insertional mutagenesis


Summary: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA can be inserted into or adjacent to a cellular proto-oncogene. Insertion of the provirus can cause mutations by interrupting coding sequences or regulatory elements, or cause unregulated expression of the proto-oncogene resulting in tumor formation.

Top Publications

  1. ncbi An Arabidopsis thaliana T-DNA mutagenized population (GABI-Kat) for flanking sequence tag-based reverse genetics
    Mario G Rosso
    GABI Kat, Max Planck Institute for Plant Breeding Research, Carl von Linne Weg 10, 50829 Köln, Germany
    Plant Mol Biol 53:247-59. 2003
  2. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
  3. ncbi Genome-wide insertional mutagenesis of Arabidopsis thaliana
    Jose M Alonso
    Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Science 301:653-7. 2003
  4. pmc A gateway cloning vector set for high-throughput functional analysis of genes in planta
    Mark D Curtis
    Institute of Plant Biology and Zurich Basel Plant Science Centre, University of Zurich, Zollikerstrasse 107, Ch 8008 Zurich, Switzerland
    Plant Physiol 133:462-9. 2003
  5. pmc Identification of 315 genes essential for early zebrafish development
    Adam Amsterdam
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:12792-7. 2004
  6. ncbi Human l1 retrotransposition is associated with genetic instability in vivo
    David E Symer
    Department of Molecular Biology and Genetics, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 110:327-38. 2002
  7. ncbi A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac
    Stephen T Thibault
    Exelixis, 170 Harbor Way, South San Francisco, California 94083 0511, USA
    Nat Genet 36:283-7. 2004
  8. ncbi Bursts of retrotransposition reproduced in Arabidopsis
    Sayuri Tsukahara
    Department of Integrated Genetics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411 8540, Japan
    Nature 461:423-6. 2009
  9. ncbi An active DNA transposon family in rice
    Ning Jiang
    Department of Plant Biology, University of Georgia, Athens, Georgia 30602, USA
    Nature 421:163-7. 2003
  10. pmc Insertional mutagenesis of genes required for seed development in Arabidopsis thaliana
    J McElver
    Syngenta, Research Triangle Park, North Carolina 27709, USA
    Genetics 159:1751-63. 2001

Detail Information

Publications371 found, 100 shown here

  1. ncbi An Arabidopsis thaliana T-DNA mutagenized population (GABI-Kat) for flanking sequence tag-based reverse genetics
    Mario G Rosso
    GABI Kat, Max Planck Institute for Plant Breeding Research, Carl von Linne Weg 10, 50829 Köln, Germany
    Plant Mol Biol 53:247-59. 2003
    ..Finally, the functionality of the GABI-Kat population was demonstrated by exemplary confirmation of several new transparent testa alleles, as well as a number of other mutants, which were identified on the basis of the FST data...
  2. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
    ..Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter...
  3. ncbi Genome-wide insertional mutagenesis of Arabidopsis thaliana
    Jose M Alonso
    Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Science 301:653-7. 2003
    ..Insertion mutations were identified in genes that are regulated in response to the plant hormone ethylene...
  4. pmc A gateway cloning vector set for high-throughput functional analysis of genes in planta
    Mark D Curtis
    Institute of Plant Biology and Zurich Basel Plant Science Centre, University of Zurich, Zollikerstrasse 107, Ch 8008 Zurich, Switzerland
    Plant Physiol 133:462-9. 2003
    ..All vectors were derived from pCambia T-DNA cloning vectors, with the exception of a chemically inducible vector, for Agrobacterium sp.-mediated transformation of a wide range of plant species...
  5. pmc Identification of 315 genes essential for early zebrafish development
    Adam Amsterdam
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:12792-7. 2004
    We completed a large insertional mutagenesis screen in zebrafish to identify genes essential for embryonic and early larval development...
  6. ncbi Human l1 retrotransposition is associated with genetic instability in vivo
    David E Symer
    Department of Molecular Biology and Genetics, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 110:327-38. 2002
    ..In a striking number of integrants, short identical sequences were shared between the donor and the target site's 3' end, suggesting a mechanistic model that helps explain the structure of L1 insertions...
  7. ncbi A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac
    Stephen T Thibault
    Exelixis, 170 Harbor Way, South San Francisco, California 94083 0511, USA
    Nat Genet 36:283-7. 2004
  8. ncbi Bursts of retrotransposition reproduced in Arabidopsis
    Sayuri Tsukahara
    Department of Integrated Genetics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411 8540, Japan
    Nature 461:423-6. 2009
  9. ncbi An active DNA transposon family in rice
    Ning Jiang
    Department of Plant Biology, University of Georgia, Athens, Georgia 30602, USA
    Nature 421:163-7. 2003
    ..Since the domestication of rice mPing MITEs have been amplified preferentially in cultivars adapted to environmental extremes-a situation that is reminiscent of the genomic shock theory for transposon activation...
  10. pmc Insertional mutagenesis of genes required for seed development in Arabidopsis thaliana
    J McElver
    Syngenta, Research Triangle Park, North Carolina 27709, USA
    Genetics 159:1751-63. 2001
    ..Other functions critical to seed development in Arabidopsis may be protected from deleterious mutations by extensive genome duplications...
  11. ncbi Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development
    Gregory Golling
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Genet 31:135-40. 2002
    To rapidly identify genes required for early vertebrate development, we are carrying out a large-scale, insertional mutagenesis screen in zebrafish, using mouse retroviral vectors as the mutagen...
  12. pmc piggyBac is a flexible and highly active transposon as compared to sleeping beauty, Tol2, and Mos1 in mammalian cells
    Sareina Chiung Yuan Wu
    Cancer Research Center, Medical College of Georgia, Augusta, GA 30912, USA
    Proc Natl Acad Sci U S A 103:15008-13. 2006
    ..The high transposition activity of piggyBac and the flexibility for molecular modification of its transposase suggest the possibility of using it routinely for mammalian transgenesis...
  13. pmc Salt stress responses in Arabidopsis utilize a signal transduction pathway related to endoplasmic reticulum stress signaling
    Jian Xiang Liu
    Plant Sciences Institute, Roy J Carver Co Laboratory, Iowa State University, Ames IA 50011, USA
    Plant J 51:897-909. 2007
    ..Thus, salt stress induces a signaling cascade involving the processing of AtbZIP17, its translocation to the nucleus and the upregulation of salt stress genes...
  14. ncbi Expression profiling and mutant analysis reveals complex regulatory networks involved in Arabidopsis response to Botrytis infection
    Synan Abuqamar
    Department of Botany and Plant Pathology, Purdue University, 915 West State Street, West Lafayette, IN 47907 2054, USA
    Plant J 48:28-44. 2006
  15. pmc Function and characterization of starch synthase I using mutants in rice
    Naoko Fujita
    Department of Biological Production, Akita Prefectural University, Akita City, Japan
    Plant Physiol 140:1070-84. 2006
    ..In summary, this study strongly suggested that amylopectin chains are synthesized by the coordinated actions of SSI, SSIIa, and SSIIIa isoforms...
  16. ncbi Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer
    Y Miki
    Department of Biochemistry, Cancer Institute, Tokyo, Japan
    Cancer Res 52:643-5. 1992
    ..This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element...
  17. ncbi Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18
    J Parkhill
    The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
    Nature 413:848-52. 2001
    ..typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis...
  18. pmc Functional genomics of eukaryotic photosynthesis using insertional mutagenesis of Chlamydomonas reinhardtii
    Rachel M Dent
    Department of Plant and Microbial Biology, University of California, Berkeley, California 94720 3102, USA
    Plant Physiol 137:545-56. 2005
    ..Here we describe the development of a resource for functional genomics of photosynthesis using insertional mutagenesis of the Chlamydomonas nuclear genome...
  19. ncbi Large-scale insertional mutagenesis using the Tnt1 retrotransposon in the model legume Medicago truncatula
    Million Tadege
    Plant Biology Division, The Samuel Roberts Noble Foundation, 2510 Sam Noble Parkway, Ardmore, OK 73401, USA
    Plant J 54:335-47. 2008
    ..Our data demonstrate that Tnt1 is an efficient insertional mutagen in M. truncatula, and could be a primary choice for other plant species with large genomes...
  20. ncbi Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene
    Patrizia Paterlini-Brechot
    INSERM Pasteur Unit 370, Necker Faculty of Medicine, Necker Enfants Malades Hospital, Paris 75015, France
    Oncogene 22:3911-6. 2003
    ..Thus, HBV frequently targets cellular genes involved in cell signalling and some of them may be preferential targets of the viral integration...
  21. pmc Comprehensive transposon mutant library of Pseudomonas aeruginosa
    Michael A Jacobs
    Department of Medicine, University of Washington Genome Center, Box 352145, Seattle, WA 98195 2145, USA
    Proc Natl Acad Sci U S A 100:14339-44. 2003
    ..The transposons used to generate the mutant collection have added features that should facilitate downstream studies of gene expression, protein localization, epistasis, and chromosome engineering...
  22. pmc Insertion sequence diversity in archaea
    J Filee
    Laboratoire de Microbiologie et Génétique Moléculaires UMR5100 CNRS, Campus Université Paul Sabatier, 118 route de Narbonne, F 31062 Toulouse Cedex, France
    Microbiol Mol Biol Rev 71:121-57. 2007
    ..In addition to ISs, we identify and list nonautonomous IS-derived elements, such as miniature inverted-repeat transposable elements. Finally, we present a possible scenario for the evolutionary history of ISs in the Archaea...
  23. ncbi Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes
    Chi Ming Li
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Genomics 79:218-24. 2002
  24. pmc Mapping and sequencing of structural variation from eight human genomes
    Jeffrey M Kidd
    Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA
    Nature 453:56-64. 2008
    ..These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects...
  25. pmc DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
    Timothy J Ley
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63108, USA
    Nature 456:66-72. 2008
    ..Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies...
  26. pmc Minos as a genetic and genomic tool in Drosophila melanogaster
    Athanasios Metaxakis
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Crete, Greece
    Genetics 171:571-81. 2005
    ..Our results suggest that Minos is a useful tool complementing the P element for insertional mutagenesis and genomic analysis in Drosophila.
  27. ncbi High-throughput insertional mutagenesis screens in mice to identify oncogenic networks
    Jaap Kool
    Division of Molecular Genetics, The Cancer Genomics Centre, The Centre of Biomedical Genetics, Academic Medical Center, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
    Nat Rev Cancer 9:389-99. 2009
    Retroviral insertional mutagenesis screens have been used for many years as a tool for cancer gene discovery...
  28. pmc Large-scale insertional mutagenesis of a coleopteran stored grain pest, the red flour beetle Tribolium castaneum, identifies embryonic lethal mutations and enhancer traps
    Jochen Trauner
    1Department of Biology, Developmental Biology, Friedrich Alexander University Erlangen, Erlangen, Germany
    BMC Biol 7:73. 2009
    ..Even so, there is a pressing need for forward genetic analysis to escape the bias inherent in candidate gene approaches...
  29. pmc Cryptococcus neoformans virulence gene discovery through insertional mutagenesis
    Alexander Idnurm
    Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Eukaryot Cell 3:420-9. 2004
    b>Insertional mutagenesis was applied to Cryptococcus neoformans to identify genes associated with virulence attributes...
  30. ncbi Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse
    Lara S Collier
    Department of Genetics, Cell Biology and Development, The Arnold and Mabel Beckman Center for Transposon Research, The Cancer Center, The University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA
    Nature 436:272-6. 2005
    ..Sleeping Beauty is a new tool for unbiased, forward genetic screens for cancer genes in vivo...
  31. pmc Trans-kingdom transposition of the maize dissociation element
    Alexander Emelyanov
    Temasek Life Sciences Laboratory, The National University of Singapore, 117604 Singapore, Singapore
    Genetics 174:1095-104. 2006
  32. pmc The fate of laterally transferred genes: life in the fast lane to adaptation or death
    Weilong Hao
    Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1
    Genome Res 16:636-43. 2006
    ..Together, this implies that many of the lineage-specific insertions are lost quickly during evolution and that perhaps a few of the genes inserted by lateral transfer are niche specific...
  33. ncbi Mutator transposons
    Damon Lisch
    Dept Plant and Microbial Biology, 111 Koshland Hall, University of California at Berkeley, 94720, USA
    Trends Plant Sci 7:498-504. 2002
    ..In addition to its utility, the means by which this widespread and highly mutagenic system is held in check should help us to address fundamental issues concerning the stability of genomes...
  34. ncbi Efficient gene delivery and gene expression in zebrafish using the Sleeping Beauty transposon
    Ann E Davidson
    The Arnold and Mabel Beckman Center for Transposon Research, Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA
    Dev Biol 263:191-202. 2003
  35. pmc Transposon vectors containing non-antibiotic resistance selection markers for cloning and stable chromosomal insertion of foreign genes in gram-negative bacteria
    M Herrero
    GBF National Research Centre for Biotechnology, Braunschweig, Federal Republic of Germany
    J Bacteriol 172:6557-67. 1990
    ..g., in open systems and natural environments), and that do not carry antibiotic resistance markers characteristic of most available cloning vectors (as is currently required of live bacterial vaccines)...
  36. pmc piggyBac-based insertional mutagenesis and enhancer detection as a tool for functional insect genomics
    Carsten Horn
    Lehrstuhl fur Genetik, Universitat Bayreuth, 95447 Bayreuth, Germany
    Genetics 163:647-61. 2003
    ..binary expression system based on the transposable element piggyBac: For the different components of this insertional mutagenesis system, we used widely applicable transposons and distinguishable broad-range transformation markers, ..
  37. ncbi A transgenic dTph1 insertional mutagenesis system for forward genetics in mycorrhizal phosphate transport of Petunia
    Sarah Wegmüller
    ETH Zurich, Institute of Plant Sciences, Experimental Station Eschikon 33, CH 8315 Lindau, Switzerland
    Plant J 54:1115-27. 2008
    ..a molecular approach in which expression of a mycorrhiza-inducible bi-functional reporter transgene and insertional mutagenesis in Petunia are combined...
  38. ncbi Molecular genetics using T-DNA in rice
    Gynheung An
    National Research Laboratory of Plant Functional Genomics, Division of Molecular and Life Sciences, Pohang University of Science and Technology POSTECH, Pohang 790 784, Korea
    Plant Cell Physiol 46:14-22. 2005
    ..This information is then used to make databases that are shared with the scientific community. International efforts on seed amplification and maintenance are needed to exploit these valuable materials efficiently...
  39. ncbi Role of plant CBP/p300-like genes in the regulation of flowering time
    Soon Ki Han
    Environmental Biotechnology National Core Research Center, Gyeongsang National University, Jinju, Korea
    Plant J 49:103-14. 2007
    ..This CBP/p300-mediated FLC repression may involve reversible protein acetylation independent of histone modification within FLC chromatin...
  40. ncbi Insertional polymorphisms of endogenous HERV-K113 and HERV-K115 retroviruses in breast cancer patients and age-matched controls
    Thomas Burmeister
    Medizinische Klinik III, Charite Campus Benjamin Franklin, 12200 Berlin, Germany
    AIDS Res Hum Retroviruses 20:1223-9. 2004
    ..This suggests that the two HERV-Ks do not play a pathogenetic role in the majority of breast cancer patients, though they may be involved in a minority of patients. The results are discussed...
  41. ncbi Steady-state transposon mutagenesis in inbred maize
    Donald R McCarty
    Plant Molecular and Cellular Biology Program, Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, USA
    Plant J 44:52-61. 2005; includes pedigree and phenotypic data for over 2000 independent seed mutants selected from a population of 31 548 F2 lines and integrated with analyses of 34 255 MuTAIL sequences...
  42. ncbi MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer
    Vassiliki Theodorou
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nat Genet 39:759-69. 2007
    We performed a high-throughput retroviral insertional mutagenesis screen in mouse mammary tumor virus (MMTV)-induced mammary tumors and identified 33 common insertion sites, of which 17 genes were previously not known to be associated ..
  43. ncbi Physiological promoters reduce the genotoxic risk of integrating gene vectors
    Daniela Zychlinski
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 16:718-25. 2008
    ..In this manner, the insertional biosafety of therapeutic gene vectors can be greatly enhanced and proactively evaluated in sensitive cell-based assays...
  44. ncbi Transposon-mediated gene trapping in zebrafish
    Tomoya Kotani
    Division of Molecular and Developmental Biology, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411 8540, Japan
    Methods 39:199-206. 2006
    ..Here, we describe how we performed the gene trap screen and characterized the gene trap insertions and will discuss the outcome of the pilot screen...
  45. ncbi Host invasion during rice-blast disease requires carnitine-dependent transport of peroxisomal acetyl-CoA
    Marilou Ramos-Pamplona
    Fungal Genomics Group, Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604
    Mol Microbiol 61:61-75. 2006
    ..Thus, carnitine-dependent metabolic activities associated with the peroxisomes, cooperatively facilitate the appressorial function of host invasion during rice-blast infections...
  46. ncbi Insertional polymorphism of endogenous retrovirus HERV-K115 in schizophrenia
    Takeshi Otowa
    Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo 113 8655, Japan
    Neurosci Lett 408:226-9. 2006
    ..These results preliminarily suggest that HERV-K115 may not be associated with schizophrenia in general, but that it could play a partial role in early precipitation of the disease...
  47. ncbi Two different heat shock transcription factors regulate immediate early expression of stress genes in Arabidopsis
    C Lohmann
    Zentrum für Molekularbiologie der Pflanzen ZMBP, Allgemeine Genetik, Universitat Tubingen, Auf der Morgenstelle 28, 72076 Tubingen, Germany
    Mol Genet Genomics 271:11-21. 2004
  48. pmc The Moraxella catarrhalis porin-like outer membrane protein CD is an adhesin for human lung cells
    Melissa M Holm
    Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614 5806, USA
    Infect Immun 72:1906-13. 2004
    ..This is the first report of M. catarrhalis ompCD mutants, and our findings demonstrate that this gene product is an adhesin for human lung cells...
  49. pmc Use of targetrons to disrupt essential and nonessential genes in Staphylococcus aureus reveals temperature sensitivity of Ll.LtrB group II intron splicing
    Jun Yao
    Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, The University of Texas at Austin, TX 78712, USA
    RNA 12:1271-81. 2006
    ..In nature, temperature sensitivity of group II intron splicing could limit the temperature range of an organism containing a group II intron inserted in an essential gene...
  50. pmc Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and gammac overexpression
    Samantha L Ginn
    Gene Therapy Research Unit of the Children s Medical Research Institute and The Children s Hospital at Westmead, Westmead, New South Wales, Australia
    Mol Ther 18:965-76. 2010
    ..sufficient strength to drive reliable immune reconstitution, but minimal propensity for enhancer-mediated insertional mutagenesis. In this study, we set out to explore the effect of promoter-enhancer selection on the efficacy and ..
  51. ncbi Murine endogenous retroviruses
    C Stocking
    Heinrich Pette Institute, Hamburg, Germany
    Cell Mol Life Sci 65:3383-98. 2008
    ..of evolution, but ERVs have also been pivotal in shaping the mouse genome by altering host genes through insertional mutagenesis, by adding novel regulatory and coding sequences, and by their co-option by host cells as retroviral ..
  52. pmc T-DNA insertional mutagenesis for activation tagging in rice
    Dong Hoon Jeong
    Department of Life Science and National Research Laboratory of Plant Functional Genomics, Pohang University of Science and Technology, Pohang 790 784, Republic of Korea
    Plant Physiol 130:1636-44. 2002
    ..Therefore, the large population of T-DNA-tagged lines transformed with pGA2715 could be used to screen for promoter activity using the gus reporter, as well as for creating gain-of-function mutants...
  53. ncbi Identification of candidate cooperative genes of the Apc mutation in transformation of the colon epithelial cell by retroviral insertional mutagenesis
    Miwa Tanaka
    Department of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, 3 10 6 Ariake, Koto ku, Tokyo 135 8550, Japan
    Cancer Sci 99:979-85. 2008
    ..To identify cooperative genes for the Apc(Min) mutation the authors carried out retroviral insertional mutagenesis (RIM) using Min mouse-derived IMCE colon epithelial cells...
  54. ncbi Alu repeats and human disease
    P L Deininger
    Department of Environmental Health Sciences, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, Louisiana, 70112, USA
    Mol Genet Metab 67:183-93. 1999
    ..3% of human genetic diseases. Between these different mechanisms, Alu elements have not only contributed a great deal to the evolution of the genome but also continue to contribute to a significant portion of human genetic diseases...
  55. pmc The GIGANTEA-regulated microRNA172 mediates photoperiodic flowering independent of CONSTANS in Arabidopsis
    Jae Hoon Jung
    Molecular Signaling Laboratory, Department of Chemistry, Seoul National University, Seoul, Korea
    Plant Cell 19:2736-48. 2007
    ..Therefore, it appears that GI-mediated photoperiodic flowering is governed by the coordinated interaction of two distinct genetic pathways: one mediated via CO and the other mediated via miR172 and its targets...
  56. pmc Insertional mutagenesis strategies in zebrafish
    Sridhar Sivasubbu
    Institute of Genomics and Integrative Biology, Council for Scientific and Industrial Research, Mall Road, Delhi 110007, India
    Genome Biol 8:S9. 2007
    We review here some recent developments in the field of insertional mutagenesis in zebrafish...
  57. ncbi Structural domains in the type III restriction endonuclease EcoP15I: characterization by limited proteolysis, mass spectrometry and insertional mutagenesis
    Katja Wagenführ
    Institute of Virology, Helmut Ruska Haus, Charite Universitatsmedizin Berlin, 10098 Berlin, Germany
    J Mol Biol 366:93-102. 2007
    ..All mutants tolerated the genetic manipulation and did not display loss of function or alteration of the DNA cleavage position...
  58. ncbi Argonaute2 is the catalytic engine of mammalian RNAi
    Jidong Liu
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Science 305:1437-41. 2004
    ..Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi...
  59. ncbi It takes two transposons to tango: transposable-element-mediated chromosomal rearrangements
    Y H Gray
    Molecular Genetics and Evolution Group, Research School of Biological Sciences, Australian National University, ACT 2601, Canberra, Australia
    Trends Genet 16:461-8. 2000
    ..The similarities between alternative transposition and V(D)J recombination are also discussed, as is the use of alternative transposition as a genetic tool...
  60. ncbi Epigenetic inheritance at the agouti locus in the mouse
    H D Morgan
    Department of Biochemistry, University of Sydney, NSW, 2006, Australia
    Nat Genet 23:314-8. 1999
    ..Because retrotransposons are abundant in mammalian genomes, this type of inheritance may be common...
  61. ncbi Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice
    G Friedrich
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030
    Genes Dev 5:1513-23. 1991
    ..Because no overt phenotype was detected in the remaining strains, these results suggest that a substantial proportion of mammalian genes identified by this approach are not essential for development...
  62. pmc Human diallelic insertion/deletion polymorphisms
    James L Weber
    Center for Medical Genetics, Marshfield Medical Research Foundation, Marshfield, WI 54449, USA
    Am J Hum Genet 71:854-62. 2002
    ..Diallelic indels comprise approximately 8% of all human polymorphisms. Their abundance and ease of analysis make them useful for many applications...
  63. pmc The Arabidopsis histidine phosphotransfer proteins are redundant positive regulators of cytokinin signaling
    Claire E Hutchison
    Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599 3280, USA
    Plant Cell 18:3073-87. 2006
    ..These data indicate that most of the AHPs are redundant, positive regulators of cytokinin signaling and affect multiple aspects of plant development...
  64. pmc Arabidopsis orthologs of maize chloroplast splicing factors promote splicing of orthologous and species-specific group II introns
    Yukari Asakura
    Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA
    Plant Physiol 142:1656-63. 2006
    ..Finally, we show that a strong AtCAF2 allele conditions an embryo-lethal phenotype, adding to the body of data suggesting that cell viability is more sensitive to the loss of plastid translation in Arabidopsis than in maize...
  65. pmc Salmonella enterica virulence genes are required for bacterial attachment to plant tissue
    Jeri D Barak
    USDA, ARS, WRRC, Produce Safety and Microbiology, 800 Buchanan St, Albany, CA 94710, USA
    Appl Environ Microbiol 71:5685-91. 2005
    ..These results reveal that S. enterica genes important for virulence in animal systems are also required for colonization of plants, a secondary host that can serve as a vector of S. enterica from animal to animal...
  66. pmc Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana
    Frank Hartung
    Botany II, University of Karlsruhe, Karlsruhe, Germany
    PLoS Genet 4:e1000285. 2008
  67. pmc Construction and characterization of transposon insertion mutations in Corynebacterium diphtheriae that affect expression of the diphtheria toxin repressor (DtxR)
    Diana Marra Oram
    Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Bacteriol 184:5723-32. 2002
    ..This is the first evidence that DtxR plays a role in protecting the cell from oxidative stress...
  68. pmc Differential alu mobilization and polymorphism among the human and chimpanzee lineages
    Dale J Hedges
    Department of Biological Sciences, Biological Computation and Visualization Center, Louisiana State University, Baton Rouge, Louisiana 70803, USA
    Genome Res 14:1068-75. 2004
    ..We propose a population-based model to account for the observed fluctuation in Alu retroposition rates across primate taxa...
  69. ncbi Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli
    B Karsten Tischer
    Cornell University, Ithaca, NY, USA
    Biotechniques 40:191-7. 2006
  70. ncbi Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system
    Adam J Dupuy
    National Cancer Institute, Center for Cancer Research, Frederick, Maryland 21702, USA
    Nature 436:221-6. 2005
    ..The tumours result from SB insertional mutagenesis of cancer genes, thus facilitating the identification of genes and pathways that induce disease...
  71. pmc Systematic insertional mutagenesis of a streptomycete genome: a link between osmoadaptation and antibiotic production
    Amy Bishop
    School of Biological Sciences, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK
    Genome Res 14:893-900. 2004
  72. pmc Efficient transposition of the Tol2 transposable element from a single-copy donor in zebrafish
    Akihiro Urasaki
    Division of Molecular and Developmental Biology, National Institute of Genetics, and Department of Genetics, Graduate University for Advanced Studies SOKENDAI, Mishima, Shizuoka 411 8540, Japan
    Proc Natl Acad Sci U S A 105:19827-32. 2008
    ..transposable element is a powerful genetic tool in model vertebrates and has been used for transgenesis, insertional mutagenesis, gene trapping, and enhancer trapping...
  73. ncbi AtMSH5 partners AtMSH4 in the class I meiotic crossover pathway in Arabidopsis thaliana, but is not required for synapsis
    James D Higgins
    School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK
    Plant J 55:28-39. 2008
  74. ncbi Type-B monogalactosyldiacylglycerol synthases are involved in phosphate starvation-induced lipid remodeling, and are crucial for low-phosphate adaptation
    Koichi Kobayashi
    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B 65 Nagatsuta cho, Midori ku, Yokohama 226 8501, Japan
    Plant J 57:322-31. 2009
    ..The widespread distribution of type-B MGD genes in land plants suggests that membrane lipid remodeling mediated by type-B MGD enzymes is a potent adaptation to Pi deficiency for land plants...
  75. pmc The ABC transporter PXA1 and peroxisomal beta-oxidation are vital for metabolism in mature leaves of Arabidopsis during extended darkness
    Hans Henning Kunz
    Department of Botany II, University of Cologne, Koeln, Germany
    Plant Cell 21:2733-49. 2009
  76. ncbi A genome-wide view of miniature inverted-repeat transposable elements (MITEs) in rice, Oryza sativa ssp. japonica
    Nobuhiko Oki
    Graduate School of Agriculture, Kyoto University, Kyoto, Japan
    Genes Genet Syst 83:321-9. 2008
    ..Our findings suggest that MITEs may have contributed to expansion of genome diversity by causing alterations not only in gene functions but also in regulation of many genes...
  77. pmc Functional characterization of the Arabidopsis AtSUC2 Sucrose/H+ symporter by tissue-specific complementation reveals an essential role in phloem loading but not in long-distance transport
    Avinash C Srivastava
    Department of Biological Sciences, University of North Texas, Denton, Texas 76203 5220, USA
    Plant Physiol 148:200-11. 2008
    ..In addition, Atsuc2 mutant plants, although debilitated, do grow, and AtSUC2-independent modes of phloem transport are discussed, including an entirely symplastic pathway from mesophyll cells to sink tissues...
  78. pmc Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks
    Anthony G Uren
    Division of Molecular Genetics and Cancer Genomics Centre, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands
    Cell 133:727-41. 2008
    ..This dataset should prove to be a rich resource for the study of genetic interactions that underlie tumorigenesis...
  79. pmc Characterization of SSIIIa-deficient mutants of rice: the function of SSIIIa and pleiotropic effects by SSIIIa deficiency in the rice endosperm
    Naoko Fujita
    Department of Biological Production, Akita Prefectural University, Akita City, Akita 010 0195, Japan
    Plant Physiol 144:2009-23. 2007
  80. pmc A high-throughput Arabidopsis reverse genetics system
    Allen Sessions
    Torrey Mesa Research Institute, Syngenta, 3115 Merryfield Row, San Diego, California 92121, USA
    Plant Cell 14:2985-94. 2002
    ..Predicted insertions were confirmed in 257 of 340 lines tested (76%). This resource has been named SAIL (Syngenta Arabidopsis Insertion Library) and is available to the scientific community at
  81. ncbi Activation tagging, a novel tool to dissect the functions of a gene family
    Miki Nakazawa
    Plant Function Exploration Team, Plant Functional Genomics Research Group, RIKEN Yokohama Institute, Genomic Sciences Center GSC, 1 7 22 Suehiro cho, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Plant J 34:741-50. 2003
    ..The pck1-D mutants have lost apical dominance, have epinastic leaves and are sterile. These results strongly suggest that activation tagging is a powerful mutant-mining tool especially for genes that make up a gene family...
  82. pmc A piggyBac transposon-based genome-wide library of insertionally mutated Blm-deficient murine ES cells
    Wei Wang
    The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom
    Genome Res 19:667-73. 2009
    ..Chemical or insertional mutagenesis of Blm-deficient mouse ES cells can be used to generate genome-wide libraries of homozygous mutant ES ..
  83. pmc The Arabidopsis HOMOLOGY-DEPENDENT GENE SILENCING1 gene codes for an S-adenosyl-L-homocysteine hydrolase required for DNA methylation-dependent gene silencing
    Pedro S C F Rocha
    Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, United Kingdom
    Plant Cell 17:404-17. 2005
    ..The same T-DNA also complemented the zygotic embryo lethal phenotype of the hog1-4 tagged mutant. A model relating the HOG1 gene, DNA methylation, and methylation-dependent HDG silencing is presented...
  84. ncbi Phospholipase C5 (NPC5) is involved in galactolipid accumulation during phosphate limitation in leaves of Arabidopsis
    Nicole Gaude
    Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476 Potsdam, Germany
    Plant J 56:28-39. 2008
  85. ncbi Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers
    Shu Chun Lin
    School of Dentistry, National Yang Ming University, Li Nong St, Sec 2, Taipei 112, Taiwan, ROC
    Cancer Lett 243:47-54. 2006
    ..This study suggested that the functional NFKB1promoter polymorphism could be valuable for assessment of cancer risk...
  86. pmc The plant-specific ssDNA binding protein OSB1 is involved in the stoichiometric transmission of mitochondrial DNA in Arabidopsis
    Vincent Zaegel
    Institut de Biologie Moleculaire des Plantes, Centre National de la Recherche Scientifique, Universite Louis Pasteur, 67000 Strasbourg, France
    Plant Cell 18:3548-63. 2006
    ..Thus, OSB1 participates in controlling the stoichiometry of alternative mtDNA forms generated by recombination. This regulation could take place in gametophytic tissues to ensure the transmission of a functional mitochondrial genome...
  87. ncbi The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide
    Michael J Allen
    School of Biosciences, Cardiff University, Museum Avenue, PO Box 911, Cardiff CF10 3US, UK
    Microbiology 152:989-1000. 2006
  88. pmc Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes
    Jaap Kool
    Division of Molecular Genetics, The Centre of Biomedical Genetics, Academic Medical Center and Cancer Genomics Centre, Netherlands Cancer Institute, 1066CX, Amsterdam, The Netherlands
    Cancer Res 70:520-31. 2010
    ..Here, we describe high-throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors...
  89. pmc Two class XI myosins function in organelle trafficking and root hair development in Arabidopsis
    Valera V Peremyslov
    Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA
    Plant Physiol 146:1109-16. 2008
    ..These results indicate that myosins XI-K and XI-2 play major and overlapping roles in the cell dynamics in Arabidopsis and highlight the redundant nature of myosin function in plants...
  90. pmc Systematic mutagenesis of the Escherichia coli genome
    Yisheng Kang
    Department of Genetics, University of Madison Wisconsin, Rm 206, 445 Henry Mall, Madison, WI 53706, USA
    J Bacteriol 186:4921-30. 2004
  91. pmc STOP1 regulates multiple genes that protect arabidopsis from proton and aluminum toxicities
    Yoshiharu Sawaki
    Laboratory of Plant Cell Technology, Faculty of Applied Biological Sciences, Gifu University, Gifu 501 1193, Japan
    Plant Physiol 150:281-94. 2009
    ..Finally, we showed that STOP1 is localized to the nucleus, suggesting that the protein regulates the expression of multiple genes that protect Arabidopsis from Al and H(+) toxicities, possibly as a transcription factor...
  92. pmc Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris
    Wei Qian
    National Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, PR China
    Genome Res 15:757-67. 2005
  93. ncbi Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres
    Tammy A Morrish
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 0618, USA
    Nature 446:208-12. 2007
    ..Thus, we propose that EN(i) retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain...
  94. ncbi Transposable element contributions to plant gene and genome evolution
    J L Bennetzen
    Department of Biological Sciences, Purdue University, West Lafayette, IN 47907 1392, USA
    Plant Mol Biol 42:251-69. 2000
    ..For these reasons, understanding plant gene and genome evolution is only possible if we comprehend the contributions of transposable elements...
  95. ncbi Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1
    Marion G Ott
    Department of Hematology Oncology, University Hospital, German Cancer Research Center, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Med 12:401-9. 2006
  96. ncbi Hsp101 is necessary for heat tolerance but dispensable for development and germination in the absence of stress
    S W Hong
    Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, AZ 85721, USA
    Plant J 27:25-35. 2001
    ..The hot1-2 mutant also expresses Hsp101 in seeds, but at a tenfold reduced level, resulting in reduced thermotolerance of germinating seeds and underscoring the importance of Hsp101 to seed stress tolerance...
  97. ncbi The plant WNK gene family and regulation of flowering time in Arabidopsis
    Y Wang
    Root Biology Center, South China Agricultural University, Guangzhou, China
    Plant Biol (Stuttg) 10:548-62. 2008
    ..Taken together, our results suggest that the Arabidopsis WNK gene family regulates flowering time by modulating the photoperiod pathway...
  98. pmc Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: application to open reading frame characterization
    A J Link
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Bacteriol 179:6228-37. 1997
    ..Because of the operon structure of this organism, traditional methods such as insertional mutagenesis run the risk of introducing polar effects on downstream genes or creating secondary mutations elsewhere ..
  99. pmc Drosophila telomeres: an exception providing new insights
    James M Mason
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
    Bioessays 30:25-37. 2008
    ..However, the subterminal arrays in both species may be involved in telomere-telomere associations and/or communication...
  100. pmc Dramatic amplification of a rice transposable element during recent domestication
    Ken Naito
    Department of Plant Biology, University of Georgia, Athens, GA 30602, USA
    Proc Natl Acad Sci U S A 103:17620-5. 2006
    ..The rapid increase in mPing copy number documented in this study represents a potentially valuable source of population diversity in self-fertilizing plants like rice...
  101. pmc The Arabidopsis synaptonemal complex protein ZYP1 is required for chromosome synapsis and normal fidelity of crossing over
    James D Higgins
    School of Biosciences, The University of Birmingham, Birmingham B15 2TT, United Kingdom
    Genes Dev 19:2488-500. 2005
    ..Importantly in the absence of ZYP1, recombination occurs between both homologous and nonhomologous chromosomes suggesting the protein is required to ensure the fidelity of meiotic chromosome associations...

Research Grants71

  1. Pilot and definitive studies to evaluate Insertional Mutagenesis
    LU TAYLOR; Fiscal Year: 2012
    ..FDA-NTP Studies of Insertional Mutagenesis - Pilot Study: 12-week pilot study has been awarded to the lab to develop and validate preclinical model ..
  2. Studies to Evaluate the Toxicological Potential of Test Articles
    LU TAYLOR; Fiscal Year: 2010
    ..FDA-NTP Studies of Insertional Mutagenesis - Pilot Study: 12-week pilot study has been awarded to the lab to develop and validate preclinical model ..
  3. Retroviral Vector-mediated Liver Gene Therapy for MPS I
    Katherine P Ponder; Fiscal Year: 2013
    ..Although no tumors developed in mice or dogs with this approach, the risk of insertional mutagenesis with an LTR-intact vector is a concern...
  4. Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary Disorders
    KARIN L GAENSLER; Fiscal Year: 2012
    ..Potential risks of transplantation of such genetically modified allogeneic HSC include GVHD and insertional mutagenesis resulting in uncontrolled clonal proliferation...
  5. Tick-Mammal Interface of Human Granulocytic Anaplasmosis
    ..By specifically disrupting Ap gene expression using insertional mutagenesis the essential processes which Ap performs to infect its different hosts can be sorted into common an host-..
  6. Gene Therapy for Retinitis Pigmentosa
    Rajendra Kumar-Singh; Fiscal Year: 2012
    ..been recently shown to cause hepatocellular carcinoma at the alarmingly high rate of 56% in animals by insertional mutagenesis. Hence, there is a need for gene therapy vectors that persist episomally...
  7. Generation of Human iPS Cells via Non-integrating Vectors
    Wen Shu Wu; Fiscal Year: 2010
    ..mainly through reactivation of c-Myc and inactivation of tumor suppressor genes resulting from viral insertional mutagenesis. Recently, mouse iPS cells were successfully generated from fibroblasts and liver cells via adenovirus-..
  8. Gene Therapy of Mucopolysaccharidosis VII
    Mark E Haskins; Fiscal Year: 2012
    ..Although no tumors developed in mice or dogs with this approach, the risk of insertional mutagenesis with an LTR-intact vector is a concern...
  9. Hematopoietic gene therapy for hemophilia A
    H Trent Spencer; Fiscal Year: 2013
    ..and 2) test recombinant lentiviral vectors that have been demonstrated to display a reduction of insertional mutagenesis compared to oncoretroviruses...
  10. Immune Tolerance in Non-clonal Immune Systems
    David Nemazee; Fiscal Year: 2013
    ..We will take advantage of a random insertional mutagenesis screen to identify genes regulating tolerance...
  11. Role of a new polyomavirus in Merkel cell carcinoma
    Patrick S Moore; Fiscal Year: 2013
    ..MCPyV may play a role in tumorigenesis through insertional mutagenesis, expression of T antigen or both...
  12. Lentiviral-MGMT gene transfer into hematopoietic stem cells
    Stanton L Gerson; Fiscal Year: 2011
    ..expression, and a recognized preferential insertion near promoter regions that increases the chance for insertional mutagenesis and leukemia. This proposal will link the advances made at Lentigen Corp...
  13. Targeting FGFR to prevent the outgrowth of metastatic breast cancer
    MICHAEL KEITH WENDT; Fiscal Year: 2013
    ..Finally, in Aim3 we will use a novel insertional mutagenesis technique to screen for potential mediators of EGFRi-insensitivity...
  14. Cellular Determinants of Apoptosis in Virus-Infected Cells
    Ganes C Sen; Fiscal Year: 2012
    ..Finally, unbiased genetic screens of the whole human genome will be conducted by using insertional mutagenesis or an appropriate shRNA library and cell survival as the end point assay...
  15. A Genetic Screen for HCC Genes
    ..this grant to model HCC using a novel system for random, Sleeping Beauty (SB) transposon-based, somatic insertional mutagenesis developed by Drs. Largaespada and Dupuy...
  16. Non-Viral Gene Therapy for Retinal Degeneration
    Rajendra Kumar-Singh; Fiscal Year: 2013
    ..also have some disadvantages, including induction of host immune responses, a limited transgene capacity, insertional mutagenesis and difficulty in production...
  17. Integration of Murine Retroviral Vectors
    Monica J Roth; Fiscal Year: 2013
    ..continue to be developed as viral vectors, despite their association with oncogenic transformation and insertional mutagenesis. This is highlighted in the past month with the association of xenotropic murine leukemia virus-related ..
  18. Genetics of mating and fruiting in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2010
    ..physiological, genetic, and genomic analysis of monokaryotic fruiting including whole genome microarray, insertional mutagenesis, and quantitative trait mapping...
  19. Role of Setbp1 in leukemic stem cell self-renewal
    Yang Du; Fiscal Year: 2013
    ..Using a novel retroviral insertional mutagenesis strategy, we have discovered and confirmed that Set binding protein 1 (Setbp1), an AT-hook transcription ..
  20. A Novel Strategy for Recombinant Adeno-Associated Virus Vector Production
    Patrick Hearing; Fiscal Year: 2013
    ..or non-dividing cells, and usually remain episomal in transduced cells greatly reducing the risk of insertional mutagenesis. Current approaches to produce rAAV vectors include transfection of producer cell lines and infection ..
  21. A forward genetic screen for PKD pathways in mice using the PiggyBac transposon
    Stefan Somlo; Fiscal Year: 2010
    ..We propose to use transposon mediated somatic insertional mutagenesis based on a uniquely modified PiggyBac (PB) transposon system to discover activating mutations on a wild ..
  22. Genetic approaches to discover host factors critical to dengue virus infection
    JAN EDUARD CARETTE; Fiscal Year: 2012
    ..Using insertional mutagenesis in a haploid human cell line, we have created cell libraries with mutations in most genes...
  23. Exploitation of Near-Haploid Human Cells for Functional Gene Discovery
    MICHAEL BENJAMIN MAJOR; Fiscal Year: 2010
    ..Retroviral insertional mutagenesis of these cells provides a means to quickly and inexpensively identify functional units within the human ..
  24. Modifiers of Tumor Susceptibility in Murine Neuroblastoma
    William A Weiss; Fiscal Year: 2012
    ..insertional mutagen, the vertebrate Sleeping Beauty (SB) transposon, and to combine use of somatic insertional mutagenesis with comparative genomic hybridization and modifier genetics to identify genes that influence ..
  25. SB Transposons for Gene Therapy
    Perry B Hackett; Fiscal Year: 2013
    ..following hydrodynamic delivery into chromosomes of dog liver to help evaluate potential risks from insertional mutagenesis. The experiments in this project will provide an assessment of the capacity of SB as a gene-transfer ..
  26. Retroviral Integration &HDAC inhibitors
    Monica J Roth; Fiscal Year: 2012
    ..A key goal of retroviral-based gene delivery is to maximize gene expression without the complication of insertional mutagenesis. The studies in this proposal examine the linkage between integration and gene expression...
  27. Development of safe and efficient gene therapy strategies for hemoglobinopathies
    Hans Peter Kiem; Fiscal Year: 2013
    ..insertion site analyses and found that lentivirus vectors and foamy virus vectors maybe less prone for insertional mutagenesis than gammaretroviral vectors...
  28. Genome stability function of APOBEC3 retroviral restriction factors
    LUBBERTUS C MULDER; Fiscal Year: 2012
    ..polymorphism) de-represses endogenous retroviruses, paving the way to oncogenic transformation via insertional mutagenesis. In our first Specific Aim, we will determine the molecular basis of HIV-1-dependent HERV infectivity...
  29. Mobile Elements and Recombination
    Prescott L Deininger; Fiscal Year: 2013
    ..Mechanisms by which they damage DNA involve Alu/Alu recombination, insertional mutagenesis, and the creation of DNA double-strand breaks...
  30. The Role of CREB in Normal Myelopoiesis and Leukemogenesis
    KATHLEEN MIHO SAKAMOTO; Fiscal Year: 2013
    ..Finally, we identified sox4 and gfi1 in a retroviral insertional mutagenesis screen in which CREB transgenic mice were infected with the MOL4070LTR retrovirus...
  31. Modeling and correcting human SCID using patient-derived iPS cells
    Juan Carlos Zuniga-Pflucker; Fiscal Year: 2013
    ..proof of principle that gene therapy can cure human diseases;however, leukemic proliferation due to insertional mutagenesis has been reported in 5 SCID patients treated by gene therapy...
  32. Utilizing PB Transposon to Generate a Comprehensive Mouse Knockout Resource
    Tian Xu; Fiscal Year: 2009
    ..pB insertions can be precisely excised to revert the mutant phenotypes. We propose to utilize this pB insertional mutagenesis system and the cost-effective animal facility in Shanghai, China to produce 100,000 independent single pB ..
  33. Stem Cell Gene Therapy for Pyruvate Kinase Deficiency Using Foamy Vectors
    Grant Trobridge; Fiscal Year: 2009
    ..More recently, insertional mutagenesis leading to leukemia, as observed in the French X-linked SCID trial, has also become a critical concern ..
  34. Gene Therapy for SCID-X1 using a self-inactivating (SIN) gammaretroviral vector
    David A Williams; Fiscal Year: 2013
    ..Recent gene transfer trials have documented efficacy, albeit with toxicity related to insertional mutagenesis. We have developed a next generation self-inactivating (SIN) vector expressing the IL-2RG gene controlled ..
  35. Generating iPS cells by reprogramming using small molecules
    Aravind Ramakrishnan; Fiscal Year: 2013
    ..currently uses retroviral transduction to generate iPS cells which raises the unacceptable concern of insertional mutagenesis. 2) A large animal pre-clinical model is needed to test the long term safety and efficacy of ..
  36. Uterine Vascular Remodeling during Pregnancy
    James K Pru; Fiscal Year: 2013
    ..In Specific Aim 1 we propose to demonstrate the functional requirement of the receptor in insertional mutagenesis studies in which cre recombinase is inserted into the receptor gene locus...
  37. Transposon-based Platform for Insertional Mutagenesis and Genome Engineering
    Darius Balciunas; Fiscal Year: 2013
    DESCRIPTION (provided by Principal Investigator): Transposon-Based Platform for Insertional Mutagenesis and Genome Engineering Abstract: The fastest, most comprehensive and cost-effective way to study human gene function is through ..
  38. Identifying Signaling Mechanisms Controlling Flagellar Length in Chlamydomonas
    PRACHEE AVASTHI CROFTS; Fiscal Year: 2011
    ..Finally I will identify novel components in this pathway using an insertional mutagenesis screen for suppressors of a long flagella mutant...
  39. Genomics Resources and Infrastucture for the Zebrafish
    Chris T Amemiya; Fiscal Year: 2012
    ..Thousands of developmental mutants have been generated via ENU and insertional mutagenesis screens, and, importantly, the majority of the genes responsible for these mutant phenotypes have human ..
  40. Nonintegrating Lentiviral Vectors Towards Clinical Trials
    Tal Kafri; Fiscal Year: 2013 applicant): Nonintegrating lentiviral viral vectors (NILVs) present a means of reducing the risk of insertional mutagenesis in nondividing cells and enabling the short-term expression of potentially hazardous gene products...
  41. Induced Pluripotent Stem Cell Approach to Glaucomatous Optic Neuropathy
    Iqbal Ahmad; Fiscal Year: 2013 recruiting endogenous pluripotency genes instead of introducing exogenous genes, which can lead to insertional mutagenesis, addresses a significant barrier to iPSC-based therapy...
  42. Role and Regulation of a Molecular Mimic in Histoplasma Pathogenesis
    William E Goldman; Fiscal Year: 2013
    ..Specific Aim 2. Identify the genes involved in CBP1 transcriptional regulation. Insertional mutagenesis will be used to generate a library of mutants that will be screened for those that no longer regulate ..
  43. Molecular Targets in T Lineage Leukemia
    Monique Dail; Fiscal Year: 2012
    ..Retroviral insertional mutagenesis (RIM) is a powerful strategy for introducing genetic alterations that can be traced and identified...
  44. Transposon-based screens for colorectal cancer genes
    ..this grant to model CRC using a novel system for random, Sleeping Beauty (SB) transposon-based, somatic insertional mutagenesis developed by Drs. Largaespada...
  45. Novel prostate cancer oncogenes identified by transposon mutagenesis
    Paul C Marker; Fiscal Year: 2013
    ..The primary screen utilized transposon-based insertional mutagenesis in mice to model genetic heterogeneity in prostate cancer and conduct a genome-wide screen for new ..
  46. Activators and repressors of NFkappaB and IRF3/7 in innate immunity
    GEORGE ROBERT STARK; Fiscal Year: 2012
    ..We will use insertional mutagenesis to identify novel inhibitors of NF-kB activation...
  47. Large-scale F1 somatic screens for new tumor suppressors and oncogenes in Drosoph
    MARLA BETH TIPPING; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Transposon-based insertional mutagenesis screens have been used successfully in numerous studies to induce mutations in Drosophila...
  48. Targeted integration of a DNA transposon-based nonviral vector
    Patrick L Sinn; Fiscal Year: 2013
    ..Non-integrating vectors may not persist and integrating vectors may cause insertional mutagenesis. There is a critical need for improved gene delivery tools that address this conundrum...
  49. L 1 element as an inrinsic factor of mammalian aging
    ..DNA endonuclease is potentially much greater than the insult to the genome caused by the element via insertional mutagenesis. We detected endogenous L1 expression in a number of somatic cells...
  50. Transposon-insertional Mutagenesis to Decipher Osteosarcomagenesis
    KEVIN BRUCE JONES; Fiscal Year: 2013
    ..Further, osteosarcoma is a model for other genetically-complex cancers, many of which are major public health burdens. ..
  51. Virulence Factor Trafficking in Cryptococcus
    Peter Williamson; Fiscal Year: 2005
    ..neoformans. We have also developed a method of insertional mutagenesis and have isolated numerous laccase-deficient mutants...
  52. DNA Double-Strand Break Repair Regulates rAAV-Mediated Gene Targeting
    Eric A Hendrickson; Fiscal Year: 2013
    ..This aspect of rAAV, however, is plagued by the same insertional mutagenesis problems associated with other vectors...
  53. The Role of Oncogenic Ras in Leukemogenesis and Response to Targeted Therapies
    Qing Li; Fiscal Year: 2012
    ..I have also utilized retroviral insertional mutagenesis (RIM) as a general strategy for introducing mutations that cooperate with oncogenic Nras and Kras in ..
  54. Molecular Pathways to Thynmic Lymphoma and Leukemia
    A Thomas Look; Fiscal Year: 2013
    ..molecular pathways that cooperate with Notch1 signaling in lymphomagenesis by analyzing the impact of insertional mutagenesis, epigenetic regulation, and miRNA-dependent regulation on the generation of T-ALL from in Notch1 ..
  55. Discovering cardiomyopathy modifiers in TOR signaling via zebrafish genetics
    Xiaolei Xu; Fiscal Year: 2013
    ..To address the latter challenge, we adapted a transposon-based insertional mutagenesis strategy that facilitates the identification of all mutants by a RFP tag...
  56. Identification of a noval oncogene using validation-based insertional mutagenesis
    Mark W Jackson; Fiscal Year: 2013
    ..Novel proteins also provide opportunities for drug development that will expand the arsenal of therapies necessary for eradicating cancer and extending the life of patients. ..
  57. 1.19Hormonal controls of zebrafish post-embryonic melanocyte development
    SARAH KELLY MCMENAMIN; Fiscal Year: 2012
    ..This screen will employ gene-breaking vectors and transposon-mediated insertional mutagenesis, allowing the efficient identification and analysis of affected loci...
    Steven Bassnett; Fiscal Year: 2012
    ..In preliminary experiments, the Lim2 locus was disrupted in mice by insertional mutagenesis, resulting in a functional null for Lim2...
    Tamara L Doering; Fiscal Year: 2013
    ..Aim I is to identify mutants in these processes, using insertional mutagenesis and automated screening...
  60. Zebrafish ES cell lines for targeted mutagenesis
    Paul Collodi; Fiscal Year: 2010
    ..regulate early development and human disease, methods are not available for targeted gene inactivation by insertional mutagenesis. The goal of this research is to develop gene targeting methods using zebrafish embryonic stem (ES) cell ..
  61. Transposon mutagenesis screen for mammalian cancer gene discovery
    Jonathan Cornett; Fiscal Year: 2010
    ..The overall aim of this proposal is to use PB insertional mutagenesis to mutate epidermal stem cells, screen for mutations that promote tumorigenesis, and identify the ..
  62. Biomedical Genomics Center: Next-Generation Sequencing Instrumentation
    Kenneth B Beckman; Fiscal Year: 2010
    ..for differences in chemotherapy response;they would like to use sequence-based characterization of insertional mutagenesis to study carcinogenesis and to uncover mutations controlling the fundamental basis of meiosis...
  63. Genetic analysis of Cryptococcus neoformans virulence
    Joseph Heitman; Fiscal Year: 2009
    ..We propose to broadly apply Insertional mutagenesis to identify genes encoding virulence attributes necessary for infection. C...
    Gary Dunny; Fiscal Year: 1990
    ..They have also made important contributions to the development of cloning systems, gene transfer systems, insertional mutagenesis systems, and immunological methods that are applicable to a wide variety of Gram-positive bacteria of ..
    James Cook; Fiscal Year: 2009
    ..behind the present proposal is that a virulence associated DEAD-box protein, Vad1, identified by insertional mutagenesis, is an important regulator of laccase and virulence in C. neoformans...
    Joseph Lipsick; Fiscal Year: 2003
    ..The c-Myb proto-oncogene has also been activated by retroviral insertional mutagenesis in avian B lymphoid and murine myeloid malignancies...
    Hsing Jien Kung; Fiscal Year: 2000
    The central theme of the present proposal continues to be the understanding of retroviral insertional mutagenesis and oncogene activation...
  68. Characterization of Cellular Proteins Involved in HIV Infection
    WILLIAM O BRIEN; Fiscal Year: 2009
    ..Gene-trap insertional mutagenesis has identified cells with genes that are not expressed;loss of these genes allows the cell to survive ..
  69. Creation of hyperactive transposons for mutagenesis in rodents
    Eric Ostertag; Fiscal Year: 2009
    ..seeks to rapidly produce rat mutants through the development of hyperactive transposons for germ line insertional mutagenesis. This approach uses randomly integrating transposons, which enables the rapid identification of sequence-..
  70. Transposon mutagenesis for modeling complex human disease in rats
    Howard Jacob; Fiscal Year: 2009
    ..We are now building upon preliminary data showing that transposon insertional mutagenesis using the Sleeping Beauty (SB) transposon system can generate heritable mutations in the rat at a rate ..
  71. Novel Strategy for BIV Vector Site-Specific Integration
    Sheila Connelly; Fiscal Year: 2006
    ..Indeed, insertional mutagenesis has recently become a reality following the discovery of three gene therapy-related leukemias in children ..