetically, all six genes of the melanin-biosynthesis gene cluster in P. marneffei were also most closely related to those in T. stipitatus, with high bootstrap supports. The polyketide synthase gene of the melanin-biosynthesis gene cluster (alb1) in P. marneffei was knocked down, which was accompanied by loss of melanin pigment production and reduced ornamentation in conidia. The survival of mice challenged with the alb1 knockdown mutant was significantly better than those challenged with wild-type P. marneffei (P melanin-biosynthesis gene cluster contributed to virulence through decreased susceptibility to killing by hydrogen peroxide. © 2010 The Authors Journal compilation © 2010 FEBS.

  6. Evolutionary and Topological Properties of Genes and Community Structures in Human Gene Regulatory Networks.

    Science.gov (United States)

    Szedlak, Anthony; Smith, Nicholas; Liu, Li; Paternostro, Giovanni; Piermarocchi, Carlo

    2016-06-01

    The diverse, specialized genes present in today's lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins' binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes' evolutionary properties. Slowly evolving ("cold"), old genes tend to interact with each other, as do rapidly evolving ("hot"), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN's community structures and its genes' evolutionary properties provide new perspectives for understanding evolutionary genetics.

  7. Reranking candidate gene models with cross-species comparison for improved gene prediction

    Directory of Open Access Journals (Sweden)

    Pereira Fernando CN

    2008-10-01

    Full Text Available Abstract Background Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc. Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models.

  8. Integrating Ontological Knowledge and Textual Evidence in Estimating Gene and Gene Product Similarity

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Tratz, Stephen C.; Gregory, Michelle L.

    2006-06-08

    With the rising influence of the Gene On-tology, new approaches have emerged where the similarity between genes or gene products is obtained by comparing Gene Ontology code annotations associ-ated with them. So far, these approaches have solely relied on the knowledge en-coded in the Gene Ontology and the gene annotations associated with the Gene On-tology database. The goal of this paper is to demonstrate that improvements to these approaches can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  9. Liposomes as a gene delivery system

    Directory of Open Access Journals (Sweden)

    C. Ropert

    1999-02-01

    Full Text Available Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.

  10. Validation of reference genes for quantifying changes in gene expression in virus-infected tobacco.

    Science.gov (United States)

    Baek, Eseul; Yoon, Ju-Yeon; Palukaitis, Peter

    2017-10-01

    To facilitate quantification of gene expression changes in virus-infected tobacco plants, eight housekeeping genes were evaluated for their stability of expression during infection by one of three systemically-infecting viruses (cucumber mosaic virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference-gene validation programs were used to establish the order of the most stable genes for the systemically-infecting viruses as ribosomal protein L25 > β-Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) genes were EF1α > Cysteine protease > Actin, and the least stable genes were GAPDH genes, three defense responsive genes were examined to compare their relative changes in gene expression caused by each virus. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Review: the dominant flocculation genes of Saccharomyces cerevisiae constitute a new subtelomeric gene family.

    Science.gov (United States)

    Teunissen, A W; Steensma, H Y

    1995-09-15

    The quality of brewing strains is, in large part, determined by their flocculation properties. By classical genetics, several dominant, semidominant and recessive flocculation genes have been recognized. Recent results of experiments to localize the flocculation genes FLO5 and FLO8, combined with the in silicio analysis of the available sequence data of the yeast genome, have revealed that the flocculation genes belong to a family which comprises at least four genes and three pseudogenes. All members of this gene family are located near the end of chromosomes, just like the SUC, MEL and MAL genes, which are also important for good quality baking or brewing strains. Transcription of the flocculation genes is repressed by several regulatory genes. In addition, a number of genes have been found which cause cell aggregation upon disruption or overexpression in an as yet unknown manner. In total, 33 genes have been reported that are involved in flocculation or cell aggregation.

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

    Science.gov (United States)

    An, Li; Obradovic, Zoran; Smith, Desmond; Bodenreider, Olivier; Megalooikonomou, Vasileios

    2009-11-01

    Association rules mining methods have been recently applied to gene expression data analysis to reveal relationships between genes and different conditions and features. However, not much effort has focused on detecting the relation between gene expression maps and related gene functions. Here we describe such an approach to mine association rules among gene functions in clusters of similar gene expression maps on mouse brain. The experimental results show that the detected association rules make sense biologically. By inspecting the obtained clusters and the genes having the gene functions of frequent itemsets, interesting clues were discovered that provide valuable insight to biological scientists. Moreover, discovered association rules can be potentially used to predict gene functions based on similarity of gene expression maps.

  13. Biological cluster evaluation for gene function prediction.

    Science.gov (United States)

    Klie, Sebastian; Nikoloski, Zoran; Selbig, Joachim

    2014-06-01

    Recent advances in high-throughput omics techniques render it possible to decode the function of genes by using the "guilt-by-association" principle on biologically meaningful clusters of gene expression data. However, the existing frameworks for biological evaluation of gene clusters are hindered by two bottleneck issues: (1) the choice for the number of clusters, and (2) the external measures which do not take in consideration the structure of the analyzed data and the ontology of the existing biological knowledge. Here, we address the identified bottlenecks by developing a novel framework that allows not only for biological evaluation of gene expression clusters based on existing structured knowledge, but also for prediction of putative gene functions. The proposed framework facilitates propagation of statistical significance at each of the following steps: (1) estimating the number of clusters, (2) evaluating the clusters in terms of novel external structural measures, (3) selecting an optimal clustering algorithm, and (4) predicting gene functions. The framework also includes a method for evaluation of gene clusters based on the structure of the employed ontology. Moreover, our method for obtaining a probabilistic range for the number of clusters is demonstrated valid on synthetic data and available gene expression profiles from Saccharomyces cerevisiae. Finally, we propose a network-based approach for gene function prediction which relies on the clustering of optimal score and the employed ontology. Our approach effectively predicts gene function on the Saccharomyces cerevisiae data set and is also employed to obtain putative gene functions for an Arabidopsis thaliana data set.

  14. Integrating various resources for gene name normalization.

    Science.gov (United States)

    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.

  15. Integrating various resources for gene name normalization.

    Directory of Open Access Journals (Sweden)

    Yuncui Hu

    Full Text Available 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.

  16. Finding approximate gene clusters with Gecko 3

    Science.gov (United States)

    Winter, Sascha; Jahn, Katharina; Wehner, Stefanie; Kuchenbecker, Leon; Marz, Manja; Stoye, Jens; Böcker, Sebastian

    2016-01-01

    Gene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often make restrictive assumptions such as short perfect conservation, conserved gene order or monophyletic gene clusters. We present Gecko 3, an open-source software for finding gene clusters in hundreds of bacterial genomes, that comes with an easy-to-use graphical user interface. The underlying gene cluster model is intuitive, can cope with low degrees of conservation as well as misannotations and is complemented by a sound statistical evaluation. To evaluate the biological benefit of Gecko 3 and to exemplify our method, we search for gene clusters in a dataset of 678 bacterial genomes using Synechocystis sp. PCC 6803 as a reference. We confirm detected gene clusters reviewing the literature and comparing them to a database of operons; we detect two novel clusters, which were confirmed by publicly available experimental RNA-Seq data. The computational analysis is carried out on a laptop computer in <40 min. PMID:27679480

  17. Bioinformatics study of the mangrove actin genes

    Science.gov (United States)

    Basyuni, M.; Wasilah, M.; Sumardi

    2017-01-01

    This study describes the bioinformatics methods to analyze eight actin genes from mangrove plants on DDBJ/EMBL/GenBank as well as predicted the structure, composition, subcellular localization, similarity, and phylogenetic. The physical and chemical properties of eight mangroves showed variation among the genes. The percentage of the secondary structure of eight mangrove actin genes followed the order of a helix > random coil > extended chain structure for BgActl, KcActl, RsActl, and A. corniculatum Act. In contrast to this observation, the remaining actin genes were random coil > extended chain structure > a helix. This study, therefore, shown the prediction of secondary structure was performed for necessary structural information. The values of chloroplast or signal peptide or mitochondrial target were too small, indicated that no chloroplast or mitochondrial transit peptide or signal peptide of secretion pathway in mangrove actin genes. These results suggested the importance of understanding the diversity and functional of properties of the different amino acids in mangrove actin genes. To clarify the relationship among the mangrove actin gene, a phylogenetic tree was constructed. Three groups of mangrove actin genes were formed, the first group contains B. gymnorrhiza BgAct and R. stylosa RsActl. The second cluster which consists of 5 actin genes the largest group, and the last branch consist of one gene, B. sexagula Act. The present study, therefore, supported the previous results that plant actin genes form distinct clusters in the tree.

  18. Gene Therapy Used in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Thomas Wirth

    2014-04-01

    Full Text Available Cancer has been, from the beginning, a target of intense research for gene therapy approaches. Currently, more than 60% of all on-going clinical gene therapy trials worldwide are targeting cancer. Indeed, there is a clear unmet medical need for novel therapies. This is further urged by the fact that current conventional cancer therapies are frequently troubled by their toxicities. Different gene therapy strategies have been employed for cancer, such as pro-drug activating suicide gene therapy, anti-angiogenic gene therapy, oncolytic virotherapy, gene therapy-based immune modulation, correction/compensation of gene defects, genetic manipulation of apoptotic and tumor invasion pathways, antisense, and RNAi strategies. Cancer types, which have been targeted with gene therapy, include brain, lung, breast, pancreatic, liver, colorectal, prostate, bladder, head and neck, skin, ovarian, and renal cancer. Currently, two cancer gene therapy products have received market approval, both of which are in China. In addition, the stimulation of the host’s immune system, using gene therapeutic approaches, has gained vast interest. The intention of this review is to point out the most commonly viral and non-viral vectors and methods used in cancer gene therapy, as well as highlight some key results achieved in clinical trials.

  19. Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms.

    Science.gov (United States)

    Li, Zhen; Defoort, Jonas; Tasdighian, Setareh; Maere, Steven; Van de Peer, Yves; De Smet, Riet

    2016-02-01

    Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of "gene duplicability" is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. © 2016 American Society of Plant Biologists. All rights reserved.

  20. Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms[OPEN

    Science.gov (United States)

    Li, Zhen; Van de Peer, Yves; De Smet, Riet

    2016-01-01

    Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of “gene duplicability” is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. PMID:26744215

  1. Analysis of gene order conservation in eukaryotes identifies transcriptionally and functionally linked genes.

    Directory of Open Access Journals (Sweden)

    Marcela Dávila López

    Full Text Available The order of genes in eukaryotes is not entirely random. Studies of gene order conservation are important to understand genome evolution and to reveal mechanisms why certain neighboring genes are more difficult to separate during evolution. Here, genome-wide gene order information was compiled for 64 species, representing a wide variety of eukaryotic phyla. This information is presented in a browser where gene order may be displayed and compared between species. Factors related to non-random gene order in eukaryotes were examined by considering pairs of neighboring genes. The evolutionary conservation of gene pairs was studied with respect to relative transcriptional direction, intergenic distance and functional relationship as inferred by gene ontology. The results show that among gene pairs that are conserved the divergently and co-directionally transcribed genes are much more common than those that are convergently transcribed. Furthermore, highly conserved pairs, in particular those of fungi, are characterized by a short intergenic distance. Finally, gene pairs of metazoa and fungi that are evolutionary conserved and that are divergently transcribed are much more likely to be related by function as compared to poorly conserved gene pairs. One example is the ribosomal protein gene pair L13/S16, which is unusual as it occurs both in fungi and alveolates. A specific functional relationship between these two proteins is also suggested by the fact that they are part of the same operon in both eubacteria and archaea. In conclusion, factors associated with non-random gene order in eukaryotes include relative gene orientation, intergenic distance and functional relationships. It seems likely that certain pairs of genes are conserved because the genes involved have a transcriptional and/or functional relationship. The results also indicate that studies of gene order conservation aid in identifying genes that are related in terms of transcriptional

  2. Recent advances in gene therapy for thalassemia

    Directory of Open Access Journals (Sweden)

    J V Raja

    2012-01-01

    Full Text Available Thalassemias are genetically transmitted disorders. Depending upon whether the genetic defects or deletion lies in transmission of α or β globin chain gene, thalassemias are classified into α and β-thalassemias. Thus, thalassemias could be cured by introducing or correcting a gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer have proved unsuccessful due to limitations of available gene transfer vectors. The present review described the newer approaches to overcome these limitations, includes the introduction of lentiviral vectors. New approaches have also focused on targeting the specific mutation in the globin genes, correcting the DNA sequence or manipulating the development in DNA translocation and splicing to restore globin chain synthesis. This review mainly discusses the gene therapy strategies for the thalassemias, including the use of lentiviral vectors, generation of induced pluripotent stem (iPS cells, gene targeting, splice-switching and stop codon readthrough.

  3. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    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. Adaptive Evolution of Gene Expression in Drosophila

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    Armita Nourmohammad

    2017-08-01

    Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

  5. MRI Reporter Genes for Noninvasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Caixia Yang

    2016-05-01

    Full Text Available Magnetic resonance imaging (MRI is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase, the receptor on the cells (e.g., transferrin receptor, and endogenous reporter genes (e.g., ferritin reporter gene. However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies.

  6. Cancer Genes in Lung Cancer

    Science.gov (United States)

    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

  7. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  8. Evolutionary signatures amongst disease genes permit novel methods for gene prioritization and construction of informative gene-based networks.

    Directory of Open Access Journals (Sweden)

    Nolan Priedigkeit

    2015-02-01

    Full Text Available 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.

  9. With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies.

    Science.gov (United States)

    Chapman, Joanne R; Waldenström, Jonas

    2015-01-01

    The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.

  10. Mathematical Models of Gene Regulation

    Science.gov (United States)

    Mackey, Michael C.

    2004-03-01

    This talk will focus on examples of mathematical models for the regulation of repressible operons (e.g. the tryptophan operon), inducible operons (e.g. the lactose operon), and the lysis/lysogeny switch in phage λ. These ``simple" gene regulatory elements can display characteristics experimentally of rapid response to perturbations and bistability, and biologically accurate mathematical models capture these aspects of the dynamics. The models, if realistic, are always nonlinear and contain significant time delays due to transcriptional and translational delays that pose substantial problems for the analysis of the possible ranges of dynamics.

  11. QB1 - Stochastic Gene Regulation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. The human crystallin gene families

    Directory of Open Access Journals (Sweden)

    Wistow Graeme

    2012-12-01

    Full Text Available Abstract Crystallins are the abundant, long-lived proteins of the eye lens. The major human crystallins belong to two different superfamilies: the small heat-shock proteins (α-crystallins and the βγ-crystallins. During evolution, other proteins have sometimes been recruited as crystallins to modify the properties of the lens. In the developing human lens, the enzyme betaine-homocysteine methyltransferase serves such a role. Evolutionary modification has also resulted in loss of expression of some human crystallin genes or of specific splice forms. Crystallin organization is essential for lens transparency and mutations; even minor changes to surface residues can cause cataract and loss of vision.

  13. Impact of gene family evolutionary histories on phylogenetic species tree inference by gene tree parsimony.

    Science.gov (United States)

    Shi, Tao

    2016-03-01

    Complicated history of gene duplication and loss brings challenge to molecular phylogenetic inference, especially in deep phylogenies. However, phylogenomic approaches, such as gene tree parsimony (GTP), show advantage over some other approaches in its ability to use gene families with duplications. GTP searches the 'optimal' species tree by minimizing the total cost of biological events such as duplications, but accuracy of GTP and phylogenetic signal in the context of different gene families with distinct histories of duplication and loss are unclear. To evaluate how different evolutionary properties of different gene families can impact on species tree inference, 3900 gene families from seven angiosperms encompassing a wide range of gene content, lineage-specific expansions and contractions were analyzed. It was found that the gene content and total duplication number in a gene family strongly influence species tree inference accuracy, with the highest accuracy achieved at either very low or very high gene content (or duplication number) and lowest accuracy centered in intermediate gene content (or duplication number), as the relationship can fit a binomial regression. Besides, for gene families of similar level of average gene content, those with relatively higher lineage-specific expansion or duplication rates tend to show lower accuracy. Additional correlation tests support that high accuracy for those gene families with large gene content may rely on abundant ancestral copies to provide many subtrees to resolve conflicts, whereas high accuracy for single or low copy gene families are just subject to sequence substitution per se. Very low accuracy reached by gene families of intermediate gene content or duplication number can be due to insufficient subtrees to resolve the conflicts from loss of alternative copies. As these evolutionary properties can significantly influence species tree accuracy, I discussed the potential weighting of the duplication cost by

  14. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  16. The iojap gene in maize

    Energy Technology Data Exchange (ETDEWEB)

    Martienssen, Robert

    2001-12-01

    The classical maize mutant iojap (Iodent japonica) has variegated green and white leaves. Green sectors have cells with normal chloroplasts whereas white sectors have cells where plastids fail to differentiate. These mutant plastids, when transmitted through the female gametophyte, do not recover in the presence of wild type Iojap. We cloned the Ij locus, and we have investigated the mechanism of epigenetic inheritance and phenotypic expression. More recently, a modifier of this type of variegation, ''Inhibitor of striate'', has also been cloned. Both the iojap and inhibitor of striate proteins have homologs in bacteria and are members of ancient conserved families found in multiple species. These tools can be used to address fundamental questions of inheritance and variegation associated with this classical conundrum of maize genetics. Since the work of Rhoades there has been considerable speculation concerning the nature of the Iojap gene product, the origin of leaf variegation and the mechanism behind the material inheritance of defective plastids. This has made Iojap a textbook paradigm for cytoplasmic inheritance and nuclear-organellar interaction for almost 50 years. Cloning of the Iojap gene in maize, and homologs in other plants and bacteria, provides a new means to address the origin of heteroplastidity, variegation and cytoplasmic inheritance in higher plants.

  17. Genes that bias Mendelian segregation.

    Directory of Open Access Journals (Sweden)

    Pierre Grognet

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

  18. Genes that bias Mendelian segregation.

    Science.gov (United States)

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

    2014-01-01

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

  19. Reporter Gene Assays in Ecotoxicology.

    Science.gov (United States)

    Elad, Tal; Belkin, Shimshon

    The need for simple and rapid means for evaluating the potential toxic effects of environmental samples has prompted the development of reporter gene assays, based on tester cells (bioreporters) genetically engineered to report on sample toxicity by producing a readily quantifiable signal. Bacteria are especially suitable to serve as bioreporters owing to their fast responses, low cost, convenient preservation, ease of handling, and amenability to genetic manipulations. Various bacterial bioreporters have been introduced for general toxicity and genotoxicity assessment, and the monitoring of endocrine disrupting and dioxin-like compounds has been mostly covered by similarly engineered eukaryotic cells. Some reporter gene assays have been validated, standardized, and accredited, and many others are under constant development. Efforts are aimed at broadening detection spectra, lowering detection thresholds, and combining toxicity identification capabilities with characterization of the toxic effects. Taking advantage of bacterial robustness, attempts are also being made to incorporate bacterial bioreporters into field instrumentation for online continuous monitoring or on-site spot checks. However, key hurdles concerning test validation, cell preservation, and regulatory issues related to the use of genetically modified organisms still remain to be overcome.

  20. Gene Ontology annotations and resources.

    Science.gov (United States)

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

    2013-01-01

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

  1. Multiconstrained gene clustering based on generalized projections

    Directory of Open Access Journals (Sweden)

    Zhu Shanfeng

    2010-03-01

    Full Text Available Abstract Background Gene clustering for annotating gene functions is one of the fundamental issues in bioinformatics. The best clustering solution is often regularized by multiple constraints such as gene expressions, Gene Ontology (GO annotations and gene network structures. How to integrate multiple pieces of constraints for an optimal clustering solution still remains an unsolved problem. Results We propose a novel multiconstrained gene clustering (MGC method within the generalized projection onto convex sets (POCS framework used widely in image reconstruction. Each constraint is formulated as a corresponding set. The generalized projector iteratively projects the clustering solution onto these sets in order to find a consistent solution included in the intersection set that satisfies all constraints. Compared with previous MGC methods, POCS can integrate multiple constraints from different nature without distorting the original constraints. To evaluate the clustering solution, we also propose a new performance measure referred to as Gene Log Likelihood (GLL that considers genes having more than one function and hence in more than one cluster. Comparative experimental results show that our POCS-based gene clustering method outperforms current state-of-the-art MGC methods. Conclusions The POCS-based MGC method can successfully combine multiple constraints from different nature for gene clustering. Also, the proposed GLL is an effective performance measure for the soft clustering solutions.

  2. Targeting Herpetic Keratitis by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Hossein Mostafa Elbadawy

    2012-01-01

    Full Text Available Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1 can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.

  3. Gene panel testing for hereditary breast cancer.

    Science.gov (United States)

    Winship, Ingrid; Southey, Melissa C

    2016-03-21

    Inherited predisposition to breast cancer is explained only in part by mutations in the BRCA1 and BRCA2 genes. Most families with an apparent familial clustering of breast cancer who are investigated through Australia's network of genetic services and familial cancer centres do not have mutations in either of these genes. More recently, additional breast cancer predisposition genes, such as PALB2, have been identified. New genetic technology allows a panel of multiple genes to be tested for mutations in a single test. This enables more women and their families to have risk assessment and risk management, in a preventive approach to predictable breast cancer. Predictive testing for a known family-specific mutation in a breast cancer predisposition gene provides personalised risk assessment and evidence-based risk management. Breast cancer predisposition gene panel tests have a greater diagnostic yield than conventional testing of only the BRCA1 and BRCA2 genes. The clinical validity and utility of some of the putative breast cancer predisposition genes is not yet clear. Ethical issues warrant consideration, as multiple gene panel testing has the potential to identify secondary findings not originally sought by the test requested. Multiple gene panel tests may provide an affordable and effective way to investigate the heritability of breast cancer.

  4. Evolution of the Vertebrate Resistin Gene Family.

    Directory of Open Access Journals (Sweden)

    Qingda Hu

    Full Text Available 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.

  5. Selection of Phototransduction Genes in Homo sapiens.

    Science.gov (United States)

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

    2013-08-13

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

  6. Application of multidisciplinary analysis to gene expression.

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-01-01

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

  7. Mining gene expression data of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Pi Guo

    Full Text Available Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined.An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score.The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

  8. Analysis of mouse embryonic gene library for the frequency of single and multiple copy genes.

    Science.gov (United States)

    Mory, Y Y; Keshet, E; Ram, D; Kaminchik, Y

    1980-12-31

    A gene library was constructed from embryonic mouse DNA by ligating DNA fragments generated by partial Eco RI digestion with Charon 4A vector and in vitro packaging. A special consideration was given to randomization of target DNA. The general applicability of a gene library prepared in this manner was assessed through cloning a variety of genes of known reiteration frequency in the mouse genome. The survey included a single copy gene--C region of the immunoglobulin heavy chain, and genes that appear in more than one copy--V region of the immunoglobulin light chain genes and the endogenous retrovirus related genes. In all cases tested the frequency of clone isolation was in good agreement with the expected incidence based on the number of genome equivalents screened and the reiteration frequency of that particular gene. Moreover, we found no preference with regard to the clonability of genes contained in fragments of a wide-size range.

  9. Autism risk factors: genes, environment, and gene-environment interactions.

    Science.gov (United States)

    Chaste, Pauline; Leboyer, Marion

    2012-09-01

    The aim of this review is to summarize the key findings from genetic and epidemiological research, which show that autism is a complex disorder resulting from the combination of genetic and environmental factors. Remarkable advances in the knowledge of genetic causes of autism have resulted from the great efforts made in the field of genetics. The identification of specific alleles contributing to the autism spectrum has supplied important pieces for the autism puzzle. However, many questions remain unanswered, and new questions are raised by recent results. Moreover, given the amount of evidence supporting a significant contribution of environmental factors to autism risk, it is now clear that the search for environmental factors should be reinforced. One aspect of this search that has been neglected so far is the study of interactions between genes and environmental factors.

  10. Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

    Directory of Open Access Journals (Sweden)

    Tintle Nathan L

    2012-08-01

    Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.

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

    Directory of Open Access Journals (Sweden)

    Zhimin Dai

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

  12. Pyviko: an automated Python tool to design gene knockouts in complex viruses with overlapping genes.

    Science.gov (United States)

    Taylor, Louis J; Strebel, Klaus

    2017-01-07

    Gene knockouts are a common tool used to study gene function in various organisms. However, designing gene knockouts is complicated in viruses, which frequently contain sequences that code for multiple overlapping genes. Designing mutants that can be traced by the creation of new or elimination of existing restriction sites further compounds the difficulty in experimental design of knockouts of overlapping genes. While software is available to rapidly identify restriction sites in a given nucleotide sequence, no existing software addresses experimental design of mutations involving multiple overlapping amino acid sequences in generating gene knockouts. Pyviko performed well on a test set of over 240,000 gene pairs collected from viral genomes deposited in the National Center for Biotechnology Information Nucleotide database, identifying a point mutation which added a premature stop codon within the first 20 codons of the target gene in 93.2% of all tested gene-overprinted gene pairs. This shows that Pyviko can be used successfully in a wide variety of contexts to facilitate the molecular cloning and study of viral overprinted genes. Pyviko is an extensible and intuitive Python tool for designing knockouts of overlapping genes. Freely available as both a Python package and a web-based interface ( http://louiejtaylor.github.io/pyViKO/ ), Pyviko simplifies the experimental design of gene knockouts in complex viruses with overlapping genes.

  13. Gene expression studies of reference genes for quantitative real-time PCR: an overview in insects.

    Science.gov (United States)

    Shakeel, Muhammad; Rodriguez, Alicia; Tahir, Urfa Bin; Jin, Fengliang

    2017-11-09

    Whenever gene expression is being examined, it is essential that a normalization process is carried out to eliminate non-biological variations. The use of reference genes, such as glyceraldehyde-3-phosphate dehydrogenase, actin, and ribosomal protein genes, is the usual method of choice for normalizing gene expression. Although reference genes are used to normalize target gene expression, a major problem is that the stability of these genes differs among tissues, developmental stages, species, and responses to abiotic factors. Therefore, the use and validation of multiple reference genes are required. This review discusses the reasons that why RT-qPCR has become the preferred method for validating results of gene expression profiles, the use of specific and non-specific dyes and the importance of use of primers and probes for qPCR as well as to discuss several statistical algorithms developed to help the validation of potential reference genes. The conflicts arising in the use of classical reference genes in gene normalization and their replacement with novel references are also discussed by citing the high stability and low stability of classical and novel reference genes under various biotic and abiotic experimental conditions by employing various methods applied for the reference genes amplification.

  14. Using GeneReg to construct time delay gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Qian Ziliang

    2010-05-01

    Full Text Available Abstract Background Understanding gene expression and regulation is essential for understanding biological mechanisms. Because gene expression profiling has been widely used in basic biological research, especially in transcription regulation studies, we have developed GeneReg, an easy-to-use R package, to construct gene regulatory networks from time course gene expression profiling data; More importantly, this package can provide information about time delays between expression change in a regulator and that of its target genes. Findings The R package GeneReg is based on time delay linear regression, which can generate a model of the expression levels of regulators at a given time point against the expression levels of their target genes at a later time point. There are two parameters in the model, time delay and regulation coefficient. Time delay is the time lag during which expression change of the regulator is transmitted to change in target gene expression. Regulation coefficient expresses the regulation effect: a positive regulation coefficient indicates activation and negative indicates repression. GeneReg was implemented on a real Saccharomyces cerevisiae cell cycle dataset; more than thirty percent of the modeled regulations, based entirely on gene expression files, were found to be consistent with previous discoveries from known databases. Conclusions GeneReg is an easy-to-use, simple, fast R package for gene regulatory network construction from short time course gene expression data. It may be applied to study time-related biological processes such as cell cycle, cell differentiation, or causal inference.

  15. Improved gene tree error correction in the presence of horizontal gene transfer.

    Science.gov (United States)

    Bansal, Mukul S; Wu, Yi-Chieh; Alm, Eric J; Kellis, Manolis

    2015-04-15

    The accurate inference of gene trees is a necessary step in many evolutionary studies. Although the problem of accurate gene tree inference has received considerable attention, most existing methods are only applicable to gene families unaffected by horizontal gene transfer. As a result, the accurate inference of gene trees affected by horizontal gene transfer remains a largely unaddressed problem. In this study, we introduce a new and highly effective method for gene tree error correction in the presence of horizontal gene transfer. Our method efficiently models horizontal gene transfers, gene duplications and losses, and uses a statistical hypothesis testing framework [Shimodaira-Hasegawa (SH) test] to balance sequence likelihood with topological information from a known species tree. Using a thorough simulation study, we show that existing phylogenetic methods yield inaccurate gene trees when applied to horizontally transferred gene families and that our method dramatically improves gene tree accuracy. We apply our method to a dataset of 11 cyanobacterial species and demonstrate the large impact of gene tree accuracy on downstream evolutionary analyses. An implementation of our method is available at http://compbio.mit.edu/treefix-dtl/ : mukul@engr.uconn.edu or manoli@mit.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  16. Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis.

    Science.gov (United States)

    Ma, Shisong; Snyder, Michael; Dinesh-Kumar, Savithramma P

    2017-07-17

    Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif's enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules. The analysis revealed known and novel gene modules regulated by the NF-Y motif. The binding of NF-Y proteins to these modules' gene promoters were verified using ENCODE ChIP-Seq data. The analyses also identified 8,048 Sp1 motif target genes, interestingly many of which were not detected by ENCODE ChIP-Seq. These target genes assemble into house-keeping, tissues-specific developmental, and immune response modules. Integration of Sp1 modules with genomic and epigenomic data indicates epigenetic control of Sp1 targets' expression in a cell/tissue specific manner. Finally, known and novel target genes and modules regulated by the YY1, RFX1, IRF1, and 34 other motifs were also identified. The study described here provides a valuable resource to understand transcriptional regulation of various human developmental, disease, or immunity pathways.

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

    Directory of Open Access Journals (Sweden)

    Hao Weilong

    2010-12-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

    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

  19. Using RNA-seq data to select reference genes for normalizing gene expression in apple roots.

    Science.gov (United States)

    Zhou, Zhe; Cong, Peihua; Tian, Yi; Zhu, Yanmin

    2017-01-01

    Gene expression in apple roots in response to various stress conditions is a less-explored research subject. Reliable reference genes for normalizing quantitative gene expression data have not been carefully investigated. In this study, the suitability of a set of 15 apple genes were evaluated for their potential use as reliable reference genes. These genes were selected based on their low variance of gene expression in apple root tissues from a recent RNA-seq data set, and a few previously reported apple reference genes for other tissue types. Four methods, Delta Ct, geNorm, NormFinder and BestKeeper, were used to evaluate their stability in apple root tissues of various genotypes and under different experimental conditions. A small panel of stably expressed genes, MDP0000095375, MDP0000147424, MDP0000233640, MDP0000326399 and MDP0000173025 were recommended for normalizing quantitative gene expression data in apple roots under various abiotic or biotic stresses. When the most stable and least stable reference genes were used for data normalization, significant differences were observed on the expression patterns of two target genes, MdLecRLK5 (MDP0000228426, a gene encoding a lectin receptor like kinase) and MdMAPK3 (MDP0000187103, a gene encoding a mitogen-activated protein kinase). Our data also indicated that for those carefully validated reference genes, a single reference gene is sufficient for reliable normalization of the quantitative gene expression. Depending on the experimental conditions, the most suitable reference genes can be specific to the sample of interest for more reliable RT-qPCR data normalization.

  20. EasyGene – a prokaryotic gene finder that ranks ORFs by statistical significance

    DEFF Research Database (Denmark)

    Larsen, Thomas Schou; Krogh, Anders Stærmose

    2003-01-01

    annotated as genes.Results: In this paper, we present a new automated gene-finding method, EasyGene, which estimates the statistical significance of a predicted gene. The gene finder is based on a hidden Markov model (HMM) that is automatically estimated for a new genome. Using extensions of similarities...... is the expected number of ORFs in one megabase of random sequence at the same significance level or better, where the random sequence has the same statistics as the genome in the sense of a third order Markov chain.Conclusions: The result is a flexible gene finder whose overall performance matches or exceeds...

  1. Gene bookmarking: keeping the pages open.

    Science.gov (United States)

    Sarge, Kevin D; Park-Sarge, Ok-Kyong

    2005-11-01

    'Gene bookmarking' is a mechanism of epigenetic memory that functions to transmit through mitosis the pattern of active genes and/or genes that can be activated to daughter cells. It is thought that, at a point before mitosis, genes that exist in an open, transcriptionally competent state are bound by proteins or marked by some kind of modification event. This is thought to facilitate the assembly of transcription complexes on the promoters in early G1, thereby ensuring that daughter cells have the same pattern of gene expression as the cell from which they derived. Little is known, however, about these 'bookmarking factors' and modifications or the mechanisms by which they mediate the transmission of transcriptional competence after mitosis is complete. Recent findings have provided new insights into the mechanisms, regulation and biological importance of gene bookmarking in eukaryotic cell function.

  2. Multiclass gene selection using Pareto-fronts.

    Science.gov (United States)

    Rajapakse, Jagath C; Mundra, Piyushkumar A

    2013-01-01

    Filter methods are often used for selection of genes in multiclass sample classification by using microarray data. Such techniques usually tend to bias toward a few classes that are easily distinguishable from other classes due to imbalances of strong features and sample sizes of different classes. It could therefore lead to selection of redundant genes while missing the relevant genes, leading to poor classification of tissue samples. In this manuscript, we propose to decompose multiclass ranking statistics into class-specific statistics and then use Pareto-front analysis for selection of genes. This alleviates the bias induced by class intrinsic characteristics of dominating classes. The use of Pareto-front analysis is demonstrated on two filter criteria commonly used for gene selection: F-score and KW-score. A significant improvement in classification performance and reduction in redundancy among top-ranked genes were achieved in experiments with both synthetic and real-benchmark data sets.

  3. Gene signatures in hepatocellular carcinoma (HCC).

    Science.gov (United States)

    Andrisani, Ourania M; Studach, Leo; Merle, Philippe

    2011-02-01

    Primary hepatocellular carcinoma (HCC) is a significant human cancer globally, with poor prognosis. New and efficacious therapy strategies are needed as well as new biomarkers for early detection of at-risk patients. In this review, we discuss select microarray studies of human HCCs, and propose a gene signature that has promise for clinical/translational application. This gene signature combines the proliferation cluster of genes and the hepatic cancer initiating/stem cell gene cluster for identification of HCCs with poor prognosis. Evidence from cell-based assays identifies the existence of a mechanistic link between these two gene clusters, involving the proliferation cluster gene polo-like kinase 1 (PLK1). We propose that PLK1 is a promising therapy target for HCC. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Gearbox gene expression and growth rate.

    Science.gov (United States)

    Aldea, M; Garrido, T; Tormo, A

    1993-07-01

    Regulation of gene expression in prokaryotic cells usually takes place at the level of transcription initiation. Different forms of RNA polymerase recognizing specific promoters are engaged in the control of many prokaryotic regulons. This also seems to be the case for some Escherichia coli genes that are induced at low growth rates and by nutrient starvation. Their gene products are synthesized at levels inversely proportional to growth rate, and this mode of regulation has been termed gearbox gene expression. This kind of growth-rate modulation is exerted by specific transcriptional initiation signals, the gearbox promoters, and some of them depend on a putative new σ factor (RpoS). Gearbox promoters drive expression of morphogenetic and cell division genes at constant levels per cell and cycle to meet the demands of cell division and septum formation. A mechanism is proposed that could sense the growth rate of the cell to alter gene expression by the action of specific σ factors.

  5. Duplicability of self-interacting human genes

    Directory of Open Access Journals (Sweden)

    Makino Takashi

    2010-05-01

    Full Text Available Abstract Background There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. Results We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD or small-scale duplication (SSD, and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. Conclusions Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.

  6. Methods for monitoring multiple gene expression

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Extensive complementarity between gene function prediction methods.

    Science.gov (United States)

    Vidulin, Vedrana; Šmuc, Tomislav; Supek, Fran

    2016-12-01

    The number of sequenced genomes rises steadily but we still lack the knowledge about the biological roles of many genes. Automated function prediction (AFP) is thus a necessity. We hypothesized that AFP approaches that draw on distinct genome features may be useful for predicting different types of gene functions, motivating a systematic analysis of the benefits gained by obtaining and integrating such predictions. Our pipeline amalgamates 5 133 543 genes from 2071 genomes in a single massive analysis that evaluates five established genomic AFP methodologies. While 1227 Gene Ontology (GO) terms yielded reliable predictions, the majority of these functions were accessible to only one or two of the methods. Moreover, different methods tend to assign a GO term to non-overlapping sets of genes. Thus, inferences made by diverse genomic AFP methods display a striking complementary, both gene-wise and function-wise. Because of this, a viable integration strategy is to rely on a single most-confident prediction per gene/function, rather than enforcing agreement across multiple AFP methods. Using an information-theoretic approach, we estimate that current databases contain 29.2 bits/gene of known Escherichia coli gene functions. This can be increased by up to 5.5 bits/gene using individual AFP methods or by 11 additional bits/gene upon integration, thereby providing a highly-ranking predictor on the Critical Assessment of Function Annotation 2 community benchmark. Availability of more sequenced genomes boosts the predictive accuracy of AFP approaches and also the benefit from integrating them. The individual and integrated GO predictions for the complete set of genes are available from http://gorbi.irb.hr/ CONTACT: fran.supek@irb.hrSupplementary information: Supplementary materials are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Gene Ontology (GO) Annotation in Biomedical Literature

    OpenAIRE

    Gálvez, Carmen

    2008-01-01

    In this paper, we propose an approach for doing Gene Ontology (GO) annotation on biomedical texts. The GO is an effort to create a controlled terminology for labelling gene functions in a more precise. Our system is based on the application of Parametrized Finite-State Graphs (P-FSG) for GO tagging. This process was implemented to the annotation of genes related with Alzehimer disease. This prototype is an undergoing work, in the future should be evaluated to verify its value

  9. Gene Therapy: A Paradigm Shift in Dentistry

    OpenAIRE

    Nida Siddique; Hira Raza; Sehrish Ahmed; Zohaib Khurshid; Muhammad Sohail Zafar

    2016-01-01

    Gene therapy holds a promising future for bridging the gap between the disciplines of medicine and clinical dentistry. The dynamic treatment approaches of gene therapy have been advancing by leaps and bounds. They are transforming the conventional approaches into more precise and preventive ones that may limit the need of using drugs and surgery. The oral cavity is one of the most accessible areas for the clinical applications of gene therapy for various oral tissues. The idea of genetic engi...

  10. Methods for monitoring multiple gene expression

    Science.gov (United States)

    Berka, Randy; Bachkirova, Elena; Rey, Michael

    2013-10-01

    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.

  11. Duplicability of self-interacting human genes.

    LENUS (Irish Health Repository)

    Pérez-Bercoff, Asa

    2010-01-01

    BACKGROUND: There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS: We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS: Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.

  12. Gradient descent optimization in gene regulatory pathways.

    Science.gov (United States)

    Das, Mouli; Mukhopadhyay, Subhasis; De, Rajat K

    2010-09-03

    Gene Regulatory Networks (GRNs) have become a major focus of interest in recent years. Elucidating the architecture and dynamics of large scale gene regulatory networks is an important goal in systems biology. The knowledge of the gene regulatory networks further gives insights about gene regulatory pathways. This information leads to many potential applications in medicine and molecular biology, examples of which are identification of metabolic pathways, complex genetic diseases, drug discovery and toxicology analysis. High-throughput technologies allow studying various aspects of gene regulatory networks on a genome-wide scale and we will discuss recent advances as well as limitations and future challenges for gene network modeling. Novel approaches are needed to both infer the causal genes and generate hypothesis on the underlying regulatory mechanisms. In the present article, we introduce a new method for identifying a set of optimal gene regulatory pathways by using structural equations as a tool for modeling gene regulatory networks. The method, first of all, generates data on reaction flows in a pathway. A set of constraints is formulated incorporating weighting coefficients. Finally the gene regulatory pathways are obtained through optimization of an objective function with respect to these weighting coefficients. The effectiveness of the present method is successfully tested on ten gene regulatory networks existing in the literature. A comparative study with the existing extreme pathway analysis also forms a part of this investigation. The results compare favorably with earlier experimental results. The validated pathways point to a combination of previously documented and novel findings. We show that our method can correctly identify the causal genes and effectively output experimentally verified pathways. The present method has been successful in deriving the optimal regulatory pathways for all the regulatory networks considered. The biological

  13. Gene expression inference with deep learning.

    Science.gov (United States)

    Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

    2016-06-15

    Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. miRNA regulation of cytokine genes

    OpenAIRE

    Asirvatham, Ananthi J.; Magner, William J.; Tomasi, Thomas B.

    2009-01-01

    In this review we discuss specific examples of regulation of cytokine genes and focus on a new mechanism involving post-transcriptional regulation via miRNAs. The post-transcriptional regulation of cytokine genes via the destabilizing activity of AU-rich elements [AREs] and miRNAs is a pre-requisite for regulating the half-life of many cytokines and achieving the temporal and spatial distributions required for regulation of these genes.

  15. Evolution of trappin genes in mammals

    Directory of Open Access Journals (Sweden)

    Furutani Yutaka

    2010-01-01

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

  16. Dynamics of bacterial gene regulation

    Science.gov (United States)

    Narang, Atul

    2009-03-01

    The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model.

  17. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  18. Gene regulation by mechanical forces

    Science.gov (United States)

    Oluwole, B. O.; Du, W.; Mills, I.; Sumpio, B. E.

    1997-01-01

    Endothelial cells are subjected to various mechanical forces in vivo from the flow of blood across the luminal surface of the blood vessel. The purpose of this review was to examine the data available on how these mechanical forces, in particular cyclic strain, affect the expression and regulation of endothelial cell function. Studies from various investigators using models of cyclic strain in vitro have shown that various vasoactive mediators such as nitric oxide and prostacyclin are induced by the effect of mechanical deformation, and that the expression of these mediators may be regulated at the transcription level by mechanical forces. There also seems to be emerging evidence that endothelial cells may also act as mechanotransducers, whereby the transmission of external forces induces various cytoskeletal changes and second messenger cascades. Furthermore, it seems these forces may act on specific response elements of promoter genes.

  19. Genetics of human gene expression.

    Science.gov (United States)

    Stranger, Barbara E; Raj, Towfique

    2013-12-01

    A steadily growing number of studies have identified and characterized expression quantitative trait loci (eQTLs) in human cell-lines, primary cells, and tissues. This class of variation has been shown to play a role in complex traits, including disease. Here, we discuss how eQTLs have the potential to accelerate discovery of disease genes and functional mechanisms underlying complex traits. We discuss how context-specificity of eQTLs is being characterized at an unprecedented scale and breadth, and how this both informs on the intricacy of human genome function, and has important ramifications for elucidating function of genetic variants of interest, particularly for those contributing to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Cómo identificar genes

    Directory of Open Access Journals (Sweden)

    N. Pineda-Trujillo

    2001-07-01

    Full Text Available En esta era de la genética, cada vez, es más posible que tengamos las herramientas de laGenética Molecular a nuestra disposición. La metodología del clonaje posicional, la cual termina con el aislamiento y caracterización degenes que contienen variantes asociadas a la característica estudiada, se inicia con la identifica-ción de la región cromosómica que contiene el gen (o genes responsables del fenotipo estudiado.Estas regiones son identificadas en la actualidad a través de dos metodologías generales: Lasparamétricas y las No-paramétricas. En general, las primeras arrojan valores de ligamiento (Lodscore y son más robustas, mientras que las segundas arrojan valores de asociación “alélica”.

  1. The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs.

    Science.gov (United States)

    Borrás, Teresa

    2017-01-01

    Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration. Copyright© 2017 Asia-Pacific Academy of Ophthalmology.

  2. DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis

    Directory of Open Access Journals (Sweden)

    Baseler Michael W

    2007-11-01

    Full Text Available Abstract Background Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. Description The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. Conclusion The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/.

  3. Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

    Science.gov (United States)

    Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

    2017-08-01

    This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  4. Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer.

    Science.gov (United States)

    Chiu, Yu-Chiao; Wang, Li-Ju; Hsiao, Tzu-Hung; Chuang, Eric Y; Chen, Yidong

    2017-10-03

    With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome-wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations.

  5. Gene-Environment Interaction in Parkinson's Disease

    DEFF Research Database (Denmark)

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen

    2016-01-01

    BACKGROUND AND PURPOSE: Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabol......BACKGROUND AND PURPOSE: Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2...

  6. Pichia stipitis genomics, transcriptomics, and gene clusters.

    Science.gov (United States)

    Jeffries, Thomas W; Van Vleet, Jennifer R Headman

    2009-09-01

    Genome sequencing and subsequent global gene expression studies have advanced our understanding of the lignocellulose-fermenting yeast Pichia stipitis. These studies have provided an insight into its central carbon metabolism, and analysis of its genome has revealed numerous functional gene clusters and tandem repeats. Specialized physiological traits are often the result of several gene products acting together. When coinheritance is necessary for the overall physiological function, recombination and selection favor colocation of these genes in a cluster. These are particularly evident in strongly conserved and idiomatic traits. In some cases, the functional clusters consist of multiple gene families. Phylogenetic analyses of the members in each family show that once formed, functional clusters undergo duplication and differentiation. Genome-wide expression analysis reveals that regulatory patterns of clusters are similar after they have duplicated and that the expression profiles evolve along with functional differentiation of the clusters. Orthologous gene families appear to arise through tandem gene duplication, followed by differentiation in the regulatory and coding regions of the gene. Genome-wide expression analysis combined with cross-species comparisons of functional gene clusters should reveal many more aspects of eukaryotic physiology.

  7. Cloning arbuscule-related genes from mycorrhizas

    DEFF Research Database (Denmark)

    Burleigh, Stephen

    2000-01-01

    Until recently little was known about the identity of the genes expressed in the arbuscules of mycorrhizas, due in part to problems associated with cloning genes from the tissues of an obligate symbiont. However, the combination of advanced molecular techniques, innovative use of the materials...... available and fortuitous cloning has resulted in the recent identification of a number of arbuscule-related genes. This article provides a brief summary of the genes involved in arbuscule development, function and regulation, and the techniques used to study them. Molecular techniques include differential...

  8. Robust gene dysregulation in Alzheimer's disease brains.

    Science.gov (United States)

    Feng, Xuemei; Bai, Zhouxian; Wang, Jiajia; Xie, Bin; Sun, Jiya; Han, Guangchun; Song, Fuhai; Crack, Peter J; Duan, Yong; Lei, Hongxing

    2014-01-01

    The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation. Based on this observation, we selected 100 genes with the highest frequency of dysregulation to illustrate the core perturbation in AD brains. The dysregulation of these genes was validated in several independent datasets for AD. We further identified 12 genes with strong correlation of gene expression with disease progression. The relevance of these genes to disease progression was also validated in an independent dataset. Interestingly, we found a transcriptional "cushion" for these 100 genes in the less vulnerable visual cortex region, which may be a critical component of the protection mechanism for less vulnerable brain regions. To facilitate the research in this field, we have provided the expression information of ~8000 relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn).

  9. Structure of the murine Thy-1 gene.

    Science.gov (United States)

    Giguére, V; Isobe, K; Grosveld, F

    1985-01-01

    We have cloned the murine Thy-1.1 (AKR) and Thy-1.2 (Balb/c) genes. The complete exon/intron structure and the nucleotide sequence of the Thy-1.2 gene was determined. The gene contains four exons and three intervening sequences. The complete transcriptional unit gives rise to a tissue and developmental stage-specific mRNA of 1850 bp. The 5' end of the gene has multiple initiation sites and a non-TATA box promoter. The 3' end shows a single polyadenylation site after a very long untranslated region. Images Fig. 3. Fig. 5. Fig. 6. Fig. 8. PMID:2866091

  10. Detecting Highways of Horizontal Gene Transfer

    Science.gov (United States)

    Bansal, Mukul S.; Gogarten, J. Peter; Shamir, Ron

    In a horizontal gene transfer (HGT) event a gene is transferred between two species that do not share an ancestor-descendant relationship. Typically, no more than a few genes are horizontally transferred between any two species. However, several studies identified pairs of species between which many different genes were horizontally transferred. Such a pair is said to be linked by a highway of gene sharing. We present a method for inferring such highways. Our method is based on the fact that the evolutionary histories of horizontally transferred genes disagree with the corresponding species phylogeny. Specifically, given a set of gene trees and a trusted rooted species tree, each gene tree is first decomposed into its constituent quartet trees and the quartets that are inconsistent with the species tree are identified. Our method finds a pair of species such that a highway between them explains the largest (normalized) fraction of inconsistent quartets. For a problem on n species, our method requires O(n 4) time, which is optimal with respect to the quartets input size. An application of our method to a dataset of 1128 genes from 11 cyanobacterial species, as well as to simulated datasets, illustrates the efficacy of our method.

  11. Differential gene expression during Trypanosoma cruzi metacyclogenesis

    Directory of Open Access Journals (Sweden)

    Marco Aurelio Krieger

    1999-09-01

    Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

  12. Maximizing biomarker discovery by minimizing gene signatures

    Directory of Open Access Journals (Sweden)

    Chang Chang

    2011-12-01

    Full Text Available Abstract Background The use of gene signatures can potentially be of considerable value in the field of clinical diagnosis. However, gene signatures defined with different methods can be quite various even when applied the same disease and the same endpoint. Previous studies have shown that the correct selection of subsets of genes from microarray data is key for the accurate classification of disease phenotypes, and a number of methods have been proposed for the purpose. However, these methods refine the subsets by only considering each single feature, and they do not confirm the association between the genes identified in each gene signature and the phenotype of the disease. We proposed an innovative new method termed Minimize Feature's Size (MFS based on multiple level similarity analyses and association between the genes and disease for breast cancer endpoints by comparing classifier models generated from the second phase of MicroArray Quality Control (MAQC-II, trying to develop effective meta-analysis strategies to transform the MAQC-II signatures into a robust and reliable set of biomarker for clinical applications. Results We analyzed the similarity of the multiple gene signatures in an endpoint and between the two endpoints of breast cancer at probe and gene levels, the results indicate that disease-related genes can be preferably selected as the components of gene signature, and that the gene signatures for the two endpoints could be interchangeable. The minimized signatures were built at probe level by using MFS for each endpoint. By applying the approach, we generated a much smaller set of gene signature with the similar predictive power compared with those gene signatures from MAQC-II. Conclusions Our results indicate that gene signatures of both large and small sizes could perform equally well in clinical applications. Besides, consistency and biological significances can be detected among different gene signatures, reflecting the

  13. Analysis of cascading failure in gene networks

    Directory of Open Access Journals (Sweden)

    Shudong eWang

    2012-12-01

    Full Text Available It is an important subject to research the functional mechanism of cancer-related genes make in formation and development of cancers. The modern methodology of data analysis plays a very important role for deducing the relationship between cancers and cancer-related genes and analyzing functional mechanism of genome. In this research, we construct mutual information networks using gene expression profiles of glioblast and renal in normal condition and cancer conditions. We investigate the relationship between structure and robustness in gene networks of the two tissues using a cascading failure model based on betweenness centrality. Define some important parameters such as the percentage of failure nodes of the network, the average size-ratio of cascading failure and the cumulative probability of size-ratio of cascading failure to measure the robustness of the networks. By comparing control group and experiment groups, we find that the networks of experiment groups are more robust than that of control group. The gene that can cause large scale failure is called structural key gene (SKG. Some of them have been confirmed to be closely related to the formation and development of glioma and renal cancer respectively. Most of them are predicted to play important roles during the formation of glioma and renal cancer, maybe the oncogenes, suppressor genes, and other cancer candidate genes in the glioma and renal cancer cells. However, these studies provide little information about the detailed roles of identified cancer genes.

  14. Dynamic Actin Gene Family Evolution in Primates

    Directory of Open Access Journals (Sweden)

    Liucun Zhu

    2013-01-01

    Full Text Available Actin is one of the most highly conserved proteins and plays crucial roles in many vital cellular functions. In most eukaryotes, it is encoded by a multigene family. Although the actin gene family has been studied a lot, few investigators focus on the comparison of actin gene family in relative species. Here, the purpose of our study is to systematically investigate characteristics and evolutionary pattern of actin gene family in primates. We identified 233 actin genes in human, chimpanzee, gorilla, orangutan, gibbon, rhesus monkey, and marmoset genomes. Phylogenetic analysis showed that actin genes in the seven species could be divided into two major types of clades: orthologous group versus complex group. Codon usages and gene expression patterns of actin gene copies were highly consistent among the groups because of basic functions needed by the organisms, but much diverged within species due to functional diversification. Besides, many great potential pseudogenes were found with incomplete open reading frames due to frameshifts or early stop codons. These results implied that actin gene family in primates went through “birth and death” model of evolution process. Under this model, actin genes experienced strong negative selection and increased the functional complexity by reproducing themselves.

  15. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    remains. More efficient interpretation requires more complete and consistent gene set representations of biological pathways, phenotypes and functional annotations. In this review, I examine different types of gene sets, discuss how inconsistencies in gene set definitions impact GSA, describe how GSA has...... and functional annotations and may hence point towards novel biological insights. However, despite the growing availability of GSA tools, the sizeable amount of variants identified for a vast number of complex traits, and many irrefutably trait-associated gene sets, the gap between discovery and interpretation...

  16. Gene expression trees in lymphoid development

    Directory of Open Access Journals (Sweden)

    Schliep Alexander

    2007-10-01

    Full Text Available Abstract Background The regulatory processes that govern cell proliferation and differentiation are central to developmental biology. Particularly well studied in this respect is the lymphoid system due to its importance for basic biology and for clinical applications. Gene expression measured in lymphoid cells in several distinguishable developmental stages helps in the elucidation of underlying molecular processes, which change gradually over time and lock cells in either the B cell, T cell or Natural Killer cell lineages. Large-scale analysis of these gene expression trees requires computational support for tasks ranging from visualization, querying, and finding clusters of similar genes, to answering detailed questions about the functional roles of individual genes. Results We present the first statistical framework designed to analyze gene expression data as it is collected in the course of lymphoid development through clusters of co-expressed genes and additional heterogeneous data. We introduce dependence trees for continuous variates, which model the inherent dependencies during the differentiation process naturally as gene expression trees. Several trees are combined in a mixture model to allow inference of potentially overlapping clusters of co-expressed genes. Additionally, we predict microRNA targets. Conclusion Computational results for several data sets from the lymphoid system demonstrate the relevance of our framework. We recover well-known biological facts and identify promising novel regulatory elements of genes and their functional assignments. The implementation of our method (licensed under the GPL is available at http://algorithmics.molgen.mpg.de/Supplements/ExpLym/.

  17. Dynamic Actin Gene Family Evolution in Primates

    Science.gov (United States)

    Zhu, Liucun; Zhang, Ying; Hu, Yijun; Wen, Tieqiao; Wang, Qiang

    2013-01-01

    Actin is one of the most highly conserved proteins and plays crucial roles in many vital cellular functions. In most eukaryotes, it is encoded by a multigene family. Although the actin gene family has been studied a lot, few investigators focus on the comparison of actin gene family in relative species. Here, the purpose of our study is to systematically investigate characteristics and evolutionary pattern of actin gene family in primates. We identified 233 actin genes in human, chimpanzee, gorilla, orangutan, gibbon, rhesus monkey, and marmoset genomes. Phylogenetic analysis showed that actin genes in the seven species could be divided into two major types of clades: orthologous group versus complex group. Codon usages and gene expression patterns of actin gene copies were highly consistent among the groups because of basic functions needed by the organisms, but much diverged within species due to functional diversification. Besides, many great potential pseudogenes were found with incomplete open reading frames due to frameshifts or early stop codons. These results implied that actin gene family in primates went through “birth and death” model of evolution process. Under this model, actin genes experienced strong negative selection and increased the functional complexity by reproducing themselves. PMID:23841080

  18. Utilizing evolutionary information and gene expression data for estimating gene networks with bayesian network models.

    Science.gov (United States)

    Tamada, Yoshinori; Bannai, Hideo; Imoto, Seiya; Katayama, Toshiaki; Kanehisa, Minoru; Miyano, Satoru

    2005-12-01

    Since microarray gene expression data do not contain sufficient information for estimating accurate gene networks, other biological information has been considered to improve the estimated networks. Recent studies have revealed that highly conserved proteins that exhibit similar expression patterns in different organisms, have almost the same function in each organism. Such conserved proteins are also known to play similar roles in terms of the regulation of genes. Therefore, this evolutionary information can be used to refine regulatory relationships among genes, which are estimated from gene expression data. We propose a statistical method for estimating gene networks from gene expression data by utilizing evolutionarily conserved relationships between genes. Our method simultaneously estimates two gene networks of two distinct organisms, with a Bayesian network model utilizing the evolutionary information so that gene expression data of one organism helps to estimate the gene network of the other. We show the effectiveness of the method through the analysis on Saccharomyces cerevisiae and Homo sapiens cell cycle gene expression data. Our method was successful in estimating gene networks that capture many known relationships as well as several unknown relationships which are likely to be novel. Supplementary information is available at http://bonsai.ims.u-tokyo.ac.jp/~tamada/bayesnet/.

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

    Science.gov (United States)

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

    2010-12-14

    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.

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

    Science.gov (United States)

    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.

  1. Sequential gene activation and gene imprinting during early embryo development in maize.

    Science.gov (United States)

    Meng, Dexuan; Zhao, Jianyu; Zhao, Cheng; Luo, Haishan; Xie, Mujiao; Liu, Renyi; Lai, Jinsheng; Zhang, Xiaolan; Jin, Weiwei

    2017-11-24

    Gene imprinting is a widely observed epigenetic phenomenon in maize endosperm; however, whether it also occurs in maize embryo remains controversial. Here, we used high throughput RNA sequencing on laser capture microdissection (LCM) and manually dissected maize embryos from reciprocal crosses between inbred lines B73 and Mo17 at six time points (3 to 13 days after pollination) to analyze allelic gene expression patterns. Co-expression analysis revealed sequential gene activation during maize embryo development. Gene imprinting was observed in maize embryos and a greater number of imprinted genes were identified at early embryo stages. Sixty-four strongly imprinted genes were identified (at the threshold of 9:1) on 5 DAP to 13 DAP manually dissected embryos (more imprinted genes on 5 DAP). Forty-one strongly imprinted genes were identified from 3 DAP and 5 DAP embryos obtained by LCM (more imprinted genes on 3DAP). Furthermore, of the 56 genes that were completely imprinted (at the threshold of 99:1), 36 were not previously identified as imprinted genes in endosperms and nor in embryos. In situ hybridization demonstrated that most of the imprinted genes were expressed abundantly in maize embryotic tissue. Our results shed lights on early maize embryo development and provide evidence supporting that gene imprinting occurs in maize embryos. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Application of Gene Shaving and Mixture Models to Cluster Microarray Gene Expression Data

    Directory of Open Access Journals (Sweden)

    S. Wen

    2007-01-01

    Full Text Available Researchers are frequently faced with the analysis of microarray data of a relatively large number of genes using a small number of tissue samples. We examine the application of two statistical methods for clustering such microarray expression data: EMMIX-GENE and GeneClust. EMMIX-GENE is a mixture-model based clustering approach, designed primarily to cluster tissue samples on the basis of the genes. GeneClust is an implementation of the gene shaving methodology, motivated by research to identify distinct sets of genes for which variation in expression could be related to a biological property of the tissue samples. We illustrate the use of these two methods in the analysis of Affymetrix oligonucleotide arrays of well-known data sets from colon tissue samples with and without tumors, and of tumor tissue samples from patients with leukemia. Although the two approaches have been developed from different perspectives, the results demonstrate a clear correspondence between gene clusters produced by GeneClust and EMMIX-GENE for the colon tissue data. It is demonstrated, for the case of ribosomal proteins and smooth muscle genes in the colon data set, that both methods can classify genes into co-regulated families. It is further demonstrated that tissue types (tumor and normal can be separated on the basis of subtle distributed patterns of genes. Application to the leukemia tissue data produces a division of tissues corresponding closely to the external classification, acute myeloid leukemia (AML and acute lymphoblastic leukaemia (ALL, for both methods. In addition, we also identify genes specifi c for the subgroup of ALL-T cell samples. Overall, we find that the gene shaving method produces gene clusters at great speed; allows variable cluster sizes and can incorporate partial or full supervision; and finds clusters of genes in which the gene expression varies greatly over the tissue samples while maintaining a high level of coherence between the

  3. Transcription of the soybean leghemoglobin genes during nodule development

    DEFF Research Database (Denmark)

    Marcker, Anne; Lund, Marianne; Jensen, Erik Ø

    1984-01-01

    of the Lb(c1), Lb(c3) and Lb(a) genes while the transcription of the Lb(c2) gene is not amplified to a similar extent. All the Lb genes retain significant activity for a long period during the lifetime of a nodule. Consequently the soybean Lb genes are not regulated by a developmental gene switching...... mechanism as is the case for vertebrate globin genes. Concomitantly with the increase in Lb gene transcription some of the other nodule specific plant genes are activated. These specific changes in the activities of the Lb and nodulin genes precede the activation of the bacterial nitrogenase gene. Thus...

  4. LNDriver: identifying driver genes by integrating mutation and expression data based on gene-gene interaction network.

    Science.gov (United States)

    Wei, Pi-Jing; Zhang, Di; Xia, Junfeng; Zheng, Chun-Hou

    2016-12-23

    Cancer is a complex disease which is characterized by the accumulation of genetic alterations during the patient's lifetime. With the development of the next-generation sequencing technology, multiple omics data, such as cancer genomic, epigenomic and transcriptomic data etc., can be measured from each individual. Correspondingly, one of the key challenges is to pinpoint functional driver mutations or pathways, which contributes to tumorigenesis, from millions of functional neutral passenger mutations. In this paper, in order to identify driver genes effectively, we applied a generalized additive model to mutation profiles to filter genes with long length and constructed a new gene-gene interaction network. Then we integrated the mutation data and expression data into the gene-gene interaction network. Lastly, greedy algorithm was used to prioritize candidate driver genes from the integrated data. We named the proposed method Length-Net-Driver (LNDriver). Experiments on three TCGA datasets, i.e., head and neck squamous cell carcinoma, kidney renal clear cell carcinoma and thyroid carcinoma, demonstrated that the proposed method was effective. Also, it can identify not only frequently mutated drivers, but also rare candidate driver genes.

  5. Novel definition files for human GeneChips based on GeneAnnot

    National Research Council Canada - National Science Library

    Ferrari, Francesco; Bortoluzzi, Stefania; Coppe, Alessandro; Sirota, Alexandra; Safran, Marilyn; Shmoish, Michael; Ferrari, Sergio; Lancet, Doron; Danieli, Gian Antonio; Bicciato, Silvio

    2007-01-01

    .... We developed a novel set of custom Chip Definition Files (CDF) and the corresponding Bioconductor libraries for Affymetrix human GeneChips, based on the information contained in the GeneAnnot database...

  6. Genes from scratch--the evolutionary fate of de novo genes.

    Science.gov (United States)

    Schlötterer, Christian

    2015-04-01

    Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  7. Genes that contribute to cancer fusion genes are large and evolutionarily conserved.

    Science.gov (United States)

    Narsing, Swetha; Jelsovsky, Zhihong; Mbah, Alfred; Blanck, George

    2009-06-01

    Numerous cancer fusion genes have been identified and studied, and in some cases, therapy or diagnostic techniques have been designed that are specific to the fusion protein encoded by the fusion gene. There has been little progress, however, in understanding the general features of cancer fusion genes in a way that could provide the foundation for an algorithm for predicting the occurrence of a fusion gene once the chromosomal translocation points have been identified by karyotype analyses. In this study, we used publicly available data sets to characterize 59 cancer fusion genes. The results indicate that all but 17% of the genes involved in fusion events are either relatively large, compared to neighboring genes, or are highly conserved in evolution. These results support a basis for designing algorithms that could have a high degree of predictive value in identifying fusion genes once conventional microscopic analyses have identified the chromosomal breakpoints.

  8. Targeted cancer gene therapy : the flexibility of adenoviral gene therapy vectors

    NARCIS (Netherlands)

    Rots, MG; Curiel, DT; Gerritsen, WR; Haisma, HJ

    2003-01-01

    Recombinant adenoviral vectors are promising reagents for therapeutic interventions in humans, including gene therapy for biologically complex diseases like cancer and cardiovascular diseases. In this regard, the major advantage of adenoviral vectors is their superior in vivo gene transfer

  9. Kinase gene haplotypes and gene-gene interactions in the Ras-Raf-MAPK signaling pathway: association with antidepressant remission.

    Science.gov (United States)

    Wang, Cong-jie; Zhang, Zhi-jun; Xu, Zhi; Shi, Yan-yan; Pu, Meng-Jia; Zheng, Zhi; Wang, Xiu-zhen; Zhang, Yu-mei; Li, Ling-jiang

    2013-09-01

    Signal transduction has been reported to be involved in antidepressant treatment outcomes; however, its mechanisms remain unclear. The aims of this study were to explore the associations between antidepressant remission and single nucleotide polymorphisms (SNPs), haplotypes, and gene-gene interactions in the Ras-Raf-MAPK intracellular signaling pathway. A total of 302 inpatients with major depressive disorder (DSM-IV Axis I) were assessed using the 17-item Hamilton Depression Rating Scale before and after 8 weeks of antidepressant treatment to determine the remission rate in the samples. Twenty-four SNPs at five kinase genes (Ras-Raf-MEK-ERK-RSK), which are a part of the Ras-Raf-MAPK signaling pathway, were identified to investigate a genetic association with antidepressant drug outcome. Correlations between 24 SNPs at the five kinase genes in the Ras-Raf-MAPK signaling pathway and antidepressant drug outcome were not found. The percentage of the CCAGA haplotype that RSK(2/3/4)-RSKL(1/2) gene loci SNPs constructed was markedly lower in the remitter group when compared with the nonremitter group in female depressed patients (P=0.04), whereas the proportion of AAAGGG haplotype that RSK(2/3/4)-RSKL(1/2) gene loci SNPs constructed in the remitter group was significantly greater than that in the nonremitter group in male patients (P=0.02). In addition, MEK1 (rs28730804) and RSK3 (rs2229712) in the Ras-Raf-MAPK signaling pathway showed a gene-gene interaction that affected antidepressant drug outcome in female depressed patients (P=0.041). Although this study did not find that SNPs at the five kinase genes in the Ras-Raf-MAPK signaling pathway are important markers for antidepressant outcome, certain haplotypes that SNPs at the RSK(2/3/4)-RSKL(1/2) gene constructed may be important markers for antidepressant drug efficacy. We observed a gene-gene interaction in this signaling pathway that influenced antidepressant efficacy in female depressed patients. Therefore, it is

  10. Gene organization and sequence analyses of transfer RNA genes in Trypanosomatid parasites

    Directory of Open Access Journals (Sweden)

    Myler Peter J

    2009-05-01

    Full Text Available Abstract Background The protozoan pathogens Leishmania major, Trypanosoma brucei and Trypanosoma cruzi (the Tritryps are parasites that produce devastating human diseases. These organisms show very unusual mechanisms of gene expression, such as polycistronic transcription. We are interested in the study of tRNA genes, which are transcribed by RNA polymerase III (Pol III. To analyze the sequences and genomic organization of tRNA genes and other Pol III-transcribed genes, we have performed an in silico analysis of the Tritryps genome sequences. Results Our analysis indicated the presence of 83, 66 and 120 genes in L. major, T. brucei and T. cruzi, respectively. These numbers include several previously unannotated selenocysteine (Sec tRNA genes. Most tRNA genes are organized into clusters of 2 to 10 genes that may contain other Pol III-transcribed genes. The distribution of genes in the L. major genome does not seem to be totally random, like in most organisms. While the majority of the tRNA clusters do not show synteny (conservation of gene order between the Tritryps, a cluster of 13 Pol III genes that is highly syntenic was identified. We have determined consensus sequences for the putative promoter regions (Boxes A and B of the Tritryps tRNA genes, and specific changes were found in tRNA-Sec genes. Analysis of transcription termination signals of the tRNAs (clusters of Ts showed differences between T. cruzi and the other two species. We have also identified several tRNA isodecoder genes (having the same anticodon, but different sequences elsewhere in the tRNA body in the Tritryps. Conclusion A low number of tRNA genes is present in Tritryps. The overall weak synteny that they show indicates a reduced importance of genome location of Pol III genes compared to protein-coding genes. The fact that some of the differences between isodecoder genes occur in the internal promoter elements suggests that differential control of the expression of some

  11. Inferring gene regression networks with model trees

    Directory of Open Access Journals (Sweden)

    Aguilar-Ruiz Jesus S

    2010-10-01

    Full Text Available Abstract Background Novel strategies are required in order to handle the huge amount of data produced by microarray technologies. To infer gene regulatory networks, the first step is to find direct regulatory relationships between genes building the so-called gene co-expression networks. They are typically generated using correlation statistics as pairwise similarity measures. Correlation-based methods are very useful in order to determine whether two genes have a strong global similarity but do not detect local similarities. Results We propose model trees as a method to identify gene interaction networks. While correlation-based methods analyze each pair of genes, in our approach we generate a single regression tree for each gene from the remaining genes. Finally, a graph from all the relationships among output and input genes is built taking into account whether the pair of genes is statistically significant. For this reason we apply a statistical procedure to control the false discovery rate. The performance of our approach, named REGNET, is experimentally tested on two well-known data sets: Saccharomyces Cerevisiae and E.coli data set. First, the biological coherence of the results are tested. Second the E.coli transcriptional network (in the Regulon database is used as control to compare the results to that of a correlation-based method. This experiment shows that REGNET performs more accurately at detecting true gene associations than the Pearson and Spearman zeroth and first-order correlation-based methods. Conclusions REGNET generates gene association networks from gene expression data, and differs from correlation-based methods in that the relationship between one gene and others is calculated simultaneously. Model trees are very useful techniques to estimate the numerical values for the target genes by linear regression functions. They are very often more precise than linear regression models because they can add just different linear

  12. Discovering gene annotations in biomedical text databases

    Directory of Open Access Journals (Sweden)

    Ozsoyoglu Gultekin

    2008-03-01

    Full Text Available Abstract Background Genes and gene products are frequently annotated with Gene Ontology concepts based on the evidence provided in genomics articles. Manually locating and curating information about a genomic entity from the biomedical literature requires vast amounts of human effort. Hence, there is clearly a need forautomated computational tools to annotate the genes and gene products with Gene Ontology concepts by computationally capturing the related knowledge embedded in textual data. Results In this article, we present an automated genomic entity annotation system, GEANN, which extracts information about the characteristics of genes and gene products in article abstracts from PubMed, and translates the discoveredknowledge into Gene Ontology (GO concepts, a widely-used standardized vocabulary of genomic traits. GEANN utilizes textual "extraction patterns", and a semantic matching framework to locate phrases matching to a pattern and produce Gene Ontology annotations for genes and gene products. In our experiments, GEANN has reached to the precision level of 78% at therecall level of 61%. On a select set of Gene Ontology concepts, GEANN either outperforms or is comparable to two other automated annotation studies. Use of WordNet for semantic pattern matching improves the precision and recall by 24% and 15%, respectively, and the improvement due to semantic pattern matching becomes more apparent as the Gene Ontology terms become more general. Conclusion GEANN is useful for two distinct purposes: (i automating the annotation of genomic entities with Gene Ontology concepts, and (ii providing existing annotations with additional "evidence articles" from the literature. The use of textual extraction patterns that are constructed based on the existing annotations achieve high precision. The semantic pattern matching framework provides a more flexible pattern matching scheme with respect to "exactmatching" with the advantage of locating approximate

  13. Cellular targeting for cochlear gene therapy.

    Science.gov (United States)

    Ryan, Allen F; Mullen, Lina M; Doherty, Joni K

    2009-01-01

    Gene therapy has considerable potential for the treatment of disorders of the inner ear. Many forms of inherited hearing loss have now been linked to specific locations in the genome, and for many of these the genes and specific mutations involved have been identified. This information provides the basis for therapy based on genetic approaches. However, a major obstacle to gene therapy is the targeting of therapy to the cells and the times that are required. The inner ear is a very complex organ, involving dozens of cell types that must function in a coordinated manner to result in the formation of the ear, and in hearing. Mutations that result in hearing loss can affect virtually any of these cells. Moreover, the genes involved are active during particular times, some for only brief periods of time. In order to be effective, gene therapy must be delivered to the appropriate cells, and at the appropriate times. In many cases, it must also be restricted to these cells and times. This requires methods with which to target gene therapy in space and time. Cell-specific gene promoters offer the opportunity to direct gene therapy to a desired cell type. Moreover, conditional promoters allow gene expression to be turned off and on at desired times. Theoretically, these technologies offer a mechanism by which to deliver gene therapy to any cell, at any given time. This chapter will examine the potential for such targeting to deliver gene therapy to the inner ear in a precisely controlled manner. Copyright (c) 2009 S. Karger AG, Basel.

  14. Gene expression profiling during murine tooth development

    Directory of Open Access Journals (Sweden)

    Maria A dos Santos silva Landin

    2012-07-01

    Full Text Available The aim of this study was to describe the expression of genes, including ameloblastin (Ambn, amelogenin X chromosome (Amelx and enamelin (Enam during early (pre-secretory tooth development. The expression of these genes has predominantly been studied at post-secretory stages. Deoxyoligonucleotide microarrays were used to study gene expression during development of the murine first molar tooth germ at 24h intervals, starting at the eleventh embryonic day (E11.5 and up to the seventh day after birth (P7. The profile search function of Spotfire software was used to select genes with similar expression profile as the enamel genes (Ambn, Amelx and Enam. Microarray results where validated using real-time Reverse Transcription-Polymerase Chain Reaction (real-time RT-PCR, and translated proteins identified by Western blotting. In situ localisation of the Ambn, Amelx and Enam mRNAs were monitored from E12.5 to E17.5 using deoxyoligonucleotide probes. Bioinformatics analysis was used to associate biological functions with differentially (p ≤0.05 expressed (DE genes.Microarray results showed a total of 4362 genes including Ambn, Amelx and Enam to be significant differentially expressed throughout the time-course. The expression of the three enamel genes was low at pre-natal stages (E11.5-P0 increasing after birth (P1-P7. Profile search lead to isolation of 87 genes with significantly similar expression to the three enamel proteins. The mRNAs expressed in dental epithelium and epithelium derived cells. Although expression of Ambn, Amelx and Enam were lower during early tooth development compared to secretory stages enamel proteins were detectable by Western blotting. Bioinformatic analysis associated the 87 genes with multiple biological functions. Around thirty-five genes were associated with fifteen transcription factors.

  15. The bystander effect of cancer gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lumniczky, K.; Safrany, G. (Department of Molecular and Tumour Radiobiology, National Research Institute for Radiobiology and Radiohygiene, Budapest (Hungary))

    2008-12-15

    Cancer gene therapy is a new, promising therapeutic agent. In the clinic, it should be used in combination with existing modalities, such as tumour irradiation. First, we summarise the most important fields of cancer gene therapy: gene directed enzyme pro-drug therapy; the activation of an anti-tumour immune attack; restoration of the wild type p53 status; the application of new, replication competent and oncolytic viral vectors; tumour specific, as well as radiation- and hypoxia-induced gene expression. Special emphasizes are put on the combined effect of these modalities with local tumour irradiation. Using the available vector systems, only a small portion of the cancer cells will contain the therapeutic genes under therapeutic situations. Bystander cell killing might contribute to the success of various gene therapy protocols. We summarise the evidences that lethal bystander effects may occur during cancer gene therapy. Bystander effects are especially important in the gene directed enzyme pro-drug therapy. There, bystander cell killing might have different routes: cell communication through gap junction intercellular contacts; release of toxic metabolites into the neighbourhood or to larger distances; phagocytosis of apoptotic bodies; and the activation of the immune system. Bystander cell killing can be enhanced by the introduction of gap junction proteins into the cells, by further activating the immune system with immune-stimulatory molecules, or by introducing genes into the cells that help the transfer of cytotoxic genes and / or metabolites into the bystander cells. In conclusion, there should be additional improvements in cancer gene therapy for the more efficient clinical application. (orig.)

  16. Medea genes, handedness and other traits

    Science.gov (United States)

    Hatfield, Jeffrey

    2015-01-01

    Medea factors or genes are maternal-effects mechanisms, found in many species, in which the mother's body selectively kills embryos of a certain genotype.Humans have a similar genetic mechanism, the gene RHD which produces Rh-factor involved in blood type.Recently I proposed that RHD acts as a maternal-effects gene that determines handedness (i.e., right handed or non-right handed) in individuals of our species. Here, I argue that RHD functions as a Medea gene as well.The handedness gene (and also RHD itself in some cases) has been implicated in autism spectrum disorders (ASD), bipolar disorder, cerebral laterality (i.e., right-brained or left-brained speech laterality), hair-whorl rotation, schizophrenia, sexual orientation, and speech dyslexia.Identifying the gene or genes that determine handedness or cerebral laterality may help uncover the mechanisms underlying these behavioral phenotypes in our species.A relatively simple test of the handedness hypothesis has been proposed:In a sample of humans for whom handedness has been evaluated, we would need to genotype for RHD by determining whether Rh+ individuals have one or two copies of the dominant allele. If RHD and perhaps also an interaction with RHCE are involved in sexual orientation, it explains how selection could favor a gene or genes which cause some people to become non-heterosexual.The literature on Medea genes provides the explanation:A Medea allele must increase in frequency, sometimes to fixation (i.e., 100% frequency) even if it reduces fecundity (e.g., birth rate).In addition, treatment for RHD maternal-fetal genotype incompatibility, which allows more fetuses to survive to term now, may be one explanation for why ASD appears to be increasing in frequency in some populations, if RHD is indeed the handedness gene, although many other mechanisms have also been suggested. One wonders if bipolar disorder and the other alternative phenotypes are also increasing in frequency.

  17. Computational algorithms to predict Gene Ontology annotations

    Science.gov (United States)

    2015-01-01

    Background Gene function annotations, which are associations between a gene and a term of a controlled vocabulary describing gene functional features, are of paramount importance in modern biology. Datasets of these annotations, such as the ones provided by the Gene Ontology Consortium, are used to design novel biological experiments and interpret their results. Despite their importance, these sources of information have some known issues. They are incomplete, since biological knowledge is far from being definitive and it rapidly evolves, and some erroneous annotations may be present. Since the curation process of novel annotations is a costly procedure, both in economical and time terms, computational tools that can reliably predict likely annotations, and thus quicken the discovery of new gene annotations, are very useful. Methods We used a set of computational algorithms and weighting schemes to infer novel gene annotations from a set of known ones. We used the latent semantic analysis approach, implementing two popular algorithms (Latent Semantic Indexing and Probabilistic Latent Semantic Analysis) and propose a novel method, the Semantic IMproved Latent Semantic Analysis, which adds a clustering step on the set of considered genes. Furthermore, we propose the improvement of these algorithms by weighting the annotations in the input set. Results We tested our methods and their weighted variants on the Gene Ontology annotation sets of three model organism genes (Bos taurus, Danio rerio and Drosophila melanogaster ). The methods showed their ability in predicting novel gene annotations and the weighting procedures demonstrated to lead to a valuable improvement, although the obtained results vary according to the dimension of the input annotation set and the considered algorithm. Conclusions Out of the three considered methods, the Semantic IMproved Latent Semantic Analysis is the one that provides better results. In particular, when coupled with a proper

  18. Gene expression in periodontal tissues following treatment

    Directory of Open Access Journals (Sweden)

    Eisenacher Martin

    2008-07-01

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

  19. A Bayesian Semiparametric Approach to Learning About Gene-Gene Interactions in Case-Control Studies

    OpenAIRE

    Bhattacharya, Durba; Bhattacharya, Sourabh

    2014-01-01

    Gene-gene interactions are often regarded as playing significant roles in influencing variabilities of complex traits. Although much research has been devoted to this area, to date a comprehensive statistical model that adequately addresses the highly dependent structures associated with the interactions between the genes, multiple loci of every gene, various and unknown number of sub-populations that the subjects arise from, seem to be lacking. In this paper, we propose and develop a novel B...

  20. Gene Name Thesaurus - Gene Name Thesaurus | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available gene names found in various databases and articles to show associations between them. Data file File name: dictionary....zip File URL: ftp://ftp.biosciencedbc.jp/archive/lsdb_gene_thesaurus/LATEST/dictionary...ary. 5. Add non-detected words to the dictionary and repeat 4-5 using other literat...ribe gene names from MEDLINE abstracts and collect unregistered names. 4. Evaluate detection performance of gene names in the diction

  1. Appendix 1:Upregulated genes in gene expression profile (P<0.05 ...

    Indian Academy of Sciences (India)

    lazi

    Appendix 1:Upregulated genes in gene expression profile(P<0.05 and foldchange≥2). Probe_S. et_ID. Gene_Symbol pvalues foldchange. Probe_S. et_ID. Gene_Symbol pvalues foldchange. 1370355. _at. Scd1. 1.35E-04. 25.77. 1393751. _at. LOC100912250. 8.06E-03. 2.55. 1398250. _at. Acot1. 2.43E-02. 12.18.

  2. Fusion gene microarray reveals cancer type-specificity among fusion genes.

    Science.gov (United States)

    Løvf, Marthe; Thomassen, Gard O S; Bakken, Anne Cathrine; Celestino, Ricardo; Fioretos, Thoas; Lind, Guro E; Lothe, Ragnhild A; Skotheim, Rolf I

    2011-05-01

    Detection of fusion genes for diagnostic purposes and as a guide to treatment is well-established in hematological malignancies, and the prevalence of fusion genes in epithelial cancers is also increasingly appreciated. To study whether established fusion genes are present within additional cancer types, we have used an updated version of our fusion gene microarray in a systematic survey of reported fusion genes in multiple cancer types. We assembled a comprehensive database of published fusion genes, including those reported only in individual studies and samples, and fusion genes resulting from deep sequencing of cancer genomes and transcriptomes. From the total set of 548 fusion genes, we designed 599,839 oligonucleotides, targeting both chimeric transcript junctions as well as sequences internal to each of the fusion gene partners. We investigated the presence of fusion genes in a series of 67 cell lines representing 15 different cancer types. Data from ten leukemia cell lines with known fusion gene status were used to develop an automated scoring algorithm, and in five cell lines the correct fusion gene was the top scoring hit, and one came second. Two additional fusion genes, BCAS4-BCAS3 in the MCF-7 breast cancer cell line and CCDC6-RET in the TPC-1 thyroid cancer cell line were validated as true positive fusion transcripts. However, these fusion genes were not new to these cancer types, and none of 548 fusion genes were identified from a novel cancer type. We therefore find it unlikely that the assayed fusion genes are commonly present across multiple cancer types. 2011 Wiley-Liss, Inc.

  3. [Gene technology in animal husbandry, new research approaches exemplified by the milk protein gene of cattle].

    Science.gov (United States)

    Geldermann, H

    1989-02-01

    For investigation of bovine milk protein genes several methods of recombinant DNA techniques are presented. Possible applications of genome research in animal breeding are given including the characterization of structure and function for single genes, gene mapping as well as screening for gene variants in populations. Hence it follows that scientific and practical developments can be expected and will be an influence on future animal production.

  4. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

    Directory of Open Access Journals (Sweden)

    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  5. Ranking differentially expressed genes from Affymetrix gene expression data: methods with reproducibility, sensitivity, and specificity

    OpenAIRE

    Shimizu Kentaro; Nakai Yuji; Kadota Koji

    2009-01-01

    Abstract Background To identify differentially expressed genes (DEGs) from microarray data, users of the Affymetrix GeneChip system need to select both a preprocessing algorithm to obtain expression-level measurements and a way of ranking genes to obtain the most plausible candidates. We recently recommended suitable combinations of a preprocessing algorithm and gene ranking method that can be used to identify DEGs with a higher level of sensitivity and specificity. However, in addition to th...

  6. Reference genes for gene expression studies in wheat flag leaves grown under different farming conditions

    Directory of Open Access Journals (Sweden)

    Cordeiro Raposo Fernando

    2011-09-01

    Full Text Available Abstract Background Internal control genes with highly uniform expression throughout the experimental conditions are required for accurate gene expression analysis as no universal reference genes exists. In this study, the expression stability of 24 candidate genes from Triticum aestivum cv. Cubus flag leaves grown under organic and conventional farming systems was evaluated in two locations in order to select suitable genes that can be used for normalization of real-time quantitative reverse-transcription PCR (RT-qPCR reactions. The genes were selected among the most common used reference genes as well as genes encoding proteins involved in several metabolic pathways. Findings Individual genes displayed different expression rates across all samples assayed. Applying geNorm, a set of three potential reference genes were suitable for normalization of RT-qPCR reactions in winter wheat flag leaves cv. Cubus: TaFNRII (ferredoxin-NADP(H oxidoreductase; AJ457980.1, ACT2 (actin 2; TC234027, and rrn26 (a putative homologue to RNA 26S gene; AL827977.1. In addition of these three genes that were also top-ranked by NormFinder, two extra genes: CYP18-2 (Cyclophilin A, AY456122.1 and TaWIN1 (14-3-3 like protein, AB042193 were most consistently stably expressed. Furthermore, we showed that TaFNRII, ACT2, and CYP18-2 are suitable for gene expression normalization in other two winter wheat varieties (Tommi and Centenaire grown under three treatments (organic, conventional and no nitrogen and a different environment than the one tested with cv. Cubus. Conclusions This study provides a new set of reference genes which should improve the accuracy of gene expression analyses when using wheat flag leaves as those related to the improvement of nitrogen use efficiency for cereal production.

  7. What is a gene? From molecules to metaphysics.

    Science.gov (United States)

    Rolston, Holmes

    2006-01-01

    Mendelian genes have become molecular genes, with increasing puzzlement about locating them, due to increasing complexity in genomic webworks. Genome science finds modular and conserved units of inheritance, identified as homologous genes. Such genes are cybernetic, transmitting information over generations; this too requires multi-leveled analysis, from DNA transcription to development and reproduction of the whole organism. Genes are conserved; genes are also dynamic and creative in evolutionary speciation-most remarkably producing humans capable of wondering about what genes are.

  8. Discovering implicit entity relation with the gene-citation-gene network.

    Directory of Open Access Journals (Sweden)

    Min Song

    Full Text Available In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner.

  9. Improving monitoring of erythromycin ribosome methylase genes in swine and cattle manures with gene targeted approaches

    Science.gov (United States)

    Macrolide antibiotics are often used in feed for animal industry to prevent diseases. Resistance to these antibiotics is associated with erythromycin ribosome methylase genes (erm genes), which were first discovered in Staphylococcus aureus. The erm gene confers resistance by methylating rRNA at the...

  10. Discover Gene Specific Local Co-Regulations from Time-Course Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    2008-01-01

    Full Text Available Discovering gene co-regulatory relationships is one of most important research in DNA microarray data analysis. The problem of gene specific co-regulation discovery is to, for a particular gene of interest (called target gene, identify the condition subsets where strong gene co-regulations of the target gene are observed and its co-regulated genes in these condition subsets. The co-regulations are local in the sense that they occur in some subsets of full experimental conditions. The study on this problem can contribute to better understanding and characterizing the target gene during the biological activity involved. In this paper, we propose an innovative method for finding gene specific co-regulations using genetic algorithm (GA. A sliding window is used to delimit the allowed length of conditions in which gene co-regulations occur and an ad hoc GA, called the progressive GA, is performed in each window position to find those condition subsets having high fitness. It is called progressive because the initial population for the GA in a window position inherits the top-ranked individuals obtained in its preceding window position, enabling the GA to achieve a better accuracy than the non-progressive algorithm. kNN Lookup Table is utilized to substantially speed up fitness evaluation in the GA. Experimental results with a real-life gene expression data demonstrate the efficiency and effectiveness of our technique in discovering gene specific co-regulations.

  11. Gene-based Association Approach Identify Genes Across Stress Traits in Fruit Flies

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Edwards, Stefan McKinnon; Sarup, Pernille Merete

    approach grouping variants accordingly to gene position, thus lowering the number of statistical tests performed and increasing the probability of identifying genes with small to moderate effects. Using this approach we identify numerous genes associated with different types of stresses in Drosophila...

  12. Twenty Years of European Union Support to Gene Therapy and Gene Transfer.

    Science.gov (United States)

    Gancberg, David

    2017-11-01

    For 20 years and throughout its research programmes, the European Union has supported the entire innovation chain for gene transfer and gene therapy. The fruits of this investment are ripening as gene therapy products are reaching the European market and as clinical trials are demonstrating the safety of this approach to treat previously untreatable diseases.

  13. Evolution of glutamate dehydrogenase genes: evidence for lateral gene transfer within and between prokaryotes and eukaryotes

    Directory of Open Access Journals (Sweden)

    Roger Andrew J

    2003-06-01

    Full Text Available Abstract Background Lateral gene transfer can introduce genes with novel functions into genomes or replace genes with functionally similar orthologs or paralogs. Here we present a study of the occurrence of the latter gene replacement phenomenon in the four gene families encoding different classes of glutamate dehydrogenase (GDH, to evaluate and compare the patterns and rates of lateral gene transfer (LGT in prokaryotes and eukaryotes. Results We extend the taxon sampling of gdh genes with nine new eukaryotic sequences and examine the phylogenetic distribution pattern of the various GDH classes in combination with maximum likelihood phylogenetic analyses. The distribution pattern analyses indicate that LGT has played a significant role in the evolution of the four gdh gene families. Indeed, a number of gene transfer events are identified by phylogenetic analyses, including numerous prokaryotic intra-domain transfers, some prokaryotic inter-domain transfers and several inter-domain transfers between prokaryotes and microbial eukaryotes (protists. Conclusion LGT has apparently affected eukaryotes and prokaryotes to a similar extent within the gdh gene families. In the absence of indications that the evolution of the gdh gene families is radically different from other families, these results suggest that gene transfer might be an important evolutionary mechanism in microbial eukaryote genome evolution.

  14. Systematic Search for Gene-Gene Interaction Effect on Prostate Cancer Risk

    Science.gov (United States)

    2011-07-01

    located in the intron of the WISP1 gene. The WISP1 gene belongs to the WNT1 inducible signaling pathway ( WISP ) protein subfamily, which is a member...transformation. The overexpression of this gene has been observed in colon tumors. Given the above evidence, we hypothesize that WISP meditates the WISP

  15. Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies.

    Science.gov (United States)

    Powers, John M; Trobridge, Grant D

    2013-09-01

    Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector provirus insertional mutagenesis. Insertional mutagenesis screens using replicating retroviruses have been used extensively to identify genes that influence oncogenesis. However, retroviral mutagenesis screens can also be used to determine the role of genes in biological processes such as stem cell engraftment. The aim of this review is to describe the potential for vector insertion site data from gene therapy studies to provide novel insights into mechanisms of HSC engraftment. In HSC gene therapy studies dysregulation of host genes by replication-incompetent vector proviruses may lead to enrichment of repopulating clones with vector integrants near genes that influence engraftment. Thus, data from HSC gene therapy studies can be used to identify novel candidate engraftment genes. As HSC gene therapy use continues to expand, the vector insertion site data collected will be of great interest to help identify novel engraftment genes and may ultimately lead to new therapies to improve engraftment.

  16. Selection of reference genes for gene expression studies in human neutrophils by real-time PCR

    Directory of Open Access Journals (Sweden)

    Sandford Andrew J

    2005-02-01

    Full Text Available Abstract Background Reference genes, which are often referred to housekeeping genes, are frequently used to normalize mRNA levels between different samples. However the expression level of these genes may vary among tissues or cells, and may change under certain circumstances. Thus the selection of reference gene(s is critical for gene expression studies. For this purpose, 10 commonly used housekeeping genes were investigated in isolated human neutrophils. Results Initial screening of the expression pattern demonstrated that 3 of the 10 genes were expressed at very low levels in neutrophils and were excluded from further analysis. The range of expression stability of the other 7 genes was (from most stable to least stable: GNB2L1 (Guanine nucleotide binding protein, beta polypeptide 2-like 1, HPRT1 (Hypoxanthine phosphoribosyl transferase 1, RPL32 (ribosomal protein L32, ACTB (beta-actin, B2M (beta-2-microglobulin, GAPD (glyceraldehyde-3-phosphate dehydrogenase and TBP (TATA-binding protein. Relative expression levels of the genes (from high to low were: B2M, ACTB, GAPD, RPL32, GNB2L1, TBP, and HPRT1. Conclusion Our data suggest that GNB2L1, HPRT1, RPL32, ACTB, and B2M may be suitable reference genes in gene expression studies of neutrophils.

  17. Efficient strategy for detecting gene × gene joint action and its application in schizophrenia

    NARCIS (Netherlands)

    Won, Sungho; Kwon, Min-Seok; Mattheisen, Manuel; Park, Suyeon; Park, Changsoon; Kihara, Daisuke; Cichon, Sven; Ophoff, Roel; Nöthen, Markus M.; Rietschel, Marcella; Baur, Max; Uitterlinden, Andre G.; Hofmann, A.; Lange, Christoph; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

    2014-01-01

    We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the

  18. Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

    Directory of Open Access Journals (Sweden)

    McDonald Karen

    2011-08-01

    Full Text Available Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

  19. Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Donghe Li

    2016-12-01

    Full Text Available Over the past decade, the detection of gene-gene interactions has become more and more popular in the field of genome-wide association studies (GWASs. The goal of the GWAS is to identify genetic susceptibility to complex diseases by assaying and analyzing hundreds of thousands of single-nucleotide polymorphisms. However, such tests are computationally demanding and methodologically challenging. Recently, a simple but powerful method, named “BOolean Operation-based Screening and Testing” (BOOST, was proposed for genome-wide gene-gene interaction analyses. BOOST was designed with a Boolean representation of genotype data and is approximately equivalent to the log-linear model. It is extremely fast, and genome-wide gene-gene interaction analyses can be completed within a few hours. However, BOOST can not adjust for covariate effects, and its type-1 error control is not correct. Thus, we considered two-step approaches for gene-gene interaction analyses. First, we selected gene-gene interactions with BOOST and applied logistic regression with covariate adjustments to select gene-gene interactions. We applied the two-step approach to type 2 diabetes (T2D in the Korea Association Resource (KARE cohort and identified some promising pairs of single-nucleotide polymorphisms associated with T2D.

  20. [Fish growth-hormone genes: functionality evidence of paralogous genes in Levanidov's charr].

    Science.gov (United States)

    Kamenskaya, D N; Pankova, M V; Atopkin, D M; Brykov, V A

    2015-01-01

    In the genome of most vertebrates growth-hormone gene is presented in a single copy, while in salmonids after one of the duplication events many genes were multiplied, including growth hormone gene. In salmonids, the growth-hormone gene exists as two independently inherited functional paralogues, gh1 and gh2. In this study, we performed a comparative analysis of gh1 and gh2 growth-hormone genes and their adjacent sequences in Levanidov's charr Salvelinus levanidovi to determine their functionality and define the potential differences. We found that both genes have the same gene structure and are composed of six exons (I-VI) and five introns (A, B, C, D, E). However, the respective gene sequences differ in length. A comparison of exons showed that the size of each exon is identical in both paralogues. The overall length of genes differs due to the varying lengths of introns. Coding sequence of both genes contains an open reading frame for 210 amino acids. We identified regulatory elements in the promoter region of both genes: TATA box, A/T-rich regions that contain binding sites for pituitary-specific transcriptional activator Pit-1, and regions responsible for interaction with other transcriptional activators and initiators, in particular hormone receptors. The obtained data indicate that both genes are functional.

  1. Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization.

    Science.gov (United States)

    Jung, Sang-Kyu; McDonald, Karen

    2011-08-16

    Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

  2. Extensive horizontal gene transfer, duplication, and loss of chlorophyll synthesis genes in the algae.

    Science.gov (United States)

    Hunsperger, Heather M; Randhawa, Tejinder; Cattolico, Rose Ann

    2015-02-10

    Two non-homologous, isofunctional enzymes catalyze the penultimate step of chlorophyll a synthesis in oxygenic photosynthetic organisms such as cyanobacteria, eukaryotic algae and land plants: the light-independent (LIPOR) and light-dependent (POR) protochlorophyllide oxidoreductases. Whereas the distribution of these enzymes in cyanobacteria and land plants is well understood, the presence, loss, duplication, and replacement of these genes have not been surveyed in the polyphyletic and remarkably diverse eukaryotic algal lineages. A phylogenetic reconstruction of the history of the POR enzyme (encoded by the por gene in nuclei) in eukaryotic algae reveals replacement and supplementation of ancestral por genes in several taxa with horizontally transferred por genes from other eukaryotic algae. For example, stramenopiles and haptophytes share por gene duplicates of prasinophytic origin, although their plastid ancestry predicts a rhodophytic por signal. Phylogenetically, stramenopile pors appear ancestral to those found in haptophytes, suggesting transfer from stramenopiles to haptophytes by either horizontal or endosymbiotic gene transfer. In dinoflagellates whose plastids have been replaced by those of a haptophyte or diatom, the ancestral por genes seem to have been lost whereas those of the new symbiotic partner are present. Furthermore, many chlorarachniophytes and peridinin-containing dinoflagellates possess por gene duplicates. In contrast to the retention, gain, and frequent duplication of algal por genes, the LIPOR gene complement (chloroplast-encoded chlL, chlN, and chlB genes) is often absent. LIPOR genes have been lost from haptophytes and potentially from the euglenid and chlorarachniophyte lineages. Within the chlorophytes, rhodophytes, cryptophytes, heterokonts, and chromerids, some taxa possess both POR and LIPOR genes while others lack LIPOR. The gradual process of LIPOR gene loss is evidenced in taxa possessing pseudogenes or partial LIPOR gene

  3. The barley Jip23b gene

    DEFF Research Database (Denmark)

    Müller-Uri, Frieder; Cameron-Mills, Verena; Mundy, John

    2002-01-01

    The barley gene (Jip23) encoding a 23,000-Da protein of unknown function was isolated and shown to be induced by jasmonate methyl ester (MeJA) in leaves. 5'upstream Jip23 sequence was isolated and fused to the beta-glucuronidase gene (GUS), and this reporter was introduced by particle bombardment...

  4. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-05-24

    May 24, 2010 ... NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained from the ... Key words: Periodontal diseases, nitric oxide synthases gene, DNA, PCR. INTRODUCTION ... various diseases' pathogenesis because of its dual role. *Corresponding author.

  5. Divergence of flowering genes in soybean

    Indian Academy of Sciences (India)

    2012-10-15

    Oct 15, 2012 ... including flowering time, first flower, pod maturity, beginning of pod, reproductive period, and seed filling period. Among the genes overlapping the QTL regions, two LHY/CCA1 genes, GI and SFR6 contained amino acid changes. The recently duplicated sequence regions of the soybean genome were ...

  6. Gene therapy in India: A focus

    Indian Academy of Sciences (India)

    Gene therapy has re-emerged as a therapeutic option with reports of success from recent clinical studies. The United States and Europe has been pioneers in this field for over two decades. Recently, reports of gene therapy have started coming in from Asian countries like China, Japan and Korea. This review focuses on ...

  7. HMM-Based Gene Annotation Methods

    Energy Technology Data Exchange (ETDEWEB)

    Haussler, David; Hughey, Richard; Karplus, Keven

    1999-09-20

    Development of new statistical methods and computational tools to identify genes in human genomic DNA, and to provide clues to their functions by identifying features such as transcription factor binding sites, tissue, specific expression and splicing patterns, and remove homologies at the protein level with genes of known function.

  8. Methylenetetrahydrofolate reductase gene polymorphism in type 1 ...

    African Journals Online (AJOL)

    In patients with type-I diabetes mellitus folate deficiency is associated with endothelial dysfunction. So, polymorphism in genes involved in folate metabolism may have a role in vascular disease. This study was designed to evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

  9. (DAD1) gene fragment of Chinese kale

    African Journals Online (AJOL)

    To clone the defective in anther dehiscence1 (DAD1) gene fragment of Chinese kale, about 700 bp product was obtained by PCR amplification using Chinese kale genomic DNA as the template and a pair of specific primers designed according to the conserved sequence of DAD1 genes of Arabidopsis thaliana and ...

  10. Standardized phenotyping enhances Mendelian disease gene identification

    NARCIS (Netherlands)

    Vissers, L.E.L.M.; Veltman, J.A.

    2015-01-01

    Whole-exome sequencing has revolutionized the identification of genes with dominant disease-associated variants for rare clinically and genetically heterogeneous disorders, but the identification of genes with recessive disease-associated variants has been less successful. A new study now provides a

  11. Maternal genes and facial clefts in offspring

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian

    2010-01-01

    -to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal...

  12. Forest gene conservation programs in Alberta, Canada

    Science.gov (United States)

    Jodie. Krakowski

    2017-01-01

    Provincial tree improvement programs in Alberta began in 1976. Early gene conservation focused on ex situ measures such as seed and clone banking, and research trials of commercial species with tree improvement programs. The gene conservation program now encompasses representative and unique populations of all native tree species in situ. The ex situ program aims to...

  13. Natural Gene Therapy in Dystrophic Epidermolysis Bullosa

    NARCIS (Netherlands)

    van den Akker, Peter C.; Nijenhuis, Albertine; Hofstra, Robert M. W.; Jonkman, Marcel F.; Pasmooij, Anna M. G.; Meijer, G.

    Background: Dystrophic epidermolysis bullosa is a genetic blistering disorder caused by mutations in the type VII collagen gene, COL7A1. In revertant mosaicism, germline mutations are corrected by somatic events resulting in a mosaic disease distribution. This "natural gene therapy" phenomenon long

  14. Targeted Gene Therapy for Breast Cancer

    Science.gov (United States)

    1999-08-01

    Jaehne, J., Altorki, N., Blundell, M., Urmacher, C., Lauwers, G., Niedzwiecki, D., and Kelsen , D. P. Amplification of HER-2/neu gene in human gastric...and integration into Moloney murine leukemia virus particles, Gene Therapy. 3: 334-342, 1996. 21 Park 14. Han , X., Kasahara, N., and Kan, Y. W. Ligand

  15. PPB | What is the DICER1 gene?

    Science.gov (United States)

    DICER1 is a gene that manages the function of other genes. Inherited changes in DICER1 can result in a variety of tumors, including pleuropulmonary blastoma (PPB). The PPB DICER1 Syndrome Study ‹an observational clinical research study is enrolling children with PPB and their families.

  16. Gene therapy in India: A focus

    Indian Academy of Sciences (India)

    2014-05-01

    May 1, 2014 ... Parkinson's disease, Leber's congenital amaurosis, etc., made its way through various stages of clinical trials. Since then, there has been a steady increase in the number of gene therapy clinical trials around the world. Several gene therapy clinical studies carried out in different parts of the world after 2008 ...

  17. Parkinson's disease and mitochondrial gene variations

    DEFF Research Database (Denmark)

    Andalib, Sasan; Vafaee, Manouchehr Seyedi; Gjedde, Albert

    2014-01-01

    Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochondrial gene variations and mutations as well as from nuclear gene variations...

  18. Isolation, characterization and mapping of genes differentially ...

    Indian Academy of Sciences (India)

    To isolate genes expressed differently between the two species during fibre development, cDNA-SRAP (sequence-related amplified polymorphism) was applied. This technique was used to analyse genes at different stages of fibre development in G. hirsutum cv. Emian22 and G. barbadense acc. 3-79, the parents of our ...

  19. EcoGene 3.0

    Science.gov (United States)

    Zhou, Jindan; Rudd, Kenneth E.

    2013-01-01

    EcoGene (http://ecogene.org) is a database and website devoted to continuously improving the structural and functional annotation of Escherichia coli K-12, one of the most well understood model organisms, represented by the MG1655(Seq) genome sequence and annotations. Major improvements to EcoGene in the past decade include (i) graphic presentations of genome map features; (ii) ability to design Boolean queries and Venn diagrams from EcoArray, EcoTopics or user-provided GeneSets; (iii) the genome-wide clone and deletion primer design tool, PrimerPairs; (iv) sequence searches using a customized EcoBLAST; (v) a Cross Reference table of synonymous gene and protein identifiers; (vi) proteome-wide indexing with GO terms; (vii) EcoTools access to >2000 complete bacterial genomes in EcoGene-RefSeq; (viii) establishment of a MySql relational database; and (ix) use of web content management systems. The biomedical literature is surveyed daily to provide citation and gene function updates. As of September 2012, the review of 37 397 abstracts and articles led to creation of 98 425 PubMed-Gene links and 5415 PubMed-Topic links. Annotation updates to Genbank U00096 are transmitted from EcoGene to NCBI. Experimental verifications include confirmation of a CTG start codon, pseudogene restoration and quality assurance of the Keio strain collection. PMID:23197660

  20. The war against cancer: Suicide gene therapy

    Directory of Open Access Journals (Sweden)

    Muzeyyen Izmirli

    2016-06-01

    Full Text Available The National Cancer Institute and the American Cancer Society announced that 1.6 million new cancer cases are projected to occur in the USA in 2016. One of the most innovative approaches against cancer is suicide gene therapy, in which suicide-inducing transgenes are introduced into cancer cells. When cancer treatments target the total elimination of tumor cells, there will be no side effects for normal cells. Cancer tissues are targeted through various targeted transport methods, followed by tissue-specific enzymes converting a systemically suitable prodrug into an active drug in the tumor. Suicidal genes are delivered by transporters, such as viral and non-viral vectors, into cancer cells. Suicide gene therapeutic strategies currently pursued are herpes simplex virus thymidine kinase gene with prodrug ganciclovir, cytosine deaminase gene, carboxyl esterase/irinotecan, varicella zoster virus thymidine kinase/6-methoxypurine arabinonucleoside, nitroreductase Nfsb/5-(aziridin-1-yl-2,4-dinitrobenzamide, carboxypeptidase G2/4-[(2-chloroethyl(2- mesyloxyethylamino]benzoyl-L-glutamic acid, cytochrome p450-isofosfamide, and cytochrome p450-cyclophosphamide. The goal of this review is to summarize the different suicide gene systems and gene delivery vectors addressed to cancer cells, with a particular emphasis on recently developed systems. Finally, we briefly describe the advantageous clinical applications and potential side effects of suicide gene therapy.

  1. Inferring gene networks from discrete expression data

    KAUST Repository

    Zhang, L.

    2013-07-18

    The modeling of gene networks from transcriptional expression data is an important tool in biomedical research to reveal signaling pathways and to identify treatment targets. Current gene network modeling is primarily based on the use of Gaussian graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which generate counts of mRNAtranscripts in cell samples.We propose a generalized linear model to fit the discrete gene expression data and assume that the log ratios of the mean expression levels follow a Gaussian distribution.We restrict the gene network structures to decomposable graphs and derive the graphs by selecting the covariance matrix of the Gaussian distribution with the hyper-inverse Wishart priors. Furthermore, we incorporate prior network models based on gene ontology information, which avails existing biological information on the genes of interest. We conduct simulation studies to examine the performance of our discrete graphical model and apply the method to two real datasets for gene network inference. © The Author 2013. Published by Oxford University Press. All rights reserved.

  2. Distribution of introns in fungal histone genes.

    Directory of Open Access Journals (Sweden)

    Choong-Soo Yun

    Full Text Available Saccharomycotina and Taphrinomycotina lack intron in their histone genes, except for an intron in one of histone H4 genes of Yarrowia lipolytica. On the other hand, Basidiomycota and Perizomycotina have introns in their histone genes. We compared the distributions of 81, 47, 79, and 98 introns in the fungal histone H2A, H2B, H3, and H4 genes, respectively. Based on the multiple alignments of the amino acid sequences of histones, we identified 19, 13, 31, and 22 intron insertion sites in the histone H2A, H2B, H3, and H4 genes, respectively. Surprisingly only one hot spot of introns in the histone H2A gene is shared between Basidiomycota and Perizomycotina, suggesting that most of introns of Basidiomycota and Perizomycotina were acquired independently. Our findings suggest that the common ancestor of Ascomycota and Basidiomycota maybe had a few introns in the histone genes. In the course of fungal evolution, Saccharomycotina and Taphrinomycotina lost the histone introns; Basidiomycota and Perizomycotina acquired other introns independently. In addition, most of the introns have sequence similarity among introns of phylogenetically close species, strongly suggesting that horizontal intron transfer events between phylogenetically distant species have not occurred recently in the fungal histone genes.

  3. Search for new breast cancer susceptibility genes

    NARCIS (Netherlands)

    Oldenburg, Rogier Abel

    2008-01-01

    This thesis describes the search for new high-risk breast cancer susceptibility genes by linkage analysis. To date 20-25% of familial breast cancer is explained by mutations in the high-risk BRCA1 and BRCA2 breast cancer susceptibility genes. For the remaining families the genetic etiology is

  4. Finding ciliary genes: a computational approach.

    Science.gov (United States)

    Henriksson, Johan; Piasecki, Brian P; Lend, Kristina; Bürglin, Thomas R; Swoboda, Peter

    2013-01-01

    In the nematode worm Caenorhabditis elegans and several other animal species, many ciliary genes are regulated by RFX (Regulatory Factor binding to the X-box) transcription factors (TFs), which bind to X-box promoter motifs and thereby directly activate ciliary gene expression. This setup (RFX TF/X-box/ciliary gene) makes it possible to search for novel ciliary gene candidates genome-wide by using the X-box promoter motif as a search parameter. We present a computational approach that (i) identifies and extracts from whole genomes genes and the corresponding promoter sequences and annotations; (ii) searches through promoters for regulatory sequence elements (like promoter motifs) by using training sets of known instances of these elements; (iii) scores (evaluates) and sorts all positive hits in a database; and (iv) outputs a list of candidate genes and promoters with a given regulatory sequence element. Evolutionary conservation across species (orthology) of genes, promoters, or regulatory sequence elements is used as an important strengthening feature during the overall search approach. Our computational approach is set up in a modular fashion: not every part needs to be used for a particular search effort. In principle, our approach has broad applications. It applies to any group of genes that share common (conserved) regulation through common (conserved) regulatory sequence elements. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Novel interactions between vertebrate Hox genes

    NARCIS (Netherlands)

    Hooiveld, MHW; Morgan, R; Rieden, PID; Houtzager, E; Pannese, M; Damen, K; Boncinelli, E; Durston, AJ

    1999-01-01

    Understanding why metazoan Hox/HOM-C genes are expressed in spatiotemporal sequences showing colinearity with their genomic sequence is a central challenge in developmental biology. Here, we studied the consequences of ectopically expressing Hox genes to investigate whether Hox-Hox interactions

  6. Exploring genes and pathways involved in migraine

    NARCIS (Netherlands)

    Eising, E.

    2017-01-01

    The research in this thesis was aimed at identifying genes and molecular pathways involved in migraine. To this end, two gene expression analyses were performed in brain tissue obtained from transgenic mouse models for familial hemiplegic migraine (FHM), a monogenic subtype of migraine with aura.

  7. Distribution of introns in fungal histone genes.

    Science.gov (United States)

    Yun, Choong-Soo; Nishida, Hiromi

    2011-01-27

    Saccharomycotina and Taphrinomycotina lack intron in their histone genes, except for an intron in one of histone H4 genes of Yarrowia lipolytica. On the other hand, Basidiomycota and Perizomycotina have introns in their histone genes. We compared the distributions of 81, 47, 79, and 98 introns in the fungal histone H2A, H2B, H3, and H4 genes, respectively. Based on the multiple alignments of the amino acid sequences of histones, we identified 19, 13, 31, and 22 intron insertion sites in the histone H2A, H2B, H3, and H4 genes, respectively. Surprisingly only one hot spot of introns in the histone H2A gene is shared between Basidiomycota and Perizomycotina, suggesting that most of introns of Basidiomycota and Perizomycotina were acquired independently. Our findings suggest that the common ancestor of Ascomycota and Basidiomycota maybe had a few introns in the histone genes. In the course of fungal evolution, Saccharomycotina and Taphrinomycotina lost the histone introns; Basidiomycota and Perizomycotina acquired other introns independently. In addition, most of the introns have sequence similarity among introns of phylogenetically close species, strongly suggesting that horizontal intron transfer events between phylogenetically distant species have not occurred recently in the fungal histone genes.

  8. Horizontal gene transfer in the phytosphere

    NARCIS (Netherlands)

    Elsas, van J.D.; Turner, S.; Bailey, M.J.

    2003-01-01

    Here, the ecological aspects of gene transfer processes between bacteria in the phytosphere are examined in the context of emerging evidence for the dominant role that horizontal gene transfer (HGT) has played in the evolutionary shaping of bacterial communities. Moreover, the impact of the putative

  9. Conrad: gene prediction using conditional random fields.

    Science.gov (United States)

    DeCaprio, David; Vinson, Jade P; Pearson, Matthew D; Montgomery, Philip; Doherty, Matthew; Galagan, James E

    2007-09-01

    We present Conrad, the first comparative gene predictor based on semi-Markov conditional random fields (SMCRFs). Unlike the best standalone gene predictors, which are based on generalized hidden Markov models (GHMMs) and trained by maximum likelihood, Conrad is discriminatively trained to maximize annotation accuracy. In addition, unlike the best annotation pipelines, which rely on heuristic and ad hoc decision rules to combine standalone gene predictors with additional information such as ESTs and protein homology, Conrad encodes all sources of information as features and treats all features equally in the training and inference algorithms. Conrad outperforms the best standalone gene predictors in cross-validation and whole chromosome testing on two fungi with vastly different gene structures. The performance improvement arises from the SMCRF's discriminative training methods and their ability to easily incorporate diverse types of information by encoding them as feature functions. On Cryptococcus neoformans, configuring Conrad to reproduce the predictions of a two-species phylo-GHMM closely matches the performance of Twinscan. Enabling discriminative training increases performance, and adding new feature functions further increases performance, achieving a level of accuracy that is unprecedented for this organism. Similar results are obtained on Aspergillus nidulans comparing Conrad versus Fgenesh. SMCRFs are a promising framework for gene prediction because of their highly modular nature, simplifying the process of designing and testing potential indicators of gene structure. Conrad's implementation of SMCRFs advances the state of the art in gene prediction in fungi and provides a robust platform for both current application and future research.

  10. Perspectives: Gene Expression in Fisheries Management

    Science.gov (United States)

    Nielsen, Jennifer L.; Pavey, Scott A.

    2010-01-01

    Functional genes and gene expression have been connected to physiological traits linked to effective production and broodstock selection in aquaculture, selective implications of commercial fish harvest, and adaptive changes reflected in non-commercial fish populations subject to human disturbance and climate change. Gene mapping using single nucleotide polymorphisms (SNPs) to identify functional genes, gene expression (analogue microarrays and real-time PCR), and digital sequencing technologies looking at RNA transcripts present new concepts and opportunities in support of effective and sustainable fisheries. Genomic tools have been rapidly growing in aquaculture research addressing aspects of fish health, toxicology, and early development. Genomic technologies linking effects in functional genes involved in growth, maturation and life history development have been tied to selection resulting from harvest practices. Incorporating new and ever-increasing knowledge of fish genomes is opening a different perspective on local adaptation that will prove invaluable in wild fish conservation and management. Conservation of fish stocks is rapidly incorporating research on critical adaptive responses directed at the effects of human disturbance and climate change through gene expression studies. Genomic studies of fish populations can be generally grouped into three broad categories: 1) evolutionary genomics and biodiversity; 2) adaptive physiological responses to a changing environment; and 3) adaptive behavioral genomics and life history diversity. We review current genomic research in fisheries focusing on those that use microarrays to explore differences in gene expression among phenotypes and within or across populations, information that is critically important to the conservation of fish and their relationship to humans.

  11. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    Conclusion: Progressive therapy with Dendrobium mixture, which has glucose- and lipid-lowering effects, is associated with multi-gene expression pathways. By treating diabetic r and wild-type rats with the mixture, the disorder is further understood at the transcriptomic level. Keywords: Diabetes, Gene expression, ...

  12. (I2 gene) from tomato cultivar Heamsona

    African Journals Online (AJOL)

    aghomotsegin

    2013-10-16

    Oct 16, 2013 ... cloned and characterized for the incompatibility against race 2 type of the pathogens. In India race 1 type of F. oxysporum f. sp. lycopersici observed commonly which require presence of I1 gene in tomato plant for the incompatibility reactions but in the present study, I2 gene was partially isolated from the.

  13. Isolation of cowpea genes conferring drought tolerance ...

    African Journals Online (AJOL)

    The main objective of this study was to identify and isolate the genes conferring drought tolerance in cowpea. A cDNA library enriched for cowpea genes expressed specifically during responses to drought was constructed. A procedure called suppression subtractive hybridisation (SSH) was successfully employed to obtain ...

  14. MOLECULAR STUDY OF NUCLEPROTEIN GENE OF RABIES ...

    African Journals Online (AJOL)

    Analysis of the 1400-b.p RT-PCR products of the N gene and the views by sequencing and restriction endonuclease analysis enabled division of isolates into 3 types. The conclusion from the study is that RT-PCR and restriction endonuclease analysis of the amplified products of the N gene would allow identification and ...

  15. Serial analysis of gene expression (SAGE)

    NARCIS (Netherlands)

    van Ruissen, Fred; Baas, Frank

    2007-01-01

    In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE

  16. Crowdsourcing the nodulation gene network discovery environment.

    Science.gov (United States)

    Li, Yupeng; Jackson, Scott A

    2016-05-26

    The Legumes (Fabaceae) are an economically and ecologically important group of plant species with the conspicuous capacity for symbiotic nitrogen fixation in root nodules, specialized plant organs containing symbiotic microbes. With the aim of understanding the underlying molecular mechanisms leading to nodulation, many efforts are underway to identify nodulation-related genes and determine how these genes interact with each other. In order to accurately and efficiently reconstruct nodulation gene network, a crowdsourcing platform, CrowdNodNet, was created. The platform implements the jQuery and vis.js JavaScript libraries, so that users are able to interactively visualize and edit the gene network, and easily access the information about the network, e.g. gene lists, gene interactions and gene functional annotations. In addition, all the gene information is written on MediaWiki pages, enabling users to edit and contribute to the network curation. Utilizing the continuously updated, collaboratively written, and community-reviewed Wikipedia model, the platform could, in a short time, become a comprehensive knowledge base of nodulation-related pathways. The platform could also be used for other biological processes, and thus has great potential for integrating and advancing our understanding of the functional genomics and systems biology of any process for any species. The platform is available at http://crowd.bioops.info/ , and the source code can be openly accessed at https://github.com/bioops/crowdnodnet under MIT License.

  17. Expression of Deinococcus geothermalis trehalose synthase gene ...

    African Journals Online (AJOL)

    A novel trehalose synthase gene from Deinococcus geothermalis (DSMZ 11300) containing 1692 bp reading-frame encoding 564 amino acids was amplified using polymerase chain reaction (PCR). The gene was ligated into pET30Ek/LIC vector and expressed after isopropyl β-D-thiogalactopyranoside induction in ...

  18. Influence of thiopurine methyltransferase gene polymorphism on ...

    Indian Academy of Sciences (India)

    Azza A. G. Tantawy

    2017-11-28

    Nov 28, 2017 ... Journal of Genetics, Vol. 96, No. ... aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). ... Keywords. thiopurine methyltransferase gene polymorphism; acute lymphoblastic leukaemia; Egyptian children; thiopurine.

  19. Divergence of flowering genes in soybean

    Indian Academy of Sciences (India)

    Soybean genome sequences were blasted with Arabidopsis thaliana regulatory genes involved in photoperiod-dependent flowering. This approach enabled the identification of 118 genes involved in the flowering pathway. Two genome sequences of cultivated (Williams 82) and wild (IT182932) soybeans were employed to ...

  20. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    firmed difference in expression profiles of the identified genes in musculus longissimus muscle tissues between the two Lan- ..... Discussion. The EEF1A2, TSG101 and TTN identified as upregulated genes in high-growth group have been reported to be involved in myotube survival and .... cDNA probes and libraries. Proc.

  1. Evaluating historical candidate genes for schizophrenia

    DEFF Research Database (Denmark)

    Farrell, M S; Werge, T; Sklar, P

    2015-01-01

    Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of thes...

  2. Pichia stipitis genomics, transcriptomics, and gene clusters

    Science.gov (United States)

    Thomas W. Jeffries; Jennifer R. Headman Van Vleet

    2009-01-01

    Genome sequencing and subsequent global gene expression studies have advanced our understanding of the lignocellulose-fermenting yeast Pichia stipitis. These studies have provided an insight into its central carbon metabolism, and analysis of its genome has revealed numerous functional gene clusters and tandem repeats. Specialized physiological traits are often the...

  3. Locus control regions and gene therapy

    NARCIS (Netherlands)

    D.D. Drabek (Dubravka)

    1999-01-01

    textabstractGene therapy is a procedure in which exogenous genetic material is introduced into the cells of a patient in order to correct an genetic error or to provide the cells of the patient with a new functional property. Correction can be achieved by gene targeting via homologous recombination,

  4. Gene finding: putting the parts together

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose

    1998-01-01

    In this paper, the author discusses ways of combining information of splice sites, coding potential, etc. into a prediction of a complete gene structure.......In this paper, the author discusses ways of combining information of splice sites, coding potential, etc. into a prediction of a complete gene structure....

  5. Noise minimization in eukaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

    2004-01-15

    All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

  6. Synaptotagmin gene content of the sequenced genomes

    Directory of Open Access Journals (Sweden)

    Craxton Molly

    2004-07-01

    Full Text Available Abstract Background Synaptotagmins exist as a large gene family in mammals. There is much interest in the function of certain family members which act crucially in the regulated synaptic vesicle exocytosis required for efficient neurotransmission. Knowledge of the functions of other family members is relatively poor and the presence of Synaptotagmin genes in plants indicates a role for the family as a whole which is wider than neurotransmission. Identification of the Synaptotagmin genes within completely sequenced genomes can provide the entire Synaptotagmin gene complement of each sequenced organism. Defining the detailed structures of all the Synaptotagmin genes and their encoded products can provide a useful resource for functional studies and a deeper understanding of the evolution of the gene family. The current rapid increase in the number of sequenced genomes from different branches of the tree of life, together with the public deposition of evolutionarily diverse transcript sequences make such studies worthwhile. Results I have compiled a detailed list of the Synaptotagmin genes of Caenorhabditis, Anopheles, Drosophila, Ciona, Danio, Fugu, Mus, Homo, Arabidopsis and Oryza by examining genomic and transcript sequences from public sequence databases together with some transcript sequences obtained by cDNA library screening and RT-PCR. I have compared all of the genes and investigated the relationship between plant Synaptotagmins and their non-Synaptotagmin counterparts. Conclusions I have identified and compared 98 Synaptotagmin genes from 10 sequenced genomes. Detailed comparison of transcript sequences reveals abundant and complex variation in Synaptotagmin gene expression and indicates the presence of Synaptotagmin genes in all animals and land plants. Amino acid sequence comparisons indicate patterns of conservation and diversity in function. Phylogenetic analysis shows the origin of Synaptotagmins in multicellular eukaryotes and their

  7. Expression of Sox genes in tooth development

    Science.gov (United States)

    KAWASAKI, KATSUSHIGE; KAWASAKI, MAIKO; WATANABE, MOMOKO; IDRUS, ERIK; NAGAI, TAKAHIRO; OOMMEN, SHELLY; MAEDA, TAKEYASU; HAGIWARA, NOBUKO; QUE, JIANWEN; SHARPE, PAUL T.; OHAZAMA, ATSUSHI

    2017-01-01

    Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development. PMID:26864488

  8. Gene regulatory mechanisms in infected fish

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Hajiabadi, Seyed Amir Hossein Jalali; Kristensen, Lasse Bøgelund Juel

    2011-01-01

    This talk will highlight the regulatory mechanisms of gene expression especially the programmed form of mRNA decay which is known as RNA interference (RNAi) and how this and other mechanisms contribute to the regulation of genes involved in immunity. In the RNAi mechanism small double stranded RNA...... molecules produced by the eukaryotic cell is used to program the RNA Induced Silencing Complex (RISC) for cleavage of specific mRNA transcripts and/or translational repression in the cytoplasm or even chromatin methylation in the nucleus. All processes leading to silencing of the target gene. MicroRNAs (or...... miRNAs) are one class of such small RNAs which are expressed from the genome. The RISC system allows for non-perfect base pairing of miRNAs to their target genes why one small RNA can in theory silence large groups of genes at the same time. It is therefore anticipated that they are able to depress...

  9. Global gene expression in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Schembri, Mark; Kjærgaard, K.; Klemm, Per

    2003-01-01

    It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance...... to antimicrobial treatments and host immune defence responses. Escherichia coli has been used as a model organism to study the mechanisms of growth within adhered communities. In this study, we use DNA microarray technology to examine the global gene expression profile of E. coli during sessile growth compared...... the transition to biofilm growth, and these included genes expressed under oxygen-limiting conditions, genes encoding (putative) transport proteins, putative oxidoreductases and genes associated with enhanced heavy metal resistance. Of particular interest was the observation that many of the genes altered...

  10. Bioinformatics methods for identifying candidate disease genes

    Directory of Open Access Journals (Sweden)

    van Driel Marc A

    2006-06-01

    Full Text Available Abstract With the explosion in genomic and functional genomics information, methods for disease gene identification are rapidly evolving. Databases are now essential to the process of selecting candidate disease genes. Combining positional information with disease characteristics and functional information is the usual strategy by which candidate disease genes are selected. Enrichment for candidate disease genes, however, depends on the skills of the operating researcher. Over the past few years, a number of bioinformatics methods that enrich for the most likely candidate disease genes have been developed. Such in silico prioritisation methods may further improve by completion of datasets, by development of standardised ontologies across databases and species and, ultimately, by the integration of different strategies.

  11. Horizontal gene transfer in human pathogens.

    Science.gov (United States)

    Juhas, Mario

    2015-02-01

    Horizontal gene transfer has a tremendous impact on the genome plasticity, adaptation and evolution of bacteria. Horizontally transferred mobile genetic elements are involved in the dissemination of antibiotic resistance and virulence genes, thus 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 horizontal gene transfer plays in pathogenicity of the emerging human pathogens: hypervirulent Clostridium difficile and Escherichia coli (including the most recent haemolytic uraemic syndrome outbreak strain) and methicillin-resistant Staphylococcus aureus (MRSA), which have been associated with largest outbreaks of infection recently.

  12. Epigenetic control of gene regulation in plants.

    Science.gov (United States)

    Lauria, Massimiliano; Rossi, Vincenzo

    2011-08-01

    In eukaryotes, including plants, the genome is compacted into chromatin, which forms a physical barrier for gene transcription. Therefore, mechanisms that alter chromatin structure play an essential role in gene regulation. When changes in the chromatin states are inherited trough mitotic or meiotic cell division, the mechanisms responsible for these changes are defined as epigenetic. In this paper, we review data arising from genome-wide analysis of the epigenetic landscapes in different plant species to establish the correlation between specific epigenetic marks and transcription. In the subsequent sections, mechanisms of epigenetic control of gene regulation mediated by DNA-binding transcription factors and by transposons located in proximity to genes are illustrated. Finally, plant peculiarities for epigenetic control of gene regulation and future perspectives in this research area are discussed. This article is part of a Special Issue entitled: Epigenetic Control of cellular and developmental processes in plants. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Expression of Sox genes in tooth development.

    Science.gov (United States)

    Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

    2015-01-01

    Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

  14. Genome-wide Analysis of Gene Regulation

    DEFF Research Database (Denmark)

    Chen, Yun

    IP-seq and small RNA-seq, we delineated the landscape of the promoters with bidirectional transcriptions that yield steady-state RNA in only one directions (Paper III). A subsequent motif analysis enabled us to uncover specific DNA signals – early polyA sites – that make RNA on the reverse strand sensitive......). Gene enrichment analysis on the detected NMD substrates revealed an unappreciated NMD-based regulatory mechanism of the genes hosting multiple intronic snoRNAs, which can facilitate differential expression of individual snoRNAs from a single host gene locus. Finally, supported by RNA-seq and small RNA...... gene regulation will disrupt the cell’s fundamental processes, which in turn can cause disease. Hence, understanding gene regulation is essential for deciphering the code of life. Along with the development of high throughput sequencing (HTS) technology and the subsequent large-scale data analysis...

  15. Homeobox Genes in the Rodent Pineal Gland

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Klein, David C

    2013-01-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential...... for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental...... functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function...

  16. Nucleosomal promoter variation generates gene expression noise.

    Science.gov (United States)

    Brown, Christopher R; Boeger, Hinrich

    2014-12-16

    Gene product molecule numbers fluctuate over time and between cells, confounding deterministic expectations. The molecular origins of this noise of gene expression remain unknown. Recent EM analysis of single PHO5 gene molecules of yeast indicated that promoter molecules stochastically assume alternative nucleosome configurations at steady state, including the fully nucleosomal and nucleosome-free configuration. Given that distinct configurations are unequally conducive to transcription, the nucleosomal variation of promoter molecules may constitute a source of gene expression noise. This notion, however, implies an untested conjecture, namely that the nucleosomal variation arises de novo or intrinsically (i.e., that it cannot be explained as the result of the promoter's deterministic response to variation in its molecular surroundings). Here, we show--by microscopically analyzing the nucleosome configurations of two juxtaposed physically linked PHO5 promoter copies--that the configurational variation, indeed, is intrinsically stochastic and thus, a cause of gene expression noise rather than its effect.

  17. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA......) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...... differences in peripheral blood mononuclear cell (MNC) gene expression patterns between 15 newly diagnosed HT patients and 15 matched healthy controls. However, the MNC expression levels of five genes were significantly upregulated in 25 IBD patients, compared to 18 matched healthy controls (CD14, FACL2, FCN1...

  18. Epigenetic regulation of monoallelic gene expression.

    Science.gov (United States)

    Shiba, Hiroshi; Takayama, Seiji

    2012-01-01

    Monoallelic expression from biallelic genes is frequently observed in diploid eukaryotic organisms. Classic examples of this phenomenon include the well-characterized cases of genomic imprinting and X-chromosome inactivation. However, recent studies have shown that monoallelic expression is widespread in autosomal genes. This discovery was met with great interest because it represents another mechanism to generate diversity in gene expression that can affect cell fate and physiology. To date, the molecular mechanisms underlying this phenomenon are largely unknown. In our original study describing the dominant ⁄ recessive relationships of pollen- determinant alleles in Brassica self-incompatibility, we found that the recessive allele was specifically methylated and silenced through the action of small RNA derived from the dominant allele. In this review, we focus on recent studies of monoallelic expression in autosomal genes, and discuss the possible mechanisms driving this form of monoallelic gene suppression.

  19. Replication timing-related and gene body-specific methylation of active human genes.

    Science.gov (United States)

    Aran, Dvir; Toperoff, Gidon; Rosenberg, Michael; Hellman, Asaf

    2011-02-15

    Understanding how the epigenetic blueprint of the genome shapes human phenotypes requires systematic evaluation of the complex interplay between gene activity and the different layers of the epigenome. Utilizing microarray-based techniques, we explored the relationships between DNA methylation, DNA replication timing and gene expression levels across a variety of human tissues and cell lines. The analyses revealed unequal methylation levels among early- and late-replicating fractions of the genome: late-replicating DNA was hypomethylated compared with early-replicating DNA. Moreover, late-replicating regions were gradually demethylated with cell divisions, whereas the methylation of early-replicating regions was better maintained. As active genes concentrate at early-replicating regions, they are overall hypermethylated relative to inactive genes. Accordingly, we show that the previously reported positive correlation between gene-body methylation (methylation of the transcribed portion of genes) and gene expression is restricted to proliferative tissues and cell lines, whereas in tissues containing few proliferating cells, active and inactive genes have similar methylation levels. We further show that active gene bodies are hypermethylated not only compared with inactive gene bodies, but also compared with their flanking sequences. This specific hypermethylation of the active gene bodies is severely disrupted in cells of an immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome patient bearing mutated DNA methyltransferase 3B (DNMT3B). Our data show that a high methylation level is preferentially maintained in active gene bodies through independent cellular processes. Rather than serving as a distinctive mark between active and inactive genes, gene-body methylation appears to serve a vital, currently unknown function in active genes.

  20. Constructing an integrated gene similarity network for the identification of disease genes.

    Science.gov (United States)

    Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin

    2017-09-20

    Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .

  1. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

    Directory of Open Access Journals (Sweden)

    Turner Renee J

    2009-08-01

    Full Text Available Abstract Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT, 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder. Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

  2. Gene expression results in lipopolysaccharide-stimulated monocytes depend significantly on the choice of reference genes

    Directory of Open Access Journals (Sweden)

    Øvstebø Reidun

    2010-05-01

    Full Text Available Abstract Background Gene expression in lipopolysaccharide (LPS-stimulated monocytes is mainly studied by quantitative real-time reverse transcription PCR (RT-qPCR using GAPDH (glyceraldehyde 3-phosphate dehydrogenase or ACTB (beta-actin as reference gene for normalization. Expression of traditional reference genes has been shown to vary substantially under certain conditions leading to invalid results. To investigate whether traditional reference genes are stably expressed in LPS-stimulated monocytes or if RT-qPCR results are dependent on the choice of reference genes, we have assessed and evaluated gene expression stability of twelve candidate reference genes in this model system. Results Twelve candidate reference genes were quantified by RT-qPCR in LPS-stimulated, human monocytes and evaluated using the programs geNorm, Normfinder and BestKeeper. geNorm ranked PPIB (cyclophilin B, B2M (beta-2-microglobulin and PPIA (cyclophilin A as the best combination for gene expression normalization in LPS-stimulated monocytes. Normfinder suggested TBP (TATA-box binding protein and B2M as the best combination. Compared to these combinations, normalization using GAPDH alone resulted in significantly higher changes of TNF-α (tumor necrosis factor-alpha and IL10 (interleukin 10 expression. Moreover, a significant difference in TNF-α expression between monocytes stimulated with equimolar concentrations of LPS from N. meningitides and E. coli, respectively, was identified when using the suggested combinations of reference genes for normalization, but stayed unrecognized when employing a single reference gene, ACTB or GAPDH. Conclusions Gene expression levels in LPS-stimulated monocytes based on RT-qPCR results differ significantly when normalized to a single gene or a combination of stably expressed reference genes. Proper evaluation of reference gene stabiliy is therefore mandatory before reporting RT-qPCR results in LPS-stimulated monocytes.

  3. Evolution of evolvability in gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Anton Crombach

    Full Text Available Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

  4. Disease gene prioritization using network and feature.

    Science.gov (United States)

    Xie, Bingqing; Agam, Gady; Balasubramanian, Sandhya; Xu, Jinbo; Gilliam, T Conrad; Maltsev, Natalia; Börnigen, Daniela

    2015-04-01

    Identifying high-confidence candidate genes that are causative for disease phenotypes, from the large lists of variations produced by high-throughput genomics, can be both time-consuming and costly. The development of novel computational approaches, utilizing existing biological knowledge for the prioritization of such candidate genes, can improve the efficiency and accuracy of the biomedical data analysis. It can also reduce the cost of such studies by avoiding experimental validations of irrelevant candidates. In this study, we address this challenge by proposing a novel gene prioritization approach that ranks promising candidate genes that are likely to be involved in a disease or phenotype under study. This algorithm is based on the modified conditional random field (CRF) model that simultaneously makes use of both gene annotations and gene interactions, while preserving their original representation. We validated our approach on two independent disease benchmark studies by ranking candidate genes using network and feature information. Our results showed both high area under the curve (AUC) value (0.86), and more importantly high partial AUC (pAUC) value (0.1296), and revealed higher accuracy and precision at the top predictions as compared with other well-performed gene prioritization tools, such as Endeavour (AUC-0.82, pAUC-0.083) and PINTA (AUC-0.76, pAUC-0.066). We were able to detect more target genes (9/18/19/27) on top positions (1/5/10/20) compared to Endeavour (3/11/14/23) and PINTA (6/10/13/18). To demonstrate its usability, we applied our method to a case study for the prediction of molecular mechanisms contributing to intellectual disability and autism. Our approach was able to correctly recover genes related to both disorders and provide suggestions for possible additional candidates based on their rankings and functional annotations.

  5. Origin of saxitoxin biosynthetic genes in cyanobacteria.

    Directory of Open Access Journals (Sweden)

    Ahmed Moustafa

    2009-06-01

    Full Text Available Paralytic shellfish poisoning (PSP is a potentially fatal syndrome associated with the consumption of shellfish that have accumulated saxitoxin (STX. STX is produced by microscopic marine dinoflagellate algae. Little is known about the origin and spread of saxitoxin genes in these under-studied eukaryotes. Fortuitously, some freshwater cyanobacteria also produce STX, providing an ideal model for studying its biosynthesis. Here we focus on saxitoxin-producing cyanobacteria and their non-toxic sisters to elucidate the origin of genes involved in the putative STX biosynthetic pathway.We generated a draft genome assembly of the saxitoxin-producing (STX+ cyanobacterium Anabaena circinalis ACBU02 and searched for 26 candidate saxitoxin-genes (named sxtA to sxtZ that were recently identified in the toxic strain Cylindrospermopsis raciborskii T3. We also generated a draft assembly of the non-toxic (STX- sister Anabaena circinalis ACFR02 to aid the identification of saxitoxin-specific genes. Comparative phylogenomic analyses revealed that nine putative STX genes were horizontally transferred from non-cyanobacterial sources, whereas one key gene (sxtA originated in STX+ cyanobacteria via two independent horizontal transfers followed by fusion. In total, of the 26 candidate saxitoxin-genes, 13 are of cyanobacterial provenance and are monophyletic among the STX+ taxa, four are shared amongst STX+ and STX-cyanobacteria, and the remaining nine genes are specific to STX+ cyanobacteria.Our results provide evidence that the assembly of STX genes in ACBU02 involved multiple HGT events from different sources followed presumably by coordination of the expression of foreign and native genes in the common ancestor of STX+ cyanobacteria. The ability to produce saxitoxin was subsequently lost multiple independent times resulting in a nested relationship of STX+ and STX- strains among Anabaena circinalis strains.

  6. Gallstones: environment, lifestyle and genes.

    Science.gov (United States)

    Stokes, Caroline S; Krawczyk, Marcin; Lammert, Frank

    2011-01-01

    Gallstone disease represents one of the most common and costly gastroenterological disorders. In Germany, 0.25% of the population undergo cholecystectomy per year, and cholelithiasis incurs annual medical expenses of more than USD 6.5 billion in the United States. The paradigm of environmental risk factors for gallstones has lately been challenged by genetic studies in experimental models and humans. The analysis of more than 40,000 Swedish twin pairs with gallstones demonstrated that genetic factors account for 25% of the phenotypic variance. Since then, studies employing genome-wide association analysis, case-control cohorts and analysis of sib-pairs in families with gallstones have expanded our knowledge of 'gallstone genes'. Indeed, gallstone disease phenotypes are likely to result from the complex interaction of genetic factors, chronic overnutrition with carbohydrates, depletion of dietary fibre and other not fully defined environmental factors including physical inactivity and infections. This hypothesis is supported by the profound increases of cholesterol gallstone prevalence rates in Native Americans, post-war European countries and current urban centres in East Asia, all of which were associated with 'westernized' nutrition. Herein, we summarise the spectrum of environmental and genetic risk factors which should pave the way to 'personalised' strategies for the prevention and therapy of gallstones. Copyright © 2011 S. Karger AG, Basel.

  7. NEUROIMÁGENES EN DEMENCIAS

    Directory of Open Access Journals (Sweden)

    Ing. Gonzalo Rojas C.

    2016-05-01

    Full Text Available Las demencias constituyen un problema severo de salud a nivel mundial, y describen una gran cantidad de síntomas. Se caracterizan por un deterioro cognitivo adquirido irreversible que afecta principalmente, pero no exclusivamente, la memoria. Además, afecta especialmente a las personas mayores, pero no constituye una consecuencia normal del envejecimiento. Existen múltiples técnicas imagenológicas que apoyan el diagnóstico, que están en etapa de investigación o que se utilizan actualmente en el aspecto clínico. Protocolos estándar de imágenes de resonancia magnética, escalas de evaluación visual de la atrofia, técnicas de volumetría cerebral, paradigmas de resonancia magnética funcional, técnicas de conectividad funcional de reposo, SPECT y PET son las técnicas que se comentarán en este artículo.

  8. Visualizing Gene Expression In Situ

    Energy Technology Data Exchange (ETDEWEB)

    Burlage, R.S.

    1998-11-02

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

  9. Kuru: genes, cannibals and neuropathology.

    Science.gov (United States)

    Liberski, Pawel P; Sikorska, Beata; Lindenbaum, Shirley; Goldfarb, Lev G; McLean, Catriona; Hainfellner, Johannes A; Brown, Paul

    2012-02-01

    Kuru was the first human transmissible spongiform encephalopathy (TSE) or prion disease identified, occurring in the Fore linguistic group of Papua New Guinea. Kuru was a uniformly fatal cerebellar ataxic syndrome, usually followed by choreiform and athetoid movements. Kuru imposed a strong balancing selection on the Fore population, with individuals homozygous for the 129 Met allele of the gene (PRNP) encoding for prion protein (PrP) being the most susceptible. The decline in the incidence of kuru in the Fore has been attributed to the exhaustion of the susceptible genotype and ultimately by discontinuation of exposure via cannibalism. Neuropathologically, kuru-affected brains were characterized by widespread degeneration of neurons, astroglial and microglial proliferation, and the presence of amyloid plaques. These early findings have been confirmed and extended by recent immunohistochemical studies for the detection of the TSE-specific PrP (PrP). Confocal laser microscopy also showed the concentration of glial fibrillary acidic protein-positive astrocytic processes at the plaque periphery. The fine structure of plaques corresponds to that described earlier by light microscopy. The successful experimental transmission of kuru led to the awareness of its similarity to Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease and formed a background against which the recent epidemics of iatrogenic and variant Creutzfeldt-Jakob disease could be studied.

  10. The gsdf gene locus harbors evolutionary conserved and clustered genes preferentially expressed in fish previtellogenic oocytes.

    Science.gov (United States)

    Gautier, Aude; Le Gac, Florence; Lareyre, Jean-Jacques

    2011-02-01

    The gonadal soma-derived factor (GSDF) belongs to the transforming growth factor-β superfamily and is conserved in teleostean fish species. Gsdf is specifically expressed in the gonads, and gene expression is restricted to the granulosa and Sertoli cells in trout and medaka. The gsdf gene expression is correlated to early testis differentiation in medaka and was shown to stimulate primordial germ cell and spermatogonia proliferation in trout. In the present study, we show that the gsdf gene localizes to a syntenic chromosomal fragment conserved among vertebrates although no gsdf-related gene is detected on the corresponding genomic region in tetrapods. We demonstrate using quantitative RT-PCR that most of the genes localized in the synteny are specifically expressed in medaka gonads. Gsdf is the only gene of the synteny with a much higher expression in the testis compared to the ovary. In contrast, gene expression pattern analysis of the gsdf surrounding genes (nup54, aff1, klhl8, sdad1, and ptpn13) indicates that these genes are preferentially expressed in the female gonads. The tissue distribution of these genes is highly similar in medaka and zebrafish, two teleostean species that have diverged more than 110 million years ago. The cellular localization of these genes was determined in medaka gonads using the whole-mount in situ hybridization technique. We confirm that gsdf gene expression is restricted to Sertoli and granulosa cells in contact with the premeiotic and meiotic cells. The nup54 gene is expressed in spermatocytes and previtellogenic oocytes. Transcripts corresponding to the ovary-specific genes (aff1, klhl8, and sdad1) are detected only in previtellogenic oocytes. No expression was detected in the gonocytes in 10 dpf embryos. In conclusion, we show that the gsdf gene localizes to a syntenic chromosomal fragment harboring evolutionary conserved genes in vertebrates. These genes are preferentially expressed in previtelloogenic oocytes, and thus, they

  11. A recently transferred cluster of bacterial genes in Trichomonas vaginalis - lateral gene transfer and the fate of acquired genes

    Science.gov (United States)

    2014-01-01

    Background Lateral Gene Transfer (LGT) has recently gained recognition as an important contributor to some eukaryote proteomes, but the mechanisms of acquisition and fixation in eukaryotic genomes are still uncertain. A previously defined norm for LGTs in microbial eukaryotes states that the majority are genes involved in metabolism, the LGTs are typically localized one by one, surrounded by vertically inherited genes on the chromosome, and phylogenetics shows that a broad collection of bacterial lineages have contributed to the transferome. Results A unique 34 kbp long fragment with 27 clustered genes (TvLF) of prokaryote origin was identified in the sequenced genome of the protozoan parasite Trichomonas vaginalis. Using a PCR based approach we confirmed the presence of the orthologous fragment in four additional T. vaginalis strains. Detailed sequence analyses unambiguously suggest that TvLF is the result of one single, recent LGT event. The proposed donor is a close relative to the firmicute bacterium Peptoniphilus harei. High nucleotide sequence similarity between T. vaginalis strains, as well as to P. harei, and the absence of homologs in other Trichomonas species, suggests that the transfer event took place after the radiation of the genus Trichomonas. Some genes have undergone pseudogenization and degradation, indicating that they may not be retained in the future. Functional annotations reveal that genes involved in informational processes are particularly prone to degradation. Conclusions We conclude that, although the majority of eukaryote LGTs are single gene occurrences, they may be acquired in clusters of several genes that are subsequently cleansed of evolutionarily less advantageous genes. PMID:24898731

  12. Gene Duplication and Gene Expression Changes Play a Role in the Evolution of Candidate Pollen Feeding Genes in Heliconius Butterflies.

    Science.gov (United States)

    Smith, Gilbert; Macias-Muñoz, Aide; Briscoe, Adriana D

    2016-09-02

    Heliconius possess a unique ability among butterflies to feed on pollen. Pollen feeding significantly extends their lifespan, and is thought to have been important to the diversification of the genus. We used RNA sequencing to examine feeding-related gene expression in the mouthparts of four species of Heliconius and one nonpollen feeding species, Eueides isabella We hypothesized that genes involved in morphology and protein metabolism might be upregulated in Heliconius because they have longer proboscides than Eueides, and because pollen contains more protein than nectar. Using de novo transcriptome assemblies, we tested these hypotheses by comparing gene expression in mouthparts against antennae and legs. We first looked for genes upregulated in mouthparts across all five species and discovered several hundred genes, many of which had functional annotations involving metabolism of proteins (cocoonase), lipids, and carbohydrates. We then looked specifically within Heliconius where we found eleven common upregulated genes with roles in morphology (CPR cuticle proteins), behavior (takeout-like), and metabolism (luciferase-like). Closer examination of these candidates revealed that cocoonase underwent several duplications along the lineage leading to heliconiine butterflies, including two Heliconius-specific duplications. Luciferase-like genes also underwent duplication within lepidopterans, and upregulation in Heliconius mouthparts. Reverse-transcription PCR confirmed that three cocoonases, a peptidase, and one luciferase-like gene are expressed in the proboscis with little to no expression in labial palps and salivary glands. Our results suggest pollen feeding, like other dietary specializations, was likely facilitated by adaptive expansions of preexisting genes-and that the butterfly proboscis is involved in digestive enzyme production. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. tRNA genes protect a reporter gene from epigenetic silencing in mouse cells.

    Science.gov (United States)

    Ebersole, Thomas; Kim, Jung-Hyun; Samoshkin, Alexander; Kouprina, Natalay; Pavlicek, Adam; White, Robert J; Larionov, Vladimir

    2011-08-15

    It is a well-established fact that the tRNA genes in yeast can function as chromatin barrier elements. However, so far there is no experimental evidence that tRNA and other Pol III-transcribed genes exhibit barrier activity in mammals. This study utilizes a recently developed reporter gene assay to test a set of Pol III-transcribed genes and gene clusters with variable promoter and intergenic regions for their ability to prevent heterochromatin-mediated reporter gene silencing in mouse cells. The results show that functional copies of mouse tRNA genes are effective barrier elements. The number of tRNA genes as well as their orientation influence barrier function. Furthermore, the DNA sequence composition of intervening and flanking regions affects barrier activity of tRNA genes. Barrier activity was maintained for much longer time when the intervening and flanking regions of tRNA genes were replaced by AT-rich sequences, suggesting a negative role of DNA methylation in the establishment of a functional barrier. Thus, our results suggest that tRNA genes are essential elements in establishment and maintenance of chromatin domain architecture in mammalian cells.

  14. Camera: a competitive gene set test accounting for inter-gene correlation

    Science.gov (United States)

    Wu, Di; Smyth, Gordon K.

    2012-01-01

    Competitive gene set tests are commonly used in molecular pathway analysis to test for enrichment of a particular gene annotation category amongst the differential expression results from a microarray experiment. Existing gene set tests that rely on gene permutation are shown here to be extremely sensitive to inter-gene correlation. Several data sets are analyzed to show that inter-gene correlation is non-ignorable even for experiments on homogeneous cell populations using genetically identical model organisms. A new gene set test procedure (CAMERA) is proposed based on the idea of estimating the inter-gene correlation from the data, and using it to adjust the gene set test statistic. An efficient procedure is developed for estimating the inter-gene correlation and characterizing its precision. CAMERA is shown to control the type I error rate correctly regardless of inter-gene correlations, yet retains excellent power for detecting genuine differential expression. Analysis of breast cancer data shows that CAMERA recovers known relationships between tumor subtypes in very convincing terms. CAMERA can be used to analyze specified sets or as a pathway analysis tool using a database of molecular signatures. PMID:22638577

  15. Gene delivery to the lungs: pulmonary gene therapy for cystic fibrosis.

    Science.gov (United States)

    Villate-Beitia, Ilia; Zarate, Jon; Puras, Gustavo; Pedraz, José Luis

    2017-07-01

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder where the defective gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is well identified. Moreover, the respiratory tract can be targeted through noninvasive aerosolized formulations for inhalation. Therefore, gene therapy is considered a plausible strategy to address this disease. Conventional gene therapy strategies rely on the addition of a correct copy of the CFTR gene into affected cells in order to restore the channel activity. In recent years, genome correction strategies have emerged, such as zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases. These gene editing tools aim to repair the mutated gene at its original genomic locus with high specificity. Besides, the success of gene therapy critically depends on the nucleic acids carriers. To date, several clinical studies have been carried out to add corrected copies of the CFTR gene into target cells using viral and non-viral vectors, some of them with encouraging results. Regarding genome editing systems, preliminary in vitro studies have been performed in order to repair the CFTR gene. In this review, after briefly introducing the basis of CF, we discuss the up-to-date gene therapy strategies to address the disease. The review focuses on the main factors to take into consideration when developing gene delivery strategies, such as the design of vectors and plasmid DNA, in vitro/in vivo tests, translation to human use, administration methods, manufacturing conditions and regulatory issues.

  16. Turning publicly available gene expression data into discoveries using gene set context analysis.

    Science.gov (United States)

    Ji, Zhicheng; Vokes, Steven A; Dang, Chi V; Ji, Hongkai

    2016-01-08

    Gene Set Context Analysis (GSCA) is an open source software package to help researchers use massive amounts of publicly available gene expression data (PED) to make discoveries. Users can interactively visualize and explore gene and gene set activities in 25,000+ consistently normalized human and mouse gene expression samples representing diverse biological contexts (e.g. different cells, tissues and disease types, etc.). By providing one or multiple genes or gene sets as input and specifying a gene set activity pattern of interest, users can query the expression compendium to systematically identify biological contexts associated with the specified gene set activity pattern. In this way, researchers with new gene sets from their own experiments may discover previously unknown contexts of gene set functions and hence increase the value of their experiments. GSCA has a graphical user interface (GUI). The GUI makes the analysis convenient and customizable. Analysis results can be conveniently exported as publication quality figures and tables. GSCA is available at https://github.com/zji90/GSCA. This software significantly lowers the bar for biomedical investigators to use PED in their daily research for generating and screening hypotheses, which was previously difficult because of the complexity, heterogeneity and size of the data. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Correlating Information Contents of Gene Ontology Terms to Infer Semantic Similarity of Gene Products

    Directory of Open Access Journals (Sweden)

    Mingxin Gan

    2014-01-01

    Full Text Available Successful applications of the gene ontology to the inference of functional relationships between gene products in recent years have raised the need for computational methods to automatically calculate semantic similarity between gene products based on semantic similarity of gene ontology terms. Nevertheless, existing methods, though having been widely used in a variety of applications, may significantly overestimate semantic similarity between genes that are actually not functionally related, thereby yielding misleading results in applications. To overcome this limitation, we propose to represent a gene product as a vector that is composed of information contents of gene ontology terms annotated for the gene product, and we suggest calculating similarity between two gene products as the relatedness of their corresponding vectors using three measures: Pearson’s correlation coefficient, cosine similarity, and the Jaccard index. We focus on the biological process domain of the gene ontology and annotations of yeast proteins to study the effectiveness of the proposed measures. Results show that semantic similarity scores calculated using the proposed measures are more consistent with known biological knowledge than those derived using a list of existing methods, suggesting the effectiveness of our method in characterizing functional relationships between gene products.

  18. Horizontal gene transfer is a significant driver of gene innovation in dinoflagellates.

    Science.gov (United States)

    Wisecaver, Jennifer H; Brosnahan, Michael L; Hackett, Jeremiah D

    2013-01-01

    The dinoflagellates are an evolutionarily and ecologically important group of microbial eukaryotes. Previous work suggests that horizontal gene transfer (HGT) is an important source of gene innovation in these organisms. However, dinoflagellate genomes are notoriously large and complex, making genomic investigation of this phenomenon impractical with currently available sequencing technology. Fortunately, de novo transcriptome sequencing and assembly provides an alternative approach for investigating HGT. We sequenced the transcriptome of the dinoflagellate Alexandrium tamarense Group IV to investigate how HGT has contributed to gene innovation in this group. Our comprehensive A. tamarense Group IV gene set was compared with those of 16 other eukaryotic genomes. Ancestral gene content reconstruction of ortholog groups shows that A. tamarense Group IV has the largest number of gene families gained (314-1,563 depending on inference method) relative to all other organisms in the analysis (0-782). Phylogenomic analysis indicates that genes horizontally acquired from bacteria are a significant proportion of this gene influx, as are genes transferred from other eukaryotes either through HGT or endosymbiosis. The dinoflagellates also display curious cases of gene loss associated with mitochondrial metabolism including the entire Complex I of oxidative phosphorylation. Some of these missing genes have been functionally replaced by bacterial and eukaryotic xenologs. The transcriptome of A. tamarense Group IV lends strong support to a growing body of evidence that dinoflagellate genomes are extraordinarily impacted by HGT.

  19. An atlas of gene expression and gene co-regulation in the human retina.

    Science.gov (United States)

    Pinelli, Michele; Carissimo, Annamaria; Cutillo, Luisa; Lai, Ching-Hung; Mutarelli, Margherita; Moretti, Maria Nicoletta; Singh, Marwah Veer; Karali, Marianthi; Carrella, Diego; Pizzo, Mariateresa; Russo, Francesco; Ferrari, Stefano; Ponzin, Diego; Angelini, Claudia; Banfi, Sandro; di Bernardo, Diego

    2016-07-08

    The human retina is a specialized tissue involved in light stimulus transduction. Despite its unique biology, an accurate reference transcriptome is still missing. Here, we performed gene expression analysis (RNA-seq) of 50 retinal samples from non-visually impaired post-mortem donors. We identified novel transcripts with high confidence (Observed Transcriptome (ObsT)) and quantified the expression level of known transcripts (Reference Transcriptome (RefT)). The ObsT included 77 623 transcripts (23 960 genes) covering 137 Mb (35 Mb new transcribed genome). Most of the transcripts (92%) were multi-exonic: 81% with known isoforms, 16% with new isoforms and 3% belonging to new genes. The RefT included 13 792 genes across 94 521 known transcripts. Mitochondrial genes were among the most highly expressed, accounting for about 10% of the reads. Of all the protein-coding genes in Gencode, 65% are expressed in the retina. We exploited inter-individual variability in gene expression to infer a gene co-expression network and to identify genes specifically expressed in photoreceptor cells. We experimentally validated the photoreceptors localization of three genes in human retina that had not been previously reported. RNA-seq data and the gene co-expression network are available online (http://retina.tigem.it). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Evaluation of Appropriate Reference Genes for Gene Expression Normalization during Watermelon Fruit Development.

    Directory of Open Access Journals (Sweden)

    Qiusheng Kong

    Full Text Available Gene expression analysis in watermelon (Citrullus lanatus fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC, β-actin (ClACT, and alpha tubulin 5 (ClTUA5 as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1, a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.

  1. Gene therapeutics and DNA vaccines; quality and regulatory aspects

    NARCIS (Netherlands)

    Schalk JAC; Hegger I; Jongen PMJM; LGM

    2001-01-01

    Transfer of genes to cells and the subsequent expression of these genes can alleviate the symptoms of a disease (gene therapy), or prevent infectious diseases (DNA vaccination). Gene therapy and DNA vaccination are based on relatively new technologies. The first gene therapeutics are expected to

  2. Reference genes for normalization: A study of rat brain tissue

    DEFF Research Database (Denmark)

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    Quantitative real-time polymerase chain reaction (qPCR) has become a widely used tool in the search for disease genes. When examining gene expression with qPCR in psychiatric diseases, endogenous reference gene(s) must be used for normalization. Traditionally, genes such as beta-actin (ActB), Gapd...

  3. Gene duplication as a major force in evolution

    Indian Academy of Sciences (India)

    Gene duplication is an important mechanism for acquiring new genes and creating genetic novelty in organisms. Many new gene functions have evolved through gene duplication and it has contributed tremendously to the evolution of developmental programmes in various organisms. Gene duplication can result from ...

  4. Molecular genetics and gene expression in atherosclerosis.

    Science.gov (United States)

    Doevendans, P A; Jukema, W; Spiering, W; Defesche, J C; Kastelein, J J

    2001-01-01

    Although molecular cardiology is a relative young discipline, the impact of the new techniques on diagnosis and therapy in cardiovascular disease are extensive. Our insight into pathophysiological mechanisms is rapidly expanding and is changing our understanding of cardiovascular disease radically and irrevocably. Molecular cardiology has many different aspects. In this paper the importance of molecular cardiology and genetics for every day clinical practice are briefly outlined. It is expected that in the genetic predisposition for atherosclerotic disease multiple genes are involved (genetics). The role of only a minority of genes involved in the atherosclerotic process is known. Far less is known about particular gene-gene and gene-environment interactions. In some families disease can be explained mostly by a single, major gene (monogenic), of which the lipid disorder Familial Hypercholesterolemia is an example. In other cases, one or several variations in minor genes (multigenic) contribute to an atherosclerotic predisposition, for instance the lipoprotein lipase gene. Although mutations in this gene influence lipoprotein levels, disease development is predominantly depending on environmental influences. Recently several additional genetic risk factors were identified including elevated levels of lipoprotein (a) [Lp(a)], the DD genotype of angiotensin converting enzyme (ACE), and elevated levels of homocysteine. This illustrates the complexity of genetics in relation to atherosclerosis and the difficulty to assign predictive values to separate genetic risk factors. Furthermore, little attention has been given to protective genes thus far, explaining why some high risk patients are protected from vascular disease. Genetics based treatment or elimination of the genetic risk factor requires complete understanding of the pathogenic molecular basis. Once this requirement is fulfilled, disease management can be strived for, provided that adequate medical management

  5. Prioritization of Susceptibility Genes for Ectopic Pregnancy by Gene Network Analysis.

    Science.gov (United States)

    Liu, Ji-Long; Zhao, Miao

    2016-02-01

    Ectopic pregnancy is a very dangerous complication of pregnancy, affecting 1%-2% of all reported pregnancies. Due to ethical constraints on human biopsies and the lack of suitable animal models, there has been little success in identifying functionally important genes in the pathogenesis of ectopic pregnancy. In the present study, we developed a random walk-based computational method named TM-rank to prioritize ectopic pregnancy-related genes based on text mining data and gene network information. Using a defined threshold value, we identified five top-ranked genes: VEGFA (vascular endothelial growth factor A), IL8 (interleukin 8), IL6 (interleukin 6), ESR1 (estrogen receptor 1) and EGFR (epidermal growth factor receptor). These genes are promising candidate genes that can serve as useful diagnostic biomarkers and therapeutic targets. Our approach represents a novel strategy for prioritizing disease susceptibility genes.

  6. Alu Elements as Novel Regulators of Gene Expression in Type 1 Diabetes Susceptibility Genes?

    Science.gov (United States)

    Kaur, Simranjeet; Pociot, Flemming

    2015-07-13

    Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate genes to identify embedded Alu elements within these genes. We observed significant enrichment of Alu elements within the T1D genes (p-value genes harboring Alus revealed significant enrichment for immune-mediated processes (p-value genes harboring inverted Alus (IRAlus) within their 3' untranslated regions (UTRs) that are known to regulate the expression of host mRNAs by generating double stranded RNA duplexes. Our in silico analysis predicted the formation of duplex structures by IRAlus within the 3'UTRs of T1D genes. We propose that IRAlus might be involved in regulating the expression levels of the host T1D genes.

  7. Human gene therapy: novel approaches to improve the current gene delivery systems.

    Science.gov (United States)

    Cucchiarini, Magali

    2016-06-01

    Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients. This article provides an overview of the most significant contributions showing how the principles of controlled release strategies may be adapted for human gene therapy.

  8. [Pyruvate oxidase gene from Streptococcus sanguis: molecular cloning and sequence analysis of the gene].

    Science.gov (United States)

    Hou, B; Zhang, R; Zhang, J; Qian, W; Zhang, Y

    2001-09-01

    To clone and sequence the gene of pyruvate oxidase (Sopox) from Streptococcus sanguis. The PCR primers for Sopox gene were designed and synthesized according to the sequence of pyruvate oxidase (spxB) gene of S. pneumonia. The amplified PCR product was cloned into pUC18 and then subcloned into M13mp18 and M13mp19. The DNA sequence of the gene was analyzed. Sopox gene was successfully amplified from S. sanguis ATCC10557. The nucleotide sequence of the whole gene was revealed to be 1788 base pairs with one open reading frame coding pyruvate oxidase with 591 amino acid residuals. The clone and DNA sequence of Sopox gene were obtained which could serve as a foundation on which to elucidate the molecular mechanisms of hydrogen peroxide production and its regulation by oral streptococci.

  9. Repeated evolution of chimeric fusion genes in the β-globin gene family of laurasiatherian mammals.

    Science.gov (United States)

    Gaudry, Michael J; Storz, Jay F; Butts, Gary Tyler; Campbell, Kevin L; Hoffmann, Federico G

    2014-05-09

    The evolutionary fate of chimeric fusion genes may be strongly influenced by their recombinational mode of origin and the nature of functional divergence between the parental genes. In the β-globin gene family of placental mammals, the two postnatally expressed δ- and β-globin genes (HBD and HBB, respectively) have a propensity for recombinational exchange via gene conversion and unequal crossing-over. In the latter case, there are good reasons to expect differences in retention rates for the reciprocal HBB/HBD and HBD/HBB fusion genes due to thalassemia pathologies associated with the HBD/HBB "Lepore" deletion mutant in humans. Here, we report a comparative genomic analysis of the mammalian β-globin gene cluster, which revealed that chimeric HBB/HBD fusion genes originated independently in four separate lineages of laurasiatherian mammals: Eulipotyphlans (shrews, moles, and hedgehogs), carnivores, microchiropteran bats, and cetaceans. In cases where an independently derived "anti-Lepore" duplication mutant has become fixed, the parental HBD and/or HBB genes have typically been inactivated or deleted, so that the newly created HBB/HBD fusion gene is primarily responsible for synthesizing the β-type subunits of adult and fetal hemoglobin (Hb). Contrary to conventional wisdom that the HBD gene is a vestigial relict that is typically inactivated or expressed at negligible levels, we show that HBD-like genes often encode a substantial fraction (20-100%) of β-chain Hbs in laurasiatherian taxa. Our results indicate that the ascendancy or resuscitation of genes with HBD-like coding sequence requires the secondary acquisition of HBB-like promoter sequence via unequal crossing-over or interparalog gene conversion. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

    Directory of Open Access Journals (Sweden)

    Boris P Hejblum

    2015-06-01

    Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

  11. Repeated Evolution of Chimeric Fusion Genes in the β-Globin Gene Family of Laurasiatherian Mammals

    Science.gov (United States)

    Gaudry, Michael J.; Storz, Jay F.; Butts, Gary Tyler; Campbell, Kevin L.; Hoffmann, Federico G.

    2014-01-01

    The evolutionary fate of chimeric fusion genes may be strongly influenced by their recombinational mode of origin and the nature of functional divergence between the parental genes. In the β-globin gene family of placental mammals, the two postnatally expressed δ- and β-globin genes (HBD and HBB, respectively) have a propensity for recombinational exchange via gene conversion and unequal crossing-over. In the latter case, there are good reasons to expect differences in retention rates for the reciprocal HBB/HBD and HBD/HBB fusion genes due to thalassemia pathologies associated with the HBD/HBB “Lepore” deletion mutant in humans. Here, we report a comparative genomic analysis of the mammalian β-globin gene cluster, which revealed that chimeric HBB/HBD fusion genes originated independently in four separate lineages of laurasiatherian mammals: Eulipotyphlans (shrews, moles, and hedgehogs), carnivores, microchiropteran bats, and cetaceans. In cases where an independently derived “anti-Lepore” duplication mutant has become fixed, the parental HBD and/or HBB genes have typically been inactivated or deleted, so that the newly created HBB/HBD fusion gene is primarily responsible for synthesizing the β-type subunits of adult and fetal hemoglobin (Hb). Contrary to conventional wisdom that the HBD gene is a vestigial relict that is typically inactivated or expressed at negligible levels, we show that HBD-like genes often encode a substantial fraction (20–100%) of β-chain Hbs in laurasiatherian taxa. Our results indicate that the ascendancy or resuscitation of genes with HBD-like coding sequence requires the secondary acquisition of HBB-like promoter sequence via unequal crossing-over or interparalog gene conversion. PMID:24814285

  12. Gene essentiality, conservation index and co-evolution of genes in cyanobacteria.

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    Tiruveedula, Gopi Siva Sai; Wangikar, Pramod P

    2017-01-01

    Cyanobacteria, a group of photosynthetic prokaryotes, dominate the earth with ~ 1015 g wet biomass. Despite diversity in habitats and an ancient origin, cyanobacterial phylum has retained a significant core genome. Cyanobacteria are being explored for direct conversion of solar energy and carbon dioxide into biofuels. For this, efficient cyanobacterial strains will need to be designed via metabolic engineering. This will require identification of target knockouts to channelize the flow of carbon toward the product of interest while minimizing deletions of essential genes. We propose "Gene Conservation Index" (GCI) as a quick measure to predict gene essentiality in cyanobacteria. GCI is based on phylogenetic profile of a gene constructed with a reduced dataset of cyanobacterial genomes. GCI is the percentage of organism clusters in which the query gene is present in the reduced dataset. Of the 750 genes deemed to be essential in the experimental study on S. elongatus PCC 7942, we found 494 to be conserved across the phylum which largely comprise of the essential metabolic pathways. On the contrary, the conserved but non-essential genes broadly comprise of genes required under stress conditions. Exceptions to this rule include genes such as the glycogen synthesis and degradation enzymes, deoxyribose-phosphate aldolase (DERA), glucose-6-phosphate 1-dehydrogenase (zwf) and fructose-1,6-bisphosphatase class1, which are conserved but non-essential. While the essential genes are to be avoided during gene knockout studies as potentially lethal deletions, the non-essential but conserved set of genes could be interesting targets for metabolic engineering. Further, we identify clusters of co-evolving genes (CCG), which provide insights that may be useful in annotation. Principal component analysis (PCA) plots of the CCGs are demonstrated as data visualization tools that are complementary to the conventional heatmaps. Our dataset consists of phylogenetic profiles for 23

  13. Gene composer: database software for protein construct design, codon engineering, and gene synthesis.

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    Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

    2009-04-21

    To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease

  14. EasyGene – a prokaryotic gene finder that ranks ORFs by statistical significance

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    Larsen Thomas

    2003-06-01

    Full Text Available Abstract Background Contrary to other areas of sequence analysis, a measure of statistical significance of a putative gene has not been devised to help in discriminating real genes from the masses of random Open Reading Frames (ORFs in prokaryotic genomes. Therefore, many genomes have too many short ORFs annotated as genes. Results In this paper, we present a new automated gene-finding method, EasyGene, which estimates the statistical significance of a predicted gene. The gene finder is based on a hidden Markov model (HMM that is automatically estimated for a new genome. Using extensions of similarities in Swiss-Prot, a high quality training set of genes is automatically extracted from the genome and used to estimate the HMM. Putative genes are then scored with the HMM, and based on score and length of an ORF, the statistical significance is calculated. The measure of statistical significance for an ORF is the expected number of ORFs in one megabase of random sequence at the same significance level or better, where the random sequence has the same statistics as the genome in the sense of a third order Markov chain. Conclusions The result is a flexible gene finder whose overall performance matches or exceeds other methods. The entire pipeline of computer processing from the raw input of a genome or set of contigs to a list of putative genes with significance is automated, making it easy to apply EasyGene to newly sequenced organisms. EasyGene with pre-trained models can be accessed at http://www.cbs.dtu.dk/services/EasyGene.

  15. Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

    Full Text Available Abstract Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene

  16. Methylation of microRNA genes regulates gene expression in bisexual flower development in andromonoecious poplar.

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    Song, Yuepeng; Tian, Min; Ci, Dong; Zhang, Deqiang

    2015-04-01

    Previous studies showed sex-specific DNA methylation and expression of candidate genes in bisexual flowers of andromonoecious poplar, but the regulatory relationship between methylation and microRNAs (miRNAs) remains unclear. To investigate whether the methylation of miRNA genes regulates gene expression in bisexual flower development, the methylome, microRNA, and transcriptome were examined in female and male flowers of andromonoecious poplar. 27 636 methylated coding genes and 113 methylated miRNA genes were identified. In the coding genes, 64.5% of the methylated reads mapped to the gene body region; by contrast, 60.7% of methylated reads in miRNA genes mainly mapped in the 5' and 3' flanking regions. CHH methylation showed the highest methylation levels and CHG showed the lowest methylation levels. Correlation analysis showed a significant, negative, strand-specific correlation of methylation and miRNA gene expression (r=0.79, P genes included eight long miRNAs (lmiRNAs) of 24 nucleotides and 11 miRNAs related to flower development. miRNA172b might play an important role in the regulation of bisexual flower development-related gene expression in andromonoecious poplar, via modification of methylation. Gynomonoecious, female, and male poplars were used to validate the methylation patterns of the miRNA172b gene, implying that hyper-methylation in andromonoecious and gynomonoecious poplar might function as an important regulator in bisexual flower development. Our data provide a useful resource for the study of flower development in poplar and improve our understanding of the effect of epigenetic regulation on genes other than protein-coding genes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Gene-level integrated metric of negative selection (GIMS prioritizes candidate genes for nephrotic syndrome.

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    Matthew G Sampson

    Full Text Available Nephrotic syndrome (NS gene discovery efforts are now occurring in small kindreds and cohorts of sporadic cases. Power to identify causal variants in these groups beyond a statistical significance threshold is challenging due to small sample size and/or lack of family information. There is a need to develop novel methods to identify NS-associated variants. One way to determine putative functional relevance of a gene is to measure its strength of negative selection, as variants in genes under strong negative selection are more likely to be deleterious. We created a gene-level, integrated metric of negative selection (GIMS score for 20,079 genes by combining multiple comparative genomics and population genetics measures. To understand the utility of GIMS for NS gene discovery, we examined this score in a diverse set of NS-relevant gene sets. These included genes known to cause monogenic forms of NS in humans as well as genes expressed in the cells of the glomerulus and, particularly, the podocyte. We found strong negative selection in the following NS-relevant gene sets: (1 autosomal-dominant Mendelian focal segmental glomerulosclerosis (FSGS genes (p = 0.03 compared to reference, (2 glomerular expressed genes (p = 4×10(-23, and (3 predicted podocyte genes (p = 3×10(-9. Eight genes causing autosomal dominant forms of FSGS had a stronger combined score of negative selection and podocyte enrichment as compared to all other genes (p = 1 x 10(-3. As a whole, recessive FSGS genes were not enriched for negative selection. Thus, we also created a transcript-level, integrated metric of negative selection (TIMS to quantify negative selection on an isoform level. These revealed transcripts of known autosomal recessive disease-causing genes that were nonetheless under strong selection. We suggest that a filtering strategy that includes measuring negative selection on a gene or isoform level could aid in identifying NS-related genes. Our GIMS and TIMS

  18. Selection of reliable reference genes for gene expression studies in peach using real-time PCR

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    Zhou Jun

    2009-07-01

    Full Text Available Abstract Background RT-qPCR is a preferred method for rapid and reliable quantification of gene expression studies. Appropriate application of RT-qPCR in such studies requires the use of reference gene(s as an internal control to normalize mRNA levels between different samples for an exact comparison of gene expression level. However, recent studies have shown that no single reference gene is universal for all experiments. Thus, the identification of high quality reference gene(s is of paramount importance for the interpretation of data generated by RT-qPCR. Only a few studies on reference genes have been done in plants and none in peach (Prunus persica L. Batsch. Therefore, the present study was conducted to identify suitable reference gene(s for normalization of gene expression in peach. Results In this work, eleven reference genes were investigated in different peach samples using RT-qPCR with SYBR green. These genes are: actin 2/7 (ACT, cyclophilin (CYP2, RNA polymerase II (RP II, phospholipase A2 (PLA2, ribosomal protein L13 (RPL13, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, 18S ribosomal RNA (18S rRNA, tubblin beta (TUB, tubblin alpha (TUA, translation elongation factor 2 (TEF2 and ubiquitin 10 (UBQ10. All eleven reference genes displayed a wide range of Cq values in all samples, indicating that they expressed variably. The stability of these genes except for RPL13 was determined by three different descriptive statistics, geNorm, NormFinder and BestKeeper, which produced highly comparable results. Conclusion Our study demonstrates that expression stability varied greatly between genes studied in peach. Based on the results from geNorm, NormFinder and BestKeeper analyses, for all the sample pools analyzed, TEF2, UBQ10 and RP II were found to be the most suitable reference genes with a very high statistical reliability, and TEF2 and RP II for the other sample series, while 18S rRNA, RPL13 and PLA2 were unsuitable as internal controls

  19. Genes and genetic testing in hereditary ataxias.

    Science.gov (United States)

    Sandford, Erin; Burmeister, Margit

    2014-07-22

    Ataxia is a neurological cerebellar disorder characterized by loss of coordination during muscle movements affecting walking, vision, and speech. Genetic ataxias are very heterogeneous, with causative variants reported in over 50 genes, which can be inherited in classical dominant, recessive, X-linked, or mitochondrial fashion. A common mechanism of dominant ataxias is repeat expansions, where increasing lengths of repeated DNA sequences result in non-functional proteins that accumulate in the body causing disease. Greater understanding of all ataxia genes has helped identify several different pathways, such as DNA repair, ubiquitination, and ion transport, which can be used to help further identify new genes and potential treatments. Testing for the most common mutations in these genes is now clinically routine to help with prognosis and treatment decisions, but next generation sequencing will revolutionize how genetic testing will be done. Despite the large number of known ataxia causing genes, however, many individuals with ataxia are unable to obtain a genetic diagnosis, suggesting that more genes need to be discovered. Utilization of next generation sequencing technologies, expression studies, and increased knowledge of ataxia pathways will aid in the identification of new ataxia genes.

  20. JGI Plant Genomics Gene Annotation Pipeline

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    Shu, Shengqiang; Rokhsar, Dan; Goodstein, David; Hayes, David; Mitros, Therese

    2014-07-14

    Plant genomes vary in size and are highly complex with a high amount of repeats, genome duplication and tandem duplication. Gene encodes a wealth of information useful in studying organism and it is critical to have high quality and stable gene annotation. Thanks to advancement of sequencing technology, many plant species genomes have been sequenced and transcriptomes are also sequenced. To use these vastly large amounts of sequence data to make gene annotation or re-annotation in a timely fashion, an automatic pipeline is needed. JGI plant genomics gene annotation pipeline, called integrated gene call (IGC), is our effort toward this aim with aid of a RNA-seq transcriptome assembly pipeline. It utilizes several gene predictors based on homolog peptides and transcript ORFs. See Methods for detail. Here we present genome annotation of JGI flagship green plants produced by this pipeline plus Arabidopsis and rice except for chlamy which is done by a third party. The genome annotations of these species and others are used in our gene family build pipeline and accessible via JGI Phytozome portal whose URL and front page snapshot are shown below.