point mutation


Summary: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.

Top Publications

  1. ncbi Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations
    Raphael Guerois
    EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Mol Biol 320:369-87. 2002
  2. ncbi A gain-of-function mutation of JAK2 in myeloproliferative disorders
    Robert Kralovics
    Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland
    N Engl J Med 352:1779-90. 2005
  3. pmc Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease
    Jizhong Zou
    Institute for Cell Engineering, The JohnsHopkins University School of Medicine, Baltimore, MD, USA
    Blood 118:4599-608. 2011
  4. ncbi Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
    E Joanna Baxter
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Lancet 365:1054-61. 2005
  5. ncbi Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
    Maria Eriksson
    Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    Nature 423:293-8. 2003
  6. ncbi A molecular marker for chloroquine-resistant falciparum malaria
    A Djimde
    Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA
    N Engl J Med 344:257-63. 2001
  7. ncbi Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease
    R Kruger
    Nat Genet 18:106-8. 1998
  8. pmc ESEfinder: A web resource to identify exonic splicing enhancers
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Nucleic Acids Res 31:3568-71. 2003
  9. ncbi Mutation in the alpha-synuclein gene identified in families with Parkinson's disease
    M H Polymeropoulos
    Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 1430, USA
    Science 276:2045-7. 1997
  10. 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

Research Grants

Detail Information

Publications274 found, 100 shown here

  1. ncbi Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations
    Raphael Guerois
    EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Mol Biol 320:369-87. 2002
    ..FOLDEF is available via a web-interface at http://fold-x.embl-heidelberg.de..
  2. ncbi A gain-of-function mutation of JAK2 in myeloproliferative disorders
    Robert Kralovics
    Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland
    N Engl J Med 352:1779-90. 2005
    ..The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases...
  3. pmc Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease
    Jizhong Zou
    Institute for Cell Engineering, The JohnsHopkins University School of Medicine, Baltimore, MD, USA
    Blood 118:4599-608. 2011
    ..This study also provides a new strategy for gene therapy of monogenic diseases using patient-specific iPSCs, even if the underlying disease-causing mutation is not expressed in iPSCs...
  4. ncbi Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
    E Joanna Baxter
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Lancet 365:1054-61. 2005
    ..We investigated the role of the cytoplasmic tyrosine kinase JAK2 in patients with a myeloproliferative disorder...
  5. ncbi Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
    Maria Eriksson
    Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    Nature 423:293-8. 2003
    ..The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing...
  6. ncbi A molecular marker for chloroquine-resistant falciparum malaria
    A Djimde
    Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA
    N Engl J Med 344:257-63. 2001
    ..Chloroquine resistance has been associated in vitro with point mutations in two genes, pfcrt and pfmdr 1, which encode the P. falciparum digestive-vacuole transmembrane proteins PfCRT and Pgh1, respectively...
  7. ncbi Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease
    R Kruger
    Nat Genet 18:106-8. 1998
  8. pmc ESEfinder: A web resource to identify exonic splicing enhancers
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Nucleic Acids Res 31:3568-71. 2003
    ..The effect of a point mutation within a coding sequence is traditionally attributed to the deduced change in the corresponding amino acid...
  9. ncbi Mutation in the alpha-synuclein gene identified in families with Parkinson's disease
    M H Polymeropoulos
    Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 1430, USA
    Science 276:2045-7. 1997
    ..This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder...
  10. 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
  11. ncbi Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification
    M E Gorre
    Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Science 293:876-80. 2001
    ..These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance...
  12. pmc I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure
    Emidio Capriotti
    Laboratory of Biocomputing, CIRB Department of Biology, University of Bologna via Irnerio 42, 40126 Bologna, Italy
    Nucleic Acids Res 33:W306-10. 2005
    ..0 as a unique and valuable helper for protein design, even when the protein structure is not yet known with atomic resolution. Availability: http://gpcr.biocomp.unibo.it/cgi/predictors/I-Mutant2.0/I-Mutant2.0.cgi...
  13. pmc The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus
    Rafael Sanjuan
    Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de Valencia, P O Box 22085, 46071 Valencia, Spain
    Proc Natl Acad Sci U S A 101:8396-401. 2004
    ..The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a gamma distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations...
  14. pmc RIPCAL: a tool for alignment-based analysis of repeat-induced point mutations in fungal genomic sequences
    James K Hane
    Australian Centre for Necrotrophic Fungal Pathogens, Faculty of Health Sciences, Murdoch University, Murdoch, Australia
    BMC Bioinformatics 9:478. 2008
    Repeat-induced point mutation (RIP) is a fungal-specific genome defence mechanism that alters the sequences of repetitive DNA, thereby inactivating coding genes...
  15. pmc Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations
    Amar bir Singh Sidhu
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Science 298:210-3. 2002
    ..pfcrt mutations increased susceptibility to artemisinin and quinine and minimally affected amodiaquine activity; hence, these antimalarials warrant further investigation as agents to control chloroquine-resistant falciparum malaria...
  16. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
    ..The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype...
  17. ncbi The genome sequence of the rice blast fungus Magnaporthe grisea
    Ralph A Dean
    Center for Integrated Fungal Research, North Carolina State University, Raleigh, North Carolina 27695, USA
    Nature 434:980-6. 2005
    ..The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation...
  18. ncbi Gene targeting by homologous recombination in Drosophila
    Y S Rong
    Department of Biology, University of Utah, Salt Lake City, UT 84112, USA
    Science 288:2013-8. 2000
    ..A method is described that enables analogous manipulations of the Drosophila genome. This technique may also be applicable to other organisms for which gene-targeting procedures do not yet exist...
  19. pmc Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4)
    S T Qureshi
    Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4
    J Exp Med 189:615-25. 1999
    ..C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved ..
  20. ncbi Auto-regulation of the circadian slave oscillator component AtGRP7 and regulation of its targets is impaired by a single RNA recognition motif point mutation
    Jan C Schöning
    Department of Molecular Cell Physiology, University of Bielefeld, D 33615 Bielefeld, Germany
    Plant J 52:1119-30. 2007
  21. pmc Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion
    Kris A DeMali
    Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    J Cell Biol 159:881-91. 2002
    ..We have mapped the binding site for the Arp2/3 complex to the hinge region of vinculin, and a point mutation in this region selectively blocks binding to the Arp2/3 complex...
  22. ncbi A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene
    Pauline Verdijk
    Department of Dermatology, Leiden University Mediacl Center, Wassenaarseweg 72, 2333, AL Leiden, The Netherlands
    J Invest Dermatol 124:714-7. 2005
    ..Expression of mutated Langerin in human fibroblasts induces tubular-like structures that are negative for BG-specific antibodies and do not resemble the characteristic structural features of BG...
  23. ncbi Mitochondrial DNA mutations in human disease
    S DiMauro
    College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Am J Med Genet 106:18-26. 2001
    ..We review recent progress in prenatal diagnosis, epidemiology, and in the development of animal models harboring mtDNA mutations...
  24. ncbi A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome
    B Lüdecke
    Universitäts Kinderklinik, Bochum, Germany
    Hum Genet 95:123-5. 1995
    ..In one family two siblings with this disease carried a point mutation in exon 11 of the tyrosine hydroxylase gene, resulting in an amino acid exchange of Gln381 to Lys381...
  25. pmc Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation
    Neal S Peachey
    Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA
    J Neurophysiol 108:2442-51. 2012
    ..The Trpm1(tvrm27/tvrm27) mutant will be useful for elucidating the role of TRPM1 in DBC signal transduction, for determining how Trpm1 mutations impact central visual processing, and for evaluating experimental therapies for cCSNB...
  26. ncbi Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids
    H Ranson
    Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
    Insect Mol Biol 9:491-7. 2000
    ..The An. gambiae sodium channel was physically mapped to chromosome 2L, division 20C. This position corresponds to the location of a major quantitative trait locus determining resistance to permethrin in the Kenyan strain of An. gambiae...
  27. pmc The S4-S5 linker couples voltage sensing and activation of pacemaker channels
    J Chen
    Department of Medicine, Division of Cardiology, Eccles Program in Human Molecular Biology and Genetics, University of Utah, Eccles Institute of Human Genetics, 15 N 2030 E, Room 4220, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 98:11277-82. 2001
    ..Our findings also suggest that opening of HCN and related channels corresponds to activation of a gate located near the inner pore, rather than recovery of channels from a C-type inactivated state...
  28. pmc Point mutation in the glycoprotein of lymphocytic choriomeningitis virus is necessary for receptor binding, dendritic cell infection, and long-term persistence
    Brian M Sullivan
    Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:2969-74. 2011
    ..This work emphasizes the importance of subtle differences in viral strains that determine disease outcomes...
  29. ncbi A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma
    Adriana M Alvares Da Silva
    Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulist de Medicina, Federal University of Sao Paulo, Brazil
    J Clin Endocrinol Metab 88:5438-43. 2003
    ..We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cysteine-rich ..
  30. pmc Inherited mitochondrial optic neuropathies
    P Yu-Wai-Man
    Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, UK
    J Med Genet 46:145-58. 2009
  31. ncbi The mutation spectrum revealed by paired genome sequences from a lung cancer patient
    William Lee
    Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, California 94080, USA
    Nature 465:473-7. 2010
    ..We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment...
  32. ncbi SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification
    G J McKenzie
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 3411, USA
    Mol Cell 7:571-9. 2001
    Adaptive point mutation and amplification are induced responses to environmental stress, promoting genetic changes that can enhance survival...
  33. pmc Polymorphism of PfATPase in Niger: detection of three new point mutations
    Maman Laminou Ibrahim
    Centre de Recherche Médicale et Sanitaire CERMES, BP 10887 Niamey, Niger
    Malar J 8:28. 2009
    ..The goal of this work was to describe the baseline polymorphism of PfATPase6 gene in Niger, at a time when the national implementation of the ACT policy had just begun...
  34. ncbi A point mutation in the FMR-1 gene associated with fragile X mental retardation
    K De Boulle
    Department of Medical Genetics, University of Antwerp UIA, Belgium
    Nat Genet 3:31-5. 1993
    ..We find a single point mutation in FMR-1 resulting in an lle367Asn substitution...
  35. ncbi Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia
    Charles G Mullighan
    Department of Pathology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 446:758-64. 2007
    ..Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and ..
  36. ncbi The relationship between microsatellite slippage mutation rate and the number of repeat units
    Yinglei Lai
    Department of Mathematics, Department of Biological Sciences, University of Southern California, USA
    Mol Biol Evol 20:2123-31. 2003
    ..Our results agree with the length-dependent mutation pattern observed from experimental data, and they explain the scarcity of long microsatellites...
  37. pmc A cytosine methyltransferase homologue is essential for repeat-induced point mutation in Neurospora crassa
    Michael Freitag
    Institute of Molecular Biology, University of Oregon, Eugene, OR 97403 1229, USA
    Proc Natl Acad Sci U S A 99:8802-7. 2002
    ..Neurospora crassa inactivates genes in duplicated DNA segments by a hypermutation process, repeat-induced point mutation (RIP)...
  38. pmc Identification of an acquired JAK2 mutation in polycythemia vera
    Runxiang Zhao
    Hematology Oncology Division, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 280:22788-92. 2005
    ..By sequencing the entire coding regions of cDNAs of candidate enzymes, we identified a G:C--> T:A point mutation of the JAK2 tyrosine kinase in 20 of 24 PV blood samples but none in 12 normal samples...
  39. pmc Gene-environment interactions in Leber hereditary optic neuropathy
    Matthew Anthony Kirkman
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, UK
    Brain 132:2317-26. 2009
    ..Based on these findings, asymptomatic carriers of a LHON mtDNA mutation should be strongly advised not to smoke and to moderate their alcohol intake...
  40. ncbi Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
    Bastien Mangeat
    Department of Genetics and Microbiology, University of Geneva, 1211 Geneva 4, Switzerland
    Nature 424:99-103. 2003
    ..We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens...
  41. pmc CUPSAT: prediction of protein stability upon point mutations
    Vijaya Parthiban
    Cologne University Bioinformatics Center, International Max Planck Research School, Cologne, Germany
    Nucleic Acids Res 34:W239-42. 2006
    ..Thus, the program serves as a valuable tool for the analysis of protein design and stability. The tool is accessible from the link http://cupsat.uni-koeln.de...
  42. pmc In silico reversal of repeat-induced point mutation (RIP) identifies the origins of repeat families and uncovers obscured duplicated genes
    James K Hane
    Faculty of Health Sciences, Murdoch University, Perth, Western Australia, 6150, Australia
    BMC Genomics 11:655. 2010
    Repeat-induced point mutation (RIP) is a fungal genome defence mechanism guarding against transposon invasion...
  43. ncbi The point mutation and polymorphism in keratoconus candidate gene TGFBI in Chinese population
    Tao Guan
    Taizhou Eye Hospital, Taizhou, Zhejiang, Zhejiang Province, China
    Gene 503:137-9. 2012
    ..To understand the region point mutations and single nucleotide polymorphisms characteristic of keratoconus candidate gene in Chinese population, the TGFBI...
  44. pmc Widespread distribution of a newly found point mutation in voltage-gated sodium channel in pyrethroid-resistant Aedes aegypti populations in Vietnam
    Hitoshi Kawada
    Department of Vector Ecology and Environment, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
    PLoS Negl Trop Dis 3:e527. 2009
    ..aegypti populations in Vietnam. The aim of this study was to determine the types and frequencies of mutations in the para gene in Ae. aegypti collected from used tires in Vietnam...
  45. pmc Spongiform encephalopathy in transgenic mice expressing a point mutation in the β2-α2 loop of the prion protein
    Christina J Sigurdson
    Department of Pathology, University of California, San Diego, La Jolla, California 92093, USA
    J Neurosci 31:13840-7. 2011
    ..These results add to the evidence that the β2-α2 loop has an important role in intermolecular interactions, including that it may be a key determinant of prion protein aggregation...
  46. ncbi Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2
    M Higuchi
    Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Heidelberg, Germany
    Nature 406:78-81. 2000
    ..We conclude that this transcript is the physiologically most important substrate of ADAR2...
  47. ncbi Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China
    G Q Zhang
    National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai 200025, China
    Trop Med Int Health 14:1266-71. 2009
    ..The main purpose of this study was to analyse the molecular markers of antimalarial resistance and thereby to assess the possibility of reintroduction of CQ or SP for falciparum malaria treatment...
  48. pmc A point mutation leading to hepatitis C virus escape from neutralization by a monoclonal antibody to a conserved conformational epitope
    Zhen Yong Keck
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Virol 82:6067-72. 2008
    ..These results highlight the challenges inherent in developing HCV vaccines and show that an effective vaccine must induce antibodies to both conserved and more invariant epitopes to minimize virus escape...
  49. ncbi Genomic evidence of repeat-induced point mutation (RIP) in filamentous ascomycetes
    A John Clutterbuck
    School of Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, UK
    Fungal Genet Biol 48:306-26. 2011
    ..Many genomes carried both intact repeats as well as others that had suffered heavily from transitions. Only one species, Chaetomium globosum, showed no evidence of directional mutation...
  50. ncbi Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand
    T Takahashi
    Osaka Bioscience Institute, Japan
    Cell 76:969-76. 1994
    ..Activated splenocytes from gld mice express Fasl mRNA. However, FasL in gld mice carries a point mutation in the C-terminal region, which is highly conserved among members of the TNF family...
  51. pmc A simplified high-throughput method for pyrethroid knock-down resistance (kdr) detection in Anopheles gambiae
    Amy Lynd
    Vector Research Group, Liverpool Tropical School of Medicine, Pembroke Place, Liverpool, UK
    Malar J 4:16. 2005
    ..Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation...
  52. pmc A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans
    Nikolay L Malinin
    Department of Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, NB50, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Med 15:313-8. 2009
    ..The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene...
  53. doi Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins
    Michela Menegon
    Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita, Rome, Italy
    Parasitol Int 57:233-5. 2008
  54. pmc Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation
    P Rodriguez-Viciana
    Imperial Cancer Research Fund, London
    EMBO J 15:2442-51. 1996
    ..A point mutation in this region, K227E, blocks the GTP-dependent interaction of PI 3-kinase p110alpha with Ras in vitro and the ..
  55. pmc Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa
    Zachary A Lewis
    Institute of Molecular Biology, University of Oregon, Eugene, Oregon, 97403 1229, USA
    Genome Res 19:427-37. 2009
    ..co-localized and defined 44 heterochromatic domains on linkage group VII, all relics of repeat-induced point mutation. Interestingly, the centromere was found in an approximately 350 kb heterochromatic domain with no detectable ..
  56. ncbi The cysteine-rich region of T1R3 determines responses to intensely sweet proteins
    Peihua Jiang
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 279:45068-75. 2004
  57. pmc Distribution of fitness and virulence effects caused by single-nucleotide substitutions in Tobacco Etch virus
    Purificación Carrasco
    Instituto de Biología Molecular y Celular de Plantas CSIC UPV, Avenida de los Naranjos s n, 46022 Valencia, Spain
    J Virol 81:12979-84. 2007
    ..4% increases. Interestingly, the only mutations showing a significant effect on virulence were hypervirulent. Competitive fitness and virulence were uncorrelated traits...
  58. pmc Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits
    Matthias Groszer
    Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Curr Biol 18:354-62. 2008
    ..In this study, we generated mice carrying an identical point mutation to that of the KE family, yielding the equivalent arginine-to-histidine substitution in the Foxp2 DNA-binding ..
  59. ncbi Disc1 point mutations in mice affect development of the cerebral cortex
    Frankie H F Lee
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
    J Neurosci 31:3197-206. 2011
    ..Overall, the histology of Disc1 mutant mouse cortex is reminiscent of the findings in schizophrenia. These results provide further evidence that Disc1 participates in cortical development, including neurogenesis and neuron migration...
  60. pmc Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA conformation: application to disease studies
    Raheleh Salari
    National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA
    Nucleic Acids Res 41:44-53. 2013
    ..Subsequently, we applied remuRNA to determine which of the disease-associated non-coding SNPs are potentially related to RNA structural changes...
  61. pmc A proposed consensus panel of organisms for determining evolutionary conservation of mt-tRNA point mutations
    John W Yarham
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Mitochondrion 12:533-8. 2012
  62. pmc Photoperiod- and thermo-sensitive genic male sterility in rice are caused by a point mutation in a novel noncoding RNA that produces a small RNA
    Hai Zhou
    State Key Laboratory for Conservation and Utilization of Subtropical Agro bioresources, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong, China
    Cell Res 22:649-60. 2012
    ..Our results reveal that the point mutation in p/tms12-1, which probably leads to a loss-of-function for osa-smR5864m, constitutes a common cause for PGMS ..
  63. ncbi Good clinical response to gefitinib in a non-small cell lung cancer patient harboring a rare somatic epidermal growth factor gene point mutation; codon 768 AGC > ATC in exon 20 (S768I)
    Katsuhiro Masago
    Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Jpn J Clin Oncol 40:1105-9. 2010
    ..Therefore, we may suggest that this rare mutation (S768I in exon 20) may not be an insensitive epidermal growth factor receptor somatic mutation in vivo...
  64. ncbi A point mutation in a glutamate-gated chloride channel confers abamectin resistance in the two-spotted spider mite, Tetranychus urticae Koch
    D H Kwon
    Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea
    Insect Mol Biol 19:583-91. 2010
    ..urticae glutamate-gated chloride channel gene (TuGluCl) identified a G323D point mutation as being tentatively related with abamectin resistance...
  65. ncbi A forkhead-domain gene is mutated in a severe speech and language disorder
    C S Lai
    Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Nature 413:519-23. 2001
    ..In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain...
  66. ncbi A point mutation in a Drosophila GABA receptor confers insecticide resistance
    R H ffrench-Constant
    Department of Entomology, 237 Russell Laboratories, University of Wisconsin, Madison 53706
    Nature 363:449-51. 1993
    ..and novel pharmacology of this GABA receptor and examine the functionality of a resistance-associated point mutation (alanine to serine) within the second membrane-spanning domain, the region thought to line the chloride ion ..
  67. pmc Site-directed mutagenesis reveals putative substrate binding residues in the Escherichia coli RND efflux pump AcrB
    Jürgen A Bohnert
    Center for Infectious Diseases and Travel Medicine, University Hospital, Department of Medicine, Albert Ludwigs University, Freiburg, Germany
    J Bacteriol 190:8225-9. 2008
    ..We found that F610A was the point mutation that had the most significant impact on substrate MICs, while other targeted mutations, including conversion ..
  68. pmc Orai3 TM3 point mutation G158C alters kinetics of 2-APB-induced gating by disulfide bridge formation with TM2 C101
    Anna Amcheslavsky
    Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697
    J Gen Physiol 142:405-12. 2013
    ..We find that point mutation of glycine 158 in the third transmembrane (TM) segment to cysteine, but not alanine, slows the kinetics of 2-..
  69. pmc Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation
    Joanna Rorbach
    Mitochondrial Research Group, Institute of Neuroscience, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Nucleic Acids Res 36:3065-74. 2008
    ..We have previously associated a homoplasmic point mutation (1624C>T) in MTTV with a profound metabolic disorder that resulted in the neonatal deaths of numerous ..
  70. ncbi Genetics of pheochromocytoma and paraganglioma in Spanish patients
    Alberto Cascon
    Hereditary Endocrine Cancer Group, Institute de Salud Carlos III Center for Biomedical Research on Rare Diseases, Madrid, Spain
    J Clin Endocrinol Metab 94:1701-5. 2009
    ..In these cases, other clinical aspects like bilaterality, multiplicity, location of the tumors, or age at onset can help to recognize the underlying genes involved...
  71. ncbi The spread of the Leu-Phe kdr mutation through Anopheles gambiae complex in Burkina Faso: genetic introgression and de novo phenomena
    A Diabate
    Institut de Recherche en Sciences de la Santé Centre Muraz, Bobo Dioulasso, Burkina Faso
    Trop Med Int Health 9:1267-73. 2004
    ..gambiae ss and these specific nucleotides were associated with kdr mutation in A. arabiensis. Ecological divergences which facilitated the spread of the kdr mutation within the complex of A. gambiae ss in West Africa, are discussed...
  72. ncbi A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy
    Robert W Taylor
    Department of Neurology, The Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK
    J Am Coll Cardiol 41:1786-96. 2003
    ..The purpose of this study was to understand the clinical and molecular features of familial hypertrophic cardiomyopathy (HCM) in which a mitochondrial abnormality was strongly suspected...
  73. ncbi A single point mutation in the novel PvCesA3 gene confers resistance to the carboxylic acid amide fungicide mandipropamid in Plasmopara viticola
    Mathias Blum
    Institute of Botany, University of Basel, Basel, Switzerland
    Fungal Genet Biol 47:499-510. 2010
    ..Our data demonstrate that the identified genes are putative cellulose synthases and that one recessive mutation in PvCesA3 causes inheritable resistance to the CAA fungicide mandipropamid...
  74. ncbi A single-point mutation converts the highly amyloidogenic human islet amyloid polypeptide into a potent fibrillization inhibitor
    Andisheh Abedini
    Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794 3400, USA
    J Am Chem Soc 129:11300-1. 2007
  75. pmc NDUFS4: creation of a mouse model mimicking a Complex I disorder
    Christopher A Ingraham
    Department of Biomedical Genetics, Univ of Rochester Medical Center, Rochester, NY, USA
    Mitochondrion 9:204-10. 2009
    ..Therefore, a mouse model harboring a point mutation in the NDUFS4 gene was created...
  76. ncbi Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression
    Thorsten Klampfl
    Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
    Blood 118:167-76. 2011
    ..Our data provide insight into the genetic complexity of MPNs and implicate new genes involved in disease progression...
  77. ncbi Point mutation of the proteasome beta5 subunit gene is an important mechanism of bortezomib resistance in bortezomib-selected variants of Jurkat T cell lymphoblastic lymphoma/leukemia line
    Shuqing Lu
    Department of Hematology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, China
    J Pharmacol Exp Ther 326:423-31. 2008
    ..The predicted structure of A108T-mutated PSMB5 shows a conformational change that suggests decreased affinity to bortezomib. In short, the G322A mutation of the PSMB5 gene is a novel mechanism for bortezomib resistance...
  78. pmc An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus
    Mark R Etherton
    Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA, USA
    EMBO J 30:2908-19. 2011
    ..Our results suggest that the cytoplasmic tail of neuroligin-3 has a central role in synaptic transmission by modulating the recruitment of AMPA receptors to postsynaptic sites at excitatory synapses...
  79. pmc Recurrent KRAS codon 146 mutations in human colorectal cancer
    Sarah Edkins
    Cancer Genome Project, Welcome Trust Sanger Institute, Hinxton, UK
    Cancer Biol Ther 5:928-32. 2006
    An activating point mutation in codon 12 of the HRAS gene was the first somatic point mutation identified in a human cancer and established the role of somatic mutations as the common driver of oncogenesis...
  80. pmc Rapid and highly efficient method for scarless mutagenesis within the Salmonella enterica chromosome
    Kathrin Blank
    Junior Research Group 3, Robert Koch Institute, Wernigerode Branch, Wernigerode, Germany
    PLoS ONE 6:e15763. 2011
    ..The presented approach is very versatile for generating in-frame deletions, point mutations or insertions within bacterial chromosomes...
  81. ncbi Structural basis of TBX5-DNA recognition: the T-box domain in its DNA-bound and -unbound form
    Christian U Stirnimann
    European Molecular Biology Laboratory, Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Mol Biol 400:71-81. 2010
    ..Interestingly, all tested TBX5 mutants differ in their ability to bind unspecific DNA, indicating that both sequence-specific and unspecific binding might contribute to the misregulation of target gene expression...
  82. ncbi Constitutive activation of the androgen receptor by a point mutation in the hinge region: a new mechanism for androgen-independent growth in prostate cancer
    Jocelyn Ceraline
    Laboratoire de Cancérologie Expérimentale et de Radiobiologie EA ULP 3430, IRCAD, Strasbourg, France
    Int J Cancer 108:152-7. 2004
    ..AR harboring the nonsense mutation Q640Stop just downstream the DNA binding domain together with the T877A point mutation. This type of mutation, which leads to a c-terminal truncated AR, has not been described yet in PCa...
  83. pmc Voltage-controlled gating at the intracellular entrance to a hyperpolarization-activated cation channel
    Brad S Rothberg
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    J Gen Physiol 119:83-91. 2002
    ..Together, these results are consistent with a voltage-controlled structure at the intracellular side of the spHCN channel that can gate the flow of cations through the pore...
  84. pmc A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons
    Kerstin E Braunstein
    Department of Neurology, University of Ulm, Ulm, Germany
    Hum Mol Genet 19:4385-98. 2010
    ..To provide such evidence, we used here a mouse strain carrying a point mutation in the dynein heavy chain gene that impairs retrograde axonal transport...
  85. pmc Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes
    R G Sewalt
    E C Slater Instituut, BioCentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands
    Mol Cell Biol 18:3586-95. 1998
    ..Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins...
  86. ncbi Two novel point mutations in the long-range SHH enhancer in three families with triphalangeal thumb and preaxial polydactyly
    Christina A Gurnett
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
    Am J Med Genet A 143:27-32. 2007
    ..However, modifier genes may be contributing to the milder phenotype in this family...
  87. pmc In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta
    Y I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Genetics 159:47-64. 2001
    ..This is supported by the observation that the pol3-Y708A mutation is recessive and its mutator effect is partially suppressed by disruption of the REV3 gene...
  88. ncbi Efficient PCR-based gene targeting with a recyclable marker for Aspergillus nidulans
    Michael L Nielsen
    Center for Microbial Biotechnology, BioCentrum DTU, Technical University of Denmark, Building 223, DK 2800 Kgs Lyngby, Denmark
    Fungal Genet Biol 43:54-64. 2006
    ..A major advance of the method is that it allows multiple subsequent genome manipulations to be performed as the selectable marker is recycled...
  89. pmc Mutations of acetylcholinesterase which confer insecticide resistance in Drosophila melanogaster populations
    Philippe Menozzi
    Groupe de biotechnologie des protéines, IPBS UMR 5089, F 31077 Toulouse, France
    BMC Evol Biol 4:4. 2004
    ..However, their relative frequency and their cartography had not yet been addressed...
  90. pmc Genetic interactions of conserved regions in the DEAD-box protein Prp28p
    T H Chang
    Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA
    Nucleic Acids Res 25:5033-40. 1997
    ..Our results thus provide the first hint of the local structural arrangement for Prp28p, and perhaps for other DBPs as well...
  91. pmc A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations
    Robert A Maue
    Department of Physiology and Neurobiology, Dartmouth Medical School, Hanover, NH 03755, USA
    Hum Mol Genet 21:730-50. 2012
    We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease: a single nucleotide change (A to G at cDNA bp 3163) that results in an aspartate to glycine change at ..
  92. ncbi Late onset of stroke-like episode associated with a 3256C-->T point mutation of mitochondrial DNA
    Tina Dysgaard Jeppesen
    The Copenhagen Muscle Research Center, National University Hospital, Rigshospitalet, Copenhagen, Denmark
    J Neurol Sci 214:17-20. 2003
    ..4 mmol/l), and in the mid-occipital region (2.3-3.2 mmol/l) that appeared normal on MRI. Further tests revealed evidence of a severe oxidative defect of muscle metabolism as well...
  93. pmc Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews
    Y Anikster
    Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
    Am J Hum Genet 69:1218-24. 2001
    ..critical interval and identified, in the intronic sequence of a gene corresponding to cDNA clone FLJ22187, a point mutation that segregated with the type III MGA phenotype...
  94. pmc Structural determinants of G-protein alpha subunit selectivity by regulator of G-protein signaling 2 (RGS2)
    Adam J Kimple
    Departments of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 284:19402-11. 2009
  95. pmc A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice
    Esther B E Becker
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom
    Proc Natl Acad Sci U S A 106:6706-11. 2009
    ..Our findings define a previously unknown role for TRPC3 in both dendritic development and survival of Purkinje cells, and provide a unique mechanism underlying cerebellar ataxia...
  96. ncbi Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle
    K Poetter
    Inherited Cardiac Diseases Section, NHLBI, NIH Bethesda, Maryland 20892 1650, USA
    Nat Genet 13:63-9. 1996
  97. ncbi Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (Asp26Glu) and less stable microtubules
    Malathi Hari
    Discovery Oncology, Wyeth, 401 North Middletown Road, Room 4709, Building 200, Pearl River, NY 10965, USA
    Mol Cancer Ther 5:270-8. 2006
    ..However, a novel point mutation (T to A) resulting in Asp26 to glutamate substitution in class I (M40) beta-tubulin was found...
  98. pmc A point mutation in the groove of HLA-DO allows egress from the endoplasmic reticulum independent of HLA-DM
    Francis Deshaies
    Departement de Microbiologie et Immunologie, Universite de Montreal, CP 6128 Succursale Centre Ville, Montreal, QC, Canada H3T 1J4
    Proc Natl Acad Sci U S A 102:6443-8. 2005
    ..Collectively, these results suggest that the binding of HLA-DM to DOalpha allows the complex to egress from the ER by stabilizing intramolecular contacts between the N-terminal antiparallel beta-strands of the DOalphabeta heterodimer...
  99. ncbi The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences
    M Krawczak
    Abteilung Humangenetik, Medizinische Hochschule, Hannover, Federal Republic of Germany
    Hum Genet 90:41-54. 1992
  100. pmc Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates
    Scott E Woodman
    Department of Melanoma Medical Oncology and Department of Systems Biology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cancer Ther 8:2079-85. 2009
    ..These data support the selective inhibitory effect of dasatinib against cells harboring the most common KIT mutation in melanoma, and thus has therapeutic implications for acrallentiginous, chronic sun-damaged, and mucosal melanomas...
  101. ncbi Repeat induced point mutation in two asexual fungi, Aspergillus niger and Penicillium chrysogenum
    Ilka Braumann
    Abteilung Botanik mit Schwerpunkt Genetik und Molekularbiologie, Botanisches Institut und Botanischer Garten, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, 24098 Kiel, Germany
    Curr Genet 53:287-97. 2008
    Repeat induced point mutation (RIP) is a gene silencing mechanism present in fungal genomes. During RIP, duplicated sequences are efficiently and irreversibly mutated by transitions from C:G to T:A...

Research Grants71

  1. Alpha B crystallin as a novel therapeutic for SIRS and Sepsis
    Jonathan B Rothbard; Fiscal Year: 2011
    ..The aims of the grant are first to demonstrate that Cryab, and not Cryab with a point mutation at residue 120, can (i...
    Paul R Odgren; Fiscal Year: 2012
    ..Our colleagues also recently discovered a dominant point mutation (R714C) in PLEKHM1 in a patient with low bone mass and focal sclerosis which we propose is a gain-of- function ..
  3. MR Monitoring of PTC124 Treatment in DMD
    KRISTA H VANDENBORNE; Fiscal Year: 2010
    ..Up to 15% of boys with DMD fail to make dystrophin because of a point mutation that creates a premature stop codon in the dystrophin mRNA...
  4. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..in vivo experiments reported here reveal impaired TLR rather than AgR signaling in "knock-in" mice harboring a point mutation that removes the Ub acceptor site of NEMO...
  5. Herpesvirus-induced telomerase dysregulation and tumor formation
    Keith William Jarosinski; Fiscal Year: 2011
    ..region 1, CR1) specifying the telomeric repeat sequence TTAGGG and the so-called H box, in which a single point mutation was identified in avirulent MDV vaccine strain CVI988...
  6. Serotonin transporter-mediated regulation of neuroendocrine exocytosis
    KEVIN P CURRIE; Fiscal Year: 2013
    ..with chromaffin cells isolated from wild type mice, SERT knockout mice, and a novel knock-in mouse with a point mutation that renders SERT insensitive to antidepressants and cocaine...
  7. Genetic Analysis of FAK Activity
    David D Schlaepfer; Fiscal Year: 2012
    ..To support this model, we have generated a kinase-dead (KD) knock in point mutation (Lys-454 to Arg, R454) in exon 21 of mouse fak by homologous recombination...
  8. Host Defense Mechanisms in Polyaromatic Hydrogen Carcinogenesis
    Craig A Elmets; Fiscal Year: 2013
    ..It is now known that the polyaromatic hydrocarbon 7,12- dimethylbenz(a)anthracene (DMBA) produces a specific point mutation in 61st codon of the H- ras oncogene and that this mutation is necessary for tumors to develop...
  9. Individual Predoctoral Dental Scientist Fellowship
    Angela Gullard; Fiscal Year: 2013
    ..CED, though rare, is most often due to a point mutation in the TGFB1 gene leading to overexpression of the mature, active TGF21 molecule...
  10. Role of the developmental regulator Gon4-like in B lymphopoiesis
    JOHN D COLGAN; Fiscal Year: 2011
    ..The causative lesion is a point mutation that dramatically reduces, but does not abolish, expression of a protein called Gon4-like, which contains ..
  11. Molecular epidemiology of drug resistance and population genetic structure of Pla
    Fangli Lu; Fiscal Year: 2013
    ..falciparum field isolates from Yunnan and Hainan provinces, China. 2. Determine the point mutation prevalence in the dhfr (pyrimethamine drug resistance) and dhps (sulfadoxine drug resistance) genes associated ..
    Michael J Bevan; Fiscal Year: 2012
    ..We have developed the helper-deficient, HD-/- mouse bearing a point mutation in the transcription factor Th-POK, as an ideal model in which to address these questions. Specific Aim 2...
  13. The amelioration of peroxisomal disorders due to defects in Pex10
    Lee A Niswander; Fiscal Year: 2013
    ..Moreover, we will determine whether the point mutation in the PEX10 zinc RING finger disrupts ubiquitination activity, which could alter recycling of the peroxisomal ..
    Eric U Selker; Fiscal Year: 2013
    ..The mutagenic process, RIP (repeat-induced point mutation), for reverse-genetics;4...
  15. A Conserved G-rich Region within Human TH Promoter Regulates Its Activity
    Soumitra Basu; Fiscal Year: 2011
    ..the context of the entire TH promoter will be determined by using GFP and luciferase reporter constructs using point mutation and deletion analysis...
  16. Delivery of Soluble FGFR3 as a Treatment for Achondroplasia
    Steven C Ghivizzani; Fiscal Year: 2013
    ..In 98% of those with achondroplasia, the phenotype is caused by a specific point mutation in FGFR3, resulting in the substitution arginine for glycine at position 380 (Gly380Arg)...
  17. Regulation of Angiogenesis by Kininogen
    Keith R McCrae; Fiscal Year: 2013
    ..Though HKa inhibits angiogenesis, recent studies in the BN-Ka rat, in which a point mutation in the kininogen gene results in deficient kininogen secretion, suggest that kininogen deficiency results in ..
  18. Development of Chemical Chaperonin for Medium Chain Acyl-CoA Dehydrogenase Defici
    AL WALID ABDEL MOHSEN; Fiscal Year: 2010
    ..A single mutation in the MCAD gene (a G985A point mutation) has been identified in 90% of the alleles in the MCAD gene in deficient patients...
  19. Treatment for Dysmyelination in PMD and SPG2
    Pamela E Knapp; Fiscal Year: 2013
    ..Aim 2, similar studies are conducted using siRNAs appropriate for jimpy mice, which have a naturally occurring point mutation that codes for a mutant PLP...
  20. Role of JAK2V617F in the Pathogenesis of Myeloproliferative Disorders.
    Golam Mohi; Fiscal Year: 2013
    ..A somatic point mutation (V617F) in the Janus Kinase 2 (JAK2) has been found in majority of patients with polycythemia vera (PV), ..
  21. A fully integrated assay and platform for detecting Clostridium difficile
    BRUCE D IRVINE; Fiscal Year: 2010
    ..difficile, BI/NAP1, has a single point mutation in this gene that results in a premature stop codon...
  22. Pl3K Regulation of Microbicidal Pathways in Macrophages in Experimental Colitis
    Erin C Steinbach; Fiscal Year: 2013
    ..in a novel mouse model of IBD where the phosphatidylinositol-3-kinase (PI3K) p110delta subunit contains a point mutation (p110delta[D910A/D910A])...
  23. Inhibition of Histone Deacetylase in Myeloproliferative Neoplasms
    Golam Mohi; Fiscal Year: 2012
    ..A somatic point mutation (V617F) in the JAK2 tyrosine kinase has been detected in most patients with PV and 50-60% patients with ET and ..
  24. Carbamazepine for severe liver disease due to antitrypsin deficiency
    David H Perlmutter; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): In the classical form of 11-antitrypsin (AT) deficiency a point mutation alters the folding of an abundant liver-derived secretory glycoprotein and also renders it prone to polymerization and ..
  25. Role of WhiB3 in M. tuberculosis virulence
    ADRIE JC STEYN; Fiscal Year: 2013
    ..Previous work had shown that a point mutation (Arg515->His) in the 4.2 domain of RpoV, the principal sigma factor in Mycobacterium bovis, is attenuating...
  26. How does misregulation of PI3,5P2 signaling lead to neurodegeneration?
    Lois S Weisman; Fiscal Year: 2013
    ..system, we identified patients with Charcot-Marie Tooth syndrome (CMT4J) whose disease corresponds to a single point mutation in Fig4. Little is known about PI3,5P2 and virtually nothing is known about its role in the nervous system...
  27. Structural and Computational Studies of LOV domain proteins and Cryptochromes
    Karen S Conrad; Fiscal Year: 2013
    ..have been associated with light- activation;thus, structural characterization of dCRY in light-induced and point mutation-designed alternative conformations will be completed using x-ray crystallography to elucidate the changes...
    ADRIE JC STEYN; Fiscal Year: 2012
    ..Previous work had shown that a point mutation (Arg ->His) in the 4...
  29. Lentiviral-MGMT gene transfer into hematopoietic stem cells
    Stanton L Gerson; Fiscal Year: 2011
    ..Using a well-characterized singe point mutation of MGMT, P140K, that is resistant to the inhibitory effects of BG, it is possible to selectively protect HP ..
  30. The regulatory function of DNA methylation in Mycobacterium tuberculosis
    SCARLET SARA SHELL; Fiscal Year: 2012
    ..These studies will be extended to investigate the functional significance of a point mutation in mrh that is present in an important clinical Mtb lineage...
  31. Role of Sterols and Insulin in Cardiac Autonomic Response
    JONAS BERNARD GALPER; Fiscal Year: 2013
    ..We previously demonstrated that the Akita diabetic mouse, which has a point mutation in the pro-insulin gene (ins2), demonstrates a markedly decreased response to parasympathetic stimulation of ..
    DAN RAY; Fiscal Year: 2009
    ..the roles of octamer-related sequences in the cyclic expression of LIG ka and the adjacent LIG k gene through point mutation of individual octamer-related sequences alone and in combination...
  33. The Significance of Isocitrate Dehydrogenase Mutations in Gliomas
    CRAIG MICHAEL HORBINSKI; Fiscal Year: 2013
    ..Thus, infiltrative gliomas are incurable. A specific point mutation in IDH1 (and a less common analogous mutation in IDH2) has been found to be quite frequent in these gliomas...
  34. Mechanistic Studies of Ras-MAPK Signals: Specialzed Cues for the T cell Lineage?
    Jeroen Roose; Fiscal Year: 2011
    ..continue our analysis of thymocyte selection and peripheral T cell function in a novel ENU mouse model with a point mutation in RasGRP1[unreadable]s C-terminal EF hand...
  35. Role of the developmental regulator Gon4-like in B lymphopoiesis
    JOHN D COLGAN; Fiscal Year: 2013
    ..The causative lesion is a point mutation that dramatically reduces, but does not abolish, expression of a protein called Gon4-like, which contains ..
    Bonita J Brewer; Fiscal Year: 2013
    ..defects: 1) Meier-Gorlin Syndrome with its point mutations in genes essential for origin licensing;2) a point mutation in a gene encoding part of the replicative helicase that is associated with breast cancer in mice and growth ..
  37. Biological Mechanism of FSGS-1
    Martin R Pollak; Fiscal Year: 2011
    ..We have developed two mouse models: an Actn4 knockout mouse and a disease-associated K255E point mutation knockin mouse...
  38. Treatment of Distal Tyrosine Pathway Disorders
    Markus Grompe; Fiscal Year: 2012
    ..in hepatocytes and renal proximal using AAV2/2 and AAV2/8 vectors harboring 4 kb of genomic homology to an Fah point mutation mouse...
  39. A TG model for functional effects of FHC mutations in b-cardiac myosin
    Susan Lowey; Fiscal Year: 2013
    ..Despite many decades of study, the effect of a single point mutation in the ? -MHC on the functional and structural properties of the myosin molecule, the filament and the complex ..
  40. Role of WhiB3 in M. tuberculosis virulence
    ADRIE STEYN; Fiscal Year: 2009
    ..Previous work had shown that a point mutation (Arg515->His) in the 4.2 domain of RpoV, the principal sigma factor in Mycobacterium bovis, is attenuating...
  41. Genetic Predisposition & Prevention of Neural Tube Defects (NTDs)
    MARGARET ELIZABETH contact ROSS; Fiscal Year: 2010
    ..In a mouse line with a folic acid (FA) responsive NTD, we identified a point mutation in Lrp6, a co-receptor for Wnt canonical signaling, which implicates several important developmental genetic ..
  42. Biological significance of Mallory-Denk bodies in mouse and human liver diseases
    Amika Singla; Fiscal Year: 2011
    ..Spontaneous MDBs have been described in mice with a point mutation in the ferrochelatase gene (fch/fch mice), which develop erythropoietic protoporphyria (EPP) due to ..
  43. Gonadotropins &Cox-2 in Ovarian Cancer Prevention
    XIANGXI MIKE XU; Fiscal Year: 2013
    ..The Wv mice harbor a point mutation in c-Kit that reduces the tyrosine kinase activity to about 1-5% (not a null mutation)...
  44. Animal models to examine role of ZPR1 protein complexes
    LAXMAN DASS GANGWANI; Fiscal Year: 2010
    ..We will create Zpr1 knock-in mice with a double point mutation and a quadruple point mutation that disrupts interaction of ZPR1 with eEF1A and result in moderate and severe ..
  45. Translational Recoding of UGA as Selenocysteine in Selenoprotein Synthesis
    Donna M Driscoll; Fiscal Year: 2013
    ..We defined a novel bipartite RNA- binding domain in SBP2 and showed that a naturally occurring point mutation in this domain, which is associated with hypothyroidism in humans, alters the SECIS-binding activity of the ..
  46. Regulation of Tyrosine Hydroxylase by CLOCK: Potential Mechanisms Underlying the
    WILBUR PUTNEY WILLIAMS; Fiscal Year: 2013
    ..Transgenic mice with a dominant negative point mutation in this gene, Clock[unreadable]19, exhibit increased dopaminergic neuronal firing, upregulated TH in the VTA, ..
  47. Mechanism of action and therapeutic potential of HMGB1 A box in sepsis
    Huan Yang; Fiscal Year: 2013
    ..In aim 1 of this proposal, we will synthesize segments of A box (over-lapping 20-mer peptides) and make point mutation mutants (cysteines at positions of 23 and 45 replaced by serine) of A box and assess the inhibition of these ..
  48. Molecular characteristics of the apical recycling system
    ..All of the patients from the Navajo tribe have a single point mutation that inactivates proper motor function...
    Michael A Gimbrone; Fiscal Year: 2013
    ..HGPS is caused by a single point mutation in the LMNA gene, which results in accumulation of a mutant form of the lamin A protein called Progerin...
  50. Eliciting protective mechanisms against alcoholism
    Emanuel Rubin; Fiscal Year: 2010
    ..the ability of single-point mismatched oligodeoxynucleotides to generate the Glu486Lys dominant-negative point mutation of ALDH2*2 in human hepatoma cells that carry the ADH gene, thus generating new cell lines that produce high ..
  51. Modifiers of Intestinal Tumor Progression
    Linda D Siracusa; Fiscal Year: 2012
    ..The ApcMin/+ mouse contains a point mutation in the Apc gene that results in a truncated protein (Moser et al. 1990;Su et al. 1992)...
  52. Effect of paternal age on mutational burden and behavior in mice
    Fernando Pardo-Manuel de Villena; Fiscal Year: 2013
    ..Since a highly-powered search for a PAE on CNV and point mutation burden in humans is difficult to assess because of low numbers of offspring, we propose to use the laboratory ..
  53. Eosinophilic Myocarditis
    Noel R Rose; Fiscal Year: 2013
    ..of Th2 differentiation for Eo-EAM development, we will employ IL4R[unreadable]F709 mice, which carry a point mutation in the IL4 receptor essentially rendering the signaling pathway hyperactive (Subaim 3.2)...
  54. Cellular Mechanisms in Hutchinson-Gilford Progeria Syndrome and Normal Aging
    Kan Cao; Fiscal Year: 2012
    ..On average, death occurs at the age of 12 from heart attack or stroke. Classic HGPS is caused by a de novo point mutation in exon 11 (1824, C->T) of the LMNA gene, activating a cryptic splice donor and resulting in a mutant lamin ..
  55. Novel therapeutic targets for Leukemia in Elderly
    Holly Martin; Fiscal Year: 2013
    ..A single point mutation of aspartic acid to valine (KITD816V) in the activation loop of KIT, found in up to 90% of SM patients and ~ ..
  56. Novel integrative method to detect biomakers of breast cancer resistance
    Sheida Nabavi; Fiscal Year: 2013
    ..a novel supervised integrative analysis tool, based on Bayesian network analysis which integrates CNV, point mutation and gene expression data...
  57. Genetic analysis of genomic instability and cancer in zebrafish
    KEITH CHI CHENG; Fiscal Year: 2012
    ..of those steps can occur by multiple mechanisms including chromosome loss, recombination, insertion, deletion, point mutation, or epigenetic modification...
  58. Biological Mechanism of FSGS-1
    Martin R Pollak; Fiscal Year: 2013
    ..We have developed two mouse models: an Actn4 knockout mouse and a disease-associated K255E point mutation knockin mouse...
  59. Insulin Sensitivity In a Novel Mouse Model of ER Stress
    MATTHEW CLAY WHEELER; Fiscal Year: 2013
    ..We have recently characterized a mouse mutant that harbors an ENU induced point mutation in the Sec6111 gene that leads to diabetes via ER stress induced 2-cell apoptosis...
  60. Engineering Microbial Rhodopsins as Optical Voltage Sensors
    ADAM EZRA COHEN; Fiscal Year: 2013
    ..GPR can be expressed and imaged in zebra fish neurons in vitro and in living zebra fish. A single-point mutation to GPR leads to a protein whose fluorescence is exquisitely sensitive to membrane potential...
  61. Biosensing in electrochemically controlled nano-junctions
    Krzysztof Slowinski; Fiscal Year: 2013
    ..The key objective of the proposed studies is to determine whether disruption of the DNA -stack via a single-point mutation or a protein binding results in an analytically effectual decrease in electrical conductivity of the helix...
  62. Distinguishing cytosolic sensing of DNA and cyclic dinucleotides in vivo
    Russell E Vance; Fiscal Year: 2013
    ..To address this problem we identified a specific point mutation in STING (R231A) that selectively abolishes the IFN response to cyclic dinucleotides without affecting the ..
  63. Innate Immunity in Experimental Arthritis of Kininogen
    Robert Colman; Fiscal Year: 2007
    ..We have found that these rats have a single point mutation $511N leading to N-glycosylation which increases the susceptibility of HK to proteolysis...
    Eric Kmiec; Fiscal Year: 1999
    Many inherited connective tissue diseases result from a point mutation or frame-shift mutation...
    Mitsuo Ikebe; Fiscal Year: 1999
    ..b>Point mutation at the S2 region may cause changes in the assembly of myosin molecules thus reducing the efficiency of ..
    Thomas Glaser; Fiscal Year: 2004
    ..In preliminary studies, we discovered that eyl is a point mutation in the Rx/rax rednal homeobox gene...
    Vincent Agnello; Fiscal Year: 2001
    ..that initially a WA+ RF- IgM is produced and that rheumatoid factor activity arises as a result of a point mutation in the CDR3 with chronic HCV infection...
  68. Msec Polymerase Chain Reaction with fMolar Detection Sensitivity using SPR
    DONALD ROPER; Fiscal Year: 2007
    ..2004) with point mutation selectivity factors of ~105:1 (Park et al., 2002)...
    George Inana; Fiscal Year: 1991
    ..The specific nature of each defect, be it gene deletion, rearrangement, point mutation or other changes will be identified...
    Jerry Radich; Fiscal Year: 1993
    ..gamma (in T cells) gene rearrangement as a "fingerprint" of the malignant clone, in AML we will use the point mutation of the N-ras oncogene as the leukemia-specific marker...
  71. The Human Colorectal Instabilitome
    Stephen Meltzer; Fiscal Year: 2007
    ..biallelic inactivation of genes showing frequent frameshift mutation by analyzing for loss of heterozygosity, point mutation, and altered expression; 2.b To determine functional differences between WT and mutant candidate proteins...